PHILIPPINE PEDIATRIC SOCIETY
Diplomate Exam Reviewer 2020
(topics were lifted from the HAB checklist)
EMERGENCY MEDICINE
------------------------------------------------------------------------------------------------------------------------------------------------------------DERMATOLOGY
҉ Skin Disorders
----------------------------------------------------҉ Skin and Soft Tissue Infections
---------------------------------------OPHTHALMOLOGY
҉ Eye Pain and Discharge ----------------------------------------------------OTOLOGY
҉ Ear Pain
----------------------------------------------------NEONATOLOGY
҉ Neonatal Fever
----------------------------------------------------҉ Neonatal Jaundice
----------------------------------------------------҉ Respiratory Distress in the Newborn ---------------------------------------҉ Delayed Meconium Passage
---------------------------------------҉ Abdominal Distention
----------------------------------------------------҉ Newborn Dysmorphology
---------------------------------------҉ Malformations
----------------------------------------------------҉ Metabolic Disorders
----------------------------------------------------҉ Chronic Child
----------------------------------------------------ENDOCRINOLOGY
҉ Weight Gain
----------------------------------------------------҉ Diabetic Ketoacidosis
----------------------------------------------------҉ Endocrine Disorders
----------------------------------------------------҉ Short Stature
----------------------------------------------------GASTROENTEROLOGY
҉ Diarrhea
----------------------------------------------------҉ Constipation
----------------------------------------------------҉ Abdominal Pain
----------------------------------------------------҉ Prolonged Jaundice
----------------------------------------------------҉ Shock
҉ Pediatric Poisonings
҉ Animal Bites
2
4
6
7
10
12
14
17
19
21
25
26
27
29
33
49
53
55
57
63
66
69
71
73
NEUROLOGY / DEVELOPMENTAL PEDIATRICS
҉ Traumatic Brain Injury
----------------------------------------------------҉ Headache
----------------------------------------------------҉ Seizures
----------------------------------------------------҉ Raised Intracranial Pressure
---------------------------------------҉ Children with Special Needs
---------------------------------------HEMATOLOGY – ONCOLOGY
҉ Anemia
----------------------------------------------------҉ Cancer
----------------------------------------------------NEPHROLOGY
҉ Dysuria
----------------------------------------------------҉ Renal Disorders
----------------------------------------------------҉ Genital Disorders
----------------------------------------------------CARDIOLOGY
҉ Hypertension
----------------------------------------------------҉ Chest Pain
----------------------------------------------------҉ Heart Murmur
----------------------------------------------------҉ Arrhythmia
----------------------------------------------------҉ Heart Failure
----------------------------------------------------PULMONOLOGY / ALLERGOLOGY
҉ Sore throat
----------------------------------------------------҉ Cough
----------------------------------------------------҉ Colds
----------------------------------------------------҉ Allergic Disorders
----------------------------------------------------RHEUMATOLOGY / ORTHOPEDICS
҉ Collagen and Vascular Disorders
---------------------------------------҉ Limping Child
----------------------------------------------------҉ Musculoskeletal Disorders
---------------------------------------INFECTIOUS DISEASE
҉ Fever
----------------------------------------------------҉ Fever and Rash
----------------------------------------------------҉ Common Viral Illnesses ----------------------------------------------------҉ Common Bacterial Infections
---------------------------------------҉ Common Bacterial Causes of Nosocomial Infections
-------------҉ Fungal Infections
----------------------------------------------------҉ Parasitic Infections
-----------------------------------------------------
74
75
79
83
85
89
92
98
100
116
120
124
129
135
138
141
143
155
156
158
168
171
173
183
188
209
231
233
235
Complex
▪ Acute process characterized by the body’s inability to deliver adequate
oxygen to meet the metabolic demands of vital organs and tissues
COMPENSATED SHOCK
▪ Compensatory mechanisms attempt to maintain BP by increasing CO
and SVR
▪ Body attempts to optimize oxygen delivery to the tissues by increasing
oxygen extraction and redistributing blood flow to the brain, heart, and
kidneys at the expense of the skin and GIT
DECOMPENSATED SHOCK
▪ Hypotension and tissue damage develop if treatment is not initiated or
is inadequate
CLINICAL MANIFESTATIONS
DIAGNOSIS
TREATMENT
COMPLICATIONS / PROGNOSIS
▪ May initially manifest only as
tachycardia ± tachypnea
▪ Progression leads to ↓ UO, poor
peripheral perfusion, respiratory distress
or failure, alteration of mental status, and
low BP
▪ Hypotension – late finding, not a
criterion for the diagnosis of shock
▪ Clinical diagnosis based on thorough history and
physical examination
(see Nelson’s 21st Ed., Fig. 88.1 and Fig. 88.2 for the algorithms for timesensitive, goal-directed stepwise management of hemodynamic support in
Newborns and Infants and Children, respectively)
▪ After the 1sthr of therapy and attempts
at early reversal of shock, focus on goaldirected end points should continue in the
PICU
(see Nelson’s 21st Ed., Table 88.6 for
Hemodynamic Variables in Different Shock
States)
(see Nelson’s 21st Ed., Table 88.4 for Pathophysiology of Shock)
HYPOVOLEMIC
▪ Most common cause of shock in children
worldwide
▪ Due to ↓ preload secondary to internal or
external losses
Etiologies:
Blood
loss,
plasma
loss,
water/electrolyte loss
▪ Cardiac pump failure secondary to poor
myocardial function → systolic and diastolic
dysfunction
CARDIOGENIC
DISTRIBUTIVE
Etiologies: CHD,
arrhythmias
cardiomyopathies,
ischemia,
▪ Abnormalities of vasomotor tone from loss of
venous & arterial capacitance → maldistribution
of blood flow away from vital organs & a
compensatory ↑ in CO
Etiologies: Anaphylaxis, neurologic (loss of
sympathetic vascular tone 2O to SCI or brainstem
injury), drugs
▪ ↓ CO 2O to direct impediment to right- or leftsided heart outflow or restriction of all cardiac
chambers
OBSTRUCTIVE
Etiologies: tension pneumothorax, pericardial
tamponade, pulmonary embolism, anterior
mediastinal masses, critical coarctation of the
aorta
PPS Oral Exam Reviewer 2020
▪ Often manifests initially as orthostatic
hypotension
▪ Dry mucous membranes, dry axillae,
poor skin turgor
▪ ↓ UO
▪ Tachypnea
▪ Cool extremities, delayed CRT, poor
peripheral and/or central pulses
▪ Declining mental status
▪ ↓ UO
▪ Manifests initially as peripheral
vasodilation and ↑ but inadequate CO
▪ Manifests as inadequate CO because of a
physical restriction of forward blood flow
(see Nelson’s 21st Ed., Table 88.2 for Criteria for
Organ Dysfunction and Table 88.3 for Signs of
Decreased Perfusion)
Hematologic Abnormalities
▪ Thrombocytopenia, prolonged PT and aPTT, ↓
serum fibrinogen level, ↑ fibrin split products, and
anemia
▪ ↑ Neutrophil counts and ↑ immature forms,
vacuolation of neutrophils, toxic granulations and
Döhle bodies can be seen with infection
▪ Neutropenia or leukopenia may be an ominous
sign of overwhelming sepsis
Hallmark of uncompensated shock: imbalance
between oxygen delivery and oxygen consumption
Falling mixed venous oxygen saturation (SVO2)
reflects an increasing O2 extraction ratio and ↓ in
O2 delivery relative to consumption
▪ Measured from a pulmonary arterial catheter
▪ Manifested clinically by ↑ lactic acid production
caused by anaerobic metabolism and a
compensatory ↑ in tissue oxygen extraction
▪ Initial assessment: airway, breathing and circulation
▪ Establish IV/IO access → rapid bolus of 20mL/kg of isotonic fluid; titrated
to normalize HR, UO, CRT and mental status (may be repeated up to 60-80
mL/kg)
▪ If shock remains refractory, vasopressor therapy should be instituted
(see Nelson’s 21st Ed., Table 88.13 and Table 88.14 for the Cardiovascular
Drug Treatment of Shock and Vasodilators/Afterload Reducers in Treatment
of Shock, respectively)
▪ Monitor and correct electrolytes
▪ Treat the hypoglycemia
▪ Hypocalcemia, which may contribute to myocardial dysfunction, should be
treated with a goal of normalizing iCa concentration
▪ Adrenal function is an important consideration
● HAA replacement may be beneficial
● Corticosteroids may be considered in patients with shock that is
unresponsive to fluid resuscitation and catecholamines
(see Nelson’s 21st Ed., Table 88.8 for GoalDirected Therapy of Organ System
Dysfunction in Shock)
▪ Hgb should be maintained at 10 g/dL,
SVO2 at >70%, and cardiac index at 3.3-6.0
L/min/m2
▪ Blood lactate levels and calculation of
base deficit – useful markers for the
adequacy of oxygen delivery
▪ Respiratory support – used as clinically
appropriate
▪ Smaller boluses of fluids (5-10mL/kg) – replace deficits and maintain
preload
▪ Early initiation of myocardial support with epinephrine or dopamine to
improve CO is important
▪ Early consideration should be given to administration of an inodilator (e.g.
milrinone) → may improve systolic function and ↓ SVR without causing a
significant ↑ in HR
▪ Dobutamine or other vasodilating agents (e.g. nitroprusside) may be
considered
▪ May benefit from early initiation of a vasoconstrictive agent to increase SVR
▪ Phenylephrine or vasopressin – to ↑ SVR in patients with SCI and spinal
shock
▪ Epinephrine – for patients with anaphylaxis
▪ Fluid resuscitation may be briefly temporizing in maintaining CO but the
primary insult must be immediately addressed
● Pericardiocentesis for pericardial effusion
● Pleurocentesis or CTT for pneumothorax
● Thrombectomy/thrombolysis for PE
● Initiation of a prostaglandin infusion for ductus-dependent cardiac
lesions
Batch Clingy
ETIOLOGY / INCIDENCE / PATHOGENESIS
2
▪ Encompasses multiple forms of shock (e.g.
hypovolemic, distributive, cardiogenic)
▪ Hypovolemia from intravascular fluid losses
occurs through capillary leak
▪ Cardiogenic shock results from the myocardialdepressant effects of sepsis
▪ Distributive shock is the result of decreased SVR
SEPTIC
▪ In the early stages, CO ↑ to maintain adequate
oxygen delivery and meet the greater metabolic
demands of the organs and tissues (warm shock)
▪ As septic shock progresses, CO ↓ in response to
the effects of numerous inflammatory mediators
→ compensatory ↑ in SVR (cold shock)
Systemic inflammatory response syndrome (SIRS)
▪ Inflammatory cascade that is initiated by the host
response to an infectious or noninfectious trigger
Sepsis
▪ SIRS 2o to a suspected or proven infectious
etiology
Severe sepsis
▪ Sepsis + organ dysfunction
Septic shock
▪ Severe sepsis + persistence of hypoperfusion or
hypotension despite adequate fluid resuscitation or
a requirement for vasoactive agents
(see Nelson’s 21st Ed., Table 88.7 for the
International Consensus Definition for Pediatric
Sepsis)
Select recommendations from the 2020 Surviving Sepsis Campaign for
Children
▪ If lactate levels can be rapidly obtained, measure blood lactate – provide a
valuable indirect marker of tissue hypoperfusion
▪ In children with septic shock, start antimicrobial therapy as soon as
possible, within 1 hour of recognition
▪ In children with sepsis-associated organ dysfunction but without shock,
start antimicrobial therapy as soon as possible after appropriate evaluation,
within 3 hours of recognition
▪ Use empiric broad-spectrum therapy with one or more antimicrobials to
cover all likely pathogens
● Once pathogens and sensitivities are available, narrow antimicrobial
coverage
● If no pathogen is identified, narrow or stop empiric therapy according to
clinical presentation, site of infection, host risk factors and adequacy of
clinical improvement
▪ Use balanced/buffered crystalloids, rather than 0.9% saline for the initial
resuscitation of children with septic shock
▪ Use either epinephrine or norepinephrine rather than dopamine in children
with septic shock
● Epinephrine is associated with a lower risk of mortality and more organ
failure-free days among survivors compared to dopamine
▪ SS suggest against using IV hydrocortisone to treat septic shock if fluid
resuscitation and vasopressor therapy are able to restore hemodynamic
stability
▪ SS suggest that either IV hydrocortisone or NO hydrocortisone may be used
if adequate fluid resuscitation and vasopressor therapy are not able to
restore hemodynamic stability
Mortality for children with sepsis ranges
from 4% to as high as 50%, depending on
illness severity, risk factors, and
geographic location
Batch Clingy
(see Nelson’s 21st Ed., Fig 88.4 for the hypothetical
pathophysiology of the septic process)
▪
Alterations
in
temperature
(hyperthermia or hypothermia)
▪ Tachycardia
▪ Tachypnea
PPS Oral Exam Reviewer 2020
3
Complex
▪ >90% occur at home
▪ Most involve a single substance
▪ Ingestion accounts for majority of exposures, minority via dermal, inhalational, and
ophthalmic routes
▪ 40% involve non drug items (ex. cosmetics, personal care items, cleaning solutions,
plants, foreign bodies)
▪ Pharmaceutical preparations account for remainder of exposures, and analgesic,
topical preparations, vitamins, and antihistamines are the most reported
▪ Common in <6yo, less common in 6-12yo, 2nd peak occurs in adolescence
SIGN
ODOR
Bitter almonds
Acetone
Rotten eggs
Wintergreen
Garlic
OCULAR SIGNS
Miosis
Mydriasis
Nystagmus
Lacrimation
Retinal hyperemia
CUTANEOUS SIGNS
Diaphoresis
Alopecia
Erythema
Cyanosis
(unresponsive to
oxygen)
ORAL SIGNS
Oral burns
Gum lines
GI SIGNS
Diarrhea
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
Common Agents Toxic to <6yo in small doses
▪ Aliphatic hydrocarbons (gasoline, kerosene, lamp oil) – acute lung injury
▪ Antimalarials (Chloroquine, quinine) – seizures, dysrhythmias
▪ Benzocaine – methemoglobinemia
▪ B-adrenergic receptor blockers – bradycardia, hypotension
▪ Ca channel blockers – bradycardia, hypotension, hyperglycemia
▪ Camphor – seizures
▪ Caustics (pH <2 or >12) – airway, esophageal, gastric burns
▪ Clonidine – lethargy, bradycardia, hypotension
▪ Hypoglycemics (sulfonylureas) – hypoglycemia, seizures
▪ Laundry detergent packets – airway issues, respiratory distress, altered mental
status
▪ MAO inhibitors – hypertension → delayed CV collapse
▪ Methylsalicylate – tachypnea, metabolic acidosis, seizures
▪ Opioids – CNS depression, respiratory depression
▪ Organophosphate pesticides – cholinergic crisis
▪ Phenothiazines – seizures, dysrhythmias
▪ Theophylline – seizures, dysrhythmias
▪ Tricyclic antidepressants – CNS depression, seizures, dysrhythmia, hypotension
DIAGNOSIS
APPROACH
▪ Stabilization
▪ Rapid assessment of ABC and mental state
▪ If with altered mental status, serum dextrose concentration
should be obtained early, and naloxone should be considered
▪ Targeted history (intentional? Witnessed? Household stress?
Brand? Generic? Timing? Symptoms – time and progression?)
▪ Past medical and Developmental history
▪ Social history
▪ Targeted PE
▪ Labs: basic chemistry panel (electrolytes, renal function,
glucose), anion gap (especially if with acidosis), ALT AST, INR
(especially for acetaminophen overdose), serum creatine kinase
(for rhabdomyolysis), serum osmolality (surrogate marker for
toxic alcohol exposure), urine pregnancy test (mandatory for all
postpubertal females)
▪ Additional lab tests based on presumed poison (ex. Quantitative
blood concentrations)
▪ Additional testing: ECG, CXR
TOXIDROMES – recognized poisoning syndromes suggestive of toxicity from
specific or class of substances
TOXIN
LABORATORY CLUES IN TOXICOLOGIC DIAGNOSIS
Cyanide
Isopropyl alcohol, methanol, paraldehyde, salicylates
Hydrogen sulfide, sulfur dioxide, methyl mercaptans
Methylsalicylate
Arsenic, thallium, organophosphates, selenium
Opioids, organophosphates, clonidine, phenothiazides, sedative-hypnotics, olanzapine
Anticholinergics, sympathomimetics, post-anoxic encephalopathy, opiate withdrawal, cathinones, MDMA
Anticonvulsants, sedative-hypnotics, alcohols, PCP, ketamine, dextromethorphan
Organophosphates, irritant gas or vapors
Methanol
Cholinergics, sympathomimetics, withdrawal syndromes
Thallium, arsenic
Boric acid, elemental mercury, cyanide, carbon monoxide, disulfiram, scombroid, anticholinergics,
vancomycin
Methemoglobinemia, amiodarone, silver
Corrosives, oxalate-containing plants
Lead, mercury, arsenic, bismuth
Antimicrobials, arsenic, iron, boric acid, cholinergics, colchicine, opioid withdrawal
Anion gap metabolic acidosis (Mnemonic = MUDPILES CAT)
▪ Methanol, metformin
▪ Uremia
▪ DKA
▪ Propylene glycol
▪ Isoniazid, iron, massive ibuprofen
▪ Lactic acidosis
▪ Ethylene glycol
▪ Salicylates
▪ Cellular asphyxiants
▪ Alcoholic ketoacidosis
▪ Tylenol
Elevated Osmolar Gap
▪ Alcohols: ethanol, isopropyl, methanol, ethylene glycol
Hypoglycemia (Mnemonic = HOBBIES)
▪ Hypoglycemics oral: sulfonylureas, meglitinides
▪ Other: quinine, unripe ackee fruit
▪ Beta Blockers
▪ Insulin
▪ Ethanol
▪ Salicylates
Hyperglycemia
▪ Salicylates (early)
▪ Ca channel blockers
▪ Caffeine
TREATMENT
▪ Poison control center
▪ Majority of exposures in <6yo can be managed without
direct medical intervention → product is not inherently
toxic, or quantity is not sufficient to produce clinically
relevant toxic effects
▪ Substances highly toxic to toddlers in small doses:
carbon monoxide, batteries, and analgesics (mainly
opioids)
POISON PREVENTION EDUCATION – integral part of all
well child visit starting 6mos
▪ Exposures in adolescence is usually intentional (suicide,
misuse, or abuse of substances) → more severe toxicity
MANAGEMENT
▪ Supportive care
▪ Decontamination
▪ Syrup of Ipecac – contains 2 emetic alkaloids that work
both in CNS and GI to produce vomiting (but AAP, AACT
and AAPCC published statements in favor of abandoning
use of ipecac)
▪ Gastric lavage – under best circumstances only
removes a fraction of gastric contents hence in most
clinical scenarios is no longer recommended
▪ Single dose activated charcoal – most likely effective
when given within 1 hour of ingestion
● Substances poorly adsorbed by activated charcoal > alcohols, caustics, cyanide, heavy metals,
hydrocarbons, iron, lithium
● Cathartics have been used in conjunction w/
activated charcoal to prevent constipation and
accelerate evacuation of charcoal-toxin complex
▪ Whole-Bowel Irrigation
▪ Directed therapy: Antidotal therapy, intralipid
emulsion therapy
▪ Enhanced elimination: urinary alkalinization,
hemodialysis, multidose activated charcoal
COMMON ANTIDOTES
POISON
Acetaminophen
Anticholinergics
Benzodiazepines
B-blockers
Ca channel blockers
Carbon monoxide
ANTIDOTE
N-acetylcysteine
Physostigmine
Flumazenil
Glucagon
Insulin
Calcium salts
Oxygen
Batch Clingy
ETIOLOGY / INCIDENCE
4
Hematemesis
Constipation
CARDIAC SIGNS
Tachycardia
Bradycardia
Hypertension
Hypotension
RESPIRATORY SIGNS
Depressed
respirations
Tachypnea
CNS SIGNS
Ataxia
Coma
Seizures
Delirium/psychosis
Sympathomimetics, anticholinergics, antidepressants, antipsychotics, methylxanthines, salicylates, cellular
asphyxiants, withdrawal, serotonin syndrome, neuroleptic malignant syndrome, MDMA, cathinones
B-blockers, Ca channel blockers, digoxin, clonidine, organophosphates, opioids, sedative-hypnotics
Sympathomimetics, anticholinergics, MAO inhibitors, serotonin syndrome, neuroleptic malignant syndrome,
clonidine withdrawal
B-blockers, Ca channel blockers, cyclic antidepressants, iron, antipsychotics, barbiturates, clonidine, opioids,
arsenic, amatoxin mushrooms, cellular asphyxiants, snake evenomation
Cyanide
Hypocalcemia
▪ Ethylene glycol
▪ Fluoride
Rhabdomyolysis
▪ Neuroleptic malignant syndrome
▪ Statins
▪ Mushrooms (Tricholoma equestre)
▪ Any toxin causing prolonged immobilization (ex. Opioids,
antipsychotics) or excessive muscle activity or seizures (ex.
Sympathomimetics)
Opioids, sedative-hypnotics, alcohol, clonidine, barbiturates
Salicylates, sympathomimetics, caffeine, metabolic acidosis, carbon monoxide, hydrocarbon aspiration
Alcohols, anticonvulsants, sedative-hypnotics, lithium, dextromethorphan, carbon monoxide, inhalants
Opioids, sedative-hypnotics, anticonvulsants, antidepressants, antipsychotics, ethanol, anticholinergics,
clonidine, GHB, alcohols, salicylates, barbiturates
Sympathomimetics, anticholinergics, antidepressants, cholinergics, isoniazid, camphor, lindane, salicylates,
nicotine, tramadol, water hemlock, withdrawal
Sympathomimetics, anticholinergics, LSD, PCP, hallucinogens, lithium, dextromethorphan, steroids,
withdrawal, MDMA, cathinones
Radiopaque substance on KUB (Mnemonic = CHIPPED)
▪ Chloral hydrate, calcium carbonate
▪ Heavy metals (lead, zinc, barium, arsenic, lithium, bismuth)
▪ Iron
▪ Phenothiazines
▪ Play-Doh, potassium chloride
▪ Enteric-coated pills
▪ Dental amalgam, drug packets
Digitalis
Ethylene glycol,
methanol
Iron
Isoniazid
Lead and other heavy
metals
Methemoglobinemia
Opioids
Organophosphates
Salicylates
Sulfonylureas
Tricyclic
antidepressants
Hydroxocobalamin
Digoxin-specific Fab
antibodies
Fomepizole
Deferoxamine
Pyridoxine
BAL (Dimercaprol)
Calcium disodium EDTA
Dimercapto-succinic acid
Methylene blue 1%
solution
Naloxone
Atropine
Pralidoxime
Na bicarbonate
Octreotide and dextrose
Na bicarbonate
Lead, arsenic, mercury, organophosphates, nicotine
Batch Clingy
Peripheral
neuropathy
Arsenic, iron, caustics, NSAIDs, salicylates
Lead
PPS Oral Exam Reviewer 2020
5
Complex
DISEASE
ETIOLOGY/INCIDENCE
Dog Bites 80-90%
3 categories: abrasions, puncture wounds, lacerations with or
without an associated avulsion
PPS Recommendations on Animal Bites
▪ Vaccinate pet dogs every year
▪ Families with pet dogs should be given rabies vaccine as
preexposure prophylaxis
▪ First aid for bites: wash wound with soap and water for 10 mins
→ antiseptic (povidone iodine or alcohol)
▪ PREEXPOSURE PROPHYLAXIS: The Rabies Act of 2007
● Rabies immunization for children aged 5-14 years living in
highly endemic areas
● 3 doses: days 0, 7 and 21 or 28
ANIMAL AND
HUMAN BITES
▪ POSTEXPOSURE PROPHYLAXIS:
● 5 intramuscular doses (days 0, 3, 7, 14 and 28) OR
● 8 intradermal doses (2 doses of 0.1mL each intradermally on
both deltoids on days 0, 3, 7, and 28 or 30)
● The doses beyond d10 may be discontinued if the dog is still
alive after 10-14 days
DIAGNOSIS
Attention to:
▪ Thorough history and PE
▪ Circumstances surrounding bite event
▪ History of drug allergies
▪ Immunization status of child (tetanus) and animal (rabies)
PE: Type, size and depth of injury, foreign material in wound,
status of underlying structures, location of injury, range of motion
of affected area
Radiograph if bone or joint was penetrated or fractured
Aerobic and anaerobic cultures from infected wound
TREATMENT
▪ Irrigation – copious amount of normal saline
▪ Debridement
▪ Wound closure (1o wound closure preferred)
Antibiotic therapy for:
▪ Moderate to severe injuries <8h old
▪ Bone or joint space penetration
▪ Deep hand wounds
▪ Immunocompromised patients
▪ Wounds adjacent to a prosthetic joint
▪ Wounds close to genital area
▪ Coverage should include Pasteurella, Eikenella, Staph, Strep and
anaerobes
▪ First choice: Co-amoxiclav
▪ No alternative tx for penicillin-allergic patients but can consider:
Clindamycin, Doxycycline, Moxifloxacin, and macrolides in
pregnant but poor coverage for anaerobes
▪ If IV is necessary: Ampisul, Cefoxitin, Ertapenem, Moxifloxacin
▪ Provide rabies & tetanus vaccination
▪ Elevation (esp. if edema present)
▪ Immobilization (ex. Use splint for hands)
▪ Follow-up (within 48hrs or sooner if worsening)
▪ Reporting
COMPLICATION
Infection is most common:
▪ Dog bite wounds (80%)
▪ Cat bite wounds (>50%)
▪ Rodent bite (rats 50%, other mammals 25%)
▪ Human bite (high risk)
Batch Clingy
▪ There is no single shot rabies vaccine that will offer sufficient
protection
▪ Bites and scratches by animal’s paw can transmit rabies, same is
true for licks on open wounds and mucus membranes
▪ Rabies vaccination is not routinely given for rat bites because
rats, mice, hamsters, guinea pigs and members of the rodent
family are not significant carriers of rabies. However, all are
tetanus prone.
▪ If a child has been previously vaccinated from a previous dog bite
and was bitten again, he will still need rabies vaccine. Since
previous vaccine has been completed, he will require only 2
booster doses (on day he was bitten and 3 days later)
▪ Unless a child is infected by the rabies virus, he cannot transmit
rabies. Playmates do not need rabies vaccine.
CLINICAL MANIFESTATIONS
▪ Dog bites: Crush injury to tissues
▪ Cat and rat bites: Puncture wounds
▪ Human bites: occlusion injury (upper and lower teeth come
together on a body par) or a clenched-fist injury (when fist strikes
the teeth of another individual)
PPS Oral Exam Reviewer 2020
6
Complex
ETIOLOGY/INCIDENCE/ PATHOGENESIS
INFANTILE HEMANGIOMA
▪ Most common tumor of infancy (5% of NB)
▪ Present at birth or more commonly in the 1 st or 2nd week of life
▪ RF: prematurity, LBW, female, white
▪ Enlarge then spontaneously involute
▪ Most are mixed (superficial + deep components)
▪ Rapid phase of expansion → stationary period → spontaneous
involution → regression (anticipated when the lesion develops
pale gray areas centrally) → small cosmetic defects
(telangiectasia, hypopigmentation, fibrofatty deposits, scar)
▪ 60% reach maximal involution by 5yo, 90-95% by 9yo
HEMANGIOMA
▪ Vascular tumors
▪ Exhibit endothelial
cell hyperplasia and
proliferation
Superficial IH
▪ 1st or 2nd month of life; Solitary or multiple
▪ On any area of the body, mostly on the face, scalp, back,
anterior chest
▪ May have patterns of facial involvement – frontotemporal,
maxillary, mandibular, frontonasal
▪ Erythematous or blue mark or area of pallor → fine
telangiectatic pattern → bright, red, protuberant, compressible,
sharply demarcated
▪ Burrowing and release of toxic or antigenic substances by the
female mite Sarcoptes scabei var. hominis
▪ Most at risk: children and sexual partners of affected individuals
▪ Transmitted rarely by fomites because isolated mite dies within
2-3 days
▪ Gravid female impregnates on the skin surface → exudes a
keratolytic substance → burrows into the s. corneum → forms a
shallow well within 30 mins → extends this tract by 0.5-5mm/day
along the boundary wall with the s. granulosum → deposits 10-25
oval eggs daily → completed egg laying in 4-5wks → female dies
within the burrow → eggs hatch in 3-5 days → release of larvae
→ move to the skin surface → molt into nymph → mature in 23wks → mate → invades the skin
PPS Oral Exam Reviewer 2020
LABORATORY FINDINGS/DIAGNOSIS
▪ GLUT-1 – immunohistochemical marker specific for IH
COMPLICATIONS
▪ Impairment of a vital function (e.g. on the eyelid interfering with
vision)
▪ Ulceration, secondary infection, permanent disfigurement
Deep IH
▪ More diffuse, less defined
▪ Cystic, firm, or compressible
▪ Overlying skin may appear normal in color or have a bluish hue
MULTIFOCAL INFANTILE HEMANGIOMA
▪ Occur in the skin and/or visceral organs
CONGENITAL HEMANGIOMA
▪ Present at birth
SCABIES
CLINICAL MANIFESTATIONS
▪ GLUT 1 positive
▪ If with >5 cutaneous IH, do abdominal PE and liver UTZ to detect
liver IH
▪ Red or blue hued with telangiectasia
▪ May have a ring of pallor
▪ Does not undergo further growth
● Non-involuting CH – stay stable
● Rapidly involuting CH – rapidly decrease in size → fibrofatty
residual tissue
● Partially involuting CH – decrease in size to a certain point
then remain stable instead of resolving completely
▪ Intense pruritus, particularly at night
▪ 1st sign of infestation: 1-2mm red papules, some excoriated,
crusted, or scaling
▪ Classic lesion: threadlike burrows – may not be seen in infants
(bullae and pustules); virtually pathognomonic of human scabies
▪ Wheals, papules, vesicles, superimposed eczematous dermatitis
▪ Infants: diffuse eczematous eruption in the scalp, neck, face
▪ Young children: palms, soles, and scalp
▪ Older children and adults: interdigital spaces, wrist flexors,
anterior axillary folds, ankles, buttocks, umbilicus, belt line, groin,
genitals (men), areola (women); Head, neck, palms, and soles are
generally spared
Nodular Scabies
▪ less common variant
▪ red-brown nodules in covered areas (axilla, groin, genitals)
TREATMENT
▪ Expectant observation if without extensive growth/severe
disfigurement
▪ Topical Timolol solution 1 drop BID
▪ Oral propranolol 1-3mkday – 1st line treatment for disfiguring,
life- or vision-threatening, or ulcerated IH
● If <8wks old, inpatient initiation of treatment – start at
1mkday TID with HR & BP monitoring 1&2h after each dose →
increase to 2mkday TID
● If OP treatment (has good social support & access to
hospital), start at 1mkday. If tolerated for 3-7days, increase to
1.5mkday → 2mkday.
● Risks: Hypoglycemia, bradycardia, hypotension, GERD,
hyperK, bronchospasm/wheezing, worsening of existing disease
▪ Systemic corticosteroids – if unable to tolerate propranolol or
has not responded after weeks of treatment
▪ Intralesional CS injection – rapid involution of IH; risks:
ulceration, tissue atrophy, blindness (if used near the orbit)
▪ Systemic propranolol
▪ Good prognosis, low morbidity
DDx: Multifocal lymphangioendotheliomatosis
▪ Vascular tumors in the skin and visceral organs
▪ GLUT 1 negative
▪ (+) Severe thrombocytopenia and GI bleeding
▪ High mortality rate
▪ GLUT 1 negative
DIFFERENTIAL DIAGNOSIS
▪ Papulovesicular – popular urticaria, canine scabies, chickenpox,
viral exanthems, drug eruptions, dermatitis herpetiformis,
folliculitis
▪ Eczematous – atopic dermatitis, seborrheic dermatitis
▪ Nodular scabies – urticaria pigmentosa, Langerhans cell
histiocytosis
COMPLICATIONS
If untreated → eczematous dermatitis, impetigo, ecthyma,
folliculitis, furunculosis, cellulitis, lymphangitis, id reaction
▪ Permethrin 5% cream – treatment of choice
● Apply to entire body from the neck down, leave on for 812hrs, reapply after 1 week
● In infants <2yo, apply also in the scalp if with lesions above
the neck
▪ Sulfur ointment 5-10%, Crotamiton 10% lotion or cream
▪ Ivermectin – 200mcg/kg/dose PO for 2 doses 2wks apart; for
severe infestations or in immunocompromised patients
▪ Treat the whole family
▪ Wash clothing, bed linens, and towels in hot water & dry using
high heat
▪ If other items cannot be washed, dry clean or store in bags for 37 days
OUTCOME
▪ Transmission of mites is unlikely >24h after treatment
▪ If pruritus persists for days to weeks, may be alleviated by topical
Batch Clingy
DISEASE
7
PEDICULOSIS
▪ Thickened and dystrophic nails
▪ Generalized lymohadenopathy
▪ Eosinophilia
CANINE SCABIES
▪ Caused by S. scabei var canis (dog mite)
▪ Acquired by cuddling an infested puppy
▪ Sudden onset, usually 1-10 days after exposure
▪ Secondary to the development of a hypersensitivity reaction to
mite antigens
▪ Most common in infants and young children (<5yo)
▪ Caused by phage group 2 staphylococci strains 71 and 55
▪ Foci of infection: nasopharynx, umbilicus, urinary tract,
superficial abrasion, conjunctivae, blood
▪ Hematogenous spread in the absence of specific antitoxin Ab of
staphylococcal epidermolytic or exfoliative toxins A or B
▪ Tiny papules, vesicles, wheals, and excoriated eczematous
plaques in the arms, chest, abdomen
▪ Burrows are not present – the mite infrequently inhabits the
human s. corneum
▪ (+) Pruritus
▪ Localized bullous impetigo to generalized cutaneous
involvement with systemic illness
▪ Rash may be preceded by malaise, fever, irritability, exquisite
tenderness of the skin
▪ Scarlatiniform erythema – accentuated in the flexural areas
▪ Inflamed, occasionally purulent, conjunctivae
▪ Circumoral erythema; Radial crusting and fissuring around the
eyes, mouth, nose
▪ Nikolsky sign - denudation of skin with gentle tangential
pressure
▪ Brightly erythematous skin → desquamative phase after 25days → healing without scarring in 10-14 days
▪ Pharyngitis, conjunctivitis, superficial erosions of the lips,
intraoral mucosal surfaces are spared
▪ Massive orthokeratosis and parakeratosis with numerous
interspersed mites
▪ Psoriasiform epidermal hyperplasia, foci of spongiosis,
neutrophilic abscesses
▪ Self-limited since humans are not a suitable host
▪ Bathe and change clothes
▪ Remove or treat the infested animal
▪ Symptomatic therapy for the pruritus
Skin Biopsy:
▪ Subcorneal, granular layer split
▪ Absence of an inflammatory infiltrate
▪ Semisynthetic antistaphylococcal penicillin (e.g. nafcillin)
▪ First-generation cephalosporin (e.g. cefazolin)
▪ Clindamycin – used in addition to other agents
▪ Vancomycin – if considering MRSA
▪ Always clean and gently moisten the skin
▪ Emollients – lubrication, decreases discomfort
▪ Recovery is usually rapid
COMPLICATIONS
▪ Excessive fluid loss, electrolyte imbalance
▪ Faulty temperature regulation
▪ Pneumonia, septicemia, cellulitis
▪ Head and pubic lice deposit 3-10eggs/day on the human host
▪ Body lice lay eggs in or near the seams of clothing, the ova or nits are glued to hairs or fibers of clothing but not directly on the body
▪ Laying of eggs → ova hatch in 1-2wks → mature in 1wk → larvae die unless a meal is obtained w/in 24h & every few days thereafter → nymphs and adult lice feed on human blood, inject their salivary juice into the host, deposit fecal matter on the skin
▪ Hallmark: pruritus
Pediculosis humanus corporis
▪ Small, intensely pruritic, red macule or papule with a central
▪ Improved hygiene
▪ Body/clothing lice; vector of human disease (typhus, trench
hemorrhagic punctum
▪ Hot water laundering of all infested clothing and bedding
fever, relapsing fever)
▪ Shoulders, trunk, or buttocks
▪ Uniform temp of 65oC for 15-30mins kills all eggs and lice
▪ Vagabond’s skin – if chronic; lichenified, scaling,
hyperpigmented plaques, often on the trunk
Pediculosis humanus capitis
▪ Translucent 0.5mm eggs near the proximal portion of the hair
▪ Malathion 0.5% in isopropanol
▪ Head lice
shaft that are adherent to one side of the shaft and cannot be
● Treatment of choice for resistance to pyrethroids; apply to
▪ Most common form of lice to affect children between 3-12 yo
moved along or knocked off the hair shaft with the fingers
dry hair until hair and scalp are wet, leave on for 12h. Reapply
▪ Modes of transmission: fomites, head-to-head contact, and
▪ Lice are not always visible, but nits are detectable on the hair
after 7-9days if necessary.
shared combs, brushes, towels
most commonly in the occipital region and above the ears
● Not for use in neonates and infants
▪ Secondary pyoderma (due to trauma from scratching) → hair
▪ Spinosad/Benzyl alcohol lotion – if >6mos old
loss
▪ Ivermectin – for difficult-to-treat head lice
▪ Matting together of the hair
▪ Cervical and occipital lymphadenopathy
▪ Treat all household members at the same time
▪ Dermatitis on the neck and pinnae
▪ Remove nits with a fine-toothed comb after application of a
▪ Id reaction – erythematous patches and plaques on the trunk
damp towel to the scalp for 30mins
▪ Launder clothing and bed linens in very hot (>130oF) water then
dry for at least 10mins at the highest setting
▪ Discard brushes and combs or coat with a pediculicide for 15mins
PPS Oral Exam Reviewer 2020
Batch Clingy
STAPHYLOCOCCAL
SCALDED SKIN
SYNDROME (Ritter
Disease)
NORWEGIAN (CRUSTED) SCABIES
▪ Highly contagious
▪ Occurs in those who are cognitively and physically debilitated,
has Down syndrome, poor cutaneous sensation (e.g. leprosy,
spina bifida), severe systemic illness (leukemia, DM), and
immunosuppressed (HIV)
▪ Mites inhabit the crusts and exfoliating scales of the skin and
scalp
corticosteroids.
▪ If >2wks still with pruritus & new lesions, reexamine for mites
▪ Scrupulous isolation measures
▪ Removal of the thick scales
▪ Repeated and careful application of permethrin 5% cream
▪ Ivermectin (200-250mcg/kg) x 1 dose in refractory patients
8
Phthirus pubis
▪ Pubic or crab lice
▪ Modes of transmission: skin-to-skin, sexual contact
▪ Common in adolescents
MOLLUSCUM
CONTAGIOSUM
▪ Poxvirus – has three types, type 1 causes most infections
▪ Acquired by direct contact or from fomites
▪ Spread by autoinoculation
▪ Otherwise well children aged 2-6yrs and those who are
immunosuppressed
▪ 80% of cases
▪ Most common precipitant: DRUGS – sulfonamides, NSAIDs,
antibiotics, anticonvulsants
▪ Affected BSA <10%
▪ Drug-specific CD8 cytotoxic T cells, perforin/granzyme B, and
granulysin trigger keratinocyte apoptosis → expanded enactment
of apoptosis
STEVEN- JOHNSON
SYNDROME
▪ Moderate to severe pruritus
▪ Secondary pyoderma from scratching
▪ Shallow excoriations
▪ Maculae cerulae – steel-gray spots <1cm in diameter on the
pubic area, chest, abdomen, thighs
▪ Oval translucent nits firmly attached to the hair shaft
▪ Grittiness when the fingers are run through infested hair
▪ Examine the trunk, thighs, axilla, beard, and eyelashes too since
pubic lice may wander or be transferred to other sites on fomites
▪ Incubation period: ≥2 weeks
▪ 1-5mm discrete, pearly, skin-colored, smooth, dome-shaped,
papules sometimes with mild surrounding erythema or an
eczematous dermatitis
▪ Has a central umbilication from which a plug of cheese material
can be expressed
▪ Anywhere in the body, commonly in the face, eyelids, neck,
axillae, thighs
▪ In adolescents, may be found in clusters on the genitals or in
the groin (may be associated with venereal dse if sexually active)
▪ Lesions may be preceded by a flulike URT illness
▪ Erythematous macules that rapidly and variably develop central
necrosis → vesicles, bullae, areas of denudation on the face,
trunk, extremities
▪ Accompanied by involvement of ≥2 mucosal surfaces – eyes,
oral cavity, upper airway or esophagus, GIT, anogenital mucosa
▪ Burning sensation, edema, and erythema of the lips and buccal
mucosa → bullae, ulceration, hemorrhagic crusting
▪ Often, severe pain from mucosal ulceration
▪ Minimal to absent skin tenderness
▪ Disseminated cutaneous bullae and erosions → increased
insensible fluid loss → high risk for bacterial superinfection and
sepsis
then thoroughly clean in boiling water
▪ If object cannot be washed, seal it in a plastic bag for 48 hours
▪ 10-min application of a pyrethrin preparation. Retreat after 7-10
days if necessary.
▪ Petrolatum 3-5x/day for 8-10 days in on the eye lashes
▪ Thoroughly launder or dry clean clothing, towels, and bed linens
▪ Self-limited
▪ Average attack lasts 6-9 months but can persist for years, can
spread to distant sites, and may be transmitted to others
▪ Avoid shared baths and towels
▪ Immunotherapy with either candida or trichophyton antigen
every 4 weeks until resolution
▪ Liquid nitrogen cryotherapy
▪ Leukocytosis
▪ Elevated ESR
▪ Occasionally, increased LFTs and decreased serum albumin
SJS-TEN Overlap Syndrome
▪ 10-30% BSA
Toxic Epidermal Necrolysis
▪ >30% BSA
▪ Most severe disorder of the spectrum
▪ Widespread blister formation & morbilliform confluent erythema
with skin tenderness
▪ Nikolsky sign in areas of erythema
Other DDx:
▪ Urticaria, M. pneumoniae-associated mucositis, drug rash w/
eosinophilia & systemic symptoms (DRESS) syndrome, viral
exanthems (e.g. KD)
▪ Mgt is supportive and symptomatic
▪ Discontinue offending drug as soon as possible
▪ Ophthalmologic exam
▪ Cryopreserved amniotic membrane – applied to the ocular
surface during the acute phase to limit destruction & prevent long
term sequelae
▪ Topical steroid for the eyes
▪ Mouthwash and glycerin swabs – oral lesions
▪ Topical (oral) anesthetics before eating for pain relief
▪ Saline or burrow solution compresses – for denuded skin lesions
▪ Observe vaginal lesions closely
▪ Complete healing may take 4-6 weeks
▪ Some may require ICU admission
▪ Systemic antibiotics for documented urinary/cutaneous
infections & for suspected bacteremia (S. aureus/P. aeruginosa)
▪ IVIg 1.5-2g/kg/day for 3 days
Batch Clingy
COMPLICATIONS
▪ Corneal ulceration, anterior uveitis, panophthalmitis
▪ Bronchitis, pneumonitis, myocarditis, hepatitis, enterocolitis
▪ Polyarthritis, hematuria, ATN → renal failure
▪ Strictures of the esophagus, bronchi, vagina, urethra, anus
PPS Oral Exam Reviewer 2020
9
Acute
ETIOLOGY/INCIDENCE/ PATHOGENESIS
▪ Infection and inflammation of loose connective tissue, limited
dermal involvement, sparing of the epidermis
▪ Secondary to a break in the skin for previous trauma, surgery, or
an underlying skin lesion
▪ Most common etiologic agents: S. aureus, S. pyogenes (GAS)
▪ In immunocompromised, may be caused by P. aeruginosa,
Aeromonas hydrophila, Enterobacteriaciae, Legionella spp., etc
CLINICAL MANIFESTATIONS
▪ Localized area of edema, warmth, erythema, and tenderness
▪ Indistinct lateral margins
▪ May produce pitting when pressure is applied
▪ Regional adenopathy and constitutional SSx (fever, chills,
malaise)
▪ S. aureus – more localized and may suppurate
▪ S. pyogenes – spread more rapidly, may be associated with
lymphangitis
LABORATORY FINDINGS/DIAGNOSIS
▪ In the neonate, do blood CS, LP
▪ Do blood CS if:
● < 1 year old
● (+) Signs of systemic toxicity
● An adequate examination cannot be carried out
● Immunocompromised
▪ Aspirate from the point of maximum inflammation
▪ Ultrasonography
DIFFERENTIAL DIAGNOSIS
▪ Skeeter Syndrome – swelling disproportionate to erythema, has
pruritus, no tenderness
▪ Cold Panniculitis – erythematous, nontender swelling after cold
exposure
CELLULITIS
COMPLICATIONS
▪ Subcutaneous abscess, bacteremia, osteomyelitis, septic
arthritis, thrombophlebitis, endocarditis, necrotizing fasciitis
ABSCESS
▪ S. aureus –
penetrates abraded
perifollicular skin
NECROTIZING
FASCIITIS
FURUNCLE (Boil)
▪ Risk Factors: obesity, hyperhidrosis, maceration, friction,
preexisting dermatitis
▪ More common in those with low serum iron levels, diabetes,
malnutrition, HIV infection, or other immunodeficiency states
▪ Recurrent furunculosis
● Carriage of S. aureus in the nares, axillae, or perineum, or
close contact with someone who is a carrier
CARBUNCLE
▪ Infection of a group of contiguous follicles accompanied by
inflammatory changes in surrounding tissues
▪ Occur in any location, most common on the lower abdomen,
buttocks, and legs
▪ Subcutaneous tissue infection, involves the deep layer of
superficial fascia
▪ Polymicrobial, approx. 4 differential organisms
▪ Most common: S. aureus, Streptococcal sp., Klebsiella sp., E.
coli, anaerobes
▪ Occur anywhere on the body, mostly perineum and trunk
▪ Most common in the immunocompromised – DM, neoplasia,
post-surgery, on IV drugs, on immunosuppressive treatment
(steroids)
▪ Can occur in healthy people – after minor puncture wounds,
blunt trauma, surgery (abdomen, GIT, GUT, perineum)
▪ Skin changes may appear over 24 – 48hrs as nutrient vessels are
thrombosed and cutaneous ischemia develops
▪ Acute onset of local or tense, edema, erythema, tenderness,
heat
▪ Fever, pain, & tenderness disproportionate to cutaneous signs
▪ (+/-) Lymphangitis and lymphadenitis
▪ Bullae formation (straw-colored → bluish → hemorrhagic fluid)
▪ Darkening of affected tissues (red → purple → blue)
▪ Skin anesthesia
▪ Frank tissue gangrene and slough
▪ Ominous signs of advanced disease: vesicles, bullae,
PPS Oral Exam Reviewer 2020
Infants and children >2mo with mild to moderate infections:
▪ PO as OP with a penicillinase-resistant penicillin (dicloxacillin) or a
1st generation cephalosporin (cefalexin), or clindamycin → shift to
IV if no improvement or with significant progression in the 1st 2448h of therapy
Infants and children >2mo with signs of systemic infection:
▪ Clindamycin or 1st gen cephalosporin (cefazolin)
Unimmunized patients:
▪ Include a 3rd gen cephalosporin (cefepime, ceftriaxone,
cefotaxime) or a β-lactam/ β-lactamase inhibitor combination
(AmpiSul) to cover for H. influenzae type b & S. pneumoniae
▪ Once erythema, warmth, edema, and fever have significantly
decreased, complete a 5- to 7-day total course of treatment
▪ Regular bathing with antimicrobial soaps (chlorhexidine)
▪ Wear loose-fitting clothing
▪ Frequent hot, moist compress – facilitate drainage of lesions
▪ Large lesions should be drained by a small incision
▪ Systemic antibiotics – for carbuncles or large/numerous furuncles
▪ Deep-seated, tender, erythematous, perifollicular nodule →
central necrosis and suppuration → rupture, discharge of a
central core of necrotic tissue and destruction of the follicle →
scar formation
▪ Sites of predilection: hair-bearing areas on the face, neck,
axillae, buttocks, groin
▪ Intense pain if the lesion is in an area where the skin is relatively
fixed (i.e. EAC, nasal cartilage)
▪ May be accompanied by fever, leukocytosis, and bacteremia
ABSCESS
▪ Community-acquired MRSA abscesses can complicate folliculitis
▪ Infection can be spread by crowding conditions, shared personal
hygiene items, and a compromised skin barrier
TREATMENT
Neonates:
▪ IV antibiotics – β-lactamase stable antistaphylococcal antibiotic
(nafcillin), Cefazolin, Vancomycin, + aminoglycoside (gentamicin) or
a 3rd generation cephalosporin (cefotaxime)
▪ Mupirocin intranasally BID for 5d + Clorhexidine (in lieu of soap)
or Diluted bleach baths (1tsp/gallon of water or ¼ cup per ¼ tub)
QD for 5d
● To reduce colonization (and hence reinfection) in patients and
in family members
▪ Definitive diagnosis is made by surgical exploration – gray
necrotic fascia and subcutaneous tissue with little resistance on
blunt probing
▪ CT and MRI – aid in delineating the extent and tissue planes of
involvement
▪ Frozen section incisional biopsy
COMPLICATIONS
▪ Compartment Syndrome – tight edema, pain on motion, loss of
distal sensation and pulses; 6P’s (pain, poikilothermia, paresthesia,
paralysis, pulselessness, pallor)
▪ Recolonization often occurs within 3mos of decolonization
attempt
▪ Incision and drainage + oral antibiotics (7-10 days)
▪ Antibiotics (w/ MRSA coverage is recommended):
● Clindamycin 10-30mkday
● TMP-SMX 8-12mkday based on TMP content
● If >8yo, may give Doxycycline
▪ Remove all devitalized tissues, repeat exploration within 24-36h
to confirm that no necrotic tissue remains
▪ Empiric antibiotic therapy
● Gram (+) – vancomycin, linezolid, or daptomycin
● Gram (-) – piperacillin-tazobactam
● May add ceftriaxone/metronidazole to cover mixed aerobicanaerobic organisms
▪ Penicillin + clindamycin – for GAS or Clostridium spp.
▪ Doxycycline + Cipro/Ceftaz – V. vulnificus
▪ Continue antibiotics for at least 5 days after resolution of SSx
Batch Clingy
DISEASE
10
▪ Rare acute GAS infection of the deeper layers of the skin and the
underlying connective tissue
ERYSIPELAS
IMPETIGO
(Pyoderma)
▪ Most common form of extrapulmonary TB in children
▪ Occur within 6-9months of initial infection by MTB
▪ Tonsillar, anterior cervical, submandibular, supraclavicular nodes
– extension of a 1o lesion of the ULF or abdomen
▪ Inguinal, epitrochlear, axillary LNs – from regional lymphadenitis
associated with TB of the skin or skeletal system
▪ Discrete, nontender, firm, but not hard LN that gradually enlarge
→ multiple LNs are infected → matted nodes
▪ Nodes feel fixed to underlying or overlying tissue
▪ Often unilateral → bilateral 2o to crossover drainage patterns of
lymphatic vessels in the chest and lower neck
▪ Reactive TST
▪ Normal CXR in 70% of cases
▪ Acute onset, rapid enlargement, tenderness, and fluctuance of
LN, with high fever
▪ Ruptured node → draining sinus tract
▪ Typical duration of treatment is 4 weeks
▪ Culture thru needle aspirate of the advancing margin of the
inflamed area
DIFFERENTIAL DIAGNOSIS
▪ HSV, VZV, Tinea corporis, kerion, arthropod bites, scabies,
pediculosis capitis
DIFFERENTIAL DIAGNOSIS
▪ Neonates: Epidermolysis bullosa, bullous mastocytosis, herpetic
infection, early SSSS
▪ Older Children: Allergic contact dermatitis, burns, erythema
multiforme, linear IgA dermatosis, pemphigus, bullous pemphigoid
▪ Definitive diagnosis requires histologic or bacteriologic
confirmation best accomplished by fine needle aspiration for
culture, stain, and histology
▪ If FNA is unsuccessful, do excisional biopsy
▪ Mupirocin 2% – apply 2-3x/day for 10-14days, localized staph
infection
▪ Cephalexin 25-50mkday 3-4x/day for 7days:
● Streptococcal infection
● Widespread staph infection
● Lesions near the mouth, where topical medicationss may be
licked off
● Evidence of deep involvement – cellulitis, furunculosis,
abscess, suppurative lymphadenitis
▪ Do a blood CS
▪ If MRSA, give clindamycin, doxycycline, or TMP-SMX
COMPLICATIONS
▪ Bacteremia with subsequent osteomyelitis, septic arthritis,
pneumonia, septicemia
▪ Cellulitis – nonbullous impetigo
▪ Lymphangitis, suppurative lymphadenitis, guttate psoriasis,
scarlet fever – streptococcal disease
▪ Acute PSGN – nephritogenic strains of GABHS; common in
children 3-7 years old 18-21 days after the skin infection
▪ Can resolve if left untreated but often progresses to caseation
and necrosis
▪ Anti-Koch’s therapy, same regimen as PTB (2HRZE, 4HR)
▪ Responds well to anti-Koch’s but LN do not return to normal size
for months or years
DIFFERENTIAL DIAGNOSIS
▪ Infection caused by nontuberculous mycobacteria
▪ Cat scratch disease, tularemia, brucellosis, toxoplasmosis,
pyogenic infection
▪ Non-infectious causes: Tumor, brachial cleft cyst, cystic hygroma
Batch Clingy
SCROFULA
▪ Most common skin infection in children throughout the world
NONBULLOUS IMPETIGO
▪ >70% of cases
▪ Predominant organism: S. aureus; may be caused by GABHS
▪ Staph spread from nose to normal skin then infect the sk
▪ GABHS colonizes the skin 10d before the dev’t of impetigo
▪ May be spread to other parts of the body by fingers, clothing,
towels
BULLOUS IMPETIGO
▪ Always caused by S. aureus strains that produce exfoliative toxins
(ETA, ETB, ETD)
▪ Toxins blister the superficial epidermis
▪ Infants and young children
ecchymoses, crepitus, anesthesia, necrosis
▪ May be accompanied by significant systemic toxicity – shock,
organ failure, death
▪ Swollen, red, very tender skin
▪ May have superficial blebs
▪ Occasional reddish streaks of lymphangitis projecting out from
the margins of the lesion
▪ Abrupt onset with SSx of systemic infection (high fever)
▪ Lesions begin on the face or extremities that have been
traumatized (insect bites, abrasions, lacerations, chickenpox,
scabies, pediculosis, burns)
▪ Tiny vesicle/pustule → honey-colored crusted plaque
▪ Lesions have little to no pain or surrounding erythema
▪ Occasional pruritus
▪ Regional adenopathy (90%)
▪ Leukocytosis (50%)
▪ Flaccid, transparent bullae on the face, buttocks, trunk,
perineum, extremities
▪ Bullae rupture easily → Narrow rim of scale at the edge of
shallow, moist erosion
▪ (-) Adenopathy and surrounding erythema
Neonatal Bullous Impetigo – can begin in the diaper area
PPS Oral Exam Reviewer 2020
11
Acute
ETIOLOGY/INCIDENCE/ PATHOGENESIS
OPHTHALMIA NEONATORUM
▪ Infants <4mos of age
▪ Most common eye disease of newborns
▪ Acquired during vaginal delivery
▪ Etiologic Agents:
● N. gonorrhea – incubation period: 2-5 days
● C. trachomatis – incubation period: 5-14 days
● P. aeruginosa – acquired in the nursery, potentially serious
▪ May be caused by silver nitrate instillation (mild, self-limited)
▪ Potentially blinding
CLINICAL MANIFESTATIONS
▪ Redness and chemosis (swelling) of the conjunctiva, edema of
the eyelids, discharge (may be purulent)
▪ Inflammation caused by silver nitrate occurs within 6-12h after
birth, clears by 24-48h
LABORATORY FINDINGS/ DIFFERENTIAL DIAGNOSIS
▪ Conjunctivitis appearing after 48h should be evaluated for an
infectious cause – gram stain and culture
N. gonorrhea
▪ Mild inflammation, serosanguineous discharge → thick and
purulent in 24hrs → edema of the eyelids, marked chemosis
▪ Gram negative diplococci
C. trachomatis
▪ Mild inflammation to severe swelling of the eyelids, copious
purulent discharge
▪ Mainly involves the tarsal conjunctivae, rarely affects the cornea
CONJUNCTIVITIS
ACUTE PURULENT CONJUNCTIVITIS
▪ EA: nontypeable H. influenzae (60-80% associated with ipsilateral
OM), pneumoccocci (20%), staphylococci (5-10%)
P. aeruginosa
▪ Days 5-18 of edema, erythema of the lids, purulent discharge,
pannus formation, endophthalmitis, sepsis, shock, death
▪ Generalized (in 50-75%) conjunctival hyperemia, edema,
mucopurulent exudate, glued eyes, & ocular pain and discomfort
▪ Little or no pruritus or periauricular LN enlargement
VIRAL CONJUNCTIVITIS
▪ Occur more often in the summer and in older children (>5yo)
▪ Adenovirus – sometimes with pharyngitis/pneumonia
▪ Enterovirus – often hemorrhagic
▪ Watery discharge
▪ Follicular changes (small aggregates of lymphocytes) in the
palpebral conjunctiva
▪ Often unilateral, often with periauricular nodes
EPIDEMIC KERATOCONJUNCTIVITIS
▪ Adenovirus serotypes 8, 19, 37
▪ Transmitted by direct contact
▪ Foreign body sensation beneath the lids, itching, burning
▪ Edema (chemosis), photophobia, large oval follicles within the
conjunctiva
▪ Preauricular adenopathy, pseudomembrane on the conjunctival
surface
▪ Subepithelial corneal infiltrates → blurring of vision (usually
disappear but may permanently reduce VA)
▪ May have associated URTI and pharyngitis
▪ Fibrin-rich exudate forms on the conjunctival surface and
permeates the epithelium
▪ Membrane is removed with difficulty and leaves raw bleeding
areas
▪ The layer of fibrin-rich exudate is superficial and can be stripped
easily, leaving the surface smooth
MEMBRANOUS CONJUNCTIVITIS
▪ Classic: Diphtheria
PSEUDOMEMBRANOUS CONJUNCTIVITIS
▪ Occurs in various bacterial and viral infections – staphylococcal,
pneumococcal, streptococcal, or chlamydial conjunctivitis;
epidemic keratoconjunctivitis, vernal conjunctivitis, SJS
PPS Oral Exam Reviewer 2020
Differential Diagnosis:
▪ Dacryocystitis – caused by NLDO with lacrimal sac distention
▪ Intracytoplasmic inclusions in Giemsa-stained epithelial cells
scraped from the tarsal conjunctivae (immunofluorescent staining,
chlamydial antigen/DNA)
▪ Hyperacute Bacterial Conjunctivitis
● Caused by gonococcal or meningococcal infection
● Treat with systemic antimicrobials
TREATMENT/ COMPLICATIONS/PREVENTION
PREVENTION
▪ 0.5% erythromycin or 1% silver nitrate drops at birth
▪ 2% povidone iodine may be given especially in developing
countries
▪ Prenatal screening and treatment of maternal gonorrhea
● If untreated, give infant Ceftriaxone 50mg/kg x 1dose IV/IM
(max 125mg, decrease dose If preterm)
● If mother’s isolate is penicillin sensitive, give infant Penicillin
50,000 units
▪ Ceftriaxone 25-50mkday x 1dose IV/IM (not to exceed 125mg)
▪ Eye irrigation with saline q10-30mins increasing to 2h intervals
until the purulent discharge has cleared
COMPLICATIONS
▪ Corneal ulceration and perforation, iridocyclitis, anterior
synechiae, panophthalmitis
▪ Erythromycin 50mkday QID PO for 2weeks – cures conjunctivitis
and prevents chlamydial pneumonia
COMPLICATION
Chlamydial Pneumonia (10-20%)
▪ Systemic antibiotics + aminoglycoside
▪ Local saline irrigation
▪ Gentamicin ophthalmic ointment
▪ Warm compress
▪ Topical antibiotics (Table 644.2):
● Aminoglycosides – gentamicin, tobramycin
● Quinolones – ciprofloxacin, ofloxacin, moxifloxacin
▪ Self-limited
▪ Acute Hemorrhagic Conjunctivitis
● Enterovirus CA 24 or 70
● Red, swollen, painful eyes with a hemorrhagic watery
discharge
▪ Prevention is key
▪ Pharyngoconjunctival Fever
● High fever, pharyngitis, bilateral conjunctivitis, periauricular
lymphadenopathy
● Highly contagious
Batch Clingy
DISEASE
12
ALLERGIC CONJUNCTIVITIS
▪ Seasonal (spring – summer)
▪ Intense itching, clear watery discharge, chemosis
VERNAL CONJUNCTIVITIS
▪ Begins in the prepubertal years
▪ May recur for many years
▪ Extreme itching and tearing
▪ Large, flattened, cobblestone-like papillary lesions of the
palpebral conjunctivae
▪ Stringy exudate, milky conjunctival pseudomembrane
▪ Horner – Trantas Dots – small elevated lesions of the bulbar
conjunctivae adjacent to the limbus
▪ Hallmarks: lymphadenopathy and conjunctivitis
PARINAUD OCULOGLANDULAR SYNDROME
▪ Bartonella henselae, transmitted from cat to cat by fleas (kittens
are more likely than adult cats to be infected)
▪ Humans can become infected when scratched by a cat or may
pass from a cat’s saliva to its fur during grooming
CHEMICAL CONJUNCTIVITIS
▪ Occurs when an irritating substance enters the conjunctival sac –
household cleaning substances, sprays, smoke, smog, metal halide
bulbs, industrial pollutants
▪ Alkalis – linger in the conjunctival tissues and continue to inflict
damage for hours or days
▪ Acid – precipitate the proteins in tissues; produce their effect
immediately
▪ Inflammation of the tissues of the orbit
▪ Mean age: 6.8 years (1wk – 16yo)
▪ Boys > girls (2:1)
▪ EA: GAS, anaerobes, S. aureus, S. pneumoniae, Haemophilus sp.
▪ Direct infection of the orbit from a wound
▪ Hematogenous seeding of organisms during bacteremia
▪ Often, direct extension or venous spread of infection from
contiguous sites – lids, conjunctiva, globe, lacrimal gland,
nasolacrimal sac, paranasal (ethmoid) sinuses
▪ Spread of infection to the orbit from the sinuses is more
prevalent in children due to:
● Thinner bony septa and sinus wall
● Greater porosity of bones
● Open suture lines
● Larger vascular foramina
▪ Spread of infection is facilitated by the venous and lymphatic
communication between the sinuses and surrounding structures
which allow flow in either direction, facilitating retrograde
thrombophlebitis
▪ Self-limited
▪ Thorough and copious irrigation
COMPLICATION
Extensive tissue damage and loss of the eye – especially if alkali
▪ TRIAD: proptosis, pain limited eye movement, decreased VA
▪ Chemosis, inflammation, and swelling of the eyelids
▪ Feels ill, febrile, appear toxic
▪ Leukocytosis
▪ Increased suspicion for intracranial extension if with HA,
vomiting, or focal neurologic deficit
▪ CT Scan with contrast of the orbit and paranasal sinuses
▪ Additional brain imaging if indicated
▪ Lumbar puncture – if with meningitis presentation provided
there is no sign of ↑ICP or FND
DIFFERENTIAL DIAGNOSIS
Idiopathic
orbital
inflammation,
myositis,
sarcoidosis,
granulomatous vasculitis, leukemia, lymphoma, histiocytic
disorders, rhabdomyosarcoma, ruptured dermoid cyst, orbital
trauma, orbital foreign body, primary/metastatic tumor in the
orbit
▪ Systemic antibiotic therapy: Ampicillin Sulbactam or
Clindamycin + Ceftriaxone, Cefepime (or Cefotaxime)
▪ If with suspicion of intracranial extension, Vancomycin +
Cefotaxime (or Ceftriaxone) + Metronidazole
▪ If without signs of improvement or if with signs of progression,
consider sinus drainage
▪ Orbital or subperiosteal abscess may require urgent drainage of
the orbit
▪ If <9yo with medial subperiosteal abscess, treat with IV
antibiotics then monitor q6 for signs of visual deterioration or
pupillary abnormalities. If with development of such, do drainage
COMPLICATIONS
▪ Visual loss secondary to ↑ orbital pressure that causes retinal
artery occlusion/optic neuritis
▪ Cavernous sinus thrombosis
▪ Meningitis, epidural/subdural empyema, brain abscess
▪ Optic atrophy, exposure keratitis, retinal/choroidal ischemia
Batch Clingy
ORBITAL
CELLULITIS
▪ Smear of the exudate – (+) eosinophils
▪ Cold compress
▪ Topical antihistamine drops for symptomatic relief
▪ Topical mast cell stabilizers or prostaglandin inhibitors
▪ Topical corticosteroid therapy
▪ Cold compress
▪ Topical mast cell stabilizers or prostaglandin inhibitors – when
long-term control is needed
PPS Oral Exam Reviewer 2020
13
Acute
ETIOLOGY/INCIDENCE/ PATHOGENESIS
▪ Most common cause of acquired hearing loss in children
▪ 1st 2yrs of life (most common at 6-20mos of age) – due to
less well-developed immunologic defenses and less favorable
eustachian tubal factors
▪ Boys > girls
Risk Factors:
▪ Poverty – crowding, limited hygienic facilities, suboptimal
nutritional facilities, limited access to medical care, limited
resources to buy meds
▪ Tobacco smoke exposure
▪ Repeated exposure to other children
▪ Season – cold weather months
▪ Congenital anomalies
● Unrepaired palatal clefts, submucous cleft palate, other
craniofacial anomalies, Down syndrome
● Due to deficiency in eustachian tube function (muscular
changes, tubal compliance, defective velopharyngeal valving)
→ disturbed aerodynamic and hydrodynamic relationships in
the nasopharynx and proximal portions of the tubes
▪ Pacifier use, bottle feeding in the recumbent position
▪ HIV infection – high risk of recurrent OM
▪ Breastmilk has a protective effect
OTITIS MEDIA
Pathogenesis
▪ Hypertrophied NP adenoid tissue/tumor or inflammatory
edema of the tubal mucosa (2o to a viral URTI) → eustachian
tube obstruction → inflammatory process – secretory
metaplasia, compromise of the mucociliary transport system,
effusion of liquid into the tympanic cavity → decreased
eustachian tube function (ventilation, protection, clearance)
● Protection and clearance – if the eustachian tube is
patulous or excessively compliant, it may fail to protect the
ME from reflux of infective NP secretions
● Mucociliary clearance – if impaired, contributes to
persistent infection
▪ Progressive ↓ in tubal wall compliance + maturation of the
innate immune system → ↓ occurrence of OM as they grow
older
CLINICAL MANIFESTATIONS
TM EXAMINATION
▪ Otoscopy
▪ Clearing the EAC
● Children’s ears are “self-cleaning” d/t squamous
migration of ear canal skin
● Cleaning with cotton-tipped swabs worsens
cerumen impaction
● If obscured by cerumen, remove using an ear
curette or gentle suction. If child is old enough to
cooperate (≥5yo), lavage then mechanically remove
TM FINDINGS
▪ Pars tensa – lower 2/3 of the TM
● Normally, pearly gray, slightly concave
● Abnormal: Full/bulging or extreme retraction
▪ Pars flaccida – more vascular in nature
▪ Normally, the TM is translucent with some degree of
opacity in the 1st few MOL
▪ If with later opacification/abnormal whiteness, (+)
scarring or underlying effusion
▪ Erythema – if alone and not intense, may be from
crying/vascular flushing
▪ If with a persistent focal white area – congenital
cholesteatoma
▪ Mobility
● Most sensitive and specific in determining the
presence or absence of MEE
● Total absence of mobility – TM perforation after
an ↑ in ME pressure associated with effusion
● Substantial impairment of mobility – more
common finding in MEE if (-) perforation
▪ Bulging TM – most specific finding of AOM (97%) but
less specific (51%)
Signs of MEE (≥2 of the following)
▪ White, yellow, amber, or (rarely)
bluish TM
▪ Opacification not caused by scarring
▪ Decreased or absent mobility
LABORATORY FINDINGS/DIAGNOSIS
▪ Always distinguish between AOM & OME – dictates
treatment
Tympanometry (Acoustic Immittance Testing)
▪ Offers objective evidence of the presence/absence of MEE
but cannot distinguish the effusion of OME from AOM
▪ May supplement PE of difficult to examine patients
▪ Helps confirm, refine, or clarify questionable otoscopic
findings
▪ Type A curve
● Steep gradient, sharp-angled peak, ME air pressure that
approximates atmospheric pressure
● Normal ME status
▪ Type B curve (flat)
● (+) ME abnormality causing ↓ TM compliance
▪ Type C curve
● Intermediate findings – shallow peak, obtuse-angled peak,
or (-) ME air pressure peak
● May or may not be associated with MEE
● Nondiagnostic/equivocal with respect to OM
● Suggest eustachian tube dysfunction & some ongoing ME
pathology
Recurrent AOM
▪ 3x in 6mos or 4x in 12mos
Conjunctivitis – Associated OM
▪ Young children and infants
▪ Often present in multiple family members
▪ Simultaneous appearance of purulent and erythematous
conjunctivitis – 2o to nontypeable H. influenzae in most
children
▪ Topical ocular antibiotics are ineffective
Asymptomatic Purulent OM
▪ No overt signs + an obvious purulent MEE and bulging TM on
otoscopy
▪ Treat with antibiotics
PREVENTION
▪ Avoid exposure to individuals with respiratory infection
▪ Appropriate vaccination – pneumococcal & influenza
▪ Breast milk feeding
▪ Avoid environmental tobacco smoke
TREATMENT
▪ Most crucial aspect of OM treatment: accurate diagnosis
▪ Most episodes of OM will spontaneously resolve
▪ Assess the pain and treat it – Acetaminophen/Ibuprofen
Bacterial Resistance
▪ Greatest risk of resistance – <2yo, in regular contact with large groups of children, or
recently received antimicrobial treatment
INTRATEMPORAL COMPLICATIONS
▪ Infectious Dermatitis
● Contamination from purulent discharge from the ME → infection of the skin of the
EAC
● Erythematous, edematous, tender skin
● Mgt: proper hygiene + systemic antibiotics + otic drops
▪ TM Perforation
▪ Chronic Suppurative OM (CSOM)
● Persistent ME infection + discharge through a TM perforation
● EA: P. aeruginosa, S. aureus
● Treatment is guided by microbiologic results
● If without cholesteatoma, parenteral antibiotics + assiduous aural cleansing
● Tympanomastoidectomy for refractory cases
▪ Mastoiditis
▪ Facial Paralysis
● Uncommon, often resolves after IV antibiotics & myringotomy
● If present, requires urgent attention. Prolonged infection → permanent facial
paralysis
▪ Cholesteatoma – cyst like growth lined by keratinized, stratified squamous epithelium
containing desquamated epithelium and/or keratin
Acquired Cholesteatoma – 2o to long-standing chronic OM
● Progressive extension → bony resorption → extend into the mastoid cavity → extend
intracranially
● Often found in the superior part of the TM (pars flaccida)
● Otoscopy: area of TM retraction/perforation with white, caseous debris persistently
overlying the area
● Treatment: tympanomastoid surgery
Congenital Cholesteatoma
● 2o to epithelial inflammation in the ME space during otologic development in utero
● Often in the anterior-superior quadrant of the TM
● Discrete, white opacity in the ME space
● Tx: surgical resection
▪ Labyrinthitis
● Spread of infection from the ME and/or mastoid to the inner ear
● Usual source: cholesteatoma or CSOM
● Vertigo, tinnitus, nausea, vomiting, hearing loss, nystagmus, clumsiness
INTRACRANIAL COMPLICATIONS
▪ Meningitis, epidural/subdural abscess, focal encephalitis, brain abscess, sigmoid sinus
thrombosis, otitic hydrocephalus
▪ Develop through direct extension, hematogenous spread, or thrombophlebitis
▪ ME infection + any systemic symptom (high grade fever, HA, extreme lethargy) or
meningismus or any CNS sign
PPS Oral Exam Reviewer 2020
Batch Clingy
DISEASE
14
▪ If suspected, do imaging, LP, ME exudate culture
▪ Myringotomy with tympanostomy tube placement
▪ Otitic hydrocephalus
● Form of idiopathic intracranial HTN or pseudotumor cerebri
● ↑ICP without ventricular dilation occurring in association with acute/chronic OM or
mastoiditis
● MRI confirms the diagnosis
● Tx: Antibiotics + acetazolamide/furosemide + mastoidectomy, repeated LP,
lumboperitoneal shunt, VP shunt
● If untreated, loss of vision 2o to optic atrophy
ACUTE OTITIS MEDIA
▪ EA: nontypeable H. influenzae, S. pneumoniae, M.
catarrhalis, GAS, S. aureus, gram-negative organisms,
Alloicoccus otitidis
▪ S. aureus & gram-negative organisms – most common in
neonates and very young hospitalized infants
▪ Viral pathogens
● Rhinovirus, RSV, influenza, adenovirus, parainfluenza
● Sets the stage for bacterial invasion (if with respiratory
infection), amplifies the inflammatory process, interferes
with resolution of the bacterial infection; still uncertain
whether viruses alone can cause AOM
▪ Complication of bronchiolitis
▪ In young children, ear pain manifested as irritability,
change in sleeping/eating habits, holding/tugging at the
ear
▪ Fever may be present & is occasionally the only sign
▪ May have systemic symptoms & URTI symptoms
▪ Purulent otorrhea of recent onset
▪ Bullous myringitis – sign of AOM, not an etiologically
discrete entity
TM Findings
▪ Malleus may be obscured
▪ TM may resemble a bagel without a hole but with a
central depression
▪ TM may be obscured or have a cobblestone
appearance
▪ AOM Diagnosis (based on the AAP 2013 guidelines):
1)
Moderate to severe bulging of the TM or new onset
otorrhea not caused by otitis externa
2)
Mild bulging of the TM + recent (<48h) onset of ear
pain or intense TM erythema
A diagnosis of AOM should not be made in
a child without MEE.
▪ To support a diagnosis of AOM instead of OME in a child with
MEE:
1)
Distinct fullness/bulging of the TM may be present
± erythema, or at a minimum,
2)
MEE + ear pain that appears clinically important
Batch Clingy
▪ See alternative antibiotics in table 658.3
▪ Duration of treatment: 10days, longer if very young or have severe episodes of whose
previous OM has been problematic
▪ Indications for Myringotomy (3rd line treatment for those who failed 2 courses of
antibiotics)
● Severe, refractory pain
● Hyperpyrexia
● Complications of AOM – facial paralysis, mastoiditis, labyrinthitis, CNS infection,
immunologic compromise from any source
▪ Tympanostomy Tube Placement
● 3eps AOM in 6mos or 4eps in 1yr with 1ep in the preceding 6mos
● If otorrhea occurs post-op, maintain ear canal dry & give ototopical treatment –
cipro/dexa, ofloxacin; have excellent coverage of even the most resistant strains + S.
aureus & P. aeruginosa
PPS Oral Exam Reviewer 2020
15
OTITIS MEDIA WITH EFFUSION
▪ 30% of cases have the same etiologic agents as AOM
▪ Often not accompanied by overt complaints of the
child but can be accompanied by hearing loss
manifested as changes in speech patterns (often goes
undetected if unilateral/mild)
▪ Balance difficulties or disequilibrium
▪ Older children may complain of mild discomfort or
sense of fullness in the ear
COMPLICATIONS
▪ Predisposition to recurring AOM
▪ Pain; Disturbance of balance; Tinnitus
▪ Pathologic MEE changes
▪TM atelectasis, retraction pocket formation
▪ Adhesive OM; Cholesteatoma formation
▪ Ossicular discontinuity
▪ Conductive and sensorineural hearing loss
TM Findings
▪ Absent or slight bulging of the TM
▪ Absent or slight erythema
▪ EA: P. aeruginosa (60%), S. aureus, Enterobacter aerogenes,
P. mirabilis, K. pneumoniae, streptococci, CoNS, diphtheroids,
fungi (Candida, Aspergillus)
▪ Result from chronic irritation and maceration from
excessive moisture in the canal
▪ Other causes: cerumen impaction with trapping of water,
trauma, loss of protective cerumen
OTITIS
EXTERNA
(Swimmer’s
ear)
Necrotizing (malignant) otitis externa
▪ Invasive infection of the temporal bone and skull base
▪ Facial paralysis, other cranial nerve abnormalities, vertigo,
SNHL
▪ Seen in the immunocompromised and severely malnourished
DIFFERENTIAL DIAGNOSIS
▪ Furunculosis – occur in the lateral hair-bearing part of the ear
canal; localized swelling of the canal limited to one quadrant
▪ Otitis Media
▪ Mastoiditis – postauricular fold is obliterated, tenderness is
noted over the mastoid and not on movement of the auricle
▪ Fig 657.2 (Flowchart for managing AOE)
PREVENTION
▪ Instillation of dilute alcohol or 2% acetic acid immediately after swimming or bathing
▪ Use of hair dryer to clear moisture after swimming
▪ Removed in the office setting without general anesthesia
▪ Gentle irrigation of the ear canal with body temperature water or saline for very small
objects (only if the TM is intact)
▪ Large, deeply embedded foreign bodies with associated canal swelling are best removed
by an ENT
▪ Disk batteries – remove immediately; leaks a basic fluid that can cause severe tissue
destruction
▪ Insects – kill first with mineral oil or lidocaine prior to removal
Batch Clingy
FOREIGN
BODY
▪ Predominant symptom: acute rapid onset (within 48h)
of ear pain, often severe, accentuated by manipulation
of the pinna or by pressure on the tragus and by jaw
motion
▪ Severity of the pain may be disproportionate to the
degree of the inflammation – skin of the external ear
canal is tightly adhered to the underlying
perichondrium and periosteum
▪ Itching – precursor of pain; characteristic of chronic
inflammation of the canal/resolving AOE
▪ Conductive hearing loss secondary to 1) edema of the
skin & TM, 2) serous/purulent secretions, or 3) canal
skin thickening associated with chronic external otitis
▪ Prominent signs of acute disease:
● Edema of the ear canal
● Erythema
● Thick, clumpy otorrhea
▪ TM cannot be adequately visualized since the canal is
often tender and swollen (concentric swelling)
▪ If TM is seen, looks normal or opaque
▪ TM mobility may be normal or reduced (if thickened)
▪ Palpable and tender periauricular lymph nodes
▪ Erythema and swelling of the pinna and periauricular
skin
▪ Postauricular fold is preserved
▪ Assess for any baseline sensory, physical, cognitive, or behavioral factors risk w/c may
signify risk of learning problems (see table 658.4)
▪ Most cases resolve without treatment within 3 months
▪ If MEE persists >3mos, do an age-appropriate hearing test and consider ENT referral
▪ If doing expectant management, examine every 3-6mos until
● (-) Effusion
● Significant hearing loss is identified
● Structural abnormalities of the eardrum/ME is suspected
▪ Antimicrobials – limited to those with associated bacterial URTI or untreated ME
infection
▪ Myringotomy + Insertion of Tympanostomy Tubes
● Nearly uniformly reverse the CHL associated with OME
▪ Adenoidectomy
● reduce the risk of recurrence in older children who underwent tube insertion and
who continues to have OM after tube extrusion
▪ Otic drops containing:
● Acetic acid with or without HAA
● Neomycin – against gram-positive organisms & some gram-negative organisms
(Proteus sp.)
● Polymyxin – against gram-negative bacilli (Pseudomonas sp)
● Quinolone (Ciprofloxacin) with or without HAA
▪ Otic drops should fill the canal and the patient should remain in place for 3-5mins
▪ Oral analgesics (Ibuprofen, Acetaminophen) – for severe pain
PPS Oral Exam Reviewer 2020
16
– Fanaroff
Acute
ETIOLOGY / INCIDENCE / PATHOGENESIS
EARLY ONSET (≤ 72 HOL)
▪ Vertical transmission – through ascending amniotic fluid infection
or through acquisition of bacterial flora from the mother’s
anogenital tract during vaginal delivery
▪ T. pallidum & L. monocytogenes - cross placenta
▪ GBS, E. coli – most common in preterm
▪ Others: S. aureus, viridans group Streptococci, Entero-cocci, GAS,
Listeria monocytogenes, Haemophilus, and other enteric Gramnegative organisms, including Klebsiella, Enterobacter, Citrobacter,
Acinetobacter, and Pseudomonas
SEPSIS
▪ Incidence: 0.77 per 1000 live births
SIRS secondary to
infection
SIRS (≥2 of the ff) ▪
Fever
▪ Hypothermia
▪ Tachycardia
▪ Tachypnea
▪ Hypervent
▪ Abnormally
high/low WBC
CLINICAL MANIFESTATIONS
▪ Variable, nonspecific
▪ Hyper- or hypothermia, lethargy, or irritability,
hypotonia, respiratory distress, cyanosis, apnea,
feeding difficulties, poor perfusion, bleeding
problems, abdominal distention
Metabolic changes
Hyper- or hypoglycemia
Acidosis
Jaundice
▪ Meningismus is uncommon – full fontanels,
irritability, lethargy, and seizures
Risk Factors
▪ Delivery
▪ Maternal GBS colonization
▪ Maternal fever
▪ Chorioamnionitis, PROM (>18 hours)
▪ Inadequate intrapartum antibiotic administration before delivery
▪ Prematurity and lower birth weight
LATE ONSET (>72 HOL – 7th DOL)
▪ Through the infant’s environment
▪ Gut microbiome often involved
URINARY TRACT
INFECTION
▪ Uncircumcised at risk: enhanced bacterial adherence to foreskin
and increased bacterial colonization in the urogenital tract
▪ Neonate: via hematogenous spread/ascending infection often
associated with anatomic abnormalities – VUR, ectopic ureter,
duplicated collecting system, renal dysplasia, and causes of
obstruction, such as posterior urethral valves and uretero-pelvic
junction stricture
▪ Additional RF: indwelling urinary catheter
E. coli
PPS Oral Exam Reviewer 2020
TREATMENT
▪ Ampicillin and aminoglycoside – cover for GBS, E. coli,
Listeria
WBC count w/ differential
▪ 6th-12thHOL – more likely to reflect pathologic
inflammatory response
▪ Leukopenia, high percentage of immature to
total WBC (>0.2)
▪ Empiric use of 3rd gen cephalosporins is not
recommended d/t resistance and increased risk for
invasive candidiasis BUT if gram (-) meningitis is
suspected, add cefotaxime
CRP
▪ ↑ within 6-8hrs after infection
▪ Peaks after 24hrs
▪ Increases sensitivity over the next 10-12hrs after
onset
▪ Preterm have lower CRP values and response
Procalcitonin
▪ Peak at 6-8hrs following infection though there is
physiologic ↑ in the 1st 24hrs after birth
▪ Not affected by AOG
▪ Better sensitivity but less specific than CRP
▪ Ceftriaxone has potential to displace bilirubin, increased
risk for kernicterus, associated w/ biliary sludging
Duration:
▪ 10 days – bacteremia without focus
▪ 10-14 days – early preterm
▪ 10-14 days – gram (-) infection
▪ 14-21 days – uncomplicated GBS meningitis
▪ 21 days or 2w beyond 1st negative CSF culture w/c ever
is longer – gram (-) meningitis
▪ Ampicillin & Aminoglycoside or Cefotaxime
Urine culture
▪ Low yield in early onset sepsis since UTI in NB is
primarily caused by renal seeding during
bacteremia
▪ Do in late onset sepsis via suprapubic
aspiration/sterile catheterization
▪ Extreme prematurity
● Greatest risk factor
● More impaired innate and adaptive immune function hence
susceptible
Other Risk Factors
▪ Use of H2 blockers and PPIs
▪ GIT pathology
▪ Indwelling foreign body, dependent on parenteral nutrition
▪ CoNS and S. aureus, invasive candidiasis, GBS, E. coli
▪ Term: 0.1 to 1%, preterm: 2%,
▪ Neonate: M>F (rare in the 1st 3 DOL)
▪ 1st 6mos: males decrease, females increase
▪ 1yo: F>M
DIAGNOSIS
▪ 1ml blood culture – gold standard
▪ Lumbar puncture
▪ Nonspecific: fever, lethargy, failure to thrive,
poor feeding, abdominal distention, vomiting,
tachypnea, and cyanosis
▪ Preterm similar to that of term infants,
although may also have hypoxia or apnea with
bradycardia
▪ Urine culture by catheterization
>1000 CFU/mL is meaningful
▪ Suprapubic bladder aspiration
Any growth of a urinary pathogen
▪ Blood cultures should be obtained
▪ Urinalysis lacks specificity and sensitivity for dx of
UTI in neonates and NOT RECOMMENDED
▪ 3rd gen cephalosporin – for suspected gram (-)
meningitis
▪ Vancomycin (instead of ampicillin) – if preterm/infants
with complex problems, surgeries, indwelling catheters
▪ Carbapenems – considered if previously given 3rd gen
cephalosporin
▪ Empiric antifungal therapy – for invasive candidiasis,
severe sepsis unresponsive to antibiotics, chronic TPN,
unexplained cytopenias
▪ Empiric: Ampicillin + Aminoglycoside
▪ Vancomycin + Aminoglycoside – for hospitalized
infants w/ late onset infection
▪ Ciprofloxacin: for multidrug-resistant, Gram-negative
disease or orally when alternative oral antibiotics are not
available
▪ Repeat urine CS after 2-3d of treatment if (+) highly
resistant pathogen / with known anatomical abnormality
▪ If still (+) evaluate for potential reservoir of infection
Duration: 7-14 days
▪ Give IV antibiotics for the entire course if with delayed
clinical response, prematurity, bacteremia, or presence
COMPLICATIONS / PROGNOSIS
▪ Harm associated with >5d of empiric
antibiotics – ↑ risk for NEC, candidemia,
mortality among preterm
▪ Early antibiotic exposure may
permanently alter the microbiome &
predispose to obesity
PREVENTION
▪ Universal antenatal screening for GBS
colonization
▪ Intrapartum antibiotic prophylaxis
PREVENTION
▪ Infection control in the postnatal
environment
▪ Hand hygiene
▪ Proper management of central venous
catheters
▪ Appropriate use of antibiotics
▪ Limited use of H2 blockers and PPIs
▪ All neonates with UTI should undergo
imaging evaluation d/t high prevalence of
urinary tract abnormalities
▪ If prenatal ultrasound data are not
available, do a renal ultrasound once
clinically stable
▪ If renal damage is suggested by
ultrasound, do renal cortical scintigraphy
to assess for renal scarring
▪ Voiding cystourethrogram
● Detects VUR, done 3-6 weeks after
completion of antibiotics
Batch Clingy
DISEASE
17
▪ Most common
▪ Can invade & replicate w/in uroepithelial cells Adhesin – ↑
adhesion to urogenital tract cells Fimbrae – promotes persistence of
infection
Others:
▪ Enterobacteriaceae: Klebsiella, Proteus, Enterobacter, Citrobacter,
Salmonella, and Serratia
▪ Gram-positive organisms – less frequent although Enterococci, S.
aureus, and coagulase-negative Staphylococci are also known to
cause UTI in newborns
▪ More common in the 1st month of life than any other age
▪ 0.3 per 1000 live births in developed countries
▪ 0.8 - 6.1 per 1000 in developing countries
Early onset
▪ Within 1st WOL, usually within 72 HOL
▪ Vertically transmitted
▪ Associated w/ complications of labor & delivery
▪ GBS, E. coli
▪ Others: Klebsiella, Enterobacter, Citrobacter, and Serratia species
(formation
of
brain
abscess),
Listeria
monocytogenes
(rhombencephalitis)
MENINGITIS
Late onset
▪ After 1st wk of life
▪ Community/ nosocomial transmission
▪ Nosocomial pathogens: CoNS, Candida, and resistant Gramnegative organisms, particularly Pseudomonas more prominent
of anatomic abnormalities
▪ Older infants w/ uncomplicated disease may be
switched to oral antibiotics after demonstration of
clinical improvement
▪ Nonspecific, similar w/ sepsis
▪ Temp instability (60%)
Common neurologic symptoms:
Irritability, emesis, lethargy, poor tone, seizures,
full but not bulging fontanels, without
meningeal signs
Other symptoms:
Poor feeding, respiratory distress, apnea,
diarrhea
▪ Blood culture
▪ CBC with differential
▪ Urine culture if >6DOL
▪ Lumbar puncture for CSF GS/CS, cell count with
differential, glucose, and protein (in order of
priority)
▪ If CSF findings not definitive in infant whose
clinical picture is otherwise suspicious, a repeat LP
at 24-48 hours later will still show pleocytosis if
true meningeal inflammation is present even with
use of antibiotics
▪ Ampicillin + aminoglycoside – early onset/ GBS
LONG-TERM OUTCOME
▪ Renal scarring
▪ Subsequent hypertension and CKD
▪ Cefotaxime/higher gen cephalosporin in addition to
ampicillin – Gram (-)
Neurologic sequelae:
Developmental
delay,
seizures,
hydrocephalus, cerebral palsy, blindness,
and hearing loss.
▪ Aminoglycoside – not used as monotherapy due to poor
CNS penetration
21%-38% – mild deficits
24%-29% – severe neurologic sequelae
▪ If improved & CSF is sterilized, treatment can be
narrowed to ampicillin or penicillin monotherapy to
continue for 14 days after 1st negative culture
Predictors of poor neurologic outcomes:
▪ Seizures >72 hours
▪ Presence of coma
▪ Hypotension requiring inotropes
▪ Leukopenia (<5.0)
▪ Abnormal EEG
▪ If LP is traumatic, not recommended to adjust
CSF WBC as this does not improve diagnostic
utility for neonates
▪ For gram (-) infection – 3rd gen (cefotaxime) for 21
days or for 14 days after the 1st (-) CSF culture. Add
aminoglycoside until CSF sterilization, which usually
takes longer for gram (-) meningitis
▪ Consider repeat LP if with complicated clinical
course,
including
seizures,
abnormal
neuroimaging, prolonged (+) CSF cultures, slow
clinical response to treatment
▪ Enterobacteriaceae family with inducible β-lactamase
resistance (e.g., Citrobacter, Enterobacter, Serratia) and
for Pseudomonas – 4th gen cephalosporin (cefepime) or
a carbapenem (meropenem) + aminoglycoside
▪ Listeria monocytogenes, Enterococcus (not susceptible
to Ceph) – Ampicillin + amino-glycoside until CSF
sterilization, followed by ampicillin monotherapy x 14
days after 1st (-) culture
Batch Clingy
▪ CoNS (preterm, foreign body in the CNS) - vancomycin x
14-21 days after CSF sterilization, with removal of any FB
if feasible.
PPS Oral Exam Reviewer 2020
18
Acute
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
Risk Factors for ↑ indirect bilirubin:
Maternal age, race (Chinese, Japanese, Korean, Native
American), maternal DM, prematurity, drugs (vitamin K3, novobiocin), altitude, polycythemia, male sex, trisomy 21, cutaneous
bruising, blood extravasation (cephalhematoma), oxytocin
induction, breastfeeding, weight loss (dehydration or caloric
deprivation), delayed bowel movement, family history of, or a
sibling who had, physiologic jaundice
CLINICAL MANIFESTATIONS / PHYSICAL EXAM
▪ Indirect bilirubin in umbilical cord serum is 1-3 mg/dL
● Rises at a rate of <5mg/dL/day → visible jaundice on
D2-3 of life
● D2-4 of life – peaks at 5-6 mg/dL
● D5-7 of life – decrease to <2mg/dL
▪ Breakdown of fetal RBCs + transient limitation in the
conjugation of bilirubin by the immature neonatal liver → (↑)
bilirubin production
DIAGNOSIS
▪ Exclude known causes of jaundice based on the
history, clinical findings, and laboratory data
Pathologic Jaundice
▪ Jaundice on the 1st 24-36 hrs after birth
▪ Rising faster than 5 mg/dL/day
▪ >12 mg/ dL in a full-term infant (especially in the
absence of risk factors) or 10-14 mg/dL in a preterm
infant
▪ Persists after 10-14 days after birth, or direct
bilirubin fraction is >2 mg/dL at any time
TREATMENT / COMPLICATIONS / PROGNOSIS
Phototherapy
▪ Bilirubin absorbs light maximally in the blue range (420-470 nm)
▪ Reversible photoisomerization reaction
● Toxic native unconjugated 4Z,15Z-bilirubin → unconjugated configurational isomer,
4Z,15E-bilirubin, which can be excreted in bile without conjugation
▪ Lumirubin – irreversible structural isomer converted from native bilirubin that can be
excreted by the kidneys in the unconjugated state
▪ Contraindication: porphyria
▪ AE: loose stools, erythematous macular rash, purpuric rash associated with transient
porphyrinemia, overheating, dehydration (increased insensible water loss, diarrhea),
hypothermia from exposure, bronze baby syndrome (direct hyperbilirubinemia)
IVIG
● 0.5-1.0 g/kg/dose; repeat in 12 hrs
● Reduces the need for exchange transfusion in hemolytic disease
PHYSIOLOGIC
JAUNDICE
Metalloporphyrin Sn-mesoporphyrin (SnMP)
▪ Competitive enzymatic inhibition of the rate-limiting conversion of hemeprotein to
biliverdin (an intermediate metabolite in the production of unconjugated bilirubin) by
heme-oxygenase
Single IM dose if ABO/G6PD jaundice anticipated
▪ AE: transient erythema if the infant is receiving phototherapy
BREASTFEEDING
JAUNDICE
ABO HEMOLYTIC
DISEASE
BREASTMILK JAUNDICE
▪ 2% of breastfed infants
▪ β-glucoronidase → deconjugation of bilirubin, ↑
enterohepatic circulation
▪ Free fatty acids, pregnanediol → interfere w/ bilirubin
conjugation
BREASTFEEDING JAUNDICE
▪ Dehydration hemoconcentrates bilirubin
▪ Fewer bowel movement → ↑ enterohepatic circulation
▪ Jaundice after 7th DOL with maximum concentration of 1030 mg/dL at 2nd-3rd wk of life
▪ 20% of cases at risk for ABO mismatch but only 1-10%
develops hemolysis because naturally occurring maternal
antibodies against ABO antigens almost exclusively IgM and do
not cross the placenta
▪ Jaundice in the 1st 24hrs
▪ (-) Pallor and hepatosplenomegaly
▪ Rarely, development of hydrops fetalis or kernicterus
▪ Jaundice on the 1st week after birth
▪ Hyperbilirubinemia - in 10–20% of affected,
unconjugated serum bilirubin may reach ≥20mg/dL
▪ Mild anemia and reticulocytosis
▪ PBS: polychromasia, nucleated RBCs, spherocytes
Complication: Rarely, kernicterus
▪ Frequent breastfeeding (>10x/day)
▪ Rooming-in with night feeding
▪ Ongoing lactation support
▪ Supplementation with formula or EBM if intake inadequate, weight loss is excessive,
(+) dehydration
▪ Phototherapy
▪ IVIG/Exchange transfusion – if severe
▪ pRBC transfusion – may be required at several weeks of age because of
hyporegenerative or slowly progressive anemia
▪ Post discharge monitoring of hemoglobin or hematocrit is essential
Batch Clingy
▪ Some group O mothers produce IgG Ab against blood group A
or B antigens → can cross the placenta → immune-mediated
hemolysis
Double Volume Exchange Transfusion if intensive phototherapy fails
▪ AE: metabolic acidosis, electrolyte abnormalities, hypoglycemia, hypocalcemia,
thrombocytopenia, volume overload, arrhythmias, NEC, infection, graft-versus-host
disease, death
▪ If BF is continued, bilirubin gradually decreases but may persist for 3-10wks at lower
levels
▪ If BF is discontinued, falls rapidly reaching normal within few days
▪ Phototherapy may be beneficial
PPS Oral Exam Reviewer 2020
19
▪ No G6PD → no NADPH → no reduced glutathione → cells
susceptible to oxidative stress → damage induced to cell
membrane of RBC → hemolysis
▪ X- linked
G6PD DEFICIENCY
*see anemia*
▪ Other substances noted in neonates: Naphthalene, herbal
medications, henna application, menthol containing
umbilical potions
▪ Falling hemoglobin and hematocrit
▪ Increasing reticulocyte count
▪ Hyperbilirubinemia
▪ Parenteral education
▪ Avoidance of known triggers
▪ Phototherapy
▪ Exchange transfusion
G6PD testing performed several weeks after acute
hemolysis
▪ May give false normal result because older RBCs,
depleted in G6PD enzyme activity may be
destroyed, leaving younger cells with higher
enzyme activity intact
G6PD-A – Africa, southern Europe, African americans
G6PD Mediterranean – mediterranean countries, middle east,
India
G6PD Canton – Asia
▪ Hemolysis or impaired conjugation → decreased excretion of
bilirubin → ↑ total bilirubin
▪ Neonatal erythrocytes are particularly susceptible to cell injury
and Heinz body formation in response to oxidative stress
▪ DIC from sepsis → hemolysis as erythrocytes traverse the
deposition of fibrin within the microvasculature
▪ Conjugated hyperbilirubinemia from hepatitis secondary to
bacterial, viral, fungal and protozoal infection
Batch Clingy
SEPSIS
*see neonatal fever*
G6PD
▪ Major part in stabilization of the RBC membrane against
oxidative damage
▪ Catalyzes the 1st step in the HMP pathway, oxidizing glucose6-phosphate to 6-phosphogluconolactone, thereby reducing
nicotinamide adenine dinucleotide phosphate (NADP) to NADPH
(essential for the regeneration of reduced glutathione from
oxidized glutathione, a substance that plays an integral part in
the body’s antioxidative mechanisms)
▪ Pathway also instrumental in stimulating catalase, another
important antioxidant
▪ Ingestion of or contact w/ fava beans (favism) → severe
hemolytic episodes, jaundice and anemia
PPS Oral Exam Reviewer 2020
20
Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Occurs in premature, 60-80% in <28 wks AOG
▪ Risk Factors: maternal DM, multiple births, CS delivery, precipitous
delivery, asphyxia, cold stress, maternal hx of prev affected infants
▪ Decreased risk: chronic or pregnancy HTN, maternal heroin use,
prolonged ROM, antenatal corticosteroid prophylaxis
▪ SURFACTANT DEFICIENCY 2o to decreased production and secretion
Surfactant:
● Appears in amniotic fluid bet 28-32wks, mature after 35w
●
Contains
dipalmitoyl
phosphatidylcholine
(lecithin),
phosphatidylglycerol, apoproteins (SP-A, B, C, D), cholesterol
● Synthesized and stored in type II alveolar cells
● Reduce surface tension, help maintain alveolar stability at end
expiration
RESPIRATORY
DISTRESS
SYNDROME
▪ Absence of pulmonary surfactant → ↑ alveolar surface tension →
atelectasis-impaired ability to attain adequate FRC
▪ Atelectasis, volutrauma, ischemic injury, oxygen toxicity →injury to
epithelial and endothelial cells → effusion of proteinaceous material and
cellular debris into the alveolar spaces forming hyaline membranes →
impaired oxygenation
▪ Alveolar atelectasis, hyaline membrane formation, interstitial edema →
less compliant lungs→ greater pressure required to expand alveoli and
small airways
▪ Highly compliant chest walls in preterms → less resistance to natural
tendency of lungs to collapse
▪ Perfused but not ventilated alveoli → atelectasis → hypoxia
▪ Decreased lung compliance, small tidal volumes, ↑ physiologic dead
space, and insufficient alveolar ventilation → hypercapnia.
▪ Hypercapnia + hypoxia, + acidosis = pulmonary arterial vasoconstriction
with ↑ R to L shunting through the foramen ovale and ductus arteriosus
and within the lung itself
TRANSIENT
TACHYPNEA OF THE
NEWBORN
▪ 3- 6 per 1000 infants
▪ Most common etiology of tachypnea in NB
▪ Self limited
Risk Factors: twin, maternal asthma, late prematurity, precipitous delivery,
GDM, CS without labor
▪ Delayed clearance of fetal lung fluid
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
▪ Within minutes of birth, tachypnea,
prominent expiratory grunting, intercostal
and subcostal retractions, nasal flaring,
cyanosis
▪ Breath sounds – normal or ↓ with a harsh
tubular quality, fine crackles on deep
inspiration
Untreated RDS: progressive worsening of
cyanosis and dyspnea, mixed respiratory
metabolic acidosis, edema, ileus, oliguria,
hypotension, respiratory failure
▪ Apnea & irregular respirations - ominous
signs
▪ Signs peak within 3 days after which
improvement is gradual
DIAGNOSIS
▪ CXR: low lung volumes, diffuse, fine reticular
granularity of the parenchyma (ground-glass
appearance), air bronchograms
▪ ABG: hyoxemia, hypercapnia, metabolic
acidosis
▪ 2DED: if no response to surfactant
▪ Lung profile (lecithin:sphingo- myelin ratio
and phosphatidyl- glycerol determination) on
a tracheal aspirate – to check surfactant
deficiency for atypical RDS
PREVENTION
▪ Avoidance of unnecessary or poorly timed
early (<39w GA) CS or induction of labor
▪ Appropriate mgt of high-risk pregnancy and
labor (antenatal corticosteroids)
▪ Prediction of pulmonary immaturity w/
possible in utero acceleration of maturation
Signs of improvement: spontaneous diuresis,
improved blood gas at lower inspired O2 levels
and/or lower ventilator support
▪ Surfactant: for symptomatic prophylactic
(immediately after birth or early rescue
(during the 1st few hrs), repeated dosing q612h for 2-4 doses
▪ iNO
▪ Early (1st 10 days) low dose steroid – 1mkd
HAA BID x 7d or 0.5mkd x 3d, reduces BPD risk
▪ Dopamine/HAA for hypotension
▪ Ampicillin +aminoglycoside
Signs of Respiratory Failure
▪ pH <7.2
▪ PaCO2 >60mmHg
▪ SaO2 <90% at O2 40-70% and
nCPAP of 5-10
▪ Persistent/severe apnea
▪ Tachypnea, retractions, expiratory grunting,
cyanosis relieved by minimal O2 (<40%)
▪ Clear BS
TREATMENT
▪ Steroids – give in those with preterm labor
between 24-36wks AOG and likely to deliver
within 1wk
▪ Maintain PaO2 50-70mmHg
▪ If SaO2 <90% at FiO2 >40-70% apply nCPAP
at 5-10cmH2O – reduces collapse of alveoli
and improves FRC and VQ match; early use
reduces need for MV
▪ INSURE
● Intubate
● Surfactant replacement, then
● Extubate back to nCPAP once the infant
is stable (usually within minutes to <1hr)
▪ Mech Vent: if with signs of respiratory
failure, use high rate (>60/min) and low tidal
volume strategy (4-6mL/kg)
▪ Diagnosis of exclusion
CXR: prominent perihilar pulmonary vascular
markings, fluid in intralobar fissures and
rarely, small pleural effusion
▪ Supportive
▪ Salbutamol
● ↑ expression of ENaC and Na-K-ATPase
● Facilitate fluid clearance
● When given early, improve oxygenation,
shorten duration of O2 therapy, expedite
COMPLICATIONS / PROGNOSIS
COMPLICATIONS OF SURFACTANT
▪ Transient hypoxia, hypercapnia, bradycardia,
hypotension, blockage of ETT, pulmonary
hemorrhage
COMPLICATIONS OF INTUBATION
▪ Pulmonary air leaks, asphyxia (obstruction/
dislodgment of the tube), bradycardia during
intubation or suctioning, subglottic stenosis,
bleeding trauma, posterior pharyngeal
pseudodiverticula, need for tracheostomy,
ulceration of the nares (pressure from the
tube), permanent narrowing of the nostril
(tissue damage and scarring from irritation /
infection around the tube), erosion of the
palate, avulsion of a vocal cord, laryngeal
ulcer, papilloma of a vocal cord, persistent
hoarseness, stridor, edema of the larynx.
Risks with umbilical arterial catheterization
▪ Vascular embolization, thrombosis, spasm,
vascular perforation, ischemic or chemical
necrosis of abdominal viscera, infection,
accidental hemorrhage, HTN, impairment of
circulation to a leg with subsequent gangrene
COMPLICATIONS
▪ Hypercapnia, acidosis, RF — uncommon but
when it occurs, resolves rapidly (<12-24h)
Rapid Recovery
Batch Clingy
DISEASE
21
▪ Ineffective expression of ENaC & Na-K-ATPase → slow absorption of fetal
lung fluid → ↓ pulmonary compliance and impeded gas exchange
▪ Meconium stained – 10-15% of birth, common in term/post term
▪ 5% requires MV, 3-5% die
▪ Fetal distress and hypoxia occur before passage of meconium
recovery
▪ Airway obstruction → respiratory distress
within 1st hours, tachypnea (may persist
many days or several weeks), retractions,
grunting
▪ Partial obstruction → pneumo-mediastinum,
pneumothorax, or both
CXR: patchy infiltrates, coarse streaking of
both lungs, increased AP diameter, flattening
of diaphragm
▪ Normal CXR with severe hypoxemia and no
cardiac malformation → Pulmonary HTN
▪ Supportive, standard mgt for RD
▪ Exogenous surfactant and/or iNO with MAS
and hypoxemic RF or pulmonary HTN
requiring MV → ↓ need for ECMO
▪ If no signs of sepsis – no role for antibiotics
PROGNOSIS
▪ Depends on extent of CNS injury from
asphyxia and presence of associated problems
(Pulmonary HTN)
▪ Mortality higher than nonstained
▪ Residual lung problems rare – symptomatic
cough, wheezing, persistent hyperinflation for
up to 5-10yrs
▪ Overdistention of chest is prominent
PREVENTION
▪ Rapid identification of fetal distress and
initiation of prompt delivery
▪ Improves within 72 hours but if it requires
assisted ventilation, high risk for mortality
MECONIUM
ASPIRATION
SYNDROME
PNEUMONIA
Fanaroff
Congenital Pneumonia
▪ Acquired in utero – aspiration of infected amniotic fluid, ascending
infection thru intact/ruptured membranes, hematogenous spread thru the
placenta
▪ Presents immediately after delivery
▪ Bacteria: GBS, E. coli (esp preterm), Klebsiella, Enterobacter, GAS,
Staphylococcus, and L. monocytogenes, anaerobes such as Bacteroides
(occasionally)
▪ Viral: Herpes simplex, adenovirus, enterovirus, mumps, rubella, an
unusual presentation of congenital CMV, syphilis and toxoplasmosis
▪ 70% with disseminated candidal infections
▪ Risk Factors: prematurity, PROM, GBS colonization, chorioamnionitis,
intrapartum maternal fever
PPS Oral Exam Reviewer 2020
▪ Nonspecific
▪ Temperature instability, lethargy, apnea,
tachycardia, metabolic acidosis, abdominal
distention,
poor
feeding,
neurologic
depression
▪ Respiratory distress – tachypnea,
retractions, cough (unusual, <1/3 of neonates)
▪ Delayed diagnosis and treatment → PPHN
and septic shock
▪ CXR: nonspecific, unilateral or bilateral
streaky densities, confluent mottled opacified
areas, or a diffusely granular appearance with
air bronchograms
▪ Blood CS, CBC, ↑CRP, neutropenia,
immature WBCs, thrombocytopenia
▪ Tracheal GS/CS within the 1st 8 hours of life
VAP CRITERIA
▪ Increased ventilator support
▪ Temperature instability
▪ New onset of purulent tracheal secretions or
a change in the character of sputum
▪ Leukopenia or leukocytosis
▪ Symptoms of respiratory distress
▪ Bradycardia or tachycardia
▪ New changes in chest radiograph that
persist in at least two consecutive films
▪ Ampicillin + Gentamicin
▪ Complete for 10-14 days if uncomplicated
pneumonia
SUPPORTIVE CARE
▪ Circulatory support – fluids and inotropes,
▪ Mechanical ventilation and O2 – correct
hypoxemia
▪ Correct acidosis, hypoglycemia, and
electrolyte imbalance
▪ Parenteral nutrition w/ amino acids,
carbohydrates, and lipids – adequate nutrition
and prevent protein catabolism & amino and
fatty acid deficiency.
▪ Feeding should be started ASAP to supply
adequate calories. In the absence of
respiratory distress or abdominal pathology
with concern for aspiration, gavage feedings
can be started
Batch Clingy
EARLY PNEUMONIA (1st 3-7 days)
▪ Aspiration of infected amniotic fluid or bacteria colonizing the birth canal
during labor
22
LATE PNEUMONIA (After 7 days)
▪ Ventilator associated pneumonia, nosocomial infection, hematogenous
spread
▪ Bacteria: coagulase-negative staphylococci and Staphylococcus aureus, S.
pyogenes, S. pneumoniae, E. coli, Klebsiella, Serratia, Enterobacter cloacae,
Pseudomonas, Bacillus cereus, and Citro-bacter
▪ Chlamydia trachomatis acquired during labor may present as late as 2-4
wks of life due to long incubation period
▪ Viral: RSV, adenovirus, enteroviruses, parainfluenza, rhinovi-ruses, and
influenza viruses
▪ Nonspecific
▪ New-onset or increased apnea, respiratory
distress, ↑ oxygen requirement or
mechanical support
▪ Abdominal distension or feeding intolerance
▪ Temperature instability
▪ Hyperglycemia
▪ Cardiovascular instability
▪ Vancomycin + Gentamicin or
▪ Vancomycin + Cefotaxime
▪ Nafcillin + Gentamicin – to ↓ vancomycin
resistance
▪ If Pseudomonas: aminoglycoside + antipseudomonal
β-lactam,
(ceftazi-dime,
cefepime, or piperacillin-tazobactam)
▪ Uncomplicated pneumonia: 7-10d
▪ Prolonged use of antibiotics and corticosteroids increase risk of candidal
pneumonia, especially in ELBW
Alveolar overdistention
▪ PPV during resuscitation
▪ Ball valve phenomenon (aspiration, bronchial/bronchiolar obstruction
AIR LEAK
SYNDROME
Spontaneous rupture
▪ Lobar emphysema, congenital lung cyst, pneumatocele
Pneumothorax with pulmonary hypoplasia
▪ 1st few hours after birth
▪ ↓ Alveolar surface area and poorly compliant lungs
Associated with:
▪ ↓ Amniotic fluid volume – potter syndrome, renal agenesis, renal
dysplasia, chronic amniotic fluid leak
▪ ↓ Fetal breathing movement – oligohydramnios, neuromuscular disease
▪ Pulmonary space occupying lesions – diaphragmatic hernia, pleural
effusion, chylothorax
▪ Thoracic abnormalities – thoracic dystrophies
Pulmonary interstitial emphysema
▪ Gas from ruptured alveolus escapes into the interstitial spaces of lung
where it tracks along small conducting airways and dissects along the
peribronchial and perivascular connective tissue sheaths to the hilum of the
lung
▪ If volume of escaped air great enough, it may collect to the:
● Mediastinal space – pneumomediastinum
● Rupture into pleural space – pneumothorax
● Subcutaneous tissue – subcutaneous emphysema
● Peritoneal cavity – pneumoperitoneum
● Pericardial sac – pneumopericardium
PPS Oral Exam Reviewer 2020
Asymptomatic Pneumothorax
▪ Hyperresonance, ↓ ipsilateral
sounds ± tachypnea
breath
Symptomatic Pneumothorax
▪ Respiratory distress, high RR to severe
dyspnea, tachypnea, cyanosis, irritability,
restlessness, apnea
▪ PE: chest asymmetry with ↑ AP diameter,
hyperresonance, ↓ or absent BS, heart and
cardiac apex displaced on contralateral side,
diaphragm displaced downward, as is the liver
causing abdominal distention
Pneumomediastinum
▪ Usually asymptomatic
▪ If great, may cause bulging of mid thoracic
area, distended neck veins, low BP
(tamponade of systemic and pulmonary
veins),
subcutaneous
emphysema
(pathognomonic)
Pulmonary Interstitial Emphysema
▪ May precede or occur independently with
pneumothorax
→
↑
PA-aO2
and
intrapulmonary shunting → ↓ compliance,
hypercapnia, and hypoxemia → ↑ respiratory
distress
Pneumothorax
▪ Edge of collapsed lung standing out in relied
against the pneumothorax
Pneumomediastinum
▪ Hyperlucency around the heart border and
between the sternum and the heart border
▪ Transillumination – affected side of the
thorax transmits excessive light
Pulmonary hypoplasia
▪ Signs of uterine compression
▪ Small thorax on CXR
▪ Severe hypoxia and hypercapnia
▪ Signs of primary disease –hypotonia,
diaphragmatic hernia, Potter syndrome
Pneumopericardium
▪ Sudden shock w/ tachycardia, muffled heart
sounds, poor pulses suggesting tamponade
▪ Close observation – small pneumothorax
▪ Frequent small feedings – prevent gastric
dilation and minimize crying
▪ 100% O2 – accelerate resorption of free
pleural air into blood by reducing the nitrogen
tension in the blood and producing a resultant
nitrogen pressure gradient from the trapped
gas in the blood
▪ Needle thoracentesis – emergency
compression for severe distress. Immediately
or after catheter aspiration, insert chest tube
and attach to underwater seal drainage.
▪ If air leak is ongoing, do continuous suction
(-5 to -20cm H2O)
▪ Surfactant –
pneumothorax
reduces
incidence
of
▪ Pneumoperitoneum vs Intestinal Perforation
– do ABDOMINAL PARACENTESIS
● IP has (+) organism in gram stain
Batch Clingy
▪ Risk Factors: mechanical ventilation and central venous lines, abnormal
neurologic conditions predisposing to aspiration pneumonia, poor
nutrition, severe underlying disease, and prolonged hospitalization
▪ Asymptomatic pneumothorax usually unilateral, 1-2 % of infants
▪ Symptomatic pneumothorax less common
▪ Risk Factors: MAS, RDS, Assisted ventilation (HFV), urinary tract
anomalies, oligohydramnios
▪ Most common cause: overdistention → alveolar rupture
23
▪ ↑ Mediastinal pressure → compressed pulmonary veins at hilum
interfering with pulmonary venous return to the heart and cardiac output
→ pulmonary air embolism, cutaneous blanching, air in IVC, air-filled heart
and vessels on chest radiograph → death
CONGENITAL
DIAPHRAGMA-TIC
HERNIA
▪ Major limiting factor for survival: Pulmonary Hypoplasia – ↓ pulmonary
mass and the number of bronchial divisions, respiratory bronchioles, and
alveoli
▪ Pathology: Abnormal septa in terminal saccules, thickened alveoli,
thickened pulmonary arterioles
▪ Biochemical abnormalities: surfactant deficiencies, ↑ glycogen in the
alveoli, ↓ phosphatidylcholine, total DNA and total lung protein all of which
contribute to limited gas exchange
▪ Associated anomalies: (30%) CNS lesions, esophageal atresia,
omphalocele, CV lesions
▪ Chromosomal syndromes: trisomy 21, 13, 18. Fryns, Brachmann-deLange,
Pallister-Killian, Turner Syndrome
▪ Respiratory distress – immediately after
birth or may have honeymoon period of up to
48 hrs which the baby is stable
▪ Early RD within 6hrs after birth – poor
prognostic sign
▪ Scaphoid abdomen, ↑ chest wall diameter,
bowel sound heard in the chest, ↓ BS
bilateral, point of max cardiac impulse may be
displaced
▪ Delayed presentation: vomiting (intestinal
obstruction or mild respi sx), incarceration →
ischemia, sepsis shock, GBS sepsis
▪ Prenatal UTZ between 16-24wks AOG –
polyhydramnios, chest mass, mediastinal
shift, gastric bubble or liver in thoracic cavity,
fetal hydrops
Predictors of outcome
▪ Liver position in the chest, observed to
expected total lung volume, and observed to
expected lung to head ratio
▪ After delivery, do CXR to confirm the
diagnosis
▪ Passage of nasal gastric tube
DDX: eventration or cystic lung lesion
▪ Delivery at tertiary center
▪ Endotracheal intubation, NGT/OGT for
decompression
▪ Arterial and central venous lines
▪ Preductal arterial SpO2 ≥ 85%
▪ Gentle ventilation with permissive
hypercapnia
▪ Avoid Pulmonary HTN
▪ Inotropes – if (+) LV dysfunction
▪ Sedation and paralysis – severe respiratory
failure and hypoxemia
Ventilation strategy
▪ Conventional MV – PIP<25, PEEP 3-5cm,
PaCO2 <65-70 mmHg
▪ HFOV – if PIP>25 is required to maintain
ventilation
▪ ECMO – if CV and HFOV fails, used before
repair of defect, lasts up to 2-4 wks; goal:
oxygenation, CO2 Elimination without
inducing volutrauma
iNO – reduces ductal shunting and pulmonary
pressures and improved ventilation, used as
bridge to ECMO
Surgical repair – 48 hours after stabilization
and resolution of pulmonary HTN
ESOPHAGEAL
ATRESIA (EA) and
TRACHEOESOPHAGEAL
FISTULA (TEF)
EA
▪ Most common anomaly of the esophagus
▪ 1.7 per 10,000 live births (of these 90% have TEF)
▪ Most common form: Type C – upper esophagus ends in a blind pouch and
TEF is connected in distal esophagus
EA
▪ Frothing and bubbling at the mouth and
nose after birth
▪ Episodes of coughing, cyanosis, and
respiratory distress.
▪ Exact cause: unknown
▪ Risk Factors: advanced maternal age, European ethnicity, obesity, low
socioeconomic status, and tobacco smoking
▪ 50% nonsyndromic without other anomalies, and the rest have associated
Isolated TEF in the absence of EA
▪ “H-type” fistula
▪ Chronic respiratory problems, including
refractory bronchospasm and recurrent
PPS Oral Exam Reviewer 2020
▪ Inability to pass an OGT/NGT
▪ Prenatal imaging: absence of the fetal
stomach
bubble
and
maternal
polyhydramnios
▪ Plain radiography:
EA w/ TEF: coiled feeding tube in the
esophageal pouch and/or an air-distended
stomach
Pure EA: airless scaphoid abdomen
▪ Patent airway, pre-operative proximal
pouch decompression – prevent aspiration of
secretions
▪ Antibiotics – prevent consequent
pneumonia
▪ Prone position – minimizes movement of
gastric secretions into a distal fistula
▪ Esophageal suctioning - minimizes
aspiration from blind pouch
▪ Surgical ligation of the sided thoracotomy
▪ Postop – monitor for worsening pulmonary
hypertension, bleeding, chylothorax, bowel
obstruction
▪ Overall survival: 71%
POOR PROGNOSIS
▪ Major anomaly
▪ Symptoms before 24hrs
▪ Severe pulmonary hypoplasia
▪ Herniation to the contralateral lung
▪ Need for ECMO; size of defect
MORBIDITIES
Pulmonary problems
▪ Decreased forced expiratory flow at 50% of
vital capacity and decreased peak expiratory
flow, highest risk: ECMO requiring and patch
repair
GERD (>50%)
▪ More common in CDH that involves
esophageal hiatus
Intestinal Obstruction (20%)
▪ Result from midgut volvulus, adhesions, or
recurrent hernia that became incarcerated
Recurrent diaphragmatic hernia (5-20%
▪ Patch repairs highest risk
Delayed growth in the 1st 2y of life
▪ Factors: poor intake, GERD, higher caloric
requirement d/t energy required to breathe
Neurocognitive defects (67% in ECMO, 24%
no ECMO)
▪ Transient and permanent developmental
delay, abnormal hearing/vision, seizures
▪ Pectus excavatum
▪ Scoliosis
▪ <1500g at birth and those with severe
associated cardiac anomalies – highest risk for
mortality
COMPLICATIONS OF SURGERY
▪ Anastomotic leak, refistulization, and
anastomotic stricture
▪ GERD – from intrinsic abnormalities of
esophageal function + delayed gastric
emptying → respiratory disease (reactive
Batch Clingy
Tension pneumothorax
▪ Accumulation of air w/in the pleural space sufficient to elevate
intrapleural pressure above atmospheric pressure. Compression of vena
cava and torsion of great vessels may interfere with venous return
▪ Communication between the abdominal and thoracic cavities ± abdominal
contents
▪ 1:2000 males, 1:5000 females
▪ 90% Bochdalek – posterolateral, 80-90% at left side
▪ 2-6% Morgagni – retrosternal
▪ Others: Hiatal (esophageal), Paraesophageal (adjacent to hiatus)
24
anomalies, most often associated with (VACTERL) syndrome.
▪ Genetic factors have a role as suggested by discrete mutations in
syndromic cases: Feingold syndrome (N-MYC), CHARGE syndrome (CHD7),
and anophthalmia-esophageal-genital syndrome (SOX2).
pneumonias
Isolated TEF: esophagogram w/ contrast
medium injected under pressure
▪ Bronchoscopy/endoscopy
TEF and primary end-to-end anastomosis of
the esophagus via R-sided thoracotomy
▪ Preterm: primary closure may be delayed by
temporizing with fistula ligation and
gastrostomy tube placement
airway disease) that complicates EA and TEF
and worsens the frequent anastomotic
strictures after repair of EA
▪ Tracheomalacia that improves as the child
grows
Complex
DISEASE
MECONIUM ILEUS
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Impaction of inspissated meconium in the distal small
bowel
CLINICAL MANIFESTATIONS
▪ Abdominal distention
▪ Vomiting often bilious
▪ 30% of neonatal intestinal obstruction
▪ Can present as early as in utero with
volvulus or perforation, peritoneal ascites,
meconium peritonitis, hydrops, fetal loss
▪ Common in cystic fibrosis (CF)
PATHOGENESIS
▪ CF → lack of fetal pancreatic enzymes inhibits
digestive mechanisms → meconium becomes viscid and
mucilaginous
MECONIUM PLUG
SYNDROME
▪ Doughy or cordlike masses of intestines
thru the abdominal wall
DIAGNOSIS
▪ (+) NBS for CF → do sweat testing when >2kg, at
least 36 wks corrected AOG
▪ Genetic testing confirms CF
▪ Prenatal UTZ:
Enlarged bowel loops/mass with distention of the
proximal small bowel
▪ Plain radiograph: Small bowel obstruction
▪ At points of heaviest meconium concentration:
infiltrated gas may create bubbly granular appearance
TREATMENT
▪ High osmolarity gastrografin enema
COMPLICATIONS / PROGNOSIS
▪ Most survive neonatal period
▪ If unsuccessful/perforation is suspected: Laparotomy –
ileum is opened at largest diameter of impaction, irrigation
▪ If associated with CF: long term prognosis
depends on severity of underlying disease
▪ 50% have associated intestinal atresia, stenosis/ volvulus
which requires surgery
▪ Some requires bowel resection w/ temporary double
barrel enterostomy ff by serial irrigations and distal
refeeding / primary anastomosis at initial operation
▪ Intestinal obstruction in the distal colon, rectum, anal
canal caused by disproportionately low amount of
water in the intestinal lumen
▪ Initial treatment
● Glycerin suppository or
● Rectal irrigation with isotonic saline
▪ Associated w/ small left colon syndrome in IDM, CF,
Hirschsprung Disease, maternal opiate use, magnesium
sulfate therapy
▪ Gastrografin enema
● Hyperosmolar water soluble, radiopaque solution
● Diagnostic & therapeutic
● Draws fluid rapidly into the intestinal lumen and
loosens the inspissated material
▪ Can cause intrauterine intestinal obstruction,
meconium peritonitis unrelated to cystic fibrosis
▪ 30% spontaneously resolves
▪ Anorectal plugs → mucosal ulceration from bowel wall
erosion and intestinal perforation
*see Constipation*
Batch Clingy
HIRSCHSPRUNG
DISEASE
PPS Oral Exam Reviewer 2020
25
Complex
DISEASE
ETIOLOGY / INCIDENCY / PATHOGENESIS
Most common life-threatening emergency of the GIT
▪ 5-10% in <1500g
▪ Mortality rate: 20-30%
▪ Increase with decrease BW and AOG
CLINICAL MANIFESTATIONS
▪ Onset: 2nd or 3rd wk of life but can be late as
3mos in VLBW
DIAGNOSIS
▪
Neutropenia,
anemia,
thrombocytopenia,
coagulopathy, metabolic disease
▪ 1st signs: nonspecific, lethargy, temperature
instability,
abdominal
distention,
feeding
intolerance, bloody stools
▪ Plain abdominal radiograph
Pneumatosis intestinalis
● Air in the bowel wall
● Diagnostic
Portal venous gas – severe
Pneumoperitoneum—perforation
▪ Cause: multifactorial
▪ Hypotension, respiratory failure common
▪ Major Risk Factors:
● Prematurity
● Bacterial colonization of the gut
● Formula Feeding
▪ NEC in term: secondary disease (history of birth
asphyxia, down syndrome, congenital heart disease,
rotavirus infection, gastroschisis, Hirschsprung disease)
NECROTIZING
ENTEROCOLITIS
PATHOGENESIS
▪ Mucosal ischemia and subsequent necrosis, gas
accumulation in the submucosa of the bowel wall
(pneumatosis intestinalis) → perforation, peritonitis,
sepsis, death
▪ Most commonly involved: distal part of the ileum and
proximal segment of colon
▪ Fatal cases: may extend from stomach to rectum (NEC
totalis)
▪ Exposure to metabolic substrate in the context of
immature intestinal immunity, microbial dysbiosis and
mucosal ischemia
▪ Progression is rapid but unusual to progress
from mild to severe after 72 hrs
▪ UTZ with Doppler: evaluate free fluid, abscess,
bowel wall thickness, peristalsis, perfusion
▪ DDx: infections, GI obstruction, volvulus, isolated
intestinal perforation
TREATMENT
▪ Supportive care and prevention of further injury
w/ cessation of feeding, nasogastric decompression
and IV fluids
▪ Attention to respiratory status, coagulation profile,
acid base and electrolyte balances
▪ Do Blood CS then start systemic antibiotics (Gram
positive, Gram negative, anaerobes)
▪ Remove umbilical catheters
▪ Assisted ventilation in apnea or abdominal
distention contributes to hypoxia and hypercapnia
▪ Crystalloid/ blood products, CV support with fluid
boluses and or inotropes and correction of
hematologic, metabolic, electrolyte abnormalities
▪ Perforation on radiograph – absolute indication
for surgery
▪ Relative indications:
Progressive clinical deterioration despite maximum
medical mgt
Single fixed bowel loop
Abdominal wall erythema
▪ Surgery should be performed after intestinal
necrosis develops but before perforation and
peritonitis.
▪ Options: Primary Peritoneal Drainage or
Exploratory Laparotomy with resection of the
necrotic intestine and usually stoma creation
COMPLICATIONS / PROGNOSIS
▪ Medical management fails in 20-40% of
patients with pneumatosis intestinalis at
diagnosis, of these 20-50% die.
EARLY POSTOP COMPLICATIONS
▪ Wound infection
▪ Dehiscence
▪ Stomal problems – prolapse, necrosis
LATE POSTOP COMPLICATIONS
▪ Intestinal strictures (10%)
▪ Short bowel syndrome (malabsorption,
growth failure, malnutrition)
▪ Complications related to central venous
catheters – sepsis, thrombosis
▪ Cholestatic jaundice
▪ Adverse growth and neurodevelopmental
outcomes
PREVENTION
▪ Use of human milk, fortification is essential
for preterm infants
▪ No clear consensus on use of probiotics,
prebiotics and synbiotics
▪ Inhibitors of gastric acid secretion (H2
blockers, PPI) or prolonged empirical
antibiotics in early neonatal period increases
risk of NEC and should be avoided.
Batch Clingy
▪ Genetic predisposition: variants in genes regulating
immunomodulation and inflammation (TLR4, IL6),
apoptosis and cellular repair (plt activating factor), oxidant
stress (VEGF, arginine, nitric oxide)
PPS Oral Exam Reviewer 2020
26
Chronic
DISEASE
DEFINITION
PATHOGENESIS
▪ Structural defect arising from a localized error
in morphogenesis that results in the abnormal
formation of a tissue or organ
Caused by:
▪ Gene mutations
● Genes are often transcription factors, part
of evolutionarily conserved signal transduction
pathways, or regulatory proteins required for
key developmental events
▪ Chromosome aberrations and copy number
variants
▪ Environmental factors
▪
Interactions
between
genetic
and
environmental factors
MALFORMATION
EXAMPLES
Trisomy 21, Teratogens
Spondylocostal dysostosis (SCD)
▪ Vertebral segmentation defects assoc w/ other malformations, such as
NTDs
▪ Etiologically heterogeneous, mutations in the gene coding for delta-like 3
(DLL3), a ligand of the Notch receptors.
APPROACH TO DIAGNOSIS /
LABORATORY TESTS
Medical History
▪ Pedigree/ family history (3 generation)
▪ Perinatal history
▪ Maternal exposures to teratogenic drugs or chemicals
▪ Natural history of phenotype
Smith-Lemli-Opitz syndrome (SLOS)
▪ Mutations in the sterol delta-7-dehydrocholesterol reductase (DHCR7)
gene, (enzyme for cholesterol biosynthesis)
▪ Syndactyly in 2nd and 3rd toes; postaxial polydactyly, anteverted nose;
ptosis; cryptorchidism; and holoprosencephaly
Physical Exam
▪ Evaluate size and formation of body structures
▪ Size and shape of head
▪ Eye position and shape
▪ Categorize defects to major/minor
● Major: significant dysfunction or require surgical
correction
Rubinstein-Taybi syndrome
▪ Heterozygous, loss-of-function deleterious sequence variants in a gene
coding for a transcriptional coactivator called CREB-binding protein (CBP)
and from deleterious sequence variants in the EP300 gene
▪ Developmental delays and intellectual disability, broad and angulated
thumbs and halluces, and congenital heart disease.
Imaging Studies
▪ Full Skeletal Survey – short/disproportionate stature
▪ Brain Imaging – microcephaly, hypotonia, neurologic
symptoms
▪ Echocardiography
▪ Renal ultrasonography
X-linked lissencephaly
▪ Severe neuronal migration defect, smooth brain with reduction or
absence of gyri and sulci in males and intellectual disability and seizures in
females
▪ Deleterious sequence variants in DCX protein (regulates the activity of
dynein motors that contribute to movement of the cell nucleus during
neuronal migration)
Diagnosis
▪ Assessment based on specificity
▪ Prioritize rarer selection or pathognomonic findings
▪ Feature index of textbook or computerized database
(OMIM)
Down syndrome
▪ Extra copy of an entire chromosome 21 or, less frequently, extra copy of
the DS critical region on chromosome 21. Chromosome 21 contains 250
genes, and thus DS have an (↑) dosage of the numerous genes encoded by
this chromosome that causes their physical differences
TREATMENT
Anticipatory guidance &
medical monitoring for
syndrome
specific
medical risks
Genetic
counseling,
include recurrence risk
provision
Lab Studies & Genetic Test
▪ Cytogenetic studies w/ Giemsa banded chromosome
analysis or karyotyping - GOLD STD
▪ Array CGH and SNP arrays enable copy number variant
detection and, in the case of SNP arrays, evaluation of loss of
heterozygosity.
▪ Abnormal organization of cells into tissues
DYSPLASIA
PPS Oral Exam Reviewer 2020
Ethanol
▪ Causes fetal alcohol syndrome (FAS), fetal alcohol spectrum disorder
(FASD), or fetal alcohol effects (FAE)
▪ Microcephaly, developmental delays, hyperactivity, and facial dysmorphic
features
▪ Toxic to the developing central nervous system (CNS), causes cell death in
developing neurons
Neurocutaneous melanosis sequence with atypical migration of
melanocyte precursor cells from the neural crest to the periphery,
manifesting as melanocytic hamartomas of skin and meninges
Batch Clingy
Neural tube defects
▪ Multifactorial, defects in folate sensitive enzymes or folic acid uptake
27
▪ Alteration in shape or structure of a structure
or organ that has developed, or differentiated,
normally
Major Intrinsic Causes:
▪ Primary neuromuscular disorders
▪ Oligohydramnios caused by renal defects
DEFORMATION
Defect resulting from the destruction of a
structure that had formed normally before the
insult
DISRUPTION
MULTIPLE
ANOMALIES
Fetal movement is required for the proper
development of the musculoskeletal system,
and restriction of fetal movement – can cause
MSK deformations
Syndrome
Pattern of multiple abnormalities that are
related by pathophysiology, resulting from a
single, defined etiology
Sequences
Multiple malformations that are caused by a
single event, although the sequence itself can
have different etiologies
Major Extrinsic Causes:
▪ Fetal crowding and restriction of fetal
movement
▪ Oligohydramnios from chronic leakage of AF,
abnormal shape of amniotic cavity d/t uterine
shape, volume of AF and size & shape of fetus,
breech
Entanglement
▪ Followed by tearing apart or amputation of
normally developed structure usually a
digit/limb
Interruption to the blood supply
▪ Infarction, necrosis, and resorption of
structures distal to the insult
▪ If early AOG, usually involves atresia/ absence
of body part
▪ Oligohydramnios produces deformations by in utero compression of limbs
● Dislocated hips, equinovarus foot deformity), crumpled ears, or small
thorax
▪ Chromosome deletion syndromes may also be identified
with specific and sensitive FISH analysis
▪ Molecular testing
▪ Most children with deformations from extrinsic causes are otherwise
completely normal, and their prognosis is usually excellent. Correction
typically occurs spontaneously.
▪ Deformations caused by intrinsic factors, such as multiple joint
contractures resulting from CNS or peripheral nervous system defects, have
a different prognosis and may be much more significant for the child
▪ Amnionic membrane rupture sequence → to amputation of fingers/ toes,
tissue fibrosis, and tissue bands
▪ The prognosis for a disruptive defect is determined entirely by the extent
and location of the tissue loss.
▪ Sanger sequencing – for single nucleotide variants, exons,
genes
▪ Panel testing – multiple relevant genes can be interrogated
for single nucleotide variants, gene deletions and duplications
▪ Whole Exome Sequencing – examines approx 200,000
exons or 1-2% of DNA that comprises the coding regions of
the genome. Performed w/ a trio approach (px and both
parents tested simultaneously) so that inheritance pattern or
segregation of deleterious sequence variants can be
determined thus simplifying analysis
▪ Whole genome sequencing - examines all the DNA content
including noncoding regions and includes analysis for
cytogenetic rearrangements in addition to copy number loss
or gain.
Pierre-Robin Sequence
▪ Small jaw (mandibular hypoplasia) → glossoptosis (tongue relatively larger
for oral cavity hence drops back) → blocking closure of posterior palatal
shelves → U shaped cleft palate
DiGeorge sequence of primary 4th brachial arch and 3rd and 4th
pharyngeal pouch defects, leading to aplasia or hypoplasia of the thymus
and parathyroid glands, aortic arch anomalies, and micrognathia
Batch Clingy
Association
Non random grouping of malformations in
which there is an unclear, or unknown,
relationship among the malformations, such
that they do not fit the criteria for a syndrome
or sequence
PPS Oral Exam Reviewer 2020
28
Chronic
MANAGEMENT
▪ Programs aimed at cognitive training, stimulation, development,
education
● Can perform activities of daily living; guardian for complex
financial, legal, medical decisions
▪ Anticipatory guidance: screening, evaluation, and care for chronic
disorders
▪ Special Olympics: recommend sports participation
● X-ray (full extension & flexion views) of neck → sports w/
hyperextension, radical flexion, pressure on neck/upper spine
(swimming, butterfly stroke, diving, pentathlon, high jump, equestrian
sports, gymnastics, football, soccer, alpine skinning, warm-up exercise)
● (+) atlantoaxial instability → participation if guardians request;
written certification from MD & acknowledgment of risks by guardian
Batch Clingy
TRISOMY
▪ Most common form of aneuploidy; Can occur in all cells or mosaic
▪ Exhibit consistent and specific phenotype depending on chromosome involved
▪ ↑ with advanced maternal age: women who are ≥35yr at delivery → offer genetic counseling & prenatal diagnosis (serum screening, UTZ, cell-free fetal DNA detection, amniocentesis, chorionic villus sampling)
DISEASE
EPIDEMIOLOGY/PATHOGENESIS
CLINICAL MANIFESTATIONS
DIAGNOSIS
▪ Most common type of trisomy in liveborn infants
Cognitive impairment + Congenital anomalies + Dysmorphic features
▪ Women in 2nd trim → quad screen: 4 maternal
▪ Most common genetic etiology of moderate intellectual
▪ Developmental delay: universal
serum tests (free β-hCG, unconjugated estriol,
disability
● Social dev’t relatively spared (but ASD may occur)
inhibin, and α-fetoprotein)
▪ Incidence in live births ~1 in 733 → twice at conception
● Difficulty in expressive language
● 80% of pregnancies (5% false positive)
(early pregnancy losses)
▪ CHD (50%): AVSD, VSD, isolated secundum ASD, PDA, TOF
▪ 1st trim: fetal nuchal translucency (NT) thickness
▪ ~95%: 3 copies of chromosome 21
▪ Pulmonary complications: recurrent respiratory infection, sleep-disordered
● Alone: ≤70% detection rate
▪ 97% supernumerary chromosome maternal origin, errors
breathing, laryngo- and tracheobronchochomalacia, tracheal bronchus,
● W/ maternal serum β-hCG and pregnancyin meiosis
pulmonary HTN, asthma
associated plasma protein-A (PAPP-A): 87%
▪ 4%: Robertsonian translocation
▪ Congenital and acquired GI anomalies (celiac disease)
● Integrated screen w/ 2nd trim screening: 95%
▪ 1%: mosaic
▪ Hypothyroidism
▪ Detection of cell-free fetal DNA in maternal plasma
▪ Partial trisomy: only a part of long arm of chromosome 21
▪ Megakaryoblastic leukemia, immune dysfunction, DM, seizures, alopecia, JIA,
● 98% detection rate; noninvasive; replace
TRISOMY 21
in triplicate
hearing & vision problems
conventional 1st- and 2nd-trimester screens
(Down syndrome)
▪ Least common: no visible chromosome abnormality
▪ Alzheimer disease–like dementia: 4th decade (incidence 2-3x higher than
▪ Chromosome analysis indicated in every person
sporadic Alzheimer)
suspected of having Down syndrome
▪ Most males sterile; some females able to reproduce, 50% chance of having
● Translocation identified → parental chromosome
trisomy 21
studies → determine translocation carrier → high
▪ 15%: misalignment of the 1st cervical vertebra (C1) → risk for spinal cord injury
recurrence risk for another affected child
w/ neck hyperextension or extreme flexion
(translocation (21;21) carriers: 100% recurrence risk
▪ ~18-38%: psychiatric comorbidity: inattentiveness, stubbornness, need for
for chromosomally abnormal child)
routine; aggression & self-injurious behavior less common (respond to
educational, behavioral, or pharmacologic interventions)
▪ Life expectancy: ~50-55yo
▪ Not possible to distinguish the phenotypes → mosaic tend to be milder
PPS Oral Exam Reviewer 2020
29
TRISOMY 13
(Patau syndrome)
▪ Relatively less common
▪ Characteristic set of congenital anomalies and severe
intellectual disability
▪ Prenatal UTZ: IUGR w/ polyhydramnios, abnormal hand positioning ("clenched hands"), choroid plexus cysts
(Uptodate)
▪ Intensive tx: resuscitation & surgical procedures → may prolong
survival
▪ "Noninterventional paradigm" supportive not intensive tx → high
mortality, severe ID in survivors >1yr, lack of cure (not universally
accepted)
(Uptodate)
▪ Tx depend on type of major/life-threatening abnormalities
▪ Multidisciplinary team
▪ "Noninterventional paradigm" → not universally accepted
(Uptodate)
Batch Clingy
TRISOMY 18
(Edwards syndrome)
▪ Classic triad: micro/anophthalmia, cleft lip and/or palate, and postaxial polydactyly
▪ Prenatal UTZ: characteristic CNS defects
▪ Survive >1yr: severe ID, seizures, failure to thrive
(Uptodate)
PPS Oral Exam Reviewer 2020
30
▪ Complete or partial monosomy of X chromosome
▪ Single X maternal origin: 80%
▪ ½ 45,X chromosome complement; ~15% mosaics
▪ ~1 in 1,500-2,500 liveborn female
● assoc w/ spontaneous abortion (~95–99%
conceptions miscarried)
TURNER
SYNDROME
▪ Mechanism of chromosome loss unknown; risk does not
increase w/ maternal age
▪ Phenotype → X-linked gene that escape inactivation
▪ SHOX: major locus w/in pseudoautosomal region of the
X chromosome (PAR1)
● important for growth in Turner syndrome, Leri-Weill
syndrome, idiopathic short stature (rare)
▪ Normal ovarian function: Xp & 2 supergenes on Xq
Recombinant human growth hormone
▪ ↑Ht velocity& ultimate stature
▪ Initiated early childhood and/or evidence of ht velocity attenuation
(specific Turner syndrome growth curves)
▪ Monitor IGF-1 → significantly ↑, dose of GH ↓
▪ Can cause excessive growth of the hands and feet
▪ Not significantly aggravate carb tolerance/cause adverse events
Oxandrolone
▪ Alone/in combination w/ GH
▪ Synthetic anabolic steroid → weak androgenic effects → monitor for sx
of pubarche, hepatotoxicity (rare)
Estrogen therapy
▪ Improve verbal and nonverbal memory
▪ Psychological preparedness
● 12yr: normal pace of puberty w/out interfering w/ GH effect on ht
▪ Delay → deleterious to bone health
▪ Glucose tolerance worsens, but fat-free mass, BP & general physical
fitness improve
▪ Neurocognitive profile unaffected by estrogen status
▪ Oral estrogen: conjugated estrogen (Premarin) 0.15-0.625mg QD;
micronized estradiol (Estrace) 0.5mg QD, 3-6mo
▪ Transdermal patches (bypass 1st hepatic metabolism, ↓ dose): 6.25µg
QD gradual ↑ over 2yr to adult dose 100-200µg QD
▪ May be cycled (days 1-23), progestin (Provera) 5-10mg QD on day 10-23
→ withdrawal bleeding 1wk after
▪ Combination OCP
Psychosocial support
▪ Psych eval: time of dx, behavior/cognition sx, before school entry
Batch Clingy
sexual infantilism,
webbed neck, and
cubitus valgus in
adult females
▪ Newborn: SGA/LBW, webbing of the neck, protruding ears, lymphedema of the hands and feet, or phenotypically normal
▪ Short stature cardinal finding → chromosomal analysis: considered routinely in short females
● UTZ of heart, kidneys and ovaries after diagnosis
▪ CHD (40%): bicuspid aortic valves, coarctation of the aorta, aortic stenosis, MVP, anomalous pulmonary venous drainage
● Complete cardiac eval (webbed neck ↑ chance of CoA)
▪ Renal anomalies: pelvic kidney, horseshoe kidney, double collecting system, complete absence of 1 kidney, UPJO
● ↑ HTN & UTI
▪ Gonadal dysgenesis
● Process of oocyte loss accelerated (absence of 1 X chromosome; nearly all oocytes gone by 2yr) → gonads streaks of fibrous tissue
- early onset of adrenarche (↑DHEAS); but delayed pubarche
- lack of secondary sex characteristics; but 10-20% spontaneous breast devt
- primary amenorrhea; small % (+)menstrual period & pregnancy
- risk of miscarriage, offspring ↑ risk of trisomy 21, premature menopause
● Gonadotropins (particularly FSH): ↑during infancy → progressive ↓ 2-3yr → nadir 6-8yr → ↑(adult castrate level)10-11yr
▪ Autoimmune thyroid disease, w/ or w/out goiter (10–30%)
● Thyroid peroxidase and/or thyroglobulin antibodies → checked periodically; if (+) → thyroxine & TSH
▪ Age-dependent abnormality in carbohydrate metabolism: abnormal glucose tolerance & insulin resistance
▪ Cholesterol levels ↑
▪ IBD (Crohn disease & ulcerative colitis), GI bleeding (abnormal mesenteric vasculature), delayed gastric emptying
▪ Celiac disease (4–6%): tissue transglutaminase immunoglobulin A antibodies → around age 4yr then q2-5yr
▪ Sternal malformations (lateral chest radiography); congenital hip dysplasia
▪ Most common skeletal abnormalities: shortening of the 4th metatarsal and metacarpal bones, epiphyseal dysgenesis in the joints of the
knees & elbows, inadequate osseous mineralization, Madelung deformity, scoliosi s (10%), inadequate osseous mineralization
▪ Eye findings: anterior segment dysgenesis & keratoconus
▪ Pigmented nevi, melanocytic nevi
▪ Recurrent bilateral otitis media (~75%)
▪ Sensorineural hearing deficits common → ↑freq w/ age
▪ Gross and fine motor sensory integration problem → fail to walk before 15mo
▪ Normal intelligence in most; early language dysfunction → raise question about developmental delay
▪ ↑ risk for social isolation, immaturity, anxiety
▪ Dyslexia, nonverbal learning disability, ADHD, deficits in perceptual spatial skills
▪ Gonadoblastoma: 7-10% of Y-positive patients
● Prophylactic gonadectomy (timing being reevaluated)
PPS Oral Exam Reviewer 2020
31
MANAGEMENT
▪ Inhibitors of mGluR (overexpressed in fragile X): clinical trials
▪ Minocycline (lowers MMP-9): preliminary trials → short-term
improvements in anxiety, mood, and the clinical Global Impression Scale
Batch Clingy
FRAGILE CHROMOSOME SITES
▪ Regions of chromosomes → tendency for separation, breakage, attenuation under particular growth conditions
▪ At least 120 chromosomal loci (many heritable) identified
EPIDEMIOLOGY / PATHOGENESIS
CLINICAL MANIFESTATIONS / DIAGNOSIS
DISEASE
▪ Distal long arm of chromosome Xq27.3
▪ Male: intellectual disability, autistic behavior, postpubertal macroorchidism, hyperextensible finger joints, characteristic facial features
▪ 3% of males w/ ID
(long face, large ears, prominent square jaw)
▪ FRAXE on Xq28 → mild intellectual disability
▪ Females: varying degrees of intellectual disability and/or learning disabilities
▪ CGG repeat expansion → silence gene producing fragile
▪ DNA testing: expansion of a triplet DNA repeat inside the FMR1 gene on X chromosome >200 repeats
FRAGILE X
X mental retardation protein (FMRP) → FMRP deficiency
● Involves area of gene that contains number of trinucleotide (CGG) repeats (typically <50 in unaffected)
SYNDROME
● upregulates metabotropic glutamate receptor
● Larger triplet repeat expansion = more significant is the intellectual disability
(mGluR) 5 pathway & alters the expression of matrix
● Fragile X–associated tremor/ataxia syndrome: males w/ premutation triple repeat expansions (55-200 repeats) → adult, late-onset,
metalloproteinase (MMP) 9
progressive neurodegenerative disorder
● Females with premutation triple repeat expansions → ↑risk for premature ovarian failure (POF)
PPS Oral Exam Reviewer 2020
32
Complex
AMINO ACID DISORDERS
ETIOLOGY / INCIDENCE / PATHOGENESIS
Classic Homocystinuria
▪ Cystathionine β-synthetase deficiency
▪ Most common IE of methionine metabolism
▪ 1 in 200,000 to 1 in 350,000 live births
▪ Autosomal recessive trait
▪ Gene for cystathionine β-synthase (CBS) is on
chromosome 21q22.3.
▪ Most affected patients are compound heterozygotes for
2 different alleles
▪ Heterozygous carriers are asymptomatic
HOMOCYSTINURIA
Homocysteine
-Intermediate compound
of methionine
-Remethylated to
methionine by
methionine synthase w/c
requires metabolite of
folic acid (5-methyltetrahydrofolate) as a
methyl donor and a
metabolite of vitamin
B12 (methylcobalamin)
as a cofactor
MAPLE SYRUP URINE
DISEASE (MSUD)
Defects in Methylcobalamin Formation
▪ 7 distinct defects in the intracellular metabolism of
cobalamin may interfere with the formation of
methylcobalamin →
cblC, cblD (including cblD variant 1), cblE (methionine
synthase reductase), cblG (methionine synthase), cblF,
cblJ, and cblX.
▪ Patients w/ cblC, cblD, cblF, cblJ, and cblX →
methylmalonic acidemia + homocystinuria – formation
of both adenosyl-cobalamin and methylcobalamin is
impaired
▪ Patients with cblE, cblG, and cblD variant 1 defects are
unable to form methylcobalamin → homocystinuria only
Deficiency of Methylenetetrahydrofolate Reductase
(MTHFR)
▪ This enzyme reduces 5,10-methylene- tetrahydrofolate
to form 5-methyltetra- hydrofolate, which provides the
methyl group needed for remethylation of homocysteine
to methionine
▪ Autosomal recessive trait
Branched-chain α-keto acid dehydrogenase deficiency
▪ Used in decarboxylation of leucine, isoleucine & valine
using thiamine pyrophosphate Vit B1 as coenzyme
▪ This enzyme consists of 4subunits: E1α, E1β, E2, and E3
▪ E3 subunit is shared with 2 other dehydrogenases,
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
▪ Birth: asymptomatic
▪ Infancy: nonspecific, FTT & developmental delay
▪ >3yo:
● Subluxation of ocular lens (ectopa lentis) →
astigmatism, glaucoma, staphyloma, cataracts, retinal
detachment, and optic atrophy
● Progressive intellectual disability, psychiatric and
behavioral disorders, seizures
● Skeletal deformities resembling Marfan (tall with
elongated limbs and arachnodactyly), scoliosis, pectus
excavatum or pectus carinatum, genu valgum, pes cavus,
high-arched palate, crowding of the teeth, fair
complexion, blue eyes, peculiar malar flush, generalized
osteoporosis esp. spine
●
Thromboembolic
episodes
(d/t
elevated
homocysteine levels → abn angiogenesis and inhibition of
fibrinolytic activity) of large & small vessels → optic
atrophy, paralysis, cor pulmonale, severe HTN from renal
infarcts
● Spontaneous pneumothorax, acute pancreatitis –
rare complications
▪ 1st few months of life
Nonspecific, vomiting, poor feeding, failure to thrive,
lethargy, hypotonia, seizures, developmental delay
▪ Late-onset forms
Neurocognitive defects, psychosis, peripheral neuropathy
DIAGNOSIS
▪ ↑ Methionine & homocysteine
● Confirmed by molecular analysis of
cystathionine B-synthase (CBS) or by assay of the
enzyme in cultured fibroblasts, phytohemagglutininstimulated lymphocytes, or liver biopsy
▪ Prenatal Diagnosis
DNA analysis or enzyme assay of cultured amniotic
cells
▪ Megaloblastic anemia, hyperhomo- cysteinemia,
homocystinuria, hypome- thioninemia
▪ DNA testing or by complementation studies in
cultured fibroblasts
TREATMENT
▪ Dietary protein restriction
▪ Methionine restriction with cysteine
supplementation
▪ Vitamin B6 supplementation – high doses
100-500mg/day
▪ Betaine (trimethylglycine, 6g/day for
adults or 200-250mkday for children)
lowers homocysteine levels in body fluids
by
remethylating
homocysteine
to
methionine which may result in elevation
of plasma methionine levels
▪ Folate (1-5mg/day) and vitamin B12 for
vitamin B6–nonresponsive
COMPLICATIONS / PROGNOSIS
▪ Vitamin B6 – responsive: fewer
complications and later age of onset of
complications than w/ vitamin B6–
nonresponsive form
▪ Cerebral edema in vit B6-nonresponsive
▪ Vitamin B12 in the form of high dose
hydroxycobalamin
▪ Improves w/ treatment
▪ Prenatal Diagnosis
Studies in amniotic cell cultures
▪ Renal artery thrombosis, HUS, pulmonary HTN, and
optic nerve atrophy have been reported
▪ Apnea, seizure, microcephaly, coma, death
▪ Developmental delay, ataxia, motor abnormalities,
peripheral neuropathy, psychiatric manifestations
▪ Thromboembolism also observed
▪ Exposure to nitrous oxide (inhibits methionine synthase)
→ neurologic deterioration → death
▪ Might present before NBS results are available
▪ Difficulty feeding, vomiting, lethargy → coma,
hypertonicity, muscular rigidity, opisthotonic posturing,
convulsions → death
▪ Periods of hypertonicity may alternate w/ bouts of
▪ Moderate homocystinemia and homocystinuria
▪ Methionine concentration is low or low-normal
(vs classic)
▪ Confirmed by molecular analysis of MTHFR
▪ Cultured fibroblasts or leukocytes.
Prenatal Diagnosis
Molecular analysis of MTHFR or measuring MTHFR
enzyme activity in chorionic villus cells/amniocytes
▪ Ketoacidosis, hypoglycemia
▪ Peculiar odor of maple syrup in urine, sweat, and
cerumen
▪ Amino acid analysis – markedly ↑ leucine,
▪ Folic acid + vitamin B6 + vitamin B12 +
methionine + betaine
▪ Hydration and hemodialysis
● Emergency treatment for symptomatic
neonates
● Rapid removal of the BCAAs & their
metabolites from tissues & body fluids
▪ Improved intellectual outcome expected
if treatment is initiated before first crisis
▪ Developmental delay in severe cases
▪ Recurrent episodes of ketoacidosis,
cerebral edema and death especially when
Batch Clingy
DISEASE
33
Phenylalanine
hydroxylase
deficiency
or
Tetrahydrobiopterin (BH4) (cofactor of PAH) biosynthesis
or recycling defects
PHENYLKETONURIA
(PKU)
▪ Excess phenylalanine metabolized to phenylketones
(phenylpyruvate & phenylacetate) → excreted in urine
▪ PAH converts PA to tyrosine (for production of the NTs
epinephrine, NE, Dopa)
▪ High levels of PA saturate transport system across BBB
→ inhibited cerebral uptake of other large neutral amino
acids (branched chain AAs, tyrosine, and tryptophan) →
impaired brain protein synthesis
TYPE I: Fumarylacetoacetate hydrolase deficiency
▪ Liver, kidney & nerve damage caused by metabolites of
tyrosine degradation esp. fumarylacetoacetate &
succinylacetone
TYROSINEMIA
▪ Autosomal recessive trait
▪ FAH gene maps to chromosome 15q25.1
▪ Common in French Canadians in Quebec
PPS Oral Exam Reviewer 2020
flaccidity → boxing & bicycling repetitive movements of
extremities
▪ ↑ Leucine competitively inhibits the uptake of other
amino acids by the large neutral amino acid (LNAA)
transporter. Once taken by the brain tissue, leucine is
metabolized by BCAA amino transferase to ⍺ketoisocaproic acid → disrupted metabolism of
neurotransmitters and amino acids glutamate, GABA,
glutamine, alanine and aspartate
▪ Can reversibly inhibit oxidative phosphorylation →
cerebral lactic acidosis → detrimental to neurons & glia
→ acute encephalopathy & brain edema (Leucinosis)
isoleucine, valine & alloisoleucine, ↓ alanine
▪ At birth: Asymptomatic
▪ After a few months:
Microcephaly, seizures, pale pigmentation, seborrheic,
eczematoid rash
▪ Later years:
Abnormal posturing, purposeless hand movements,
rhythmic rocking, athetosis, mental retardation,
behavioral or psychiatric disturbances, low bone mineral
density, osteopenia
▪ Musty/Mousy Odor
Severe PAH deficiency/Classic PKU:
▪ Plasma phenylalanine >20mg/dL
Patients with BH4 defects
▪ Additional neurologic problems 2o to dopamine and
serotonin deficiency
▪ Extrapyramidal signs, hypersalivation, swallowing
difficulties
▪ Sx progressive & marked diurnal fluctuation
▪ Hyperprolactinemia d/t hypothalamic dopamine
deficiency
▪ Might present before NBS results are available. Most at
2-6 mos of age.
▪ Earlier presentation, poorer prognosis
BH4 defects
▪ Measure Neopterin & Biopterin levels
▪ ↓ Dopamine & serotonin metabolites in CSF
analysis
▪ BH4 loading test with oral BH4 20mg/kg –
normalize PA & PA: tyrosine ratio within 4-12hrs
▪ Molecular testing & enzyme assay
▪ Severe liver failure, jaundice, ascites, and bleeding
diathesis – herald onset of disease, precipitated by
intercurrent illness that produces catabolic state
▪ Boiled cabbage odor – due to ↑ methionine
metabolites
▪ Peripheral neuropathy resembling acute porphyria,
triggered by minor infection, severe pain in the legs →
extensor hypertonia of neck & trunk, paralytic ileus,
marked weakness → respiratory failure, seizures
● Crisis lasts 1-7 days but recuperation from paralytic
crises require weeks to months
▪ Renal Fanconi syndrome (hyperphospha- turia,
hypophosphatemia, normal AG metab acidosis) → vitD
resistant rickets, nephromegaly, nephrocalcinosis
▪ Urine – ↑ Leucine, isoleucine, valine and their
ketoacids (few drops of 2,4-dinitrophenylhydrazine
reagent (0.1% in 0.1N HCl) to urine → yellow ppt of
2,4-dinitrophenylhydrazone)
▪ Neuroimaging: cerebral edema (cerebellum, dorsal
brainstem, cerebral peduncle & internal capsule) →
after recovery, hypomyelination & cerebral atrophy
Mild hyperphenylalaninemia:
▪ Between 2-10mg/dL
PAH deficiency
▪ Tandem mass spectrometry
▪ Blood PA level rise as early as 4hrs after birth
▪ NBS obtained in 1st 24-48hrs of life after feeding
protein
▪ ↑ Succinylacetone in serum and urine
▪ ↑ AFP
▪ ↑ Liver transaminases
▪ ↓ Liver synthesized coagulation factors
▪
Hypoglycemia
hyperphosphaturia,
hypophosphatemia, generalized aminoaciduria
Prenatal screening
Measurement of succinylacetone in AF
▪ Sufficient calories & nutrients – reverse
catabolic state
▪ Mannitol, diuretics, hypertonic saline – if
with Cerebral edema
▪ Supplementation w/ isoleucine & valine
– compete with leucine for the LNAA
transporter at the BBB → ↓ leucine entry
into CNS and help in the prevention and tx
of leucine encephalopathy
▪ Dietary protein restriction
▪ Leucine, isoleucine, valine restriction
▪ Thiamine supplementation (10-100
mg/day) for thiamine-responsive px
▪ Liver transplantation
▪ Dietary protein restriction
● Start at PA level >10mg/dL or if
persistent >6mg/dL
▪ Phenylalanine restriction – maintain level
at 2-6mg/dL
▪ Sapropterin dihydrochloride – a synthetic
BH4 analogue; for responsive patients
▪ Administration of LNAAs
▪ Some may require sapropterin
dihydrochloride plus dopa/carbidopa, 5hydroxytryptophan,
and/or
other
medications
“e” Mgt for Symptomatic Neonates:
▪ Dietary protein restriction
▪ Phenylalanine and tyrosine restriction
▪ NTBC (nitisinone) – selective enzyme
inhibitor of the tyrosine degradative
pathway
▪ Liver transplantation when HCC is
suspected
ill, surgery or fasting
▪ Acrodermatitis enteropathica –in infants
with very low plasma isoleucine/valine
▪ Normal development if diet is instituted
early although a mild decrease in IQ and
behavioral difficulties relative to unaffected
sibs
▪ Patients with biopterin defects: ↑ risk for
neurologic problems (seizures, dystonia)
▪ Liver disease could progress despite
dietary treatment
▪ NTBC treatment improves liver, kidney,
neurologic function, and reduces risk for
hepatocellular carcinoma
▪ Liver transplantation might still be
required
Prenatal diagnosis
DNA analysis of amniocytes or of chorionic villi if
familial pathogenic variants are known
Batch Clingy
pyruvate
dehydrogenase
and
α-ketoglutarate
dehydrogenase
▪ Deficiency of any of these subunits causes MSUD
34
▪ Rare autosomal recessive disorder
▪ Caused by tyrosine aminotransferase (TAT) gene
pathogenic variants, causing deficiency of cytosolic TAT
activity in liver
▪ TAT maps to chromosome 16q22
TYPE III: 4-Hydroxy-phenylpyruvate
deficiency
▪ Age of presentation: 1-17 mos
▪ Autosomal recessive
dioxygenase
GENERALITIES
▪ Catabolism of amino acids → ammonia production, which in high concentration is
toxic to the CNS
▪ Mammals detoxify ammonia to urea through a series of reactions known as the urea
cycle which is composed of 5 enzymes: carbamoyl phosphate synthetase 1 (CPS1),
ornithine
transcarbamylase
(OTC),
argininosuccinate
synthetase
(ASS),
argininosuccinate lyase (ASL), and arginase 1
▪ A 6th enzyme, N-acetylglutamate (NAG) synthetase (NAGS), catalyzes synthesis of
NAG, which is an obligatory activator (effector) of the CPS1 enzyme
▪ 1 in 35,000 live births
▪ Most common genetic causes of hyperammonemia in infants
Goals of Treatment in Acute Hyperammonemia
▪ Removal of ammonia from the body in a form other than urea
▪ Minimize endogenous protein breakdown and favor endogenous protein synthesis by
providing adequate calories & essential amino acids
DISEASE
ARGININEMIA
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Arginase deficiency
▪ Autosomal recessive
▪ 2 genetically distinct arginases in humans: Cytosolic
(ARG1) in liver & erythrocytes, (ARG 2) in renal & brain
mitochondria
PPS Oral Exam Reviewer 2020
▪ Developmental delay, seizures, intermittent ataxia, selfinjurious behavior
▪ Liver and renal abnormalities absent
▪ Assay of plasma tyrosine concentration: marked
hypertyrosinemia (>500μmol/L and may reach
1,100-2,750μmol/L)
▪ 4-hydroxyphenylpyruvic acid and its metabolites
are ↑ in urine
▪ Phenylalanine and tyrosine restriction
▪ Eye and skin lesions resolve with
treatment and intellectual outcome
improves
▪ Sustained moderate ↑ in plasma tyrosine (350-700
mmol/L on a N diet)
▪ (+) 4-hydroxyphenylpyruvic acid and its
metabolites in urine
▪ Low-phenylalanine, low-tyrosine diet
▪ Trial of Vitamin C – cofactor of 4-HPPD
▪ Improved intellectual outcome
UREA CYCLE DISORDERS
ACUTE TREATMENT OF HYPERAMMONEMIA
▪ IVF + electrolytes + glucose (10–15%) + lipids (1-2 g/kg/day) + minimal protein (0.25g/kg/day)
▪ Kidneys clear ammonia poorly, its removal from the body must be expedited by formation of compounds with a high renal
clearance
▪ Acylation therapy – uses an exogenous organic acid that is acylated endogenously with nonessential amino acids to form a
nontoxic compound with high renal clearance. Eg. sodium salts of benzoic acid and phenylacetic acid.
▪ Benzoate forms hippurate with endogenous glycine in the liver
▪ Phenyl acetate conjugates with glutamine to form phenylacetylglutamine, which is readily excreted in the urine.
▪ IV infusion of arginine, effective in all patients (except with arginase deficiency). It supplies the urea cycle with ornithine
which leads to formation of citrulline & arginosuccinate which are less toxic than ammonia and more readily excreted by the
kidneys
▪ Hemodialysis – if initial ammonia level is <500 μmol/L & if ongoing treatment fails within 4-6hrs
▪ Extracorporeal Detoxification – if >500 μmol/L
▪ Exchange Transfusion –if dialysis cannot be employed promptly or when the patient is a newborn with hyperbilirubinemia
▪ Oral neomycin limits growth of intestinal bacteria that can produce ammonia. Limited use in patients (e.g., neonates) in
whom reduction of hyperammonemia is an urgent priority.
▪ Oral lactulose acidifies the intestinal lumen → ↓ diffusion of ammonia across the intestinal epithelium. Limited applicability
in newborns, who have a high risk of acidemia and dehydration.
▪ Cooling as therapeutic adjunct in NB with metabolic encephalopathy caused by hyperammonemia
CLINICAL MANIFESTATIONS
DIAGNOSIS
▪ Rarely symptomatic in neonatal period
▪ Marked ↑ arginine in plasma & CSF
▪ Insidious onset
▪ Urinary orotic acid can be ↑
▪ Progressive spastic di-/tetraplegia, scissoring of the lower
▪ Determination of amino acids in plasma
extremities, choreoathetotis, loss of developmental
▪ Guanidino compounds (α-keto-guanidino- valeric acid and
milestones, failure to thrive, opisthotonus, seizures, cerebral
α-keto-argininic acid) are markedly ↑ in urine
LONG TERM THERAPY
▪ Protein restriction, sodium benzoate (250 mg/kg/24 hr), sodium
phenylbutyrate (250-500 mg/kg/24hr), and arginine (200-400 mg/kg/24hr) or
citrulline (in patients with OTC deficiency, 200-400 mg/kg/24 hr) is effective in
maintaining blood deficiency
▪ Arginine and citrulline are contraindicated in patients with argininemia
▪ Patients w/ difficulty taking sodium phenylbutyrate: trial of glycerol
phenylbutyrate (not for <2 months of age)
▪ Growth parameters, especially head circumference, and nutritional indices
(blood albumin, prealbumin, pH, electrolytes, amino acids, zinc, selenium)
should be followed closely
▪ Catabolic states (infections, fasting) that may trigger hyperammonemia should
be avoided. Must be treated vigorously if they occur
▪ Avoid valproic acid (can elevate blood ammonia)
TREATMENT
▪ Dietary protein restriction
▪ Alternative pathway drugs for
removing
ammonia
(sodium
benzoate and phenylbutyrate)
▪ Liver transplantation
COMPLICATIONS / PROGNOSIS
▪ Improved neurologic outcome but
some develop intellectual disability
Batch Clingy
TYPE II: Tyrosine aminotransferase deficiency
▪ Survivors develop chronic liver disease with ↑ risk of
HCC and cirrhosis
Ocular manifestations
▪ As early as 6 mos
▪ Excessive tearing, redness, pain, photophobia, corneal
lesions caused by tyrosine deposition
Skin lesions
▪ Later in life
▪ Painful, nonpruritic hyperkeratotic plaques on soles,
palms, fingertips
Intellectual disability
▪ Mild to moderate
35
▪ Argininosuccinate acid lyase deficiency
▪ Autosomal recessive
▪ 1 in 220, 000 live births
▪ ASL gene on chromosome 7q11.21
ARGININOSUCCINIC
ACIDEMIA
edema, death
▪ Low risk of symptomatic hyperammonemia –
hepatomegaly may be present
▪ Might present before NBS results available
▪ Anorexia, vomiting, lethargy → coma, seizures, intellectual
disability, failure to thrive, hypertension, gallstones, liver
fibrosis, hepatomegaly
▪ If untreated, trichorrhexis nodosa – dry and brittle hair
▪ Confirmed by assaying arginase activity in erythrocytes or
by the identification of the mutant gene.
▪ Hyperammonemia, moderate ↑ in liver enzymes
▪ Nonspecific ↑ in plasma glutamine and alanine
▪ Moderate ↑ in plasma citrulline (less than in citrullinemia)
▪ Marked ↑ in the concentration of argininosuccinic acid in
plasma, urine, and CSF
Prenatal diagnosis
▪ Enzyme assay, identification of variants in ASL gene;
argininosuccinic acid elevated in AF
▪ Argininosuccinate synthetase deficiency
▪ Autosomal recessive
▪ 1:250,000 live births
▪ Gene ASS1 on chromosome 9q34.11
CITRULLINEMIA TYPE I
CITRULLINEMIA TYPE II
▪ Citrin deficiency
▪ Citrin
● Aspartate-glutamate carrier protein
● Mitochondrial transporter encoded by a gene
(SLC25A13) located on chromosome 7q21.3
● Transports aspartate from mitochondria into
cytoplasm and replenishes the cytosolic aspartate pool
required for converting citrulline to argininosuccinic acid
▪ If aspartate is unavailable to the cytoplasmic component
of the urea cycle, urea will not be formed at a normal rate,
and citrulline will accumulate
▪ ASS activity is diminished in the liver of these patients,
but no pathogenic variant in the ASS1 gene has been
found. It is postulated that citrin deficiency interferes with
translation of messenger RNA for ASS enzyme in the liver.
Severe/Neonatal Form
▪ Most common, 1st few days of life
▪ Refusal to eat, vomiting, tachypnea, lethargy → deep
coma, seizures, hepatomegaly, increased ICP, bulging
fontanelle, dilated pupils
Subacute/Mild Form
▪ After 1yr of life
▪ FTT, frequent vomiting, developmental delay, dry brittle
hair
▪ Anorexia, vomiting, lethargy, seizures, coma, possibly
leading to death
Neonatal-onset form
▪ <1yo
▪ FTT, hepato(spleno)megaly, cholestatic jaundice
Early childhood-onset form
▪ Dietary preference for protein-rich and/or lipid-rich foods
▪ Aversion to carbohydrate-rich foods
▪ Failure to thrive, pancreatitis
Adult-onset form
▪ Neuropsychiatric problems – disorientation, delirium,
delusion, aberrant behavior, tremors, frank psychosis
Neonatal-Onset
▪ Hypoglycemia, abnormal AA profile
▪ Mild to moderately ↑ plasma ammonia
▪ Mild-mod conjugated hyperbilirubinemia, marked
hypoproteinemia
▪ Clotting dysfunction (prolonged PT, PTT)
▪ ↑ serum glutamyltransferase and alkaline phosphatase
activities
▪ Liver transaminases are usually normal.
▪ Ammonia & citrulline are usually normal, some w/ mod
elevations.
▪ ↑ Methionine, tyrosine, alanine, threonine, galactose, AFP
▪ Liver biopsy: fatty infiltration, cholestasis with dilated
canaliculi, and a moderate degree of fibrosis
Adult-onset
▪ Moderate hyperammonemia and hypercitrullinemia
▪ Fatty liver
ETIOLOGY / INCIDENCE / PATHOGENESIS
GLUTARIC ACIDEMIA
TYPE I (GAI)
▪ Glutaryl-CoA dehydrogenase deficiency
▪ Glutaric acid is an intermediate in the degradation of
PPS Oral Exam Reviewer 2020
▪ Improved intellectual outcome if
treatment is initiated early
▪ Developmental delay if severe
▪ Recurrent hyperammonemic episodes
Common Sequelae
▪ Intellectual disability
▪ Persistent hepatomegaly with mild
increases in liver enzymes
▪ Bleeding tendencies as a result of
abnormal clotting factors
▪ Improved intellectual outcome if
treatment is initiated early
▪ Developmental delay if severe
▪ Recurrent hyperammonemic episodes
Neonatal-onset
▪ Lactose-free diet
▪ MCT and fat-soluble vitamin
supplementation
Neonatal-onset
▪ Transient neonatal cholestasis and
variable hepatic dysfunction
▪ Some develop cirrhosis and have a
poor prognosis
▪ Hyperammonemia w/ marked ↑ plasma glutamine and
alanine with ↓ arginine
▪ Blood level of urea is usually low
▪ Greatly ↑ plasma citrulline (50-100x)
▪ Moderately ↑ urinary excretion of orotic acid →
crystalluria (orotate precipitation)
▪ Confirmed by DNA analysis/enzyme assay
Early childhood-onset
▪ Dyslipidemia
▪ Normal–slightly ↑ plasma ammonia
DISEASE
“e” Mgt for Symptomatic Neonates:
▪ Dietary protein restriction
▪
Essential
amino
acid
supplementation
▪ Arginine supplementation
▪ Alternative pathway drugs for
removing
ammonia
(sodium
benzoate and phenylbutyrate)
▪ Liver transplantation
ORGANIC ACIDEMIAS
CLINICAL MANIFESTATIONS /
DIAGNOSIS
PHYSICAL EXAM
▪ Rarely symptomatic in neonatal period, although
▪ Mild to moderate metabolic acidosis, ketosis,
macrocephaly may be present (at birth/1styr)
hypoglycemia,
hyperammonemia,
↑
serum
Early childhood-onset
Same diet as above
▪ MCT and fat-soluble vitamin
supplementation
▪
Sodium
pyruvate
supplementation
Adult-onset
▪ Low calorie, low carbs, high
protein diet – diet enriched with
protein and lipids helps restore
cytosolic aspartate pool and
stimulate ureagenesis
▪ MCT, arginine, and sodium
pyruvate supplementation
▪ Liver transplantation
TREATMENT
“e” Mgt for Symptomatic Neonates:
▪ Cessation of protein intake for 24 hr
Early childhood-onset
▪ Variable
Adult-onset
▪ Poor prognosis, improved with liver
transplantation
▪
Pancreatitis,
hyperlipidemia,
hepatoma - major complications
COMPLICATIONS / PROGNOSIS
▪ Improved intellectual
treatment is initiated early
outcome
if
Batch Clingy
▪ ARG1 in chromosome 6q23.2
36
lysine, hydroxylysine, tryptophan
▪ GCDH located on chromosome 19p13.2
▪ Delayed onset of motor milestones, irritability, feeding
problems
▪ Onset of the condition is usually heralded by acute
encephalopathic findings – loss of normal
developmental milestones (head control, rolling over, or
sitting), seizures, generalized rigidity, opisthotonos,
choreoathetosis, and dystonia caused by acute striatal
injury. These symptoms may occur suddenly in an
apparently normal infant after a minor infection.
▪ Insidious form
● Hypotonia & choreoathetosis → rigidity & dystonia
● Acute episodes of metabolic decompensation with
vomiting, ketosis, seizures, and coma also occurs.
GLUTARIC ACIDEMIA
TYPE II (GAII)
▪ Electron transfer flavoprotein (ETF) deficiency; ETF
dehydrogenase deficiency
▪ ETF and ETF-DH transfer electrons into the mitochondrial
ETC from dehydrogenation reactions catalyzed by VLCAD,
MCAD, and SCAD, as well as by glutaryl-CoA
dehydrogenase and 4 enzymes involved in BCAA oxidation
▪ Deficiencies of ETF or ETF-DH → illness w/ combined
features of impaired fatty acid oxidation and impaired
oxidation of amino acids.
▪ Commonly manifests in the neonatal period:
hypotonia, hepatomegaly, congenital anomalies – facial
dysmorphism and cystic kidney disease, coma
▪ Sweaty Feet Odor (d/t isovaleryl-CoA dehydrogenase
inhibition
▪ Generally lethal
▪ Late-onset forms variable, rarely have structural birth
defects
▪ Partial deficiency may mimic MCAD deficiency or other
milder fatty acid oxidation defects; have attacks of
fasting hypoketotic coma.
▪ 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
▪ This enzyme catalyzes the conversion of 3-HMG CoA to
acetoacetate and is a rate-limiting enzyme for ketogenesis
▪ Autosomal recessive
▪ 3-HMG-CoA lyase is encoded by gene HMGCL
3-HYDROXY-3METHYLGLUTARIC
ACIDURIA
▪ 30% 1st few days of life
▪ >60% bet 3-11 mos old
▪ Similar to 3-HMG-CoA synthase deficiency –
acute hypoketotic hypoglycemia, vomiting, severe
hypoglycemia, hypotonia, acidosis with mild or no
ketosis,
dehydration,
lethargy,
ataxia,
coma,
hepatomegaly
▪ Episodic hypoglycemia may contribute to
developmental delay
transaminases
▪ High concentrations of glutaric
acid in urine, blood, and CSF
▪ ↑ Glutarylcarnitine (C5-DC) in blood & urine
▪ Replacement of lost calories using
carbohydrates or lipids, IV L-carnitine, IV
dextrose
▪ Prompt treatment of infection
▪ Control of fever
▪ NBS: glutarylcarnitine levels
▪ Brain Imaging: ↑ Extraaxial (particularly frontal)
fluid with stretched bridging veins, striatal lesions,
dilated lateral ventricles, cortical atrophy (mainly in
frontotemporal region), and fibrosis
Prenatal diagnosis
▪ ↑ Glutaric acid in amniotic fluid
▪ Enzyme activity in amniocytes or chorionic villus
samples
▪ Identification of the known pathogenic variants in
GCDH
▪ Metabolic acidosis
▪ Hypoglycemia, hyperammonemia
▪ Acylcarnitine profile and urinary organic acids:
abnormalities corresponding to blocks in the
oxidation of fatty acids (ethylmalonate and C6-C10
dicarboxylic acids), lysine (glutarate), BCAAs
(isovaleryl-, isobutyryl-, ⍺-methylbutyryl-glycine)
▪ Confirmed by genetic testing for ETF (2 genes, A
and B) and ETF dehydrogenase
Partial deficiency
▪ Urinary organic acid profile: primarily elevations of
dicarboxylic acids and ethylmalonate, derived from
short-chain fatty acid intermediates
▪ Secondary carnitine deficiency is present
▪
Hypoglycemia,
moderate
to
severe
hyperammonemia, acidosis
▪ Mild or no ketosis
▪ Cat Urine Odor – urinary excretion of 3-hydroxy-3methylglutaric acid and other proximal intermediate
metabolites of leucine catabolism (3-methylglutaric
acid,
3-methylglutaconic
acid,
and
3hydroxyisovaleric acid)
▪ Dietary protein restriction
▪ Lysine & tryptophan restriction
▪ Arginine supplementation
▪ Riboflavin and carnitine supplementation
▪ Poor neurologic outcome if treatment is
started after acute neurologic injury
occurs
▪ Treatment might slow neurologic
deterioration
▪ Prone to subdural hematoma and retinal
hemorrhage following minor falls and
head traumas
▪ If with movement disorder: Baclofen,
diazepam, trihexy-phenidyl, and injectable
botulinum toxin A
“e” Mgt for Symptomatic Neonates:
▪ Dietary low-fat/low-protein diet
▪ Carnitine supplementation
▪ Riboflavin supplementation for responsive
cases (mild forms)
▪ Treatment for neonatal-onset forms is of
limited benefit but might be helpful for
patients with late-onset disease
▪ Most severely affected infants do not
survive neonatal period
▪ Frequent feedings
▪ Low-fat / low-protein (leucine-restricted)
diet
▪ Carnitine supplementation
▪ Glucose infusion for hypoglycemia
▪ Bicarbonate to correct acidosis
▪
RRT
for
severe
recalcitrant
hyperammonemia
▪ Improved intellectual outcome if
treatment is initiated early
▪ Developmental delay if severe
▪ Recurrent hypoglycemic episodes
decrease in frequency and severity with
age
Long term complications
Dilated cardiomyopathy, hepatic steatosis,
and pancreatitis
▪ Isobutyryl-CoA dehydrogenase deficiency
ISOBUTYRIC ACIDEMIA
PPS Oral Exam Reviewer 2020
▪ Uncertain because number of cases is small
▪ May be benign
▪ Case reports of cardiomyopathy associated with
carnitine deficiency
▪ Carnitine supplementation if deficiency
present
Batch Clingy
▪ Glutaric and dicarboxylic acids may also be ↑ in
urine during acute attacks
▪ Secondary carnitine deficiency
▪ Confirmed by molecular analysis of HMGCL or by
enzyme assay in cultured fibroblasts, leukocytes, or
liver specimens
37
▪ Might present before NBS results available
▪ Vomiting, lethargy, convulsions, and coma, possibly
death
▪ Sweaty Feet / Rancid Cheese Odor
ISOVALERIC ACIDEMIA
(IVA)
▪ Thrombocytopenia, leukopenia, occ pancytopenia,
BM
suppression,
hypocalcemia,
anemia,
ketoacidosis, moderate to severe hyperammonemia
▪ Accumulating derivatives of isovaleric acid,
isovalerylcarnitine (C5-carnitine w/c is found in NBS),
isovalerylglycine,
and 3-hydroxyisovaleric acid
▪ Confirmed by molecular analysis of IVD gene
Prenatal diagnosis
▪ Enzyme assay in cultured amniocytes
▪ IVD gene analysis
3-KETOTHIOLASE
DEFICIENCY
2-METHYL- BUTYRYLGLYCINURIA
3METHYLCROTONYLGLYCI
NURIA
2-METHYL-3HYDROXYBUTYRIC
ACIDEMIA
▪ Mitochondrial acetoacetyl CoA thiolase deficiency
▪ This reversible mitochondrial enzyme is involved in the
final steps of isoleucine catabolism and in ketolysis
▪ In the isoleucine catabolic pathway, the enzyme cleaves
2-methylacetoacetyl-CoA into propionyl-CoA and acetyl
coA
▪ In the fatty acid oxidation pathway, the enzyme
generates 2 moles of acetyl-CoA from 1 mole of
acetoacetyl-CoA. The same enzyme synthesizes 2methyacetoacetate-CoA and acetoacetyl-CoA in the
reverse direction
▪ Autosomal recessive
▪ ACAT1 gene located on chromosome 11q22.3
▪ Might present before NBS results are available
▪ Hallmark: ketoacidosis – triggered by infections,
prolonged fasting and large protein load
▪ Cognitive impairment, vomiting, lethargy and coma,
possibly death
▪ Abnormal odor
▪ 2-Methylbutyryl-CoA dehydrogenase deficiency (aka:
short/ branched chain acyl-CoA dehydrogenase)
▪ Most patients ascertained by NBS are clinically
asymptomatic and remain so, although several patients
have been described with a variety of problems
▪ Onset: between 3 weeks-3yo
▪ Highly variable phenotype
▪ Many patients asymptomatic
▪ Some w/ developmental delay w/o episodes of
metabolic decompensation, seizures, hyperammonemia,
and metabolic acidosis
▪ Severe 3-MCC deficiency: Acute episode of vomiting,
hypotonia, lethargy, and convulsions after a minor
infection, w/c may progress to Reye syndrome, coma
▪ 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC)
▪ Heteromeric enzyme consisting of ⍺(biotin containing)
and β subunits, encoded by genes MCCC1 and MCCC2,
respectively
▪ 1:2400 - 1:68, 000 live births
▪ Autosomal recessive
▪ Gene for ⍺-subunit (MCC1) located on chromosome
3q27.1; β subunit (MCC2) on chromosome 5q13.2
Maternal 3-MCC deficiency
▪ Mothers have variable neurologic phenotype
▪ 2-Methyl-3-hydroxybutyryl CoA dehydroge- nase
deficiency (aka:17-beta-hydroxysteroid dehydrogenase X
deficiency)
Mild: some males may have normal neurologic
development. Affected females have less severe disease.
Severe: Neurodegenerative disease, associated with
mental retardation, rigidity, choreoathetosis, seizures,
and cerebral atrophy
▪ Clinical variability has been observed in this X-linked
disorder
PPS Oral Exam Reviewer 2020
▪ Thrombocytopenia, leukopenia, anemia
▪ Possible basal ganglia damage
▪ Ketoacidosis, hypo/ hyperglycemia
▪ Mild-mod hyperammonemia
▪ Urine: large amounts of 2-methyl- acetoacetate and
its decarboxylated products butanone, 2-methyl-3hydroxybutyrate, and tiglylglycine
▪ Plasma acylcarnitine profile: ↑ C5:1 and C5-OH
carnitines
▪ Confirmed by molecular analysis of ACAT1 gene or
enzyme assay of leukocytes or cultured fibroblasts
▪ Mild to mod metabolic acidosis, ketosis,
hypoglycemia,
hyperammonemia,
↑
serum
transaminase
▪ Urine: Large amounts of 3-hydroxyisovaleric acid
and 3-methylcrotonylglycine
▪ ↑ 3-hydroxyisovalerylcarnitine (C5-OH) in NBS
▪ Severe secondary carnitine deficiency
▪ Confirmed by molecular analysis or measurement
of enzyme activity
“e” Mgt for Symptomatic Neonates:
▪ Hydration, reversal of catabolic state,
correction of met acidosis, facilitate
isovaleric acid excretion
▪ Dietary protein restriction <24hr
▪ Leucine restriction
▪ L-Carnitine
supplementation
(100
mg/kg/24hr oral) – ↑ removal of isovaleric
acid
by
forming
isovalerylcarnitine
(excreted in urine)
▪ Glycine supplementation (250 mg/kg/
24hr)
–
enhance
formation
of
isovalerylglycine (high urinary clearance)
▪ Renal replacement therapy if all else fails
“e” Mgt for Symptomatic Neonates:
▪ IVF and bicarbonate treatment
▪ 10% glucose w/ electrolytes to suppress
protein catabolism, lipolysis & ketogenesis
▪ Dietary protein restriction
▪ Isoleucine restriction
▪ Avoidance of fasting
▪
L-Carnitine
100mg/kg/day)
supplementation
▪ Improved intellectual outcome if
diagnosed and treated early
▪ If treated appropriately, most have
normal development
▪ Recurrent metabolic episodes
▪ Highly variable clinical course
▪ Improved intellectual outcome if
diagnosed and treated early
▪ If recognized and treated appropriately,
some patients have normal development
▪ Recurrent metabolic episodes
(50-
▪ The need for treatment with a low-protein
diet has not been established
▪ Generally good
▪ Hydration
▪ Glucose & sodium bicarbonate – correct
hypoglycemia and metabolic acidosis
▪ Dietary protein restriction
▪ Selected amino acid (leucine) restriction
▪ L- Carnitine supplementation
▪ Generally, good
▪ Mother might benefit from carnitine
supplementation if she has carnitine
insufficiency
▪ Dietary protein restriction improves the
metabolic markers but does not alter clinical
outcome
▪ Mother
treatment
generally
improves
with
▪ Poor for severe affected patients but
better for mildly affected patients
Batch Clingy
▪ Isovaleryl-CoA dehydrogenase deficiency → impaired
leucine degradation
38
▪ Deficiency of either mutase or its coenzyme →
accumulation of methylmalonic acid and its precursors
METHYLMALONIC
ACIDEMIA
(MMA)
Group of metabolic
disorders of diverse
etiology characterized by
impaired conversion of
methylmalonyl CoA into
succinyl-CoA
▪ Two biochemical forms of deficiency:
mut0 – no detectable enzyme activity, not responsive to
hydroxocobalamin therapy
mut− – indicates residual, although insufficient, mutase
activity
▪ 1:50,000 to 1:100,000 live births
▪ Gene for mutase (MUT) on the short arm of
chromosome 6p12.3
“e” Mgt for Symptomatic Neonates:
▪ Ketosis, metabolic acidosis, hyperglycinemia,
hypoglycemia,
anemia,
neutropenia,
thrombocytopenia
▪ Hyperammonemia (inhibition of proximal urea
cycle in the mitochondrial matrix)
▪ Large quantities of methylmalonic acid in body fluid
▪ Metabolites of propionic acid
(3-hydroxypropionate and methylcitrate) in the urine
▪ ↑ Propionylcarnitine (C3)
“e” Mgt for Symptomatic Neonates:
▪ Dietary protein restriction
▪ Isoleucine, methionine, threonine, valine
restriction
▪ Daily hydroxycobalamin IM injection if px
responsive
▪ Oral carnitine supplementation
▪ Antibiotic suppression of gut flora
(metronidazole or neomycin)
▪ Liver &/or kidney transplantation might be
required
▪ Confirmed by identifying pathogenic variants in the
causal gene, by measuring propionate incorporation
with complementation analysis in cultured
fibroblasts, and by measuring the specific activity of
the mutase enzyme in biopsies or cell extracts.
vitamin
B12
(adenosylcobalamin)
▪ Propionyl-CoA carboxylase deficiency
▪ Propionic acid is an intermediate metabolite of
isoleucine, valine, threonine, methionine, odd-chain fatty
acids, and side chains of cholesterol
▪ Normally, propionic acid in the form of propionyl-CoA
undergoes carboxylation to D-methylmalonyl-CoA,
catalyzed by the mitochondrial enzyme propionyl-CoA
carboxylase which requires biotin as a cofactor.
▪ Autosomal recessive
▪ 1:105,000 to 1:250,000 live births
▪ Gene for ⍺ subunit (PCCA) is located on chromosome
13q32.3 and that of the β-subunit (PCCB) is mapped to
chromosome 3q22.3
▪ Variable, depending on specific disorder
Mild:
▪ Episodes of metabolic decompensation less frequent,
but still at risk for intellectual diability seizures, long QTc
interval, severe cardiomyopathy
Severe:
▪ 1st few days of life
▪ Might present before NBS results are available
▪ Poor feeding, vomiting, seizures, hypotonia, lethargy,
dehydration, a sepsis like picture, and clinical signs of
severe ketoacidosis progress rapidly to coma and death.
▪ Moderate to severe intellectual disability and
neurologic manifestations reflective of extrapyramidal
(dystonia, choreoathethosis, tremor) & pyramidal
(paraplegia)
▪ Damage to basal ganglia esp. to globus pallidus
(metabolic stroke) d/t metabolic decompensation
▪
Thrombocytopenia,
leukopenia,
anemia,
neutropenia
▪ Ketoacidosis, hypoglycemia
▪ Moderate to severe Hyperammonemia (perturbed
biochemical and pH environment of the
mitochondrial matrix)
▪ Mild to moderate ↑ in blood lactate and lysine; N
to ↓ plasma glutamine
▪ Concentrations of propionylcarnitine, 3hydroxypropionic acid, and methylcitric acid ↑ in
plasma & urine
▪ ↑ Propionylglycine & other intermediate
metabolites of branched chain amino acid
▪ Secondary carnitine deficiency
▪ NBS: elevated propionylcarnitine (C3)
▪ Brain Imaging: cerebral atrophy, delayed
myelination, and abnormalities in the globus pallidus
and other parts of the basal ganglia
▪ Confirmed by molecular analysis of PCCA and PCCB
or by measuring the enzyme activity in leukocytes or
cultured fibroblasts
Prenatal diagnosis
PPS Oral Exam Reviewer 2020
▪ Improved outcome if diagnosed and
treated early
▪ Recurrent metabolic episodes and longterm sequelae may still occur
▪ Renal failure often develops despite
appropriate therapy
Long-term Sequelae
Psychomotor
retardation,
seizures,
pyramidal and extrapyramidal movement
disorder, basal ganglia strokes, interstitial
renal
disease,
cardiomyopathy,
pancreatitis, BM suppression, osteopenia,
optic nerve atrophy
▪ Close monitoring of blood pH, essential
amino acid levels, blood and urinary
concentrations of methylmalonate, and
growth parameters as well as kidney
function, vision, hearing, and bone
mineral density
NBS: measuring propionylcarnitine (C3)
Defect affecting
metabolism
PROPIONIC ACIDEMIA
(PA)
Mild:
▪ Later in life
▪ Hypotonia, FTT, developmental delay
Severe:
▪ 1st few days of life
▪ Lethargy, feeding problems, vomiting, sepsis-like
picture, tachypnea (from metabolic ketoacidosis),
hypotonia
▪ May progress to hyperammonemic encephalopathy,
coma, and death if left untreated
▪ Injury to basal ganglia, metabolic stroke → movement
disorder
Same as above, plus:
▪ Daily intramuscular injection of
hydroxocobalamin
▪ Daily oral betaine supplementation, if
methylcobalamin also involved
▪ Dietary protein restriction <24hr
▪ If enteral feedings cannot be tolerated
after 48hrs of protein restriction, give
parenteral nutrition
▪ Hydration w/solutions containing glucose;
correction of acidosis
▪ Isoleucine, methionine, threonine, valine
restriction
▪ Carnitine supplementation
▪
Liver
transplantation
(recurrent
hyperammonemia, frequent
metabolic decompensations, poor growth)
▪ Suppression of propionogenic gut
microflora (metronidazole or neomycin) –
prolonged use of metronidazole avoided d/t
reversible peripheral neuropathy and ↑ QTc
interval hence baseline & interval ECG
before & after metro
▪ Hemodialysis to remove ammonia & other
toxic compounds
▪ N-carbamoylglutamate
(carglumic acid) and nitrogen scavengers
▪ mut0 and severe forms of
cblB deficiency – least favorable prognosis
▪ mut- and cblA defects – better
outcome
▪ Improved outcome if diagnosed and
treated early
▪ Recurrent metabolic episodes
Long-term Sequelae
Cardiomyopathy and pancreatitis, FTT,
optic
nerve
atrophy,
pancreatitis,
cardiomyopathy, osteopenia, permanent
neurodevelopmental deficit
such as tremor, dystonia, chorea, and
spasticity, osteoporosis leading to
fractures
▪ Over restriction of methionine esp in
1styrs of life may contribute to reduced
brain growth & microcephaly
▪
Bicarbonate
substitution
(citric
acid/sodium citrate) to correct chronic
acidosis
▪ Close monitoring of plasma ammonia,
plasma amino acids obtained 3-4hrs after
the last typical meal (especially isoleucine,
leucine, valine, threonine) and growth
parameters7
Batch Clingy
▪ Methylmalonyl-CoA mutase deficiency
▪ Converts L-methylmalonyl-CoA to
succinyl-CoA
w/c
requires
adenosylcobalamin,
(metabolite of B12) as coenzyme
39
▪ Identification of variants in PCCA or PCCB
/measuring enzyme activity in cultured amniotic cells
MULTIPLE CARBOXYLASE
DEFICIENCY
(Defects of Biotin Cycle)
▪ Holocarboxylase synthetase deficiency
▪ Free biotin (water soluble vitamin that is cofactor for all
4 carboxylase enzymes in humans: pyruvate carboxylase,
acetyl-CoA carboxylase, propionyl-CoA carboxylase, and 3methylcrotonyl-CoA carboxylase. The latter 2 are involved
in the catabolic pathways of leucine, isoleucine, and
valine) must form a covalent bond with the
apocarboxylases to produce the activated enzyme
(holocarboxylase)
▪ Binding catalyzed by holocarboxylase synthetase
▪ Autosomal recessive
▪ May present in the newborn period (few hrs after birth
to as late as 8yo)
After birth:
Breathing difficulties, tachypnea,
problems, vomiting, hypotonia
apnea,
feeding
If untreated:
Generalized erythematous rash w/exfoliation &
alopecia, FTT, irritability, seizures, lethargy, coma,
impaired T-cell immunity hence susceptible to infection,
seizures, and developmental delay
▪ Tomcat Urine – peculiar odor in urine
▪ Metabolic ketoacidosis
▪ Hyperammonemia
▪ Presence of a variety of organic acids (lactic acid,3methylcrotonic
acid,
3-methylcrotonylglycine,
tiglylglycine, 3-OH
propionicacid,
methylcitric
acid,
and
3hydroxyisovaleric acid) in body fluids
(sodium benzoate, sodium phenylacetate,
sodium phenylbutyrate) can aid in the
treatment of acute hyperammenomia
▪ Biotin supplementation (10-20 mg/day PO)
▪ Most patients
supplementation
respond
to
biotin
▪ Poor or no response to biotin: may have
significant residual neurologic impairment
▪ NBS: elevated C5-OH -carnitine on tandem mass
spectrometry
▪ Confirmed by identification of pathogenic variants
in HLCS or by enzyme assay in lymphocytes or
cultured fibroblasts
Prenatal diagnosis
Molecular analysis of the known pathogenic variants
in HLCS or by assaying enzyme activity in cultured
amniotic cells.
BIOTINIDASE
DEFICIENCY
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Biotinidase deficiency
▪ Delay in onset of symptoms may be d/t presence of free
biotin derived from mother or the diet
▪ Autosomal recessive
▪ 1 in 60, 000 live births
▪ Gene for biotinidase (BTD) is located on chromosome
3p25.1
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Carnitine uptake defect
● Only genetic defect in which carnitine deficiency is
the cause, rather than the consequence
▪ Involves the plasma membrane sodium gradientdependent carnitine transporter present in heart, muscle,
& kidney
CARNITINE UPTAKE
DEFECT
OTHER
CLINICAL MANIFESTATIONS /
DIAGNOSIS
PHYSICAL EXAM
▪ Generally, does not manifest in neonatal period,
▪ Lab findings and the pattern of organic acids in body fluids same
several months or years old
w/ holocarboxylase synthetase deficiency (see above)
▪ Symptoms similar to holocarboxylase synthetase
▪ Measurement of the enzyme activity in the serum or by the
deficiency
identification of the mutant gene
▪ Atopic or seborrheic dermatitis, candidiasis, alopecia,
ataxia, seizures (usually myoclonic), hypotonia,
Prenatal diagnosis
developmental delay, optic nerve atrophy, sensorineural
Identification of the known pathogenic variants in BTD, or less
hearing loss, & immunodeficiency from impaired T-cell
frequently by the measurement of the enzyme activity in the
function
amniotic cells
FATTY ACID OXIDATION
CLINICAL MANIFESTATIONS /
DIAGNOSIS
PHYSICAL EXAM
▪ Does not generally manifest in neonatal period (1-4yo)
▪ Hypoketotic hypoglycemia
▪ Extremely ↓ carnitine levels in plasma and muscle
▪ Progressive Cardiomyopathy
(1-2% of normal)
▪ Skeletal myopathy
▪ Fasting ketogenesis may be normal because liver
▪ Inability to tolerate prolonged fasting
carnitine transport is normal, but it may become
impaired if dietary carnitine intake is interrupted
Fasting urinary organic acid profile
▪ Hypoketotic dicarboxylic aciduria pattern if hepatic
fatty acid oxidation is impaired but is otherwise
unremarkable
▪ Severe reduction in renal carnitine threshold or by
in vitro assay of carnitine
uptake using cultured fibroblasts or lymphoblasts
PPS Oral Exam Reviewer 2020
TREATMENT
▪ Free biotin (5-20 mg/day)
TREATMENT
▪ Carnitine supplementation
● High-dose, high-frequency
● Oral carnitine (100-200 mkday)
COMPLICATIONS / PROGNOSIS
▪ Good
COMPLICATIONS / PROGNOSIS
▪ Good response to treatment, prevents
and/or reverses cardiomyopathy, skeletal
myopathy, and impaired ketogenesis
Batch Clingy
DISEASE
40
▪ CPT II deficiency
CARNITINE
PALMITOYLTRANSFERASE TYPE II
(CPT II)
DEFICIENCY
Partial Translocase deficiency
▪ Milder disease
▪ Without cardiac involvement
Severe form (neonatal period)
▪ Lethargy → coma, cardiomyopathy with ventricular
arrhythmias, hepatic dysfunction, skeletal myopathy,
congenital malformation (brain and cystic renal disease),
hypoketotic hypoglycemia, mild facial anomalies
Intermediate form (infancy)
▪ Similar (but milder) features, w/o congenital brain and
kidney malformations
▪ Fasting induced hepatic failure, cardiomyopathy, and
skeletal myopathy w/ hypoketotic hypoglycemia, but not
assoc. w/ severe developmental changes
▪ LCHAD deficiency/TFP deficiency
▪ LCHAD enzyme is part of the MTP, which also contains 2
other steps in β-oxidation: long-chain 2,3-enoyl CoA
hydratase and long-chain β-ketothiolase
LONG-CHAIN 3HYDROXYACYL-COA
DEHYDROGENASE
(LCHAD) DEFICIENCY
or
TRIFUNCTIONAL
PROTEIN
(TFP)
DEFICIENCY
MEDIUM-CHAIN ACYLCOA DEHYDROGENASE
(MCAD) DEFICIENCY
▪ Commonly manifests in neonatal period
▪ Lethargy → coma, hepatomegaly/hepatic dysfunction,
Cardiomyopathy with ventricular arrhythmia, skeletal
myopathy
▪ MCAD deficiency
▪ Most common fatty acid oxidation disorder
▪ MCAD missense mutation, an A-G transition at cDNA
position 985 (c.985A>G) that changes a lysine to glutamic
acid at residue 329 (p.K329E)
Mild, late-onset form (childhood/adult)
▪ Weakness and exercise-induced rhabdomyolysis
▪ Aching muscle pain & myoglobinuria that may cause
renal failure
Severe form (neonatal period)
▪ Cardiomyopathy with arrhythmia, hypotonia, hepatic
dysfunction, hypoketotic hypoglycemia, sudden death
▪ Adult: mutation, c.338C>T, p.S113L; produces a
heat-labile protein that is unstable to (↑) muscle
temperature during exercise →
myopathic
presentation
Diagnosis
Molecular genetic analysis and demonstrating
deficient enzyme activity in muscle or other tissues
and in cultured fibroblasts
▪ Acute hypoketotic hypoglycemia similar to MCAD
deficiency
▪ ↑ Blood spot or plasma 3-hydroxy acylcarnitines of
chain lengths C16-C18
▪ ↑ Levels of 3-hydroxydicarboxylic acids of chain
lengths C6-C14.
▪ Secondary carnitine deficiency
▪ Mutation in the ⍺-subunit, E474Q
▪ Severe neonatal cases: poor outcome
and early death
▪ Patient with later onset might respond to
treatment, but they often succumb to
chronic skeletal-muscle weakness or
cardiac arrhythmias
Severe
▪ Avoid fasting, may require continuous
enteral feeding
▪ High-carbohydrate, low-fat diet, including
MCT oil
▪ Carnitine supplementation
Severe
▪ Have poor outcome and early death
Intermediate
▪ Treated with an attenuated regimen of the
above
Late-onset
▪ Generally do well
Intermediate
▪ Milder problems than those with
neonatal-onset form
Late-onset
▪ Treated with an attenuated regimen of the
above
Severe
▪ Avoid fasting
▪ High-carbohydrate, low-fat diet with MCT
oil supplementation (to bypass the defect in
long-chain fatty acid oxidation and
docosahexaenoic acid (for protection against
the retinal changes)
▪ Carnitine supplementation
▪ Liver transplantation
▪ Prognosis for severe form is guarded
despite therapy
▪ Early diagnosis and treatment generally
improve outcome for patients with
infantile/childhood form but risk of
peripheral
neuropathy
and
visual
impairment persists
Infantile/childhood form
▪ Milder form of “severe” disease and later develop
rhabdomyolysis, peripheral neuropathy, and pigmentary
retinopathy (d/t toxic effects of fatty acid metabolites)
Infantile/childhood
▪ Treat with an attenuated regimen of the
above,
plus
supplementation
with
docosahexanoic acid
Maternal disease
▪ Heterozygous pregnant women are at risk for acute
fatty liver of pregnancy, HELLP syndrome, if they are
carrying an affected (homozygous or compound
heterozygous) fetus
▪ Generally, does not manifest in neonatal period
▪ 1st 3mos to 5yrs of life
▪ Triggered by prolonged fasting (>12-16hrs) ▪ Breastfed
are at higher risk because of early poor caloric intake
Maternal treatment
▪ Early delivery
▪ Carnitine supplementation if deficient
▪ Prognosis guarded for pregnant woman
▪ Avoid fasting – limit overnight fasting
periods to <10-12hrs
▪ Fluid containing 10% dextrose to correct &
prevent hypoglycemia and to suppress
lipolysis as rapidly as possible
▪ Heart healthy diet (≤30%)
▪ Carnitine supplementation
▪ Excellent intellectual and physical
outcome generally seen if treatment is
initiated before irreversible neurologic
damage occurs, but some may sustain
permanent brain injury
▪ Recurrent episodes of lethargy, vomiting, coma,
seizures, and possibly sudden death
PPS Oral Exam Reviewer 2020
▪ Creatine kinase ↑ to 5,000-100,000 units/L
▪ Muscle biopsy: increased deposition of neutral fat
▪ Avoid fasting
▪ Continuous enteral feeding in severe cases
▪ High-carbohydrate, low-fat diet
▪ Carnitine supplementation
▪ Hypoketotic hypoglycemia, ↑ liver enzymes, ↑
blood ammonia, prolonged PT, PTT
▪ Liver biopsy: micro- or macrovesicular steatosis
from triglyceride accumulation
▪ Low concentrations of ketones and ↑ levels of
medium-chain dicarboxylic acids (adipic, suberic, and
sebacic acids)
▪ Fasting tolerance improves with age;
Batch Clingy
CARNITINE/
ACYLCARNITINE
TRANSLOCASE (CACT)
DEFICIENCY
▪ Carnitine/acylcarnitine translocase deficiency
▪ This defect of the inner mitochondrial membrane carrier
protein for long-chain acylcarnitines blocks the entry of
long-chain fatty acids into the mitochondria for oxidation
▪ Characterized by a severe and generalized impairment of
fatty acid oxidation.
▪ Mutations in the organic cation/carnitine
transporter (OCTN2) underlie this disorder
▪ Hypoketotic hypoglycemia ± hyperammonemia
▪ ↑ Plasma long-chain acylcarnitines of chain lengths
C16-C18 are reported
▪ Confirmed using genetic analysis
▪ Functional carnitine: acylcarnitine translocase
activity measured in cultured fibroblasts or
lymphoblasts
41
▪ Cardiomyopathy not generally seen
▪ Liver may be slightly enlarged with fat deposition
▪ SCAD deficiency
▪ Harmless
▪ Autosomal recessive
▪ Most px detected by NBS are asymptomatic
▪ Some with severe manifestations – dysmorphic facial
features, feeding difficulties/failure to thrive, metabolic
acidosis, ketotic hypoglycemia, lethargy, developmental
delay, seizures, hypotonia, dystonia, myopathy
▪ VLCAD deficiency
▪ No ability to oxidize physiologic long-chain fatty acids
▪ Usually more severely affected than those with MCAD
Severe (neonatal)
▪ Lethargy progressing to coma
▪ Cardiomyopathy & ventricular arrhythmias, hepatic
dysfunction,
skeletal
myopathy,
hypoketotic
hypoglycemia
VERY LONG-CHAIN ACYLCOA DEHYDROGENASE
(VLCAD) DEFICIENCY
Intermediate (infancy)
▪ Similar (but milder) features than the severe form
▪ Nightly
(optional)
▪ 2DED: LV may be hypertrophic/dilated with poor
contractility
▪ Lab features similar to those of MCAD
▪ Nonketotic dicarboxylic aciduria with (↑) levels of
C6-12 dicarboxylic acids.
Severe
▪ Avoid fasting, consider continuous enteral
feeding
▪
High-carbohydrate,
low-fat
diet
supplemented with MCT oil
▪ Carnitine supplementation
Diagnosis
▪ Suggested by an abnormal acyl dicarboxylic acids or
blood spot C14:0, 14:1, 14:2 acylcarnitine
Late-onset (childhood/adulthood)
▪ Weakness and exercise-induced rhabdomyolysis
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Galactose-1-phosphate uridyltransferase deficiency
▪ Autosomal recessive
▪ 1 in 47,000 live births
GALACTOSE-1PHOSPHATE
URIDYLTRANSFE-RASE
(GALT)
DEFICIENCY
▪ 2 FORMS:
Complete/Near
Complete
deficiency
(Classic
Galactosemia)
● Serious disease with onset by 2nd half of 1stwk of life
● 1 in 60,000 live births
● Without the transferase enzyme, infant unable to
metabolize galactose-1-phosphate, accumulation of which
→ injury to kidney, liver, brain
Partial Transferase Deficiency
GALACTOSEMIAS
CLINICAL MANIFESTATIONS
DIAGNOSIS
▪ May present in the neonatal period
▪ (+) Reducing substance in urine while on diet
▪ Lethargy, poor feeding, jaundice with hepatic
containing human/cow milk /formula containing
dysfunction, hepatomegaly, vomiting, hypoglycemia,
lactose via chromatography/ enzymatic test specific
seizure, irritability, poor weight gain, failure to gain
for galactose
weight
▪ Amino acids may be detected in urine since they
are excreted together with glucose because of a
If untreated
proximal renal tubular syndrome
▪ Nuclear cataracts, vitreous hemorrhage, hepatic
▪ Confirmed by Direct enzyme assay using
failure, cirrhosis, ascites, splenomegaly, or intellectual
erythrocytes
disability, ↑ risk for E. coli neonatal sepsis, pseudotumor
cerebri causing bulging fontanel
▪ Death from liver, kidney failure, sepsis
Chronic problems
▪ Growth failure, cirrhosis, cataracts,
intellectual disabilities, ovarian failure
supplementation
▪ Normal diet
▪ Carnitine supplementation
demonstrates deficiency
if
testing
risk of illness also decreases
▪ The need for and efficacy of treatment is
unknown
Severe: Poor outcome and early death
Intermediate & Late: Generally, do well
Intermediate
▪ Treated with an attenuated regimen of the
above
Late-onset
▪ Treated with an attenuated regimen of the
above
TREATMENT
▪ Strict dietary galactose restriction with
adequate calcium supplementation –
reverses growth failure and renal and
hepatic dysfunction
▪
Use
non–lactose-containing
milk
substitutes (casein hydrolysates, soybeanbased formula)
COMPLICATIONS / PROGNOSIS
▪ Improved intellectual outcome, but may
have milder problems such as speech
delay, if diagnosed and treated early
▪ Cataracts regress, and most patients
have no impairment of vision
▪ Ovarian failure with 1o/2o amenorrhea,
decreased
bone
mineral
density,
developmental
delay
&
learning
disabilities, that ↑ in severity with age
may still develop
▪ Hypergonadotropic hypogonadism (80-90% of women)
▪ Recurrent metabolic episodes may occur
seizures,
Partial transferase deficiency
▪ Generally asymptomatic
▪ More common than classic, dx in NBS because of
moderately ↑ blood galactose and/or low transferase
activity
PPS Oral Exam Reviewer 2020
cornstarch
Batch Clingy
SHORT-CHAIN ACYL-COA
DEHYDROGENASE
(SCAD)
DEFICIENCY
▪ Secondary carnitine deficiency: reflects competition
between ↑ acylcarnitine levels and free carnitine for
transport at the renal tubular plasma membrane
▪ ↑ Plasma C6:0, C8:0, C10:0, and C10:1 acylcarnitine
species and ↑ urinary acylglycines, (hexanoylglycine,
suberyl gly- cine, 3-phenylpropionylglycine)
▪ Confirmed by A985G mutation or sequencing the
MCAD gene.
▪ Neonatal hypoglycemia w/ normal ketone
▪ NBS: ↑ butyrylcarnitine (C4-carnitine)
▪ ↑ Excretion of urinary ethylmalonic acid and
butyrylglycine.
42
UDP-GALACTOSE-4EPIMERASE
(GALE)
DEFICIENCY (Epimerase
Deficiency Galactosemia)
DISEASE
Generalized epimerase deficiency
▪ Poor feeding, vomiting, weight loss, jaundice, liver
dysfunction, hepatomegaly, hypotonia, cataracts,
generalized aminoaciduria, nerve deafness
Peripheral or intermediate form
▪ Benign; detected in NBS
▪ Generally, remain clinically well since enzyme
deficiency limited to leukocytes & erythrocytes
▪ May tolerate a normal diet
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ ⍺-L-Iduronidase deficiency
HURLER SYNDROME
(MPS I)
MPS I – mutations of
the IUA gene on
chromosome 4p16.3
encoding ⍺-Liduronidase
Homozygous nonsense
mutations: severe
Missense mutations:
milder; preserve some
residual enzyme
activity
POMPE DISEASE (GSD
II)
(Acid Maltase
Deficiency)
▪ Cataracts, with no other medical problems
▪ Pseudotumor Cerebri – rare complication
▪ Heterozygous carriers: risk for presenile cataracts
▪ -Glucosidase deficiency – enzyme responsible for
the degradation of glycogen in lysosomes
▪ Enzyme defect → lysosomal glycogen
accumulation in multiple tissues and cell types,
predominantly cardiac, skeletal, & smooth muscle
cells
▪ As disease progresses: lysosomal rupture &
leakage → presence of cytoplasmic glycogen as
well
▪ Autosomal recessive
PPS Oral Exam Reviewer 2020
▪ ↑ Concentration of blood galactose levels,
provided the infant has been fed a lactose containing
formula
▪ Absence of galactokinase activity in erythrocytes or
fibroblasts
▪ Transferase activity is normal
▪ Abnormally accumulated metabolites similar to
transferase deficiency
▪ ↑ in cellular uridine diphosphate (UDP) galactose
▪ Confirmed by assay of epimerase in erythrocytes
Prenatal diagnosis
▪ Enzyme assay of cultured amniotic fluid cells
LYSOSOMAL STORAGE DISEASES
DIAGNOSIS
Severe
▪ Failed neonatal hearing tests
▪ Onset w/in 1st year of life; progressive
▪ Radiograph of chest, spine, pelvis, hands: skeletal
▪ Short stature, coarse facial features, hirsutism,
dysplasia
(Dysostosis
multiplex);
earliest
large tongue
symptoms: thick ribs & ovoid vertebral bodies
▪ Corneal clouding, glaucoma, retinal degeneration,
▪ Other skeletal abnormalities:
and hearing loss
● Enlarged, coarsely trabeculated diaphyses of
▪ Cardiomyopathy/ valvular disease (incompetence
the long bones w/ irregular metaphyses and
of mitral & aortic valves, narrowing of coronary
epiphyses
arteries)
● With disease progression, macrocephaly
▪ Hepatosplenomegaly, inguinal hernias, stiff joints
develops w/ thickened calvarium, premature
▪ Hydrocephalus → progressive ventricular
closure of lambdoid and sagittal sutures, shallow
enlargement & increased ICP & spinal cord
orbits, enlarged J-shaped sella, and abnormal
compression, intellectual disabilities
spacing of teeth with dentigerous cysts
▪ Recurrent URTI, ear infection, noisy breathing,
▪ Assay the urinary excretion of GAGs;
persistent copious nasal discharge, obstructive
semiquantitative spot tests for ↑ urinary GAG
airway disease
excretion
▪ Limited language skills d/t intellectual disability,
▪ Quantitative analysis of single GAG and/or
combined conductive & neurosensory hearing loss
oligosaccharides by mass spectrometry detection
and enlarged tongue
tests: type-specific profiles in urine, serum, plasma,
▪ Death by cardiorespiratory failure by 10yo
and dried blot spots
▪ Confirmed by enzyme assay on serum, leukocytes,
Mild
cultured fibroblasts
▪ Normal intellectual development and moderate
▪ Gene panels
somatic manifestations at age 2yo, with variable
disease progression
Early infantile form
▪↑ CK activity, AST, ALT, LDH
▪ Within the first 6mos of life; progressive
-Hypotonia,
macroglossia,
cardiomegaly
or
▪ Urine glucose tetrasaccharide – glycogen
hypertrophic cardiomyopathy, bulbar weakness,
breakdown metabolite, biomarker for disease
hepatomegaly, progressive weakness (floppy infant
severity & treatment response
appearance)
▪ Death in the first 2y of life (Fanaroff), 1 year
▪ CXR – Massive cardiomegaly
(Nelsons) if untreated w/ ERT
▪ ECG – High-voltage QRS complex, WPW
syndrome, shortened PR interval
Later-onset form (Juvenile, Childhood, Adult)
▪ 2DED: Thickening of both ventricles and/or
CLINICAL MANIFESTATIONS
▪ Milk restriction only
▪ Rapid initiation of milk restriction may
resolve cataracts that were already present
▪ Good
▪ Lactose/
required
▪ Similar to GALT deficiency, with no
evidence of ovarian failure if maintained
on proper diet
galactose-restricted
diet
is
▪ Galactose-restricted diet is not generally
required for peripheral form
TREATMENT
Severe
▪ Initiate enzyme replacement therapy following
diagnosis: appropriate for mild CNS involvement or
to stabilize extraneural manifestations in young
patients before stem cell transplantation.
▪ Hematopoietic stem cell transplant (HSCT) if <2yo
with baseline mental developmental index >70;
careful consideration of risk vs. benefit advised if
>2yo
Mild
▪ HSCT not recommended for mild form because of
treatment complications
▪ Symptomatic therapy
● Focuses on respiratory and CV complications,
hearing loss, carpal tunnel syndrome, spinal cord
compression, hydrocephalus
▪ Enzyme replacement therapy w/ recombinant
human -glucosidase ASAP
▪ CRIM-negative patients should receive immune
tolerance induction before initiating therapy
▪ MTX, rituximab, IVIG – immunomodulation
therapy for patients who develop enzyme
neutralizing antibodies after starting ERT
Late-onset form:
▪ Enzyme replacement therapy
Good
COMPLICATIONS / PROGNOSIS
Severe
▪ Early initiation of enzyme replacement therapy
followed by HSCT improves outcome, except for
skeletal changes
▪ Comprehensive symptomatic treatment
HSCT
▪ ↑ Life expectancy with resolution or
improvement of growth, hepatosplenomegaly, joint
stiffness, facial appearance, skin changes, OSA,
heart disease, communicating hydrocephalus,
hearing loss. Enzyme activity in
serum & urinary GAG excretion normalize.
ERT w/ -L-iduronidase
▪ Reduces organomegaly and ameliorates rate of
growth, improves joint mobility, reduces the
number of episodes of sleep apnea and urinary
GAG excretion.
▪ Rapid initiation of enzyme replacement therapy
(ERT) improves outcome
Late-onset
▪ Variable depending on age of onset and age of
initiation of therapy
Batch Clingy
GALACTOKINASE (GALK)
DEFICIENCY
▪ Galactokinase (GALK) deficiency
▪ This enzyme catalyzes the phosphorylation of galactose
▪ Primary metabolites that accumulate are galactose &
galactitol
▪ 2 genes that encode galactokinase: GK1
on chromosome 17q24 and GK2 on chromosome 15.
▪ UDP-galactose-4- epimerase deficiency
▪ GALE located on chromosome 1 at 1p36
43
▪ 1 in 40,000 live births in Caucasians
▪ 1 in 18,000 in Han Chinese
▪ Gene for acid ⍺-glucosidase
(GAA) is on chromosome
17q25.2.
▪ Generally, >12 months
▪ Slowly progressive, proximal limb girdle muscle
weakness (within 1yr to 6th decade of life,
lower>upper limb) – mostly pelvic girdle, paraspinal
muscles, diaphragm
▪ Respiratory insufficiency: somnolence, morning
headache, orthopnea, exertional dyspnea → sleep
disordered breathing & RF
▪ Cardiac involvement – rhythm disturbances, less
severe cardiomyopathy
▪ Lingual weakness, ptosis & dilation of blood
vessels (basilar artery, ascending aorta) → basilar
artery aneurysm w/rupture
▪ GI: postprandial bloating, dysphagia, early satiety,
diarrhea, chronic constipation, IBD
▪ GU: bladder & bowel incontinence, weak urine
stream, dribbling
intraventricular septum and/or LVOT obstruction
▪ Muscle Biopsy: Vacuoles that stain (+) glycogen;
acid phosphatase increased (compensatory
increase if lysosomal enzymes)
▪ EM: Glycogen accumulation within a membranous
sac and in the cytoplasm
▪ EMG: Myopathic features with excessive electrical
irritability of muscle fibers and pseudomyotonic
discharges
▪ Peripheral Nerve Biopsy: Glycogen accumulation
in neurons and Schwann cells
▪ Enzyme assay: Dried blood spots, leukocytes,
blood mononuclear cells, muscle, or cultured skin
fibroblasts – deficient acid α-glucosidase activity.
▪ High protein diet
▪ Respiratory muscle strength training
Approaches under development
▪ Chaperone molecules to enhance rhGAA delivery
▪ neoGAA, which is a second-generation ERT with a
high number of mannose-6-phosphate (M6P) tags
that enhances M6P receptor targeting and enzyme
uptake
▪ Gene therapy to correct endogenous enzyme
production pathways
▪ Confirmed by Gene sequencing: 2 pathogenic
variants in the GAA gene
Prenatal diagnosis
Amniocytes/chorionic villi
X-LINKED
ADRENOLEUKODYSTROPHY
Most common
peroxisomal disorder
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Impaired peroxisomal metabolism of very longchain fatty acids
▪ Accumulation of saturated VLCFAs (carbon chain
length of ≥24) & progressive dysfunction of adrenal
cortex & CNS d/t genetically deficient peroxisomal
degradation of FA
▪ Defective gene (ABCD1) codes for peroxisomal
membrane protein (ALD protein) → disruption of
transport of saturated fatty acids into the
peroxisome
→
continued
elongation
of
progressively longer FA
▪ Excess hexacosanoic acid (C26:0)
● Most characteristic feature
● Increases the viscosity of the plasma
membrane, which may interfere with receptor &
other cellular function
▪ Males 1 in 21,000
▪ Combined males & heterozygous females 1 in
17,000
▪ Lamellar cytoplasmic inclusions (w/c probably
consists of cholesterol esterified with VLCFA) in
adrenocortical cells, testicular Leydig cells, and
nervous system macrophages; most prominent in
zona fasciculata of the adrenal cortex (cells
distended w/ abnormal lipids)
▪ Severity of illness & rate of progression correlate
with intensity of the inflammatory response which
may be partially cytokine mediated and may involve
an autoimmune response triggered in an unknown
way by the excess of VLCFAs. Mitochondrial
PPS Oral Exam Reviewer 2020
PEROXISOMAL DISORDERS
CLINICAL MANIFESTATIONS /
DIAGNOSIS
PHYSICAL EXAM
Childhood-onset (4-8 yo)
▪ High levels of VLCFAs in plasma, RBCs, or
▪ M > F, X-linked recessive
cultured skin fibroblast
▪ Intracerebral inflammatory response → demyelination →
▪ Mutation analysis – most reliable method for
accumulation of perivascular lymphocytes
the identification of carriers
▪ Adrenal insufficiency, impaired cortisol response to ACTH
▪ Neuroimaging MRI:
stimulation, mild hyperpigmentation
● White matter lesions, symmetric, involve
▪ Regression of cognition, behavior, vision (involvement of
splenium of the corpus callosum and
parietooccipital cortex)
periventricular white matter in the posterior
▪ Hyperactivity, inattention, and worsening school performance
parietal and occipital lobes
▪ Loss of hearing (Impaired Auditory discrimination) and motor
● Garland of contrast enhancement adjacent
function follow the initial symptoms → total disability
& anterior to the posterior hypodense lesions
▪ Spatial orientation impaired, ataxia, poor handwriting,
w/c corresponds to zone of intense perivascular
seizures, strabismus.
lymphocytic infiltration where the BBB breaks
▪ Progress rapidly with ↑ spasticity and paralysis, visual and
down
hearing loss, and loss of ability to speak or swallow.
▪ ↑ ACTH in plasma & subnormal rise of cortisol
▪ Death/vegetative state generally by 1.9 years
levels in plasma after IV injection of 250μg of
▪ May continue veg. state for >10yrs
ACTH
Adolescent ALD (10-21 yo)
▪ Like childhood form but progression slower
▪ 10%: acute status epilepticus, adrenal
encephalopathy, coma
crisis,
acute
Later-onset (late adolescence/a
dulthood)
▪ M>F, with females more mildly affected
▪ Adrenomyeloneuropathy beginning in late 20s (paraparesis,
sphincter and sexual dysfunction, and adrenal insufficiency) –
distal axonopathy that affects long tracts of the spinal cord
TREATMENT
COMPLICATIONS / PROGNOSIS
Childhood-onset
▪ Immediate HSCT – if neurologic involvement is
not yet present
▪ Bone marrow – derived cells do express ALDP,
the protein that is deficient in ALD. Favorable
effect cause by modification of the brain
inflammatory response. Does not arrest the
course in those who already had severe brain
involvement and may accelerate disease
progression. Not recommended in patients with
performance IQ significantly <80.
Childhood-onset
▪ May improve neurologic outcome (further
follow-up studies are underway)
Later-onset
▪ HSCT
▪ Corticosteroid replacement therapy
▪ Lorenzo’s oil
● 4:1 mixture of glyceryl trioleate and
glyceryl trierucate
● Lower plasma levels of VLCFAs, but not to
alter disease progression in males with cerebral
disease
Supportive Treatment
▪ Parent support groups, low-level resource
services within a regular school program to
home- and hospital – based teaching programs
▪ As leukodystrophy progresses, modulation of
Later-onset
▪ Limited benefits of HSCT for neurologic
problems after onset of symptoms
▪ Adrenal insufficiency – avoidable
complication
▪ The most difficult neurologic problems are
those related to bed rest, contracture, coma,
and swallowing disturbances
Other complications
▪ Behavioral disturbances and injuries
associated with defects of spatial orientation,
impaired vision, hearing, seizures
▪ Brain MRI every 6mos in neurologically
asymptomatic boys and adolescents aged 3-15
yr. If the MRI is normal, BMT not indicated.
Genetic Counselling and Prevention
▪ Identification of asymptomatic males permits
institution of steroid replacement therapy
when appropriate and prevents adrenal crisis
▪ Plasma VLCFA assay is recommended in all
male patients with Addison disease
▪ DNA analysis permits accurate
identification of carriers
Batch Clingy
DISEASE
44
damage and oxidative stress also appear to
contribute.
▪ Inflammatory response mild/absent
▪ Adrenal insufficiency precedes and dominates neurologic
abnormalities
Addison only (male w/ addison, 25% have defect in ALD)
▪ Intact CNS/subtle neuro symptoms
▪ Many acquire adrenomyeloneuropathy in adulthood
muscle tone & support of bulbar muscular
function are major concerns. Baclofen in
gradually increasing doses (5mg BID to 25mg
QID) for treatment of acute episodic painful
muscle spasms. Changing the diet to soft and
pureed or eventually use of gastrostomy tube
▪ Anticonvulsants for seizures
Batch Clingy
Asymptomatic ALD
▪ With biochemical defect but free or CNS/Endo disturbances
PPS Oral Exam Reviewer 2020
45
Batch Clingy
PPS Oral Exam Reviewer 2020
46
Batch Clingy
PPS Oral Exam Reviewer 2020
47
Batch Clingy
PPS Oral Exam Reviewer 2020
48
Chronic
ETIOLOGY / INCIDENCE / PATHOGENESIS
DUCHENNE MUSCULAR DYSTROPHY (DMD)
▪ Most common hereditary neuromuscular disease
▪ X-lined recessive trait
▪ 1 in 3600 infant boys
▪ Abnormal gene at Xp21 locus (one of the largest genes)
CLINICAL MANIFESTATIONS
Characteristic clinical features: progressive weakness, intellectual impairment, hypertrophy
of the calves, with proliferation of connective tissue and fibrosis in muscle
▪ Rarely symptomatic at birth or early infancy, some are mildly hypotonic
▪ Early gross motor skills (rolling over, sitting, standing) – achieved or mildly delayed
▪ Distinctive facies – not an early feature; facial muscle weakness is late event (in later
childhood, a “transverse” or horizontal smile may be seen)
▪ Gower’s sign – may be seen at 3yo; always evident at 5 or 6yo
▪ Trendelenburg (waddling) gait appears at this time as well
Common presentation in toddlers: delayed walking, frequent falling, toe walking, trouble
running or going upstairs, developmental delay, malignant hyperthermia after anesthesia
CONGE NITAL
NEUROMUSCULAR
DISORDERS
HYPOXIC-ISCHEMIC
ENCEPHALOPATHY
BECKER MUSCULAR DYSTROPHY
▪ Similar to DMD
▪ Onset after 5 or 7yo
▪ Genetic defect at same locus of DMD
CONGENITAL MYOTONIC DYSTROPHY
▪ Second most common muscular dystrophy
▪ Autosomal dominant
▪ Genetic defect causing dysfunction in multiple organ
systems
(striated
muscle,
smooth
muscle,
endocrinopathies, immunologic deficiencies, cataracts,
dysmorphic facies, risk for malignancies, intellectual
impairment, neuro abnormalities)
TYPES
Classic myotonic dystrophy (type 1)
▪ DM1 or Steinert disease
▪ Caused by CTG trinucleotide expansion on chromosome
19q13.3 in the 3’ untranslated region of DMPK (gene that
encodes serine-threonine protein kinsase)
Type 2 (DM2) – unstable CCTG tetranucleotide repeat
expansion on chromosome 3q21 of an intron of the zinc
finger 9 protein gene
Late form (DM3) – identified at locus 15q21-q24
Hypoxemia – ↓ arterial concentration of oxygen resulting
in
Hypoxia – ↓ oxygenation to cells or organs
Ischemia – blood flow to cells or organs that is
inadequate to maintain physiologic function
Major neonatal encephalopathies or seizure – due to
PERINATAL EVENTS
PPS Oral Exam Reviewer 2020
▪ Age of complete loss of ambulation: 10-14yo
▪ Contractures most often involve ankles, knees, hips and elbows, neck lateral rotation,
shoulders, elbows
▪ Scoliosis is common
▪ Cardiomyopathy – occurs after loss of independent ambulation
▪ Intellectual impairment occurs in majority although 20-30% have IQ <70
▪ Milder and more protracted course than DMD
▪ Remain ambulatory until late adolescence or adulthood
▪ Given the increased level of activity, cardiac manifestations may be evident earlier
▪ Learning disabilities are less common
▪ DM1 symptomatic at any age
▪ DM2 rarely expressed in infancy or early childhood
Facial appearance is characteristic: inverted V-shaped upper lip, thin cheeks, scalloped
concave temporalis muscle, head narrow, palate high and arched, tongue thin and atrophic,
long thin cylindrical contour neck
▪ Weakness is often mild in first few years (childhood onset form) or may not even become
evident until adulthood (classic/adult-onset form)
▪ Progressive wasting of DISTAL muscles – exception to general rule of myopathies having
proximal and neuropathies having distal distribution patterns
▪ Proximal muscles eventually undergo atrophy, scapular winging appears
▪ Gower’s sign is progressive
▪ Tendon stretch reflex usually preserved
▪ Myotonia evident until about 5yo → not a painful muscle spasm
▪ Poorly articulated speech
IUGR with ↑vascular resistance
▪ 1st indication of chronic fetal hypoxia before peripartum period
▪ Variable or late deceleration pattern
At delivery – meconium stained amniotic fluid → fetal distress occurred
▪ Depressed, fail to breathe, remain hypotonic or change to hypertonic state
▪ Pallor, cyanosis, periodic breathing with apnea, slow heart rate and unresponsiveness to
stimulation – signs of HIE
▪ Cerebral edema develops next 24 hours – profound brainstem depression → during this
DIAGNOSIS
Serum CK level
▪ Consistently greatly elevated (even in pre
symptomatic stages)
▪ 15,000-35,000 IU/L (Normal is <160 IU/L)
2DED and ECG
▪ Done every other year
▪ Yearly if have symptoms or reaches 10 yo)
EMG
▪ Shows characteristic myopathic features but is
not specific – no denervation found
Genetic evaluation
Muscle biopsy
▪ Primary dx test: DNA analysis of blood
▪ Classic EMG myogram is not found in infants but
evident in early school years
▪ Serum CK and other enzymes may be normal or
slightly elevated in hundreds (never thousands)
▪ ECG should be done yearly
▪ UTZ of abdomen and Xray of chest and abdomen
w/ GI motility or swallowing studies
▪ Endocrine assessment (coz hypothyroidism and
adrenocortical insufficieny is common), and
glucose tolerance test
▪ Immunologic studies
Differential Diagnosis for seizure
▪ IVH, hypocalcemia, hypoglycemia, CNS infection
Diffusion weighted MRI – imaging of choice, most
sensitive for detecting hypoxic brain injury
CT scan – limited
UTZ – limited in term
TREATMENT / COMPLICATIONS
▪ No medical cure at this time
▪ Mainstay: Supportive and preventive care
▪ Glucocorticoids – slow decline in muscle strength and
increase time of independent ambulation (initiate at 46yo)
▪ Cardiac care: ACE inhibitors, ARBS or B blockers
▪ Promptly treat pulmonary infections
▪ Preserve good nutritional state
▪ Physiotherapy
COMPLICATIONS
DMD
▪ Death occurs in late teens to 20s
▪ Causes:
● Respiratory failure during sleep
● Intractable heart failure
● Pneumonia
● Aspiration or airway obstruction
BMD
▪ Lifespan is into 40-50s
▪ Cause of death: cardiac and pulmonary complications
▪ No specific medical treatment, but the cardiac,
endocrine, GI, and ocular complications can be treated
▪ Anesthesia precautions
▪ 20-30% die in neonatal period and 33-50% of
survivors are left with permanent neurodevelopmental
abnormalities
(CP,
↓
IQ,
learning/cognitive
impairment)
▪ Cerebral or body systemic therapeutic hypothermia
reduces mortality and major neurodev impairment at
18mo of age (33.5C within 1st 6 hours after birth and
maintained for 72 hr)
Batch Clingy
DISEASE
49
Fetal hypoxia may be caused by:
▪ Inadequate oxygenation of maternal blood from
hypoventilation during anesthesia
▪ Low maternal BP from acute blood loss, spinal
anesthesia, or compression of vena cava by gravid uterus
▪ Uterine tetany – inadequate relaxation of uterus for
placental filling
▪ Abruption placenta
▪ Compression or knotting of cord
▪ Placental insufficiency from toxemia
After birth hypoxia may be caused by:
▪ CHD or severe pulmo disease
▪ Severe anemia (hemorrhagic/hemolytic disease)
▪ Shock (sepsis, blood loss, IVH)
▪ Failure to breathe after birth because of in utero CNS
injury or drug-induced suppression
PATHOGENESIS
Hypoxia and ischemia → anaerobic metabolism → ↑
lactate and inorganic phosphates
Glutamate accumulates in damaged tissue →
overactivation of NMDA, AMPA and kainate receptors →
↑ cellular permeability to Na and Ca ions → intracellular
accumulation → cytotoxic edema and neuronal death
Initial response: shunt blood through the ductus venosus,
ductus arteriosus, foramen ovale with maintenance of
perfusion of the brain, heart, adrenals
Effects
▪ Congestion and petechiae in pericardium, pleura,
thymus, heart, adrenals and meninges
time seizures may occur (although most often sec to HIE, seizures may also be caused by
vascular events, metab derangements, CNS infection and cerebral dysgenesis or genetic
disorders
▪ Heart failure and cardiogenic shock, PPHN< RDS, GI perforation, hematuria → associated
with asphyxia due to inadequate perfusion
CNS
Multiorgan Systemic Effects of Asphyxia
EFFECTS
HIE, infarction, intracranial hemorrhage, seizures,
cerebral edema, hypotonia, hypertonia
CV
Myocardial ischemia, poor contractility, cardiac
stunning, tricuspid insufficiency
Pulmo
Pulmo HTN, pulmo hemorrhage, RDS
Renal
Acute tubular or cortical necrosis
Adrenal
Adrenal hemorrhage
GI
Perforation, ulceration with hemorrhage, necrosis
SYSTEM
Skin
Inappropriate secretion of ADH, hyponat, hypogly,
hypocal, myoglobinuria
Subcutaneous fat necrosis
Hema
DIC
Metabolic
Poor predictive variables for death/disability after HIE:
▪ Low (0-3) 10 min Apgar score
▪ Need for CPR in delivery room
▪ Delayed onset (≥20 min) of spontaneous breathing
▪ Severe neuro signs (coma, hypotonia, hypertonia)
▪ Seizures onset ≤12hrs or difficult to treat
▪ Severe, prolonged (~7 days) EEG findings including burst suppression pattern
▪ Oliguria/anuria >24hrs
▪ Abnormal neuro exam ≥14 days
aEEG (amplitude integrated EEG) – who is at risk
for long term brain injury
▪ Hypothermia decreases rate of apoptosis, suppresses
neurotoxic mediators like glutamate, free radicals,
nitric oxide, lactate
Phenobarbital (DOC)
▪ Loading dose 20mg/kg
▪ Additional 5-10mg/kg
▪ Maintenance 3-5mg/kg
For refractory seizures → Phenytoin or Lorazepam
(first line), Levetiracetam (first or second line)
▪ Monitor vital signs, prevent hypotension, acid base
balance
COMPLICATIONS
▪ Greatest risk of adverse outcome → severe fetal
acidosis (pH <6.7) and a base deficit >25mmol/L
▪ Brain death after HIE is diagnosed from clinical
findings of:
● Coma unresponsive to pain, auditory or visual
stimulation
● Apnea with PCO2 rising from 40 to >60mmHg
● Absence of brainstem reflexes
▪ Because of inconsistencies, there is no universal
agreement reached regarding the definition of neonatal
brain death
Stages of HIE in Term infants
PPS Oral Exam Reviewer 2020
STAGE 1
STAGE 2
STAGE 3
Hyperalert
Lethargic
Stupor, coma
Muscle tone
Normal
Hypotonic
Flaccid
Posture
Normal
Flexion
Decerebrate
Reflexes/clonus
Hyperactive
Hyperactive
Absent
Myoclonus
Present
Present
Absent
Moro reflex
Strong
Weak
Absent
Pupils
Mydriasis
Miosis
Unequal, poor
light reflex
Seizures
None
Common
Decerebration
Batch Clingy
SIGNS
Consciousness
50
EEG findings
Normal
Low voltage
changing to
seizure
activity
Duration
<24hr
if
progresses;
otherwise may
remain normal
24hrs to 14
days
Days to weeks
Outcome
Good
Variable
Death,
deficits
Burst
suppression to
isoelectric
severe
INTRAVENTRICULAR
HEMORRHAGE
STATIC ENCEPHALOPATHY
Nonprogressive Brain
Disorders like Cerebral
Palsy and Mental
Retardation
PERIVENTRICULAR LEUKOMALACIA (PVL)
▪ Involves intrauterine and postnatal events
▪ Hypoxia, venous obstruction from IVH, or undetected
fetal stress may result in decreased perfusion to the
brain, leading to periventricular hemorrhage and necrosis
▪ Risk for PVL increases in infants with IVH or
ventriculomegaly
CEREBRAL PALSY
▪ Group of permanent disorders of movement and
posture → activity limitation attributed to nonprogressive
disturbance in the fetal or infant brain
▪ Considered as a static encephalopathy but some
features like movement disorders and orthopedic
complications can progress over time
▪ 80% of cases point to antenatal factors, few had
congenital anomalies external to CNS, 10% have evidence
of intrapartum asphyxia.
▪ Intrauterine exposure to maternal infection was
associated with significant ↑ in CP in normal BW infants
▪ Intracerebral hemorrhage and periventricular
leukomalacia are the major lesions that contribute to CP
in preterm infants
PPS Oral Exam Reviewer 2020
▪ Preterms <32 weeks evaluated with routine
cranial UTZ to check
▪ Infants <1000gms highest risk, UTZ within 3-7th
day of life
▪ Ff up at 36-40 weeks AOG to check for PVL
MRI – more sensitive for evaluation of extensive
periventricular injury, more predictive of longterm outcome
GRADING
Grade 1 – bleeding isolated to subependymal area
Grade 2 – bleeding within ventricle without ventricular dilatation
Grade 3 – IVH with ventricular dilatation
Grade 4 – IVH with Parenchymal hemorrhage
▪ Usually clinically asymptomatic until neuro sequelae of white matter damage become
apparent in later infancy – as spastic motor deficits
▪ May be present at birth but occurs later
▪ Divided into major motor syndromes
▪ Commonly associated with a spectrum of developmental disabilities (intellectual
impairment, epilepsy, visual, hearing, speech, cognitive and behavioral abnormalities)
Classification of Cerebral Palsy and Major Causes
MOTOR
NEUROPATHO/MRI
MAJOR CAUSES
SYNDROME
Spastic diplegia
(35%)
PVL, periventricular
cysts or scars in white
matter, enlarged
ventricles, squared off
posterior ventricles
Prematurity
Ischemia
Infection
Endocrine/metabolic
Spastic
quadriplegia
(20%)
PVL, multicystic
encephalomalacia,
cortical malformations
Endocrine/ metabolic/
genetic/
developmental
▪ Antenatal steroids – 24-34 weeks at risk for preterm
delivery → decrease risk IVH
▪ Post hemorrhagic hydrocephalus – VPS insertion
▪ Symptomatic
Seizures – anticonvulsant drugs
Anemia and coagulopathy – PRBC or FFP
Insert VP shunt
Serial LP and ventricular taps – temporizing but not
therapeutic
COMPLICATIONS
▪ Post hemorrhagic hydrocephalus
▪ Hydrocephalus – 2-4 weeks after
PROGNOSIS
▪ Neuro development (CP, mental devt index if
<1000gm)
MRI (check table from previous column)
Multidisciplinary team
▪ Neurodev pediatrician
▪ Child neuro
▪ Rehab med
▪ OT, PT, speech patho
▪ Social workers
▪ Educators
▪ Dev psychologists
▪ MgSO4 given to mothers in premature labor with
birth imminent <32wks AOG showed significant
reduction of CP at 2yo
▪ Cooling term infants with HIE to 33.3C for 3 days
starting within 6hr birth decreases dyskinetic or spastic
quadriplegia form of CP
▪ Spastic diplegia → assistance of adaptive equipment
(orthoses, walkers, poles, standing frames)
▪ Quadriplegia → motorized wheelchair, feeding
devices modified typewriters, customized seating
arrangements
Batch Clingy
▪ Develops spontaneously, or due to trauma and asphyxia, often with preterm infants (IVH)
▪ Can be associated with fetal alloimmune thrombocytopenia, cerebral hemorrhage, or porencephalic cyst
▪ VLBW infants – IVH and PVL
IVH
▪ Deterioration on 2nd or 3rd day of life
▪ Preterm
▪ Hypotension, apnea, pallor or cyanosis, poor suck, abnormal eye signs, high pitched shrill
▪ Occur in the gelatinous subependymal germinal matrix
cry, convulsions, decreased muscle tone
▪ Immature blood vessels plus poor tissue support
▪ Metabolic acidosis, shock
▪ Decreased hematocrit or failure to rise after transfusion
51
▪ Primarily in infants born <32wks AOG
▪ Alveolar hypoplasia with concomitant small airway
dysfunction and impaired pulmonary vascular growth
▪ Result of lung injury in infants requiring mech vent and
supplemental O2
▪ Interference with lung anatomic maturation
CAUSES
▪ Early gestational age
▪ Low birth weight
▪ Lung barotrauma
▪ Exposure to hyperoxia
▪ Lung inflammation
▪ Pre and postnatal infections
▪ Potential modifier genes
▪ Epigenetic factors
BRONCHOPULMONARY
DYSPLASIA / CHRONIC
LUNG DISEASE
New BPD
▪ BW <1000 grams
▪ <28 weeks AOG
Features in new BPD
▪ Alveolar hypoplasia
▪ Variable saccular wall fibrosis
▪ Minimal airway disease
Hemiplegia
(25%)
Stroke: in utero or
neonatal
Focal infarct or cortical,
subcortical damage
Cortical malformations
Thrombophilic
disorders, infection,
genetic/
developmental,
periventricular
hemorrhagic
infarction
Extrapyramidal
(athetoid,
dyskinetic) (15%)
Asphyxia: symmetric
scars in putamen and
thalamus
Kernicterus
Mitochondrial
Asphyxia, kernicterus,
mitochondrial,
genetic/ metabolic
▪ Tachypnea, head bobbing, retractions when ill or at baseline depending on severity
▪ Breath sounds may be clear but many have baseline wheeze or coarse crackles
▪ Persistent fixed wheeze or stridor suggests subglottic stenosis or large airway malacia
▪ Fine crackles present in those prone to fluid overload
▪ No improvement on 3rd or 4th day of ventilation → increased need for O2 and ventilator
support
▪ RD worsens → hypoxia, hypercapnia, O2 dependence, R sided heart failure
▪ Alveolar collapse and volutrauma from mech vent →
lung injury
▪ Free radicals from O2, immaturity, infection, PDA,
malnutrition → contribute to BPD
COMPLICATIONS
Quality of life
Trauma
Infection
CXR: air trapping, focal atelectasis, interstitial
changes and/or peribronchial thickening
Chronic respiratory insufficiency
▪ ↑ Serum bicarbonate
▪ ↑ CO2
▪ Hypoxemia
▪ Polycythemia
▪ After discharge, high risk of rehospitalization
▪ Nutritional support – calories
▪ Fluid restriction
Drugs
▪ Furosemide + KCl supplementation – for fluid
overload, decreases PIE and PVR
▪ Inhaled bronchodilators (albuterol, CV or DV)
Maintenance of oxygenation
▪ Severe may require chronic O2 support
▪ Target O2 sat is ≥ 92%
FOUR PATHOLOGIC STAGES
▪ Acute lung injury
▪ Exudative bronchiolitis
▪ Proliferative bronchiolitis
▪ Obliterative fibroproliferative bronchiolitis
Chronic respi insufficiency
▪ Tracheostomy, mech ventilation
FEATURES
MILD
MODERATE
SEVERE
<32wk AOG
at birth
O2 reqt for
at least 28
days
Breathing
RA at
36wk PMA
or at
discharge,
whichever
comes first
<30%
supplemental
O2 at 36wks
PMA or at
discharge,
whichever
comes first
>30%
supplemental
O2 and/or
PPV at 36wk
PMA or at
discharge
whichever
comes first
>32wk AOG
at birth
O2 reqt for
at least 28
days
Breathing
RA at 56
DOL or at
discharge,
whichever
comes first
<30%
supplemental
O2 at 56 DOL
or at
discharge,
whichever
comes first
>30%
supplemental
O2 at 56 DOL
or at
discharge,
whichever
comes first
▪ Occurrence indirectly proportional to gestational age
▪ Vit A supplementation in VLBW infants ↓ risk of BPD
▪ Rhizotomy
▪ Serial botulinum toxin injection
▪ Prevention of respiratory viral illness
▪ Monitor for development of pulmonary HTN
PROGNOSIS
▪ Prognosis better for neonates >1500gms
▪ Prognosis is generally good for infants with BPD and
most are weaned off by 1yr of life (those requiring
mech vent at home are often weaned during
toddlerhood)
▪ Mortality – highest in those who are ventilator
dependent >6mos
COMPLICATIONS
▪ Growth failure, psychomotor retardation, parental
stress,
nephrolithiasis,
osteopenia,
electrolyte
imbalance
▪ Airway problems – subglottic stenosis, vocal cord
paralysis,
▪ Cardiac – pulmonary HTN, systemic HTN
▪ Aspiration from dysphagia and/or GER
▪ Pulmonary exacerbation is triggered during viral
respiratory infections
Batch Clingy
▪ Severe BPD – prolonged mech vent; gradual weaning
PPS Oral Exam Reviewer 2020
52
Acute
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Imbalance of caloric intake and expenditure
▪ Affected by environmental factors – food, physical activity,
changes in health behavior and sleep, genetics
Sensitive periods (increased risk for obesity): infancy, adiposity
rebound (when body fat is lowest approx. 5.5 yo), adolescence
OBESITY
Neuroendocrine Feedback loops – appetite and weight negative
feedback system
▪ Links adipose tissue, GI tract and CNS
▪ GI hormones – CCK, glucagon like peptide 1, peptide YY and
vagal neuronal feedback- promote satiety
▪ Ghrelin – stimulates appetite
▪ Adipose tissue – feedback regulates energy levels to brain
through release of leptin (low leptin stimulates food intake,
high leptin inhibits hunger) and adiponectin (reduced levels if
obese, increased if fasting
▪ Peptide YY – reduces food intake via the vagal-brainstemhypothalamic pathway (lower levels in obese children)
▪ Result of abnormally high blood cortisol levels of other
glucocorticoids
▪ Can be iatrogenic or result of endogenous cortisol secretion
(adrenal gland tumor or hypersecretion of ACTH by pituitary)
▪ Most common cause – exogenous administration of
glucocorticoid hormones
▪ Endogenous Cushing (infants) – by functioning adrenocortical
tumor (signs of cortisolism along with hypersecretion of
steroids, androgens, estrogen and aldosterone)
▪ Endogenous Cushing (children >7 yrs) – Cushing disease,
excessive ACTH secreted by pituitary adenoma (microadenoma)
→ bilateral adrenal hyperplasia
CUSHING
SYNDROME
▪ Ectopic ACTH secretion (ACTH dependent - uncommon in
children) – islet cell carcinoma of pancreas, NB, Wilms, thymic
carcinoid
▪ ACTH independent CS – nodular hyperplasia and adenoma
formation occurs in McCune Albright syndrome
▪ Mutation of G protein where ACTH receptor normally signals,
if mutation present, cortisol and cell division stimulated
independently
CLINICAL MANIFESTATIONS
Endocrine causes – may show SLOW linear growth
Genetic causes – may manifest with extreme hyperphagia,
coexisting dysmorphic features, cognitive impairment,
vision and hearing abnormalities and short stature
DIAGNOSIS
Overweight – BMI in 85–95th percentile
Obese – BMI ≥95th percentile
Check comorbidities
Developmental delay, hearing impairment, difficulty snoring, sleeping or daytime
sleepiness → sleep apnea
Family history – parental obesity (increased risk)
▪ Check BP, acanthosis nigricans (insulin resistance), hirsutism (PCOS), Tanner
staging
▪ Labs – FBS, Triglycerides, LDL, HDL, liver function tests
▪ 24-hour food recall
▪ Seen in infants <1yo
▪ More severe in infants
▪ Rounded face with prominent cheeks and flushed
appearance (moon facies)
▪ Generalized obesity common
Children with adrenal tumors
▪ Signs of abnormal masculinization occur
▪ Hirsutism of face and trunk
▪ Pubic hair, acne deepening of voice
▪ Enlargement of clitoris (girls)
▪ Impaired growth (length below 3 rd percentile
▪ Hypertension → may lead to heart failure
▪ Increased susceptibility to infection
Older children
▪ Obesity and short stature
▪ Severe obesity of face and trunk compared with
extremities
▪ Striae on hips, abdomen and thighs
▪ Puberty delayed, amenorrhea
▪ Weakness, headache and emotional lability
COMPLICATIONS
▪Increased risk for morbidity
-CVD, type 2 DM, HTN, hyperlipidemia, nonalcoholic fatty liver disease (cirrhosis)
▪ Mechanical – OSA, orthopedic complications
▪ Low self-esteem, depression, eating disorders
Cortisol levels – diurnal (normally elevated 8am, decrease to <50% by midnight)
▪ Cushing – midnight cortisol levels high (>4.4 mg/dl)
▪ Can be measured saliva samples
↑ Urinary excretion of free cortisol – measure 24hour urine sample
Single dose Dexamethasone suppression test
▪ 25-30mg/kg (max 2mg) given at 11pm
▪ In normal people – plasma cortisol at 8am <5mcg/dL
Glucose tolerance test – abnormal
Electrolytes – may be decreased
If Cushing syndrome established – determine if caused by:
▪ Pituitary adenoma – ACTH may be normal
▪ ACTH secreting tumor – high ACTH
▪ Cortisol secreting adrenal tumor – ACTH suppressed
Bolus of CRH
▪ Patients with ACTH dependent CS – exaggerated ACTH and cortisol response
▪ Adrenal tumors – no increase in ACTH and cortisol
TREATMENT / COMPLICATIONS / PROGNOSIS
Nutrition + exercise + cognitive behavioral approaches
▪ Recommendations about caloric intake
▪ Eating patterns
▪ Traffic light diet (groups food into green, yellow, red)
▪ Limit screen time and more physical activity
Adolescents – Sibutramine (NE or serotonin reuptake
inhibitor) and Orlistat (intestinal lipase inhibitor)
Bariatric surgery – considered only in kids with:
▪ Complete or near complete skeletal maturity
▪ BMI >40
▪ Medical complication of obesity after they have failed
6mos of a multidisciplinary weight management program
Transsphenoidal pituitary microsurgery
▪ TOC
▪ Relapses tx with re-operation or pituitary irradiation
Cyproheptadine
▪ Centrally acting serotonin antagonist that blocks ACTH
release
▪ Used in adults, rare in children
Adrenalectomy
▪ If pit adenoma no response to tx or if ACTH secreted by
ectopic metastatic tumor
▪ May lead to ↑ ACTH secretion by unresected pit
adenoma → Nelson syndrome
▪ s/p Adrenalectomy – preop and post op replacement tx
with corticosteroid
COMPLICATIONS
Post op: sepsis, pancreatitis, thrombosis, poor wound
healing, sudden collapse
CT scan – detects adrenal tumors >1.5cm
MRI – may detect ACTH secreting pituitary adenomas
Bilateral inferior petrosal blood sampling – measure ACTH before and after CRH,
required to localize tumor
DIFFERENTIAL DIAGNOSIS
Cushing – Obesity + striae + HTN
Simple Obesity
▪ Tall (CS short or decelerating growth)
▪ Salivary nighttime levels of cortisol are normal
PPS Oral Exam Reviewer 2020
Batch Clingy
▪ HTN, hyperglycemia, osteoporosis
53
▪ Cortisol secretion suppressed by oral dexamethasone
Generalized glucocorticoid resistance
▪ ↑ Cortisol and ACTH
HTN, hypokalemia, precocious puberty
Complex
DISEASE
PRADER WILLI
SYNDROME
ETIOLOGY / INCIDENCE / PATHOGENESIS
Uniparental disomy – both chromosomes of a pair or areas of 1 chromosome
inherited from single parent
UPD chromosome 15 – Prader willi (maternal UPD, paternal contribution missing) and
Angelman syndrome
▪ Paternal deficiency of HB11-85 snoRNAs (small nucleolar RNAs)
▪ Early in life: hypotonic that they cannot consume enough calories to maintain weight
▪ NGT feeding, FTT common
▪ 1st 4 yrs of life – muscle tone improves
▪ Voracious appetite
DIAGNOSIS
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Initial management of hypotonia and feeding
▪ Evaluate for hypogonadism or hypopituitarism
▪ Management of obesity
▪ Monitoring for scoliosis
▪ Therapy for behavioral issues
▪ Surgery – cryptorchidism, scoliosis, tonsillectomy (if with OSA)
Batch Clingy
▪ Associated with advanced maternal age
▪ Embryo starts off as trisomy 15 then loss of paternal chromosome
CLINICAL MANIFESTATIONS
▪ Hypotonia of prenatal onset
▪ Postnatal growth delay
▪ Almond shaped eyes, small hands and feet, developmental disability
▪ Hypogonadotrophic hypogonadism and obesity after infancy
PPS Oral Exam Reviewer 2020
54
Complex
PREDIABETES
DIABETES MELLITUS
TYPE 1
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Individuals with abnormalities in blood glucose homeostasis who are at ↑
risk of diabetes
▪ Not a clinical entity but a risk factor for future diabetes and CV disease
▪ Often associated with metabolic syndrome – insulin resistance,
compensatory hyperinsulinemia, obesity, dyslipidemia, HTN
▪ Most common type in childhood (median age 7-15yo)
▪ Autoimmune destruction of pancreatic islet B cells → permanent insulin
deficiency
▪ Genetic predisposition: HLA and other genes
▪ Unknown environmental insult – triggers autoimmune process
▪ Factors:
● Cow’s milk feeding at early age
● Viral infections (Coxsackie, CMV, enteroviruses, mumps) – direct
infection of B cells → lysis and release of self-antigens; clearest evidence is in
congenital rubella syndrome (70% associated with B cell autoimmunity,
development of type 1 DM in 40, time lag may be as high as 20yrs, no
association if rubella appears after birth or when vaccinated)
● Vit D deficiency and environmental
▪ T cell mediated, Ab to islet cell antigens months to years before onset of B
cell dysfunction
▪ Less common types – genetic defects of insulin receptor or inherited
abnormalities in sensing of glucose concentration by pancreatic B cells
FINDINGS / CLINICAL MANIFESTATIONS
Defined by:
▪ Impaired fasting glucose (FBS 100-125mg/dL)
▪ Impaired glucose tolerance (2h postprandial glucose 140-199mg/dL)
▪ HbA1c values of 5.7-6.4%
▪ FBS of 99mg/dL  upper limit of normal
▪ Associated features: Lean or weight loss at diagnosis, thyroid autoimmunity, celiac disease
▪ DKA at presentation (25%)
Based on 4 glucose abnormalities
▪ FBS >126mg/dl
▪ Random venous plasma glucose >200mg/dL with symptoms of hyperglycemia
▪ Abnormal OGTT with 2hr post prandial >200mg/dL
▪ HbA1C >6.5%
Classic Presentation: POLYURIA + POLYDIPSIA + POLYPHAGIA AND WEIGHT LOSS (reflecting hyperglycemic
and catabolic physiologic state)
▪ Other symptoms: fatigue, weakness, general feeling of malaise
▪ Hyperglycemia – insulin secretory capacity inadequate to enhance peripheral glucose uptake and suppress
hepatic and renal glucose production
▪ Insulin deficiency – causes postprandial hyperglycemia then fasting hyperglycemia
▪ Ketogenesis – sign of more complete insulin deficiency
▪ Lack of suppression of gluconeogenesis and glycogenolysis exacerbates hyperglycemia
▪ Fatty acid oxidation generates ketones → B hydroxybutyrate, acetoacetate, acetone
● Protein stores in muscle and fat stores in adipose tissue are metabolized to provide substrates for
gluconeogenesis and fatty acid oxidation
DIABETES MELLITUS
TYPE 2
DIABETIC
KETOACIDOSIS
▪ Insulin resistance and progressive non-autoimmune B cell failure
▪ Common in adults but with ↑ incidence in childhood and adolescence due
to rise in obesity (rarely younger than 10yo)
▪ No insulin → persistent partial hepatic oxidation of fatty acids to ketone
bodies
▪ 2/3 ketone bodies (organic acids) → elevated anion gap
▪ Lactic acidosis – severe dehydration, ↓ tissue perfusion
▪ Osmotic diuresis from hyperglycemia → dehydration
▪ Vomiting from acidosis and tachypnea → ↑ dehydration
PPS Oral Exam Reviewer 2020
▪ Glycosuria –serum glucose exceeds renal threshold for glucose reabsorption (160-190mg/dl) →
polyuria/nocturia begins
● Osmotic diuresis (lose Na, K, electrolytes) → dehydration
● Female patients develop vulvovaginal candidiasis from chronic glycosuria
▪ Polydipsia and polyphagia – triggered by daily losses of as high as 5L water and 250g glucose (representing
1000 calories or 50% average daily caloric intake
▪ Weight loss – persistent catabolic state and loss of calories through glycosuria and ketonuria
When disease progress, ketoacids accumulate → abdominal pain, nausea, emesis → inability to replace
urinary water losses → dehydration accelerates manifested by weakness, orthostasis and further weight
loss → DKA
▪ Presentation is more insidious: excessive weight gain and fatigue, or incidental glycosuria on routine PE
▪ DKA at presentation (5-20%)
▪ Acanthosis nigricans (dark pigmentation of skin creases in nape of neck) – present in majority w/
accompanying hyperinsulinemia
▪ Associated features: PCOS, HTN, hyperlipidemia, fatty liver disease, family history
▪ Dehydration, N/V, lethargy, altered mental status, in extreme cases – coma
Advanced ketoacidosis symptoms
▪ Abdominal pain – mimics acute abdomen (2 vomiting or paralytic ileus)
*presence of polyuria (despite dehydration) – differentiates DKA from GI disorders
▪ Kussmaul respiration – deep, heavy, non-labored rapid breathing, respiratory compensation for acidosis
▪ Fruity breath odor (from acetone) – detected patient’s breath
TREATMENT
▪ Lifestyle modification
Goal: maintain blood glucose as close to normal and delay onset of
complications (retinopathy, nephropathy, neuropathy)
▪ <5yo – maintain between 80-180
▪ School age – 80-150
▪ Adolescents – 70-130
Insulin
▪ Fast acting insulin during meals
▪ Long acting insulin at bedtime
Nutrition
▪ CHO 50-65%
▪ Protein 12-20%
▪ Fat 30%
▪ 3 meals and 3 snacks
Blood glucose testing
▪ Before each meal and bedtime
▪ If sick, measure urine ketones also
Long term control: HgbA1C – reflect blood glucose for the past 3 months
▪ <6yo – target 7.5%-8.5%
▪ 6-13yo – <8%
▪ 13-18yo – <7.5%
COMPLICATIONS
▪ Annual ophthalmologic exam for retinopathy
▪ Check urine for microalbuminuria annually
▪ Chronic autoimmune lymphocytic thyroiditis
hypothyroidism
common
→
▪ Lifestyle modification
▪ Metformin
▪ Insulin
▪ NPO
▪ Monitor I&O and neurologic status
▪ Have Mannitol at bedside (1g/kg IV push for cerebral edema)
TREATMENT PROTOCOL
1st hour (Quick Volume Expansion)
▪ Initial IV bolus 10-20cc/kg PNSS or LRS
Batch Clingy
DISEASE
55
▪ Electrolyte abnormalities – lost in urine
▪ Hydrogen ions accumulate – IC K exchanged for H ions
● Serum K ↑, then ↓ when excreted by kidney
● ↓ Serum K ominous sign of body K depletion
▪ Phosphate depletion – ↑ renal phosphate excretion
▪ Na depletion – renal loss Na and GI losses (vomiting)
Classification Of DKA
NORMAL
CO2
20-28
7.35pH
7.45
No
change
MILD
16-20
7.257.35
Oriented
Alert but
fatigued
Clinical
MODERATE
10-15
▪ Prolonged corrected Q-T interval
▪ Diminished neurocognitive function
▪ Coma
▪ Fever- uncommon, search for infectious sources
SEVERE
<10
7.15-7.25
<7.15
Kussmaul
respirations
Kussmaul or
depressed
respirations
Oriented
but sleepy
Arousable
Sleepy to
depressed
sensorium
Coma
Honeymoon Phase
▪ If new onset, beta cell mass not yet completely destroyed
▪ Period of stable glucose control usually starts first few weeks of therapy, can
last for 2 years
Cardinal biochemical abnormalities
▪ ↑ Blood and urine ketones
▪ ↑ Anion gap
▪ ↓ Serum bicarbonate and pH
▪ ↑ Effective serum abnormality
▪ Hyponatremia is commonly present with hyperglycemia – 2o to osmotic dilution as water shifts to ECF
▪ Potassium and phosphate depletion is common after prolonged polyuria but may be masked by acidosis
which leads to extracellular shifting of these ions
COMPLICATIONS
▪ Cerebral edema (can lead to herniation) – most serious complication
▪ Osmolar shift → fluid accumulation in IC compartment and cell swelling
▪ ↓ Sensorium, sudden severe HA, vomiting, change in vital signs (bradycardia, HTN, apnea), dilated pupil,
ophthalmoplegia, or seizure
▪ ↑ Risk for cerebral edema
● Higher initial BUN concentration, lower initial PCO2, failure of serum Na to increase, treat wit HCO3
● Signs – obtundation, papilledema, pupillary dilation or inequality, HTN, bradycardia, apnea
● Tx – rapid use of IV Mannitol, endotracheal intubation, ventilation
▪ Thrombosis or infarction
▪ ATN with ARF by severe dehydration
▪ Pancreatitis
▪ Arrhythmias 2o to electrolyte abnormalities
▪ Pulmonary edema, bowel ischemia
▪ Peripheral edema – elevations in ADH and aldosterone
▪ Mauriac syndrome – growth failure and hepatomegaly 2 o to excess glycogen accumulated in liver, related
to chronic underinsulinization
LONG TERM COMPLICATIONS
▪ Diabetic retinopathy
▪ Diabetic nephropathy
▪ Diabetic neuropathy
▪ Skeletal complications (ex. fractures)
● To avoid rapid shifts osmolality
● Use NSS for replacement 1st 4-6hrs then 0.45 NaCl
▪ Insulin drip at 0.05 to 0.10u/kg/hr
● Serum glucose should ↓ at a rate of 100mg/dL/hr
2nd hour until DKA resolution
▪ 0.45% NaCl plus continue insulin drip
▪ 20meq/L Kphos and 20meq/L KAc
● If K<3meq/L, give 0.5-1.0meq/kg as oral K solution or ↑ IV K to
80meq/L
▪ 5% glucose if blood sugar <250mg/dL
● If serum glucose <250-300 – glucose infusion in IV should be done
● Insulin infusion should not be discontinued before resolution of
acidosis
Variable
▪ Oral intake w/ subcutaneous insulin
▪ No emesis, CO2 ≥16meq/L, normal electrolytes
NOTE: Initial IV bolus is considered part of total fluid allowed in the first
24 hours and subtracted before calculating IV rate
Acidosis
▪ Insulin decreases production of FFA and protein catabolism, enhances
glucose usage in tissues
▪ Avoid HCO3 – ↑ in CNS acidosis (↑ diffusion of CO2 in BBB)
▪ Acidosis corrected – urine ketones may rise
Electrolyte imbalance
▪ Serum K can ↓rapidly as insulin and glucose therapy improves acidosis
→ potassium exchanged for IC hydrogen ion
▪ If with adequate UO, add K to IV fluids
▪ Give 50% KCl and 50% K phosphate (20-40meq/L)
▪ If serum K >6, don’t add K!
Monitoring
▪ Initial labs – serum glucose, Na, K, Cl, HCO3, BUN, Crea, Calcium,
Phosphate, and Mg, ABGs for arterial and venous pH, and urinalysis
▪ Serum glucose monitored every hour
▪ Electrolytes every 2-3 hours
▪ Ca, Ph, Mg measured every 4-6hrs
▪ Assess neuro and mental status
▪ If with HA or deterioration of mental status, check for cerebral edema
Batch Clingy
Transition to outpatient
▪ If acidosis corrected, patient tolerates oral feedings → insulin d/c
▪ SC insulin given 30 mins before d/c IV insulin
▪ Insulin starting 0.5-0.7u/kg.24hrs (prepubertal)
▪ 0.7-1 u/kg/24hr for adolescents
▪ Serum glucose assessed before each meal, at bedtime, and periodically
at 2 or 3 am
PPS Oral Exam Reviewer 2020
56
Complex
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
Adrenal cortex
▪ Outer: Zona glomerulosa – mineralocorticoids (aldosterone)
▪ Middle: Zona fasciculata – glucocorticoids (cortisol)
▪ Inner: Zona reticularis – adrenal androgens
Adrenal medulla
▪ Neuroendocrine (chromaffin) cells – catecholamines (dopamine, norepinephrine, epinephrine)
▪ Glial (sustentacular) cells
LABORATORY FINDINGS / DIAGNOSIS
TREATMENT
▪ Hypothalamus (CRH) → Pituitary (ACTH, Corticotropin) → ACTH → synthesis and release of cortisol and adrenal androgens
▪ Primary Adrenal insufficiency or cortisol deficiency (defect in adrenal gland) → over secretion of ACTH
▪ Cortisol deficiency (from ACTH or CRH deficiency) → ↓ serum ACTH and cortisol
▪ Endogenous glucocorticoids feedback – inhibit ACTH and CRH
▪ RAA and K – regulate aldosterone secretion
▪ Fetal CRH-ACTH adrenal axis operational in utero, deficiencies in cortisol synthesis lead to EXCESSIVE ACTH
ex. 21 hydroxylase def – fetal adrenal gland secretes excess androgens, virilizing the fetus
ADDISON DISEASE
▪ Acquired primary adrenal insufficiency
▪ Autoimmune destruction of adrenal cortex (marked lymphocytic
infiltration)
▪ Most patients have antiadrenal cytoplasmic antibodies in their
plasma
▪ 21-hydroxylase (CYP21) is the most commonly occurring
biochemically defined autoantigen
▪ Form of 1o adrenal insufficiency with absence of glucocorticoid
and mineralocorticoid
▪ Hyperpigmentation
▪ Salt craving
▪ Orthostatic hypotension
▪ Fasting hypoglycemia
▪ Anorexia
▪ Weakness
▪ Episodes of shock during severe illness
▪ Most definitive test: measurement of serum cortisol before and
after administration of ACTH
▪ ↓ Cortisol
▪ ↑ ACTH
▪ ↓ Na (90%)
▪ ↑ K (occur later) and Ca
▪ ↑ Plasma renin
▪ Hypoglycemia and ketosis
▪ Eosinophilia, lymphocytosis, anemia
▪ ↑ Urinary excretion of Na and Cl, ↓ urinary K
▪
Glucocorticoid
replacement
(Hydrocortisone)
and
mineralocorticoid replacement (Fludrocortisone) if salt wasting +
NaCl supplementation
● Double or triple doses during stressful states (ex. Infection or
surgery)
▪ Surgical correction ambiguous genitalia (ex. Vaginoplasty and
clitoral recession for females)
▪ Elevated serum androgens – suppressed with glucocorticoids
▪ If diagnosed prenatally, can start prenatal treatment with
Dexamethasone 20ug/kg prepregnancy maternal weight daily in 2
or 3 divided doses
COMPLICATIONS
▪ Overtreatment – growth stunting and excessive weight gain
(Cushingoid features)
▪ Undertreatment – excessive height gain, skeletal advance and
early appearance of puberty, testicular adrenal tumors for males
Treatment must be immediate and vigorous:
▪ D5PNSS – correct hypoglycemia, hypovolemia, and
hyponatremia
▪ Avoid hypotonic fluids – can precipitate or exacerbate
hyponatremia
▪ If severe hyperK, give IV calcium or bicarbonate, intrarectal K
binding resin, or IV glucose and insulin
▪ Water soluble form of IV HAA: Hydrocortisone sodium succinate
*caution if w/ concomitant hypothyroidism as thyroxine can
increase cortisol clearance
Once acute manifestations are under control:
▪ Replacement treatment with hydrocortisone
▪ Mineralocorticoid replacement w/ fludrocortisone (monitored
PPS Oral Exam Reviewer 2020
Batch Clingy
ADRENAL
DISORDERS
▪ Normal variation serum cortisol and ACTH levels – diurnal – ↑ in morning (highest at 8am) and ↓ at night (reduced by 50%) → lost in Cushing syndrome – ↑ midnight cortisol levels
CONGENITAL ADRENAL HYPERPLASIA
▪ Female – virilization of external genitalia (uterus, ovaries and FT
▪ ↓ Cortisol
▪ Autosomal recessive
remains unaffected) – mild clitoromegaly to complete fusion of
▪ ↑ ACTH
▪ Most common cause of adrenocortical insufficiency in infancy
labioscrotal folds, to severe clitoromegaly making a phallus
▪ Very high baseline and ACTH stimulated 17-OHP (hundred to
▪ 21 hydroxylase deficiency (>90%)
▪ Male – appears normal at birth
thousand-fold)
● Glucocorticoid deficiency only (simple virilizing disease)
● May present with mineralocorticoid deficiency (salt wasting
Late onset CAH
▪ If with salt wasting crisis: hyponatremia, hyperkalemia, ↑
crisis). These 2 forms are collectively termed classic 21▪ Years after birth
plasma renin
hydroxylase deficiency. (Nonclassic has mildly elevated androgens
▪ Milder manifestations without ambiguous genitalia
and may be asymptomatic)
▪ Acne, hirsutism, irregular menstrual cycles or amenorrhea (may
Late onset CAH – ACTH stimulation test shows abnormally high
● Blocks conversion of 17OHP to 11-deoxycortisol → ↓ cortisol
be confused with PCOS)
response
→ ↑↑ ACTH → synthesis of steroids, shunting to overproduction
of androgens
▪ Next most common cause of CAH is 11B hydroxylase deficiency
57
PHEOCHROMOCYTOMA
▪ Catecholamine secreting tumors arising from chromaffin cells
▪ Most common site of origin is adrenal medulla, R>L
▪ May be associated with genetic syndromes such as von Hippel
Lindau disease
▪ Component of multiple endocrine neoplasia (MEN2A, MEN2B)
▪ Abnormally ↑ cortisol or other glucocorticoids
▪ Progressive central or generalized obesity
▪ Moon facies
▪ Short stature
▪ Hirsutism
▪ Weakness
▪ Nuchal fat pad
▪ Acne, striae
▪ HTN, hyperglycemia
▪ Delayed puberty
▪ Amenorrhea
▪ Emotional lability
▪ Osteoporosis
▪ HTN
▪ HA, palpitations, abdominal pain, dizziness, pallor, vomiting,
sweating, seizures
▪ If severe, precordial pains radiating to arms, pulmonary edema,
cardiac and hepatic enlargement, growth failure
▪ Internal and external genitalia formed at 6-13wks AOG
▪ Fetal gonad and external genitalia – bipotential, can develop into male and female phenotype
▪ Presence of SRY → differentiates into a testis → Leydig cells secrete testosterone → converted to DHT → enlargement, rogation, and
fusion of the labioscrotal folds into scrotum → penis
▪ Female phenotype develops unless specific male influences alter development
▪ Total absence of androgens → female
HYPOFUNCTION OF THE TESTES
▪ From puberty onwards → testosterone deficiency, infertility, or
▪ During fetal life, can be a component of disorders of sex
both
development and lead to degrees of ambiguous genitalia
▪ No evidence for prepubertal children since they do not yet
produce significant amount of testosterone and are not yet
producing sperm
DISORDERS OF
GONADS
(Sexual
Development)
▪ ↑ 24-hour urinary cortisol secretion
▪ Single dose dexamethasone suppression test (25-30ug/kg)
given at 11pm → ↓ cortisol level at 8am in normal individuals
▪ ↑ Nighttime salivary cortisol levels
▪ 2 step dexamethasone (30 and 120ug/kg/day in 4 divided doses)
● In pituitary Cushing syndrome, the larger dose suppresses
cortisol levels
● In ACTH independent Cushing syndrome, cortisol levels are
not suppressed
CT scan detects adrenal tumors >1.5cm
MRI may detect ACTH secreting pituitary adenomas
▪ Proteinuria, glucosuria
▪ Polycythemia
▪ ↑ Blood and 24hr urinary metanephrine
▪ Urinary excretion of VMA is increased but vanilla containing
foods and fruits can give falsely elevated results hence no longer
routinely measured
CT scan or MRI to localize tumors
APPROACH to infant with GENITAL AMBIGUITY
▪ PE – noted where urethral opening lies and check fusion of
anterior portion of labioscrotal folds
▪ If vaginal opening open but clitoris enlarged – late exposure to
androgens
▪ Fully formed scrotum, normal and small penis (microphallus) –
normal exposure to androgen during 9-13wks AOG
▪ GOAL: identify life threatening disorders (CAH)
▪ 46XY – small phallus that does not increase in size after
androgen therapy → usually raised as female, some revert to
male gender
Primary hypogonadism (testes):
▪ 47XXY Klinefelter syndrome, males with >1 X chromosome, and
XX males
▪ Testes and penis are abnormally small at birth
▪ 2o sex characteristics will not develop
▪ Long extremities (eunuchoid), fat accumulation in hips, buttocks,
breasts, and abdomen
▪ ↑ Gonadotropins (hypergonadotropic)
▪ ↑ FSH and LH
▪ ↓ Testosterone at all ages
▪ Continuously ↑ AMH at puberty
▪ Noonan syndrome
▪ Short stature, webbing of neck, pectus carinatum or excavatum,
cubitus valgus, R sided CHD (pulmo valvular stenosis, hypertrophic
cardiomyopathy or ASD), characteristic facies, cryptorchidism,
small testes
▪ High frequency sensorineural hearing loss
▪ Hepatosplenomegaly, hematologic diseases
▪ Serum inhibin-B – marker of Sertoli cell function for Noonan
syndrome
Secondary hypogonadism (pituitary gonadotropic hormone
deficiency): tumors, infiltrative disease, autoimmune disease,
trauma, stroke
▪ Kallman syndrome – most common form of hypogonadotropic
hypogonadism
▪ Anosmia or hyposmia, synkinesia, hearing loss, midfacial defects,
renal agenesis
▪ Low or absent levels (hypogonadotropic)
▪ Chromosomal analysis
▪ MRI to look for tumors and other anomalies in the
hypothalamic-pituitary region
PPS Oral Exam Reviewer 2020
▪ Surgical removal
Replace deficient hormones
▪ Cortisol in CAH
▪ Testosterone in child with androgen biosynthetic defects
▪ Human growth hormone therapy in Noonan and Turner
▪ Oxandrolone ± growth hormone for Turner
▪ Replacement therapy w/ estrogen is indicated for Turner but no
consensus as to when to initiate
Psychological support
Batch Clingy
CUSHING SYNDROME
▪ Most common cause – exogenous administration (long term
steroids)
▪ Endogenous – adrenal adenoma, carcinoma, nodular adrenal
hyperplasia, ACTH secreting pituitary microadenoma (→ bilateral
adrenal hyperplasia → Cushing disease → most common
endogenous etiology in children >7yo)
by plasma renin activity and Na and K)
▪ Replacement of DHEA is still controversial
▪ Transsphenoidal pituitary microsurgery – treatment of choice in
pituitary Cushing disease
▪ Parenteral glucocorticoids – given during and after surgery to
avoid acute adrenal insufficiency
58
HYPOFUNCTION OF THE OVARIES
Primary (hypergonadotropic): Premature ovarian failure – arrest
of normal ovarian function before 40yo
▪ 45X Turner syndrome
▪ Sexual infantilism, webbed neck, cubitus valgus, broad chest,
widely spaced nipples, short stature (cardinal finding), cardiac
defects (bicuspid aortic valve, CoA, TAPVR), renal malformations,
IBD, autoimmune thyroid disease, recurrent bilateral otitis media
▪ UTZ of heart, kidneys and ovaries + thyroid peroxidase
antibodies and thyroglobulin antibodies + transglutaminase
immunoglobulin A antibodies to screen for celiac disease for
Turner’s syndrome
▪ Females with Noonan syndrome (46XX chromosomes) and
▪ Show similar anomalies with Turner
normal sexual maturation usually occurs but delayed on 2yr
average
▪ Central (hypogonadotropic): Multiple pituitary hormone
deficiencies, chronic diseases
▪ Hypopituitarism
▪ Isolated deficiency of gonadotropins
Hypothalamus secretes GnRH → pituitary releases LH and FSH → gonads secrete sex steroids (testosterone from testes, estradiol and
progesterone from ovaries)
Serum gonadotropin levels obtained – determine if HYPO or
HYPER gonadotropic
Females: FSH – ovarian production of estrogen, in puberty causes formation and support of corpus luteum
Males: LH – production of testosterone from Leydig cells, later FSH stimulates development and support of seminiferous tubules
Sex steroids and inhibin (produced by gonads) –suppress the secretion of gonadotropins
Ultrasound of pelvic structures
Permanent condition – replacement with sex steroids
▪ Transdermal estradiol or conjugated estrogens
breakthrough bleeding happens
▪ Combined progesterone and estrogen used after
until
▪ Males – testosterone enanthate and cypionate given IM once
every 4 weeks
GnRH released in episodic pulses vary during development and menstrual period
▪ Onset of puberty, ↑ at night then during the day
▪ Adrenarche then Gonadarche
▪ Constitutional delay- may be given low dose steroids for 3-6
months
Females – thelarche (due to gonadarche), pubarche (due to adrenarche) then menarche (2-3 yrs later)
▪ Adequate calcium intake (risk for osteoporosis)
Males – Scrotal thinning → enlargement of testes and appearance of pubic hair
▪ Turner – promote growth with exogenous human GH
supplementation and induction of secondary sexual
characteristics
DELAYED PUBERTY – girls 13yrs old, boys 14yrs old
DISORDERS OF
PUBERTY
Constitutional delay in Growth and Adolescence
▪ With family hx delayed puberty
▪ Delayed onset of pubertal development
▪ Significant bone age delay (2 SD below mean, 1.5-2y delay)
Hypogonadotrophic Hypogonadism
▪ Difficult to distinguish from constitutional delay
▪ Normal dev’t in childhood and early puberty
▪ In adulthood, may have eunuchoid proportions
Isolated Gonadotropin Deficiency
▪ Inability to release gonadotropin but no other pituitary
abnormality
▪ Kallman syndrome – isolated gonadotropin deficiency with
disorders of olfaction
Syndromes of Hypogonadotropic Hypogonadism
▪ Anorexia nervosa – 1o or 2o amenorrhea, pubertal development
PPS Oral Exam Reviewer 2020
▪ ↓ Gonadotropin function when dieting, malnutrition, or if with
chronic disease resulting in weight loss (<80% ideal weight)
Batch Clingy
Abnormalities of the CNS
▪ CNS tumors (pituitary adenoma, glioma, prolactinoma,
craniopharyngoma)
▪ Idiopathic hypopituitarism – congenital absence of various
combinations of pituitary hormones
59
absent or minimal
▪ Athletic amenorrhea – female athlete triad: anorexia,
amenorrhea, osteoporosis
▪ Chronic or systemic illness (cystic fibrosis, DM, IBD) → pubertal
delay or amenorrhea
▪ Hypothyroidism – inhibits onset of puberty and delays
menstrual periods
Hypergonadotropic Hypogonadism
▪ Ovarian failure – Turner syndrome (45XO) (common cause of
ovarian failure and short stature)
Klinefelter syndrome (47XXY) – most common cause of testicular
failure
Primary Amenorrhea
▪ Mayer Rokitansky Kauser Huster syndrome – congenital absence
of uterus
▪ Imperforate hymen or vaginal septum
▪ Androgen insensitivity – normal feminization, absence of pubic
and axillary hair, 1o amenorrhea
▪ All mullerian structures (ovaries, FT, vagina) lacking
SEXUAL PRECOCITY (precocious puberty) – 2o sexual development
<9yo boys, <8yo girls
▪ Determine which part of normal puberty present and whether
estrogen effect of androgen effects or both are present
Central Precocious Puberty (GnRH dependent Precocious Puberty)
▪ Premature activation of hypothalamic-pituitary-gonadal axis
▪ Endocrine and physical aspect is normal but too early
▪ Diff r/o – CNS diseases (hydrocephalus, meningitis, encephalitis,
suprasellar cysts, head trauma, epilepsy, mental retardation,
irradiation)
▪ Hamartomas, germinomas, optic or hypothalamic gliomas,
astrocytomas, ependymomas
▪ Tall stature
▪ Advanced bone age
▪ ↑Sex steroid and pulsatile gonadotropin secretion
▪ ↑ Response of LH to GnRH
Peripheral Precocious Puberty (GnRH Independent Precocious
Puberty)
▪ Does not involve HPG axis
▪ Mc Cune Albright – most common cause, girls > boys
▪ Precocious gonadarche
▪ Bone disorder with polyostotic fibrous dyplasia
▪ Hyperpigmented macules (café au lait)
▪ Adrenal carcinomas and adenomas
Males –familial GnRH independent sexual precocity with
premature Leydig cell maturation
▪ HCG secreting tumors
VARIATIONS in PUBERTAL DEVELOPMENT
Isolated premature Thelarche
▪ ↑ Gonadotropins and ↓ sex steroid levels resulting from
primary gonadal failure
Labs
▪ Sex steroid levels (testosterone,
androstenedione)
▪ LH (pubertal) and FSH (prepubertal)
▪ Thyroid hormone
estradiol,
DHEAS,
▪ Long acting analogs of GnRH (Leuprolide) – suppress
gonadotropin secretion by downregulating GnRH receptors
MRI of CNS
▪ Isolated appearance of uni- or bilateral breast tissue in girls
(6mos to 3yrs)
▪ Inhibitor of testosterone synthesis (ketoconazole), antiandrogen
(spironolactone) and aromatase inhibitor (testolactone)
▪ Surgical removal if with tumor
▪ If no other signs, evaluate every 6-12mos to monitor if with
precocious puberty
Gynecomastia
▪ 45-75% boys
▪ Prepubertal – suggests unusual source of estrogen, exogenous
sources or from endogenous sources
PPS Oral Exam Reviewer 2020
▪ Ultrasound to check hyperplastic adrenals or ovarian tumor
Batch Clingy
Isolated Premature Adrenarche (Pubarche)
▪ Girls <6-7yo, boys <9yo
▪ If w/ other signs investigate for virilization, r/o CAH
60
Calcium and phosphate – regulated by 3 hormones
▪ Total serum Calcium measured, but ionized calcium preferable
because it more nearly reflect physiologic adequacy
Parathyroid hormone
▪ Secreted in response to a decrease in serum ionized calcium level (Ca ↓, PTH ↑)
▪ Stimulates 1a-hydroxylase in the kidney → enhanced production of 1-25dihydroxycholecalciferol (1,25(OH2)D3) → induced calcium
binding protein (calbindin 3) in intestinal mucosa → Ca absorption
▪ Mobilizes calcium from bone to serum and enhances reabsorption of Ca by kidney while inducing PO4 excretion → ↑ Ca, ↓ PO4
Vitamin D
▪ 1,25 dihydroxyvitamin D – enhances Ca absorption from the GIT, increases serum Ca levels and bone mineralization
Calcitonin
▪ Secreted by parafollicular (C cells) of thyroid gland
▪ Inhibits bone resorption by decreasing the number and activity
disease)
▪ Greater effect on fetus rather than child/adult
HYPOCALCEMIA
▪ Common in neonates between 12 and 72 hr of life (especially in
premature, asphyxiated, born to diabetic moms)
▪ Albumin major reservoir of protein bound calcium
DISORDERS OF
PARATHYROID
▪ ↓ Serum Ca is low, ↑ phosphorus
▪ N or ↓ alkaline phosphatase
▪ ↓ 1,25(OH2)D3 (high in severe hypocalcemia)
▪ N magnesium (but should always be checked in hypoCa)
▪ ↓ PTH
▪ Severe tetany or seizures – 5-10mL or 1-3mg/kg of IV 10%
calcium gluconate at 0.5-1ml/min, monitor cardiac status for
bradycardia
▪ Hypoparathyroidism – administer Vit D (calcitriol) and calcium;
monitor levels to avoid nephrocalcinosis and renal impairment
Bone radiographs: ↑ density in metaphyses or lamina dura
Xray or CT scan of skull: calcifications in basal ganglia
of bone-resorbing osteoclasts (hence used in treatment of Paget
ECG: prolonged QT interval
▪ Sxs result from ↑ neuromuscular activity – muscle cramps,
carpopedal spasm (tetany), weakness, paresthesia, laryngospasm,
seizure like activity
▪ Teeth erupt late, enamel formation is irregular → teeth may
appear soft
▪ Dry scaly skin, nails have horizontal lines, cataracts
▪ Tetany (Chovstek sign) – tapping facial nerve in front of ear
▪ Trousseau sign – carpal spasms exhibited when arterial blood
flow to hand occluded for 3-5 mins (BP inflated to 15mmHg above
SBP)
▪ ↑ Serum calcium
▪ ↓ Serum phosphorus and magnesium
▪ N calcitonin
▪ Surgical exploration – all cases
▪ Others have been treated successfully with bisphosphonates and
calcimimetics
Radiology: resorption of subperiosteal bone best seen on
phalanges of hands (most consistent finding)
Batch Clingy
PRIMARY HYPOPARATHYROIDISM
▪ Causes hypocalcemia but does not cause rickets
Etiologies:
▪ Congenital malformation: DiGeorge syndrome - del 22q11.2; Hypocalcemia occurs in 60%, transitory in majority (assoc abnormalities:
conotruncal heart defects, velopharyngeal insufficiency, cleft palate, renal anomalies, thymic aplasia)
▪ Surgical procedures: thyroidectomy or parathyroidectomy
▪ Autoimmune – can destroy thyroid gland, often associated with Addison disease and chronic mucocutaneous ca ndidiasis
PSEUDOHYPOPARATHYROIDISM
(hypocalcemia
and
hyperphosphatemia)
▪ Autosomal dominant; may present at birth or later
▪ Associated with Albright hereditary osteodystrophy
▪ Short stature, stocky body, round facies, short 4th & 5th MCPs,
subcutaneous calcification, dev delay
▪ Hypomagnesemia – may cause 2o hypocalcemia (giving calcium
will be ineffective, but giving magnesium promptly corrects both
hypoMg and hypoCa)
HYPERPARATHYROIDISM
▪ Muscle weakness, HA, fatigue, anorexia, abdominal pain, n/v,
▪ Excessive production from primary defect of the parathyroid
constipation, polydipsia, polyuria, weight loss, fever
glands
like
adenoma
or
hyperplasia
(primary
▪ Nephrocalcinosis, osseous changes
hyperparathyroidism)
▪ More often compensatory, aimed at correcting hypocalcemic
states (2o hypoparathyroidism)
PPS Oral Exam Reviewer 2020
61
RICKETS
▪ Disease of growing bone caused by unmineralized matrix at the
growth plates in children only before fusion of the epiphyses
Causes:
Nutritional Vit D deficiency
▪ Calcium not absorbed from intestine
▪ Poor vitamin D intake and avoidance of sunlight → rickets
▪ Fat malabsorption from hepatobiliary disease (biliary atresia,
neonatal heap) → Vit D deficiency (because it’s a fat-soluble
vitamin)
▪ Defects in vit D metabolism by liver and kidney can also cause
rickets
Phosphorus deficiency
▪ Familial hypophosphatemic rickets
● Defect in mineral metabolism – failure of kidney to
adequately reabsorb filtered phosphate
● ↓ Serum pH, ↑ urine pH
● X linked, more in males
▪ Growth plate thickens; proportion of osteoid (extensive) → bone
becomes soft and metaphyses of long bones widen (→ classic
symptoms of widening of wrist and ankles, bone deformities,
craniotabes)
▪ Older infants – poor linear growth, bowing of the legs on weight
bearing (windswept deformity), thickening at wrists and knees,
prominence of costochondral junctions (rachitic rosary)
Assess mineral and Vit D status:
▪ Calcium
▪ Phosphate
▪ PTH
▪ 25OHD
▪ Rickets – treat with 1,25 dihydroxyvitamin D and supplemental
calcium
Radiology: rachitic changes easily visualized on PA radiographs of
the wrist, fraying and cupping
▪ Nutritional rickets – given Vit D as one large does or weekly
doses
▪ Hypophosphatemic rickets – PO4 supplementation with vitamin
D therapy
Obtain:
▪ Dietary history
▪ Cutaneous synthesis
▪ Maternal risk factors
▪ Medication use
▪ History of renal disease
Calcium deficiency
▪ Rickets of prematurity
Batch Clingy
Renal losses
PPS Oral Exam Reviewer 2020
62
Complex
Idiopathic GH deficiency – most common cause of BOTH
congenital and acquired GH deficiency
Less often by anatomic defects of the pituitary gland (pituitary
aplasia) and other midline defects
Hereditary forms of GH deficiency – heterogenous defects of
gene for GH, GRF or GH receptor
Classic GH deficiency – ↓ to absent secretions of GH
GROWTH
HORMONE
DEFICIENCY
Acquired GH deficiency
▪ Late onset growth failure suggests tumor of hypothalamus or
pituitary
▪ Causes: radiotherapy for malignancy, meningitis, histiocytosis,
trauma
Congenital GH deficiency
▪ Normal or near normal BL and BW at term
▪ Growth rate slows after birth (2-3yo) – become shorter for age,
tends to have elevated weight to height ratio, appears chubby and
short
▪ If severe, GH production or action fall >4 SD below the mean by
1yo
Classic GH deficiency
▪ Cherubian facies (chubby immature appearance)
▪ High pitched voice from immature larynx
▪ Normal intellect, growth, and age appropriate speech (unless
hypogly or midline defects occur)
Males with isolated GH deficiency
▪ Micropenis – stretched penile length <2cm, N 3-5cm)
▪ Fasting hypoglycemia
GH resistance/GH insensitivity (rare)
▪ Abnormal number or function of GH receptors (ex. Laron
syndrome)
PE:
▪ Round head, short and broad face, prominent frontal bone,
depressed nose bridge and saddle shaped, small nose,
underdeveloped mandible and chin, teeth erupt late and is
overcrowded
▪ Short neck, small larynx, high pitched voice until puberty, small
hands, and feet
▪ Genitals small for age, sexual maturation delayed or absent
▪ Intelligence normal for age
FAILURE TO
THRIVE
(FTT)
▪ Children who are not growing as expected (related to
environmental and psychosocial causes)
▪ Studies advocated use of term MALNUTRITION
▪ Malnutrition = undernutrition → imbalance between nutrient
requirements and intake or delivery → deficits of energy, protein
or micronutrients that negatively affect growth and development
→ wasting, stunting (months after)
▪ Weight that falls or remains <3rd percentile for age
▪ <80% median height of the child
▪ Weight that decreases 2 major percentiles on the chart
▪ Acute malnutrition – duration of <3 mos
PPS Oral Exam Reviewer 2020
▪ WFH is usually normal, but an excess of body fat and a deficiency
of muscle mass contribute to a pudgy appearance
▪ Inadequate weight-for-corrected age, failure to gain adequate
weight over a period of time (weight gain velocity), height
velocity, weight-for-height, BMI (review WHO growth charts)
▪ Include prenatal history, family, and travel history
▪ List symptoms – vomiting, diarrhea, fever, respiratory symptoms
▪ Feeding history (quantity, quality, frequency of meals), feeding
behavior
▪ Psychosocial assessment of the family
▪ Complete PE and dev screening, neuro exam
PE findings:
▪ ↓ Subcutaneous fat
LABORATORY FINDINGS / DIAGNOSIS
Screening tests
▪ Metabolic panel for kidney and liver function
▪ CBC r/o anemia
▪ Celiac panel r/o celiac disease
▪ Carotene and folic acid levels to r/o malabsorption
Definitive: demonstration of absent or ↓ levels of GH in response
to stimulation
2 GH tests
▪ Target hormone measurement – IGF-1, IGFBP3
▪ Provocative tests: Arginine, levodopa, Insulin, clonidine, or
glucagon administration (to rapidly ↑ GH level)
▪ Thyroid hormone is a prerequisite for normal GH synthesis hence
must always be assessed first before provocative testing.
CT scan – suprasellar calcifications associated with
craniopharyngioma, or bony changes accompanying histiocytosis
MRI – small anterior pituitary gland, missing or attenuated
pituitary stalk, ectopic posterior pituitary
Plain film of hand – bone age
DIFFERENTIAL DIAGNOSIS
▪ Hormonal: Primary hypothyroidism, Cushing disease
▪ Systemic
● IBD, Celiac disease, occult renal disease, anemia
● Patients with systemic conditions have a greater deficit of
weight than length
▪ Severe psychosocial deprivation
▪ Genetic: Turner syndrome, SHOX gene defects
▪ Chronic illness
▪ Undernutrition
▪ Nonsyndromic family trait
▪ Constitutional delay of growth and development
▪ CBC w/ PC (IDA)
▪ Screen BLL
▪ Urinalysis
▪ Urine CS
▪ Serum electrolytes (renal function)
▪ TSH (check for hypothyroidism)
▪ Liver function tests
▪ Screen for TB
▪ Secure patient’s newborn screening results
TREATMENT
Recombinant hGH (rhGH) – given subcutaneously once daily, no
long-acting form available yet
Approved indications for rhGH use accdg to US FDA:
1.
GH deficiency
2.
Turner syndrome
3.
Chronic renal failure before transplant
4.
Idiopathic short stature
5.
SGA short stature
6.
Prader-Willi syndrome
7.
SHOX gene abnormality
8.
Noonan syndrome
Recommended initial dose: 0.16-0.24mg/kg/wk (22-25ug/kg/day)
▪ GH therapy is started as soon as possible and continued until
near-final height is achieved
Criteria to stop:
▪ Decision by parent that he/she is tall enough
▪ Growth rate <1inch/yr
▪ Bone age >14y/o in girls and >16y/o in boys
COMPLICATIONS
▪ Some patients develop hypothyroidism or adrenal insufficiency
during GH treatment hence periodic evaluation of thyroid and
adrenal function is indicated
▪ GH treatment influences glucose homeostasis hence ↑ risk for
type 2 diabetes
▪ Address the child’s nutritional requirements and social issues of
family
▪ Caloric supplementation
Nutritional management
▪ 1.5x expected calorie and protein intake for their age
▪ Initiation of catch up growth may take 2 weeks
▪ Consider a speech therapist for suck-and-swallow evaluation
▪ If no response after 2-3mos of outpatient therapy, admit with
NGT feed
Batch Clingy
▪ Presence of height 3.5 SD below mean, height velocity below 5th percentile for age, or height below target height for midparental height
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
▪ May be accompanied by hypoadrenalism, hypothyroidism, and
Infants: apnea, cyanosis, severe hypoglycemia, w/ or w/o seizures,
gonadotropin deficiency
prolonged neonatal cholestatic jaundice, nystagmus
63
▪ Causes: Environmental, GIT, Congenital, Infection, Metabolic,
Neurologic, Renal and Hematologic
Illness-related causes mechanisms:
▪ Failure to ingest sufficient calories / starvation (ex. Cardiac
failure or fluid restriction)
▪ ↑ Nutrient losses (ex. enteropathy / diarrhea)
▪ ↑ Metabolic demands (ex. Burns)
▪ Altered nutrient absorption or utilization (ex. Cystic fibrosis or
short bowel syndrome)
CONGENITAL HYPOTHYROIDISM
▪ Caused by dysgenesis (aplasia, agenesis, hypoplasia, or ectopia)
or dyshormogenesis (rare)
▪ Bamforth-Lazarus syndrome: thyroid dysgenesis, spiky or curly
hair, cleft palate, choanal atresia, bifid epiglottis
▪ Goiter – reflects IEM in pathway of iodide incorporation, or
reflects transplacental passage of antithyroid drugs of mom
(thyroid glands respond normally to ↑ TSH stimulation, a goiter is
almost always present)
▪ ↓ Free T4, ↑ TSH
▪ NBS (measures TSH) – results after 1 week
▪ If positive, do immediate confirmatory test
▪ Pendred syndrome: sensorineural deafness and goiter
HYPOTHYROIDISM
Primary – defect of
thyroid dysgenesis
Central or 2o –
isolated TSH
deficiency
MALNUTRITION
*check failure to
CENTRAL (SECONDARY) HYPOTHYROIDISM
▪ Associated with developmental defects of the pituitary or
hypothalamus
▪ Not detected by neonatal screening
▪ Suspected if with ↓ growth velocity, especially if NOT associated
with weight loss
Hashimoto thyroiditis (chronic lymphocytic autoimmune
thyroiditis)
● Most common cause of acquired hypothyroidism
● Autoimmune process targeted against thyroid gland with
lymphocytic infiltration and lymphoid follicle and germinal center
formation preceding fibrosis and atrophy
▪ May have associated autoimmune diseases (DM type I, adrenal
insufficiency, hypoparathyroidism)
▪ Iodine deficiency – endemic cretinism
▪ Drugs with iodides can cause hypothyroidism through WolffChaikoff effect: Expectorants, nutritional supplements
▪ Other drugs that can cause hypothyroidism: Amiodarone,
phenytoin, phenobarbital, valproate, lithium, rifampin,
thalidomide, etc.
▪ Not a cause of permanent developmental delay
▪ Critical window for maternal and child undernutrition: between a
woman’s pregnancy and her child’s second birthday, later coined
“the first 1,000 days”
PPS Oral Exam Reviewer 2020
▪ ↓ Muscle mass
▪ Dermatitis
▪ Hepatomegaly
▪ Cheilosis or edema
▪ Delayed puberty (check tanner stage)
COMPLICATIONS
▪ Malnutrition infection cycle
▪ Refeeding syndrome (ph, Ca, Mg and K) → life threatening
cardiac, pulmonary or neurologic problems
MUAC – useful when weight may be distorted by use of steroids
or fluid status
Hand-grip strength – for ≥6yo, more accurate than MUAC because
muscle function reacts earlier to changes in nutritional status than
muscle mass
▪ Initially asymptomatic at birth – due to transplacental passage
of maternal T4, although despite this, infants with 1o
hypothyroidism have ↑ TSH and ↓ T4 levels which is detected
during screening, hence, symptoms more evident weeks or
months later
▪ After birth, nonspecific symptoms: prolonged jaundice, large
fontanels (clue to early recognition), ↑ HC (due to myxedema of
brain), cry little, sleep much, poor appetite, sluggish, respiratory
difficulties, constipation, abdominal distention, umbilical hernia,
hypothermia of extremities, mottled skin, edema of genitals, slow
pulse, murmurs, cardiomegaly, asymptomatic pericardial effusion
▪ Thyroid hormones crucial for maturation and differentiation of
tissues (bone and brain)
▪ Slowing of growth – first clinical manifestation
▪ Goiter – common presenting feature
Hashimoto thyroiditis
▪ Firm, nontender euthyroid, hypothyroid, or rarely hyperthyroid
(hashitoxicosis) diffuse goiter with pebble like surface
▪ Onset: >6yo
▪ Peak incidence: adolescence
▪ F>M
▪ Ectodermal – poor growth, dull facies, thick lips, periorbital
edema, dry scaly skin, brittle hair, diminished sweating,
carotenemia, vitiligo
▪ Circulatory – sinus bradycardia, cold extremities, cold
intolerance, pallor, ECG low voltage QRS complex
▪ Neuromuscular – weakness, hypotonia, constipation, umbilical
hernia, myxedema, myalgia, dev delay, physical and mental
lethargy, delayed reflexes, paresthesia, cerebellar ataxia
▪ Skeletal – delayed bone age
▪ Metabolic – serous effusions, weight gain, menstrual
irregularity, arthralgia, macrocytosis, hypercholesterolemia,
hyperprolactinemia, precocious puberty
Criteria for identifying children with severe acute malnutrition for
treatment:
▪ Measure MUAC and assess WFL/WFH status of infants and
Newborn screening
▪ TSH, T4 (T3 are often normal and not helpful in diagnosis)
▪ Delay of osseous development (distal femoral and proximal tibial
epiphyses are absent)
Ultrasound – presence or absence of anatomically normal gland
(but can miss ectopic glands)
Scintigraphy – demonstrate ectopic thyroid gland
▪ Demonstration of ectopic thyroid tissue is diagnostic for thyroid
dysgenesis and establishes need for lifelong treatment
▪ Serum TSH and fT4
▪ Thyroglobulin or TPO – diagnostic for autoimmune thyroiditis
Ultrasonography – not indicated unless PE raises suspicion of
thyroid nodule
Biopsy or thyroid scan – not indicated but thyroid scan with ↓
uptake can differentiate hashitoxicosis from Graves
Levothyroxine
▪ 10-15ug/kg/day (37.5-50ug/day for term infants)
▪ Initiate at < 1 month after birth, prognosis for normal intellect is
excellent
▪ If after 6 months, likelihood for normal intellect decreased
▪ Should not be mixed with soy protein formulas, concentrated
iron, or calcium → can ↓ absorption
Monitoring: TSH and fT4
▪ Every 1-2mos in the 1st 6mos, then
▪ Every 2-4mos between 6mos to 3yo
L-T4
▪ 1-3yo: 4-6ug/kg
▪ 3-10yo: 3-5ug/kg
▪ 10-16yo: 2-4ug/kg
Monitoring: TSH
▪ Every 4-6mos, and
▪ 4-6wks after any change in dosage
Bone age x-ray may suggest the duration and severity of
hypothyroidism based on degree of bone age delay
10 Steps to Recovery:
1.
Treat/Prevent hypoglycemia
2.
Treat/Prevent hypothermia
Batch Clingy
▪ Symmetric FTT (weight, height, HC) – long standing malnutrition,
chromosomal abnormalities, congenital infection, or teratogenic
exposures
64
thrive for
malnutrition based
on nelson’s
*the following in
this table are from
pps and who
guidelines on
malnutrition
▪ ↑ Nutritional needs to support rapid growth and development
▪ At most risk of malnutrition and infection
▪ Chronic exposure to inadequate nutrition = STUNTING
▪ Outcome of brain development by age 2 years determines
person’s mental capacity for the rest of his/her life
▪ Children who get right nutrition during first 1,000 days are 10x
more likely to overcome life threatening conditions, 4.6x more
grades in school, earn 21% more wages as adults
children 6-59mos of age
▪ Examine for B pitting edema
▪ Those who have MUAC <115cm, WFH/WFL below -3 z score or
who have any degree of B edema should be referred for full
assessment and admitted to a program for management of severe
acute malnutrition
3.
4.
5.
6.
7.
8.
9.
10.
Treat/Prevent dehydration
Correct electrolyte imbalance
Treat the infection
Correct the micronutrient deficiencies
Start cautious feeding
Rebuild wasted tissue (Catch-up growth)
Provide stimulation, play and loving care
Prepare for follow-up after discharge
Proven services, practices, and policy interventions to prevent
malnutrition based on PPS:
Adolescence/Pregnancy
▪ Improved use of locally available food
▪ Food fortification including salt iodization
▪ Micronutrient supplementation
▪ Deworming
▪ Fortified food supplements for undernourished moms
▪ Antenatal care including HIV testing
Birth
▪ Delayed cord clamping
▪ Neonatal Vit K administration
▪ Early initiation of breastfeeding
▪ Appropriate infant practices
▪ Immunization
▪ Newborn Screening
0-5 months
▪ Exclusive breastfeeding
▪ Appropriate infant feeding practice
▪ Immunization
▪ Vit A supplementation in first 8 weeks after delivery
▪ Multi-micronutrient supplementation
▪ Improved use of locally available foods, fortified foods
Batch Clingy
6-23 months
▪ Complementary feeding
▪ Continued breastfeeding
▪ Micronutrient supplementation: Vit A, Zinc
▪ Deworming
▪ Food fortification
▪ Handwashing
▪ Improved water and sanitation practice
▪ Immunization
PPS Oral Exam Reviewer 2020
65
Acute
ETIOLOGY / INCIDENCE / PATHOGENESIS
Rotavirus – most common cause
Bacteria: Nontyphoidal Salmonella, Shigella, Campylobacter,
Yersinia
Parasites: Gardia intestinalis, Cryptosporidium spp, Cyclospora
cayetenensis, E. histolytica
▪ Viral AGE → cytolytic infection of the small intestinal villus
tips → ↓ absorption of water, disaccharide malabsorption,
inflammation and cytokine activation
▪ Rotavirus NSP4 (enterotoxin) produces secretory diarrhea
→ activation of CAMP and CGMP → secretion of water and
electrolytes
activates the enteric nervous system → ↓ gastric emptying
and ↑ intestinal mobility
▪ Bacterial AGE possesses an invasive phenotype → elicitation
of inflammatory cytokines with or without toxin production
▪ Shigella → ulcers and microabscesses
ACUTE
GASTROENTERITIS
TREATMENT
COMPLICATIONS / PROGNOSIS
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS / DIAGNOSIS
Diarrhea – passage of ≥3 abnormally loose or liquid stools
per day
Medical History
▪ Duration of diarrhea
▪ Description of stools – frequency, amount, presence of blood
or mucus
▪ Fever – duration, magnitude
▪ Vomiting – onset, amount, frequency
▪ Amount and type of solid or liquid oral intake
Evaluate clinical signs of dehydration
▪ Urine output
▪ Sunken eyes
▪ Mental status
▪ Thirst
▪ Recent weight measurement
▪ Skin turgor, capillary refill time
Viral Diarrhea
▪ Vomiting → passage of watery non bloody stools with
fever
▪ Contains mucus but lacks fecal leukocytes
Bacterial Diarrhea
▪ Fever >40C
▪ Overt fecal blood
▪ Abdominal pain
▪ No vomiting before diarrhea onset
▪ High stool frequency (>10 per day)
Bacterial agents can present with 1 of 5 syndromes:
▪ Acute diarrhea
▪ Bloody diarrhea
▪ Invasive, nonfocal disease (enteric fever)
▪ Extraintestinal invasive infections
▪ Vertical transmission
STEC
▪ Crampy abdominal pain, nonbloody diarrhea
▪ Large volume stools, rarely with fever (STEC hemorrhagic
colitis)
ETEC – traveler’s diarrhea
C. difficile – pseudomembranous colitis (diarrhea,
abdominal cramps, fever with 2-5mm raised yellowish
plaques on colonic mucosa)
LABS
Stool specimens can be examined for:
▪ Mucus
▪ Blood
▪ Neutrophils
▪ Fecal lactoferrin
*>5 leukocytes/hpf or (+) lactoferrin
enteropathogen
Hydration
▪ Correct dehydration in 4-6 hours
▪ Oral rehydration – preferred method, ORS 75
▪ IVF resuscitation necessary:
● Shock
● Decreased level of consciousness
● Ileus
● Intussusception
● Carbohydrate intolerance
● Severe emesis
● High stool output (>10ml/kg/hr)
Enteral feeding and Diet selection
▪ Continued breastfeeding and refeeding with age-appropriate unrestricted diet
▪ Withdrawal of milk and replacement with specialized lactose-free formulations
are unnecessary
Zinc supplementation
▪ Reduces duration and severity, preventS recurrences
▪ Oral zinc 20mg/day for 10-14 days
→
bacterial
Stool cultures should be restricted to the ff:
▪ Clinical features suggestive of bacterial AGE
▪ Moderate or severe disease
▪ Immunocompromised
▪ Outbreaks with suspected HUS
▪ Highly suggestive epidemiologic history
Rectal swab – done if the child has not passed stool and
antibiotics will be started
Measure serum electrolytes:
▪ Severe dehydration
▪ IVF are administered
▪ Skin feels doughy without delayed recoil
▪ Inappropriate rehydration fluids have been administered
Blood culture – if with systemic bacterial infection
Probiotics – does not support a recommendation for use in all settings
Ondansetron – reduces incidence of emesis
▪ Sublingual dose of 4mg (4-11yo), 8mg (>11yo)
Antibiotic therapy
▪ Treat severe infections
▪ Prevent complications in high risk hosts
▪ Limit spread of infection
PREVENTION
▪ Exclusive breastfeeding for 6 months
▪ Vitamin A supplementation
▪ Rotavirus immunization
COMPLICATIONS
▪ Dehydration
▪ Electrolyte and Acid-Base Derangements
▪ Poor growth and nutrition
▪ Secondary infection
▪ Micronutrient deficiencies
▪ Intussusception (viral AGE)
▪ Bacteremia
Shigella & C. difficile are assoc. with:
▪ Toxic megacolon
▪ Intestinal perforation
▪ Rectal Prolapse
PPS Oral Exam Reviewer 2020
Batch Clingy
DISEASE
66
▪ Stool antigen testing or PCR
▪ Indirect hemagglutination – most sensitive
Trophozoites invade mucosa of large intestine, secrete
substances that cause intestinal secretion and damage →
inflammatory type of diarrhea
Tissue invasion → flask shaped ulcers → if spreads to the liver
→ abscess
▪ Giardia duodenalis
▪ 1-5 years old common
PARASITIC
INFECTION
(Giardia lamblia)
Amebic colitis
▪ Colicky abdominal pain
▪ Frequent bowel movements (6-8/day)
▪ Tenesmus
▪ Common in 1-5 years old
▪ Persistent diarrhea
▪ Malabsorption with fatty stools
▪ Abdominal pain
▪ Bloating
▪ Trophozoites colonize the lumen of duodenum and proximal
jejunum
▪ Flattening of intestinal epithelium
▪ Cysts and trophozoites of G. duodenalis seen in stool
specimen (3 specimens increase sensitivity to 90%)
▪ Stool Enzyme Immunoassay
▪ Direct fluorescent antibody test
ALTERNATIVE
▪ Albendazole >6yo: 400mg QD for 5 days
▪ Quinacrine 6mkday ÷ 3 doses for 5 days
▪ Foodborne, waterborne
▪ Spread by fecal-oral route
▪ Caused by excessive intake of sweetened liquids (sorbitol),
overwhelming the disaccharide absorptive capacity of the
intestine
▪ <4 yrs old
TODDLER’S
DIARRHEA
▪ Frequent watery stools in the setting of normal growth
and weight gain
▪ Clinical diagnosis
▪ Distinguish secretory from osmotic: put on NPO, if diarrhea
stops → osmotic
▪ Reduce or change beverage intake
▪ CDI – from mild, self-limited diarrhea to explosive watery
diarrhea with occult blood or mucus
▪ Pseudomembranous colitis – bloody diarrhea, fever,
abdominal pain, cramps, nausea, vomiting
▪ C. difficile toxin in stool of a symptomatic patient – tissue
culture
▪ Discontinue antibiotics
▪ Metronidazole 7.5mkdose TID or QID x 10 days PO or
▪ Vancomycin 10mkdose QID x 10 days PO
▪ Type of osmotic diarrhea – malabsorbed substance pulls
water into bowel lumen
▪ Fermentation of malabsorbed substances (lactose) often
occurs, resulting in gas, cramps and acidic stools
▪ Clostridium difficile
▪ Antibiotic associated diarrhea
▪ Produce toxin A and B
PSEUDOMEMBRANOUS
COLITIS
COMPLICATIONS
▪ Acute necrotizing colitis
▪ Ameboma
▪ Toxic megacolon
▪ Extraintestinal extension
▪ Local perforation and peritonitis
▪ Tinidazole >3yo: 50 mg/kg once or
▪ Nitazoxanide
1-3yo: 100mg (5mL) BID for 3 days
4-11yo: 200mg (10mL) BID for 3 days
>12yo: 500mg BID for 3 days, or
▪ Metronidazole 15mkday ÷ 3 doses for 5-7 days
Toxin producing strain → impaired normal GIT response,
induce an inflammatory response → diarrhea and
pseudomembrane formation
PPS Oral Exam Reviewer 2020
▪ Small gut involvement, bacteremia, abscess formation,
toxic megacolon and death may occur
▪ Symptoms begin a week after colonization and develop
during or weeks after antibiotic exposure, more severe in
immunocompromised
▪ EIA
▪ NAAT
PROGNOSIS
▪ 95% response rate to initial treatment
▪ Recurrence rate 5-20% within 4 weeks of treatment
Batch Clingy
PROTOZOAL
INFECTION
(Amoebiasis)
▪ 4 species:
E. dispar – most prevalent; does not cause symptomatic
disease
E. moshkovskii – can cause diarrhea in infatns and children
E. histolytica – main pathogenic species
E. Bangladeshi
Hemolytic Uremic Syndrome (HUS)
▪ Leading cause of acquired renal failure in children
▪ 5-10% of patients infected with STEC
▪ Diagnosed 2-14 days after the onset of diarrhea
▪ Unlikely to occur once diarrhea has remained resolved for 2-3 days with no
evidence of hemolysis
▪ Risk Factors: 6mos to 4yo, bloody diarrhea, fever, ↑ leukocyte count, treatment
with antibiotics and antimotility agents
▪ Metronidazole 35-50mkday ÷ 3 doses for 7-10 days or
▪ Tinidazole 50mkday QD for 3 days
Followed by
▪ Paromomycin 25-35mkday ÷ 3 doses for 7 days or
▪ Iodoquinol 30-40mkday ÷ 3 doses for 20 days or
▪ Diloxonide furoate for >2yo 20mkday ÷ 3 doses for 7 days
67
Complex
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Immune-mediated systemic disorder elici
ted by gluten
▪ Affects genetically susceptible individuals
▪ Strongest association with HLA DQ2.5 gene
MALABSORPTION
(Celiac Disease)
CLINICAL MANIFESTATIONS
▪ Malabsorption and malnutrition
▪ 1st 2yrs of life – FTT, chronic diarrhea, vomiting, abdominal
distention, muscle wasting, anorexia, irritability
▪ Extraintestinal – IDA, unresponsive to iron therapy, short
stature, endocrinopathies, arthritis, arthralgia, epilepsy,
cardiomyopathy
LABORATORY FINDINGS / DIAGNOSIS
▪ Small bowel biopsy – definitive
● Villous atrophy with hyperplasia of the crypts
● Abnormal surface epithelium
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Gluten free diet
▪ Wheat, barley and rye free diet
▪ Anti TG2A antibodies
▪ Serum total IgA to exclude IgA deficiency
▪ T cell mediated chronic inflammatory disorder
▪ Altered processing by intraluminal enzymes, changes in
intestinal permeability and activation of innate immunity
mechanisms precede the activation of the adaptive
immune response
▪ Idiopathic chronic intestinal inflammation
▪ Unpredictable exacerbations and remissions
▪ Most common onset: Preadolescent/ adolescent era and
young adulthood
▪ Genetic and environmental influences
ULCERATIVE COLITIS (UC)
▪ Localized to the colon
▪ Remission and relapse
Associated with type 1 DM, autoimmune thyroid disease,
Addison disease, Sjögren syndrome, rheumatoid arthritis,
autoimmune cholangitis, autoimmune hepatitis, primary
biliary cholangitis, selective IgA deficiency and Down, Turner,
and Williams syndromes
▪ Blood, mucus, pus in the stool
▪ Diarrhea
▪ Fever, diarrhea, hypoalbuminemia, leukocytosis and >5
stools/day for 5d → FULMINANT COLITIS
▪ CBC: anemia, leukocytosis if severe
▪ Hypoalbuminemia
▪ Elevated ESR and CRP
▪ Flexible sigmoidoscopy – confirm the presence of UC
▪ Colonoscopy – extent of disease
▪ Upper endoscopy – more sensitive than contrast studies in
detecting proximal CD involvement
▪ Video capsule endoscopy – may be done except if there is
stricturing disease
Endoscopic findings:
▪ Diffuse carpeting of the distal or entire colon with tiny ulcers and
loss of haustral folds
▪ Extraintestinal manifestations: pyoderma gangrenosum,
sclerosing cholangitis, chronic active hepatitis, ankylosing
spondylitis
INFLAMMATORY
BOWEL DISEASE
▪ Colitis, diarrhea, blood, and mucus in stool
▪ Small bowel involvement – loss of appetite, crampy,
postprandial pain, poor growth, delayed puberty, fever,
anemia, lethargy
▪ Severe CD with fibrosis→ partial or complete small bowel
obstruction
Perianal disease – skin tags and fistulas
Extraintestinal manifestations more common– arthritis,
erythema nodosum, uveitis or iritis, renal or gallstones
Endoscopic findings:
▪ Larger ulcerations with linear branching, skip areas usually present
(cobblestone appearance)
Aminosalicylates
▪ 5-ASA (Mesalamine 50-100mkday) – packaged in capsules to be taken
as suppository
▪ Sulfasalazine 30-100mkday – least expensive
▪ If cannot be controlled by ASA, use steroids (Prednisone 1-2mkday)
▪ Immunosuppressive – 6 mercaptopurine & azathioprine → if failed
treatment, use cyclosporine or anti-tumor necrosis factor
▪ Probiotics (for adults) – prevent pouchitis
▪ Surgical colectomy with ileoanal anastomosis – option for
unresponsive disease, reduce risk of colon cancer
Step up: steroids and less immunomodulating agents
Top down: start with strong DMARDs
▪ Responds less to ASA
▪ Metronidazole – first line for perianal disease and if with infectious
complications
▪ Steroids – induces remission; Prednisone or Budesonide
▪ Immunomodulators – 6-MP, azathioprine, MTX
▪ Biologics – Infliximab, Adalimumab, Vedolizumab
▪ Enteral Nutrition Therapy – effective than steroids for mucosal healing
▪ Surgery – but must be limited and length of bowel resection must be
minimized; >50% recurrence rate
Batch Clingy
CROHN DISEASE (CD)
▪ Any region of the alimentary tract from mouth to anus
▪ Eccentric and segmental often with skip areas
▪ Transmural involvement
COMPLICATIONS
▪ Toxic megacolon – fever, abdominal distention and pain, massively
dilated colon, anemia, and low serum albumin because of fecal protein
losses
PPS Oral Exam Reviewer 2020
68
Acute
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
DIAGNOSIS
▪ Delay or difficulty in defecation present for
>1month and causes significant distress to the
patient
▪ Contraction of gluteal muscles → stiffening legs while lying
down, holding on to furniture while standing, squatting
quietly in corners
▪ Acute stressor precedes the chronic course
Encopresis – voluntary or involuntary passage of feces into
inappropriate places at least 1x a month for 3 consecutive
months once a chronologic or developmental age of 4 has
been reached
ROME IV CRITERIA
Neonates and Toddlers:
Must include 1 month of ≥2 of the following in infants to 4 mos old:
• ≤2 defections weekly
• History of excessive stool retention
• History of hard/painful bowel movements
In toilet trained children, the following additional criteria may be used:
• History of large-diameter stools
• Presence of a large fecal mass in the rectum
• At least 1 weekly episode of incontinence after being toilet trained
• History of large-diameter stools that may clog the toilet
Children and Adolescents (Developmental age of ≥4yo):
Must include ≥2 of the following ≥1/wk for ≥1mo with insufficient criteria to diagnose irritable bowel
syndrome
• ≤ 2 defecations in the toilet per week
• ≥1 episode of fecal incontinence per week
• History of retentive posturing or excessive volitional stool retention
• History of painful or hard bowel movements
• Presence of a large fecal mass in the rectum
• History of large diameter stools that can obstruct the toilet
• After appropriate evaluation, symptoms cannot be fully explained
by another medical
condition
▪ Large volume of stools palpated in the suprapubic area
▪ Dilated rectal vault with guaiac negative stool
▪ Underwear soiling
FUNCTIONAL
CONSTIPATION
TREATMENT / COMPLICATIONS / PROGNOSIS
Rapid Rectal Disimpaction
▪ Glycerin suppositories
▪ Phosphate enema
Slow oral disimpaction for children
Over 2-3 days
▪ PEG with electrolytes
Over 5-7 days
▪ PEG without electrolytes
▪ Milk of magnesia
▪ Mineral oil
▪ Lactulose or Sorbitol
Maintenance Therapy
Long Term
▪ Milk of magnesia
▪ Mineral oil
▪ Lactulose or sorbitol
▪ PEG 3350
Short Term
▪ Senna
▪ Glycerin enemas
▪ Bisacodyl suppository
Nonretentive Fecal Incontinence
≥1mo history of the following symptoms:
• Defecation into places inappropriate to the sociocultural context
• No evidence of fecal retention
• After appropriate evaluation, symptoms cannot be fully explained
by another medical condition
Complex
HIRSCHSPRUNG
DISEASE
Congenital Aganglionic
Megacolon
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Absence of ganglion cells in the submucosal and myenteric plexus
▪ Most common cause of lower intestinal obstruction in neonates
CLINICAL MANIFESTATIONS
▪ Usually diagnosed in the neonatal period
▪ Failure to pass meconium in 48 hours
▪ M:F ratio: 4:1 for short-segment disease, 2:1 for total aganglionosis
▪ May be associated with other congenital defects
▪ Arrest of neuronal migration from proximal to distal bowel →
absence of neuronal innervation
▪ Absence of submucosal and myenteric plexus → inadequate
relaxation of the bowel wall and bowel wall hypertonicity → intestinal
obstruction
▪ Signs of obstruction: distended abdomen, bilious
emesis/aspirate with feeding intolerance
▪ Constipation starting in infancy that has not responded to
medical management
▪ DRE: explosive discharge of foul-smelling feces and gas
▪ Small pellet stools, ribbon-like with fluid consistency
▪ 80% – limited to the rectosigmoid
▪ 10-15% – long segment (proximal to the sigmoid colon)
▪ 5% – total colonic aganglionosis
PPS Oral Exam Reviewer 2020
Enterocolitis → diarrhea, abdominal tenderness, sepsis, signs
of bowel obstruction
Currarino triad (older patients) – anorectal, sacral and
presacral anomalies
DIAGNOSIS
Rectal suction biopsy – gold standard
▪ Demonstrate hypertrophied nerve bundles that stain
positively for acethylcholinesterase
Anorectal Manometry
▪ Shows failure of the internal anal sphincter to relax to
rectal distention and absence of
rectoanal inhibitory reflux
Contrast enema
▪ Abrupt narrow transition zone (normal dilated proximal
colon and obstructed distal aganglionic segment)
▪ If no transition zone, compare rectal vs sigmoid diameter
▪ Check 24 hour delayed contrast films for delayed
contrasts
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Placement of temporary ostomy
▪ Endorectal pull through
▪ Anal botulism injection – for ultrashort-segment Hirschsprung
disease
▪ If total colonic aganglionosis → ileal-anal anastomosis
PROGNOSIS
Satisfactory prognosis post-surgery
COMPLICATION
Hirschsprung associated enterocolitis – leading cause of death
Batch Clingy
DISEASE
69
CONGENITAL
HYPOTHYROIDISM
SPINAL CORD
ABNORMALITIES
▪ Usually true constipation in neonatal period due to Hirschsprung,
intestinal pseudoobstruction and hypothyroidism
▪ Constipation that does not respond to treatment
▪ Large abdomen with umbilical hernia
▪ Defective rectal filling because of defective colonic peristalsis
▪ Leads to excessive drying of stool—distention of colon and rectum
lessens defecation reflex and effectiveness of peristalsis
Tethered cord – spinal cord ends below L2
▪ Other features: prolonged jaundice, large fontanels,
abdominal distention, lethargy and poor feeding, edema,
umbilical hernia, large tongue, dry skin, hoarse cry
▪ Presence of an open myelomeningocele or by cutaneous
manifestations of dysraphism
MRI
▪ Diagnostic of choice for anatomy of tethering lesion
▪ May present with 1 of 4 manifestations: neurologic,
orthopedic, bowel/bladder and/or pain symptoms
UTZ of the bladder and urodynamic studies
▪ Assessment of bladder function
Constipation progressing to incontinence – lax sphincter due
to impaired innervation
GI symptoms: anorexia, abdominal pain, vomiting and
constipation – seen in kids with BLL >20mcg/dl
Blood lead levels – gold standard
▪ ≥5ug/dl means exposure and requires second testing
▪ Spinal cord is fixed at any point → movement is restricted → spinal
cord and nerve roots are stretched
▪ Fixed spinal cord regardless of cause (i.e. lipomyelomeningocoele,
myelocystocele and diastematomyelia) + pain, neurologic dysfunction,
bowel/bladder dysfunction → TETHERED CORD SYNDROME
Paint chips – most common source
▪ Most common pathway – hand to mouth activity of children
▪ Absorbed → disseminated via blood → bound to erythrocytes
▪ Retained lead → accumulates in bone
▪ Affects heme pathway → lead inhibitory effects → accumulation of
excess amounts of heme precursors → increases erythrocyte
protoporphyrin levels (>35ug/dl) → toxicity
▪ Also competes with calcium – prevents normal intracellular and
intercellular signaling
▪ Prevents development of normal tertiary brain structure → ADHD
Levothyroxine – 10-15ug/kg/day PO
PROGNOSIS
Delay in diagnosis and treatment → severe delay in growth and
development, irreversible brain damage
▪ BLL of 45ug/dl → chelation therapy
▪ KUB radiograph → radiopaque flecks
▪Prophylactic surgery before deterioration occurs
▪ Microsurgical dissection with release of SC attachment to the
overlying dura
PROGNOSIS
Good outcome however, patients with symptomatic tethered cord
who
undergo
repair
of
a
myelomeningocele
or
a
lipomyelomeningocele → recurrent tethering and recurrent symptoms
Chelation with
2,3 DMSA acid: 350mg/m2BSA/dose (not 10 mg/kg) q8h PO for 5 days
→ q12h for 14 days
Dimercaprol: 300-500mg/m2BSA/day; IM only divided q4h for 3-5
days. Only for blood lead level ≥70 μg/dL
Penicillamine 10 mkday for 2 wk increasing to 25-40 mg/kg/day; oral,
divided q12h. For 12-20 wk
2
CaNa2EDTA: 1,000-1,500 mg/m body surface area/day; IV infusion—
continuous or intermittent; IM divided q6h or q12h for 5 days
Successful intervention → greatest fall in BLL occurs 1st 2 months
after therapy is initiated
Batch Clingy
LEAD POISONING
CNS symptoms: Lead Encephalopathy, headache and changes
in mentation, lethargy, papilledema, seizures and coma (due
to increasing cerebral edema and inc ICP); BLL of 70 to above
100mcg/dl
Newborn screening – measure levels of T4, then if low
measure TSH
PPS Oral Exam Reviewer 2020
70
Acute
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most common surgical emergency in childhood
▪ Peak in the second decade (10-18yo)
▪ Uncommon in < 5 years old
▪ Luminal obstruction, inspissated fecal material, lymphoid
hyperplasia, ingested foreign body, parasites, tumors →
increasing intraluminal pressure, lymphatic and venous
congestion and edema → impaired arterial perfusion →
ischemia of the appendiceal wall → bacterial proliferation and
invasion of the wall and necrosis
ACUTE APPENDICITIS
CLINICAL MANIFESTATIONS
▪ Visceral inflammation → periumbilical pain
▪ Somatic pain → migration to the RLQ
▪ Nausea and vomiting follow the onset of abdominal pain by
several hours
▪ Anorexia – classic and consistent finding
▪ Diarrhea and urinary symptoms – 2o to inflamed peritoneum
▪ Fever
▪ Localized abdominal tenderness
▪ Rebound tenderness
▪ Guarding
▪ Rovsing, Dunphy, Psoas, and Obturator signs
LABORATORY FINDINGS / DIAGNOSIS
▪ Mildly elevated WBC (11,000-16,000) with left shift
▪ Plain Film of the abdomen – for complicated cases i.e. small
bowel obstruction
▪ Ultrasound – first choice
● Wall thickness>/= 6mm
● Luminal distention
● Lack of compressibility
● Complex mass in the RLQ
● Appendicolith
● 25-60% cannot visualize the appendix
▪ CT scan – gold standard; fat stranding
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Broad spectrum antibiotic (Zosyn or equivalent) – directed
for anaerobes and gram-negative organisms
▪ Surgical – (Laparoscopic) Appendectomy
▪ If with perforation, after IV antibiotics, discharge with 7-10
days of Ciprofloxacin and Metronidazole
Pediatric Appendicitis Score: <4 less likely, >8 highly likely
Alvarado MANTRELS rule scores
1 point
2 points
Pain migration to RLQ
RLQ tenderness
Anorexia
WBC >10,000
Nausea/vomiting
Rebound pain
Temp at least 37oC
WBC shift >75% neut
*score of 7 or greater increase likelihood
MALROTATION WITH
MIDGUT VOLVULUS
▪ Sudden onset of severe paroxysmal colicky pain that recurs at
frequent intervals
▪ Straining efforts with knees flexed and loud cries
▪ Lethargy disproportionate to the abdominal pain
▪ Bilious vomiting
▪ Currant jelly stool
▪ GIT infection or introduction of new food proteins → swollen
peyer patches and lymphoid hyperplasia → lead points (more
common >2yo)
▪ Most commonly ileocolic
▪ Upper portion of bowel (intussusceptum), invaginates into the
lower (intussuscipiens) → obstruction in venous return →
engorgement, edema, bleeding
Predictive value:
Pain + palpable sausage-shaped abdominal mass + currant jelly
stool: <30%
Pain + palpable mass + vomiting: > 90 %
If with rectal bleeding = 100%
▪ Incomplete rotation of the intestine during fetal development
▪ Intestinal nonrotation or incomplete rotation around the SMA
▪ Nonrotation → jejunum and ileum occupy the right side, colon
on the left and cecum move to the RLQ
▪ Mesentery including SMA → tethered by a narrow stalk →
twist and cause a midgut volvulus
▪ Ladd bands (abnormal mesenteric attachments) extend from
cecum to duodenum → partial obstruction
▪ 75-85% present in the 1st yr of life
▪ Bilious emesis, acute bowel obstruction
▪ Malabsorption, protein losing enteropathy
▪ Volvulus → life threatening → septic
PPS Oral Exam Reviewer 2020
Abdominal Ultrasound
▪ Tubular mass in longitudinal views and doughnut or target
appearance
▪ Coiled spring sign if with contrast
▪ Manual operative reduction if reduction by air or barium
(w/o perforation)
▪ If bowel not viable – resection of intussusception
PROGNOSIS
▪ Fatal if untreated
▪ 10% recurrence rate, 2-5% after surgical reduction
Plain Abdominal Film
▪ Gasless abdomen, double bubble sign
Upper GI series – gold standard
▪ Checks for position of ligament of Treitz, corkscrew appearance
of bowel, bird’s beak appearance
Abdominal Ultrasound
▪ Duodenal obstruction, thickened bowel loops to the right of the
spine, free peritoneal fluid
▪ Surgical – bowel untwisted, and Ladd bands divided (Ladd’s
Procedure)
▪ Mesentery flattened out and cecum moved to left side of
abdomen
COMPLICATION
Extensive intestinal ischemia → short bowel syndrome
Batch Clingy
INTUSSUSCEPTION
▪ A portion of the alimentary tract is telescoped to an adjacent
segment
▪ Most common cause of intestinal bowel obstruction between
5 months and 3 years of age
▪ Most common abdominal emergency in children <2yo
▪ 90% are idiopathic
71
▪ Nonreducible mass in the inguinal canal
▪ Can include small bowel, appendix, omentum, colon or rarely
Meckel’s diverticulum
▪ Rarely ovary or FT in girls
▪ Irritability, pain in groin and abdomen, feeding intolerance
▪ Abdominal distention, vomiting
▪ Onset of ischemic changes → bilious vomiting or feculent
▪ Bloody stools
▪ Greatest risk: <6 months old
▪ Tense non fluctuant mass in THE inguinal region and can extend to
scrotum or labia majora
▪ Mass is well defined, tender, and does not reduce
▪ With edema and erythema of overlying skin, fever, signs of
obstruction
▪ Testes may be normal or swollen because of venous congestion
▪ Clinical diagnosis
▪ Xray – features of partial or complete intestinal obstruction
▪ Gas within the incarcerated segments
INCARCERATED HERNIA
*also see Genital
Disorders*
Strangulated hernia – contents have become necrotic and
gangrenous
▪ In children, non-reducible hernias rapidly progress to
strangulation with potential infarction
▪ Pressure on herniated viscera → impaired lymphatic and
venous drainage → compression, arterial occlusion → gangrene
or perforation
▪ Most common <1yo
▪ Beyond 1-2yo → female preponderance (1:10)
▪ E. coli- most common cause
URINARY TRACT
INFECTION
*also see Renal
Disorders*
If incarcerated – NGT, IV fluids, correct electrolyte imbalance
Surgery – reduce contents, separate from spermatic cord
vessels, and high ligation of sac at the internal ring (patent
processus vaginalis)
PROGNOSIS
▪ Wound infection increases to 5-7% if incarcerated
Acute Pyelonephritis
▪ Abdominal, back or flank pain
▪ Fever (>39C for >24h in males and >48h in females)
▪ Malaise
▪ Nausea, vomiting
▪ Diarrhea
Urine Culture – gold standard
▪ Suprapubic tap – gram (-) bacteria (any count)
▪ Transurethral catheterization – >50,000cfu/ml of single organism
▪ Midstream urine sample (3 specimens: 95% probability)
▪ If count is <105 but patient is symptomatic, infection likely
Ultrasound – first line type of imaging
Cystitis
▪ Dysuria, urgency, frequency, suprapubic pain, incontinence
▪ Malodorous urine
Bottom up approach: UTZ + VCUG
Top down approach: DMSA → VCUG
COMPLICATIONS
▪ Recurrent hernia – 50% within 1yr of repair, 75% by 2yrs
▪ Iatrogenic cryptorchidism (trapped testicle)
▪ Injury to the vas deferens and infertility
Acute Pyelonephritis
▪ 7 to 14 days oral/parenteral antibiotics
▪ IV: Ceftriaxone (50mday, not to exceed 2 g) or cefepime
(100mkday q12h) or cefotaxime (100-150mkday in 3-4
divided doses)
Cystitis
▪ 3 to 5 days of TMP-SMX
COMPLICATIONS
▪ Renal scarring
▪ ESRD
*see Diarrhea*
*see Constipation*
Batch Clingy
ACUTE
GASTROENTERITIS
CONSTIPATION
▪ Ascending infection
▪ Attachment of type II P fimbriae (mannose resistant) to
umbrella cells of the bladder → form intracellular bacterial
communities → become filamentous → evades attack by WBCs
in the urine → form quiescent intracellular reservoirs → source
of recurrent infections and antiBiotic resistance
Surgery
▪ Timing of operative repair includes age, general condition,
and comorbid conditions
▪ If <1yo – prompt repair, high chance of incarceration
▪ If >1yo, less chance of incarceration
PPS Oral Exam Reviewer 2020
72
Complex
DISEASE
BILIARY ATRESIA
Noncystic
obliterative
cholangiopathy
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most frequent identifiable cause of obstructive jaundice in the
first 3 months of life
▪ Most common form is the 3rd type or non-patency of the entire
extrahepatic biliary system and intrahepatic bile ducts at the
hilum (85%)
▪ 85-90% are normal at birth and have a postnatal progressive
obliteration of bile ducts
▪ May be associated with other congenital anomalies (BASM
syndrome) or an immune or infection mediated process
CLINICAL MANIFESTATIONS
▪ Generally, acholic stools with onset at about 2 weeks old
▪ Average birth weight
▪ Hepatomegaly with firm to hard consistency
DIAGNOSIS
▪ Ultrasound: Triangular cord sign
▪ Normal hepatic uptake of dye on radionucleotide scan (HIDA, DISIDA)
with absent duodenal excretion
▪ Biopsy: Bile duct proliferation, bile plugs, portal or perilobular fibrosis
and edema, and intact lobular structure
BA
Jaundice at birth
Jaundice
presentation
▪ Impedance of bile flow through the intrahepatic and
extrahepatic biliary trees after it is formed
▪ Bile plugging of the interlobular bile ducts, portal expansion and
bile duct proliferation in association with centrilobular cholate
injury
Dark yellow urine
Hepatomegaly
Splenomegaly
Acholic stools
Alpha-fetoprotein
CHOLEDOCHAL CYST
▪ Junction of the CBD and pancreatic duct before their entry into
the Sphincter of Oddi → reflux of pancreatic enzymes →
inflammation, localized weakness and dilatation of the duct
▪ Uncorrectable lesions – obstruction at or above the porta
hepatis → Kasai Portoenterostomy
▪ 90% success rate if performed before the 8 th week of life
Differential Diagnosis: BA vs Idiopathic Neonatal Hepatitis
▪ Female predominance
▪ Congenital dilatations of the common bile duct
▪ Most common variant is Saccular or Fusiform dilation of the CBD
(Type 1)
▪ 75% appear in childhood
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Correctable lesions – patent distal portion of extrahepatic
duct, distal atresia → surgical resection
▪ Cholestatic Jaundice
▪ Severe liver dysfunction – ascites and coagulopathy
▪ Older Child: abdominal pain, jaundice, mass
Features of acute cholangitis
▪ Fever
▪ RUQ tenderness
▪ Jaundice
▪ Leukocytosis
INH
Never
Rarely
2-4 weeks
2-4 weeks
yes
yes
yes
Sometimes
(cirrhosis)
yes
May be absent
PROGNOSIS
Life expectancy with untreated EHBA > 2 yrs
▪ 75% with SX <2months
▪ 10% with SX >3 months
yes
More common
Transient/
incomplete
Frequently (+)
▪ Ultrasound
▪ MRI – for preoperative assessment of choledochal cyst anatomy
▪ Primary excision of
choledochojejunostomy
the cyst
and a
Roux-en-Y
COMPLICATIONS
▪ Cholangiocarcinoma
▪ Recurrent cholangitis
▪ Distal congenital stenotic segment of the biliary tree → ↑
intraluminal pressure and proximal biliary dilatation
Batch Clingy
▪ Part of the spectrum of an infectious disease
PPS Oral Exam Reviewer 2020
73
Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Mechanisms of TBI: motor vehicle crashes, falls,
assaults, and abusive head trauma
▪ Most TBIs in children are from closed-head injuries
Primary injury – produces irreversible tissue disruption
2 types of secondary injury
● Ultimate damage seen in the injured brain evolves
over hours or days
● Injured brain is vulnerable to additional insults
because injury disrupts normal autoregulatory defense
mechanisms
▪ Epidural, subdural and parenchymal intracranial
hemorrhages can result
▪ Injury to gray or white matter is also commonly seen
(e.g. focal cerebral contusions, diffuse cerebral swelling,
axonal injury, and injury to the cerebellum or brainstem)
CLINICAL MANIFESTATIONS
▪ Classified as mild, moderate, or severe
MILD
(from 2018 CDC Guideline on the Diagnosis and Mgt. of
mTBI among Children)
▪ Acute brain injury resulting from mechanical energy to
the head from external physical forces including:
● ≥1 of the ff: confusion or disorientation, loss of
consciousness for ≤30 mins, post-traumatic amnesia for
<24hrs, and/or transient neurological abnormalities (e.g.
focal signs, symptoms, or seizure)
● GCS score of 13-15 30 mins. post-injury or later
upon presentation for healthcare
MODERATE
▪ GCS 9-12
▪ Has the potential for deterioration especially in those
with significant contusion due to progressive swelling
SEVERE
▪ GCS 3-8
▪ Coma is seen immediately after injury and is sustained
Development of increased ICP with impending
herniation may be heralded by: new-onset or worsening
HA, depressed LOC, VS changes (hypertension,
bradycardia, irregular respirations), and signs of 6 th or 3rd
CN palsy
▪ In cases of epidural hematoma, child may be alert on
presentation but may deteriorate after a period of hours
▪ “Talk-and-die” scenario in children with diffuse swelling
DIAGNOSIS
▪ Diagnosis is generally obvious from the hx and PE
▪ Cranial CT should be obtained immediately after
resuscitation and stabilization
For mild TBI, the 2018 CDC Guidelines recommends that:
▪ HCP should not routinely obtain head CT for diagnostic
purposes in children with mTBI
▪ HCP should use validated clinical decision rules to
identify children with mTBI at risk for intracranial injury.
Risk factors include:
● Age <2yo
● Vomiting
● Loss of consciousness
● Severe mechanism of injury
● Severe or worsening headache
● Amnesia
● Non frontal scalp hematoma
● GCS less than 15
● Clinical suspicion for skull fracture
▪ Skull radiographs should not be used in the diagnosis of
pediatric mTBI
TREATMENT
▪ Infants and children with severe or moderate TBI receive ICU
monitoring
▪ Initial stabilization: rapid sequence intubation with spine
precautions,
maintenance
of
normal
extracerebral
hemodynamics, MAP, and temperature
▪ Euvolemia is the target; plain saline is the fluid of choice
▪ Vasopressors may be needed as guided by monitoring of CVP
▪ Trauma survey should be performed
COMPLICATIONS / PROGNOSIS
▪ Mortality rates range between 10-30%
▪ Ability to control ICP is related to patient
survival
▪ Motor and cognitive sequelae resulting from
severe TBI generally benefit from rehabilitation
Cerebral herniation – pupillary dilation, systemic hypertension,
bradycardia, extensor posturing, should be treated as a medical
emergency
● Hyperventilation with FiO2 of 100%
● IV thiopental or pentobarbital
● Mannitol (0.2-1g/kg IV) or hypertonic saline (3% solution, 510 mL/kg)
▪ ICP should be maintained at <20mmHg
▪ First-tier therapy:
● Elevation of head of bed
● Midline positioning of the head
● Controlled mechanical ventilation
● Analgesia and sedation
● EEG monitoring if under neuromuscular blockade to check
for status epilepticus
● Use of osmolar agents (e.g. hypertonic saline and mannitol)
▪ Second-tier therapy:
● Decompressive craniectomy for refractory traumatic
intracranial hypertension
● Pentobarbital infusion
● Mild hypothermia (32-34OC)
● Hyperthermia must be avoided
Batch Clingy
(see Nelson’s 21st ed., Fig. 85.13 for Approach to Management of
a child with severe TBI)
PPS Oral Exam Reviewer 2020
74
Acute
MIGRAINE without AURA
▪ Most common form of migraine in both children and adults
▪ Status migrainosus – migraine beyond 72hrs
Triggers: skipping meals, inadequate or irregular sleep, dehydration and
weather changes, menstrual periods,
RED FLAGS FOR HA d/t ↑ ICP
▪ Daily or near daily morning vomiting
▪ HA waking the child up from sleep
▪ Remits with maintenance of upright posture
▪ Diagnostic Criteria (ICHD-3 beta) – recurrent (at least 5 attacks)
lasting 4-72hrs in children and adolescents (may be as short as 2
hours)
Has 2 of the ff. 4 characteristics:
▪ Unilateral/focal (more commonly bilateral in younger children)
▪ Pulsating quality (difficult to elicit in young children; drawing or
demonstration might help)
▪ Moderate or severe pain intensity
▪ Aggravation by or causing avoidance of routine physical activity (e.g.
reduction in play or physical activity; limitation or restriction of sports
activity or exercise during attack)
During HA, at least 1 of the ff:
▪ Nausea and/or vomiting (sporadic episodes that are not worsening is
more likely to be migraine; getting up and going about normal, upright
activities make it worse)
▪ Photophobia and phonophobia (more apparent as the child matures)
MIGRAINE
MIGRAINE with AURA
▪ Aura: neurologic warning that a migraine is going to occur
Importance of aura duration:
▪ Lasting >5mins – differentiates migraine aura from a seizure with
postictal headache)
▪ 60-min maximum – to separate migraine aura from a more prolonged
neurologic event like TIA
HEMIPLEGIC MIGRAINE
MIGRAINE WITH BRAINSTEM AURA
▪ Basilar-type migraine
▪ Formerly considered a disease of the basilar artery
PPS Oral Exam Reviewer 2020
In younger children, n/v may outweigh HA itself → overlap with GI
periodic diseases (e.g. cyclic vomiting, abdominal migraine) → ↑
propensity for the later development of migraine
TYPICAL AURA
▪ Visual, sensory, or dysphasic, lasts >5 mins and <60 mins with the HA
starting w/in 60mins
▪ Visual aura: photopsia (flashes of light or light bulbs going off
everywhere) is the most common; less likely types are fortification
spectra or shimmering scotoma
▪ Sensory aura: less common, unilateral, insects crawling from hand up
to face with numbness
▪ Dysphasic aura: least common, difficulty to respond verbally
ATYPICAL AURA – hemiplegia (weakness), vertigo, distortion (Alice in
Wonderland syndrome)
Transient unilateral weakness lasting a few hours, may persist for days
Vertigo, tinnitus, diplopia, blurred vision, scotoma, ataxia, occipital HA
ANCILLARIES / DIAGNOSIS
▪ Thorough history and PE including a neurologic
examination
Family history
▪ Headaches and any other neurologic, psychiatric and
general health conditions
▪ For identification of migraine within the family as well
as possible secondary headache disorders
▪ Familial penetrance of migraine is so robust that the
absence of a family history of migraine or its equivalent
phenomena should raise the concern that the diagnosis
may not be migraine and warrants further history taking,
referral to a headache specialist, or investigation
Neuroimaging: warranted when neuro exam is abnormal
or unusual neurologic features occur during the migraine
▪ HA that awakens the child from sleep
▪ HA present on first awakening and remit with upright
posture
▪ Brief HA that only occur when coughing or bending
over
▪ HA mostly in the occipital area
▪ Migrainous headache with absolutely (-) family hx of
migraine or its equivalent
*see Nelson’s 21st ed., Table 613.7 for more indications
MRI: Imaging of choice
If child has HA that instantaneously at its worst at onset
(thunderclap headache) – CT scan looking for blood is
the best initial test. If negative, do LP to look for
xanthochromia of the CSF
▪ Other labs or EEG is not beneficial in a typical migraine
without aura or migraine with aura
TREATMENT
Goals of treatment (American Academy of Neurology)
▪ ↓ HA frequency, severity, duration, and disability
▪ ↓ Reliance on poorly tolerated, ineffective, or unwanted
acute pharmacotherapies
▪ Improvement in quality of life
▪ Avoidance of acute HA medication escalation
▪ Education and enabling of patients to manage their
disease to enhance personal control of their migraine
▪ ↓ HA-related distress and psychological symptoms
ACUTE TREATMENT
Goal: headache relief within 1hr with return to function 10
of 10 headaches
*2019 AAN Clinical Practice Guidelines
▪ Initial tx: Ibuprofen 10 mg/kg
▪ For adolescents: triptans can be given
▪ If with contraindication to NSAIDs: Paracetamol 15
mg/kg
▪ If ibuprofen is not effective: Naproxen in similar doses
▪ Limit NSAIDs to ≤2-3 times/week
▪ Prevent medication-overuse headaches
▪ If weekly allowance of analgesics has been maximized,
next step is to only use hydrating fluids for the rest of the
week
▪ If migraine is especially severe, NSAIDs alone may not be
sufficient; a triptan may be considered (e.g. almotriptan
(12-17 y/o); rizatriptan (as young as 6 y/o); intranasal
Zolmitriptan (12 y/o and older))
▪ If 1 triptan fails to provide pain relief, offer an alternative
triptan
▪ SE: tightness in the jaw, chest, and fingers, feeling of
grogginess and fatigue
▪ For an acute attack, NSAIDs can be repeated once in 34hrs; triptans can be repeated once in 2hrs
▪ Other therapies: antiemetics (e.g. prochlorperazine and
metoclopramide)
PREVENTIVE THERAPY
Indications: HAs are frequent (>1HA/wk) or disabling
(missing school, home or social activities or having a
PedMIDAS score >20)
Goal: ↓ Frequency (to ≤1-2HA /mo); ↓ Level of disability
▪ Given 4-6 mos then tapered off
▪ Prophylactic agents:
Flunarizine – only medication which demonstrated a
substantial level of effectiveness
Batch Clingy
PRIMARY HEADACHE: recurrent, episodic; often sporadic; most common forms: migraine & tension-type headaches; neurologic exam should be normal
SECONDARY HEADACHE: symptom of an underlying illness; common causes: head trauma, viral illness, sinusitis; serious causes: increased ICP
DISEASE
ETIOLOGY / INCIDENCE
CLINICAL MANIFESTATIONS
▪ Most frequent type of recurrent headache
▪ Episodic HA moderate to severe intensity, focal in location, throbbing
▪ Occur in up to 10.6% of children between 5-15 years old and up to 28%
quality, associated with nausea, vomiting, light sensitivity and sound
of older adolescents
sensitivity
▪ May be associated with typical (visual, sensory or dysphasic) or
atypical aura (hemiplegia, Alice in wonderland)
75
CHILDHOOD PERIODIC SYNDROMES
▪ Group of potentially related symptoms that occur in increased frequency
in children with migraine
Hallmark: recurrent episodic nature of the events
Cyclic Vomiting
▪ Many have a FHx of migraine and have a higher than average likelihood
of developing migraine as they grow older
▪ Diagnosis of exclusion
▪ Must be differentiated from GI disorders, abnormal GIT motility and
pelviureteric junction, metabolic causes (e.g. disorders of amino acid
metabolism, organic acidosis, CHO metabolism), acute porphyria and CNS
lesions
▪ Uncontrollable vomiting → dehydration
▪ Occurs in a predictable time schedule
Abdominal Migraine
▪ To meet the criteria, child must complain at the time of the abdominal
pain at least 2 of the ff: anorexia, nausea, vomiting and pallor
▪ Migraine without the headache
▪ Episodic
▪ Mid abdominal pain with pain free periods between attacks
▪ Dull pain, may be moderate to severe, persisting for 1-72hrs, may be
periumbilical or poorly localized
Diagnostic Criteria (ICHD-3 beta)
▪ At least 10 eps of HA occurring on <1d/mo on average (<12d/year)
▪ Lasting 30 mins to 7 days
▪ At least 2 of the ff. 4:
● Bilateral location
● Pressing or tightening (nonpulsating) quality
● Mild or moderate intensity
● Not aggravated by routine physical activity
▪ Both of the ff:
● No nausea/vomiting
● No more than 1 photophobia or phonohobia
▪ Common in children and adolescents (prevalence may be as high as 48%)
▪ An underlying psychological stressor is often suspected but difficult to
identify/confirm
TENSION HEADACHE
ACUTE SINUSITIS
Subtypes
▪ Infrequent (<12 times per year)
▪ Frequent (1-15 times per month)
▪ Chronic (>25 times per month)
Amitriptyline – SE: sleepiness, wt. gain; may cause
prolonged QT syndrome so avoid in patients w/
arrhythmia
Antiepileptics
(e.g.
topiramate,
valproic
acid,
levetiracetam) – effective for migraine prophylaxis in
adults but limited studies in children w/ migraine
Propanolol
▪ B-blocker best studied in pediatric migraine prevention
▪ CI: asthma or allergic disorders, diabetes
Cyproheptadine – may be effective in very young children
▪ GI: colic, motion sickness, recurrent abdominal pain, recurrent
vomiting including cyclic vomiting and abdominal migraine
▪ Sleep disorders: sleep walking sleep talking, night terrors, sometimes
seizures
BEHAVIORAL THERAPY
▪ Adherence to treatment plan is important
▪ Avoid triggers (e.g. skipping meals, dehydration,
decreased or altered sleep), adequate fluid intake without
caffeine, regular exercise, adequate sleep
▪ Thorough history and PE including a neurologic
examination ensure exclusion of secondary etiologies
Same general principles and medications used in migraine
can be applied to children with TTH
▪ Simple analgesics (e.g. ibuprofen or acetaminophen) can
be effective for acute treatment
▪ Amitriptyline has the most evidence of effective
prevention of TTH
▪ Biobehavioral intervention can be useful as well
*see Fever*
Complex
DISEASE
CLINICAL MANIFESTATIONS
Can present with clinical features observed in primary headache
disorders (i.e. tension-type, migraine, and cervicogenic headaches)
ANCILLARIES / DIAGNOSIS
TREATMENT
▪ In the absence of purulent nasal discharge, fever or
chronic cough, dx of sinus headache should not be made
▪ HA present for >15days/mo for >3mos and
▪ Intake of a simple analgesic >15 days/mo and/or
▪ Prescription medications >10 days/mo
Batch Clingy
SECONDARY CAUSES
OF HEADACHE
ETIOLOGY / INCIDENCE
POST TRAUMATIC HEADACHE
ICHD-3b classification
▪ Acute (last less than 3 mos)
▪ Persistent (last > 3 mos)
▪ Begin within 7 days after injury to the head or after regaining
consciousness (may be arbitrary)
SINUS HEADACHE
▪ Most over diagnosed form of recurrent headaches
▪ When HA are recurrent and respond within hours to analgesics, migraine
should be considered first
MEDICATION OVERUSE HEADACHE
▪ Suspect if with increasing use of analgesics with decreased effectiveness
or frequently wearing off
PPS Oral Exam Reviewer 2020
76
IDIOPATHIC
INTRACRANIAL
HYPERTENSION
Pseudotumor Cerebri
BRAIN TUMORS
DIFFERENTIAL DIAGNOSIS
Serious causes – due to increased ICP
▪ Can be due to mass (tumor, vascular malformation, cystic structure) → mass effect and local pressure on dura, or
▪ Intrinsic ↑ in pressure (i.e. idiopathic intracranial hypertension) → diffuse pressure on the dura
● Etiology may be d/t intake of excessive amounts of soluble compounds, hormonal changes, or blockage in venous drainage
▪ If ↑ ICP is suspected, MRI with MRA and MRV should be performed followed by LP (if no mass or vascular anomaly noted)
Other causes not due to ↑ ICP: AVMs, collagen vascular diseases affecting CNS, hypertensive encephalopathy, acute subarachnoid hemorrhage, stroke
▪ Frequently considered a potential cause of HA with papilledema in
▪ Most frequent symptom: chronic (weeks-to-months), progressive,
children with normal brain MRI findings
frontal HA that may worsen with postural changes or a Valsalva
▪ A large proportion of children with possible/probable IIH will have a
maneuver
secondary IH identified after thorough Hx/PE.
▪ Vomiting may occur, rarely persistent & insidious
▪ Transient visual obscuration (transient graying out or vision loss often
CAUSES
associated with postural changes or Valsalva maneuvers)
▪
Metabolic
Disorders:
galactosemia,
hypoparathyroidism,
▪ Diplopia secondary to abducens nerve dysfunction ▪ Pulsatile tinnitus
hypophospatasia, prolonged corticosteroid therapy or rapid withdrawal,
▪ Children are alert and lack constitutional symptoms
refeeding syndrome, hypervitaminosis A, severe vit A deficiency, Addison
disease, obesity, menarche, OCP use, pregnancy
▪ Papilledema with an enlarged blind spot is the most consistent sign
▪ Infection: chronic OM, mastoiditis, GBS
▪ Presence of focal neurologic signs – investigate other causes
▪ Drugs: doxycycline, minocycline, tetracycline, nitrofurantoin,
isotretinoin, sodium valproate
▪ Hematologic Disorders: polycythemia, various anemias, WAS
▪ Obstruction of intracranial drainage by cerebral venous thrombosis
▪ Second most common malignancy overall
▪ Depends on tumor location, type, and age of child
▪ Most common solid organ malignancy in childhood and adolescence
▪ Some Ssx are related to obstruction of CSF drainage paths by the
tumor → ↑ ICP or focal brain dysfunction
▪ Familial syndromes account for approx. 5% of cases
SUPRATENTORIAL LESIONS
▪ Cranial exposure to ionizing radiation is associated with a higher
▪ Subtle changes in personality, mentation, speech
incidence
▪ More frequently associated with focal disorders – motor weaknesses,
▪ Incidence is highest in infants and children <5yrs old
sensory changes, speech disorders, seizures, reflex asymmetry
▪ Premature hand preference in infants
▪ Age related differences in primary location:
0-1 y/o: supratentorial tumors predominate – choroid plexus tumors and
INFRATENTORIAL LESIONS
teratoma
▪ Classic triad: HA, n/v, and papilledema
1-10 y/o: infratentorial tumors predominate – medulloblastoma, juvenile
▪ Blurred vision, diplopia, and nystagmus are also associated
PA
After 10 y/o: supratentorial tumors again predominate – diffuse
BRAINSTEM LESIONS
astrocytoma most common
▪ Gaze palsy, multiple CN palsy, upper motor neuron deficits
(hemiparesis, hyperreflexia, clonus)
Cranial MRI: papilledema or enlargement of the optic
never sheaths/pituitary fossa
MR venography: to exclude a venous thrombosis and
identify tapering of the lateral sinuses (commonly seen in
intracranial hypertension)
Measurement of CSF pressure: ideally, using an
electronic transducer (minimize falsely elevated readings)
▪ When LP opening pressure is measured under GA, it is
important to record a normal end-tidal partial pressure of
CO2
MRI – neuroimaging standard
Serum and CSF measurements of β-HCG and alpha
fetoprotein to check germ cell tumors
LP with CSF analysis
▪ For tumors that spread to meninges
▪ Contraindicated in those with hydrocephalus 2o to CSF
obstruction
▪ Any cause of secondary IH should be treated
▪ Obese children with IIH need a weight-loss regimen
▪ Acetazolamide (10-30 mkday) probably is an effective
regimen
▪ Serial monitoring of visual function and serial optic
nerve examination is essential
▪LP may be diagnostic and therapeutic
COMPLICATIONS
▪ Optic atrophy
▪ Visual impairment
COMPLICATIONS
50% with chronic problems
▪ Chronic neurologic deficit – focal and sensory
abnormalities
▪ Seizure disorders
▪ Neurocognitive deficits - developmental delays, learning
disabilities
▪ Neuroendocrine deficiencies – hyperthyroidism, growth
failure, delay or absence of puberty
SUPRASELLAR TUMORS
▪ Neuroendocrine deficits (DI, galactorrhea, precocious puberty,
delayed puberty and hypothyroidism)
▪ Diencephalic syndrome: FTT, emaciation despite normal caloric intake,
inappropriately normal or happy affect
▪ Parinaud syndrome: paresis of upward gaze, pupillary dilation reactive
to accommodation but not to light, nystagmus to convergence or
retraction, eyelid retraction
SPINAL CORD TUMORS
PPS Oral Exam Reviewer 2020
Batch Clingy
OPTIC PATHWAY TUMORS
▪ Visual disturbances, ↓ visual acuity, Marcus Gunn pupil, nystagmus,
visual field defects
77
▪ Long nerve tract motor and/or sensory deficits, bowel and bladder
deficits, back or radicular pain
TYPES OF BRAIN TUMOR
1) ASTROCYTOMA (40%)
Low grade astrocytoma (LGA): predominant in children; indolent clinical
course
▪ Surgery + chemoRT
▪ Pilocytic astrocytoma (PA)
● Most common astrocytoma in children
● Classic sites cerebellum & optic pathway region
▪ Seen as contrast enhancing nodule within the wall of a
cystic mass
▪ Presence of Rosenthal fibers helps establish dx
▪ Diffuse astrocytoma (DA)
● 2nd most common astrocytoma
● Occur anywhere in the CNS with a predilection to supratentorial
locations
▪ MRI: lack of enhancement after contrast infusion
Medulloblastoma
▪ Cerebellar tumor
▪ Occur predominantly in males
▪ Median age: 5-7yrs old
5) PINEAL PARENCHYMAL TUMORS
▪ 2nd most common malignancy in the pineal region after germ cell tumors
Pineoblastoma – subgroup of childhood PNETs
6) CRANIOPHARYNGIOMA
7) GERM CELL TUMORS
▪ Arise in midline structure of pineal and suprasellar regions
▪ Peak incidence: 10-12 y/o
8) TUMORS OF THE BRAINSTEM
9) METASTATIC TUMORS
▪ Uncommon
▪ Rarely can occur from lymphoma, neuroblastoma, rhabdomyosarcoma,
Ewing sarcoma, osteosarcoma and clear cell sarcoma of the kidney
▪ Childhood ALL & non-Hodgkin lymphoma can spread to leptomeninges
causes sx of communicating hydrocephalus
PPS Oral Exam Reviewer 2020
▪ Noninvasive but extends into the ventricular lumen; can
lead to hydrocephalus
▪ Signs of ↑ ICP, macrocephaly, focal neuro deficits
▪ Ssx of ↑ICP and cerebellar dysfunction
▪ Irradiation with surgery
▪ Surgery
▪ Histology: small, blue round cell tumor; presence of
Homer Wright rosettes
▪ Surgery + chemoRT
▪ Chemotherapy
▪ Endocrine abnormalities – growth failure, delayed sex maturation)
▪ Visual field changes – decreased visual acuity, decreased visual field
deficits
▪ Surgery – main treatment
▪ No role for chemotherapy
▪ Alpha fetoprotein and β-hCG useful in diagnosis and
response to treatment
▪ Motor weakness, CN deficits, cerebellar deficits, signs of increased ICP
▪ Depends if germinoma or non-germinomatous
▪ Surgery ± radiation and chemo
▪ Surgical resection for focal and dorsally exophytic
tumors
▪ Radiation therapy for the others
Batch Clingy
Malignant astrocytoma: less common in children, expressed p53 prognostic
2) EPENDYMAL TUMORS (10%)
▪ From ependymal lining of ventricular system; approx. 70% occur in
posterior fossa
▪ Mean age: 6yrs old
3) CHOROID PLEXUS TUMORS
▪ Most common CNS tumor in children <1yo
▪ Account for 10-20% of tumors in infants
4) EMBRYONAL TUMORS or PRIMITIVE NEUROECTODERMAL TUMORS
(PNETs)
▪ Most common group of malignant CNS tumors of childhood
▪ Have the potential to metastasize to the neuraxis and beyond
78
Acute
PPS Oral Exam Reviewer 2020
TREATMENT
Parent education
▪ If seizure lasts >5mins, acute treatment with
lorazepam, midazolam or diazepam is needed
▪ Antiepileptic therapy, continuous or intermittent, is
not recommended for children with ≥1 simple FS – risk
of SE and lack of demonstrated long-term benefits
▪ Antipyretics can decrease the discomfort of the child
but do not reduce the risk of having a recurrent FS
COMPLICATIONS / PROGNOSIS
▪ SFS do not have an increased risk of
mortality
▪ CFS may have an approx. 2-fold longterm increase in mortality rates, as
compared to the general population,
over the subsequent 2 yr, prob. 2O to a
coexisting pathology
2018 DOH National Antibiotic Guidelines
▪ Subdural effusions (10-30%)
▪ SIADH → hyponatremia and ↓ serum
osmolality → exacerbate cerebral edema
or result in seizures
▪ Risk for nosocomial infections
>2mos – 5yo
▪ S. pneumoniae, Hib, N. meningitides
▪ Ceftriaxone 100mkday q12-24h OR
▪ Chloramphenicol 100 mkday q8h
▪ If penicillin- or cephalopsporin-resistant S.
pneumoniae, add: Vancomycin 15-20 mg/kg q8-12h
▪ If Hib is suspected, add Dexamethasone 0.15mkday
q6h x 4 days and Rifampin prophylaxis to eradicate
carrier state
>5 – 18 yo
▪ S. pneumoniae, N. meningitides
▪ Ceftriaxone 100mkday q12-24h OR
▪ Chloramphenicol 100mkday q8h
2015 PIDSP/CNSP CPG on Acute Bacterial Meningitis
Drug of choice for specific etiology
▪ Hib: Ceftriaxone for 7-10 days (alt: chloramphenicol)
▪ S. pneumoniae: Penicillin for 10-14 days (alt:
chloramphenicol or ceftriaxone)
▪ N. meningitides: Penicillin for 7 days (alt: ampicillin,
ceftriaxone, chloramphenicol, and cefotaxime)
▪ Highest mortality rates are observed
with pneumococcal meningitis
▪ Seizures that persist after the D4 of
illness suggest poor prognosis and can be
refractory to treatment
▪ Severe neurodevelopmental sequelae
may occur in 10-20% of patients:
● Sensorineural hearing loss (most
common)
● Cognitive impairment
● Recurrent seizures
● Language delay
● Visual impairment
● Behavioral problems
▪ Vaccination (PCV, MCV and Hib) and
antibiotic prophylaxis (all close contacts
of patients with Hib & meningococcal
Batch Clingy
SEIZURE – a transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
DIAGNOSIS
▪ Occur between the ages of 6 and 60mos (peak 12SIMPLE FEBRILE SEIZURE
Lumbar Puncture
18mos)
▪ Generalized, tonic-clonic
▪ Meningitis should be considered
▪ Temperature ≥38oC
▪ Maximum of 15mins
▪ Should be performed in:
▪ Not the result of CNS infection or any metabolic
▪ Not recurrent within a 24h-period
● All infants younger than 6mos of age who present with fever
imbalance
and seizure
▪ Occur in the absence of a history of prior afebrile
COMPLEX FEBRILE SEIZURE
● Child is ill-appearing
seizures
▪ More prolonged (>15mins) and/or
● At any age if there are clinical signs or symptoms of concern
▪ Focal and/or
▪ An option in:
▪ Between 2% and 5% of neurologically healthy
▪ Recurs within 24hrs
● A child 6-12mos of age who is deficient in Hib and S.
infants and children experience at least one, usually
pneumoniae immunizations or for whom the immunization status is
simple, febrile seizure
(see Nelson’s 21st Ed., Table 611.6 for Risk
unknown
Factors for Occurrence of Subsequent
● Children pretreated with antibiotics
FEBRILE SEIZURE
(see Nelson’s 21st Ed., Table 611.5 for Risk Factors for
Epilepsy After a FS)
Recurrence of Febrile Seizures)
EEG
▪ Need not be performed in a child presenting with the first FS and
▪ Pathophysiology remains unclear
is otherwise neurologically healthy
▪ HHV-6 and HHV-7 infections – high reported rate of
▪ Restricted to special cases in which epilepsy is highly suspected
association with FS
(done after 2 weeks have passed)
▪ The genetic contribution to the incidence of FS is
manifested by a positive FHx for FS in many patients
Neuroimaging
▪ In some families, it is inherited as an autosomal
▪ Not recommended in evaluating a first simple FS
dominant trait
▪ Workup of children with complex FS needs to be individualized
and can include EEG and neuroimaging if the child is neurologically
abnormal
▪ CNS infection primarily affecting the meninges
Common symptoms
Lumbar Puncture
▪ Typically, due to bacterial colonization of the
▪ HA, N/V, anorexia, photophobia,
▪ Most important step in the diagnosis
nasopharynx with subsequent invasion into the
restlessness, altered state of consciousness,
▪ Obtain CSF for cytology, Gram stain and culture
bloodstream → breach BBB and enter the CNS to
irritability
● Neutrophilic pleocytosis (CSF leukocyte count
>1,000/mm3
cause infection and inflammation
with 75-95% PMN), ↑ protein and ↓ glucose concentrations could
Common signs
be suggestive of a diagnosis of bacterial meningitis; findings usually
ETIOLOGIES
▪ Fever, neck pain and rigidity, focal
persist for several days after administration of appropriate
Nelson’s 21st Ed. (in order of incidence)
neurologic deficits, seizures, obtundation,
antibiotics
▪ S. pneumoniae
coma
● Gram stain is positive in >70% of patients with untreated
▪ N. meningitides
bacterial meningitis; can be negative as early as 2-4hrs after
▪ H. influenza Type b
▪ Rash of meningococcemia – initial petechial
administration of antibiotics
ACUTE BACTERIAL
rash → ecchymotic and purpuric lesions
● CSF culture is the gold standard for the diagnosis
MENINGITIS
2015 PIDSP/CNSP CPG on Acute Bacterial Meningitis
▪ Kernig sign and Brudzinski sign (both not
▪ Contraindications:
3mos to <5yo
consistently present in those <12-18mos)
● Evidence of increased ICP such as 3rd or 6th CN palsy with a ↓
▪ H. influenza Type b
▪ Signs of increased ICP
LOC, or the Cushing reflex
▪ S. pneumoniae
● Severe CP compromise requiring prompt resuscitation
≥5yo
● Infection of the skin overlying the site of the LP
▪ S. pneumoniae – most common
▪ If LP is delayed, empiric antibiotic therapy should be initiated
▪ N. meningitides – occur in epidemics or sporadically
Neuroimaging
▪ Routine scans prior to LP are not recommended unless the patient
is at risk for ↑ ICP
Blood cultures
▪ Performed in all patients with suspected meningitis
79
▪ An acute inflammatory process involving the
meninges and/or brain parenchymal tissue
VIRAL MENINGO
ENCEPHALITIS
BRAIN ABSCESS
TOXIC INGESTION
METABOLIC &
ELECTROLYTE
DISTURBANCES
▪ Neurologic damage is caused by direct invasion and
destruction of neural tissues by actively multiplying
viruses or by a host reaction to viral antigens
● In HSV-1 encephalitis, the temporal lobes are
severely affected
● Arbovirus - affects the entire brain
● Rabies – predilection for the basal structures
▪ Contiguous spread from an assoc. infection –
meningitis, OM, mastoiditis, sinusitis, SSTI of the face
or scalp, orbital cellulitis, or dental infections
● Direct compromise of the BBB due to
penetrating head injuries or surgical procedures
● Embolic phenomena (endocarditis)
● CHD with R to L shunts
● Immunodeficiency
● Infection of foreign material inserted to the CNS
EEG
▪ Typically shows diffuse slow-wave activity
▪ Exanthems can precede or accompany CNS
signs, especially with enteroviruses, VZV,
measles, rubella and WNV
▪ Nuchal rigidity without significant localizing
neuro changes
MRI
▪ May demonstrate focal brain lesions that correlate with clinical
disease
▪ Asymptomatic early in the course
▪ Non-specific symptoms – low grade fever,
headache, lethargy
▪ Vomiting, severe HA, seizures, papilledema,
focal neuro signs, coma
Brain MRI with contrast – diagnostic test of choice
Cranial CT scan – can be an alternative to provide more rapid
imaging results but cannot provide the fine tissue detail offered by
MRI
Lumbar Puncture – not routinely recommended (could cause
herniation)
(see Nelson’s 21st Ed., Table 621.4 for Antibiotics Used
for the Treatment of Bacterial Meningitis)
▪ For most causes, no effective antiviral agents exist
● Members of the herpesvirus family can be
treated with acyclovir, ganciclovir, cidofovir and
foscarnet
meningitis)
▪ Recovery depends on the severity of the
clinical illness, the specific causative
agent, and the age of the child
▪ Supportive and rehabilitative efforts are
very important after recovery
▪ Treatment is primarily supportive care
● IV fluids for poor oral intake
● NSAIDs for symptomatic relief of HA
● Monitor for seizures, cerebral edema, fluid and
electrolyte imbalance, aspiration, respiratory failure,
cardiac arrest
▪ Empiric therapy combination (3rd gen cephalosporin
and metronidazole) often with vancomycin to provide
MRSA coverage – duration depends on the organism
and response to treatment but is most typically 6wks
▪ Aspiration of the abscess – recommended for
diagnostic cultures and decompression unless
contraindicated
▪ Mortality rate: 5-10%
Long-term sequelae
▪ Hemiparesis
▪ Seizures
▪ Hydrocephalus
▪ CN abnormalities
▪ Behavioral and learning difficulties
ETIOLOGIES
▪ Streptococci – most common
▪ S. aureus – 2nd most common
▪ Gram negative and anaerobes
▪ Seizures can occur in the setting of alcohol or BDZ withdrawal
▪ Can occur acutely in the setting of alcohol intoxication or illicit drug use (amphetamines, cocaine, narcotics)
▪ Other drugs: INH, aminophylline/theophylline, TCA, oral hypoglycemic agents
▪ Hypernatremia → brain hemorrhage due to movement of water out of the cell
▪ Hyponatremia → cerebral edema
▪ Hypomagnesemia → secondary hypocalcemia
▪ Hypocalcemia
▪ Hypophosphatemia
▪ Hypoglycemia
*see Traumatic Brain Injury*
Batch Clingy
TRAUMA
Etiologies
▪ Most common: enteroviruses, parechoviruses
▪ Most common arboviral cause: West Nile virus,
Japanese encephalitis virus
▪ HSV type 1 – important cause of severe, sporadic
encephalitis
▪ VZV may cause CNS infection in a close temporal
relationship with chickenpox
▪ CMV – can occur with congenital infection or
disseminated disease in immunocompromised hosts
▪ CNS Ssx are generally preceded by a
nonspecific febrile illness of a few days’
duration
▪ Presenting manifestations in older children:
HA (often frontal or generalized) and
hyperesthesia; in infants: irritability, lethargy
▪ Fever, N/V, photophobia, pain the neck,
back and legs
▪ Focal neurologic signs may be persistent,
fluctuating, or migratory
CBC, CRP, ESR and procalcitonin should not be used to routinely
determine which patients should receive antibiotics
CSF Analysis
▪ Pleocytosis of leukocytes with counts typically <1,000/mm3
▪ Very early in the disease, cells are often PMN whereas
mononuclear cells predominate for the remainder of the duration
▪ Protein tends to be elevated
▪ Glucose level is typically normal
▪ Primary means of detecting nonbacterial pathogens is nucleic acid
amplification
PPS Oral Exam Reviewer 2020
80
Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
The ILAE has refined the definition of SE to reflect
▪ The time at which treatment should be initiated
(t1), and
▪ Time at which continuous seizure activity leads to
long-term sequelae (t2)
▪ Continuous convulsive activity or recurrent
generalized convulsive seizure activity without
regaining of consciousness (t1 = 5 min; t2 ≥ 30 min);
focal seizures with impaired awareness (t1 = 10 min;
t2 = 30 min) and absence SE (t1 = 10-15 min; t2 =
unknown)
STATUS
EPILEPTICUS
PATHOGENESIS
▪ Failure of desensitization of AMPA glutamate
receptors → persistent ↑ excitability, and
▪ ↓ GABA-mediated inhibition 2o to intra- cellular
internalization of GABAA receptors
ETIOLOGY
▪ New-onset epilepsy of any type
▪ Drug intoxication, drug & alcohol abuse
▪ Drug withdrawal or overdose in patients taking
AEDs
▪ Hypoglycemia, hypocalcemia, hyponatremia,
hypomagnesemia
▪ Acute head trauma
▪ Meningoencephalitis
▪ Autoimmune encephalitis
▪ Stroke (ischemic or hemorrhagic)
▪ IEM, MELAS
▪ Brain tumors
▪ Disorder of the brain characterized by an enduring
predisposition to generate seizures
● At least 2 unprovoked (or reflex) seizures
occurring >24hrs apart
● Enough EEG and clinical information to
convincingly
demonstrate
an
enduring
predisposition to develop recurrences
EPILEPSY
Epileptic syndrome
▪ ≥1 specific seizure type, has a specific age of onset
and a specific prognosis
4 distinct, often sequential, mechanistic processes
Underlying etiology
▪ Any pathology or pathologic process that can
disrupt neuronal function and connectivity (e.g.
disorder in ion channel function and/or structure,
gene mutations affecting neurotransmitter function,
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
CONVULSIVE SE
▪ GTC, tonic, or clonic
▪ Most common type of SE
FEBRILE SE
▪ Most common type of SE in children
NONCONVULSIVE SE
▪ Confusional state, dementia, hyperactivity with
behavioral problems, fluctuating impairment of
consciousness, fluctuating mental status, hallucinations,
paranoia, aggressiveness, catatonia, and/or psychotic
symptoms
REFRACTORY SE
▪ Failed to respond to therapy, usually with at least 2
medications
SUPERREFRACTORY SE
▪ Failed to resolve, or recurs within 24hrs or more despite
therapy that includes a continuous infusion such as
midazolam and/or pentobarbital
GENERALIZED MOTOR SEIZURES
▪ Starts with LOC, upward rolling of the eyes, and a
generalized tonic contraction → clonic phase that shows
slowing of the rhythmic contractions until the seizure
stops
ABSENCE SEIZURES
▪ Usually starts at 5-8yo
▪ Do not have an aura, usually lasts for only a few seconds
▪ Eyelid flutter or upward rolling of the eyes
▪ No postictal period
▪ Immediate resumption of what the patient was doing
before the seizure
▪ EEG: 3-Hz spike and slow wave discharges
DIAGNOSIS
Labs
▪ Glucose, Na, Ca, Mg, CBC, basic metabolic panel
▪ AED levels in patients known already to be taking these
drugs
▪ Toxic drug screens and screens for IEM, if warranted
EEG
▪ Helpful in ruling out pseudo-SE or other movement
disorders
▪ Helpful in identifying the type of SE
Neuroimaging
▪ Considered once the child is stabilized, especially if
indicated by the clinical manifestations, by an asymmetric
or focal nature of the EEG abnormalities or by lack of
knowledge of the underlying etiology
TREATMENT
▪ SE is a medical emergency
▪ Secure airway, breathing and circulation
▪ Admit to PICU for completion of therapy and
monitoring
American Epilepsy Society SE Guidelines
▪ BZD – started for convulsive seizures lasting
>5mins (IV lorazepam, IV diazepam or IM
midazolam)
▪ If seizures persist 5 min after the initial BZD dose,
give a 2nd dose
▪ If still unsuccessful, fosphenytoin, valproate or
levetiracetam is the recommended option
● IV phenobarbital is an alternative option if the
above are not available
▪ If seizure persists, decision must be made
regarding re-dosing with another second-line
agent or proceeding to a continuous infusion
COMPLICATIONS / PROGNOSIS
▪ Mortality rate: 4-5%, mostly 2o to the
underlying etiology rather than to the
seizures
▪ SE carries an approximately 14% risk of
new neurologic deficits, most of them 2o
to the underlying pathology
(see Nelson’s 21st Ed., Fig 611.7 for the Proposed Algorithm
for SE)
Diagnosis of select generalized epilepsy syndromes
DRAVET SYNDROME
▪ Myoclonic epilepsy of infancy
▪ Starts as focal febrile SE or focal FS and later manifests as
myoclonic and other seizure types
WEST SYNDROME
▪ Starts between 2-12mos
▪ Triad: infantile epileptic spams that occurs in clusters,
developmental
regression,
and
typical
EEG
(hypsarrhythmia)
LENNOX-GASTAUT SYNDROME
▪ Starts between 2-10yo
▪ Triad: developmental delay, multiple seizure types that
include atypical absences, and myoclonic, astatic, and tonic
seizures and specific EEG findings
▪ Educate the family and the child
▪ Drug therapy should be based on the type of
seizure and the epilepsy syndrome
● Oxcarbazepine and levetiracetam –first
choice for focal seizures and epilepsies
● Levetiracetam – first drug to use in other
primary generalized seizures
▪ Monotherapy should be the goal
● Dose is increased until complete control is
achieved or until SE prohibit further increases
● Only then may another drug be added, and
the initial drug be subsequently tapered
▪ Epilepsy carry a risk of increased
mortality rates (two or more times the
standardized mortality rates of the
general population) mostly related to
conditions assoc. with or underlying the
epilepsy, poor seizure control and poor
compliance with prescribed therapies
(see Nelson’s 21st Ed., Table 611.7 for
Sports and Special Considerations for the
Child with Epilepsy)
▪ Dravet syndrome – BZD; keto diet can be useful
▪ West syndrome – hormonal therapy (either ACTH
or oral steroids)
Batch Clingy
DISEASE
81
autoAb)
Epileptogenesis
▪ Mechanism through which the brain, or part of it,
turns epileptic
▪ Repeat seizures → rewiring of the brain and longterm epilepsy
Epileptic state of increased excitability
▪ Dysregulation of glutamatergic excitation vs.
GABAergic inhibition occurs
Seizure-related neuronal injury
FOCAL SEIZURES WITH PRESERVED AWARENESS
▪ Can be sensory seizures (aura) or brief motor seizures
(most common)
▪ Brief motor seizures include focal tonic, clonic, or atonic
szs with a Jacksonian march, adversive head and eye
movements to the contralateral side or postictal Todd
paralysis
FOCAL SEIZURES WITH IMPAIRED AWARENESS
▪ Last 1-2 min and preceded by an aura
▪ ↓ Responsiveness, staring, looking around seemingly
purposelessly
and
automatisms
(automatic
semipurposeful movements of the mouth, or the
extremities)
▪ LGS – treatment varies according to predominant
seizure type
DOOSE SYNDROME
▪ Myoclonic astatic epilepsy
▪ Similar but milder than LGS
▪ Usually do not have tonic seizures or polyspike bursts in
sleep
Diagnosis of select epilepsy syndromes with focal seizures
▪ Absence seizures – treat initially with
ethosuximide; alternatives are lamotrigine and
valproate
BENIGN CHILDHOOD EPILEPSY WITH CENTROTEMPORAL
SPIKES
▪ Most common
▪ Starts at 3-10yo; outgrown by adolescence
▪ Child wakes up at night due to a focal seizure with
preserved awareness causing buccal and throat tingling
and tonic or clonic contractions of one side of the face,
with drooling and inability to speak but with preserved
consciousness and comprehension
▪ EEG: wide-based centrotemporal spikes that are markedly
increased in freq. during drowsiness and sleep
BENIGN EPILEPSY WITH OCCIPITAL SPIKES
▪ Panayiotopolous type: Occur in early childhood; manifests
with focal seizures with impaired awareness and ictal
vomiting
▪ Gastaut type: Appear later in childhood as focal seizures
with impaired awareness, visual auras, and migraine HAs
that occur independently or postictally
▪ Both are typically outgrown in a few years
*see Headache*
Batch Clingy
BRAIN TUMOR
▪ EEG: 1- to 2-Hz spike and slow waves, polyspike bursts in
sleep and slow background in wakefulness
PPS Oral Exam Reviewer 2020
82
Complex
DISEASE
GENERALITIES / PATHOGENESIS
▪ A diverse group of conditions that result from impaired
circulation and/or absorption of CSF
Normal physiology: CSF is produced in the choroid plexus
→ lateral ventricles → foramen of Monro → 3rd ventricle
→ aqueduct of Sylvius → 4th ventricle → foramen of
Luschka and Magendie → basal cisterns → convexities of
the cerebral hemispheres → absorbed by arachnoid villi
Normal rate of production: 20 mL/hr
Normal value: 50mL in infants; 150mL in adults
Obstructive/Non-communicating
▪ Obstruction within ventricular system
▪ Most commonly because of an abnormality of the
aqueduct of Sylvius (e.g. aqueductal stenosis, aqueductal
gliosis 2O neonatal meningitis or SAH in a premature
infant) or a lesion in the fourth ventricle (e.g. posterior
fossa brain tumors, Chiari malformation and the DandyWalker syndrome)
HYDROCEPHALUS
Non-obstructive/communicating
▪ Obliteration of subarachnoid cisterns or malfunction of
arachnoid villi
▪ Most commonly follows a SAH 2O to IVH in a premature
infant
▪ Pneumococcal and TB meningitis have a propensity to
produce a thick, tenacious exudate that obstructs the
basal cisterns
▪ Leukemic infiltrates can seed the subarachnoid space and
produce communicating hydrocephalus
CLINICAL MANIFESTATIONS
Infants
▪ Accelerated rate of head enlargement
▪ Wide bulging anterior fontanel
▪ Dilated scalp veins
▪ Broad forehead
▪ Eyes deviate downward (setting sun eye sign)
▪ Long tract signs (brisk tendon reflexes, spasticity, clonus, and
Babinski sign)
▪ Macewen sign: cracked pot sound on percussion of skull
(indicates separation of sutures)
Foreshortened occiput: Chiari malformation
Prominent occiput: Dandy-Walker
Older children
▪ Signs are subtler
▪ Irritability, lethargy, poor appetite, vomiting
▪ Headache is a prominent symptom
▪ Gradual change in personality and deterioration in academic
productivity suggest a slowly progressive form of hydrocephalus
Chiari Malformation
Type I
▪ Produces s/sx during adolescence or adult life; not assoc. with
hydrocephalus
▪ Recurrent HA, neck pain, urinary frequency and progressive LE
spasticity
Type II
▪ Progressive hydrocephalus w/ myelomeningocoele
▪ 10% produce symptoms during infancy (stridor, weak cry and
apnea)
▪ Relieved by shunting or decompression of posterior fossa
Neuroimaging:
▪ Plain skull films: separation of sutures, erosion of posterior clinoids (in
older children), increase in convolutional markings on the inside of the skull
(d/t long-standing increased ICP)
▪ CT/MRI and UTZ – most important studies to identify cause and severity of
hydrocephalus
DIFFERENTIALS FOR INCREASED HEAD SIZE
▪ Chronic anemia (thalassemia), rickets, osteogenesis imperfect, epiphyseal
dysplasia
Megalencephaly
▪ Anatomic disorder of brain growth
▪ Brain weight:volume ratio of >98th percentile for age (≥ 2 SD above the
mean)
▪ Causes: storage and degenerative diseases; anatomic and genetic causes
▪ Benign familial megalencephaly: most common anatomic cause
▪ Sotos syndrome (cerebral gigantism): most common megalencephalic
syndrome
▪ High forehead with frontal bossing, sparse hair in frontoparietal syndrome,
downslanting palpebral fissures, apparent hypertelorism, long narrow face,
prominent mandible, malar flushing
▪ Hypotonia, poor coordination and speech delay
TREATMENT / PROGNOSIS
Depends on cause
▪ Acetazolamide and furosemide: temporary relief by
reducing rate of CSF production
▪ VP shunt in most cases
COMPLICATIONS OF SHUNTING
▪ Headache
▪ Papilledema
▪ Emesis
▪ Mental status changes
▪ Bacterial infection
PROGNOSIS
▪ Depends on the cause of dilated ventricles
▪ Increased risk for dev disabilities
● Mean IQ is reduced
● Abnormalities in memory function
● Vision problems (strabismus, visuospatial abnormalities,
visual field defects, optic atrophy)
▪ Some show aggressive and delinquent behavior
▪ Accelerated pubertal development in pts. with shunted
hydrocephalus because of ↑ gonadotropin secretion in
response to increased ICP
Hydranencephaly
▪ Cerebral hemispheres absent or represented by membranous sacs
▪ Midbrain and brainstem intact
▪ Transillumination shows absence of cerebral hemispheres
▪ Irritable, feeds poorly, develops seizures and spastic quadriparesis, little or
no cognitive dev’t
Batch Clingy
Dandy walker formation
▪ Cystic expansion of 4th ventricle in posterior fossa and midline
cerebellar hypoplasia (dev failure of roof of 4 th ventricle during
embryogenesis)
▪ 90% have hydrocephalus with assoc. anomalies (agenesis of
posterior cerebellar vermis and corpus callosum)
▪ Rapid ↑ in head size and prominent occiput
ANCILLARIES / DIAGNOSIS
▪ Inspect, palpate, auscultate skull and spine
▪ Inspect back for midline lesions
▪ Prominent forehead or abnormalities in the shape of the occiput can
suggest hydrocephalus
▪ Cranial bruit: vein of Galen AVM
▪ (+) Transillumination: massive dilation of the ventricular system or DandyWalker syndrome
▪ (+) Chorioretinitis: suggestive of intrauterine infection (e.g. toxoplasmosis)
as cause of hydrocephalus
PPS Oral Exam Reviewer 2020
83
▪
Nontraumatic
intracranial
hemorrhage:
intraparenchymal bleeds or intraventricular hemorrhage
▪ Bleeding outside the brain: SAH, subdural and epidural
hematomas
HEMORRHAGIC
STROKE Intracranial
Hemorrhage
▪ Cause and risk factors for HS include vascular
malformations and systemic disorders (see Nelson’s 21 st
ed., Table 619.4)
● Arteriovenous malformations: most common cause
of childhood SAH and intraparenchymal HS
● Other vascular malformations: cavernomas, dural AV
fistulas, vein of Galen malformations
● Cerebral aneurysms: less common cause of SAH;
suggest underlying disorder
● Bleeding from a preexisting brain tumor is another
common cause
● Additional causes: hypertensive hemorrhage,
hematologic disorders (e.g. ITP, hemophilia, DIC),
anticoagulant therapy, or illicit drug use
● Ischemic infarcts may undergo hemorrhagic
transformation
▪ Vary according to location, cause and rate of bleeding
▪ CT scan is highly sensitive
▪ LP may be required to exclude SAH
▪ Angiography – to exclude vascular abnormalities
▪ Cranial UTZ in neonatal HS – detect neonatal parenchymal bleeds,
especially in the preterm, where bleeds are located centrally within the
cranium (germinal matrix bleeding and intraventricular hemorrhage) and in
the cerebellum
Acute hemorrhages
▪ Instantaneous (thunderclap headache)
▪ Loss of consciousness
▪ Nuchal rigidity
▪ Focal neurologic deficits
▪ Seizures
PROGNOSIS
▪ Likely depends on lesion size, location, and etiology
▪ Compared with arterial ischemic stroke, HS mortality rate is
higher but long-term deficits are less common
▪ Recurrence risk for those with structural lesions is
significant
Vascular malformations
▪ Pulsatile tinnitus
▪ Cranial bruit
▪ Macrocephaly
▪ High output heart failure
Abusive head trauma
▪ Subtle scalp, suborbital, or ear bruising
▪
Retinal
hemorrhages
in
▪ Chronic failure to thrive
▪ Emergent neurosurgical intervention
▪ Neuroprotection
▪ Reversal of anticoagulant therapy (e.g. vit K or FFP) but
other medical interventions like FVII are unstudied in
children
▪ Definitive repair or removal of the vascular malformation
multiple
layers
Abusive head trauma: may present as primary subdural or
parenchymal hemorrhage
● Epidural hematoma: nearly always caused by trauma
(e.g. middle meningeal artery injury assoc. w/ skull
fracture)
● Subdural hematoma: can occur spontaneously or
with trivial trauma
*see Headache*
*see Seizures*
Batch Clingy
BRAIN TUMOR
CNS INFECTIONS
PPS Oral Exam Reviewer 2020
84
Chronic
DEFINITION / EPIDEMIOLOGY
ETIOPATHOGENESIS
DIAGNOSTIC CRITERIA / SYMPTOMS
DIFFERENTIALS
SCREENING AND ASSESSMENT
MANAGEMENT
▪ Neurobiologic disorder with onset
in early childhood
▪ Result from
disrupted neural
connectivity
▪ Primarily impacted by genetic variations
affecting early brain development
● Animal models and studies of
individuals with ASD indicate changes in
brain volume and neural cell density in
the limbic system, cerebellum, and
frontotemporal regions
● Numerous genes involved in brain
development and synaptic function have
been associated with ASD
DSM-V criteria focus on symptoms in 2 primary
domains: social communication and social interaction
and restrictive and repetitive behavior
● Symptoms should be present since the early
developmental period
● Significantly impact functioning
● Not better explained by other diagnosis
(see Nelson’s 21st ed., Table 54.1 for full DSM-V
criteria)
Language disorder
▪ Impaired social communication and play but
social and play skills are at par
▪ No associated restricted/ repetitive behavior
Universal screening at age 18mos
and 24mos
▪ Screening should also occur when
there is increased risk for ASD (child
with an older sibling who has ASD or
concern for possible ASD)
▪ MCHAT-R/FU: most common
screening tool
▪ Thorough history and detailed
physical examination including direct
behavioral
observations
of
communication and play
Developmental and educational
programming: primary treatment for
ASD
▪ Earlier age at initiation of tx and
higher intensity leads to better
outcomes
Key features:
▪ Impaired social communication and
social interaction and
▪ Restricted and repetitive behaviors
▪ 4:1 male predominance
▪ Prevalence increased in siblings (up
to 10%) particularly in identical twins
▪ No racial or ethnic differences in
prevalence
▪ There is also evidence for environmental
contributions
● Older maternal or paternal age may
increase the risk
● Factors influencing the intrauterine
environment (maternal obesity or
overweight, short interval from prior
pregnancy, premature birth, certain
perinatal infections)
AUTISM SPECTRUM
DISORDER
▪ Multiple research studies and metaanalyses have failed to show an
association of vaccines with ASD
Social Communication and Social Interaction
▪ Difficulty understanding and engaging in social
relationships
▪ Pervasive and impact 3 major areas:
Social-emotional reciprocity
▪ Young child with ASD may not respond to name
calling, exhibit limited showing and sharing behaviors,
prefers solitary play
▪ Older child with ASD may have an interest in peers
but does not know how to initiate or join in play
Nonverbal communication
▪ Reduced eye contact and gestures
▪ Limited range of facial expression
Understanding of social relationships
▪ Limited insight regarding social relationships
Restrictive and Repetitive Behavior
(At least 2 of 4 symptoms)
▪ Stereotyped motor movements or speech (e.g. hand
flapping, spinning, echolalia, lining up objects)
▪ Insistence on sameness (i.e. insist certain routines or
schedules)
▪ Restricted interests (i.e. intense interest that seem
out of the norm in comparison to same-age peers)
▪ Hypo- or Hyperreactivity to Sensory Input
▪ Most common neurobehavioral
disorder of childhood
ATTENTIONDEFICIT/
HYPERACTIVITY
DISORDER
Characterized by:
▪ Inattention
▪ Poor impulse control
▪ ↓ Self-inhibitory capacity and
motor overactivity
▪ Motor restlessness
▪ 5-10% of school-age children are
affected
▪ Mothers of children with ADHD are
PPS Oral Exam Reviewer 2020
Dopamine hypothesis
▪ Disturbances in the dopamine system
may be related to the onset of ADHD
▪ Brain MRI studies indicated a reduction
or even loss of the normal hemispheric
asymmetry in the brain as well as smaller
brain volumes in the prefrontal cortex and
basal ganglia (both rich in dopamine
receptors)
▪ Dopaminergic MOA of medication
treatment for ADHD
▪ Genetic studies have primarily
implicated 2 candidate genes: Dopamine
transporter gene (DAT1) and Dopamine 4
Intellectual disability/GDD
▪ Delays in social and communication skills as
well as stereotyped behavior but social and
communication skills are commensurate with
their cognitive and adaptive functioning
Hearing loss
▪ Poor response to name but typically develop
nonverbal communication and play skills
▪ No stereotyped or restricted behavior patterns
ADHD
▪ May present with reduced eye contact and
response to name caused by poor attention
rather than lack of social awareness
▪ No impairments in shared enjoyment and social
reciprocity or repetitive behaviors
▪ Examination should include
measurement of HC, evaluation for
dysmorphic features, screening for
tuberous sclerosis with Wood lamp
exam, genetic testing, audiology
examination and a lead test (in
children with pica)
Additional medical or behavioral
health treatment is often required
for mgt of co-occurring conditions in
ASD
There are currently no medications
that treat the core symptoms of ASD
Social anxiety
▪ Shy children may have reduced eye contact and
social initiation; Anxious children can be
resistant to change
▪ Have preserved social interest and insight and
will not exhibit high levels of stereotyped
behavior
Reactive attachment disorder
▪ Difficult to distinguish from ASD particularly in
younger children with hx of trauma but social
behaviors improve with positive caretaking
▪ Symptoms vary from motor restlessness and
aggressive and disruptive behavior (common in
preschool children) to disorganized, distractible and
inattentive symptoms (typical in older adolescents
and adults)
▪ Difficult to diagnose in preschoolers because
distractibility and inattention are often considered
developmental norms during this period
Chronic illness
▪
E.g.
migraine,
absence
seizures,
asthma/allergies, hema d/o, diabetes, childhood
CA
▪ Can impair children’s attention and school
performance because of either the disease itself
or the medications used to treat or control the
underlying illness
▪ DSM-V criteria state that the behavior must be
developmentally inappropriate (substantially different
from that of other children of the same age and
developmental level) beginning before 12yo, present
for at least 6 mos. in 2 or more settings as reported
Substance abuse
▪ Can result in declining school performance and
inattentive behavior
Sleep disorders (e.g. OSA)
▪ The clinical interview allows a
comprehensive understanding of
whether the symptoms meet the
diagnostic criteria for ADHD
▪ Behavior rating scales are useful in
establishing the magnitude and
pervasiveness of symptoms but not
sufficient alone to make a diagnosis
Behaviorally Oriented treatments
▪ Goal: identify target behaviors that
cause impairment in the child’s life
and for the child to work on
improving his/her skill in these areas
▪ Modestly successful at improving
core ADHD symptoms
▪ First-line treatment in preschool
age children
▪ No laboratory tests are available to
identify ADHD
● Presence of HTN, ataxia, or
symptoms of sleep or thyroid d/o
Medications
▪ Most widely used medications are
the
presynaptic
dopaminergic
agonists called psychostimulants
Batch Clingy
DISEASE
85
receptor gene (DRD4)
by independent observers and not secondary to
another disorder
▪ Three different presentations of ADHD
● Inattentive: more common in females; assoc. w/
high rates of anxiety and low mood
● Hyperactive-impulsive: more common in males
together w/ combined type
● Combined
(see Nelson’s 21st ed., Table 49.1 for full DSM-V
criteria)
▪ Group of permanent disorders of
movement and posture causing
activity limitation
▪ Most common and costly form of
chronic motor disability that begins
in childhood
CEREBRAL PALSY
Attributed
to
nonprogressive
disturbances in the developing fetal or
infant brain
SPASTIC HEMIPLEGIA
▪ 34% had injury to the white matter
in utero
▪ 27% had a focal lesion resulted
from a stroke
▪ Other children with hemiplegic CP
had malformations from multiple
causes: infections, disorders of
neuronal migration
SPASTIC DIPLEGIA
▪ Strongly associated with damage to
immature WM during the vulnerable
period of immature oligodendroglia
(20-34 wks AOG)
▪ 15% of cases result from in utero
lesions in infants who go on to
delivery at term
Periventricular leukomalacia
▪ Most common neuropathologic finding
▪ Visualized in MRI
SPASTIC QUADRIPLEGIA
▪ Most severe form of CP
▪ Most common lesions: severe PVL and
multicystic cortical encephalomalacia
PPS Oral Exam Reviewer 2020
(see Nelson’s 21st Ed., Table 616.1 for Classification of
Cerebral Palsy and Major Causes)
▪ ↓ Spontaneous movements on the affected side
▪ Hand preference at a very early age
▪ Arm often more involved than the leg
▪ Walking is delayed until 18-24mos with a
circumductive gait
▪ Ankle clonus and Babinski sign may be present
▪ Approx. 25% have cognitive abnormalities including
ID
▪ 1/3 have a seizure disorder that usually develops in
the first 2yrs
▪ Bilateral spasticity of the legs > arms
▪ Infants uses arms normally when crawling but drags
the legs behind (commando crawl) instead of 4limbed crawl
▪ Spastic legs with brisk reflexes, ankle clonus and
bilateral Babinski
▪ Scissoring posture of the LE when suspended by the
axillae
▪ Likelihood of seizures is minimal
▪ Normal intellectual development
▪ Some may have learning disabilities or vision
abnormalities
▪ Marked motor impairment of all extremities
▪ High assoc. with ID and seizures
▪ Swallowing difficulties → aspiration pneumonia and
growth failure
▪ ↑ Tone and spasticity in all extremities, ↓
▪ Can result in behavioral and emotional
symptoms that can resemble or exacerbate
ADHD
should prompt work-up
▪ Identify any possible vision or
hearing problems
Depression and anxiety disorders
▪ Can mimic sx of ADHD but can also be a comorbid condition
(e.g.
methylphenidate,
dexmethylphenidate, amphetamine)
▪ Children with a positive personal or
FHx of cardiomyopathy, arrhythmias,
or syncope require an ECG and
possible cardio consult before
starting stimulants
OCD
▪ Can mimic ADHD esp. when recurrent and
persistent thoughts, impulses or images are
intrusive and interfere with normal activities
Adjustment disorders
▪ Can result in symptoms similar to ADHD
▪ Hereditary spastic diplegias
▪ Monoamine transmitter disorders
IEM
▪ History and PE should r/o a
progressive disorder of the CNS
▪ MRI – to determine the location
and extent of structural lesions or
assoc. congenital malformations
▪ Test of hearing and visual function
▪ IV MgSO4 – for mothers in
premature labor with birth imminent
<32wks showed significant ↓ in the
risk of CP at 2yo
▪ Cooling term infants with HIE to
33.3OC x 3 days within 6h of birth –
↓ the risk of dyskinetic or spastic
quadriplegia
▪ Multidisciplinary mgt. is needed
▪ Drugs for spasticity: Baclofen,
Botox
▪ Movement of the good side is
constrained with casts
▪ The impaired extremities perform
exercises that induce improved hand
and arm functioning
▪ Treated initially with assistive
equipment – orthoses, walkers,
poles, standing frames
▪ Rhizotomy procedure – produces
considerable
improvement
in
selected patients with severe spastic
diplegia and little or no basal ganglia
involvement
▪ Motorized wheelchairs
▪ Special feeding devices
▪ Modified typewriters
▪ Customized seating arrangements
Batch Clingy
more likely to experience birth
complica-tions (e.g. toxemia, lengthy
labor, complicated delivery)
● Maternal drug use
● Maternal smoking, alcohol use
during pregnancy, and prenatal or
postnatal exposure to lead
86
ATHETOID (extrapyramidal) CP
▪ Most likely to be associated to birth
asphyxia
● Assoc. with bilaterally symmetric
lesions in the posterior putamen and
ventrolateral thalamus
▪ Can also be caused by kernicterus
▪ MRI: lesions in the globus pallidus
bilaterally
▪ Group of disorders that have in
common significant impairment in
general intellectual function, social
skills, and adaptive behavior
▪ >2/3 will not have a readily identifiable
underlying diagnosis
▪ 2 overlapping populations of children
with ID with differing corresponding
etiologies
▪ Mild ID: assoc. more with environmental
influences; highest risk among children of
low socioeconomic status
▪ Most common biologic causes of mild
ID: genetic or chromosomal syndromes
with multiple, major, or minor congenital
anomalies, IUGR, prematurity, perinatal
insults, intrauterine exposure to drugs
and sex chromosomal abnormalities
▪ Severe ID: more freq. linked to biologic
and genetic causes (e.g. chromosomal and
other geneic and epigenetic disorders,
abnormalities of brain development, IEM,
neurodegenerative d/o)
▪ Nonsyndromic severe ID may be a result
of inherited or de novo gene mutations,
as
well
as
microdeletions
or
microduplications not detected on
standard chromosomal analysis
Global Developmental Delay
▪ Diagnosis given to children <5yo
who display significant delay (> 2SD)
in acquiring early childhood devt’l.
milestones in ≥2 domains (receptive
and expressive language, gross and
fine motor function, cognition, social
and personal development, ADLs)
▪ Not all children who meet criteria
for GDD go on to meet criteria for ID
after 5 yo
INTELLECTUAL
DISABILITY
spontaneous movements, brisk reflexes, plantar
extensor responses
▪ Speech and visual abnormalities
▪ Infants are characteristically hypotonic with poor
head control and marked head lag
▪ Develop variably increased tone with rigidity and
dystonia
▪ UE are more affected than LE
▪ Tongue thrust and drooling are prominent
▪ Speech is affected d/t oropharyngeal muscle
involvement
▪ UMN signs are not present, seizures are uncommon,
intellect is preserved
Significant impairment in general intellectual
function
▪ Performance on an individually administered test of
intelligence that is approx. 2 SD below the mean
Significant impairment in adaptive behavior
▪ The degree that the cognitive dysfunction impairs
daily function
▪ Adaptive behavior: skills required for people to
function in their everyday lives
▪ 3 broad set skills: conceptual, social and practical
● Conceptual skill: language, reading, writing,
time, number concepts, and self-direction
● Social skills: interpersonal skills, personal and
social responsibility, self-esteem, gullibility, naiveté,
and ability to follow rules, obey laws, and avoid
victimization
● Practical skills: ADLs (dressing, feeding,
toileting/bathing, mobility), instrumental ADLs
(housework, managing money, taking medication,
shopping,
preparing
meals,
using
phone),
occupational skills, and maintenance of a safe
environment
▪ For a deficit to be present, a significant delay in at
least 1 of the 3 skill areas must be present
Onset before age 18 y/o or adulthood
▪ Distinguishes dysfunctions that originate during the
developmental period
▪ Diagnosis of ID may be made after 18yo but the
cognitive and adaptive dysfunction must have been
manifested before age 18
▪ Sensory deficits – severe hearing and vision loss
▪ Communication disorders
▪ Refractory seizure disorders
▪ Poorly controlled mood disorders
▪ Unmanaged severe attention deficits can mimic
ID
▪ Many children with CP or ASD also have ID
(see Nelson’s 21st ed., Fig. 53.1 for
algorithm for the evaluation of the
child with unexplained GDD or ID)
Microarray
analysis:
replaced
karyotyping as first-tier testing
▪ A child with a progressive
neurologic disorder, developmental
regression or acute behavioral
changes
needs
metabolic
investigation
▪ A child with seizure-like episodes
should have an EEG
▪ MRI of the brain may be useful in
some instances
▪ Interdisciplinary mgt
▪ Periodic reevaluation
▪ Family counseling
▪ Transition to adulthood
(see Nelson’s 21st ed., Table 53.5 for
Suggested Evaluation of the Child
with ID or GDD)
Bayley Scales of Infant and Toddler
Development
▪ Most commonly used infant
intelligence test
▪ Used in children between 1-42
mos.
▪ Differentiates infants with severe
ID from typically developing infants
Wechsler Scales
▪ Most commonly used test for
children older than 3yo
Batch Clingy
(see Nelson’s 21st ed., Table 53.4 for Common
Presentations of Intellectual Disability by Age)
PPS Oral Exam Reviewer 2020
87
SLD with an impairment in math /
Math learning disability (MLD)
▪ Difficulties mastering number
sense, number facts, or fluent
calculation and difficulties with math
reasoning (DSM-V)
SPECIFIC LEARNING
DISORDER
(SLD)
SLD with impairment in written
expression (IWE)
Oral language
▪ Complex process that typically
develops in the absence of formal
instruction
Written language
▪ Requires instruction in acquisition
(word
reading),
understanding
(reading
comprehension),
and
expression
(spelling
and
composition)
Broad Cognitive Processes
▪ Children with MLD have significantly
poorer math achievement than children
with low IQ and have severe deficits in
math not accounted for by their cognitive
functioning
▪ Children with MLD have shown deficits
in working memory and are often slower
to complete math problems than their
typically developing peers
Math Specific Processes
▪ Procedural Errors
▪ The type of errors made by children with
MLD are typical for any child but with a 23year lag in understanding the concept
▪ Memory for Math Facts
▪ Committing math facts to or retrieving
facts from memory have consistently
been found to be problematic for children
with MLD
Children with IEW have skill deficits in:
Transcription
▪ Tend to write slowly, or when writing at
reasonable speed, the legibility degrades
Oral Language
▪ Writing difficulties are assoc. with
deficits in both expression and
comprehension of oral language
▪ Symptoms in the DSM-V criteria must be present for
a minimum of 6 months and persist despite
interventions to address the learning challenges
▪ Risk Factors for MLD:
● Child is at or below the 20 th percentile in any
math area, as reflected by standardized testing or
ongoing measures of progress monitoring
● Teacher expresses concern about the child’s
ability to “take the next step” in math
● Positive FHx for MLD
▪ Parents think they have to “reteach” math concepts
to their child
▪ Explicit instruction on solving
specific types of problems: most
effective intervention
(see Nelson’s 21st ed., Table 51.3 for full DSM-V
criteria)
▪ Weak graphomotor skills may not
necessarily require intervention from
an OT but may help
▪ Explicit instruction of writing
strategies
combined
with
implementation and coaching in selfregulation
Dysgraphia
▪ Often used synonymously with IWE but the two are
distinct conditions
▪ Primarily a deficit in motor output (paper/pencil
skills) and IWE is a conceptual weakness in
developing, organizing, and elaborating on ideas in
writing
Executive Functions
▪ Poor writers seldom engage in the
necessary planning and struggle to selfmonitor and revise effectively
Batch Clingy
Working Memory
▪ Weak WM limits the space available to
devote to other tasks
PPS Oral Exam Reviewer 2020
88
IRON
DEFICIENCY
ANEMIA
G6PD
DEFICIENCY
THALASSEMIA
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ 2% of adolescent girls – secondary to adolescent growth spurt and
menstrual blood loss
▪ Teenagers who are or have been pregnant – highest risk of IDA (>30%)
▪ Breastfed infants absorb iron 2-3x more efficiently than infants fed
cow’s milk but are at risk of developing IDA if without regular intake of
iron-fortified food by 6mos old
▪ In neonates, iron is in circulating Hgb → Hgb levels fall during the first
2-3 mos of life → iron is recycled and sufficient for blood formation in
the first 6-9 mos of life (if term)
▪ In infants and toddlers, due to excessive consumption of cow’s milk
(low iron content, blood loss from milk protein colitis) in a child who is
often overweight or bottle feeding beyond 12mos old
▪ May be due to blood loss – menstrual losses, recurrent nosebleeds,
intravascular hemolysis with hemoglobinuria (e.g. in malaria), peptic
ulcer, Meckel diverticulum, polyp, hemangioma, IBD, chronic diarrhea,
chronic intestinal blood loss induced by exposure to whole cow’s milk
protein
▪ Hookworm infections (developing countries) – Trichuris trichiura,
Plasmodium
▪ Gastric bypass procedures / H. pylori infection – interferes with iron
absorption since iron is absorbed in the proximal duodenum by the
assistance of gastric acid
Acute
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS/DIAGNOSIS
▪ Most are asymptomatic
▪ ↓ serum ferritin (depleted tissue iron stores) → ↓ serum iron
▪ Pallor – most recognized clinical sign (Hgb 7-8mg/dL)
→ ↑ serum transferrin → ↓ transferrin saturation
▪ Depleted iron stores → iron is unavailable to form with
Mild to Moderate IDA (Hgb 6-10g/dL)
protoporphyrin to form heme → impaired Hgb synthesis → no
▪ Mild irritability only because of effective compensatory
available Hgb in each cell → ↓and varied RBC size (↑ RDW), ↓
mechanisms (↑2,3 DPG; shift of O2 dissociation curve)
MCV and MCH, ↓ RBC count
▪ ↑ TIBC
Severe (Hgb <5g/dL)
▪ N or mod ↑ reticulocyte count
▪ Irritability, anorexia, lethargy, systolic flow murmurs
▪ Elliptocytic or cigar shaped cells are often seen
▪ Tachycardia and high output cardiac failure can occur
▪ Bone marrow iron staining – most accurate method of
diagnosing IDA; invasive, expensive, unnecessary
Non-hematologic systemic effects:
▪ N WBC count, often ↑ platelet
▪ Impaired neurocognitive function in infancy → may
▪ Occult blood test (stool) – to exclude blood loss as case of IDA
lead to irreversible cognitive defects
▪ Pica (nonnutritive substances) → ingestion of leadSerum ferritin
containing substances → plumbism
▪ Iron-storage protein, provides an estimate of body iron stores in
▪ Pagophagia (ice)
the absence of inflammatory disease
▪ A low SF value is diagnostic of IDA in a patient with anemia
Serum transferrin
▪ Iron binding capacity of the serum
Increase in Hgb ≥1g/dL after 1 mo of iron therapy – most
practical means to establish the diagnosis
▪ Most frequent disease involving enzymes of the HMP
▪ Asymptomatic
▪ Precipitous fall in Hgb and Hct
▪ X-linked deficiency; inheritance of any of a large number of abnormal
▪ Neonatal jaundice and hemolytic anemia if triggered by
▪ If severe, haptoglobulin (Hgb binding protein) are saturated, and
alleles of the gene responsible for the synthesis of the G6PD protein
infection, drugs (ASA, sulfonamides, rasburicase,
free Hgb may appear in plasma and urine
▪ 4.9% global prevalence, M>F
antimalarials), or ingestion of fava beans
▪ Heinz bodies (precipitated Hgb) – seen only within the first 3-4
▪ 2 clinical syndromes
▪ Hemolysis after 24-48hrs of ingestion of substances
days of illness in unstained RBCs, rapidly cleared from the blood
● Episodic hemolytic anemia
with oxidant properties → hemoglobinuria and jaundice
▪ Bite cells
● Chronic, nonspherocytic hemolytic anemia
if severe → ↓ Hgb level
▪ Polychromasia – bluish, larger RBCs; represent reticulocytosis
▪ Glucose 6 phosphate → G6PD → phosphogluconic acid → NADPH →
▪ The dx is suspected when G6PD is within the low-normal range
GSH (reduced, functional form of glutathione)
▪ Favism – acute severe hemolytic syndrome (more of
in the presence of a high reticulocyte count
▪ GSH – provides protection against oxidant threats from certain drugs
G6PD B-variant); fava beans contain divicine, isouramil,
▪ Newborn screening – confirmatory test to check enzyme activity
and infection that can cause precipitation of Hgb (Heinz bodies) or
and convicine → production of H2O2 and other reactive
damage RBC membrane
O2 products
▪ Disorders of globin chain production – imbalance between the α and β globin chains
▪ Primary pathology stems from the quantity of globin produced
▪ Inadequate β-globin gene production leading to ↓HbA + unbalanced α- and β-globin chain production leading to ineffective erythropoiesis
α – THALASSEMIA
α-thalassemia trait – microcytic anemia that can be
α-thalassemia trait – N Hgb analysis except in the NB period;
▪ Absence or ↓ α-globin production due to deletions of α-globin genes
mistaken as IDA
↓MCV and MCH
α0-thalassemia – no α-chains produced from that chromosome (--/)
α+-thalassemia – ↓ amount of α-globin chain (-alpha/)
Silent carrier – deletion of 1 α-globin gene; common in African
Americans
α-thalassemia trait – deletion of 2 α-globin genes
HbH Disease – deletion of 3 α-globin genes
Hydrops fetalis – complete absence of the α-globin chain (4)
▪ ↓ α-globin chains → excess of β- and γ-globin chains → Bart Hgb in
PPS Oral Exam Reviewer 2020
HbH Disease – mild splenomegaly, scleral icterus,
cholelithiasis
Hydrops fetalis
● In utero anemia, fetal loss d/t insufficient α-chains
needed to produce HbF
● Intrauterine infusions may rescue the fetus but
congenital abnormalities and neurodevelopmental delay
often result
HbH Disease – diagnosed in the NB period: >25% HbH, (+) Bart
Hgb; marked microcytosis, anemia, Hgb range 7-11g/dL, MCV 5173fL
Silent Carrier – not identified hematologically; diagnosed after the
birth of a child with a 2-gene deletion or HbH
DIFFERENTIALS
Alpha/Beta thalassemia
▪ N/↑ RBC
▪ N serum ferritin, TIBC,
and transferrin saturation
Anemia of Inflammation
▪ Usually normocytic but
can also be microcytic
▪ ↑ Serum ferritin
▪ ↓ TIBC
TREATMENT
▪ 3-6mkday elemental iron QD or BID (max
150-200 mg/day) for 2-3 months
▪ Dietary counselling – limit cow’s milk,
increase dietary iron
▪ If mild anemia – repeat CBC after 4 weeks.
Hgb must in↑ by at least 1-2g/dL and has
often normalized
▪ If severe, reticulocytosis within 2-4d. Hgb
will then start to ↑ by 0.1-0.4 g/dL/day
▪ Blood transfusion – if with heart failure or
with ongoing blood loss
Lead poisoning
▪ Microcytic
PREVENTION
▪ Breastfeeding
▪ At 4mos, add supplemental iron
▪ If not BF, use iron-fortified formula (12mg
Fe/L) for the 1st year then limit cow’s milk to
<20-24oz/d thereafter – encourages the
ingestion of foods richer in iron, prevents
blood loss as a result of cow’s milk-induced
enteropathy
▪ Routine screening (H&H) at 9-12mos, earlier
if at 4 mos assessed to be high risk for iron
deficiency
▪ Prevention of hemolysis is the most important therapeutic measure
▪ The usual doses of ASA and TMP-SMX do not cause clinically relevant
hemolysis in the A- variety
▪ ASA used for acute rheumatic fever (60-100mkday) may produce a severe
hemolytic episode
▪ Infants with severe neonatal jaundice require G6PD deficiency testing
▪ If with severe hemolysis, may require blood transfusions although
recovery is the rule when the oxidant agent is discontinued
▪ Parental and Family Testing
▪ Detailed family/genetic counseling
▪ Lifelong transfusion dependence if severe
HbH Disease
▪ On going monitoring of growth and organ dysfunction
▪ Dietary supplement with folate
▪ MVTs without iron – because of risk of iron overload
▪ Vit D supplementation if level is low
▪ Adequate dietary calcium intake
▪ Intermittent transfusion requirements during intercurrent infection
▪ Splenectomy in some patients → ASA or other anticoagulant therapy postop due to high risk of thrombosis
▪ Avoid oxidative medications
Batch Clingy
DISEASE
89
β0-thalassemia – absence of production of β-globin; homozygous for
the β0 gene; 15-20% may have a clinical course similar to β-thalassemia
intermedia
β+-thalassemia – ↓ amount of normal β-globin (HbA); 25% may have
transfusion-dependent thalassemia
β-thalassemia major – transfusion-dependent
β-thalassemia intermedia – non-transfusion dependent
Carrier – has a single β-globin mutation
▪ ↓ β-globin chains → excess in α-globin chains → formation of αglobin tetramers (α4) w/c appear as RBC inclusions → precipitate in RBC
precursors → damaged RBC membrane → shortened RBC survival →
anemia + ↑ erythroid production → early erythroid precursor death in
the BM
▪ Chronic anemia + ↑ erythroid drive → ↑ iron absorption from the
GIT → 2o hemosiderosis-induced organ injury
▪ No/↓ β-globin chains → α-chains combine with γ-chains → HbF (α
2γ2)
Signs of Ineffective Erythropoiesis
● Growth failure
● Bone deformities 2o to BM expansion
● Hepatosplenomegaly
Classic presentation of a child with severe disease – 1o
seen in countries w/o access to chronic transfusion
therapy; may develop in patients with mod anemia d/t
severe compensatory ineffective erythropoiesis
● Thalassemic Facies – maxillary hyperplasia, flat nasal
bridge, frontal bossing
● Pathologic bone fractures
● Marked hepatosplenomegaly
● Cachexia
Carrier – generally asymptomatic,
microcytosis and mild anemia
except
for
β0-thalassemia – progressive anemia, profound
weakness, cardiac decompensation during the 2 nd 6mos
of life
β-thalassemia intermedia
▪ May not be chronically transfused after infancy but may
be sporadically transfused throughout their lifetime
▪ Microcytic anemia w/ Hgb ~7g/dL (range 6-10g/dL)
▪ Many develop hemosiderosis 2 o to increased GI
absorption of iron-requiring chelation
β-thalassemia major – symptomatic only after birth
when HbA predominates
Thalassemia Trait
▪ Often misdiagnosed as IDA; use a short course of iron
to identify if further evaluation is needed
▪ Persistently N RDW, ↓ MCV
▪ On Hb analysis, ↑ HbA2 and variably ↑ HbF
▪ Microcytosis, hypochromia, target cells, nucleated RBCs, marked
anisopoikilocytosis, relative reticulocytopenia
▪ Progressive fall in Hgb to <6g/dL unless given transfusions
▪ Inappropriately low reticulocyte count (<8%) compared to the
degree of anemia caused by ineffective erythropoiesis
▪ Elevated unconjugated serum bilirubin
▪ Newborn Screening
● Not definitive
● Detection of only HbF on Hgb electrophoresis in those with βthalassemia major
● Detection of Hgb FE pattern in Hgb E β0-thalassemia
▪ DNA Diagnosis + testing for common genetic modifiers of the
clinical phenotype is recommended
COMPLICATIONS
▪ Transfusion-induced hemosiderosis
● Major clinical complication of transfusion-dependent
thalassemia
● Physiologically, the body cannot eliminate excess iron
● Fe is deposited in the liver → endocrine organs
(hypothyroidism, hypogonadotropic gonadism, GH deficiency,
hypoparathyroidism, DM) → heart (heart failure, arrhythmias)
● Prevented by iron chelation therapy
▪ Heart Disease – leading cause of death in inadequately chelated
patients
▪ Even if the child does not receive transfusions, iron eventually
accumulates with ↑ serum ferritin and transferrin saturation
PREVENTIVE MONITORING
▪ Cardiac Disease
● Serial echocardiograms – evaluate cardiac function & PAP
● Cardiac T2* MRI – after ~8y of chronic transfusion therapy
(when cardiac hemosiderosis may occur)
● Periodic ECG – after 10yo due to risk of arrhythmia from
cardiac iron overload
▪ Endocrine Disease
● Monitoring for dysfunction starting at 5yo or after at least 3y
of chronic transfusions
● Monitor height, weight, pubertal assessment, and sitting
height semiannually
● Bone density starting in the 2nd decade of life d/t risk of
osteopenia
● Nutritional assessments
● Vit C, D, and zinc replacement
● Routine assessment of fertility
▪ Psychosocial Support
● Culturally sensitive anticipatory counselling
● Early social service consultation to address financial and
social issues
▪ At-risk couples for hydrops fetalis should be offered molecular diagnosis
on fetal tissue obtained early in pregnancy
TRANSFUSION THERAPY
▪ Improves the quality of life and reduces the complications of severe
disease
▪ 1mL pRBC contains ~1mg of iron
▪ Transfuse every 3-4 weeks
▪ Goal: maintain a pretransfusion Hgb of 9.5-10.5g/dL
▪ Give RBCs depleted of leukocytes and matched for D, C, c, E, e, and Kell
antigens
▪ If stem cell transplant candidate, transfuse CMV-safe units
IRON OVERLOAD MONITORING
▪ Serial serum ferritin levels – screen for iron balance trends but may not
accurately predict quantitative iron stores
▪ Quantitative Liver Iron approved by R2 or R2* MRI – best indicator of total
body iron stores; should be obtained after starting chronic transfusion
therapy
▪ Quantitative cardiac iron by T2* MRI – obtained at 10yo, earlier if w/
severe iron overload or if transfusion & chelation history is unknown
CHELATION THERAPY
▪ To prevent hemosiderosis-induced tissue injury
▪ Start as soon as the patient becomes significantly iron-overloaded:
● Generally, occurs after 1yr of transfusion therapy
● Serum ferritin >1000ng/dL and/or
● Liver iron concentration >5000mcg/g dry weight
IRON CHELATORS
▪ Deferoxamine (Desferal) – SC/IV due to poor oral bioavailability and short
half-life (<30mins)
● 25 to 60mg/kg (in heavily iron-overloaded patients)
● May be given as continuous infusion over at least 8h/day, 5-7days/wk
● AE: local skin reaction, ototoxicity, retinal changes, bone dysplasia with
truncal shortening
▪ Deferasirox – PO QD, half-life >16h
● Dispersible tablet – 20 to 40mkday depending on the iron burden;
dissolved in water or juice
● Film-coated tablet and granule – dose is 30% lower, 14-28mkday
● AE: GI symptoms, hepatic transaminitis (>5x the UL of N), potential
kidney damage (occur commonly in the setting of dehydration)
▪ Deferiprone – 75-99mkday PO TID, half-life 3h
● Effectively enters cardiac tissue thus, more effective in reducing
cardiac hemosiderosis
● AE: transient agranulocytosis (1%)
▪ Deferoxamine + Deferiprone for those with increased cardiac iron
HYDROXYUREA
▪ DNA antimetabolite; increases HbF production; 10-20mkday
▪ Used in β-thalassemia intermedia patients
▪ Mean increase in Hgb of 1g/dL (range 0.1-2.5g/dL)
▪ Reduces risk of leg ulcers, pulmonary HTN, and extramedullary
hematopoiesis
▪ AE: cytopenias
HEMATOPOIETIC STEM CELL TRANSPLANTATION
PPS Oral Exam Reviewer 2020
Batch Clingy
fetal life (γ4) → HbH (β4) after birth →
▪ Most frequent in SE Asia (5-10% carry alleles)
β – THALASSEMIA
▪ Usually requires a β-thalassemia mutation in both β-globin genes
▪ Ineffective erythropoiesis + massive marrow expansion
90
▪ All children who have an HLA-matched sibling should be offered BM
transplant
▪ At least 90% survival, 80% event-free survival
▪ Clinically, lead is purely a toxicant
▪ May occur in utero thru redistribution from endogenous stores i.e. the
mother’s skeleton or newly acquired from ongoing environmental
exposure (lead readily crosses the placenta from maternal blood)
▪ Batteries, paint, cable sheathing, cosmetics, mineral supplements,
plastics, toys, traditional medicines
LEAD
POISONING
▪ Non-nutritive hand-to-mouth activity of young children – most
common pathway for lead to enter the body, some through the skin
▪ Lead is more absorbed in an empty stomach; calcium and iron
decrease lead absorption by direct competition for binding sites
▪ Lead circulates in the body bound to erythrocytes (97%)
▪ Most retained lead accumulates in bone (resides for years) but it has
multiple effects in all cells
Mechanisms of Lead Toxicity
▪ Binds to enzymes with sulfhydryl groups → changed contour →
decreased function; accumulation of excess amounts of heme
precursors are toxic
▪ Competes with calcium → abnormal intra- and intercellular signaling
(e.g. neurotransmitter release)
▪ Affects the normal neuronal pruning process → elimination of
multiple intercellular brain connections → prevention of the
development of the normal tertiary brain structure
GI Symptoms (BLL >20mcg/dL)
▪ Anorexia, abdominal pain, vomiting, and constipation,
occurring and recurring over a period of weeks
CNS Symptoms (BLL >100mcg/dL; may be seen as low as
70mcg/dL)
▪ Related to worsening cerebral edema and increased ICP
▪ Headache, change in mentation, lethargy, papilledema,
seizures, coma → death
▪ Blood Lead Level (BLL) – gold standard
● ≥5mcg/dL – (+) exposure; requires second round of testing
● ≥45mcg/dL – requires prompt chelation therapy
▪ Erythrocyte Protoporphyrin (EP) Level
● >35mcg/dL – (+) lead poisoning, iron deficiency, or recent
inflammatory disease
● Useful for monitoring biochemical lead toxicity
● If elevated, can be an indicator of lead effect and a useful
means of assessing the success of treatment
● Will begin to fall a few weeks after successful interventions
▪ X-ray fluorescence (XRF) – assess bone lead stores; not available
for clinical use in children
▪ Urine lead level – spontaneous lead excretion is low even with
high BLLs; excretion may be stimulated by treatment with
chelating agents
▪ KUB Radiograph – radiopaque flecks in the intestinal tract
consistent with recent ingestion of lead-containing plaster or paint
chips; absence of flecks does not rule out lead poisoning; used in
children with acute symptoms and whose BLL result is not
immediately available
Other organs
▪ Renal tubular dysfunction (BLL >100)
▪ Reversible fanconi syndrome
▪ ↓ RBC survival → hemolytic anemia
▪ Iron deficiency and hemoglobinopathies → anemia
▪ Peripheral neuropathy → wrist drop, foot drop, HTN
Physiologic Anemia of Prematurity
▪ Decline is more extreme and rapid
▪ At 3-6 wks old, Hgb 7-9 g/dL; may be lower in very small premature infants
▪ Same mechanism as term infants but exaggerated; intensified by blood loss from repeated phlebotomies
▪ Shortened RBC lifespan (40-60 days), accelerated RBC mass expansion
▪ In utero, liver produces EPO. If born preterm, still relies on the liver (no switch to kidney yet) → diminished responsiveness to
anemia
Drug treatment
▪ Given if BLL ≥45mcg/dL
▪ 2,3-DMSA and Penicillamine – given PO
▪ CaNa2EDTA and BAL dimercaprol – given IV
▪ BLL 44-70 mcg/dL – monotherapy (preferably DMSA)
▪ BLL >70mcg/dL – two-drug treatment
● CaNa2EDTA + DMSA or BAL – if (-) encephalopathy
● CaNa2EDTA + BAL – if (+) encephalopathy
▪ No drug removes ALL lead from the body
▪ Within days to weeks after completion of treatment, BLL rises, due to
presence of lead in bone. If BLL rebounds to ≥45mcg/dL, repeat chelation.
Drug-related toxicities
▪ GI distress, transient elevation in transaminases, active urinary sediment,
neutropenia
PREVENTION
▪ Handwashing immediately before nutritive hand-to-mouth activity
Term
▪ No treatment
▪ Ensure proper diet
Preterm
▪ Transfusions may be needed (pRBC 10-15mL/kg)
▪ If feeding well and growing normally with no iatrogenic blood loss, no
treatment
▪ Iron therapy (1-2mkday of elemental iron) starting at 1 month of age until
1yo
Batch Clingy
PHYSIOLOGIC
ANEMIA OF
INFANCY
▪ Physiologic adaptation to extrauterine life
▪ At birth, term infants have higher Hgb levels and larger RBCs than
older children and adults
▪ 1st week of life, decline in levels and persists for 6-8 weeks
▪ Onset of respiration, more oxygen for Hgb binding → switch from HbF
(high oxygen affinity) to adult Hgb (low oxygen affinity) synthesis →
increase in blood oxygen content and delivery → downregulation of
EPO production → suppression of erythropoiesis → removed aged
RBCs are not replaced → decreased Hgb levels
▪ Hgb level declines until tissue oxygen needs > O2 delivery – reached
between 8-12 wks old (Hgb 11g/dL) → increased EPO production →
erythropoiesis resumes
▪ May be aggravated by folic acid deficiency
▪ Shorter height – for every 10mcg increase in BLL, the
child is 1cm shorter
▪ Decreased cognitive test scores
▪ Delayed puberty – chronic lead exposure
▪ Hyperactivity in young school aged children
▪ Aggression and behaviors predictive of later juvenile
delinquency in older children with higher bone lead
content
SPLENECTOMY
▪ For those who develop hypersplenism – falling steady-state Hgb level
and/or a rising transfusion requirement
Main goals: Prevent cognitive/behavioral effects from occurring and
prevent further ingestion
▪ Identify and eliminate environmental sources of lead exposure
▪ Reduce nonnutritive hand-to-mouth activity
▪ Dietary counseling – ensure sufficient intake of calcium (1g/day) and iron
(6mg/day for infants, 12mg/day for adolescents)
PPS Oral Exam Reviewer 2020
91
Complex
DISEASE
ANEMIA OF
CHRONIC
DISEASE
(Anemia of
Inflammation)
ETIOLOGY/INCIDENCE/ PATHOGENESIS
▪ Found in conditions where there is ongoing immune activation –
infections, malignancies, chronic renal disease, autoimmunity, GVHD
CLINICAL MANIFESTATIONS
▪ Mild to moderate anemia
▪ The important signs and symptoms are those of the
underlying disease
▪ ↓ RBC life span
▪ Inflammation-associated excess synthesis of hepcidin (key regulatory
protein that controls intestinal iron absorption and tissue distribution)
→ alterations in Fe metabolism
▪ Low levels of serum Fe → accumulation of Fe in RE macrophages →
functional Fe deficiency → impaired heme synthesis and Fe-restricted
erythropoiesis → anemia
DIAGNOSIS
▪ Hgb is generally at 6-9 g/dL
▪ Often normocytic, normochromic anemia but some may have
modest hypochromia and microcytosis if there is concomitant Fe
deficiency
▪ N/↓ absolute reticulocyte count
▪ Leukocytosis
▪ ↓ serum iron, low to normal serum transferrin
▪ Serum ferritin may be elevated secondary to inflammation
▪ BM has normal cellularity; adequate/↓ RBC precursors
▪ ↑ Marrow hemosiderin; granulocytic hyperplasia may be
present
▪ Soluble transferring receptor (sTfR) – diagnostic test to
distinguish ACD from IDA; N in ACD, ↑ in IDA
TREATMENT
▪ Treat the underlying disorder
▪ If the associated systemic disease can be controlled, the anemia will
improve or resolve
▪ Transfusions raise the Hgb concentration temporarily but are rarely
indicated
▪ Recombinant human EPO increase the Hgb level and improve activity and
the sense of well-being. Give iron to produce optimal effect.
▪ ACD does not respond to iron alone unless there is concomitant
deficiency
Chronic
LEUKEMIA
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINCAL MANIFESTATIONS
LABORATORY FINDINGS / DIAGNOSIS
▪ Most common malignant neoplasms in childhood (31% of all malignancies in <15yo)
▪ Group of malignant diseases where genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells
▪ Cells have ↑ proliferation and ↓ spontaneous apoptosis → disrupted normal marrow function → marrow failure
▪ See table 522.1 for the factors predisposing to childhood leukemia
ACUTE LYMPHOBLASTIC LEUKEMIA
▪ Initial presentation is nonspecific and brief
▪ Polymerase Chain Reaction (PCR) and Fluorescence in situ
▪ 77% of childhood leukemia
▪ Anorexia, fatigue, malaise, irritability, intermittent lowhybridization (FISH) – pinpoint molecular genetic abnormalities,
▪ Peak incidence at 2-3yo and more common in boys
grade fever, bone/joint pain (lower extremities)
can be used to detect small numbers of malignant cells at
▪ More common in children with chromosomal
▪ Severe pain that can wake the patient at night
diagnosis as well as during follow-up (MRD, minimal residual
abnormalities – Down syndrome, Blood syndrome, ataxia▪ Sometimes, symptoms may be of several months’
disease)
telangiectasia, Fanconi anemia
duration, may be localized predominantly to the
▪ Morphology alone is often adequate to establish a diagnosis
▪ Unknown etiology, but most are thought to be d/t somatic
bones/joints, and may include joint swelling
▪ Diagnosis is strongly suggested by PBS findings indicating BM
mutations in lymphoid cells
▪ Exquisite tenderness over the bone, joint swelling, and
failure
effusion
▪ Anemia, thrombocytopenia, most present with total leukocyte
B-lymphoblastic Leukemia (85%)
▪ Eventually, SSx of BM failure – pallor, fatigue, exercise
counts <10,000
▪ Onset between 1-10yo
intolerance, bruising, oral mucosal bleeding/ epistaxis,
▪ ± Leukemic cells – often reported as “atypical lymphocytes”
▪ Median leukocyte count at presentation: 33,000
listlessness, purpura and petechiae, mucous membrane
▪ Elevated LDH
T-lymphoblastic Leukemia (15%)
hemorrhage
▪ When PBS suggests leukemia, examine the BM – BMA biopsy,
▪ Has a higher leukocyte count
▪ With marrow involvement, (+) deep bone pain, (-)
flow cytometry, cytogenetics, molecular studies
Burkitt Leukemia
tenderness
▪ >25% Lymphoblasts in the BM – diagnostic of ALL
▪ Rare leukemia of mature B cells
▪ Signs of organ infiltration – lymphadenopathy,
▪ CSF Examination
▪ One of the most rapidly growing cancers in humans
hepatosplenomegaly,
testicular
enlargement,
CNS
● Included in the initial evaluation (if traumatic initial LP, risk
involvement (HA, seizures, cranial neuropathies)
of CNS relapse)
▪ Signs of ↑ ICP (papilledema, retinal hemorrhage, CN
● If (+) lymphoblasts and ↑ leukocyte count, (+) overt CNS or
palsies) – CNS leukemia
meningeal leukemia
o
▪ Respiratory distress – 2 to severe anemia or mediastinal
node compression of the airways (e.g. in thymus/nodes;
DIFFERENTIAL DIAGNOSIS
frequently seen in adolescent boys with T-cell ALL)
▪ Pancytopenia – aplastic anemia, myelofibrosis, familial HLH
▪ Failure of a single cell line – ITP, congenital/ acquired
neutropenia, transient erythroblastopenia of childhood
▪ Acute onset of fever & lymphadenopathy – infectious
mononucleosis
▪ Fever, bone pain, (-) tenderness, joint swelling – JIA
PPS Oral Exam Reviewer 2020
TREATMENT
▪ Treatment is the single most important prognostic factor in ALL
▪ Risk-directed therapy
● Accounts for age at diagnosis, initial WBC count, immunophenotypic and
cytogenetic characteristics of blast populations, rapidity of early treatment
response (how quickly the leukemic cells can be cleared from the
marrow/peripheral blood), and MRD assessment at the end of induction therapy
● Standard Risk: age 1-10y, WBC <50,000
● High Risk: age <1 or >10, WBC >50,000, T-cell immunophenotype, slow
response to initial therapy
▪ Imatinib – inhibits the BCR-ABL kinase resulting from the translocation (t (9;22),
Philadelphia chromosome)
Remission Induction Phase
▪ Initial therapy; to eradicate the leukemic cells from the BM
▪ Given for 4 weeks – Vincristine weekly + CS (dexamethasone/ prednisone) + 1
dose asparaginase
▪ If high risk, add daunomycin weekly
▪ Give intrathecal (IT) chemotherapy at the start of treatment and at least once
more during induction
▪ Remission – <5% blasts in the marrow + return of neutrophil & platelet counts to
near-normal after 4-5 weeks of treatment
Consolidation Phase
▪ Intensive CNS therapy + continued intensive systemic therapy
▪ To prevent later CNS relapses (↓ to <5%)
▪ Give repeated IT chemotherapy by LP
Intensification Phase
▪ To eradicate residual disease
Batch Clingy
DISEASE
92
SUPPORTIVE CARE
▪ Allopurinol/urate oxidase
● Prevent or treat kidney failure associated with ↑ serum uric
acid
▪ Erythrocyte and Platelet Transfusion
● For severe myelosuppression produced by chemotherapy –
requires a high index of suspicion
▪ Aggressive empirical antimicrobial therapy
● For sepsis in children with febrile neutropenia
▪ Antibiotic prophylaxis
● For Pneumocystiis jiroveci pneumonia during chemotherapy
and for several months after treatment completion
▪ Watch out for tumor lysis syndrome as therapy is initiated in
patients with high WBC count
PROGNOSIS
Overall 5yr survival rate: 90%
▪ 14-28 weeks of multiagent chemotherapy – cytarabine, MTX, asparaginase,
vincristine
▪ Delayed intensification – aggressive treatment
▪ Interim maintenance – nontoxic phase
Maintenance Phase
▪ Lasts for 2-3 years
▪ Daily mercaptopurine, weekly oral MTX, with intermittent doses of vincristine
and a corticosteroid
▪ After chemotherapy for 2-3 years, most achieve remission at the end of
induction phase
▪ Minimal Residual Disease
● Provide an estimate of the burden of leukemic cells present in the marrow
● If high at the end of induction phase, poorer prognosis and higher risk of
relapse
● MRD >0.01% on D29 of induction – significant risk factor for shorter eventfree survival for all risk categories, compared with patients with (-) MRD
▪ Adolescents and young adults have an inferior prognosis compared to children
<15yo
Acute Promyelocytic Leukemia (APL)
▪ Subtype that is more common in certain parts of the world
▪ Gene rearrangement involving the retinoic acid receptor
▪ Responsive to all-trans-retinoic acid (ATRA, tretinoin) +
anthracyclines + cytarabine
PPS Oral Exam Reviewer 2020
▪ BM failure → replacement of BM by malignant cells → SSx
of AML
▪ May present with any or all the findings associated with
marrow failure in ALL
▪ Blueberry muffin lesions – subcutaneous nodules; seen
especially in infants
▪ Infiltration of the gingiva
▪ Signs & lab findings of DIC (especially in APL)
▪ Chloromas/granulocytic sarcomas – discrete masses, can
occur in the absence of apparent BM involvement;
associated with t(8;21) translocation
▪ BMA biopsy – hypercellular marrow consisting of a monotonous
pattern of cells, >20% blast cells with features similar to those
that characterize early differentiation states of the myeloidmonocyte-megakaryocyte series of blood cells
▪ Flow cytometry + stains – assist in identifying myeloperoxidasecontaining cells, confirming both the myelogenous origin of the
leukemia and the diagnosis
SUPPORTIVE CARE
▪ Prolonged hospitalization, filgrastim (GCSF), prophylactic
antimicrobials
● Due to prolonged BM suppression with a very high incidence
of serious infections especially viridans streptococcal sepsis and
fungal infection
PROGNOSIS
▪ Remission in 85-90% of patients
▪ Up to 5% die of either infection or bleeding before a remission can be achieved
▪ 60-70% survival rate
Batch Clingy
ACUTE MYELOGENOUS LEUKEMIA
▪ 11% of childhood leukemia
▪ Frequency increases in adolescence – 36% of leukemia in
15-19-year-olds
RELAPSE
▪ Outcomes remain poor among those who relapse
▪ Most important prognostic indicators – time of diagnosis and site of relapsed
disease
Bone Marrow Relapse (15-20% of patients)
● Carries the most serious implications especially if it occurs during or shortly
after completion of therapy
● Treatment: Intensive chemo with agents not previously used followed by
allogeneic stem cell transplantation
CNS Relapse (<5%)
● May be discovered at a routine LP in an asymptomatic patient
● SSx of ↑ ICP and isolated CN palsies
● Diagnosis: (+) Leukemic cells in the CSF
● Treatment: IT chemotherapy, cranial/craniospinal irradiation, must include
systemic chemotherapy (because of high risk for subsequent BM relapse)
Testicular Relapse (<2% of boys)
● Painless swelling of 1 or both testes
● Diagnosis: biopsy of the affected testis
● Treatment: Systemic chemotherapy ± local irradiation
▪ Induction Phase
● Aggressive multiagent chemotherapy – anthracycline + high dose cytarabine
▪ Post remission therapy – chosen based on the 1) cytogenetic and molecular
markers of the leukemia and 2) response to induction chemotherapy (MRD
assessment)
▪ Stem cell transplantation
● Recommended only after a relapse for selected patients with favorable
prognostic features and improved with chemotherapy alone
● May be beneficial in 1st remission to those who have inferior outcome with
chemotherapy
93
2) Transient Myeloproliferative Disorder
▪ 10% of neonates with Down syndrome
▪ Hepatosplenomegaly
▪ High leukocyte count, blast cells in the peripheral blood,
anemia, thrombocytopenia
CHRONIC MYELOGENOUS LEUKEMIA
▪ 2-3% of childhood leukemia
▪ 99% are characterized by a specific translocation,
t(9;22)(q34;q11) – Philadelphia chromosome
▪ Fever, fatigue, weight loss, anorexia
▪ Splenomegaly may be present → LUQ pain
▪ Diagnosis is suggested by a high WBC count with myeloid cells
at all stages of differentiation in the PBS and BM
▪ Diagnosis is confirmed by cytogenetic and molecular studies
that show (+) Philadelphia chromosome and the BCR-ABL gene
rearrangement – characteristic of CML but seen in a small
percentage of ALL
JUVENILE MYELOMONOCYTIC LEUKEMIA
▪ <1% of childhood leukemia
▪ Affects children <2yo
▪ Patients with NF1 and Noonan syndrome have a
predilection for this type of leukemia
INFANT LEUKEMIA
▪ 2% of leukemia during childhood occurs before 1 year old
▪ ALL: AML = 2:1
▪ Leukemic clones in cord blood at birth before symptoms
appear
▪ Chromosome translocation can occur in utero
LYMPHOMA
▪ 3rd most
common cancer
in adolescents
(>25% of newly
diagnosed
cancers in
children 15-19
yo)
HODGKIN LYMPHOMA (HL)
▪ 6% of childhood cancers
▪ Most common malignancy in adolescents (15%)
▪ Bimodal age distribution – 15-35yo and >50yo
▪ In developing countries, the early peak occurs before
adolescence
▪ Male predominance but decreases with age
▪ EBV Infection – 4-fold higher risk of developing HL
▪ Arise in lymphoid tissue and spread to adjacent LN areas
▪ Hematogenous spread → involvement of the liver, spleen,
bone, BM, brain
▪ Reed-Sternberg (RS) Cell
● Pathognomonic of HL
● Large cell with multiple/multilobulated nuclei
● Hallmark of HL but can be found in infectious
PPS Oral Exam Reviewer 2020
Chronic Phase
▪ ↑ Leukocyte count with a predominance of mature forms
but with ↑ numbers of immature granulocytes
▪ Mild anemia, thrombocytosis
▪ Terminates 3-4y after onset
Accelerated Phase (Blast crisis)
▪ Blood counts rise dramatically
▪ Clinical picture is indistinguishable from acute leukemia
▪ Hyperleukocytosis → ↑ blood viscosity → ↓ CNS infection
→ neurologic symptoms
▪ Rash, lymphadenopathy, splenomegaly, hemorrhagic
manifestations
▪ ↑ Leukocyte count
▪ ↑ Monocytes, thrombocytopenia, anemia
erythroblasts
▪ BM: myelodysplastic pattern with <20% blasts
with
(+)
▪ Sensitive to MTX and other antimetabolites – results in substantial toxicity when
standard doses are administered
▪ ALL: outcome of treatment is slightly inferior to that of other children d/t lack of
good prognostic characteristics – ETV6-RUNX1, trisomies, IKZF1
▪ AML: better outcome than non-Down syndrome children; >80% long-term
survival rate
▪ Can require temporary transfusion support
▪ Do not require chemotherapy unless with life-threatening complications
▪ Abnormal PE and blood count resolve within the 1 st 3mos of life
▪ Close follow-up – 20-30% will develop typical leukemia (often acute
megakaryocytic leukemia) by 3yo (mean onset: 16mos)
▪ Imatinib
● Standard treatment for pediatric CML
● Inhibit the BCR-ABL tyrosine kinase
● Produce major cytogenetic responses in >70% of patients
▪ Hydroxyurea – controls the disabling or threatening signs and symptoms during
the chronic phase; gradually returns the leukocyte count to normal
▪ Stem cell transplantation offers the best opportunity for cure but outcomes are
still poor
▪ Extensive tissue infiltration – organomegaly, including CNS
disease
▪ Diffuse pulmonary infiltration by leukemic cells →
leukemia cutis (subcutaneous nodules) and tachypnea
▪ >80% have rearrangements of the KMT2A (MLL) gene – found at
the site of 11q23 band translocation, majority are t(4;11)
▪ Hyperleukocytosis
▪ Large, irregular lymphoblasts, with a phenotype
(-) CD10 marker
▪ Poor prognosis
▪ Painless, nontender, firm, rubbery, cervical, or
supraclavicular lymphadenopathy with some mediastinal
involvement
▪ Hepatosplenomegaly
▪ SSx of airway obstruction – dyspnea, hypoxia, cough
▪ Pleural or pericardial effusion
▪ Hepatocellular dysfunction
▪ Bone marrow infiltration – anemia, neutropenia,
thrombocytopenia
▪ B symptoms
● Unexplained fever >38oC
● Weight loss >10% total body weight over 6mos
● Drenching night sweats
● Others (not of prognostic significance): pruritus,
lethargy, anorexia, pain
▪ Chest Radiography
● Any patient with persistent, unexplained lymphadenopathy
unassociated with inflammation or infection
● To identify the presence of a large mediastinal mass before
undergoing lymph node biopsy
● Determines “bulk” disease
▪ Formal Excisional Biopsy
● Preferred over needle biopsy to ensure that adequate tissue
is obtained
▪ Once the diagnosis is established, determine the extent of
disease
● CT scan of the chest – defines the extent of the mass, hilar
nodes, and pulmonary parenchymal involvement
● CT scans of the neck, abdomen, and pelvis
● BMA biopsy – to rule out advanced disease
● Bone scan – for patients with bone pain and/or ↑ alkaline
▪ Risk adapted – chemotherapy ± low-dose involved-field radiation therapy
▪ Determined largely by disease stage, ± B symptoms, and presence of bulky nodal
disease
Batch Clingy
DOWN SYNDROME and
1) Acute Leukemia
▪ Leukemia is 15-20x more frequently in children with Down
syndrome than in the general population
▪ In the 1st 3yrs of life, AML > ALL
94
mononucleosis, NHL, etc.
● Arises from the germinal center B cells but has lost
most B-cell gene expression and function
▪ HLA-A – asymptomatic patients
▪ HLA-B – patients with any B symptoms
▪ HLA-E – extralymphatic disease 2o to direct extension of an
involved LN region
phosphatase
● Fluorodeoxyglucose (PET) scan – prognostic in HL
▪ CBC to identify abnormalities that might suggest BM
involvement; ESR; Serum ferritin – if abnormal at diagnosis, used
to evaluate treatment effects
PROGNOSIS
▪ 85-90% event-free survival rate (EFS) – for those with favorable
prognostic factors and early-stage disease
▪ >95% overall survival rate (OSR) at 5yrs
▪ 80-85% EFS for those with advanced-stage disease
▪ After relapse, those who relapse >12mo after treatment have
the best prognosis and a long-term survival rate of 40-50%
POOR PROGNOSTIC FEATURES
▪ Reactive infiltration of eosinophils and CD68 + macrophages
▪ ↑ IL-1, IL-6, and TNF
▪ Tumor bulk
▪ Presence of B symptoms
▪ Decreased/slow response to therapy
NONHODGKIN LYMPHOMA (NHL)
▪ 60% of lymphomas in children
▪ 90-95% survival rate for localized disease
▪ 80-95% survival rate for advanced disease
Lymphoblastic Lymphoma (LBL)
PPS Oral Exam Reviewer 2020
▪ Depend on the pathologic subtype and sites of
involvement
▪ 70% present with advanced disease (stage III or IV),
including extranodal disease with bone marrow and CNS
involvement
▪ Painless, rapid, LN involvement
▪ For initial diagnosis: CBC, electrolytes, LDH, BUA, Ca,
phosphorus, BUN, creatinine, bilirubin, alanine & aspartate
aminotransferase, BMA, LP, CXR, Abdominal UTZ
▪ For staging: CT of the neck, chest, abdomen, pelvis
▪ For suspected CNS disease: MRI of the brain and spine
▪ PET Scan – for functional imaging and for judging treatment
RELAPSE
▪ Most occur within the 1st 3years after diagnosis, but may occur as late as 10 yrs
after
▪ Myeloablative Therapy and Autologous Stem Cell Transplant ± RT – for patients
who achieve an initial chemosensitive response but relapse or progress before
12mos from diagnosis
▪ Multiagent systemic chemotherapy and/or immunotherapy with intrathecal
chemotherapy
▪ Surgery – used mainly for diagnosis
▪ Radiation Therapy for special circumstances – CNS involvement in LBL or the
presence of acute superior mediastinal syndrome or paraplegias
▪ Newly diagnosed patients (esp. BL/LBL) are at high risk for TLS
Batch Clingy
COMPLETE RESPONSE
▪ Complete resolution of disease on clinical examination and imaging studies, or at
least 70-80% reduction of disease, and
▪ A change from initial positivity to negativity on PET scanning – reflects residual
fibrosis
95
▪ Arises from precursor T lymphocytes, less often from B
lymphocytes
Mature B-cell Lymphoma
▪ Burkitt Lymphoma (BL) – express the CD20 antigen
▪ Diffuse large B-cell Lymphoma (DLBCL) – express the CD20
antigen
● Germinal center B-cell-like – majority of DLBCL cases;
favorable prognosis
● Activated B-cell-like – poorer prognosis
● Mediastinal B-cell subtype – shares molecular signature
akin to Hodgkin Lymphoma
Anaplastic Large Cell Lymphoma (ALCL)
▪ Most are of mature T-cell origin; express the CD30 antigen
▪ Cough/dyspnea with thoracic involvement
▪ Superior mediastinal syndrome – 2o to a large mediastinal
mass → obstruction of blood flow or respiratory airways
▪ Ascites, ↑ abdominal girth
▪ Intestinal obstruction with an abdominal mass
▪ Nasal congestion, ear pain, hearing loss, tonsil
enlargement with Waldeyer ring involvement
▪ Localized bone pain
▪ Tumor Lysis Syndrome (TLS)
● 2o to rapid cell turnover; common in BL
● ↑ BUA, phosphate, potassium, ↓ calcium
▪ Can present as a life-threatening oncologic emergency
COMPLICATIONS
▪ Multiagent Chemo: Serious mucositis, infections, and
cytopenias that require RBC and platelet transfusions, electrolyte
imbalance, poor nutrition
▪ Long-term complications: Risk of growth retardation cardiac
toxicity, gonadal toxicity with infertility, secondary malignancies
PROGNOSIS
▪ Excellent for most forms
▪ Localized disease: 90-100% survival rate
▪ Advanced disease: 80-95%
● Vigorous hydration + frequent electrolyte monitoring + xanthine oxidase
inhibitor (allopurinol 10mkday PO TID) or urate oxidase (rasburicase 0.2mkday IV
QD x 5d)
▪ Rituximab – mAb directed at CD20’ when combined with standard
chemotherapy, improves outcome
Lymphoblastic Lymphoma
▪ Requires 12-24mos of therapy – chemo, IT, cranial radiation (if CNS +)
▪ Best results are obtained using therapeutic approaches mirroring those of
childhood acute leukemia – induction. Consolidation, interim maintenance,
reinduction (if advanced disease), year-long maintenance phase with 6-MP & MTX
▪ If relapse disease, poor outcome (10% OS)
BL and DLBCL
▪ Give the same mature B-cell NHL chemoimmunotherapy regimen
▪ If with localized disease, chemo for 6 weeks; good prognosis – 4yr overall survival
rate of 90%
▪ If with advanced disease, chemo for 4-6 months – overall survival rate of 79-90%
Primary Mediastinal B-cell Lymphoma (PMBCL)
▪ 2% of mature B-NHLs
▪ Prolonged infusional chemotherapy, rituximab, chimeric antigen receptor cells
expressing anti-CD19 mAbs
Anaplastic Large Cell Lymphoma
▪ If localized disease, surgical resection alone
▪ If advanced, multiagent chemotherapy
Relapsed Non-Hodgkin Lymphoma
▪ Reinduction chemotherapy + allogeneic/autologous stem cell transplantation
except ALCL (prolonged low-dose vinblastine)
▪ MRD – prognostic marker, aids in risk stratification
Batch Clingy
LBL
▪ Symptomatic mediastinal mass
▪ Has a predilection for spreading to the BM, CNS, testes
BL
▪ Diffuse leukemia presentation or massive abdominal
(sporadic type) or head & neck (endemic type) tumor
▪ Can metastasize to the BM or CNS
ALCL
▪ B symptoms can be seen but are not prognostic
▪ Manifests either as a 1o cutaneous manifestation (10%) or
a systemic disease (90%) with dissemination to liver, spleen,
lung, or mediastinum; rare BM/CNS involvement
response
▪ Tumor tissue should be tested by flow cytometry for
immunophenotypic origin (T, B, or null) and cytogenetics
(karyotype)
▪ FISH/RT-PCR – for specific gene translocations, T- and B-cell
gene rearrangement studies, molecular profiling
PPS Oral Exam Reviewer 2020
96
Batch Clingy
PPS Oral Exam Reviewer 2020
97
Acute
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most result from blunt trauma – fall, athletic
activities, motor vehicle crash
Risk Factors
▪ Child – greater risk of blunt renal injury than adults
because the kidneys are not located behind the ribs
▪ Pre-existing renal anomaly – hydronephrosis 2o to
UPJO, horseshoe kidney, renal ectopia
▪ Fall → deceleration injury → injury to the renal
pedicle → interrupted blood flow to the kidney
▪ Blunt lower abdominal trauma in a full bladder →
bladder rupture
▪ Straddle injury → trauma to the bulbous urethra
TRAUMA
CLINICAL MANIFESTATIONS
▪ Gross or microscopic hematuria
▪ Bleeding from the urethral meatus
▪ Abdominal or flank pain
▪ Flank mass
▪ Fractured lower ribs or lumbar transverse processes
▪ Perineal or scrotal hematoma
▪ In >50% of cases, major injuries to the brain, spinal cord,
skeleton, lungs, or abdominal organs
Penile Injury
▪ Uncommon
▪ Can be d/t partial or complete glans amputation during NB
circumcision → immediate surgical repair
▪ Can be during toilet training → injury to the glans if the toilet lid
falls while urinating →
● Hematoma covering the distal half of the glans, no difficulty
urinating → no extensive evaluation
● Inadvertent hair coil injury or strangulation injury → very
narrow constriction → severe distal penile swelling and pain
LABORATORY FINDINGS / DIAGNOSIS
See Figure 561.1
▪ If with significant abdominal injury, gross hematuria or >50RBCs/HPF, or
suspicion of renal injury (deceleration injury, flank pain or bruise), do renal
imaging
▪ Catheterize the bladder unless blood is dripping from the urethral meatus –
potential urethral injury
● Passing a catheter in the presence of urethral injury → ↑ extent of the
damage, convert a partial membranous urethral tear into total disruption
● Do a retrograde urethrogram
▪ 3-phase spiral CT scan
● To evaluate the kidneys, uterus, bladder
● Delayed images – to detect renal extravasation of blood or urine
▪ If with a pelvic fracture, suspect a urethral transection injury
TREATMENT
Kidney Injury (See Table 561.1)
▪ If minor, bed rest and VS monitoring until abdominal or flank
discomfort and gross hematuria have resolved
▪ If major,
● Admit to ICU
● IV antibiotics
● Manage nonoperatively – because Gerota’s fascia often
causes tamponade of bleeding from the kidney and dramatic
healing of the parenchyma can occur even with significant urinary
extravasation
● 10% undergo surgical exploration d/t associated abdominal
injuries
▪ The kidney can be salvaged by emergency renal
revascularization only if the kidney is explored within 2-3hrs of
the injury
▪ Long-term Complications: loss of renal function, renin mediated
HTN
Bladder Rupture
▪ If intraperitoneal, bladder repair
Testicular Injury
▪ Uncommon in children because of the small size of the testes
and their mobility within the scrotum
▪ Often result from blunt trauma during athletic activity
▪ Significant scrotal swelling, testicular pain and tenderness
▪ Ultrasound: rupture of the tunica albuginea (capsule of the
testis) + surrounding hemorrhage
Membranous Urethral Injury
▪ Temporary suprapubic cystostomy with continuous bladder
drainage for 3-6mos → open or endoscopic urethroplasty
▪ Late complications: erectile dysfunction, urethral stricture,
urinary incontinence
Penile Injury
▪ If strangulation injury, identify and incise the hair → prompt
resolution of the edema
▪ If penetrating penile injury, emergency debridement & repair
Zipper Injury
▪ Affects either the scrotum or foreskin
▪ Occurs generally in males who do not wear underwear
Testicular Injury
▪ Prompt surgical treatment increases the salvage rate
SEXUALLY
TRANSMITTED
DISEASE / CHILD
ABUSE
PPS Oral Exam Reviewer 2020
▪ Painful genital ulceration + inguinal lymphadenopathy (usually
unilateral)
▪ Incubation period: 4-7 days
▪ Small, inflammatory papule on the preputial orifice or frenulum
in men and on the labia, fourchette, or perineal region in women
→ pustular, eroded, and ulcerative in 2-3 days
▪ Ulcer edge is ragged and undermined
▪ Painful, tender inguinal lymphadenitis (>50% of cases, mostly
men) → can become fluctuant → buboes (can spontaneously
rupture)
▪ Without treatment, persists for weeks to months
▪ Diagnosis in infants and children is strong evidence of sexual abuse
▪ Diagnosis is established by the clinical presentation and the exclusion of both
syphilis and HSV infections
▪ Gram stain of ulcer secretions: gram-negative coccobacilli in parallel clusters
(school of fish)
▪ Culture: expensive, requires special media, only 80% sensitive
▪ Evaluate for other STIs (syphilis, HBV, HIV, chlamydia, gonorrhea) – 10% have a
concomitant syphilis or genital herpes
DIFFERENTIAL DIAGNOSIS
▪ Lymphogranuloma venereum
▪ Genital herpes – vesicular lesions with a history of recurrence
Alternative regimens:
▪ Erythromycin 500mg PO TID x 7 days
▪ Ciprofloxacin 500mg PO BID x 3 days if ≥18yo
▪ Fluctuant nodes may require drainage
▪ Symptoms often resolve within 3-7 days
▪ Relapses can be treated successfully with original treatment
regimen
Batch Clingy
CHANCROID
▪ Haemophilus ducreyi – fastidious, gram (-) bacillus
▪ Risk factor for HIV transmission
▪ Male circumcision lowers the risk for chancroid
Zipper Injury
▪ Cut the zipper with bone or metal cutters
▪ Most are resistant to penicillin and ampicillin because of
plasmid-mediated β-lactamase production
▪ Easy to treat if recognized early
▪ Azithromycin 1g PO x 1 dose OR Ceftriaxone 250mg/IM x 1 dose
98
▪ Suspect resistance if with persistence of the ulcer and the
organism after therapy
▪ All sexual contacts should be evaluated and treated
▪ If initial HIV/syphilis testing is negative, re-test in 3mos because
of the high rate of co-infections
COMPLICATIONS
▪ Phimosis
▪ Secondary bacterial infection
▪ Bubo formation
▪ Increased risk for HIV transmission
UTI
VULVOVAGINI-TIS
GONORRHEA, SYPHILIS, CHLAMYDIA
HIV, HBV
TRICHOMONIASIS
*see Renal Disorders*
*see Genital Disorders*
*see Common Bacterial Infections*
*see Common Viral Illnesses*
*see Parasitic Infections*
Complex
DISEASE
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS / DIAGNOSIS
TREATMENT
*see Renal Disorders*
Batch Clingy
UROLITHIASIS
ETIOLOGY / INCIDENCE / PATHOGENESIS
PPS Oral Exam Reviewer 2020
99
EPIDEMIOLOGY / PATHOGENESIS
▪ Most common <1yo
▪ 1st year of life – M:F 2.8:5.4
● 20% in febrile uncircumcised males <1yo
▪ Beyond 1-2yr — M:F 1:10
● Female 1st UTI often by 5yo; peak during infancy, toilet
training & onset of sexual activity
▪ Colonic bacteria: E. coli (54–67%), Klebsiella spp, Proteus spp,
Enterococcus, Pseudomonas; S saprophyticus, GBS; less
common, S aureus, Candida spp, & Salmonella spp
▪ 2-24mo risk factor
● Female: white race, <12 mo, >39°C, fever >2days, absence
of another source
● Male: nonblack race, >39°C, fever >24hr, absence of
another source
URINARY TRACT
INFECTION
▪ Ascending infections; rarely, hematogenous
▪ Simple & compound papillae in kidney: antireflux mech
prevent urine in renal pelvis to enter collecting tubules → some
compound papillae (upper & lower) allow intrarenal reflux →
infected urine stimulate immunologic & inflammatory response
→ renal injury and scarring (highest risk <2yo)
▪ Grade III, IV, or V VUR & febrile UTI: 90% (+) acute
pyelonephritis on renal scintigraphy
▪ Bowel-bladder dysfunction
● Toilet training → retain urine to stay dry → uninhibited
contractions of bladder forcing urine out → ↑pressure,
turbulent urine flow, incomplete bladder emptying →
bacteriuria
● School-age children who refuse to use school bathroom →
urinary retention
● Constipation w/ fecal impaction
▪ Obstructive uropathy → hydronephrosis → urinary stasis
▪ Neurogenic bladder → clean intermittent catheterization →
organisms w/ more antibiotic resistance
▪ Bacterial pili or fimbriae:
● Type I → mannose sensitive (D mannose block attachment
to target cells) → no role in pyelonephritis
● Type II → mannose resistant, receptor is glycosphingolipid
in uroepithelial membrane & RBC: Gal 1-4Gal w/c agglutinate by
P blood group erythrocyte → “P fimbriae”
● E coli: 76-94% (+) P fimbriae, 19-23% cystitis strain
● Attachment to mannose receptor on umbrella cells → take
E. coli into cell → replicate in nutrient-rich environment →
intracellular bacterial communities (IBCs); E coli become
filamentous → bladder shed infected cells → IBCs break out &
repopulate the urine → filamentous E coli evade WBC → taken
up in bladder wall → quiescent intracellular reservoirs (QIRs) →
protected from antibiotics → recurrent infections
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS / LABORATORY FINDINGS
UTI = symptoms + positive culture
(urine culture necessary for confirmation & appropriate therapy)
PYELONEPHRITIS: parenchymal involvement
▪ Most common serious bacterial infection in <24mo w/ fever
without focus
▪ Fever: may be only sx; consider >39C w/out another source for
>24hr in males and > 48hr in females
▪ Abdominal, back or flank pain, malaise, N/V, occ diarrhea
▪ Newborns: nonspecific, poor feeding, irritability, jaundice, weight
loss
Acute pyelitis: no parenchymal involvement
Acute lobar nephronia: localized renal parenchymal mass by acute
focal infection w/out liquefaction; more in older children; may be
early stage renal abscess
Renal abscess → hematogenous spread w/ S aureus or occur ffg
pyelonephritis by uropathogens; most unilateral & R-sided → ↑risk
for renal scarring
Perinephric abscess → sec to contiguous infection in perirenal area
(vertebral osteomyelitis, psoas abscess) or pyelonephritis that
dissects to renal capsule → diffuse throughout the capsule, not
walled of; if no communication w/ collecting system, normal
UA/culture
Xanthogranulomatous
pyelonephritis:
rare,
granulomatous
inflammation w/ giant cells & foamy histiocytes; manifest as renal
mass, acute or chronic infection; risk factor: renal calculi, obstruction,
Proteus ssp, E coli; may require total/partial nephrectomy
CYSTITIS: bladder involvement
▪ Dysuria, urgency, frequency, suprapubic pain, incontinence,
malodorous urine
▪ Does not cause high fever & renal injury
Acute hemorrhagic cystitis: E coli, adenovirus types 11 and 21
(adenovirus cystitis: M>F, self-limiting, hematuria ~4days);
immunocompromised (adenovirus & polyomavirus)
Eosinophilic cystitis (hematuria) or interstitial cystitis (irritative
voiding sx): (-) culture
UA & culture
▪ Toilet-trained children: midstream urine; introitus cleaned;
uncircumcised males, prepuce retracted; prepuce not retractable →
may be unreliable, contaminated with skin flora
▪ Not toilet trained: catheterized/suprapubic aspirate
● Application of adhesive, sealed, sterile collection bag after
disinfection of skin: useful if negative → NPV from “bag” specimen:
99%; ↑rate of contamination, mixed organisms → not used if tx
planned immediately after collection
▪ Nitrites & leukocyte esterase: bacterial metabolism of nitrate to
nitrite: 4hrs → not detected if organism does not convert (notably
COMPLICATIONS / PROGNOSIS
Goal of imaging studies: identify anatomic abnormalities,
determine active renal involvement, assess whether renal
function is normal or at risk
“Bottom-up”
▪ Renal sonogram + VCUG → identify upper and lower UT
abnormalities: VUR, bladder–bowel dysfunction, bladder
abnormalities (paraureteral diverticulum)
“Top-down”
▪ Reduce VCUG exam
▪ DMSA renal scan → identify areas of acute pyelonephritis:
photopenic, enlarged kidney → ~50% develop renal scarring
▪ (+) DMSA → VCUG → (+) scan in 90% of children w/ dilating
reflux
COMPLICATIONS
▪ Chronic renal damage → arterial HTN & end-stage renal
insufficiency
▪ Renal scarring: ↑between days 2-3 of fever; ↑w/ eps of
pyelonephritis; grade of reflux → parental education,
prompt tx
▪ Bacteremia in pyelonephritis: 3–20% of cases; most
common <90 days old & obstructive uropathy → blood
culture before antibiotic
▪ Atypical features: failure to respond w/in 48hr of
appropriate antibiotics, poor urine flow, abdominal flank or
suprapubic mass, non–E coli pathogen, urosepsis, ↑crea
TREATMENT / PREVENTION
▪ Acute cystitis: tx promptly to prevent pyelonephritis; severe sx →
presumptive tx pending culture; mild sx → tx delayed til culture
● TMP-SMX 6-12mg TMP/kg/day ÷ 2doses, 3-5days
● Nitrofurantoin 5-7mkday ÷ 3-4doses (advantage: active against
Klebsiella and Enterobacter)
● Amoxicillin 50mkday ÷ 2doses (effective initial tx, ↑ resistance)
▪ Pyelonephritis: 7-14days, agent capable of reaching significant tissue
levels; oral & IV equally efficacious → IV: dehydrated, vomiting, unable to
drink, urosepsis
● Ceftriaxone 50mkday (not to exceed 2g)
● Cefepime 100mkday q12
● Cefotaxime 100-150mkday ÷ 3-4doses
● Oral 3rd-gen ceph (cefixime): choice for oral tx
● Cephalexin: considered given ↑resistance of Gram (-) to amoxicillin
● Nitrofurantoin: not routine w/ febrile UTI; does not achieve
significant renal tissue levels
● Ciprofloxacin: alternative agent for resistant, particularly P
aeruginosa, >17yo, weigh risk vs benefit (short course therapy for
younger w/ P aeruginosa); levofloxacin, alternative quinolone w/ good
safety profile
● IM loading dose ceftri ffd by oral 3rd gen ceph
▪ Culture: negative w/in 24hr of tx → repeat culture after tx not routine
▪ Acute lobar nephronia: same antibiotics as pyelonephritis; 14-21 days
▪ Renal/perirenal abscess or with infection in obstructed urinary tract:
IV antibiotics (10-14days IV ffd by 2-4wk oral) + percutaneous drainage
typically attempted prior to surgery
● Immediate percutaneous drainage: abscess >3-5 cm; <3cm may
initially be treated w/ antibiotics alone
● 48-hr trial of IV antibiotics before sx in otherwise stable children
● Kidney loss: 10–20% of cases of renal abscess
● ID of causative organism: advantage of percutaneous drainage of
perinephric abscess (infection isolated from collecting system based on
the location)
▪ PNSP: antibiotic switch → poor response after 28-72hr, culture has diff
sensitivity
● Probiotic & cranberry for UTI prevention inconclusive
● Breastfeeding & circumcision may ↓ risk
▪ Identify & manage predisposing factor
● Behavioral modification for constipation
● Bowel-bladder dysfunction: hx of cystitis, wetting, Vincent’s curtsy
(female squat on heels in response to uninhibited bladder contraction),
recurrent upper tract infection; VCUG: tightening the pelvic floor during
urination seen as a spinning-top urethra, UTZ: residual urine, thick
bladder wall, urodynamics: intermittent stream w/ ↑activity in pelvic
floor muscles
▪ Prophylaxis
● ↓ recurrence; rate of renal scarring same; ↑rate of UTI by resistant
organism; need for daily meds
● AAP: does not recommend routine use w/ 1st ep of pyelonephritis
in anatomically normal urinary tract
● PNSP: prophylaxis reduce risk of recurrences, considered in
Batch Clingy
Acute
DISEASE
100
Enterococcus) or (+) urinary frequency
▪ Febrile infants <60 days old: pyuria, nitrite or leukocyte esterase,
↑Sn&Sp
▪ Microscopic hematuria: alone does not suggest UTI
▪ WBC casts (rare) suggest renal involvement
▪ Pyuria: >3-6WBC/hpf, indicative in symptomatic; asymptomatic
bacteriuria can have pyuria
● sterile pyuria: (+) leukocytes (-) culture → partially treated
bacterial UTIs, viral, urolithiasis, renal TB, renal abscess, UTI in
urinary obstruction, urethritis due to STI, inflammation near
ureter/bladder
(appendicitis,
Crohn
dx),
Kawasaki
dx,
schistosomiasis, neoplasm, renal transplant rejection, interstitial
nephritis (eosinophils)
▪ Urine at room temp >60min → overgrowth of minor contaminant
→ refrigeration (storing urine til culture)
▪ Culture >50,000 CFU/mL of single pathogen (suprapubic/catheter)
and UA (+) pyuria or bacteriuria in symptomatic child = UTI
▪ Bag sample UA (+) in symptomatic child → obtain catheter sample
for culture
susceptible patients wherein benefit outweigh risk
● Urologic conditions that might benefit: neuropathic bladder, urinary
tract stasis and obstruction, severe VUR, urinary calculi
AAP UTI and VUR in Infants and Children 2010
▪ Prophylactic dose: ¼ to ½ of therapeutic dose for acute infection
● TMP-SMX: TMP 2mg/kg as a single dose or
5mg/kg of TMP twice per week
● Nitrofurantoin: 1-2mg/kg as a single daily dose
● Cephalexin: 10mg/kg as a single daily dose
● Ampicillin: 20mg/kg as a single daily dose
● Amoxicillin: 10mg/kg as a single daily dose
NOTE:
▪ ↑ Resistance of E coli: ampi & amox are less effective; not used for
beyond the first 2 postnatal months
▪ Neonatal period: avoid TMP-SMZ
▪ Toilet-trained children: at bedtime (not evidence-based)
CBC: leukocytosis & neutrophilia
↑ESR, procalcitonin, CRP
KUB UTZ: 1st line imaging (enlarged kidney w/ possible mass if w/
acute lobar nephronia/renal abscess); 2-24mo 1st ep UTI
VCUG → hydronephrosis, scarring, suggestive of reflux, obstructive
uropathy, atypical complex features, recurrent febrile UTI
CT scan: more Sn&Sp for lobar nephronia (wedge-shaped, lowerdensity area after contrast)
Acute Uncomplicated UTI
Preferred regimen
Infants < 2 months
Cefotaxime
Age
Weight
<7days
>7days
<1200g
50mg/kg/dose q 12hr
>7days
>1200g
50mg/kg/dose q 8 hr
PLUS
Amikacin
Age
E. coli, Klebsiella,
Enterobacter,
Dose
50mg/kg/dose q 12hr
>1month
100-200 mg/kg/d divided q 6hr
Weight
Dose
0-4 week
<1200g
7.5mg/kg OD
<7days
1200-2000g
7.5mg/kg OD
<7days
>2000g
7.5-10mg/kg OD
>7days
>1200-2000g
7.5 mg/kg OD
>7days
>2000g
10g/kg OD
Duration of Treatment: 10-14 days
>2 months to 18 years
Oral options
PPS Oral Exam Reviewer 2020
Comments
If there are signs of sepsis, treat as
neonatal sepsis.
Adjust therapy based on culture.
Early onset is usually due to maternal
transmission.
Use ceftriaxone if cefotaxime is not
available and the neonate is not
jaundiced.
UTI, recurrent, catheter related or with other co-morbidities. These patients require a referral to a pediatric
infectious disease specialist, pediatric nephrologist and pediatric urologist.
Etiology
Enterobacteria
ceae,
Pseudomonas
aeruginosa,
Enterococcus
Preferred regimen
Ceftriaxone
Age
<7days
Dose
50mg/kg/dose q 24hr
>7days
<2000g
50mg/kg/dose q 24hr
>7days
>200g
50-75 mg/kg/dose q 24hr
If Pseudomonas is suspected,
use Ceftazidime instead if
Cefotaxime.
Infants & children: 50-100 mg/kg/dose q24
Adjust antibiotics depending on
results of culture.
AND/OR
Amikacin
Age
Oral therapy is equally effective to IV
therapy. IV therapy is preferred for
Weight
Comments
Use Cefotaxime instead of
Ceftriaxone in jaundiced
patients.
Weight
Dose
0-4 week
<1200g
7.5mg/kg OD
<7days
1200-2000g
7.5mg/kg OD
<7days
>2000g
7.5-10mg/kg OD
>7days
>1200-2000g
7.5 mg/kg OD
>7days
>2000g
10g/kg OD
Infants and children: 15-22.5 mg/kg/d as single daily dose
Cephalosporins are not active
against Enterococcus.
Batch Clingy
Etiology
E. coli, Klebsiella,
Enterobacter,
Enterococcus,
Group B Strep
101
Amoxicillin-clavulanate:
<40 kg: 20-40 mg (amoxicillin)/kg/d q8h or
25-45 mg/kg/d q12h using the 20 mg/5mL or
400 mg/5mL >40 kg: 500-875 mg q8h;
maximum dose: 2g/d
seriously ill children and for those who
cannot take oral therapy.
or q8h; max dose: 24 g/d
Treat for 7-14 days depending on response.
Switch to oral therapy once patient has
been afebrile for 24h and able to take
oral medications.
OR
Cephalosporins are not useful if
Enterococcus is suspected.
Nitrofurantoin should NOT be used for
pyelonephritis and renal sepsis due to
poor serum concentrations.
Cefuroxime >3 mos - 12 yrs:
20 - 30 mg/kg/d q12h PO
Adolescents:
Cefuroxime 250-500 mg q12h PO OR
Nitrofurantoin (only for cystitis) 5-7 mg/kg/d q6h, maximum dose: 400
mg/d
IV options
Ampicillin-Sulbactam100-200 mg/kg/d of ampicillin q6h IM or IV infusion
over 10-15 min OR
Clinical response is expected in 24-48
hours.
Antibiotic coverage should be reassessed if still unwell in 24-48h
Cefuroxime 75-150 mg/kg/d q8h; max dose: 6 g/d.
For those >40 kg, use adult dose.
Duration of therapy (IV/PO): 7-14 days
Test
Leukocyte esterase
Nitrite
Leukocyte esterase or nitrite positive
Microscopy (WBC)
Microscopy (bacteria)
Leukocyte esterase test, nitrite, or
microscopy positive
WBC >5/HPF in centrifuged
WBC >10/uL in uncentrifuged
Bacteriuria (+)
Bacteriuria (-)
Nitrite (+)
Nitrite (-)
Collection Method
Suprapubic aspiration
Catheterization
Clean catch, midstream
urine
ACUTE
GLOMERULONEPHRITIS
▪ Tea/cola
colored urine
(painless
hematuria but
assoc w/ flank
pain when
acute/severe)
ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
▪ Nephritogenic strain of GABHS
▪ 1-2wk after pharyngitis; 3-6wk after pyoderma
▪ Glomeruli: enlarged & relatively bloodless, diffuse mesangial
cell proliferation, polymorphonuclear leukocyte infiltration
(early), crescents & interstitial inflammation (severe); IF:
“lumpy-bumpy” deposits of Ig & complement; EM: electrondense deposits/“humps” on epithelial side of glomerular BM
▪ Mechanisms of immunologic injury → molecular mimicry; in
situ immune complex formation; complement activation
▪ Most common: 5-12yr; uncommon <3yr
PPS Oral Exam Reviewer 2020
▪ UA: RBC casts, proteinuria, polymorphonuclear leukocytes; CBC:
normochromic anemia (hemodilution, ↓grade hemolysis); ↓C3 in >
90% in acute phase
▪ Confirm: clear evidence of prior streptococcal infection → (+) throat
culture (support dx or carrier state), ASO titer (↑pharyngeal
infection, rare in skin infections), antideoxyribonuclease B level (best
single Ab titer document cutaneous infection), streptozyme screen
(measure multiple Ab to different streptococcal antigens)
▪ MRI: severe neurologic sx, PRES in parietooccipital areas (T2weighted images)
▪ CXR → sx of heart failure or pulmonary edema
Sensitivity (Range)
%
83 (67–94)
53 (15–82)
93 (90–100)
73 (32–100)
81 (16–99)
Specificity (Range)
%
78 (64–92)
98 (90-100)
72 (58–91)
81 (45–98)
83 (11–100)
99.8 (99–100)
70 (60–92)
Pyuria (+)
Pyuria (-)
Send for urine CS
Treat as UTI
Start antibiotics
Send for urine CS
Start antibiotics if with symptoms
Leukocyte (+)
Send for urine CS
Treat as UTI
Start antibiotics
Send for urine CS
Start antibiotics if with symptoms
Colony Count (cfu/ml)
Any growth
>105
104 - 105
>104 (boy)
>105 (girl) (3 specimens)
>105 (girl) (2 specimens)
>105 (girl) (1 specimen)
▪ Nephrotic syndrome: <5%
▪ HTN 60% → HTN encephalopathy 10% → neurologic
sequelae often reversible → severe prolonged HTN →
intracranial bleeding
▪ HyperK, hyperphosphatemia, hypoCa, acidosis, seizures,
uremia
▪ Acute renal failure → dialysis
▪ Hypervolemia → pulmonary edema & heart failure
▪ Complete recovery: >95%
● Recurrence extremely rare
▪ Severe acute phase → glomerulosclerosis and chronic renal
Send for urine CS
Treat as UTI
Start antibiotics
Not UTI
Leukocyte (-)
Send for urine CS
Treat as UTI
Start antibiotics
Not UTI
Probability
of infection (%)
>99%
95%
Infection likely
Infection likely
95%
90%
85%
▪ Acute phase: generally, resolves w/in 6-8wk
● Urinary protein excretion; HTN: normalize 4-6wk after onset
● C3: 6-8wk
● Persistent microscopic hematuria: persist for 1-2yr
▪ Management → renal dysfunction and HTN
▪ 10-day antibiotic therapy w/ penicillin: limit spread of nephritogenic
organisms, not affect natural history
▪ Sodium and fluid restriction, diuretics, and pharmacotherapy w/ Cachannel antagonists, vasodilators, or ACE inhibitors → hypertension
▪ Prevention: early systemic antibiotic therapy for streptococcal
infections does not eliminate risk of GN (family of patients w/ acute GN,
Batch Clingy
Citrobacter
102
▪ Other causes of postinfectious GN: coagulase-positive/negative staphylococci, S pneumoniae, Gram(-) bacteria,
influenza, parvovirus
Diseases
commonly
manifesting as
AGN
▪ Postinfectious
GN
▪ IgA
Nephropathy
▪ MPGN
▪ HSP Nephritis
▪ SLE Nephritis
▪ Granulomatosis with
polyangiitis
(formerly
Wegener
granulomatosis)
▪ Microscopic
PAN (please see
NOTE below)
▪ Goodpasture
syndrome
▪ HUS
(page 2718)
IgA NEPHROPATHY (Berger nephropathy)
▪ Most common chronic glomerular disease in children
▪ Immune complex disease → excessive amounts of poorly
galactosylated IgA1 in the serum → production of IgG and IgA
autoantibodies
▪ Predominance of IgA (often accompanied by C3) w/in
mesangial glomerular deposits in absence of systemic disease →
mesangial proliferation w/ epithelial cell crescent formation &
sclerosis
▪ Findings similar to HSP → hypothesis → disease of same
spectrum
▪ Familial clustering: linkage to 6q22-23; high predisposition in
Southeast Asia, ↓prevalence Africa
▪ M>F
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
(MPGN, Mesangiocapillary glomerulonephritis)
▪ Primary (idiopathic) or secondary (subacute & chronic
infection: hep B & C, syphilis, subacute bacterial endocarditis,
infected shunts, especially ventriculoatrial shunts → shunt
nephritis), lupus nephritis
▪ Recent URI,
skin, GI infection
→ postinfectious
GN, HUS, HSP
nephritis
▪ Rash & joint
complaints →
HSP or SLE
Nephritis
Please see Fig
536.1 and Fig
537.6
NOTE:
On page2307,
Microscopic
Polyangiitis
(MPA) was
previously the
microscopic
variant of
polyarteritis
Primary MPGN
▪ Type I: common; accentuated lobular pattern from diffuse
mesangial expansion, ↑mesangial cells & matrix; thickened
glomerular capillary walls; crescents → poor prognosis; IF: C3,
lesser amt of Ig in mesangium & peripheral capillary walls
(lobular pattern); EM: deposits in mesangial and subendothelial
regions
▪ Type II (dense deposit disease): similar LM findings; IF: C3
prominent w/out concomitant Ig; EM: lamina densa undergoes
dense transformation w/out immune complex-type deposits
(C3GN related but separate category)
Primary & secondary type I indistinguishable; immune
complexes trapped in glomerular subendothelial space → injury
→ proliferative response & mesangial expansion (complement
activation through classic pathway in 50%)
▪ Type II → not mediated by immune complexes; pathogenesis
not known → deranged complement regulation
● ↓C3, other complement normal; C3 nephritic factor (anti–
C3 convertase antibody) → activates alternative complement
pathway
HSP NEPHRITIS
▪ ~50% develop renal manifestations (>8 yr 3-fold greater risk)
▪ Severity of systemic manifestations not correlated w/ severity
of nephritis
▪ Similar pathogenesis, nearly identical renal histology w/ IgA
nephropathy
PPS Oral Exam Reviewer 2020
▪ Biopsy: ARF, nephrotic syndrome, no evidence of strep infection,
normal complement level; hematuria & proteinuria, ↓renal fx, ↓C3
level >2mo after onset
● Persistent hypocomplementemia: chronic form of postinfectious
GN, MPGN
● Purpuric rash: can’t diff from HSP w/out biopsy
▪ Gross hematuria: w/in 1-2days of onset of URI or GI infection, may
be assoc w/ loin pain
▪ Proteinuria: <1,000mg/24hr in patient w/ asymptomatic
microscopic hematuria
▪ Mild to moderate HTN if w/ nephritic or nephrotic syndrome (rarely
severe to cause HTN emergency)
▪ Normal C3; IgA levels no diagnostic value (↑ in only 15% of pedia)
disease: <2%
especially young children → at risk → culture for group A β-hemolytic
streptococci → treat; family pets, particularly dogs, reported as carriers)
▪ Most: does not lead to significant kidney damage
▪ Progressive disease develops in 20–30% of adult patients
15-20yr after onset (need for careful long-term ffup)
▪ Poor prognostic indicators: persistent HTN; ↓renal
function; significant, increasing, or prolonged proteinuria;
histology: diffuse mesangial proliferation, extensive
glomerular crescents, glomerulosclerosis, & diffuse
tubulointerstitial changes, including inflammation & fibrosis
▪ BP control, mgt of proteinuria: ACEIs, ARBs → ↓proteinuria, ↓rate of
progression (individual/ combination)
▪ Fish oil (antiinflam omega-3 PUFA): ↓rate of progression in adults
▪ RAS blockade ineffective, proteinuria persists → steroids → improve
renal function (patients w/ eGFR >60mL/ min/m2)
▪ Cyclophosphamide/azathioprine → not appeared effective, RCTs in
progress
▪ Tonsillectomy w/out significant tonsillitis in assoc w/ IgA nephropathy
→ not recommended
▪ Targeted-release oral budesonide combined with RAS blockade (pilot
study to reduce proteinuria)
▪ Kidney transplant → recurrent disease frequent
▪ Most common in 2nd decade of life; M=F; more common in
Caucasian
▪ Equal proportions w/ nephrotic syndrome, acute nephritic
syndrome, or persistent asymptomatic microscopic hematuria and
proteinuria
▪ ↓C3
▪ Diagnosis by renal biopsy: nephrotic syndrome in older child,
significant
proteinuria
w/
microscopic
hematuria,
hypocomplementemia >2mo in child w/ acute nephritis
● C3 but no Ig deposition: genetic testing & functional assays
(defects of complement cascade regulation)
▪ Untreated, idiopathic MPGN, regardless of type: poor
prognosis
● 10yr: 50% ESRD
● 20yr: 90% lost renal fx
▪ Nephrotic syndrome & HTN at presentation → renal failure
more rapidly
▪ Determine if idiopathic or secondary (lupus or chronic infection) → tx
causative disease
▪ No definitive therapy → extended course of alternate-day prednisone
(years) → preserve renal function
▪ C3GN: interruption of complement activation pathways → complement
factor H replacement, eculizumab (anti–C5 antibody) → prevent
progression of renal disease
▪ Classic tetrad: palpable purpura, arthritis/arthralgia, abdominal
pain, evidence for renal dx
Mild: isolated microscopic hematuria w/out significant proteinuria
Severe: combined acute nephritic & nephrotic syndrome (hematuria,
HTN, renal insufficiency, significant proteinuria)
▪ Most urinary abnormalities by 1mo, nearly all by 3-6mo after onset
▪ Mild: majority → spontaneous & complete resolution of
nephritis; occ progress despite resolution of other HSP
features
▪ Untreated → CKD
▪ Moderate/severe HSP nephritis → likely to progress to CKD
▪ Approach in severe clinical renal involvement (nephrotic range
proteinuria, HTN, ↑crea)
● Prednisone (1mkday for 3mo)
● ACE inhibitors
● persists: Azathioprine, MMF
Batch Clingy
▪ Facial/body
edema
▪ Hypertension
▪ Oliguria (renal
dysfunction)
103
Although GN not
typical (page
1322), PAN part
of differential
diagnostic
algorithm (Fig
537.6) presenting
with hematuria.
▪ Mucosal infection/food antigen trigger ↑production of
pathogenic IgA1 → defective glycosylation of hinge region of
IgA1 + autoantibodies → immune complexes deposited in
glomerular mesangium
▪ IF: pathognomonic IgA deposits in glomerular mesangium
of HSP
▪ UA 1x/wk during active clinical disease → 1x/mo up to 6mos
▪ All UA normal during ffup interval: nephritis unlikely to develop
▪ Kidney biopsy: significant proteinuria (urine protein >1g/day or
UPCr > 1.0), significant HTN, ↑ crea
SLE NEPHRITIS
▪ More common & more severe in children
▪ 80% of pediatric px w/ SLE; common w/in 1styr of dx
▪ Most impt cause of morbidity & mortality in SLE
▪ Result of deposition of circulating immune complexes & direct
binding of autoAb to glomerular components w/ resultant
complement stimulation
▪ Renal histopathology: gold standard
▪ IF: full-house immune staining; granular deposition of Ig isotypes
(IgG, IgM, IgA), complements (C3, C4, C1q) in glomerular mesangium
and capillary walls
WHO classification (1980)
▪ Class I nephritis (minimal mesangial LN)
● LM: no histologic abnormalities; IM/EM: mesangial
immune deposits
▪ Class II nephritis (mesangial proliferative nephritis)
● Mesangial hypercellularity, ↑matrix, mesangial
deposits containing Ig & complement
▪ Class III nephritis
● <50% glomeruli w/ involvement
▪ Class IV nephritis
● >50% glomeruli w/ involvement
● Poorer outcomes; successfully tx w/ aggressive
immunosuppressive therapy
▪ Class V nephritis (membranous LN)
● Isolated lesion, resembles idiopathic membranous
nephropathy w/ subepithelial immune deposits
*WHO class III & class IV: interrelated, characterized by
mesangial and endocapillary lesions; subclassification
scheme: severity of proliferative lesion → segmental vs
global
*Chronic injury → glomerular sclerosis
*Active disease: capillary walls thickened sec to
subendothelial deposits (wire-loop lesion), necrosis,
crescent formation
GRANULOMATOSIS WITH POLYANGIITIS (GPA)
▪ Wegener granulomatosis
▪ Necrotizing granulomatous small & medium vessel vasculitis,
targets upper & lower respiratory tract and kidneys
▪ Occurs at all ages; female predominance, 3-4:1
● Pediatric GPA prevalent in Caucasian
▪ EULAR/PReS Classification Criteria for Pediatric-Onset GPA
(Dx: 3 out of 6)
● Histopath showing granulomatous inflam
● Upper airway involvement
● Laryngeal, tracheal or bronchial involvement
● ANCA positivity
● Renal involvement
● Proteinuria, hematuria, RBC casts, necrotizing pauci-
PPS Oral Exam Reviewer 2020
International Society of Nephrology and the Renal
Pathology Society (2004)
[Widely preferred but most RCTs based on WHO]
Class I (Minimal mesangial LN) – No renal findings
Class II (Mesangial proliferative LN)
● Mild clinical renal dx; minimally active urinary sediment;
mild to moderate proteinuria (never nephrotic) but may
have active serology
Class III (Focal proliferative LN, <50% glomeruli)
[A. Active; A/C. Active and chronic; C. Chronic]
● More active sediment changes; often active serology;
↑proteinuria (>25% nephrotic); HTN may be present; some
evolve into class IV pattern; active lesions require tx;
chronic do not
Class IV (Diffuse proliferative LN, >50% glomeruli); all may
be w/ segmental or global involvement (S or G) [A. Active;
A/C. Active and chronic; C. Chronic]
● Most severe renal involvement w/ active sediment, HTN,
heavy proteinuria (freq nephrotic syndrome) often ↓GFR;
serology very active. Active lesion require tx
Class V (Membranous LN glomerulonephritis)
● Significant proteinuria (often nephrotic) w/ less active
lupus serology
Class VI (Advanced sclerosing LN)
● >90% glomerulosclerosis; no tx prevent renal failure
GPA
▪ Early disease: nonspecific constitutional sx (fever, malaise, wt loss,
myalgias, arthralgias)
▪ Upper airway involvement: sinusitis, nasal ulceration, epistaxis,
otitis media, hearing loss
▪ Lower respiratory tract: cough, wheezing, dyspnea, hemoptysis
▪ Childhood GPA: more frequently complicated by subglottic stenosis
▪ Inflammation-induced damage to the nasal cartilage → saddle nose
deformity
▪ Pulmonary hemorrhage → rapid respiratory failure
▪ Ophthalmic involvement: conjunctivitis, scleritis, uveitis, optic
neuritis, invasive orbital pseudotumor (causing proptosis)
▪ Perineural vasculitis or direct compression on nerves by
granulomatous lesions → cranial & peripheral neuropathies
▪ Renal survival (defined as CKD w/out need for ESRD
therapy): 80% 10yr post-diagnosis of SLE nephritis
▪ Highest risk for progression to ESRD: diffuse proliferative
WHO class IV lupus nephritis, poor renal function at
presentation, persistent nephrotic-range proteinuria
▪ ↑ Risk of malignancy/infertility: receiving cumulative dose
of >20g of cyclophosphamide or other immunosuppressant
therapies
▪ Upper respiratory tract lesions can invade orbit → threaten
optic nerve
▪ Lesions in the ear → permanent hearing loss
▪ Respiratory complications: life-threatening pulmonary
hemorrhage & upper airway obstruction (subglottic stenosis)
▪ Chronic lung dx sec to granulomatous inflammation,
cavitary lesions, scarring → infectious complications
▪ Chronic GN → ESRD (advanced/undertreated disease)
▪ Course variable
▪ Relapse: 60% of patients
▪ Mortality ↓ w/ introduction of cyclophosphamide & other
immunosuppressive agents
▪ Compared w/ adults, children more likely to develop
multiorgan involvement, renal involvement & subglottic
▪ Severe histologic manifestations (>50% glomerular crescents): IV
methylprednisolone pulses (3days); ffd by prednisone (3mo) +
azathioprine or MMF (extended course)
▪ Most severe histology (>75% glomerular crescents), progressive renal
failure: IV steroids + plasmapheresis
▪ ESRD: renal transplant
▪ Immunosuppression: cornerstone of therapy → clinical remission
(normalization of renal function & proteinuria); serologic remission
(normalization of anti-DNA antibody, C3, C4)
▪ Prednisone 1-2mkday in divided doses → slow steroid taper over 4-6mo
beginning 4-6wk after achieving serologic remission
▪ Severe forms (WHO classes III and IV): steroid therapy alone insufficient
to induce remission
● Induction phase: 6 monthly IV infusions of cyclophosphamide 5001,000mg/m2; pulse IV methylprednisolone 1,000mg/m2 + oral steroids;
alternative: MMF 600mg/m2/dose BID (SE: diarrhea, leucopenia,
teratogenicity)
● Maintenance phase: cyclophosphamide (Cytoxan) infusions q3mo
for 18mo (SE: infections, hair loss, hemorrhagic cystitis, gonadal failure);
MMF; azathioprine 1.5-2mkdose QD (steroid-sparing agent in WHO class
I or II)
▪ Rituximab, chimeric monoclonal antibody specific for human CD20:
resistance to conventional tx
▪ Plasmapheresis: ineffective unless w/ accompanying TTP or
antineutrophilic cytoplasmic antibody–associated dx
▪ Belimumab, fully humanized monoclonal antibody against type II
transmembrane protein: requires further study
▪ Hydrochloroquine: for extrarenal SLE manifestations; effect in
maintaining remission in lupus nephritis
▪ Antihypertensive, ACE inhibitors, ARBs
▪ Lower respiratory tract/kidneys significantly involved: initial induction
tx: prednisone (2mg/kg/day) or IV methylprednisolone (30mg/kg/day,
3days) + daily oral or monthly IV cyclophosphamide
▪ Rituximab, mono-clonal antibody to CD20 on activated B cells, option
for induction (study primarily in adults)
▪ Plasmapheresis + methylprednisolone: severe dx (pulmonary
hemorrhage or ESRD: potential for ↓dialysis dependency)
▪ Transition to less toxic maintenance medication: methotrexate,
azathioprine, MMF w/in 3-6mo once in remission
▪ TMP-SMX (one 180mg/800mg tab 3days/wk): prophylaxis
(Pneumocystis jiroveci); ↓upper respiratory bacterial colonization w/ S
aureus (trigger dx activity)
▪ Disease limited to upper respiratory tract: steroids (1-2 mg/kg/day),
methotrexate (0.5-1.0mg/kg/wk)
Batch Clingy
nodosa.
104
MICROSCOPIC POLYANGIITIS (MPA)
▪ Small vessel necrotizing vasculitis; clinically similar to GPA
w/out granulomas & upper airway involvement
▪ Rare in children
▪ Cardinal histologic feature (GPA/MPA): necrotizing vasculitis
● Kidney biopsy: crescentic GN w/ little or no immune
complex deposition (“pauci-immune”)
● Granulomatous inflammation common in GPA & Churg
Strauss Syndrome (CSS); not present in MPA
● Perivascular eosinophilic infiltrates distinguish CSS from
MPA & GPA
▪ Etiology of ANCA-associated vasculitis unknown
● Neutrophils, monocytes & endothelial cells involved in
pathogenesis
● Neutrophils & monocytes activated by ANCAs, specifically
ANCA-associated
antigens
proteinase-3
(PR3)
&
myeloperoxidase (MPO) → release proinflammatory cytokines
(TNF-α, IL-8)
● Localization of inflammatory cells to endothelium →
vascular damage
POLYARTERITIS NODOSA
▪ Systemic necrotizing vasculitis → small & medium-size arteries;
aneurysms & stenoses form at irregular intervals throughout
affected arteries
▪ Cutaneous PAN limited to the skin
▪ PAN rare in childhood
● Boys & girls equally affected; mean age 9yr
▪ Cause unknown
▪ Devt ffg infections (GAS, chronic hep B) → may represent
postinfectious autoimmune response
● Other: EBV, MTB, CMV, parvo B19, hep C virus
▪ Assoc w/ familial Mediterranean fever
▪ Biopsy: necrotizing vasculitis w/ granulocytes & monocytes
infiltrating walls of small & medium-size arteries → usually
segmental, at vessel bifurcations
▪ Granulomatous inflammation not present
▪ Deposition of complement & immune complex rare
▪ Different stages of inflammation found: mild inflammatory
changes to panmural fibrinoid necrosis assoc w/ aneurysm
formation, thrombosis, vascular occlusion
▪ Immune complexes → pathogenic → poorly understood
▪ Inflamed vessel wall thickened & narrowed → impeding blood
flow → contributing to end-organ damage
▪ No clear genetic association
● Deficiency in adenosine deaminase 2 (DADA2) (caused by
mutation in CECR1 gene) → familial form of vasculitis in
Georgian Jewish patients w/ autosomal recessive inheritance
Proposed Classification Criteria: Pediatric-Onset PAN
(5 criteria: Sn 89.6%, Sp 99.6%)
● Histopath: necrotizing vasculitis in medium/small art
PPS Oral Exam Reviewer 2020
▪ Hematuria, proteinuria, HTN → signal renal disease
▪ Cutaneous lesions: palpable purpura & ulcers
▪ Venous thromboembolism: rare but potentially fatal complication
MPA
▪ closely resemble GPA, sinus disease less common
▪ systemic features dominant: fever, malaise, wt loss, myalgia,
arthralgia
▪ predominantly affects kidney & lungs
▪ distinguished from PAN: (+) ANCAs, tendency for small vessel
involvement
▪ no clear correlation between ANCA titers & disease activity/relapse
▪ DDx: ANCAs absent in other granulomatous diseases (sarcoidosis,
TB); Goodpasture syndrome (Ab to GBM); meds (PTU, hydralazine,
minocycline) associated w/ drug-induced ANCA (perinuclear ANCA)
vasculitis; SLE and HSP (present as pulmonary hemorrhage, nephritis)
▪ Presentation variable, reflect distribution of inflamed vessels
▪ Constitutional sx present in children at disease onset
▪ Wt loss, severe abdominal pain → mesenteric arterial inflammation
& ischemia
▪ Renovascular arteritis → HTN, hematuria, proteinuria; GN not
typical
▪ Cutaneous: purpura, livedo reticularis, ulcerations, digital ischemia,
painful nodules
▪ CNS: CVA, TIA, psychosis, ischemic motor/sensory peripheral
neuropathy (mononeuritis multiplex)
▪ Myocarditis, coronary arteritis → heart failure, MI, pericarditis,
arrhythmias
▪ Arthralgias, arthritis, myalgias
▪ Pulmonary vasculature usually spared
▪ Biopsy or angiography: demonstration of vessel involvement
● Biopsy of cutaneous lesions: small/medium vessel vasculitis
● Kidney biopsy: necrotizing arteritis
● Sural nerve biopsy: vasculitis
▪ EMG: peripheral neuropathy identifies affected nerves
▪ Conventional arteriography: gold standard diagnostic, reveals areas
of aneurysmal dilation & segmental stenosis, classic “beads on a
string”
▪ MRA & CTA: less invasive, gaining acceptance; not effective
identifying small vessel dx or in younger children
▪ Nonspecific lab: ↑ESR, CRP; anemia, leukocytosis,
hypergammaglob; abnormal urine sediment, proteinuria, hematuria
→ renal disease; ↑hepatic enzyme→ hep B/C; serologic tests for
hepatitis (hep B surface antigen, hep C Ab)
▪ DDx: early skin lesions → resemble HSP (finding of nodular lesions &
presence of systemic features distinguish PAN); pulmonary vascular
involvement very rare in PAN, lesions suggest ANCA-associated
stenosis
*Renal involvement uncommon in CSS (inflammation of upper & lower
respiratory tracts: recurrent rhinitis/sinusitis, nasal polyposis, nonfixed
pulmonary lesions, difficult-to-treat asthma; eosinophilia (>10%) w/
pulmonary infiltrates before vasculitic phase; mepolizumab, anti-IL5
monoclonal Ab, may have role in tx)
Feature
S/sx of small vessel vasculitis
IgA-dominant immune deposits
Circulating antineutrophil
cytoplasmic antibodies
Necrotizing vasculitis
Granulomatous inflammation
Asthma and eosinophilia
▪ Cutaneous nodules → ulcerate, become infected
▪ Renovascular involvement → HTN, chronic renal disease
▪ Cardiac involvement → ↓cardiac function, CAD
▪ Mesenteric vasculitis → predispose to bowel infarction,
rupture, malabsorption
▪ Stroke and rupture of hepatic arterial aneurysm:
uncommon
▪ Course varies from mild disease w/ few complications to
severe, multiorgan disease ↑morbidity & mortality
▪ Poor prognostic factors
● ↑ Crea, proteinuria, severe GI involvement,
cardiomyopathy, CNS involvement
▪ Early and aggressive immunosuppressive tx: ↑clinical
remission, minimize potential long term vascular
complications
▪ Compared w/ adults, childhood PAN less mortality
▪ Cutaneous PAN → unlikely to transition to systemic disease
HSP
+
+
GPA
+
-
CSS
+
-
MPA
+
-
-
+(PR3)
+(MPO > PR3)
+(MPO)
-
+
+
-
+
+
+
+
-
▪ Mainstay: prednisone (1-2mg/kg/day) or IV pulse methylprednisolone
(30 mg/kg/day)
▪ Oral/IV cyclophosphamide: used as adjunctive tx
▪ Plasma exchange: life-threatening
▪ Hepatitis B identified → antiviral therapy
▪ Cutaneous PAN: less intense → steroids alone, NSAIDs, methotrexate
▪ Azathioprine, MMF, IVIG, thalidomide, cyclosporine, anti-TNF agents
(infliximab) → refractory cutaneous or systemic PAN (clinical trials
lacking)
▪ Infectious trigger for PAN → antibiotic prophylaxis considered
Batch Clingy
immune GN
105
HEMOLYTIC UREMIC SYNDROME
▪ Most common form of thrombotic microangiopathy (TMA) in
children
▪ Common cause of community-acquired AKI in young children
▪ Most common form: 90% diarrhea-associated HUS (STEC-HUS
→ E coli O157:H7 most common; Asia & South Africa, Shigella
dysenteriae type 1)
● Undercooked meat, unpasteurized milk and apple cider;
cross-contaminated cuttingboards; water supply; petting farms
● Enteropathic organism → produce toxin → absorbed from
colonic mucosa to systemic circulation → bind to endothelial
cells in glomerulus → endothelial cell damage; Shiga toxin
directly activate platelets → aggregation → mechanical injury to
RBCs passing through thrombotic microvasculature → severe
nonimmune anemia w/ (-)direct Coombs test
▪ Pneumococcal-associated HUS → neuraminidase cleaves sialic
acid on membranes of endothelial cells, RBC, platelets → expose
ThomsenFriedenreich (T) antigen → IgM react w/ T antigen →
hemolysis → anemia w/ (+)direct Coombs test
▪ Genetic form (atypical, nondiarrheal): 2nd major category →
probably predispose but not cause dx → absence of preceding
diarrheal prodrome → insidious onset/relapsing (trigger; mild
nonspecific infection)
▪ In each form of HUS
PPS Oral Exam Reviewer 2020
vasculitis/Goodpasture disease; other: SLE (characteristic targetorgan involvement, autoantibodies); prolonged fever & weight loss
→ IBD/malignancy
▪ Combination of pulmonary hemorrhage with acute AGN
▪ Hemoptysis from pulmonary hemorrhage → can be life-threatening
▪ AGN: hematuria, nephritic urinary sediment w/ cellular casts,
proteinuria, HTN →rapidly progressive course → renal failure w/in
days to weeks of clinical
● Less common: anti-GBM nephritis → isolated, rapidly
progressive GN w/out pulmonary hemorrhage
▪ Fever may be present; other systemic complaints (malaise,
arthralgia) usually absent (presence raise suspicion for systemic
vasculitis)
▪ (+) anti-GBM Ab in serum and/or kidney; C3 normal
▪ ↑ANCA: 10–40% (along with the anti-GBM Ab; patients doubly
positive → more severe disease)
▪ Anti-GBM Ab titer correlated w/ severity of renal involvement →
accuracy of serology variable → biopsy (unless contraindicated) →
histology guide therapy
▪ DDx: pulmonary-renal syndrome → SLE, HSP, nephrotic syndrome–
associated pulmonary embolism, GPA, MPA
Triad: microangiopathic hemolytic anemia, thrombocytopenia, renal
insufficiency
▪ Microangiopathic hemolytic anemia w/ schistocytes; mild at
presentation, rapidly progresses
▪ Thrombocytopenia usually 20,000-100,000/mm3; petechiae, severe
bleeding rare
▪ Normal partial thromboplastin & prothrombin times
▪ Leukocytosis
▪ UA: microscopic hematuria, low-grade proteinuria
▪ Renal failure + severe hemolysis → life-threatening hyperkalemia
▪ Volume overload, HTN, severe anemia → heart failure
▪ ≤20%: severe CNS involvement: seizures, significant
encephalopathy → HTN & focal ischemia sec to microvascular CNS
thrombosis
▪ Intestinal complications: severe inflammatory colitis, ischemic
enteritis, bowel perforation, intussusception, pancreatitis
Diarrhea form: most common in preschool & school-age
▪ Onset of HUS: 5-7days after onset of gastroenteritis (fever,
vomiting, abdominal pain, diarrhea w/ or w/out blood)
▪ Sudden onset of pallor, weakness, lethargy → onset of HUS: dev of
microangiopathic hemolytic anemia
▪ Oliguria in early stage may be masked by diarrhea
▪ Significant dehydration or volume overload depend on whether
▪ Untreated, poor prognosis
▪ Tx early, good renal outcome in majority
▪ Oligoanuria, ↑proportion of glomerular crescents, kidney
failure requiring dialysis → worse renal & patient survival
rate
▪ Tx initiated emergently: plasmapheresis, ↑dose IV methylprednisolone,
cyclophosphamide → induce remission, improve survival times
▪ Plasmapheresis: remove circulating anti-GBM Ab
▪ Initial immunosuppression w/ steroids & cyclophosphamide: inhibit
ongoing Ab production
▪ Rituximab: substitute → cyclophosphamide toxicity
▪ Tx guided by clinical response & serial anti-GBM titers
▪ Maintenance therapy: lower dose of prednisone and azathioprine (or
MMF) continued for 6-9mo
▪ Survive acute pulmonary hemorrhage & rapidly progressive GN → still
progress to ESRD despite immunosuppressive therapy → kidney
transplant → relapse & recurrent dx after transplant uncommon
▪ Mortality rate: diarrhea-associated HUS is <5% w/ early tx;
50%: severe AKI requiring dialysis usually about 2wk → most
recover renal function completely, 5% remain dependent on
dialysis, 30% some degree of chronic renal insufficiency
▪ Annual exam: no residual urinary abnormalities after 1yr →
long-term sequelae unlikely
▪ Recovery of platelet count → renal recovery ~5days later
→ resolution of anemia
▪ Not associated w/ diarrhea: more severe
▪ Supportive care: F&E balance; control of HTN, early institution of
dialysis (oliguric, anuric, hyperkalemia)
▪ RBC transfusion: pneumococci-associated HUS → washed → remove
residual plasma → endogenous IgM → accelerate disease
▪ Platelets: generally, not administered → consumed by active
coagulation → worsen
▪ Antibiotic to clear STEC → ↑toxin release, not recommended
▪ Tx of causative pneumococcal infection → important
▪ Plasma infusion, plasmapheresis: serious CNS involvement BUT
contraindicated in pneumococcal associated HUS
▪ Eculizumab, anti-C5 antibody: atypical familial HUS; give meningococcal
vaccine prior
Pneumococci-associated HUS: >80% require dialysis,
mortality rate 20%
Genetic form: insidiously progressive/ relapsing, poor
prognosis → ID specific factor deficiencies for directed
therapy
Kidney biopsy
▪ Risks during active phase; dx by clinical criteria
▪ Early changes: thickening of capillary walls (swelling of
endothelial cells) & accumulation of fibrillar material between
endothelial cells and GBM → narrowing capillary lumens;
platelet–fibrin thrombi in glomerular capillaries, thrombi in
afferent arterioles & small arteries w/ fibrinoid necrosis of
arterial wall → renal cortical necrosis
▪ Late findings: glomerular sclerosis & obsolescence sec to
severe direct glomerular involvement or glomerular ischemia
from arteriolar involvement
Batch Clingy
● Angiographic abnormalities: aneurysm, stenosis, or occlusion
of medium/small artery not from noninflammatory cause
● Cutaneous findings: livedo reticularis, tender subcutaneous
nodules, superficial skin ulcers, deep skin ulcers, digital necrosis,
nail bed infarctions, or splinter hemorrhages
● Muscle involvement: myalgia/muscle tenderness
● Hypertension: SBP/DBP >95th percentile for height
● Peripheral neuropathy: sensory peripheral neuropathy, motor
mononeuritis multiplex
● Renal involvement: proteinuria (>300mg/24hr equiv),
hematuria/RBC casts, impaired renal function (GFR <50%
normal)
GOODPASTURE DISEASE
▪ Autoimmune disease: pulmonary hemorrhage, rapidly
progressive GN, ↑anti–GBM antibody titer
▪ Rare in childhood
▪ Ab against epitopes of type IV collagen; located w/in alveolar
basement membrane & GBM
▪ Acquired conformational change in noncollagenous 1 domain
of alpha 3-chain of type IV collagen → production of pathologic
autoAb → high affinity to GBM → rapidly progressive kidney
disease
▪ Kidney biopsy: crescentic GN; IF: pathognomonic continuous
linear deposition of IgG along GBM
106
▪ Nephrotic
Range Proteinuria
(>3.5g/24hr OR
UpCr Ratio >2)
▪ Hypoalbumine
mia (≤2.5g/dL)
▪ Edema
▪ Hyperlipidemia
(chol >200
mg/dL)
1o/Idiopathic
(90%)
▪ Minimal Change
Disease (most
common)
▪ FSGS
▪ MPGN (GN
Associated)
▪ C3
Glomerulopathy ▪
Membranous
Nephropathy
2o to Systemic
Disease
▪ SLE
▪ HSP
▪ Malignancy
(Lymphoma and
Leukemia
▪ Infections
(Hepatitis, HIV,
Malaria)
▪ Hereditary
Proteinuria
Syndrome
Please see Table
545.1
Please see Table 545.2
MINIMAL CHANGE NEPHROTIC SYNDROME
▪ ~85%; glomeruli appear normal or minimal ↑mesangial cells &
matrix, IF: (-), EM: effacement of epithelial cell foot processes;
>95% respond to steroid
▪ M>F (2:1); 85-90% <6yr (most commonly 2-6yr); only 20-30%
of adol
▪ absence of HTN and gross hematuria (nephritic features)
MESANGIAL PROLIFERATION
▪ LM: diffuse ↑mesangial cells & matrix on light microscopy; IF:
trace to 1+ mesangial IgM and/or IgA; EM: mesangial cells &
matrix; effacement of epithelial cell foot processes; ~50%
respond to steroid
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
▪ LM: mesangial cell proliferation & segmental scarring; IF:
(+)IgM & C3 in segmental sclerosis; EM: segmental scarring of
glomerular tuft w/ obliteration of glomerular capillary lumen;
20% respond to steroid; often progressive to ESRD
▪ Most common cause of ESRD in adol
PPS Oral Exam Reviewer 2020
enteritis or renal insufficiency from HUS predominates
▪ Stool culture often negative
Pneumococci-associated HUS: pneumonia, empyema, bacteremia
Genetic form: risk for recurrence, severe prognosis, benefit from
different therapy
Edema: most common presenting sx
▪ Underfill hypothesis: proteinuria → ↓plasma protein level →
↓intravascular oncotic pressure → edema & secretion of vasopressin
and atrial natriuretic factor → ↑Na and water retention
▪ Overfill hypothesis: primary Na retention → volume expansion →
edema
▪ Misdiagnosed as allergic disorder: periorbital swelling that ↓at end
of day
▪ DDx of marked edema: protein-losing enteropathy, hepatic/heart
failure, acute/chronic GN, protein malnutrition
▪ Goal: gradual reduction of edema w/ diuretics, Na restriction,
cautious use of IV albumin
Hyperlipidemia
▪ ↑Synthesis & ↓catabolism of lipids; ↑cholesterol, triglycerides,
LDL, VLDL; HDL unchanged or low; ↑CV in adults, in children not as
serious
↑ Susceptibility to infection: cellulitis, spontaneous bacterial
peritonitis, bacteremia
▪ Hypoglobulinemia: urinary loss of IgG, complement factors
(predominantly C3 & C5), alternative pathway factors B & D →
impaired opsonization
▪ Encapsulated bacteria
▪ Spontaneous bacterial peritonitis: fever, abdominal pain, peritoneal
signs → pneumococcus (most frequent), Gram (-) bacteria →
peritoneal leukocyte counts >250 cells/µL
▪ Appropriate cultures, treated promptly & empirically
Hypercoagulability
▪ Vascular stasis (hemoconcentration, intravascular volume
depletion), ↑Plt number & aggregability, changes in coagulation
factor levels; ↑ fibrinogen + urinary losses of antithrombotic factors
(antithrombin III & protein S)
▪ DVT → cerebral venous sinus, renal vein, pulmonary veins
▪ Low in children (2–5%) compared with adults; potential for serious
consequences
▪ Initial ep/relapse: follow infections, rxn to insect bites
▪ Rule out secondary forms: children ≥10yo, C3 level, ANA, anti
dsDNA; hepatitis B & C, HIV in high-risk
▪ Kidney biopsy: ≥ 12yr, does not fit picture of MCNS
▪ 3+ or 4+ proteinuria; microscopic hematuria
▪ Spot UPCr > 2.0
▪ Creatinine normal; ↑ if diminished renal perfusion from
contraction of intravascular volume
▪ Albumin < 2.5 g/dL; ↑serum cholesterol & triglyceride levels
▪ Serum complement: normal
▪ Steroid-resistant nephrotic syndrome (most often FSGS) →
poorer prognosis → ESRD requiring dialysis/kidney
transplant
Response: attainment of remission w/in initial 4wk
of steroid
Remission: UPCr ratio <0.2 or <1+ protein on urine
dipstick for 3 consecutive days
▪ MCD respond to daily prednisone w/in the first 23wk
Relapse: ↑ First morning UPCr >0.2 or 2+ and
higher for 3 consecutive days
Frequently relapsing: 2 or more relapses w/in 6mo
after initial therapy or 4 relapses in a 12-mo period
Steroid dependent: relapse during steroid tapering
or a relapse w/in 2wk of discontinuation
Steroid resistance: inability to induce remission
w/in 4wk of daily steroid
–
Trace
+
++
+++
++++
PROTEINURIA
Negative
10-20 mg/dL
30mg/dL
100mg/dL
300mg/dL
1000-2000 mg/dL
▪ Prednisone/prednisolone single daily dose 60mg/m2/day or 2mkday
(max 60mg daily) for 4-6wk; ffd by alternate-day prednisone (starting at
40mg/m2 QD or 1.5mg/kg QD) ranging 8wk to 5mo w/ tapering
● Duration controversial; prolonged tx w/ tapering 2-5mo ↓incidence
of relapse; KDIGO: at least 12wk
▪ Severe symptomatic edema (large pleural effusions, ascites, severe
genital edema) → hospitalized
● HypoNa+: fluid & Na restriction (<1,500 mg daily)
● Diuresis: loop diuretics (furosemide) extreme caution → aggressive
diuresis → intravascular volume depletion, ↑risk for ARF & intravascular
thrombosis
● Edema w/ intravascular volume depletion (hemoconc, hypotension,
tachycardia), IV 25% albumin (0.5-1.0g/kg) slow infusion ffd by IV
furosemide 1-2mkdose → monitor volume status, BP, elec balance, renal
function → complication (esp rapid infusion): volume overload (HTN,
heart failure, pulmonary edema)
▪ Dyslipidemia: low-fat diet (limit to <30% of calories w/ saturated fat
intake of <10% calories); dietary cholesterol <300mg/day
▪ Parent educ: sx of cellulitis, peritonitis, bacteremia
● Blood culture; broad coverage antibiotics: include Pneumococcus,
Gram(-) bacteria; 3rd-gen ceph common choice
● Spontaneous bacterial peritonitis: peritoneal fluid cell count, GS,
culture
▪ Thromboembolism: imaging confirm presence of clot
● Heparin, LMW heparin, warfarin
▪ Relapses → triggered by URI or GI infections
● Tx similar to initial ep except daily prednisone course shortened
● Duration of alternate-day therapy depend on freq of relapses
▪ Steroid resistance → failure to achieve remission after 8wk of steroid →
kidney biopsy, eval kidney function, quantitation of urine protein
excretion → reduced life expectancy
▪ Steroid-dependent, frequent relapsers, steroid-resistant → alternative
(particularly steroid toxicity: cushingoid appearance, HTN, cataracts,
and/or growth failure)
▪ Cyclophosphamide (2mg/kg single PO dose, 8-12wk) prolong remission,
↓number of relapse in children w/ frequently relapsing & steroiddependent NS; SE: neutropenia, disseminated varicella, hemorrhagic
cystitis, alopecia, sterility, ↑risk future malignancy
● Alternate-day prednisone often continued
● WBC monitored weekly; withheld if <5,000/mm3
● Cumulative threshold dose >250mg/kg: oligospermia/ azoospermia
▪ Calcineurin inhibitors (cyclosporine/tacrolimus): initial tx for steroidresistant; SE: HTN, nephrotoxicity, hirsutism, gingival hyperplasia
▪ Mycophenolate: maintain remission in steroid-dependent, frequently
relapsing NS
▪ Levamisole, antihelminthic w/ immunomodulating effect: ↓risk of
relapse in comparison to prednisone
Batch Clingy
NEPHROTIC
SYNDROME
● Capillary & arteriolar endothelial injury in kidney →
localized thrombosis → ↓glomerular filtration
● Microvascular injury → progressive platelet aggregation →
consumptive thrombocytopenia
● Mechanical damage to RBC passing through
damaged/thrombotic microvasculature → microangiopathic
hemolytic anemia
▪ 1-3 per 100,000 children <16yr
▪ W/out tx: ↑risk of death, most commonly from infections
▪ 80%: respond to steroids
▪ Podocyte, GBM and fenestrated glomerular endothelium →
glomerular filtration barrier
▪ Podocyte: structural support of the capillary loop; major
filtration barrier to proteins; involved in synthesis & repair of
GBM
▪ Slit diaphragm: major impediments to protein permeability;
not simple passive filters, consist of numerous proteins →
contribute to complex signaling pathways, play important role in
podocyte function
▪ Nephrin, podocin, CD2AP, α-actinin 4: important component
protein of slit diaphragm
▪ Immune & nonimmune insults to podocyte → foot process
effacement, ↓functional podocytes, altered slit diaphragm →
↑permeability of the glomerular capillary wall → massive
proteinuria & hypoalbuminemia
▪ Pathogenesis of idiopathic nephrotic syndrome (hypothesis):
either immune mediated (systemic podocyte-derived circulating
factor) or genetic (mutations assoc w/ steroid-resistant
nephrotic syndrome)
▪ Genetic screening cohort: mutations in NPHS1, WT1, and
NPHS2 → steroid-resistant nephrotic syndrome and congenital
nephrotic syndrome
107
SECONDARY NEPHROTIC SYNDROME
▪ > 8yr w/ HTN, hematuria, renal dysfunction, extrarenal sx (rash,
arthralgias, fever), ↓serum complement levels
▪ Present at birth: edema caused by massive proteinuria
▪ Delivered w/ enlarged placenta (>25% of infant’s wt)
▪
Severe
hypoalbuminemia,
hyperlipidemia,
hypogammaglobulinemia: from loss of filtering selectivity at
glomerular filtration barrier
▪ Prenatal dx: ↑maternal and amniotic AFP levels
▪ Denys-Drash syndrome (mutations in the WT1 gene): abnormal
podocyte function; early-onset nephrotic syndrome, progressive
renal insufficiency, ambiguous genitalia, Wilms tumors
▪ Pierson syndrome: mutations in LAMB2 gene → abnormalities of
β2-laminin, critical component of the glomerular and ocular
basement membranes → bilateral microcoria (fixed narrowing of
pupil)
▪ Galloway-Mowat syndrome: microcephaly w/ hiatal hernia &
congenital nephrotic syndrome; kidney biopsy: loss of or poor
basement membrane formation or permeation of their basement
membranes with fibrils
▪ Clinical dx: severe generalized edema, poor growth & nutrition w/
hypoalbuminemia, ↑susceptibility to infections, hypothyroidism
(urinary loss of thyroxin-binding globulin), ↑risk of thrombotic
events
Most: progressive renal insufficiency
Batch Clingy
CONGENITAL NEPHROTIC SYNDROME
▪ Nephrotic syndrome manifesting at birth or w/in the first
3mos of life
▪ Primary (syndromes inherited as autosomal recessive
disorders) or secondary to utero infections (CMV, toxoplasmosis,
syphilis, hep B and C, HIV), infantile SLE, mercury exposure
▪ Structural and functional abnormalities of glomerular filtration
▪ European cohort of children: 85% mutations in four genes:
NPHS1, NPHS2, WT1 (components of glomerular filtration
barrier) and LAMB2
● Finnish type: mutations in NPHS1 or NPHS2 gene →
encodes nephrin and podocin
▪ Rituximab: prolong remissions steroid-dependent and/or steroidresistant NS; less effective in patients treated w/ calcineurin inhibitors &
steroids and w/ multidrug-resistant NS
▪ ACE inhibitor/ARBs: ↓proteinuria in steroid-resistant
▪ PCV13 & PPSV23, influenza vaccine to child & contacts
● Defer live vaccines til on prednisone 1mkday or 2mg/kg on alternate
days; contraindicated receiving cyclophosphamide/ cyclosporine
● Close contact w/ varicella infection, give VZIG
● Immunize household contacts w/ live vaccines → minimize risk of
transfer; avoid direct exposure of child to GI or respiratory secretions of
vaccinated contacts for 3-6wk after vaccination
▪ Intensive supportive care; IV γ-globulin, albumin & diuretic infusions;
high amounts of protein (3-4g/kg), lipids, high caloric intake to maintain
nutrition, vitamin and thyroid hormone replacement; unilateral
nephrectomy; ACE inhibitor, angiotensin II receptor inhibitors, and
prostaglandin synthesis inhibitors
● Conservative fails, suffer from persistent anasarca/repeated severe
infections → bilateral nephrectomy, chronic dialysis
● Renal transplant: definitive treatment (recurrence reported after
transplant)
● Some centers: more aggressive, bilateral nephrectomy at 1-2yr of
age, weight >7kg, initiation of peritoneal dialysis w/ subsequent kidney
transplantation
▪ Secondary congenital nephrotic syndrome resolves w/ tx of underlying
cause
PPS Oral Exam Reviewer 2020
108
Complex
URINARY
LITHIASIS
EPIDEMIOLOGY / PATHOGENESIS
▪ Genetic, climatic, dietary, and socioeconomic factors
▪ Adolescents: 10x more likely to have symptomatic
calculus than children 0-3yr
▪ ↑stone disease (in US): obesity, changes in dietary
habits (↑Na and fructose intake, ↓Ca and water intake)
▪ Southeast Asia: urinary calculi endemic, related to diet
▪ Contamination of infant formula w/ the organic base
and illegally added nitrogen-containing food additive
melamine: China (2008)
▪ ~90%: contain Ca; 60% composed of Ca oxalate
▪ Renal calculi: crystals that form on calyx
▪ Bladder calculi: formed in the kidney → traveled down
ureter; form primarily in bladder
▪ ↓Urine volume, ↓urine pH, Ca, sodium, oxalate,
urate: promote stone formation
▪ Many inorganic (citrate, magnesium) and organic
(glycosaminoglycans, osteopontin) substance: inhibit
stone formation
▪ Stone formation depends on four factors
● Matrix: mixture of protein, nonamino sugars,
glucosamine, water & organic ash that make up 2–9% of
dry wt of stones; arranged in organized concentric
laminations
● Precipitation-crystallization: supersaturation of
urine w/ specific ions → crystals aggregate by chemical
& electrical forces; ↑saturation of urine w/ ions →
↑rate of nucleation, crystal growth, aggregation →
↑stone formation & growth
● Epitaxy: aggregation of crystals of diff composition
but similar lattice structure → forming stones of
heterogeneous nature; lattice structures of Ca oxalate &
monosodium urate have similar structure → Ca oxalate
aggregate on nucleus of monosodium urate crystals
● Absence of inhibitors of stone formation (citrate,
diphosphonate, magnesium ion) in the urine
CLINICAL MANIFESTATIONS / LABORATORY FINDINGS
▪ Gross or microscopic hematuria
▪ Calculus: ureteral or renal pelvic obstruction → severe flank (renal colic) or abdominal
pain
● Areas of narrowing: ureteropelvic junction, where ureter crosses iliac vessels,
ureterovesical junction (most narrow segment); ureter progressively narrows distally
● Pain radiates anteriorly to scrotum or labia; intermittent (periods of obstruction of
urine flow ↑pressure in collecting system)
● Distal ureter: irritative sx, dysuria, urgency, frequency; stone pass into bladder→
asymptomatic
● In the urethra: dysuria & diff voiding (particularly in males)
● Some children: pass small amounts of gravel-like material
▪ ~90%: calcified to some degree → radiopaque on plain abdominal film
● Only a few mm in diameter → difficult to see (particularly in the ureter)
● Struvite (magnesium ammonium phosphate) stones: radiopaque
● Cystine, xanthine, uric acid calculi: may be radiolucent but often slightly opacified
▪ Suspected renal colic → most accurate: unenhanced spiral CT of abdomen & pelvis; Sn &
Sp 96% in delineating number and location of calculi, demonstrates if involved kidney is
hydronephrotic
● Pediatric imaging centers use low-dose CT (similar to 3 CXR)
● Alternative: plain radiograph of abdomen & pelvis plus renal UTZ → hydronephrosis,
possibly calculus on radiograph; calculus not visualized on UTZ unless adjacent to
bladder/renal pelvis; renal calculi <3mm typically not seen
● Balance risks of CT imaging against ↓Sn of plain abdominal film plus sonography
● Difficult to determine whether hydronephrosis is sec to obstructing stone, UPJO or
both
Please refer to Table 562.3 Urine Chemistry: Normal Values
Metabolic Evaluation of Children with Hypercalciuria
RestricFasting
Type
Serum Ca
ted Ca
Ca
(Urine)
(Urine)
Absorptive
N
N or ↑
N
Ca Load
(Urine)
PTH
(serum)
↑
↑
Renal
N
↑
↑
↑
N
Resorptive
↑
↑
↑
↑
↑
▪ Metabolic evaluation (note: structural, infectious, metabolic factors often coexist)
● Eval not undertaken in child in the process of passing stone → altered diet and
PPS Oral Exam Reviewer 2020
COMPLICATIONS / PROGNOSIS
▪ May be asymptomatic (but uncommon to
pass a ureteral calculus w/out sx)
▪ Child diagnosed w/ calculus: serial plain xrays or renal UTZ → follow status of calculus,
↑/↓ size, has moved; renal pelvic calculus →
suspect UPJO
▪ Decision to remove: location, size,
composition (if known), presence of
obstruction and/or infection
TREATMENT / PREVENTION
▪ Pain: NSAIDs, opiates
▪ Small ureteral calculi pass spontaneously (child might experience
severe renal colic)
▪ Narrowest segment (ureterovesical junction): calculi <5mm will pass
80–90% of the time
▪ α-adrenergic blocker tamsulosin, 0.4mg at bedtime → ↓ureteral
pressure below stone, ↓frequency of peristaltic contractions → medical
expulsive therapy
▪ Ureteral stent: relieve pain, dilate ureter (allow to pass)
▪ Uric acid calculus or furosemide-associated calculus → dissolution
alkaline therapy
▪ Calculus does not pass, assoc UTI → removal: lithotripsy; ESWL;
percutaneous nephrostolithotomy; laparoscopic removal (Please see
Table 562.5 for comparison)
▪ Maintaining continuous ↑UO: ↑fluid intake effective method of
preventing further stones → continued at night → necessary for child to
get up at least once a night to urinate and drink more water
▪ Daily fluid intake of 2-2.5 L in adolescent stone formers, ↑intake during
summer
▪ ↓sodium, ↓protein diet: ↓urine Ca & oxalate excretion
▪ Avoid excess Ca intake, however, children require Ca for bone
development → Ca restriction avoided
▪ Thiazide diuretics: ↓renal Ca excretion
▪ Potassium citrate (inhibitor of Ca stones) 1-2mEq/kg/24hr
● Source of citrate: lemonade (4oz lemon juice = 84mEq citric acid);
daily mixture of 4oz of reconstituted lemon juice in 2L of water ↑urinary
citrate level
▪ Neutral orthophosphate (difficult cases, poorly tolerated)
▪ Uric acid: allopurinol (xanthine oxidase inhibitor), ↓production uric
acid and 2,8-dihydroxyadenine; urine alkalinization (≥6.5) w/ Na
bicarbonate/Na citrate
▪ Cystine: more soluble when urinary pH >7.5
● D-penicillamine, chelating agent binds to cysteine or homocysteine;
poorly tolerated, effective in dissolving & prevent recurrence when
hydration & alkalinization fail
▪ N-Acetylcysteine: low toxicity, control cystinuria (lack long-term
experience)
▪ Type 1 RTA: correct metabolic acidosis, replace lost Na and K+ (sodium
or potassium citrate therapy)
▪ Primary hyperoxaluria: liver transplant (defective hepatic enzymes);
ideally, performed before renal failure
▪ Severe cases: kidney transplant
Batch Clingy
DISEASE
109
hydration status, effect of obstruction on the kidney → alter result
● Hypercalciuria → studies of Ca excretion w/ dietary Ca restriction & Ca loading are
necessary
Calcium Oxalate and Calcium Phosphate Calculi
▪ Most common metabolic abnormality: normocalcemic hypercalciuria; 30-60% of children w/ Ca stones
▪ Hypercalciuria: absorptive, renal or resorptive
● Primary disturbance in absorptive hypercalciuria: intestinal hyperabsorption of Ca
● Renal hypercalciuria: impaired reabsorption of Ca → mild hypocalcemia → ↑PTH → ↑intestinal absorption of Ca & ↑mobilization of Ca stores
● Resorptive hypercalciuria: uncommon; primary hyperparathyroidism → ↑PTH secretion
▪ Hyperoxaluria: ↑Ca oxalate precipitation
● Primary hyperoxaluria: rare autosomal recessive disorder
● Secondary hyperoxaluria: more common, ↑intake of oxalate (tea, coffee, spinach, rhubarb), precursors (vit C), pyridoxine deficiency, intestinal
malabsorption
▪ Enteric hyperoxaluria: IBD, pancreatic insufficiency, biliary disease → GI malabsorption of fatty acids w/c bind intraluminal Ca → form salts excreted
in feces
● Normally, Ca forms complex w/ oxalate → ↓oxalate absorption
▪ Hypocitraturia: ↓excretion of citrate (inhibitor of Ca stone: form complex w/ Ca, ↑solubility, inhibit aggregation of Ca phosphate & Ca oxalate
crystal)
● Idiopathic; chronic diarrhea, intestinal malabsorption & RTA
▪ Type 1 RTA: urine pH never <5.8, hyperchloremic hypokalemic acidosis → nephrolithiasis, nephrocalcinosis, muscle weakness, osteomalacia
▪ Cystic fibrosis
▪ Hyperuricosuria: epitactic growth of Ca oxalate around nucleus of uric acid crystals; action of uric acid as counterinhibitor of urinary
mucopolysaccharides
▪ Heterozygous cystinuria: mechanism unknown; may be similar to uric acid
▪ Sarcoidosis: ↑sensitivity to vit D3 → ↑absorption of Ca from GI
▪ Lesch-Nyhan syndrome: excessive uric acid synthesis
▪ Immobility: hypercalciuria by mobilization of Ca stores
▪ High dose steroids: hypercalciuria & Ca oxalate precipitation
▪ Furosemide: NICU → severe hypercalciuria, urolithiasis, nephrocalcinosis
▪ Idiopathic: complete metabolic evaluation performed prior to this dx
RENAL TB
(Nelson’s + PPS
TB Guidelines)
▪ Rare in children, incubation several years (up to 1520yr after primary infection):
● Local study on extrapulmonary TB, constituted 3%
● GU tract TB mostly seen in >7yo
▪
Tubercle
bacilli
reach
kidney
during
lymphohematogenous dissemination → tubercles in
glomeruli → caseating sloughing lesions discharge TB
bacilli into tubules
PPS Oral Exam Reviewer 2020
▪ Infection can be unilateral or bilateral, can spread caudad to bladder
▪ Clinically silent in early stages → sterile pyuria and microscopic hematuria
▪ Dysuria, flank or abdominal pain, and gross hematuria develop as disease progresses
▪ (PPS: insidious in onset; 75% sx related to urinary tract inflammation)
▪ Suspected in presence of destructive pulmonary TB w/ persistent, painless, sterile
pyuria, assoc albuminuria & hematuria
▪ Urine cultures for M tuberculosis: positive 80–90% of cases (PPS: repeated culture
advisable; complete urologic investigation mandatory for those w/ persistent pyuria)
Cystine Calculi
▪ Cystinuria: rare autosomal recessive disorder of epithelial cells of renal tubule → prevent absorption of 4 dibasic amino
acids (cystine, ornithine, arginine, lysine) → excessive urinary excretion → ↓solubility of cystine
▪ Acidic urine → ↑rate of precipitation
Struvite Calculi
▪ UTI (urea-splitting organisms: Proteus, occ Klebsiella, E coli, Pseudomonas) → urinary alkalinization, ↑production of
ammonia → precipitation of magnesium ammonium phosphate (struvite) & Ca phosphate
▪ calculi → staghorn configuration → obstruction, perpetuate infection, gradual kidney damage
▪ metabolic abnormalities, neuropathic bladder (particularly undergone urinary tract reconstructive procedure)
Uric Acid Calculi
▪ Hyperuricosuria w/ or w/out hyperuricemia
▪ Stones: radiolucent
▪ Inborn errors of purine metabolism, Lesch-Nyhan syndrome, G6PD, short-bowel syndrome, rapid turnover of purine w/
tumors & myeloproliferative diseases
▪ Uric acid calculi/“sludge” fill entire upper collecting system → renal failure, anuria
▪ Present w/in Ca containing stones → more than one predisposing factor for stone formation
Indinavir Calculi
▪ Indinavir sulfate: protease inhibitor for HIV infection → 4% acquire symptomatic nephrolithiasis
● 12% excreted unchanged in urine → rectangles, fan-shaped or starburst crystals
● Soluble at pH <5.5; urinary acidification w/ ammonium chloride or ascorbic acid
▪ Mostly radiolucent
Nephrocalcinosis
▪ Ca deposition w/in the renal tissue
▪ Furosemide (premature neonates → hypercalciuria), distal RTA, hyperparathyroidism, medullary sponge kidney,
hypophosphatemic rickets, sarcoidosis, cortical necrosis, hyperoxaluria, prolonged immobilization, Cushing syndrome,
hyperuricosuria, monogenetic causes of HTN, renal candidiasis
▪ Superinfection by other bacteria common →
PPS
delay recognition of TB
2HRZE/4HR
▪ Hydronephrosis or ureteral strictures
▪ Category I: Pulmonary or Extra-pulmonary TB, new (whether
▪ PPS: children whose urine reveal presence of
bacteriologically-confirmed or clinically-diagnosed) except CNS/bones or
tubercle bacilli are considered to be highly
joints
infectious & should be isolated until urine
2HRZES/1HRZE/5HRE
sterile
▪ Category II: Pulmonary or Extra-pulmonary TB, previous treated drugsusceptible TB (whether bacteriologically-confirmed or clinically-
Batch Clingy
Please see Table 562.1
110
▪ Organism recovered from urine in cases of miliary TB &
some w/ PTB in absence of renal parenchymal dx
▪ True renal TB: small caseous in renal parenchyma
▪ Infection spreads locally to ureters, prostrate or
epididymis
▪ Genital tract TB: uncommon in prepubescent boys &
girls
● Lymphohematogenous spread, direct spread from
intestinal/urinary tract or bone
● PPS: frequently, other forms of TB w/ initial
infection (pleural effusion)
● Adolescent girls: can develop genital tract TB during
primary infection → fallopian tubes 90–100% of cases;
endometrium 50%; ovaries 25%; cervix 5%
▪ Non–anion gap (hyperchloremic) metabolic acidosis in
normal/near-normal GFR
Genital TB: systemic manifestation usually absent, CXR normal in majority, TST usually
reactive
▪ Adolescent female: lower abdominal pain, dysmenorrhea or amenorrhea, lower
abdominal mass, free peritoneal fluid; PPS: considered in mothers when managing
newborns suspected of infection (congenital TB) in perinatal period; TB of external
genitalia → consider child abuse
▪ Adolescent male: epididymitis or orchitis; present as painless, unilateral nodular swelling
of the scrotum; involvement of glans penis extremely rare; PPS: may develop primary TB
of penis after circumcision presenting as massive inguinal lymphadenopathy
▪ Genital abnormalities, (+) TST, adolescent → genital tract TB
4 main types:
▪ Proximal (type II) (impaired HCO3 reabsorp)
▪ Classic distal (type I) (failure to secrete acid)
▪ Hyperkalemic (type IV)
▪ Combined proximal and distal (type III)
▪ Hx: growth & devt, diarrhea, family hx of mental retardation, failure to thrive, ESRD,
infant deaths, or miscarriages
▪ PE: growth parameters and volume status, dysmorphic features
▪ Patient with suspected RTA → confirm normal anion gap metabolic acidosis, elec
imbalance, assess renal fx, r/o other causes of bicarb loss
● Metabolic acidosis in diarrheal dehydration: common, improve w/ fluid correction;
depletes total-body bicarb stores, persistent acidosis despite volume restoration → allow
several days for reconstitution of total-body bicarb stores before full eval for RTA
● Acidosis persists → serum elecs, BUN, Ca+, phosphorus, crea, pH; traumatic blood
draws, small vol of blood in adult-size tubes, prolonged specimen transport time at room
temp → falsely low bicarb levels, ↑serum K+
● Blood anion gap: [Na+] − [Cl− + HCO3−]
- <12: absence of anion gap; >20: presence of anion gap
- anion gap: lactic acidosis, DKA, IEM, ingested toxins
- tachypnea → ABG → possibility of mixed acid–base disorder
▪ Urine pH → distal (pH <5.5) vs proximal (pH >6.0)
● Urine anion gap ([urine Na+ + urine K+] − urine Cl−) confirm diagnosis of distal RTA
● (+) gap: deficiency of ammoniagenesis → possibility of distal RTA
● (-) gap: proximal tubule bicarb wasting (or GI wasting)
diagnosed)
▪ Prognosis: depend on underlying disease
▪ Treated isolated proximal or distal RTA →
improvement in growth, provided serum
bicarb in normal range
▪ Systemic illness & Fanconi syndrome →
growth failure, rickets, sx related to underlying
dx
▪ Rickets: bone pain, growth retardation,
osteopenia, pathologic fractures
Finding
Plasma [K+]
Urine pH with acidosis
Urine net charge
Fanconi lesion
Fractional
bicarbonate
excretion
U−BPco2
Response to therapy
Associated features
▪ UA: glycosuria, proteinuria, hematuria → global tubular damage or dysfunction
▪ Random or 24hr urine Ca and crea → identify hypercalciuria
▪ Renal UTZ: identify underlying structural abnormalities, obstructive uropathies,
nephrocalcinosis
▪ Mainstay of therapy in all forms: Bicarbonate replacement
Proximal
Classic Distal
Low
<5.5
Negative
Present w/ acquired
pRTA
>10–15% during alkali
therapy
Normal
Least responsive
Low
>5.5
Positive
Absent
Fanconi syndrome
2–5%
Low
Responsive
Nephrocalcinosis/
hyperglobulinemia
Generalized Distal
Dysfunction
High
<5.5 or >5.5
Positive
Absent
5–10%
Low
Less responsive
Renal insufficiency
Batch Clingy
RENAL TUBULAR
ACIDOSIS
▪ Acid–base balance by kidneys: reabsorption of filtered
HCO3− & excretion of H+
● H+ secretion from tubule cells into lumen → key in
reabsorption of HCO3− and formation of titratable acid
(H+ bound to buffers, HPO42−) & NH4+ ions
● Loss of filtered HCO3− equivalent to addition of H+
to body; all filtered HCO3− absorbed before dietary H+
can be excreted
● ~90% of filtered bicarbonate absorbed in proximal
tubule; 10% in distal segments, mostly thick ascending
limb and outer medullary collecting tubule
● In proximal tubule & TAL of loop of Henle, H+ from
water → secreted by the Na+-H+ exchanger on luminal
membrane; H+ combines w/ filtered HCO3− →
formation of H2CO3 → splits into water and CO2 in
presence of carbonic anhydrase IV
● CO2 diffuse freely back into cell → combine with
OH− (from H2O) to form HCO3− in presence of carbonic
anhydrase II → returns to systemic circulation via Na+HCO3 − cotransporter at basolateral membrane of cell
● In collecting tubule, H+ secreted into lumen by
H+ATPase (adenosine triphosphatase) and HCO3−
returned to systemic circulation by HCO3–-Cl−
exchanger on basolateral membrane
● H+ secreted proximally and distally in excess of
filtered HCO3− → excreted in the urine as titratable acid
(H2PO4−) or as NH4+
▪ AFB of large volumes of urine sediment: positive 50–70% of cases
▪ TST nonreactive: up to 20% of patients
▪ Pyelogram or CT scan: mass lesions, dilation of the proximal ureters, multiple small filling
defects, and hydronephrosis if ureteral stricture present
PPS Oral Exam Reviewer 2020
111
DISTAL (TYPE I) RTA
▪ Result from damaged/impaired functioning of one or
more transporters or proteins involved in the
acidification process (including H+/ATPase, HCO3−/Cl−
anion exchangers, or components of the aldosterone
pathway)
▪ Shared features w/ pRTA: non–anion gap metabolic
acidosis, growth failure
▪
Distinguishing
features:
nephrocalcinosis,
hypercalciuria; phosphate & massive bicarb wasting
generally absent
ACUTE KIDNEY
INJURY
Abrupt loss of
kidney function
→
↓GFR,
accumulation of
waste products
HYPERKALEMIC (TYPE IV) RTA
▪ Impaired aldosterone production (hypoaldosteronism)
or impaired renal responsiveness to aldosterone
(pseudohypoaldosteronism)
▪ Aldosterone → direct effect on H+/ATPase (responsible
for hydrogen secretion); potent stimulant for K+
secretion in collecting tubule
● no aldosterone → hyperkalemia; further affects
acid–base status → inhibiting ammoniagenesis and H+
excretion
▪ Prerenal (prerenal azotemia): ↓effective circulating
arterial volume (dehydration, sepsis, hemorrhage,
severe hypoalbuminemia, cardiac failure) → inadequate
renal perfusion, ↓GFR; absent structural kidney damage
▪ Intrinsic renal: renal parenchymal damage (sustained
hypoperfusion, ischemic/hypoxic injury, nephrotoxic
insults; assoc w/ cardiac, oncologic, urologic, renal, and
genetic disorders or prematurity)
● severe and prolonged ischemic/hypoxic injury &
PPS Oral Exam Reviewer 2020
▪ Growth failure in the 1st year of life; polyuria, dehydration (from sodium loss), anorexia,
vomiting, constipation, hypotonia
▪ Fanconi syndrome: rickets sec to phosphate wasting
▪ UA: isolated pRTA generally unremarkable (urine pH acidic (<5.5) because distal
acidification intact); Fanconi syndrome: phosphaturia, aminoaciduria, glycosuria,
uricosuria, ↑urinary sodium or potassium
▪ Isolated autosomal recessive pRTA: mutation in gene encoding Na bicarbonate
cotransporter NBC1; ocular abnormalities (band keratopathy, cataracts, glaucoma, often
leading to blindness), short stature, enamel defects of teeth, intellectual impairment, occ
basal ganglia calcification
● Autosomal dominant pattern: identified in a single pedigree w/ 9 members:
hyperchloremic metabolic acidosis; normal ability to acidify urine &renal function, growth
retardation.
▪ Cystinosis: mutations in CTNS gene; defect of cysteine metabolism → accumulation of
cystine crystals in major organs of body (kidney, liver, eye, brain)
● Infantile or nephropathic cystinosis: most severe form; present in 1st or 2nd year of
life w/ severe tubular dysfunction, growth failure → not treated, ESRD by end of 1st
decade
▪ Lowe syndrome (oculocerebrorenal syndrome of Lowe): rare X-linked disorder;
mutations in the OCRL1 gene; congenital cataracts, mental retardation, Fanconi syndrome
▪ Impaired H+ ion excretion → urine pH cannot be reduced to <5.5 despite severe
metabolic acidosis
▪ Loss of Na bicarbonate distally (lack of H+ to bind to in tubular lumen) → ↑Clabsorption → hyperchloremia
▪ Inability to secrete H+ → compensated for by ↑K+ secretion distally → hypoK+
▪ Hypercalciuria → nephrocalcinosis/nephrolithiasis
▪ Chronic metabolic acidosis → impaired urinary citrate excretion → hypocitraturia →
↑risk of Ca deposition in tubules
▪ Mobilization of organic components from bone to serve as buffers to chronic acidosis →
bone dx
▪ Medullary sponge kidney: relatively rare sporadic disorder
● cystic dilation of terminal portions of collecting ducts as they enter renal pyramids;
UTZ: medullary nephrocalcinosis; normal renal function through adulthood →
complications: nephrolithiasis, pyelonephritis, hyposthenuria, distal RTA; assoc w/
Beckwith-Wiedemann syndrome or hemihypertrophy
▪ Aldosterone deficiency → adrenal gland disorders (Addison disease, some forms of CAH)
▪ Aldosterone unresponsiveness: more common cause in children → can occur transiently
(acute pyelonephritis, acute urinary obstruction) or chronically (obstructive uropathy)
▪ Growth failure in 1st few years of life; polyuria & dehydration (from salt wasting); rarely
(esp pseudohypoaldosteronism type 1) life-threatening hyperK+
▪ Obstructive uropathy → acute pyelonephritis
▪ Hyperkalemic non–anion gap metabolic acidosis
▪ Alkaline/acidic urine
▪ ↑Urinary Na w/ inappropriately ↓urinary K+ (lack aldosterone effect)
▪ Defined as: ↑serum creatinine by ≥0.3 mg/dL from baseline within 48h or ↑serum
creatinine to ≥1.5times baseline within the prior 7 days
or urine volume ≤ 0.5 mL/kg/hr for 6 hr
▪ Carefully taken hx → define cause of AKI
● Infant, 3-day hx of vomiting & diarrhea → prerenal (volume depletion) or consider
HUS
● 6yo, recent pharyngitis, periorbital edema, HTN, gross hematuria → intrinsic
(postinfectious GN)
● Critically ill, hx of protracted hypotension/exposure to nephrotoxic meds → ATN
Rickets: hypophosphatemia & phosphaturia
from generalized proximal tubular dysfunction
▪ Bicarb & oral phosphate → heal rickets
▪ VitD – offset 2o hyperparathyroidism
complicating oral phosphate therapy
▪ Require large quantities of bicarbonate → up to 20 mEq/kg/24hr
▪ Na bicarbonate or Na citrate (Bicitra or Shohl solution)
▪ Fanconi syndrome: phosphate supplementation
Bone demineralization w/out overt rickets
▪ Dissolution of bone → Ca carbonate in bone
→ serves as buffer against metabolic acidosis
▪ Administration of sufficient bicarb → reverse
acidosis → reverse
bone dissolution & hypercalciuria
▪ Base rqmt: 2-4 mEq/kg/24hr (individualize)
▪ Monitor hypercalciuria
● Symptomatic (recurrent eps of gross hematuria), nephrocalcinosis,
nephrolithiasis → thiazide diuretic → ↓urine Ca excretion
▪ Chronic tx for hyperK+ → sodium–potassium exchange resin (sodium
polystyrene sulfonate)
Please see Table 550.5
▪ Functional AKI induced by dehydration →
usually reversible w/ early fluid therapy
▪ Mortality rate: depends on underlying dx
process rather than on renal failure itself
● AKI caused by renal-limited condition:
↓mortality rate (<1%)
● AKI related to multiorgan failure:
▪ Volume status → no overload/cardiac failure → isotonic saline,
20mL/kg over 30min → hypovolemic patient void w/in 2 hr → failure
suggests intrinsic/postrenal AKI
▪ Diuretic: after adequate BV established → furosemide 2-4mg/kg single
IV dose (alternative: bumetanide 0.1mg/kg) → UO not improved →
continuous diuretic infusion
▪ ↑renal cortical blood flow → dopamine 2-3µg/kg/min (no controlled
data but clinicians use)
▪ mannitol: prevent pigment (myoglobin, hemoglobin)-induced renal
Batch Clingy
PROXIMAL (TYPE II) RTA
▪ Inherited and persistent from birth or occur as
transient phenomenon during infancy
▪ Occurs as component of global proximal tubular
dysfunction or Fanconi syndrome (low-molecular-weight
proteinuria, glycosuria, phosphaturia, aminoaciduria,
pRTA)
● ifosfamide (Wilms tumor & other malignancies) →
secondary Fanconi syndrome
112
nephrotoxic insult → ATN → most often critically ill
infants & children → pathology: tubular cell necrosis;
mechanism of injury: alteration in intrarenal
hemodynamics, tubular obstruction, passive backleak of
glomerular filtrate across injured tubular cells into
peritubular capillaries
● tumor lysis syndrome: specific form related to
spontaneous or chemotherapy-induced cell lysis in
lymphoproliferative malignancies → primarily caused by
obstruction of tubules by uric acid crystals
● acute interstitial nephritis: result of hypersensitivity
rxn to therapeutic/infectious agent
▪ Postrenal: obstruction of urinary tract
● 2 functioning kidneys: obstruction must be bilateral
to result in AKI → relief of obstruction → recovery,
except w/ renal dysplasia or prolonged obstruction
● Neonate, hx of hydronephrosis on prenatal UTZ, palpable bladder → congenital
urinary tract obstruction (probably related to posterior urethral valves)
▪ PE: careful attention to volume status
● Tachycardia, dry mucous membrane, poor peripheral perfusion → inadequate
circulating volume → prerenal AKI
● HTN, peripheral edema, rales, cardiac gallop → volume overload → intrinsic AKI from
GN or ATN
● Rash, arthritis → SLE or HSP nephritis
● Palpable flank masses → renal vein thrombosis, tumors, cystic disease, urinary tract
obstruction
▪ Anemia: dilutional or hemolytic (SLE, renal vein thrombosis, HUS)
▪ Leukopenia (SLE, sepsis)
▪ Thrombocytopenia (SLE, renal vein thrombosis, sepsis, HUS)
▪ Hyponatremia (dilutional)
▪ Metabolic acidosis
▪ ↑Serum BUN, crea, uric acid, potassium, phosphate (diminished renal function)
● Serum creatinine: measure kidney function but insensitive & delayed measure
following AKI
▪ Hypocalcemia (hyperphosphatemia)
▪ ↓ Serum C3 level (postinfectious GN, SLE, MPGN)
▪ Antibodies detected: streptococcal (PSGN), nuclear (SLE), neutrophil cytoplasmic
(granulomatosis with polyangiitis, microscopic polyarteritis), glomerular basement
membrane (Goodpasture disease)
▪ Hematuria, proteinuria, RBC or granular urinary casts: intrinsic AKI (glomerular dx, ATN)
▪ WBC and WBC casts w/ low-grade hematuria & proteinuria: tubulointerstitial dx
▪ Urinary eosinophils: drug-induced tubulointerstitial nephritis
▪ Urinary indices: prerenal vs intrinsic
● Prerenal AKI: ↑specific gravity (>1.020), ↑urine osm (UOsm >500mOsm/kg), ↓urine
sodium (UNa <20mEq/L), fractional excretion of sodium <1% (<2.5% in neonates)
● Intrinsic AKI: specific gravity of <1.010, ↓urine osm (UOsm <350 mOsm/kg), ↑urine
sodium (UNa >40mEq/L), fractional excretion of sodium >2% (>10% in neonates)
▪ CXR: cardiomegaly, pulmonary congestion (fluid overload), pleural effusions
▪ renal UTZ: hydronephrosis/hydroureter (urinary tract obstruction), nephromegaly
(consistent w/ intrinsic renal disease)
▪ renal biopsy: determine precise cause of AKI (patient not have clearly defined
pre/postrenal AKI)
↑mortality rate (>50%)
▪ Recovery of renal function: depend on
disorder that precipitated AKI
▪ Sequelae of AKI → chronic renal insufficiency,
HTN, RTA, urinary concentrating defect
INDICATIONS FOR DIALYSIS
1. Anuria/oliguria
2. Volume overload with HTN/
pulmonary edema refractory to
diuretic therapy
3. Persistent hyperK+
4.
Severe
metabolic
acidosis
unresponsive to mgt
5.
Uremia
(encephalopathy,
pericarditis, neuropathy)
6. Ca:phosphorus imbalance w/
uncontrolled hypoCa tetany
7. Additional: inability to provide
adequate nutrition due to severe fluid
restriction
Intermittent hemodialysis
Relatively stable hemodynamic status; 3-4hr
sessions using pump-driven extracorporeal
circuit & large central venous catheter; 37times/wk
Peritoneal dialysis
Neonates & infants; hyperosmolar dialysate
dwell for 45-60min, drained by gravity,
repeated for 8-24hr/day (based on F&E),
anticoagulation
not
necessary;
surgically/percutaneously placed peritoneal
dialysis catheter; contraindicated w/ significant
abdominal pathology
Please see Table 550.4 Urinalysis, Urine Chemistries and Osmolality in AKI
PPS Oral Exam Reviewer 2020
CRRT
Unstable, concomitant sepsis, multiorgan
failure in ICU; continuous (24hr/day) using
specialized pump-driven machine; doublelumen catheter (IJV/femoral vein)
failure
▪ no response to diuretic challenge → discontinue; fluid restriction
● Relatively normal intravascular volume: 400mL/m2/24hr (insensible
losses) plus fluid equal to UO for that day
● Extrarenal (blood, GI tract) fluid losses: replaced, mL for mL, w/
appropriate fluids
● Markedly hypervolemic patients: further fluid restriction → omit
replacement of insensible fluid losses, UO, extrarenal losses
● Fluid intake, urine/stool output, body weight, serum chem
monitored daily
▪ Hyperkalemia (>6 mEq/L)
● Earliest ECG change: peaked T waves → ffd by widened QRS
intervals, ST segment depression, ventricular arrhythmias, cardiac arrest
● Exogenous sources (dietary, IV, TPN) eliminated
● Sodium polystyrene sulfonate resin (Kayexalate) 1g/kg, orally or by
retention enema
● More severe elevation (>7 mEq/L) esp w/ ECG change → emergency
measures
Calcium gluc 10% sol, 100mg/kg/dose (max 3000mg/dose)
Sodium bicarbonate, 1-2mEq/kg IV, over 5-10min
Regular insulin, 0.1 units/kg (with glucose 50% solution, 1 mL/kg, over
1hr)
▪ Mild metabolic acidosis: retention of H+ ions, phosphate, sulfate; rarely
requires treatment
● Severe (arterial pH <7.15; serum bicarb <8mEq/L) or contributes to
hyperK+ → correct partially: IV bicarbonate to raise arterial pH to 7.20
(approximates serum bicarb 12 mEq/L); remainder of correction: oral Na
bicarbonate after normalization of serum Ca and phosphorus
● IV bicarb → ↓ionized Ca conc → precipitate tetany
▪ Hypocalcemia: primary tx by ↓phosphorus level (↓diet phosphorus,
phosphate binders); IV Ca not given except tetany
▪ Hyponatremia: dilutional → fluid restriction; hypertonic (3%) saline for
symptomatic hypoNa+ or serum Na <120mEq/L
acute correction of serum Na to 125 mEq/L
mEq sodium required = 0.6 x wt in Kg x (125 – serum Na)
▪ GI bleeding: uremic platelet dysfunction, ↑stress, heparin exposure
(hemodialysis or CRRT) → H2 blockers (ranitidine)
▪ HTN: hyperreninemia, expansion of extracellular fluid volume
● Salt & water restriction, diuretic administration
● Rapid: isradipine (0.05-0.15mg/kg/dose, max 5mg QID)
● Longer-acting oral agents for maintenance:
- CCB (amlodipine 0.1-0.6mg/kg/24hr QD or BID)
- β blockers (labetalol 4-40mg/kg/24hr BID or TID)
● Severe symptomatic HTN (urgency or emergency)
- continuous infusions of nicardipine (0.5-5.0 µg/kg/min), Na
nitroprusside (0.5-10.0µg/kg/min), labetalol (0.25-3.0mg/kg/hr),
esmolol (150-300 µg/kg/min)
▪ seizure: benzodiazepines (most effective for acute control) → tx
precipitating cause
▪ mild dilutional anemia (hgb 9-10g/dL)
● HUS, SLE, active bleeding, prolonged AKI → pRBC transfusion hgb
falls below 7g/dL
● Hypervolemic → slow BT (4-6hr; pRBC 10 mL/kg)
● Fresh, washed RBC: ↓hyperkalemia & risk of sensitization
Batch Clingy
(BUN, Crea),
dysregulation of
extracellular
volume &
electrolyte
homeostasis
113
▪ Clinical presentation depends on underlying etiology and CKD stage
▪ CAKUT & some genetic forms of renal disease (familial nephronophthisis): growth
failure, vomiting, polyuria, polydipsia
▪ UTI: common w/ urologic abnormalities
▪ Glomerular forms of CKD: edema, HTN, hematuria, proteinuria; severe GN, malnutrition
▪ Develop uremic symptoms (worsening fatigue, weakness, nausea, vomiting, anorexia,
poor sleep patterns), edema, HTN, fluid overload, regardless of cause
▪ PE: focus on overall growth & devt, eval of BP, skin (pallor), extremities (edema; bony
abnormalities of rickets seen in untreated renal osteodystrophy)
Please see Fig 550.2
▪ ↑BUN & serum crea; hyperK+, hypoNa+ (sec to either renal salt wasting vs volume
overload), hyperNa+ (loss of free water), acidosis, hypocalcemia, hyperphosphatemia,
↑uric acid
▪ Heavy proteinuria → hypoalbuminemia
▪ CBC: normochromic, normocytic anemia; dyslipidemia
▪ GN: hematuria & proteinuria; congenital lesions such as renal dysplasia, ↓sp gravity w/
minimal other abnormalities
▪ Renal function: estimated by GFR; inulin clearance → gold standard (no longer readily
available); other methods: iohexol or various radioisotopes (99mTc-DTPA, 51Cr-EDTA,
125Iothalamate)
▪ Estimating GFR by endogenous markers (creatinine and/or cystatin C) most utilized
eGFR (mL/min/1.73m2) = 0.43 × height (cm)/serum creatinine (mg/dL)
▪ CKD Mineral & Bone Disease (CKD-MBD): systemic disorders of Ca, phosphorus, PTH, &
vit D metabolism → bone disorders (renal osteodystrophy), vascular and soft tissue
calcification
● High-turnover bone disease (osteitis fibrosa cystica): most common; hypoCa,
hyperphosphatemia, ↑ALP & PTH values, Xray: subperiosteal bone resorption,
metaphyseal widening; bone pain, fractures w/ minor trauma; rachitic changes, varus &
valgus deformities of long bones, SCFE
● Low-turnover bone disease (adynamic renal osteodystrophy): PTH oversuppression,
hyperCa, ↓ALP; pediatric dialysis px receiving tx for secondary hyperparathyroidism
● Vascular calcification
▪ Plans for RRT initiated at stage 4 CKD (GFR <30 mL/min/1.73m2)
▪ Dialysis initiation considered as GFR approaches 10-15mL/min/BSA
▪ 85% of children from birth-5yr: peritoneal dialysis → excess body water removed by
osmotic gradient created by relatively ↑dextrose conc in dialysis fluid; wastes removed
by diffusion from peritoneal capillaries into dialysis fluid
● Continuous ambulatory PD or automated therapy using cycler
● Cycler-driven PD: allow uninterrupted day of activities (↓school interruption),
↓number of dialysis catheter connections & disconnections (↓risk of peritonitis), less
strict fluid & dietary restriction, ↓time required to perform dialysis (↓caregiver fatigue)
● PD not as efficient as hemodialysis, done at least 6x/wk; CI: anatomic abnormalities
(surgical adhesions, omphalocele, gastroschisis, bladder exstrophy), peritoneal injury (sec
to previous severe peritoneal infections), lack of appropriate caregiver
▪ 50% of children ≥13yr: hemodialysis
● Performed in hospital or OPD; IJV preferred catheter site
● Intensified HD programs (short daily HD, intermittent nocturnal HD, daily nocturnal
HD): improved control of BP, fluid overload, phosphorus, anemia, improved growth; CI:
PPS Oral Exam Reviewer 2020
▪ Variable timing of CKD progression (minimal
renal injury to onset of ESRD)
▪ Nonmodifiable risk factors assoc w/ more
rapid progression: older age, glomerular
etiology, CKD severity, onset of puberty
▪ Potential modifiable risk factors: ↑BP,
persistent nephrotic range proteinuria,
anemia, dyslipidemia, no ACE/ARB use
▪ Prompt tx of infection & dehydration →
minimize additional loss of renal parenchyma
▪ Potentially beneficial: avoid tobacco,
prevention of obesity, avoid potential
nephrotoxic meds (NSAIDs, illegal street drugs,
herbal and/or homeopathic meds)
▪ Dialysis-associated infection (peritonitis,
hemodialysis-related bloodstream infections):
leading cause of hospitalization, 2nd-leading
cause of death in pediatric dialysis patients
▪ Ultimate goal: successful kidney transplant →
most normal lifestyle, improved mortality &
morbidity rates
Batch Clingy
CHRONIC
KIDNEY FAILURE
▪ CKD determined by presence of kidney damage and
level (or severity) of kidney function (GFR)
▪ ESRD: patients treated w/ dialysis/kidney
transplantation; subset of patients with stage 5 CKD
▪ pediatric CKD prevalence ~18 per 1M
▪ Etiology: congenital, acquired, inherited, metabolic
renal dx; subdivided into nonglomerular or glomerular in
origin
● <5yr: congenital abnormalities of kidney & urinary
tract (renal hypoplasia, dysplasia, obstructive uropathy);
prenatal UTZ
● >5yr: acquired or inherited forms of GN
▪ Hyperfiltration injury: important final common
pathway of glomerular destruction, independent of
underlying cause
● Nephrons lost → remaining nephrons undergo
structural & functional hypertrophy (↑glomerular blood
flow) → compensatory hyperfiltration (temporarily
preserves renal function) → ↑hydrostatic pressure,
toxic effect of ↑protein traffic → ↑excretory burden
▪ Proteinuria: direct toxic effect of protein on tubular
cells & recruit monocytes and macrophages →
glomerular sclerosis & tubulointerstitial fibrosis
▪ Uncontrolled HTN → arteriolar nephrosclerosis;
↑hyperfiltration injury
▪ Hyperphosphatemia → Ca phosphate deposition in
renal interstitium & blood vessels
▪ Hyperlipidemia: oxidant-mediated injury
▪ Progression of tubulointerstitial fibrosis → primary
determinant of CKD progression
● (+) Hypervolemia or hyperkalemia, BT during dialysis
▪ Nutrition: Na, K & phosphorus restricted; protein moderately
restricted, maximize caloric intake (minimize accumulation of
nitrogenous wastes)
▪ Supportive: screen for and tx metabolic complications
▪ Close monitoring of blood/urine studies (quantitative proteinuria:
spot/24hr UPCr ratio), clinical symptomatology
▪ Gold std for BP eval: ambulatory BP monitoring
● Masked HTN: normal office BP, abnormal ABPM; 35% of pediatric
pre dialysis CKD patient; 4-fold ↑risk of LVH
▪ Nutrition: calories balanced → carbs, unsaturated fat in physiologic
ranges, protein restriction not suggested → adverse effect on growth &
dev; CKD st 2-5 100% DRI of vit & trace elements; water-soluble vit
supplement for dialysis
▪ CKD-MBD: ↓phosphorus intake; low-phosphorus formula (Similac PM
60/40); phosphate binders (given w/ meals) at onset of
hyperphosphatemia
● ergocalciferol, cholecalciferol → correct 25OH vit D insufficiency →
delay onset of sec hyperparathyroidism in predialysis CKD patients,
improve bone mineralization (25OH vitamin D sufficiency ≥30ng/mL)
● active vit D sterols (calcitriol, paricalcitol, doxercalciferol) → ↑Ca &
phosphorus absorption from GI ↓PTH values
▪ ↑BP or edema: Na restriction, diuretic therapy, fluid restriction
▪ HyperK+: ↓K+ intake, oral alkalinizing agents, Kayexalate
▪ Metabolic acidosis: Bicitra (1mEq Na citrate/mL) or Na bicarb tab
(650mg = 8mEq of base) → maintain serum bicarb ≥22mEq/L
▪ Short stature: recombinant human growth hormone (rHuGH) SQ daily
→ reach 50th %tile for midparental height, achieve final adult height, or
undergoes kidney transplantation
▪ Anemia (inadequate erythropoietin production, renal function falls
below 40 mL/min/BSA):
- hgb <5% for age and gender; alternatively:
- <11g/dL: 0.5-5yr
- <11.5g/dL: 5-12yr
- <12g/dL: F >12yr, M 12-15yr
- <13g/dL: M >15yr
● iron supplement (oral/IV): transferrin saturation (TSAT) ≤20%,
ferritin ≤100ng/mL
● erythropoiesis-stimulating agents (ESAs) (erythropoietin &
darbepoetin alfa) ↓need for transfusion
▪ HTN: SBP or DBP >90% for age, gender, height → titrate meds to
achieve SBP or DBP <50% (esp w/ proteinuria)
● Na restriction (<2g/24hr), lifestyle modifications → healthy weight
● ACE inhibitors (enalapril/lisinopril), ARB (losartan): anti-HTN
irrespective of level of proteinuric renal dx, potential ability to slow CKD
● thiazide (hydrochlorothiazide, chlorothiazide), loop diuretic
(furosemide): related to salt and fluid retention; thiazide become
ineffective when eGFR falls below 30mL/min/BSA
● Ca channel blockers (amlodipine), β-blockers (propranolol,
atenolol), centrally acting agents (clonidine) → adjunctive agent, BP
cannot be controlled
▪ Immunization: receive all standard immunizations; withhold live
vaccines → receiving immunosuppressive meds (make every attempt to
administer live vaccine before kidney transplant); yearly influenza
114
(studies suggest CKD child might respond suboptimally to
immunizations)
▪ Dose adjustment for drugs excreted by kidney → maximize
effectiveness, minimize risk of toxicity → lengthening interval bet doses,
↓absolute dose or both
Batch Clingy
inadequate vascular access
PPS Oral Exam Reviewer 2020
115
Acute
UNDESCENDED
TESTES
(Cryptorchidism)
RETRACTILE TESTES
HYDROCELE
INGUINAL HERNIA
EPIDEMIOLOGY / PATHOGENESIS
▪ Most common disorder of sexual differentiation in males
▪ At birth, ~4.5% of males
▪ Testicular descent: 7-8mo AOG → 30% of preterm male;
3.4% at term
▪ 50% descend spontaneously 1st 3mo of life (incidence
↓1.5% at 6mo) → temporary testosterone surge
(minipuberty during 1st 2mo + significant penile growth)
▪ Not descended by 4mo → remain undescended
▪ 10% bilateral
▪ Some older males: scrotal testis “ascends” (low inguinal
position) → requires orchiopexy
▪ 1–2% post-hernia repair → secondary cryptorchidism:
scar tissue along spermatic cord
▪ Process of descent: genetic, hormonal, mechanical
factors
●
Testosterone,
dihydrotestosterone,
MIF,
gubernaculum, intraabdominal pressure & genitofemoral
nerve
▪ 7-8 weeks AOG: testis develops in abdomen (ILF-3
controls transabdominal phase)
▪ 10-11 weeks AOG: Leydig cells produce testosterone:
differentiation of Wolffian (mesonephric) duct →
epididymis, vas deferens, seminal vesicle, ejaculatory duct
▪ 32-36 weeks AOG: begins descent → gubernaculum
guides testis into scrotum → patent processus vaginalis
(hernia sac) normally involutes
▪ Normally descended testes (neonatal period) → pulled
into suprascrotal position by cremasteric reflex (Uptodate)
▪Accumulation of fluid in tunica vaginalis
▪1-2% of neonates
▪noncommunicating (processus vaginalis obliterated) →
disappears by 1yo
▪Patent processus vaginalis → persists; small in morning,
larger during day
▪Abdominoscrotal hydrocele → large, tense, extending
into lower abdominal cavity (rare)
▪Older male: inflammatory condition → testicular torsion,
torsion of appendix testis, epididymitis, testicular tumor,
trauma
▪ Overall incidence 0.8–4.5% term; ~30% premature and
LBW
▪ 99%: congenital indirect hernias (patent processus
vaginalis)
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS / DIAGNOSIS
▪ Classified as
● Abdominal: nonpalpable → will not descend after
3mo of age
● Peeping: abdominal but can be pushed into the
upper part of the inguinal canal
● Inguinal
● Gliding: can be pushed into scrotum but retracts
immediately to the pubic tubercle
● Ectopic: superficial inguinal pouch or, rarely, perineal
▪ PE: undress child → nondominant hand: over pubic
tubercle, pushed inferiorly toward scrotum → dominant
hand: examine scrotum & inguinal canal, palpate testis →
most are palpable just distal to inguinal canal over pubic
tubercle
▪ Nonpalpable → soap test → soap applied to inguinal
canal and examiner’s hand → reduces friction
▪ Pulling on scrotum pull a high inguinal testis
▪ Contralateral testicular hypertrophy (not 100%
diagnostic)
▪nonpalpable testes → 50% viable testes in abdomen/high
inguinal canal, 50% atrophic (w/in scrotum, sec to
spermatic cord torsion in utero/vanishing testis)
▪ Sonography: identify if testis present; abdominal testis
& atrophic testis not identified; inguinal/scrotal UTZ:
obese males w/ nonpalpable testis
▪ CT scan: relatively accurate, radiation exposure
significant
▪ MRI: more accurate; disadvantage: sedation in young
▪ Routine imaging discouraged: not 100% accurate, not
add to decision making
>1yo: brisk cremasteric reflex, child anxious/ticklish →
testis difficult to manipulate into scrotum → examine w/
legs in relaxed frogleg position: testis manipulated into
scrotum comfortably → retractile
▪ Smooth & nontender
▪ Transillumination: confirms fluid-filled nature
▪ Palpate testis → testis tumor
▪ Testis nonpalpable → UTZ: testis present and normal
▪ Compression of fluid-filled mass → completely reduces
hydrocele → inguinal hernia
▪ ~50% present in 1st yr: asymptomatic/minimal sx
▪ Classic hx: intermittent groin, labial (usually upper
portion), or scrotal swelling/bulge, spontaneously reduces
→ gradually enlarge, more persistent, difficult to reduce
DIFFERENTIAL DIAGNOSIS
▪ Disorder of sex development
● Newborn phenotypic male w/ bilateral
nonpalpable testes → virilized female w/ CAH
▪ Retractile testes
● misdiagnosed as undescended
COMPLICATIONS / PROGNOSIS
▪ Poor testicular growth, infertility, testicular
malignancy, assoc hernia, torsion of
cryptorchid testis, psychological effect of
empty scrotum
▪ Risk of a germ cell malignancy: 4x higher
than gen population
● Peak age: 15-45yo
● Most common: seminoma (65%) (↓ by
orchiopexy;
after
orchiopexy,
nonseminomatous tumors (65%) (selftesticular exam)
▪ Acquired/ascending undescended testis:
usually 4-10yo, hx of retractile testis,
incomplete involution of processus vaginalis,
restricted spermatic cord growth during
male’s somatic growth
TREATMENT
▪ Surgery at 6mo appropriate; should be tx surgically
by 9-15mo (no spontaneous descent after 4mos)
▪ Orchiopexy: mobilization of testis and spermatic
cord + correction of indirect inguinal hernia; OPD
procedure: 98% success rate
▪ Two-stage orchiopexy: high abdominal testis
▪ Nonpalpable testis: diagnostic laparoscopy →
assessment if intraabdominal
▪ Orchiectomy: difficult cases, testis atrophic
▪ Testicular prostheses: older children & adol;
psychological effect
● Saline testicular implant
● Solid silicone “carving block” implants
● Placement early in childhood for anorchia
(absence of both testes)
*Please see Table 560.1 American Urological
Association for Evaluation and Treatment and Fig
560.1 for Management Algorithm
Monitor q6-12mo → 1/3 develop acquired
undescended testis → orchiopexy (<7yo
greatest risk)
(Data not available) generally thought not
↑risk for infertility/malignancy
Difficulty differentiating between undescended,
retrac- tile, ectopic testes (any age) → refer to
urologist (Uptodate)
▪Inguinal Hernia
▪ Varicocele: painless/dull ache; “bag of
worms”
▪ Spermatocele: painless, cystic
▪ Testicular CA: painless, hard,
(-) transillumination
▪ HSP: bilateral, painful, (+) purpura
▪ Epididymitis: pain, erythema
▪ Testicular torsion
▪ Scrotal hematoma
▪Meconium peritonitis
▪ Long-term risk of communicating hydrocele:
inguinal hernia
▪ Congenital hydrocele → resolve by 12mo
(reabsorption of hydrocele fluid)
▪ Large and tense → consider early surgical
correction → verify presence of hernia; spontaneous
disappearance rare
▪ Persist beyond 12-18mo → often communicating →
repair
▪ Surgical correction similar to herniorrhaphy
▪ Older male: diagnostic laparoscopy → determine
presence of patent processus vaginalis
Incarcerated inguinal hernia
▪ 2/3 in 1st yr of life; greatest in <6mo
▪ Prematurity ↑risk
▪ Content: small bowel, appendix, omentum,
▪ Prompt repair: prevent incarceration &
complications
▪ Full-term, healthy infants (<1yr): w/in 2-3wk ffg dx
*based on Table 560.3/560.4
Inguinal–scrotal mass
▪ Acute hydrocele: consolable, tolerates
feeding, flat inguinal region (transillumination
misleading thin wall of infant intestine “+”)
Batch Clingy
DISEASE
116
INDIRECT INGUINAL HERNIA → 12wk AOG: processus
vaginalis present → 28wk AOG: testes descend from
retroperitoneum (urogenital ridge) to internal ring → 2836wk AOG: final descent → last few weeks of
gestation/shortly after birth: obliteration of processus
vaginalis
▪ Patency rate of PV at birth ≈80%; 1styr of life ≈40%;
persistent at 2yr ≈20% of males
▪ Females: obliterates earlier ~7mo AOG (could explain
↓incidence)
▪ Involution left PV precedes right → 60% R-sided indirect
inguinal hernias (30% L-sided, 10% bilateral)
Ectopic testes → cordlike structures of gubernaculum pass
to perineum/femoral region
▪ Reason for failure of PV closure unknown → common in
cryptorchidism & prematurity
COMPLETE INGUINAL HERNIA: protrusion of contents
extending into scrotum
▪ Males: hernia sac contains intestines
▪ Females: often have ovary and fallopian tube
DIRECT (ACQUIRED) INGUINAL HERNIA
▪ Weakness in transversus abdominis (floor of inguinal
canal)
▪ Originate medial to deep inferior epigastric vessels &
external to cremasteric fascia; protrudes directly through
posterior wall of inguinal canal not through external ring
▪ 1/3: hx of prior indirect hernia repair (possible missed dx
direct hernia/injury to floor muscles); (+) connective tissue
dx: Ehlers-Danlos syndrome, Marfan syndrome,
mucopolysaccharidosis (Hunter-Hurler syndrome)
IMPERFORATE
HYMEN
FEMORAL HERNIA: medial to femoral vein, descends
inferior to inguinal ligament along femoral canal →
protrudes on medial aspect of thigh, below inguinal
region, does not enter scrotum/labia
▪ Most common obstructive anomaly
▪ Familial occurrence reported
▪ ~1 in 1000
PPS Oral Exam Reviewer 2020
▪ Most visible: crying, irritable, straining, coughing; after
bathing or urination
▪ Hallmark sx: smooth, firm mass; emerge through
external inguinal ring lateral to pubic tubercle; enlarges
w/ ↑intraabdominal pressure → inspect protruding
mass/examining finger invaginating the scrotum to
palpate at the external ring → reduce spontaneously as
child relaxes/by gentle pressure
▪ Bimanual exam: palpate internal ring per rectum, other
hand gentle pressure on inguinal region over internal ring
→ intraabdominal viscera palpated extending through
internal ring
● Quiet infant: stretch the infant out supine w/ legs
extended, arms held straight above the head → infants
struggle to get free → ↑intraabdominal pressure
● Older children: ask to perform the Valsalva maneuver
by blowing a balloon/coughing; examine while standing,
after voiding
▪ Torsion of undescended testis: painful
erythematous mass; absence of gonad
ipsilateral side
▪ Epididymitis/orchitis: swelling & tenderness
of testis, confined to the scrotum; assoc
urinary sx
▪ Suppurative inguinal lymphadenitis:
superficial infected, crusted skin lesion; more
inferior and lateral location
Ambiguous genitalia
▪ Disorders of sexual devt → inguinal hernia
often containing a gonad
▪ Female patient w/ inguinal hernia + bilateral
inguinal mass, consider testicular feminization
syndrome
▪ Silk glove sign: rolling spermatic cord beneath index
finger at pubic tubercle → feeling of layers of hernia sac
as they slide over spermatic cord
colon, bladder, rarely, Meckel diverticulum;
females: ovary, fallopian tube or both, rarely,
uterus in infants
▪ Pressure on herniated viscera → impaired
lymphatic & venous drainage → swelling →
↑compression → total occlusion of arterial
supply → progressive ischemic changes →
gangrene (strangulated hernia) and/or
perforation
▪ Irritable, feeding intolerance, abdominal
distention, pain
▪ Inconsolable, no flatus/stool → complete
obstruction → bilious/feculent vomiting;
bloody stool
▪ Nonreducible, tense, tender mass, erythema
(extending
from
inguinal
area
to
scrotum/labia)
▪ Abdominal x-ray: partial/ complete
obstruction, gas w/in incarcerated bowel
segments seen below the inguinal ligament or
w/in scrotum.
SURGICAL COMPLICATIONS
▪ Wound infection: fever & irritability 3-5days
post-sx; wound warm, erythema, fluctuant;
mgt: draining, antibiotics, daily wound
dressing; most common: Gram(+) (Stap &
Strep spp), consider MRSA; heal in 1-2wk
▪ Recurrent hernia
▪ Iatrogenic cryptorchidism: malposition of
testis
▪ Injury to vas deferens & male fertility:
injured from incarcerated hernia or during
OR; underreported (unlikely recognized until
adulthood & possibly only if bilateral)
▪ ‘E’ repair ↑risk for testicular atrophy, bowel
ischemia, wound infection & recurrence than
elective
▪ Sliding hernias: content adherent w/in sac, not reducible
→ in females: fallopian tube/ovary palpated as firm,
slightly mobile, nontender mas
▪ Clinical diagnosis → reduce spontaneously in young →
unequivocal PE → UTZ (distinguish hernia, hydrocele,
lymphadenopathy) or refer to surgeon
(Older child: ↓risk of incarceration, parents reassured &
educated → plan for period of observation (take picture
at home)
▪ Diagnostic laparoscopy: increasingly used for suspected
hernia (particularly infants: ↑risk incarceration)
▪ 30%: testicular atrophy after incarceration <3mo
▪ 70% incarcerated requiring ‘E’ repair: <11mo
▪ Children >1yo: ↓risk of incarceration, less urgency
→ elective, OPD → full recovery in 48hrs
▪ Prophylactic antibiotics – used if w/ co-morbids
(CHD, VPS, BPD)
▪ Preterm & LBW: controversy in timing → before
NICU discharge: ↑risk incarceration but also ↑risk
complications, hemodynamic instability, wound
infection, recurrent hernia; open repair preferred:
can be done under gen anes or regional (avoid
intubation in BPD, chronic lung disease)
▪ Incarcerated, irreducible hernia without
strangulation/ obstruction, peritonitis, hemodynamic instability:
nonopera-tive, manual
reduction under sedation → observe feeding
tolerance → herniorrhaphy after 1-4days (less
edema, easier handling of sac, ↓ complications)
▪ Irreducible, prolonged incarceration, peritoneal
irritation, obstruction → NGT, IVF, broad-spectrum
antibiotics, correct F&E imbalance → surgery
▪ Female: sliding hernias, irreducible, (-) strangulation
→ repair w/in 24-48hrs
▪ Necrotic ovaries & testes at OR → not predict future
functionality (ischemic appearing testes: survive
~50%, testicular atrophy 2.5–15%, avoid testicular
resection unless frank necrosis present)
▪ 85%: unilateral inguinal hernia → controversy in
contralateral groin exploration → pro: avoid parental
anxiety, 2nd surg & anes, contralateral incarceration;
con: injury, ↑OR & anes time, often unnecessary
OPEN INGUINAL REPAIR: standard of care; ↓rate of
recurrence, vas deferens injury, testicular atrophy
LAPARASCOPIC REPAIR: better cosmesis, faster
recovery, greater ability to visualize & repair
contralateral hernia; ↑risk assoc w/ gen anes,
hemodynamic effect of abdominal insufflation
(acidosis), technical challenge
Post op pain: acetaminophen 24-48hr; older child:
brief period of post op narcotic
▪ Newborn period & early infancy: Mucocolpos
● Bulging membrane
● From maternal estrogen stimulation of the vaginal
▪ Variants: hymenal membranes do not
undergo
complete
resorption
→
microperforate, cribriform, septate-shaped
▪ Can obstruct urinary outflow
▪ Resection: prevent/relieve outflow tract obstruction
● Symptomatic, done at time of dx
● Elective excision: after age 1-2yr to puberty,
Batch Clingy
● Full-term newborn infants: 3.5–5.0%
● Preterm & LBW: 9-11%
● Preterm (<28wk AOG) & VLBW: 30%
● (+) Family hx: 11.5%
▪ M>F → 8:1 ratio but
● bilateral inguinal hernias: ↑females (~25%) vs males
(~12%)
▪ Rare in children
● Direct/acquired hernia 0.5–1.0%
● Femoral hernia <0.5%: more females 2:1 ratio
▪ ~50% manifest 1st yr of life (↑1st 6mo)
117
OVARIAN TORSION
VULVOVAGINITIS
Vulvitis
External genital
pruritus, burning,
redness, rash
▪ Adnexal torsion (ovary and/or fallopian tube): 5th most
common gynecologic emergency
▪ Children and adolescents > adults
▪ Can occur w/ normal adnexa
▪ More often: adnexa enlarged by cystic (follicular, tubal)
changes or ovarian (teratoma, cystadenoma) neoplasms
▪ Torsion → venous outflow obstruction → fallopian
tube/ovary swells, hemorrhagic → arterial flow
interrupted → necrosis
▪ Most common gynecologic-based problem for
prepubertal children: incidence 17–50%
▪ Peak age: 4-8yo
▪ Caused by inadequate OR excessive hygiene (chemical
irritants)
▪ ~75% nonspecific: lack of vaginal estrogenization →
atrophy, alkalinic pH; poor perianal hygiene; proximity of
anus to vagina w/out geographic barriers (flattened labia,
no pubic hair
▪ Infectious vulvovaginitis: fecal/respiratory pathogens (E
coli, S pyogenes, S aureus, H influenzae, E vermicularis;
rarely Candida spp) → transmitted by improper toilet
hygiene & manually from the nasopharynx to the vagina
● STI in prepubertal children: cooperation w/ CPU →
acquired after neonatal period → gonorrhea, syphilis,
chlamydia virtually 100% sexual contact; HPV, HSV unclear
Vaginitis
Inflammation of
vagina; discharge
w/ or w/out odor or
bleeding
mucosa
● Reabsorbed if not too large/symptomatic
▪ More often diagnosed at menarche: Hematocolpos
● Menstrual fluid accumulates
● Bulging blue-black membrane
● Cyclic abdominal pain/pelvic mass
● Primary amenorrhea
● Normal secondary sex characteristics
▪ Acute lower abdominal pain: episodic or constant
▪ Nausea, vomiting, bowel/bladder sx, peritonitis
▪ Pelvic UTZ: unilateral enlargement of adnexa, with or
without Doppler flow, free pelvic fluid, “whirlpool sign,”
“beak sign”
▪ Hx: hygiene (wiping from front to back); exposure to
chemical irritants (bath soap, bubble bath, detergents,
pools/hot tubs); recent diarrhea, perianal itching,
nighttime itching; possibility of foreign objects into the
vagina (young child unlikely to recall)
▪ Infectious vulvovaginitis
● Perianal redness, introital inflammation, yellowgreen/mildly bloody discharge
● Child grabbing genital area or “digging” in underwear
(stained yellow-brown discharge)
● Failed attempt to tx w/ antifungal med (leads to
more irritation)
▪ Diaper dermatitis
● Most common dermatologic problem in infancy (1/2
of all diaper-wearing children) → moisture, contact w/
urine and feces irritates skin, colonization with Candida
spp ↑severity
▪ Physiologic leukorrhea
● Neonates & peripubertal girls → white/clear/mucus
discharge (physiologic effect of estrogen)
● Complaints of moisture and mucus → hygiene
measures may help; reassure the px and mother
hymen → interfere w/ tampon use →
resection elective (patient preference)
▪ Acute pelvic pain + adnexal mass
▪ Ectopic pregnancy: (+) hcg, UTZ, (+) vaginal
bleeding
▪ Ruptured ovarian cyst: UTZ (also show
hemoperitoneum/free pelvic fluid), classic hx:
sudden onset pelvic pain midcycle often ffg
sexual intercourse
▪ Tubo-ovarian abscess: indolent course, (+)
fever, UTZ (complex multilocular mass)
(Uptodate)
▪ Culture: cotton swabs or urethral
(Calgiswab)
swabs
moistened
with
nonbacteriostatic saline
▪ NAAT: gonorrhea, chlamydia; special
media/collection procedure:
Shigella, H
influenzae
▪ Shigella: blood-tinged purulent discharge;
Candida: common cause diaper rash,
uncommon cause of vaginitis prepubertal
(alkaline pH)
▪ Pinworms: transparent adhesive tape/anal
swab
▪ Foreign body: serosanguineous vaginal
discharge, foul odor, fails to respond to
hygiene measures → vaginal irrigation,
vaginoscopy
ideally prior to menses; discouraged in very young
(under anes)
▪ Prepubertal child: heal best if topical estrogen
placed at site for a few days
▪ Not known how long adnexa remain viable
▪ Observation for viability: necrotic-appearing
recover function (Doppler flow and follicular
devt 6wk postop) → long-term preservation
of fertility
▪ Untreated: pelvic thrombophlebitis,
hemorrhage, infection, peritonitis, and
autoamputation of the adnexa
▪ Prompt detorsion
▪ Cystectomy completed if possible: ↓risk of
recurrence
▪ Removal of fallopian tube/ovary: reserved for
grossly necrotic tissue, malignant tumors (FS)
▪ Oophoropexy (plication) of affected & contralateral
adnexa: controversial
▪ Diabetic, immunocompromised, taking
prolonged antibiotics: ↑risk for fungal
vaginitis
▪ Untreated lichen sclerosis: labial resorption,
obliteration of clitoris, narrowing of introitus,
painful fissures, infection
▪ Condition improved by hygiene
▪ Specific vulvovaginitis: directed at the organism
causing symptoms
▪ Nonspecific vulvovaginitis: Sitz baths, avoid harsh
soaps/chemicals, tight clothing that abrades the
perineum, fabric softeners; use cotton underwear,
parent counseling
▪ Diaper dermatitis: hygiene measures (↑freq of
diaper change, allowing infant to be diaper free, freq
bathing, application of water-repellant barriers: zinc
oxide); persists or classic satellite lesions of Candida
→ tx w/ topical antifungal
▪ Genital ulcer: pain mgt, urinary diversion w/
catheter; topical Xylocaine 2% jelly, sitz baths, good
hygiene, acetaminophen (NSAIDSs avoided, possible
causative link); topical steroids (clobetasol 0.05%
ointment), oral for recurrent outbreak/extensive dx
▪ Lichen sclerosis: eval q6-12 for recurrence
*Please see Table 564.1 Specific Vulvar Disorders in
Children
and
Table
564.2
Antibiotic
Recommendations for Specific Vulvovaginal Infections
▪ Acute genital ulcers (Please see Fig 564.3 Algorithm)
● Young adolescents not sexually active
● 1/3 associated w/ oral aphthous ulcers; painful
red/white lesion evolve into sharply demarcated red-
PPS Oral Exam Reviewer 2020
Batch Clingy
▪ Labial agglutination (adhesion)
● Secondary to inflammatory response +
hypoestrogenic state
● Asymptomatic: seen on routine exam
● Sx: difficulty voiding, persistent infection, pain → tx
118
rimmed ulcers w/ necrotic or eschar-like base
● 10-14 days until remission
● Flu-like prodrome (fever, nausea, abdominal pain);
dysuria and vulvar pain → urinary diversion
● Biopsy nondiagnostic (acute/chronic inflammatory
changes)
Batch Clingy
▪ Dermatoses (check skin elsewhere on body)
● Lichen sclerosis
● Vitiligo acquired skin depigmentation (autoimmune
against epidermal melanocytes); test for hypothyroidism,
Graves disease, Addison disease, pernicious anemia,
insulin-dependent DM)
● Vulvar psoriasis
PPS Oral Exam Reviewer 2020
119
Complex
DISEASE
EPIDEMIOLOGY
PATHOGENESIS
Primary HTN
▪ Older school-age, adolescents
▪ ↑ Prevalence in parallel w/ obesity
epidemic
PRIMARY HYPERTENSION
▪ ≥6 years, (+) family hx in a parent and/or grandparent, overweight
and/or obesity (AAP)
▪ Older school age & adolescent
▪ BP values at/or only slightly above 95th %tile for age
▪ Isolated systolic HTN more consistent w/ primary HTN (diastolic
HTN suggest a secondary cause)
▪ Multifactorial; obesity, genetic alterations in Ca and Na transport,
vascular smooth muscle reactivity, RAAS, sympathetic nervous
system overactivity, insulin resistance, ↑uric acid levels
▪ Salt-sensitive hypertension: some children/adol, ameliorated w/ wt
loss and Na restriction
Children w/ BP >90th %tile: 2.4-fold
greater risk of HTN as adults
Adolescent HTN: independent predictor of
ESRD and LV dysfunction in middle-aged
men
Infants and young children: prevalence
<1% → 2o HTN
*Please see Table 472.2/472.3/472.4
Risk factors for CV disease: ▪ Obesity
▪ ↑serum cholesterol
▪ ↑Na intake
▪ Sedentary lifestyle
▪ Alcohol and tobacco use – ↑arterial wall
rigidity & blood viscosity assoc w/
exposure to tobacco)
RENAL/RENOVASCULAR DISEASE
▪ Renal dx (chronic GN, reflux or obstructive nephropathy, HUS,
polycystic kidney dx, congenital anomalies of kidney & urinary tract)
+ renovascular HTN = ~90% of secondary HTN
▪ Renal parenchymal dx & renal artery stenosis → water & sodium
retention sec to ↑renin secretion
▪ ↑index of suspicion: HTN in <6yo
CLINICAL MANIFESTATIONS / DIAGNOSIS
Primary hypertension: usually asymptomatic
▪ BP elevation mild, detected during routine exam
▪ May be obese
Secondary hypertension: mild to severe BP elevation
▪ Unless sustained or rising rapidly, does not usually produce symptoms
▪ Sx reflect underlying dx – growth failure: CKD
Acute severe hypertension
▪ BP elevation >st 2 HTN
▪ Severe sx represent acute target-organ injury
Subclinical hypertensive target-organ injury: common in children w/ 1o HTN
*Please see Table 472.5/472.6 and Fig 472.5
MANAGEMENT / PREVENTION
▪ Prevention of ↑BP → prevent of CV disease & stroke
▪ Asymptomatic mild HTN w/out target-organ damage: lifestyle
modification w/ dietary changes & regular exercise
● Weight loss: obesity related HTN
● DASH diet beneficial ↓BP in adolescents – Dietary Approaches to
Stop Hypertension: ↓Na intake (adult: standard diet 2300mg, low
sodium diet 1500mg); ↑K+, Ca, Mg-containing food; 6-8servings
whole grains, 4-5 servings fruits, 4-5servings veg per day, ↓fat dairy
● Regular aerobic physical activity: at least 30-60min most days;
sedentary activities to <2hr/day
Indications for Pharmacologic Therapy:
Symptomatic HTN, stage 2 HTN without modifiable risk factor, HTN in
DM or CKD, persistent HTN despite nonpharmacologic measures
▪ Initiate as single agent at low dose → ↑ dose until goal BP achieved,
max dose reached, SE develop
▪ Add 2nd drug from diff class, complementary MOA
▪ BP control not achieved → add 3rd drug or refer
Initial agents: ACEIs, ARBs, CCBs, thiazide diuretics → tailored to
etiology
Recommended goal: BP <90th percentile for age or <130/80 mmHg
(whichever is lower) → lower for child w/ CKD
▪ ACEIs/ARBs: children with diabetes and microalbuminuria or
proteinuric renal disease
*Please see Table 472.8/472.9
HYPERTENSION
(Nelson’s + AAP)
ACUTE SEVERE HTN
(accelerated HTN or hypertensive crisis)
CARDIAC/VASCULAR
▪ Coarctation of aorta: discrete narrowing of aortic arch (generally
level of aortic isthmus)
● Right arm BP ≥20mmHg than lower extremity BP
● Repair: infants o surgical, adol w/ angioplasty/stenting
▪ Long-segment narrowing of abdominal aorta: refractory HTN,
upper extremity SBP exceeds lower extremity SBP by 20mmHg
▪ Abdominal aortic obstruction may have neurofibromatosis,
Williams syndrome, Alagille syndrome, Takayasu arteritis Patients
PPS Oral Exam Reviewer 2020
Ambulatory BP monitoring
▪ Records BP q20-30min for 24hrs; compute mean daytime/sleep BP, mean BP over
24hr; cuff placed in nondominant arm; journal of sleep & awake times, meds, events;
feasible in ≥6-7yo
▪ Determine proportion of BP in HTN range (BP load), appropriate ↓during sleep
▪ ICU admission, arterial line for continuous BP monitoring, IV drug
infusion: labetalol, nicardipine, Na nitroprusside
▪ Rapid ↓BP: interfere w/ adequate organ perfusion
▪ Stepwise reduction in pressure: not >25% of planned reduction over
the 1st 8hr → gradual normalization over next 24-48hr
▪ Less severe symptoms (headache, N&V): clonidine, isradipine (if oral
meds tolerated), short-acting IV hydralazine, labetalol
Secondary
HTN:
tx
underlying
disease
(chronic
renal
dx,
Batch Clingy
▪ Headache, dizziness, nausea/vomiting – HTN urgency
▪ More severe cases, retinopathy, encephalopathy, cardiac failure,
renal injury, seizures – HTN emergency
▪ No absolute distinction (nomenclature lead to confusion); treatment
depend on clinical judgment
▪ HTN encephalopathy (generalized or PRES) – headache, vomiting, ↑
temp, visual disturbances, ataxia, ↓ LOC, imaging abnormalities,
seizures
▪ ↓vision (cortical blindness), papilledema, congestive heart failure,
accelerated deterioration of renal function
120
with coarctation
▪ Recoarctation in repaired patients: 4 extremity BP & echo;
ambulatory BP monitoring - gold std for HTN after coarctation repair
ENDOCRINE
▪ Thyroid, parathyroid, adrenal glands
▪ Hyperthyroidism: systolic HTN & tachycardia common; DBP not
usually↑
▪ Hypercalcemia (sec to hyperparathyroidism or other): ↑vascular
tone, mild ↑BP
▪ Adrenocortical disorders – aldosterone-secreting tumors, Naretaining CAH, Cushing syndrome: ↑mineralocorticoid secretion
▪ Real/apparent mineralocorticoid excess → ↓renin level (±
hypokalemia)
▪ Pheochromocytoma: catecholamine-secreting tumors → cardiac &
peripheral vascular effects of epi & norepi; sustained rather than
intermittent/exercise-induced HTN
▪ Pseudohyperaldosteronism: ↓renin
▪ Liddle syndrome: mineralocorticoid excess, glucocorticoidremediable aldosteronism
DRUGS
▪ Cocaine: rapid ↑BP → seizures/intracranial hemorrhage
▪ Phencyclidine: transient become persistent in chronic abusers
▪ Tobacco
▪ Sympathomimetic agents – nasal decongestants, appetite
suppressants, stimulants for ADHD: peripheral vasoconstriction,
varying degrees of cardiac stimulation
▪ OCP
▪ Immunosuppressant agents: cyclosporine & tacrolimus in organ
transplant recipients, effect is exacerbated by co-administration of
steroids
▪ Heavy metal (lead, cadmium, mercury)
(nocturnal dip, normal decrease >10% from awake values)
▪ Diagnose whitecoat HTN (↑BP in office, normal ABPM), masked hypertension
(normal in office, ↑ABPM)
▪ BP pattern in high risk: CKD, solid organ transplant, DM, severe obesity
▪ Correlated w/ target organ damage than office readings
▪ AAP: performed for confirmation of HTN w/ office BP in elevated BP category for 1
year or more or with stage 1 HTN over 3 clinic visits (limited to children ≥5yr who can
tolerate procedure, for whom reference data available)
hyperthyroidism, pheochromocytoma, CoA, renovascular HTN)
Renovascular stenosis: anti-HTN, angioplasty, surgery; bilateral
renovascular HTN or renovascular dx in solitary kidney suspected →
drugs acting on RAAS contraindicated (↓GFR, AKI)
▪ Recognition of ↑BP → evaluate underlying causes of HTN, comorbidities, screening
for target-organ damage
Birth hx: prematurity, perinatal events (UA catheterization, renal artery thrombosis,
BPD)
Family hx: metabolic & renal dx, early CV events, secondary HTN
Growth parameters: detect chronic disease
BP of 4 extremities: coarctation (thoracic/abdominal) of aorta
Detect renal disease: UA, electrolytes, BUN, creatinine, CBC; renal UTZ
↑suspicion of secondary HTN: assess for discrepancies in renal size, structural
abnormalities
Hypokalemia: renovascular HTN, many monogenic forms (Liddle syndrome,
glucocorticoid remedial aldosteronism, and apparent mineralocorticoid excess)
Hyperkalemia: Gordon syndrome
Renovascular HTN: assoc w/ other dx or isolated
▪ MR angiography: Sn 80%, Sp 63%
▪ CT angiography: Sn 88%, Sp 81%
▪ Intraarterial angiography needed to detect intrarenal vascular stenoses & in
infants/young children (noninvasive imaging not helpful because of small vessel size)
▪ Doppler renal UTZ: poor cooperation, imaging difficulties related to obesity,
operator inexperience; Sn ~60–65%, Sp 95% (AAP: normal-wt, ≥8yrs, cooperative)
Screen for comorbidities ↑CV risk: dyslipidemia, glucose intolerance
▪ Non fasting lipid panel → do fasting panel if abnormal
Screen for sleep-disordered breathing → assoc w/ ↑BP, particularly overweight
Most common extracranial solid tumor in
children
NEUROBLASTOMA
Most commonly diagnosed malignancy in
infants
>15% of mortality from cancer
▪ Median age at dx: 22 mo
▪ 90% diagnosed by 5yr
▪ Incidence: slightly ↑ in boys
PPS Oral Exam Reviewer 2020
Embryonal Ca of peripheral sympathetic nervous system
Derived from primordial neural crest cells, variable degrees of
neural differentiation: tumors w/ primarily undifferentiated small
round cells (neuroblastoma) to consisting of mature and maturing
schwannian stroma with ganglion cells (ganglioneuroblastoma or
ganglioneuroma)
▪ Resemble other small round blue cell tumors: rhabdomyosarcoma,
Ewing sarcoma, non-Hodgkin lymphoma
LVH: most common manifestation of target-organ damage
▪ LV mass measurements: indexed to height (account for effect of body size & BSA)
▪ LV mass >51g/m2.7 or LV mass >115g/BSA for boys, >95g/BSA for girls
▪ AAP: echocardiography obtained when tx w/ anti-HTN considered
Localized disease: asymptomatic mass or sx from mass effect – spinal cord
compression, bowel obstruction, superior vena cava syndrome
Metastatic disease: fever, irritability, failure to thrive, bone pain, cytopenias, bluish
SQ nodules, orbital proptosis, periorbital ecchymoses
▪ Neurologic sx: originating in superior cervical ganglion → Horner syndrome
▪ Paraspinal neuroblastoma tumors → invade neural foramina → SC and nerve root
compression
▪ Paraneoplastic syndrome of autoimmune origin (opsoclonus-myoclonus–ataxia
syndrome) rapid, uncontrollable jerking eye & body movements, poor coordination,
LOW RISK: surgery for stage L1 & L2; observation for asymptomatic
stage MS: cure rate >90%
▪ Chemotherapy/radiation for rare child w/ local recurrence →
curative
▪ SC compression at dx: urgent chemo, surgery, or RT → avoid
neurologic damage
▪ Stage MS: favorable prognosis
▪ Many regress spontaneously w/out therapy
▪ Chemotherapy/resection of primary tumor → not improve survival
rates → infants w/ massive liver involvement & respiratory
Batch Clingy
HTN retinopathy: ↑carotid intima-to-media thickness, ↑vascular stiffness
121
▪ May develop at any site of sympathetic nervous system tissue
▪ ½ arise in adrenal glands; remainder originate in paraspinal
sympathetic ganglia
▪ Metastatic spread (more common in children >1yo at dx): local
invasion, distant hematogenous, lymphatic routes; most common
sites: regional/distant lymph nodes, long bones and skull, bone
marrow, liver, and skin (lung & brain metastases rare, <3%)
cognitive dysfunction
▪ Some tumors: produce catecholamines (↑sweating and HTN), vasoactive intestinal
peptide (profound secretory diarrhea)
▪ Extensive tumors: tumor lysis syndrome, DIC
▪ Infants <18mo: stage MS → widespread SQ tumor nodules, massive liver
involvement, limited BM disease, small 1o tumor w/out bone involvement or other
metastases; can spontaneously regress
Plain radiography, CT, MRI: mass or multiple masses; often contains calcification,
hemorrhage
Prenatal dx of perinatal neuroblastoma (sometimes possible)
Tumor markers: catecholamine metabolites homovanillic acid (HVA) &
vanillylmandelic acid (VMA) ↑in urine ~95%
▪ W/out biopsy: dx w/ small round blue tumor cells in BM samples + ↑HVA & VMA
Metastatic evaluation: CT/MRI of chest & abdomen, bone scans (detect cortical bone
involvement); at least 2 independent BMA & biopsies to evaluate marrow dx
▪ Iodine-123 metaiodobenzylguanidine (123 I-MIBG): define extent of dx
▪ MRI of spine: suspected or potential spinal cord compression; imaging of brain not
routine (unless dictated by presentation)
International Neuroblastoma Risk Group (INRG) Staging System (INSS): stage based
on extent of disease as determined by imaging at diagnosis
▪ Extent of locoregional disease is based on specific local image-defined risk factors
(IDRFs)
▪ L1 (previously INSS st 1): localized, confined to 1 body compartment w/out any
IDRFs
▪ L2 (INSS st 2 & 3): localized tumors w/ presence of IDRFs
▪ M (INSS st 4): disseminated tumors w/ metastases to bones, BM, liver, distant
lymph nodes, and other organs
▪ MS (previously st 4S): neuroblastoma in children <18mo, w/ dissemination to liver,
skin, or bone marrow w/out bone involvement & w/ primary tumor that would
otherwise be staged as L1/L2
10% occur in children (6-14yo)
PHEOCHROMOCYTOMA
Most common site of origin (~90%):
adrenal medulla
▪ May develop anywhere along abdominal
sympathetic chain, located near aorta at
the level of inferior mesenteric artery or at
its bifurcation
▪ Also appear in the periadrenal area,
urinary bladder or ureteral walls, thoracic
cavity,
cervical
region
▪ Vary from 1-10cm diameter
▪ R side > L side
▪ >20% bilateral
PPS Oral Exam Reviewer 2020
▪
Catecholamine-secreting
tumors
arising
from
chromaffin cells
▪ Associated w/ genetic syndromes: von Hippel-Lindau dx, as
component of MEN2A and MEN2B, rarely w/ neurofibromatosis
(type 1) or tuberous sclerosis
▪ Classic features of von Hippel-Landau syndrome (1 in 36,000):
retinal & CNS hemangioblastomas, renal clear cell Ca,
pheochromocytomas
● Germline mutations in VHL tumor-suppressor gene on
chromosome 3p25-26
▪ Mutations of RET protooncogene on chromosome 10q11.2 →
MEN2A & MEN2B
● Medullary thyroid Ca & parathyroid tumors
● ~50%: pheochromocytoma (mutations at codon 634 of RET
gene: ↑ risk)
▪ NF 1: mutations present in NF1 gene on chromosome 17q11.2
PROGNOSIS
Varies w/ histologic features of tumor as dictated by presence & amount of
schwannian stroma, degree of tumor cell differentiation, and mitosis-karyorrhexis
index
▪ Detected by surveillance of known carriers (asymptomatic)
▪ HTN ← excessive secretion of metanephrines, epinephrine & norepinephrine
▪ Paroxysmal HTN (sustained rather than paroxysmal in children)
● Paroxysms: usually infrequent at first → frequent → continuous
● Between attacks, free of symptoms; during attacks, HA, palpitations, abdominal
pain, dizziness, pallor, vomiting, sweating
▪ Seizures & other manifestation of HTN encephalopathy
▪ Severe: precordial pains radiate into arms, pulmonary edema, cardiac & hepatic
enlargement
▪ Exacerbated by exercise, nonprescription meds containing stimulants
(pseudoephedrine)
▪ Good appetite; hypermetabolic state may not gain weight → severe cachexia
▪ Polyuria, polydipsia: suggest diabetes insipidus
▪ Growth failure
▪ BP range: SBP 180-260mmHg, DBP 120-210mmHg diastolic
compromise
▪ Chemotherapy/radiation alleviate sx; child requiring tx for sx: survival
rate 81%
INTERMEDIATE RISK: surgery, chemo, RT
▪ Chemotherapy: moderate doses of cisplatin or carboplatin,
cyclophosphamide, etoposide and doxorubicin given over several mos
▪ RT: tumors w/ incomplete response to chemo
▪ L2 & M disease (both w/ favorable characteristics): >90% survival
▪ Determination of underlying biologic features: Shimada pathologic
classification and MYCN gene amplification → unfavorable
characteristics → more aggressive tx
HIGH RISK: intensive chemotherapy, high-dose chemotherapy with
autologous stem cell rescue, surgery, RT, and 13-cis -retinoic acid
(isotretinoin, Accutane)
▪ Induction chemotx: cyclophosphamide, topotecan, doxorubicin,
vincristine, cisplatin, and etoposide
↓
resection of residual primary tumor
↓
high-dose chemotherapy w/ autologous stem cell rescue & focal
RT to tumor sites
▪ Long-term survival rates 25-35%; frequent relapses → recurrent
neuroblastoma: <50% response rate to alternative regimens
▪ Remove surgically
▪ Careful preoperative, intraoperative, postoperative management →
manipulation & excision → ↑ catecholamine secretion that ↑BP
↑HR
▪ Preoperative α- and β-adrenergic blockade required
▪ Tumors often multiple in children → thorough transabdominal
exploration of all usual sites
▪ Appropriate choice of anes & expansion of blood volume with
appropriate fluids before and during surgery critical → avoid
precipitous ↓BP during OR or w/in 48hr postop
▪ Surveillance continues postop
▪ May appear malignant histologically but accurate indicators of
malignancy → presence of metastatic dx or local invasiveness that
precludes complete resection, or both
▪ ~10% of all adrenal pheochromocytomas are malignant → rare in
childhood
Batch Clingy
Etiology remains unknown
▪ Familial neuroblastoma: 1–2%, younger age at dx, linked to
mutations in PHOX2B & ALK genes
▪ BARD1 gene: major genetic contributor to neuroblastoma risk
▪ Assoc w/ other neural crest disorders: Hirschsprung disease,
central hypoventilation syndrome, NF type 1, potentially congenital
cardiovascular malformations
▪ ↑incidence in children w/ Beckwith-Wiedemann syndrome and
hemihypertrophy
▪ Assoc w/ some maternal and paternal occupational chemical
exposures, farming, work related to electronics; no single
environmental exposure shown to directly cause
122
▪ 30–40% found in both adrenal &
extraadrenal areas or only in an
extraadrenal area
Pheochromocytoma: may occur in kindreds along w/
paragangliomas, particularly in head & neck
▪ Mutations in SDHB, SDHD, rarely SDHC genes (encoding subunits
of mitochondrial enzyme succinate dehydrogenase)
▪ ~50% w/ SDHB → malignant
Assoc w gastrointestinal stromal tumors (GISTs; association termed
CarneyStratakis dyad) and/or pulmonary chondromas (CarneyStratakis triad) & adrenocortical tumors; heterogenous genetic
etiologies, often involve mutations in SDH gene
▪ Ophthalmologic exam: papilledema, hemorrhages, exudate, arterial constriction
▪ Urine: protein, few casts, occ glucose; gross hematuria suggest tumor is in bladder
wall
▪ Occ polycythemia
▪ Normally, plasma norepinephrine derived from both adrenal gland & adrenergic
nerve endings; epinephrine derived primarily from adrenal gland
● In contrast to adults (↑norepinephrine & epinephrine), children predominantly
excrete norepinephrine in urine
● Urinary excretion of metanephrines (particularly normetanephrine) ↑
● Daily urinary excretion by unaffected children ↑ w/ age
▪ ↑Urinary VMA (3-methoxy-4-hydroxymandelic acid), major metabolite of
epinephrine and norepinephrine (vanilla-containing foods & fruits: falsely ↑ no
longer routinely measured)
▪ ↑ Plasma free catecholamines and metanephrines
▪ Best Sn & Sp: plasma normetanephrine using gender-specific pedia reference; next
best: plasma norepinephrine (plasma metanephrine & epinephrine not reliably ↑ in
children)
● Avoid caffeinated drinks, acetaminophen (interfere w/ plasma normetanephrine
assays); sample obtained from indwelling IV catheter, avoid acute stress assoc w/
venipuncture
▪ Pediatric malignant pheochromocytomas more frequently in
extraadrenal sites; often assoc w/ mutations in the SDHB gene
▪ Prolonged ff-up: functioning tumors at other sites manifest many
years after initial OR
▪ Exam relatives of affected patient → reveal asymptomatic individuals
w/ unsuspected tumors
▪ CT/MRI: localize most tumors in adrenal gland; extraadrenal tumors difficult to
detect
▪ 123 MIBG: taken up by chromaffin tissue anywhere in body; useful for localizing
small tumors
▪ PET-CT/PET-MRI w/ MIBG, DOPA, succinate, or FDG: highly Sn; for difficult to
localize tumors
▪ Venous catheterization w/ sampling of blood at different levels for catecholamine
determinations: only rarely necessary for localizing tumor
Batch Clingy
DIFFERENTIAL DIAGNOSIS
Renal or renovascular disease; CoA; hyperthyroidism; cerebral disorders, DI, DM;
Cushing syndrome; deficiencies of 11β-hydroxylase, 17α-hydroxylase, or 11βhydroxysteroid dehydrogenase (type 2 isozyme); primary aldosteronism;
adrenocortical tumors; and, rarely, essential hypertension
● Nonfunctioning kidney: result from compression of ureter/renal artery by
pheochromocytoma
● Paroxysmal HTN: assoc w/ porphyria or familial dysautonomia
● HTN in NF: renal vascular involvement or concurrent pheochromocytoma
● Neuroblastoma, ganglioneuroblastoma, ganglioneuroma freq produce
catecholamines
- urinary catecholamines higher w/ pheochromocytoma
- dopamine & homovanillic acid usually higher in neuroblastoma
- secreting neurogenic tumors: HTN, excessive sweating, flushing, pallor, rash,
polyuria, polydipsia
chronic diarrhea assoc w/ these tumors, particularly ganglioneuroma (sufficiently
persistent to suggest celiac disease)
PPS Oral Exam Reviewer 2020
123
Complex
Batch Clingy
▪ Chest pain is a common presenting complaint among children and adolescents.
▪ Many causative factors:
● Idiopathic (12-85%)
● Musculoskeletal (15-76%)
● Pulmonary (12-21%)
● Psychogenic (4-17%)
● GI (4-8%)
● Miscellaneous (4-25%)
▪ Children younger than 12 years old are more likely to have cardiopulmonary cause, adolescents older than 12 years old more likely to have idiopathic or psychogenic causes
PPS Oral Exam Reviewer 2020
124
DISEASE
MUSCLE STRAIN
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most identifiable cause of chest pain due to its association with
localized tenderness elicited by specific manipulation of the thorax
▪ Involves the ribs, costochondral junctions, costal cartilages,
intercostal muscles, sternum, clavicle or spine
▪ Occurs in young children with URTI – frequent coughing →
straining of extrinsic muscles; among teenagers active in
gymnastics and most other sports
▪ Self-limited with intermittent exacerbations during adolescence
▪ Same as above
▪ Unilateral sharp, stabbing pain along the upper 2 or more
contiguous costochondral joints
▪ Pain exacerbated by deep breathing and lasts from a few
seconds to a few minutes
LABORATORY FINDINGS / DIAGNOSIS
▪ Clinically diagnosed based on history and physical
examination
▪ Diagnosis of exclusion
TREATMENT / COMPLICATIONS / PREVENTION
▪ Reassurance, analgesia, rest or any combination of these 3
measures
▪ NSAIDs for 1 week – decrease inflammation and pain
▪ In most circumstances, allaying the fears of the patient and
parents by counselling them about the benign nature of
condition helps to relieve concern and reduce the degree of chest
pain
Batch Clingy
COSTOCHONDRITIS
Costosternal Syndrome
CLINICAL MANIFESTATIONS
▪ Localized or pinpoint pain
▪ Pain is worse with movement, certain body positions,
coughing, inspiration
▪ Some are described in relations to specific patterns of
muscular pain (i.e. Pectoral syndrome, coracoid syndrome,
xiphoid process syndrome)
PPS Oral Exam Reviewer 2020
125
PLEURAL EFFUSION
3 STAGES
Exudative/Stage of uncomplicated effusion
▪ Airway and parenchymal infection → aspiration of the
microorganisms into subpleural alveoli → causes migration and
adherence of PMNs
▪ Oxygen metabolites and products of activated PMNs →
endothelial injury of subpleural and pleural vessels, and increase
capillary permeability
▪ The parapneumonic fluid initially tends to be small volume of
sterile, PMN-dominant exudate
PPS Oral Exam Reviewer 2020
▪ Dyspnea
▪ Chest pain
▪ Respiratory symptoms
▪ Older children: sharp pleuritic pain
● Pain on inspiration with subsequent shallow breaths or
cough
● Due to stretching of parietal pleura
● As the effusion increases and separates the pleural
membranes, pleuritic pain becomes a dull ache and disappears
▪ Dullness and decreased breath sound over the affected area
▪ Decreased vocal fremitus
▪ Fullness of intercostal spaces
▪ Pleural rub
● Due to roughened pleural surfaces
● Can be present in the early phase
● Disappears as fluid accumulates
CXR: identifies severity of lung contusion – correlates with
impairment of oxygenation, CO2 exchange, and duration of
mechanical ventilation
▪ Minor – supportive care in the form of supplemental oxygen,
pulmonary toilet, and fluid restriction
▪ Severe – require mechanical ventilation in up to 30% of children
CT scan: more sensitive, for better imaging of chest
Long-term outcomes
▪ Spontaneous resolution
▪ Normal lung function
CXR (PA view)
▪ Primary tool for diagnosing pleural effusion
▪ Obliteration of costophrenic sinus is the earliest diagnostic
sign of the effusion
▪ Lateral decubitus film – quality and quantity of underlying
parenchyma
▪ IV antibiotics directed at the underlying infection
● Continued until the child is afebrile for at least 7-10 days
● Oral antibiotics administered for 1-3 weeks
Ultrasound
▪ Can differentiate pleural thickening from effusion, amount of
fluid
▪ Helps identify best site for thoracentesis or insertion of
thoracostomy tube
▪ Detects loculations and determine quality of effusion
▪ Drainage of infected fluid by thoracentesis or CTT
● Less effective at the 2nd stage of disease
● When CTT reaches 30-50ml/day and symptoms improve,
chest tube may be removed
▪ VATS or early lung decortication
● Considered in selected children who have parapneumonic
effusion or empyema whose clinical course does not improve,
severe lung trapping, multiple loculi or an extensive pleural peel,
or empyema caused by infectious bacteria other than S. aureus
Pleural fluid examination (see table below)
▪ Most patients with uncomplicated parapneumonic effusion
respond well to appropriate antibiotic therapy and do not require
thoracostomy, with no residual lung damage
▪ Patients with empyema have more prolonged and complicated
Batch Clingy
CONTUSION Pulmonary
Contusion
▪ Range in severity from being an isolated asymptomatic
radiographic finding, to significant respiratory failure requiring
mechanical ventilation
▪ Direct lung injury from thoracic trauma → transmission of force
through the relatively thin and compliant chest wall to the
underlying organs → pulmonary contusions, lacerations, traumatic
pneumatoceles
▪ 34 – 100% of children with thoracic trauma
▪ Results in damage at the level of the alveoli → hemorrhage and
edema → poor gas exchange
▪ Fluid in the pleural space
Causes:
▪ Infection (50-70% parapneumonic effusion)
▪ CHF (5-15%)
▪ Malignancy (rare)
Bacterial causes: S. aureus (<2yo), S. pneumoniae (25%), H.
influenzae, Group A streptococci
126
Fibrinopurulent/Second or Bacterial invasive stage
▪ Endothelial injury more pronounced → pleural fluid formation
increases – characterized by ↑ PMNs, ↓ glucose (increased
glycolysis by PMNs and bacterial metabolism)
▪ ↓ pH, ↑ LDH
▪ Pleural fluid is clottable because procoagulants may move in the
space and fibrinolytic activity may be lost due to mesothelial injury
hospital courses
Stage of organization (third stage of empyema)
▪ Thick, purulent coagulum
▪ The resultant inelastic peel impairs pleural fluid drainage and
inhibits lung expansion
Type of Effusion
STARLING PRINCIPLE
▪ Fluid accumulates in the pleural cavity whenever filtration >
removal mechanism, and may be the result of ↑ filtration
associated with impaired absorption or of normal filtration
associated with inadequate removal
Pleural/Serum Concentration
Ratio
CHON
LDH
CHON
LDH
pH level
Transudate
< 3 g/dL
< 2/3
< 0.5
< 0.6
> 7.45
Exudate
≥ 3 g/dL
> 2/3
≥ 0.5
≥ 0.6
< 7.3
*Pleural LDH should be <2x the upper level of serum LDH
▪ Infants and toddlers: vomiting, feeding problems, poor weight
gain
▪ Peripheral eosinophilia
▪ Elevated IgE
▪ Older children and adolescents: solid food dysphagia,
occasional food impactions or strictures, heartburn, chest or
epigastric pain
▪ Search for food (aerodigestive) and environmental allergies
via skin prick (IgE mediated) and patch (non-IgE mediated)
tests to guide decisions regarding dietary elimination and
future food challenges
▪ Incidence: 5 per 100,000
▪ Prevalence: 29.5 per 100,000
▪ Mostly male; mean age at diagnosis: 7 years old
▪ Duration of symptoms: 3 years
ESOPHAGITIS
▪ Pathogenesis involves mainly T helper type 2 cytokine-mediated
(IL-5 & 13) pathways leading to production of a potent eosinophil
chemoattractant, eotaxin-3, by esophageal epithelium
INFECTIVE ESOPHAGITIS
▪ Often affects immunocompromised children
▪ EA: fungi – Candida albicans, Torulopsis glabrata
▪ Candida – leading cause
immunocompromised children
in
immunocompetent
PPS Oral Exam Reviewer 2020
Topically acting swallowed corticosteroids (ie fluticasone
without spacer, viscous budesonide suspension) – for those who
refuse, fail to adhere, or have a poor response to restricted diets
▪ Histologic remission is observed in 65-77% children and adults
treated with fluticasone for 3 months
▪ Odynophagia
▪ Dysphagia
▪ Retrosternal or chest pain
▪ Fever, nausea, vomiting
and
PILL ESOPHAGITIS
▪ Produced by contact with a damaging agent
▪ Common meds: tetracycline, doxycycline, KCl, FeSO4, NSAIDs,
cloxacillin and alendronate
Dietary restrictions
▪ Elimination diets guided by circumstantial evidence and food
allergy test results
▪ “6 food elimination diet” removing the major food allergens
▪ Elemental diet composed exclusively of an amino acid-based
formula
▪ Elimination diets are generally successful, with highest
histologic response observed in nearly 91% on elemental diet and
in 72% to empiric dietary elimination
Candida – concurrent oropharyngeal infection
▪ Acute discomfort
▪ Progressive retrosternal pain
▪ Odynophagia
▪ Dysphagia
Diagnosis is made by endoscopy
▪ White plaques in Candida
▪ Multiple superficial ulcers or volcano ulcers in HSV
▪ Single deep ulcer in CMV
Histologic exam
▪ Yeast and pseudohyphae in Candida
▪ Tissue invasion distinguishes esophagitis from mere
colonization
Endoscopy – focal lesion often localized to 1 of the anatomic
narrowed regions of the esophagus or to an unsuspected
pathologic narrowing
▪ Appropriate antimicrobial agents
▪ Supportive
▪ Sucralfate, antacids, topical anesthetics and bland or liquid diets
– often used, lacks evidence
▪ Offending pill may be restarted after complete resolution of
Batch Clingy
▪ ↑ Capillary permeability – infection, SLE, toxin, tumors
▪ ↑ Capillary hydrostatic pressure – CHF, pericarditis
▪ ↓ Hydrostatic or interstitial space pressure – post thoracentesis
or trapped lung
▪ ↓ Plasma oncotic pressure – hypoalbuminemic state, nephrosis,
hepatic cirrhosis
▪ ↑ Oncotic pressure of interstitial space – pulmonary infarction
EOSINOPHILIC ESOPHAGITIS
▪ Esophageal dysfunction and infiltration of esophageal epithelium
by >15 eosinophils/hpf
▪ Many have other atopic diseases and associated with food
allergies
▪ EREFS (endoscopic reference score – Edema, Rings, Exudates,
Furrows, Strictures)
Pleural Liquid Concentration
127
▪ Most often, offending tablet is ingested at bedtime with
inadequate water
▪ Imbalance between myocardial oxygen supply and demand
▪ If left untreated → angina pectoris, myocardial stunning,
myocardial hibernation
▪ Under the most severe instances, acute coronary syndromes like
myocardial infarctions
▪ Increased myocardial oxygen demand in the presence of a severe
fixed stenosis
▪ Coronary spasm due to local release of vasoactive mediators
▪ Transient thrombus formation
ISCHEMIA
▪ Main mechanisms by which MI can occur
● Reduction in myocardial supply of oxygen
● Increase in myocardial oxygen demand
Chest pain is more likely ischemic in nature when associated
with:
▪ Exertion more than at rest
▪ Dyspnea
▪ Diaphoresis
▪ Syncope
and characterized as:
▪ Substernal pressure or burning rather than pain
▪ Pressure that radiates to neck or arm
▪ Fairly reproducible with similar activity
▪ Short lived (2-10 mins)
ECG
▪ Whether the ischemia is subendocardial or transmural will
affect the ST changes and the interpretation of the ECG
▪ Acute transmural ischemia – tall peaked T waves with ST
elevation are produced from epicardial injury representing the
ischemic zone at risk of myocardial injury
▪ The location that represents the ischemic zone is represented
by the placement of the surface ECG
symptoms, if deemed necessary, though with clear emphasis on
ingestion with adequate volume of water, usually at least 4 oz
-Immediate therapeutic interventions involves reducing
myocardial oxygen demand with betablocker
therapy, antiplatelet agents, diagnostic testing to delineate the
cause, and finally definitive treatment
Cardiac troponins T and I and creatine kinase MB isoenzyme
(CK-MB)
▪ Biomarkers of myocardial injury
▪ When elevated, signify myocardial damage with good
sensitivity and specificity
▪ After injury occurs, within 2 hours, these enzymes will rise
and may continue to rise for several hours
▪ By 12 hours, the CK-MB will begin to decrease and by 24 hours
the sensitivity of the troponins
remains high whereas the CK-MB sensitivity diminishes
Cardiac MRI (CMR) and CT
▪ Tests of choice for diagnosing anomalous coronary arteries,
coronary fistulae, coronary aneurysm, and ostial coronary
artery disease following coronary reimplantation
▪ More common in adolescents
▪ Children and adolescents may have a history of anxiety and/or
stressful life events that are not easily apparent but can have a
large impact on their perception of pain
ANXIETY/
STRESS
▪ Within anxiety disorders, chest pain and other symptoms are
temporally related to stressful situations. Anxiety-related
psychogenic chest pain is 4x as likely to occur in a patient with a
family history of chest pain (often an adult with a history of cardiac
ischemia), and the pain is often fleeting and vague in its
description
*see Chronic Cough*
*see Arrhythmia*
▪ Hardest to treat, often requiring consultation with behavioral
pediatricians, counselors, and/or psychologists
▪ Rapid breathing
▪ Dyspnea and anxiety to the degree that systemic symptoms
result – paresthesia, dizziness, lightheadedness, palpitations,
and confusion
▪ Sharp, non-radiating pain over the left precordium – easiest to
diagnose when these symptoms arise without exertion
▪ Rest
▪ Detect underlying cause
▪ Referral to psychiatrist as needed
Batch Clingy
GERD
RHYTHM DISTURBANCE
▪ Most common etiologies
● Hyperventilation
● Underlying psychiatric illness – anxiety, depression, or
somatoform disorders (conversion or somatization)
HYPERVENTILATION SYNDROME
▪ Most often in the setting of a panic attack
▪ Can occur as an acute one-time episode or can represent an
underlying panic disorder if recurrent
▪ Somatic symptoms – breathlessness, fatigue, nervousness,
near-syncope, palpitations
▪ Demonstrate more bodily worries, more limitation of general
activity, and more school absences
▪ Psychologic forms of chest pain is typically recurrent with
stressors.
PPS Oral Exam Reviewer 2020
128
Complex
ATRIAL SEPTAL
DEFECT
ASD
▪ Despite the large pulmonary blood flow, PAP is initially normal –
absence of a high-pressure communication between the pulmonary and
systemic circulations
ATRIOVENTRICULAR SEPTAL DEFECTS
▪ Ostium primum and Atrioventricular canal/Endocardial cushion defects
▪ Deficiency of AV septum
▪ Severity of the AV valve abnormality varies
▪ Complete AV septal defect common in children with Down syndrome
Basic abnormality
▪ Combination of L-to-R shunt across atrial defect and
▪ Mitral (or occ tricuspid) insufficiency
▪ Complete AV septal defects: L-to-R shunting occurs at atrial and
ventricular level
▪ Often asymptomatic
▪ PE same as secundum ASD, but with apical holosystolic
murmur
▪ Hyperdynamic precordium
▪ Normal or accentuated S1
▪ Wide, fixed splitting of S2
▪ Pulmonary SEM preceded by click
▪ Low-pitched, mid-diastolic rumbling murmur at the
lower left sternal edge or apex
Complete AV septal defects
▪ Infancy: CHF and intercurrent pulmonary infection
▪ Mod to marked cardiac enlargement
▪ Systolic thrill at lower sternal border
▪ If small with minimal L-to-R shunts, no RV enlargement: closure not
required
▪ Infants with small to moderate-sized ASDs: watch closely – defects
often grow smaller in the 1 st year of life
Transcatheter device or surgical closure for:
● All symptomatic patients
● Asymptomatic patients with Qp:Qs ratio ≥2:1
● RV enlargement
▪ Done after the 1st YOL and before school entry
▪ Repair is preferred during early childhood because surgical mortality
and morbidity are significantly greater in adulthood
Percutaneous catheter device closure
▪ Procedure of choice for most patients
▪ Uses an atrial septal occlusion device, implanted transvenously in the
cardiac catheterization laboratory
PROGNOSIS
▪ Results after surgical or device closure in children with moderate to
large shunts are excellent
▪ Secundum ASDs are well tolerated during childhood
▪ Significant symptoms do not usually appear until the 3rd decade or
later
CXR (complete AV septal defects):
▪ Moderate to severe cardiac enlargement
▪ Large PA
▪ ↑ Pulmonary vascularity
Surgical treatment of complete AVSD:
▪ More complex
▪ Highly successful
▪ Must be performed during infancy
ECG (complete AV septal defects) – distinctive and
diagnostic:
▪ Superior orientation of the mean frontal QRS axis with axis
deviation to the RUQ (QRS negative in both lead I and lead
aVF)
▪ Counterclockwise inscription of QRS vector loop (Q wave in
leads I and aVL)
▪ Signs of biventricular hypertrophy or isolated RV
hypertrophy
▪ RV conduction delay (rSR’ pattern in leads V3R and V1)
▪ N or tall P waves
▪ Occasional prolongation of the PR interval
Pulmonary arterial banding – reserved for patients with lesions that
make early corrective surgery too risky
2DED: “Gooseneck” deformity of the LVOT
PPS Oral Exam Reviewer 2020
TREATMENT / COMPLICATIONS / PREVENTION
PROGNOSIS
If unrepaired complete AVSD, depends on:
▪ Magnitude of L-to-R shunt
▪ Degree of PVR elevation
▪ Severity of AV valve insufficiency
COMPLICATIONS
▪ Pulmonary HPN
▪ Early tendency to increase PVR
Batch Clingy
DISEASE
ACYANOTIC HEART DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS /DIAGNOSIS
▪ May occur in any portion of the atrial septum – secundum, primum, or sinus venosus, depending on which embryonic septal stru cture has failed to develop normally
▪ Majority are sporadic
OSTIUM SECUNDUM DEFECT
▪ Often asymptomatic
CXR
▪ Most common form of ASD
▪ Younger children: subtle failure to thrive
▪ RA and RV enlargement depending on size of the shunt best
▪ Normal AV valves
▪ Older children: varying degrees of exercise intolerance
appreciated on lateral view (RV protrudes anteriorly as its
▪ May be single or multiple (fenestrated atrial septum)
volume increases)
▪ Openings >2cm in diameter are common in symptomatic older
▪ Widely split and fixed S2 during all phases of respiration
▪ Enlarged PA
children
– constantly ↑ RV diastolic volume, prolonged ejection
▪ ↑ Pulmonary vascularity
▪ May be associated with MVP and partial anomalous pulmonary venous
time in all phases of respiration
return (PAPVR)
ECG
▪ Systolic ejection murmur (SEM)
▪ RV volume overload
▪ Degree of L-to-R shunting depends on the size of the defect, the
● Not > grade 3/6, medium-pitched, without harsh
▪ RAD or N QRS axis
relative compliance of the RV and LV, and the relative vascular
qualities
▪ Minor RV conduction delay (rSR’ pattern in the R precordial
resistance in the pulmonary and systemic circulations
● Seldom accompanied by a thrill
leads)
● Best heard at the left middle and upper sternal border
▪ In large defects, a considerable shunt of oxygenated blood flows from
● Produced by the ↑ flow across the RV outflow tract
2DED
LA to RA. This blood is added to the usual venous return to the RA and is
into the PA
▪ RV volume overload
pumped by the RV to the lungs (ratio of pulmonary-to-systemic blood
▪ ↑ RV end-diastolic dimension
flow (Qp:Qs) is between 2:1 and 4:1)
▪ Short rumbling mid-diastolic murmur
▪ Flattening and abnormal motion of the ventricular septum
● d/t the ↑ volume of blood flow across the TV
(septal motion either flattened or reversed)
▪ Paucity of symptoms in infants with ASDs is related to the structure of
● Audible at the left lower sternal border
the RV in early life – thick and less compliant muscular wall → limited Lto-R shunt
▪ As the infant grows and PVR drops, the RV wall becomes thinner → ↑
L-to-R shunt across the ASD → ↑ blood flow through the R side of the
heart → RA and RV enlargement, PA dilation
▪ ↑ Pulmonary blood flow returns to the LA → LA enlargement
129
VENTRICULAR
SEPTAL DEFECT
(VSD)
Small VSDs with trivial L-to-R shunts and normal PAP –
most common and asymptomatic
CXR: cardiomegaly with prominent ventricles, LA and PA
▪ Physical size of the VSD – major determinant of the size of the L-to-R
shunt
▪ Large defects: level of PVR to SVR – major determinant of the shunt’s
magnitude
▪ When the PVR/SVR ratio approaches 1:1, the shunt becomes
bidirectional → Eisenmenger syndrome → signs of CHF
▪ Wall of ductus deficient in both the mucoid endothelial layer and the
muscular media
▪ F>M
▪ Associated with maternal rubella and prematurity
PATENT DUCTUS
ARTERIOSUS
DISEASE
▪ High aortic pressure → blood flows through the aorta → PDA: blood
shunts L-to-R from aorta to pulmonary artery
▪ Extent of the shunt depends on 1) size of the ductus, 2) PVR/SVR ratio
▪ Large PDA: PAP elevated to systemic levels during systole and diastole
ETIOLOGY / INCIDENCE / PATHOGENESIS
4 COMPONENTS
▪ Obstruction to RV outflow (pulmonary stenosis)
▪ Malalignment type of VSD
▪ Overriding aorta
▪ RVH
TETRALOGY OF
FALLOT
PPS Oral Exam Reviewer 2020
ECG normal but may suggest LVH
Large VSDs – signs of CHF:
▪ Dyspnea
▪ Feeding difficulties
▪ Poor growth
▪ Profuse perspiration
▪ Recurrent pulmonary infections in early infancy
▪ Loud, harsh or blowing holosystolic murmur at the L left
sternal border with a thrill
▪ Prominence of the left precordium
▪ Palpable parasternal lift
▪ Laterally displaced apical impulse
▪ Apical thrust
Small PDA: asymptomatic
Large PDA:
▪ Growth retardation
▪ Bounding peripheral arterial pulses
▪ Wide pulse pressure
▪ Classic continuous murmur (machinery-like) begins after
S1, reaches max intensity at end of systole, and wanes in
late diastole
▪ Thrill, maximal in the 2nd left ICS, radiating toward the left
clavicle
2DED
▪ Estimates shunts size
▪ Calculates pressure gradient across the defect
PROGNOSIS
Results of primary surgical repair are excellent; long-term
prognosis excellent
ECG
▪ Normal if small
▪ Large: LVH or biventricular hypertrophy
CXR (large PDA)
▪ Prominent PA
▪ ↑ Pulmonary vascular markings
CYANOTIC HEART DISEASE
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS / DIAGNOSIS
“tet” or “blue” spells – paroxysmal hypercyanotic attacks
CXR: Coeur en sabot (boot shaped heart)
▪ 1st year of life
▪ Frequently in the morning or after episodes of crying
ECG
▪ Relieved with squatting
▪ RAD, RVH
▪ Dominant R wave in right precordial chest leads (V1, V2), or an
Older children with unrepaired tetralogy:
RSR’ pattern
▪ Dyspnea on exertion
▪ Dusky blue skin, gray sclerae with engorged blood vessels
2DED
▪ Marked clubbing of fingers and toes
▪ Extent or aortic override of the septum
▪ Location and degree of RVOT obstruction
▪ Left anterior hemithorax may bulge anteriorly (long-standing
▪ Size of the pulmonary valve annulum and main and proximal
RVH)
branch pulmonary arteries and side of the aortic arch
▪ Substernal RV impulse
▪ Systolic thrill along the left sternal border in the 3rd and 4th
Cardiac Catheterization
parasternal spaces
▪ Systolic pressure in RV = systemic pressure
▪ Loud and harsh systolic ejection murmur most intense at the
left upper sternal border
COMPLICATIONS
Cerebral thromboses
▪ In cerebral veins or dural sinuses; <2yo
▪ Sequelae of extreme polycythemia and dehydration
▪ Tx: adequate hydration, supportive measures; if extremely
polycythemic, phlebotomy and volume replacement with albumin
Small defects
▪ Close spontaneously
▪ 1st 2 years of life
▪ Small muscular VSDs more likely to close
Goals in infants with large VSD:
▪ Control symptoms of CHF
▪ Prevent pulmonary vascular disease
Indications for surgical closure
▪ Any age with large defect and clinical symptoms and failure to thrive
cannot be controlled medically
▪ Infants 6-12 mos old with moderate to large defects assoc with
pulmonary HPN
▪ Older than 24 mos old with Qp:Qs ratio greater than 2:1
Antibiotic prophylaxis is no longer recommended for dental visits or
surgical procedures
Irrespective of age, requires either catheter or surgical closure  good
prognosis
Small PDA:
▪ Closure to prevent bacterial endarteritis or other late complications
▪ Closed with coils
Moderate to large PDA:
▪ Closure to treat heart failure and prevent the pulmonary vascular
disease
▪ Closed with umbrella-like device
TREATMENT / COMPLICATIONS / PREVENTION
“Tet” spells:
▪ Place infant on the abdomen in knee-chest position (make sure infant’s
clothing not restrictive)
▪ Oxygen
▪ Morphine/SC in a dose not >0.2 mg/kg
▪ If tet spell is unusually severe, metabolic acidosis may develop → rapid
correction with IV Na bicarbonate
▪ If still resistant, intubation and anesthetic sedation
IV phenylephrine
▪ ↑ SVR
▪ Improve RV outflow
▪ Decrease the R-to-L shunt
B-adrenergic blocker
▪ IV propranolol (0.1-0.2mg/kg)
Corrective open-heart surgery
▪ Early infancy and critically ill newborn
▪ Early physiologic correction allows improved growth of the branch
pulmonary arteries.
▪ Infants with less severe cyanosis and can be maintained with good growth
and absence of hypercyanotic spells, primary repair is performed electively
Batch Clingy
▪ Most common cardiac malformation
▪ 25% of CHDs
▪ Most common are the membranous type
130
or saline
Brain abscess
▪ >2yo
▪ Low-grade fever, gradual change in behavior, HA, n/v, seizure
▪ Do CT or MRI to confirm
▪ Tx: surgical drainage + antibiotics
Bacterial endocarditis: right infundibulum or pulmonic, aortic, or
tricuspid valve
Heart failure
TRANSPOSITION OF
THE GREAT
ARTERIES
(TGA)
▪ A risk factor is
GDM
L-TGA “Physiologically corrected TGA”
▪ L – looped TGA
▪ AV relationships are discordant (atrioventricular
discordance/ventricular inversion): RA → LV; LA → RV
▪ Desaturated systemic venous blood returns via the vena
cava to a normal RA → bicuspid atrioventricular (mitral)
valve → R-sided ventricle (with architecture and smooth
wall morphologic features of the normal LV) →
transposed PA → lungs → oxygenated pulmonary venous
blood returns to a normal LA → L-sided ventricle (has
trabeculated morphologic features of a normal RV) →
transposed aorta
▪ The double inversion of the atrioventricular and
ventriculoarterial relationships result in desaturated RA
blood appropriately flowing to the lungs, and oxygenated
pulmonary venous blood appropriately flowing to the
aorta (physiologically corrected circulation)
▪ Total mixing of systemic venous and pulmonary venous
blood flow within the heart
TOTAL
ANOMALOUS
PULMONARY
VENOUS RETURN
(TAPVR)
PPS Oral Exam Reviewer 2020
▪ Cyanosis and tachypnea within the few hours or days of life →
survival in immediate NB period provided by foramen ovale and
ductus arteriosus
ECG: normal
▪ S2 usually single and loud
▪ Soft systolic ejection murmur
2DED – diagnostic; confirms:
▪ Transposed ventricular-arterial connections size of the interatrial
communication
▪ Ductus arteriosus
▪ Degree of mixing
Cardiac catheterization
▪ Done if unusual coronary artery anomaly is suspected, or require
emergency balloon atrial septostomy (Rashkind procedure)
Hypoxemia depends on
▪ Degree of atrial level shunting
▪ Whether the ductus is partially open or totally closed
CXR: classic egg-shaped heart
ECG
▪ Atrioventricular conduction disturbances
▪ Abnormal P waves
▪ Absent Q waves in V6
▪ Abnormal Q waves in leads III, aVR, aVF, V1
▪ Upright T waves across the precordium
Palliative systemic-in-pulmonary artery shunt (Blalock-Taussig shunt)
▪ Indication: co-morbidities such as other major congenital anomalies or
prematurity
▪ Augment pulmonary artery blood flow to decrease the amt of hypoxia and
improve linear growth
▪ Augment growth of the branch pulmonary arteries
▪ After successful total correction, patients are asymptomatic and can lead
unrestricted lives
Prostaglandin E1 (PGE1, 0.01-0.02 ug/kg/min); maintains patency of the
ductus arteriosus
Rashkind balloon atrial septostomy
▪ In infants who remain severely hypoxic or acidotic despite PGE1 infusion
▪ If significant delay in surgery is necessary
Arterial switch (Jatene) procedure
▪ Surgical treatment of choice for neonates (d-TGA with intact VSD)
ithin the first 2 weeks of life
▪ >95% Survival rate for uncomplicated d-TGA
Atrial switch procedure (Mustard or Senning operation)
▪ Excellent early survival (85-90%)
▪ Significant long-term morbidities
▪ Reserved for those whose anatomy are not candidates for the arterial
switch procedure
Double switch procedure:
▪ Atrial switch – reroute the systemic and pulmonary venous returns
▪ Arterial switch – reroute ventricular outflows
CXR: suggest abnormal position of the great arteries
▪ Ascending aorta occupies the upper left border of the cardiac
silhouette
2DED: atrioventricular discordance
▪ Manifestations depend on the presence or absence of
obstruction of the venous channels
▪ If obstructed pulmonary venous return → severe pulmonary
congestion and pulmonary hypertension
▪ Neonates with severe obstruction to pulmonary venous
return: severe cyanosis, respiratory distress
Mild or no obstruction to pulmonary venous return:
▪ Heart failure as the pulmonary vascular resistance falls
▪ Mild to moderate degrees of desaturation
ECG: RVH – usually qR pattern in V3R and V1 and P waves are
frequently tall and spiked
Obstructed TAPVR – surgical emergency because prostaglandin therapy is
usually not effective
CXR
▪ Neonates with marked pulmonary venous obstruction – very
dramatic perihilar pattern of pulmonary edema
▪ In older children: snowman appearance of heart
▪ Surgical correction: infancy
▪If surgery cannot be performed urgently, ECMO may be required to
maintain oxygenation
2DED
▪ Any vein with doppler flow away from the heart is
pathognomonic
▪ Large RA and RV
PROGNOSIS
▪ Early post-op results are generally good, even for critically ill neonates
Batch Clingy
d-TGA
▪ 5% of all CHDs
▪ Aorta is anterior and to the right of the pulmonary
artery (d – dextropositioned aorta)
▪ Systemic and pulmonary circulations exist as 2 parallel
circuits:
● Aorta arises from the anterior RV and systemic veins
return to the LA
▪ AV concordance (RA → RV; LA → LV)
o
at 4-6 months of age
131
TRUNCUS
ARTERIOSUS
▪ Single arterial trunk arises from the heart and supplies
the systemic, pulmonary and coronary circulations
▪ Total mixing lesion with complete admixture of
pulmonary and systemic venous return
▪ VSD always present, TA overrides VSD
▪ Ventricles are at systemic pressure and eject blood into
the truncus
▪ When PVR is relatively high immediately after birth,
pulmonary blood flow may be normal. But as PVR drops
in the 1st month of life, blood flow to the lungs is greatly
increased and heart failure ensues.
▪ If lesion is left untreated, PVR eventually increases,
pulmonary blood flow decreases, and cyanosis becomes
more prominent (Eisenmenger physiology)
Immediate NB period
▪ Signs of heart failure absent
▪ Murmur & minimal cyanosis may be only finding
▪ No outlet from the RA to RV
▪ Entire systemic venous return leaves the RA and enters
the L side of the heart through the foramen ovale or
atrial septal defect
▪ Physiology of the circulation and the clinical
presentation will depend on the presence of other
congenital heart defects
▪ Some degrees of cyanosis at birth, extent depending on the
degree of limitation to pulmonary blood flow
▪ Increased LV impulse
▪ Single S2
▪ Pulses in lower extremities may be weak, or absent if with CoA
1-2 mos old
▪ Heart failure with mild cyanosis
▪ Wide pulse pressure and bounding pulses
▪ Hyperdynamic precordium
▪ S2 is loud and single
▪ Systolic ejection murmur, accompanied by a thrill audible
along the left sternal border and frequently preceded by an
early systolic ejection click
▪ Apical mid-diastolic rumbling murmur audible as heart failure
develops
TRICUSPID ATRESIA
▪ Enlarged PA
▪ N or small LA and LV
Cardiac catheterization
▪ Done if there is question about the drainage of 1 or more
pulmonary veins
▪ Shows that O2 sat of blood in both atria, ventricles and aorta is
similar
ECG: RVH, LVH or combined ventricular hypertrophy
CXR
▪ Cardiac enlargement, with prominence of both ventricles
▪ Prominent shadow that follows the normal course of the
ascending aorta and aortic knob
2DED: diagnostic
▪ Large truncal artery overriding the VSD
▪ Pattern of origin of the branch pulmonary arteries
▪ Evaluate truncal valve regurgitation
ECG:
▪ LAD and LV hypertrophy – unique features
▪ Right precordial leads: prominent R wave replaced by an rS
complex
▪ Left precordial leads:
● qR complex, followed by a normal, flat, biphasic, or inverted T
wave
● RV6 is normal or tall
● V1 is deep
● P waves usually biphasic, with initial component tall and spiked
in lead II
● Combination of cyanosis and left axis deviation is highly
suggestive
Cardiac catheterization: Indicated only if questions remain after
echo, shows normal or slightly elevated right atrial pressure with a
prominent a wave
COARCTATION OF
THE AORTA
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ 98% are juxtaductal coarctation – just below the origin of the left
subclavian artery, at the origin of the ductus arteriosus
▪ Discrete juxtaductal coarctation: ascending aortic blood flows
through the narrowed segment to reach the descending aorta
▪ More severe juxtaductal coarctation: RV blood is ejected through the
ductus to supply the descending aorta (perfusion of lower part of the
body is RV output dependent)
PPS Oral Exam Reviewer 2020
▪ First few weeks of life, infants can be managed with anti-congestive
medications
▪ As PVR falls in infants, heart failure symptoms worsen and surgery is
indicated, within the 1st few months
● VSD is closed
● PA separated from truncus
● Continuity is established between RV and pulmonary arteries
▪ Delay in surgery → increase the likelihood of pulmonary vascular disease
▪ Surgical results have been excellent
Cardiac catheterization: L-to-R shunt at the ventricular level, with Rto-L shunting into the truncus
2DED: fibromuscular membrane in place of a tricuspid valve, a
variably small RV, VSD and large LV
DISEASE
COMPLICATIONS
▪ Patients where diagnosis was delayed, or with severe obstruction,
recurrent stenosis and development of pulmonary veno-occlusive disease
may occur
▪ Aggressive veno-occlusive disease: heart-lung transplantation is only
option
CLINICAL MANIFESTATIONS
▪ Classic sign: disparity in pulsation and BP in the arms and
legs – femoral, popliteal, posterior tibial and dorsalis pedis
pulses are weak
▪ Radial-femoral delays
Blood flow to the descending aorta is dependent on
collaterals
Femoral pulse is felt after the radial pulse
Severely cyanotic neonates:
▪ IV infusion of PGE1 (0.01-0.02 ug/kg/min) until a surgical aortopulmonary
shunt procedure can be performed
▪ Blalock-Taussig procedure: preferred anastomosis
Next stage surgery: bidirectional Glenn shunt
▪ Creation of an anastomosis between SVC and pulmonary arteries
▪ 2-6 mos old
▪ Reduces volume load on the LV
▪ Lessens the chance of LV dysfunction
Modified Fontan operations
▪ Preferred approach to larger surgical management
▪ Between 2 and 3 years old, after patient is ambulatory
▪ Anastomose RA or atrial appendage directly to PA
Cavopulmonary isolation procedure
▪ Modified modified Fontan
▪ IVC anastomose to pulmonary arteries
▪ Decrease risk of right atrial dilation
LABORATORY FINDINGS / DIAGNOSIS
CXR
▪ Mildly or moderately enlarged heart – d/t LV prominence
▪ Prominent shadow in left superior mediastinum – d/t
enlarged L subclavian artery
▪ Notching of the inferior border of the ribs (inverted 3 sign)
– d/t pressure erosion by enlarged collateral vessels
TREATMENT / COMPLICATIONS / PREVENTION
PGE1
▪ Neonates with severe coarctation
▪ Reopen the ductus, re-establish adequate LE blood flow
Anti-congestive meds
▪ Older infants with heart failure but good perfusion:
▪ Improve clinical status before surgical intervention
ECG
▪ Delay is unwarranted, especially after the 2nd decade of life
Batch Clingy
▪ Systolic murmurs at left sternal border
▪ Gallop rhythm
132
▪ Unless surgically corrected in infancy, coA results in development of
an extensive collateral circulation to by-pass coA
▪ Occurs twice as often in males vs females
▪ Short systolic murmur at the 3rd and 4th ICS, L sternal
border, transmitted to the L infrascapular area and occ to
the neck
▪ Normal in young children
▪ LV hypertrophy in older infants
2DED: demonstrate specific site of obstruction
PULMONARY
STENOSIS
▪ Frequently associated with other types of CHDs
▪ High incidence in infants with congenital rubella syndrome
▪ 5% of cardiac malformations
▪ One of the causes of sudden cardiac death
AORTIC STENOSIS
▪ Most common form: valvular aortic stenoses – leaflets are thickened,
commissures are fused to varying degrees
▪ Subvalvular (subaortic) stenosis – discrete fibromuscular shelf below
the AV → an important form of LVOT obstruction
▪ Supravalvular aortic stenosis – least common
▪ More frequent in males (3:1)
DISEASE
▪ Valvular lesions begin as small verrucae composed of fibrin and blood
cells along the borders of ≥1 heart valves → repeated attacks of RF →
new verrucae form near the previous ones → mural endocardium and
chordae tendinae become involved
CLINICAL MANIFESTATIONS
▪ ARF + echo findings of MV/AV involvement
▪ Subclinical carditis – (+) 2DED evidence of mitral or aortic
valvulitis, (-) auscultatory findings
ECG: in severe stenosis, RVH and RAE
CXR: cardiomegaly, prominence of MPA
2DED: acceleration of blood flow through stenoses
CXR: prominent ascending aorta, N heart size
2DED
▪ Site and severity of obstruction
▪ Number of valve leaflets and morphology, and presence of
a subaortic membrane or supravalvar stenosis
▪ Catheter balloon dilation, sometimes with placement of an
intravascular stent
▪ Balloon valvuloplasty: procedure of choice for moderate to severe
valvular AS
▪ Surgical treatment reserved for 1) extremely dysplastic aortic valves,
not amenable to balloon therapy, 2) subvalvar or valvar stenosis
▪ Konno procedure: AS in association with severe tunnel-like sub-aortic
obstruction
PROGNOSIS
In older infants and children with mild to moderate aortic stenosis,
prognosis is reasonably good, although disease progression over 5-10
years is common
LABORATORY FINDINGS / DIAGNOSIS
TREATMENT / COMPLICATIONS / PREVENTION
▪ Do 2DED for all cases of confirmed or suspected ARF
Batch Clingy
RHEUMATIC HEART
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most important sequela of acute rheumatic fever (ARF)
▪ Mitral valve most often affected → aortic valve
▪ Severe coarctation: cardiac enlargement, pulmonary
congestion
▪ Continuous SEM in widespread locations
▪ Immediate NB period: soft SEM over either or both lung
fields and disappears by 1-2mos old
▪ Less severe: asymptomatic, normal growth and
development, murmur is discovered during routine PE
▪ Louder, harsher, and longer murmur with greater degree
of obstruction
▪ Murmur is audible maximally at the R upper sternal
border and radiates to the neck and left midsternal border
accompanied by a thrill in the suprasternal notch
▪ Normal splitting of S2 in mild to moderate obstruction
Severe AS:
▪ Heart failure
▪ Cardiomegaly
▪ Pulmonary edema
▪ Weak pulses in all extremities
▪ Pale or grayish skin
▪ ↓ S1 d/t ↓ compliance of the thickened LV
▪ Significant number of infants operated before 1yo require revision
later in childhood; must be monitored for recoarctation and aortic
anastomotic aneurysm (if recoarctation occur, balloon angioplasty is
procedure of choice)
PPS Oral Exam Reviewer 2020
133
MITRAL INSUFFICIENCY
Structural changes:
▪ Loss of valvular substance
▪ Changes to the subvalvular apparatus
▪ Elongation of chordae
Structural changes in the valve → ↑ volume load → LV dilates → LA
also dilates to accommodate the regurgitant volume → ↑ LA pressure
→ pulmonary congestion and symptoms of L-sided heart failure
MITRAL STENOSIS
▪ Fibrosis of the mitral ring, commissural adhesions and contracture of
the valve leaflets, chordae and papillary muscles over time
▪ Chronic, takes >10yrs for lesion to be fully established
Significant MS → ↑ LA pressure → enlargement and hypertrophy of
LA, pulmonary venous HPN, ↑PVR → overt pulmonary HPN → RV
hypertrophy and RA dilation → RV dilation, TR, R-sided heart failure
AORTIC INSUFFICIENCY
▪ Poor coaptation of the leaflets or leaflet prolapse
Chronic AI → valve sclerosis → distortion and retraction of the cusps
→ regurgitation of blood → LV volume overload → dilation and
hypertrophy of LV
Mild
▪ No signs of heart failure
▪ High-pitched holosystolic murmur at the apex, radiating
to the axilla
Severe
▪ Signs of acute or chronic heart failure
▪ Heart enlarged
▪ Apical systolic thrill
▪ S2 may be accentuated if pulmonary HPN is present
▪ 3rd heart sound or gallop prominent
Mild: asymptomatic
Severe: exercise intolerance and dyspnea
▪ Orthopnea, PND, overt pulmonary edema, atrial
arrhythmias
▪ Pulmonary HPN: functional tricuspid insufficiency,
hepatomegaly, ascites, edema, increased JVP, accentuated
S2
▪ Parasternal RV lift
▪ Loud first heart sound
▪ Opening snap of mitral valve
▪ Long, low-pitched, rumbling mitral diastolic murmur with
presystolic accentuation at the apex
▪ Palpitations d/t large SV
▪ Sweating and heat intolerance d/t excessive vasodilation
▪ Wide pulse pressure, with bounding peripheral pulse
(water-hammer or Corrigan pulse)
Severe AI
▪ Enlarged heart
▪ LV apical heave, diastolic thrill
▪ Murmur begins with S2 and continues until late in
diastole, heard over the upper L and mid-L sternal border
with radiation to the apex and upper R sternal border, with
high-pitched blowing quality
ECG
▪ Severe: longer duration and often bifid P waves, LVH, RVH
CXR
▪ Severe: Prominent LA and LV, congestion of perihilar
vessels if with pulmonary venous HPN
2DED
Acute MI:
▪ LAE and LVH
▪ Mitral annular dilation
▪ Chordal elongation
▪ Chordal rupture resulting in flail leaflet
▪ Nodular leaflet tips
▪ Prolapse of anterior MV leaflet tip
Chronic MI:
▪ Leaflet and chordal thickening
▪ Chordal fusion
▪ Restricted leaflet
ECG
▪ Severe – prominent and notched P waves, RVH
▪ Late manifestations: AFib, atrial arrhythmia
CXR (Severe)
▪ LAE; prominent PA, RA, RV
▪ Kerley B lines in lower lung periphery
2DED
▪ Thickened MV and chordal apparatus
▪ Restricted motion of the valve
▪ Elbow or dog leg appearance of anterior leaflet of MV
▪ LA dilation
▪ Narrow jet with flow acceleration
▪ Variable degrees of tricuspid insufficiency
ECG: LVH, prominent P waves
CXR: Enlargement of LV and aorta
▪ Mild: prophylaxis against recurrences of RF
▪ Significant MI: Prophylaxis + corticosteroids
Afterload-reducing agents (ie. ACEI or ARBs)
▪ Reduce regurgitant volume
▪ Attenuate pathologic compensatory mechanisms
▪ Preserve LV function
Diuretics
Surgery for:
▪ Despite adequate medical therapy, have persistent heart failure
▪ Dyspnea with moderate activity
▪ Progressive cardiomegaly, often with pulmonary HPN
In patients with prosthetic MV replacement, prophylaxis against
bacterial endocarditis is warranted for dental procedures.
▪ Diuretics and B-blockers – for symptom control
▪ Surgical valvotomy or balloon catheter mitral valvuloplasty
▪ ACEIs or ARBs
▪ Prophylaxis against ARF recurrence
▪ Surgical intervention (aortic valve replacement) – done in advance of
heart failure, pulmonary edema and angina
2DED
▪ Dilated LV
▪ Diastolic mitral valve flutter or oscillations
▪ Aortic valve may show irregular or focal thickening
▪ Decreased systolic excursion
▪ Coaptation defect and leaflet prolapse
Batch Clingy
Austin Flint murmur: apical presystolic murmur (resembles
MS)
PPS Oral Exam Reviewer 2020
134
Complex
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
LABORATORY FINDINGS / DIAGNOSIS
TREATMENT / COMPLICATIONS / PREVENTION
▪ Sinus rhythm with heart rate greater than the upper limit of normal for age
▪ Usually precipitated by fever or hyperthermia, pain, anxiety, and severe infection
▪ May also be compensatory to loss of intravascular volume (e.g. diarrhea, blood loss), or compromised cardiac output
SUPRAVENTRICULAR TACHYCARDIA
▪ Includes all forms of paroxysmal or incessant tachycardia except
ventricular tachycardia
▪ May occur when the patient is at rest or exercising
▪ In infants, may be precipitated by acute infection
▪ May be exacerbated by exposure to caffeine, nonprescription
decongestants, or bronchodilators
▪ Abrupt onset and termination
▪ 1 in 250,000 to 1 in 250
▪ Peak incidence in the 1st 2mos of life
Older children
▪ Heart rate >180 bpm
▪ Palpitations, chest pain, abdominal pain, syncope during
exertion, rarely, sudden cardiac death
Three Mechanisms:
AV re-entry tachycardia (AVRT)
▪ Most common
▪ Ues an accessory pathway as the retrograde limb and the AV node as
the antegrade limb of the tachycardia
▪ Vagal stimulation – place the face in ice water (older children) or
place an ice bag over the face (infants) (diving reflex)
▪ Vagal maneuvers – valsalva maneuver, straining, breath holding, or
standing on their head
▪ If vagal stimulation failed, give Adenosine – drug of choice, 0.1mg/kg
(max 6mg), by rapid bolus followed by saline flush using central line or
antecubital vein. If SVT fails to terminate, give a 2nd dose at 0.2mg/kg
(max 12mg)
2DED to determine presence of heart disease and intracardiac
thrombus
▪ If with symptoms of severe heart failure, do synchronized
cardioversion (0.5-2 J/kg)
▪ As maintenance therapy, for patients without antegrade accessory
pathway, β-adrenergic blockers are mainstay of drug therapy.
Contraindicated in WPW.
AV node re-entry tachycardia (AVNRT)
▪ Rare in infancy
▪ Involves the slow antegrade limb and the fast pathway as the
retrograde limb of the tachycardia or “slow-fast” pathway most of the
time
Atrial tachycardia
▪ Has a focus in the atrium which beats faster than the sinus node;
ectopic or automatic tachycardias
VENTRICULAR TACHYCARDIA
▪ May be associated with myocarditis, anomalous origin of a coronary
artery, arrhythmogenic cardiomyopathy, MVP, primary cardiac tumors,
dilated or hypertrophic cardiomyopathy, drug use (cocaine,
amphetamine)
▪ May develop years after intraventricular surgery (especially TOF and
related defects) or occur without obvious organic heart disease
▪ In neonates, may be associated with an anomalous left coronary
artery or a myocardial tumor
VENTRICULAR FIBRILLATION
▪ Chaotic rhythm that results in death unless an effective ventricular
beat is rapidly established
▪ Lethal event
▪ May be seen in the setting of hypoxemia, anesthesia, hyper- or
hypokalemia, hereditary arrhythmias
PPS Oral Exam Reviewer 2020
ECG or rhythm strip
▪ Wide QRS tachycardia
▪ HR >120 bpm or >25% of the sinus rate
▪ At least 3 PVCs at >120bpm
▪ Clear capture and fusion beats – confirm the diagnosis
2DED to document presence of heart disease
▪ Syncope or sudden death
ECG: Rapid, irregular and polymorphic complexes
▪ Must be promptly treated because may result to hypotension and
degeneration into Vfib
▪ IV amiodarone, lidocaine or procainamide – initial drugs of choice if
hemodynamically stable. If successful, correct underlying
abnormalities after.
▪ Amiodarone – treatment of choice during cardiac arrest
▪ Immediate direct current (DC) cardioversion (VT with pulse:
synchronized cardioversion; pulseless VT: defibrillation) if
hemodynamically unstable
▪ Chronic tx: amiodarone, B-blocker, sotalol, phenytoin
▪ Defibrillation at 2 J/kg as initial dose + PALS algorithm
▪ If defibrillation is ineffective or VF recurs, give amiodarone or
lidocaine per IV and repeat defibrillation
▪ Electrophysiology study (EPS) – indicated for patients who survived
VF unless a clearly reversible cause is identified
▪ For patients in whom no correctable abnormality can be found, an
Batch Clingy
SINUS TACHYCARDIA
Infants
▪ Heart rate >220 bpm
▪ Signs and symptoms of congestive heart failure, rapid
heartbeat, irritability, poor feeding, hypothermia, poor
perfusion
ECG
▪ Narrow QRS complex tachycardia
▪ No visible P wave
▪ Fixed R-R interval
135
ATRIAL FLUTTER
▪ HR 250-300bpm in children
▪ HR 400-600bpm in neonates
▪ Diagnosis is confirmed by ECG: rapid, regular atrial sawtoothed flutter waves
Intraatrial Reentrant Tachycardia
▪ In older children, usually occurs in the setting of CHD; neonates
usually have normal hearts
▪ May occur during acute infectious illnesses but is most often seen in
patients with large stretched atria (ie. Long-standing mitral or tricuspid
insufficiency, tricuspid atresia, Ebstein anomaly or rheumatic mitral
stenosis)
▪ Can occur after palliative or corrective intraatrial surgery
▪ HR 400-700bpm
FIRST DEGREE
▪ May be found in normal children, patients with acute rheumatic
fever, myocarditis, congenital heart disease (ASD, AVSD), Duchenne
muscular dystrophy, myotonic dystrophy, trichinosis
▪ Can be due to anti-arrhythmic drugs
HEART BLOCK
ECG
▪ No distinct P waves
▪ Undulating baseline with narrow QRS complexes
▪ Changing R-R intervals
▪ Irregularly irregular ventricular rates – due to variability of
conduction from the atria to the AV node to the ventricles
COMPLICATIONS
▪ If uncontrolled, may precipitate heart failure
▪ Chronic atrial flutter in the setting of CHD may be at ↑ risk for
thromboembolism and stroke, and should undergo anticoagulation
before elective cardioversion
▪ Rate control is the best initial treatment, most effectively with
calcium channel blockers to limit the ventricular rate during atrial
fibrillation
▪ Do immediate DC cardioversion if hemodynamically unstable
PROGNOSIS
▪ ↑ Risk for thromboembolism and stroke → anti-coagulation with
warfarin
ECG
▪ Sinus rhythm
▪ Rate is below the normal for age
▪ If asymptomatic, no intervention needed
ECG
▪ Has a P wave preceding each QRS complex
▪ PR interval is prolonged but constant – all atrial impulses are
conducted to the ventricle
▪ No active intervention necessary
▪ Address the underlying cause
SECOND DEGREE
▪ Not every atrial impulse is conducted to the ventricle
Mobitz type 1
▪ Wenckebach Phenomenon
▪ Possible causes: myocarditis, digitalis toxicity, and CHDs
▪ Asymptomatic
ECG: Progressive prolongation of the PR interval until a P
wave is not conducted (drop beat)
▪ In the absence of heart failure or hemodynamic compromise, no
treatment is needed
Mobitz type 2
▪ Regular non-conducted P waves such that atrial rate exceeds the
ventricular rate
▪ Less common conduction defect but has more potential to cause
syncope, and may be progressive
▪May be asymptomatic
▪ When there is progression of the bradycardia, syncope
can occur
ECG:
▪ Identical P waves
▪ PR interval for conducted P waves is constant
▪ No progressive conduction delay or subsequent shortening
▪ No need for acute intervention unless associated with symptomatic
bradycardia, hemodynamic compromise, or heart failure
▪ Treatment is indicated for post-operative cases with advanced
second-degree AV block that is not expected to resolve and for cases
PPS Oral Exam Reviewer 2020
Batch Clingy
SINUS
BRADYCARDIA
▪ Mechanism of common atrial flutter: reentrant rhythm originating in
the RA circling the tricuspid valve annulus
▪ Because the AV node cannot transmit such rapid impulses, some
degree of AV block is virtually present
ATRIAL FIBRILLATION
▪ Atrial excitation is chaotic and more rapid and produces irregularly
irregular ventricular response and pulse
▪ Often associated with atrial enlargement or disease
▪ May be seen in older children with rheumatic MV stenosis
▪ May be due to thyrotoxicosis, pulmonary embolism, pericarditis, or
cardiomyopathy, in a previously normal older child
▪Complication of dilated atria from congenital or acquired heart
disease, particularly RHD among Filipino adolescents
▪ Seen in normal children during sleep or in any condition with
increased vagal tone, in athletes, in patients with sinus node
dysfunction, in children with increased intracranial, intrathoracic or
intraabdominal pressure
implantable cardioverter defibrillator (ICD) is almost always indicated
because of the high risk of sudden death
▪ Synchronized DC cardioversion – treatment of choice; usually
converts it immediately to sinus rhythm
▪ β-blockers or calcium channel blockers – may be used to slow the
ventricular response in atrial flutter by prolonging AV node refractory
period
▪ Class I agents (procainamide or propaferone) or class III agents
(amiodarone or sotalol) – may be used to maintain sinus rhythm
▪ Catheter ablation has been used in patients with normal hearts and
those with CHD with moderate success
136
▪ Possible causes: myocarditis, digoxin toxicity, and CHDs
of the PR interval after a blocked beat
which persist at least 7 days after cardiac surgery
▪ When symptomatic, do implantation of a permanent pacemaker
Holter monitoring may be indicated in some cases to
document whether symptoms occur together with this
rhythm.
THIRD DEGREE
▪ No impulse from the atria reach the ventricles
▪ Absence of meaningful association between atrial (P wave) and
ventricular (QRS complex) depolarization, despite regular and constant
P-P (distance between P waves) and R-R (distance between QRS
complex) intervals
▪ Atria and ventricles fire electrical impulses independently from each
other
▪ Can be congenital or acquired (myocarditis, diphtheria) and cardiac
surgery involving area around AV node like VSD closure or repair of
complex lesions
▪ Known complication of myocardial abscess secondary to endocarditis
▪ 1 in 22,000
▪ Some are asymptomatic
▪ Most will present with signs of ↓ cardiac output (from
easy fatigabil ity to syncope)
▪ In older children with normal hearts, often
asymptomatic, although syncope and sudden death may
occur
▪ Infants and toddlers may have night terrors, tiredness
with frequent naps and irritability
▪ Prominent peripheral pulse – d/t the compensatory large
ventricular stroke volume and peripheral vasodilation
▪ JVP occur irregularly and may be large when the atrium
contracts against a closed tricuspid valve (cannon wave)
▪ Systolic murmurs along the left sternal border and apical
mid-diastolic murmurs are unusual
▪ Variable first heart sound – d/t variable ventricular filling
with AV dissociation
▪ AV block results in enlargement of the heart based on ↑
diastolic ventricular filling
ECG
▪ Wide QRS complex
▪ Varied PR intervals
▪ Atrial rate > ventricular rate
▪ Confirms the diagnosis
Holter monitoring – to diagnose variation in heart rate,
pauses, ventricular tachycardia and other arrhythmias
▪ Permanent pacemaker implantation for symptomatic children and
for infants with a HR < 55 bpm
▪ Cardiac pacing – for neonates with HR <55bpm, evidence of heart
failure, wide complex rhythms, or CHD (with ventricular rates <70
bpm)
▪ Isoproterenol, atropine, epinephrine – may be tried to temporarily
↑ the heart rate until pacemaker placement can be arranged
PROGNOSIS: Usually favorable
Batch Clingy
CONGENITAL AV BLOCK
▪ Infants born to mothers with SLE (develops within 1 st 3-6 months after
birth) or Sjogren’s syndrome
▪ Autoimmune injury of the fetal conduction system by maternally
derived IgG antibodies (anti-SSA/Ro, anti-SSB/La) in a mother with
overt or asymptomatic SLE or Sjogren syndrome
▪ Ventricular rate lies within the range of 15-75bpm
PPS Oral Exam Reviewer 2020
137
Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Clinical and pathological syndrome that results from either
ventricular dysfunction or volume or pressure overload
▪ Heart is unable to pump enough blood in a quantity commensurate
with body requirements, to dispose of venous return adequately, or a
combination of the 2.
▪ Overall incidence and prevalence are unknown
CONGESTIVE HEART
FAILURE
▪ May be due to CHD or acquired heart diseases
▪ CHD with volume or pressure overload
● Most common cause of CHF in the pediatric age group (90%
manifests before 1 yo)
● VSD, PDA, and AVSD – most common causes of CHF in the 1 st 6
months of life
▪ In acquired heart disease, the most common causes are RHD and
myocarditis
CO = HR x SV
SV: determined by preload (volume work), contractility (intrinsic
myocardial function), and afterload (pressure work)
▪ ↑ Preload may stretch the myocardial fibers to a degree that CO can
no longer be increased
▪ Salt and water retention (preload) would only contribute to
pulmonary and systemic congestion and increased diastolic stress for
the myocardium
▪ Tachycardia and enhanced contractility may initially augment CO but
impose greater workload on the heart, as would vasoconstriction
(increased afterload)
▪ LV remodeling with progressive structural deterioration induced by
catecholamines, angiotensin II and aldosterone, can lead to more
severe heart failure and increase the risk of ventricular arrhythmias
▪ Inflammation of the heart muscle arising from the interplay of a
causative agent and the host’s immune response
▪ EA: Coxsackievirus (particularly Coxsackie B), adenovirus, parvovirus,
EBV, parechovirus, influenza virus and CMV
▪ Virus – most common causative agents in children
MYOCARDITIS
▪ True incidence is underestimated because the disease can be
subclinical or mild
▪ Bimodal distribution – prominent peaks in infants and mid-teenage
years
▪ Myocardial inflammation aggravated by the immunological response
of the host → myocyte injury → ↓ cardiac contractility or ↓ LV
systolic function → compromised CO, inadequate oxygen delivery to
the body, heart failure
▪ Myocardial insult arises from both direct damage by the pathogen
and action of inflammatory cells and mediators
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
▪ Poor growth, feeding difficulties, failure to thrive,
respiratory distress, exercise intolerance, fatigue
▪ Older children: puffy eyelids, swollen feet, tachypnea,
dyspnea on exertion, orthopnea
▪ Tachycardia, gallop rhythm, weak and thready pulses –
compensatory responses to impaired cardiac function
▪ Increased perspiration and cold wet skin – signs of ↑
sympathetic response; frequently seen in infants
LABORATORY FINDINGS / DIAGNOSIS
CXR: cardiomegaly
ECG:
▪ Nonspecific changes ST-segment or T-wave changes
▪ For diagnosis of heart defect and rhythm disorders
2DED
▪ Reveals ventricular chamber size and systolic/diastolic
function
▪ Determines the cause of CHF
▪ Useful in the serial evaluation of efficacy of therapy
Inotropes
▪ Augment cardiac contractility
▪ Digitalis, catecholamines, PDE inhibitors (milrinone)
Diuretics
▪ Loop diuretics – most potent, diuretics of choice in heart failure
▪ Aldosterone antagonist – anti-aldosterone and potassium sparing
effect, good drug to combine with loop diuretics
Vasodilators
▪ ↓ Either preload, afterload or both
▪ ↓ Afterload reduction → ↓ wall tension, ↑ CO → ventricular
emptying
▪ ACE inhibitors – vasodilators of choice d/t its angiotensin II suppressing
effects
Carvedilol
▪ β- and α-blocker
▪ Improve cardiac function and symptoms in children with
cardiomyopathy
PROGNOSIS
▪ In contrast to HF secondary to CHD, the outcome of
children with cardiomyopathy remains poor, with a 5-year
risk for death or cardiac transplantation of around 50% for
patients with dilated cardiomyopathy (DCM)
SUPPORTIVE MEASURES
▪ Rest – semi-fowler position; oxygen
▪ Diet: ↑ Na, give potassium supplementation
▪ Improve physical and metabolic requirements: temperature, pH,
glucose, calcium, hgb
▪ Control heart rate
▪ Ensure electrolyte and metabolic balance
Cardiac MRI
▪ Standard imaging modality for diagnosis
▪ Presence and extent of edema, hyperemic capillary leak,
myocyte necrosis, LV dysfunction
Troponin – more sensitive and specific in the diagnosis
Endomyocardial biopsy
▪ For identifying inflammatory cell infiltrates or myocyte
damage
▪ For performing molecular viral analysis
▪ Primary therapy is supportive and centered on management of
symptoms and complications – beta blockers and ACE inhibitors
▪ Diuretics
▪ Non-pharmacologic therapy: oxygen, bed rest, high back rest,
correction of anemia and metabolic disturbances
▪ Cardiomegaly
▪ Signs of pulmonary venous congestion – d/t L-sided heart
failure
▪ Wheezing and rales
▪ Hepatomegaly – sign of systemic venous congestion
▪ Distended neck veins
▪ Ankle edema
▪ Infants and young children
● Fulminant presentation
● Fever, respiratory distress, tachycardia, hypotension
● Gallop rhythm
● Cardiac murmur (apical systolic murmur of mitral
insufficiency)
▪ Chest discomfort, palpitation, easy fatigability, syncope
TREATMENT / COMPLICATIONS / PREVENTION
GOALS
▪ Relief of symptoms
▪ Correction of the underlying causes
▪ Elimination of precipitating factors
▪ ↓ Morbidity and ↑ survival
PROGNOSIS
▪ Better in children and adolescents
▪ Poor in newborns (75% mortality)
2DED
▪ ↓ Ventricular systolic function
▪ Cardiac chamber enlargement
▪ Mitral insufficiency
▪ Occ pericardial effusion
Batch Clingy
DISEASE
138
PERICARDITIS
▪ In the Philippines, the common etiologies are:
● Tuberculosis
● Rheumatic fever
● Bacterial infections
Chest pain
▪ Main presenting manifestation
▪ Relieved by sitting up and leaning forward
▪ Aggravated by lying supine
▪ True incidence is difficult to ascertain because asymptomatic or
minimally symptomatic episodes are likely undetected
Pericardial friction rub
▪ Pathognomonic of a small amount of pericardial fluid
▪ Best heard along the left sternal border with the patient
leaning forward
▪ Amount of fluid in the non-distensible pericardial space becomes
excessive → ↑ pressure within the pericardium → pressure is
transmitted to the heart → compressed chambers → impaired filling
▪ Small to moderate amounts of pericardial effusions can be welltolerated and clinically silent
2DED
▪ Most sensitive for identifying the size and location of a
pericardial effusion
▪ Treatment is aimed at the underlying pathology
▪ Salicylates or NSAIDs – for chest pain
▪ IV antibiotics – for 4-6 weeks
▪ Corticosteroids – for severe rheumatic carditis, post-pericardiotomy
syndrome, and TB pericarditis
▪ Pericardiocentesis – for detecting etiology, relieving symptoms in large
effusions, and preventing cardiac tamponade
▪ Tachycardia, cough, dyspnea, abdominal pain, vomiting,
fever
▪ Muffled heart sounds when fluid accumulation is large
CARDIAC TAMPONADE
▪ Complication of pericarditis
▪ Pulsus paradoxus
▪ Neck vein engorgement
▪ ↑ central venous pressure, narrow pulse pressure
▪ 2DED: Compression and collapse of the RA and/or RV
Bacterial pericarditis: purulent effusion
Tuberculous fluid: fibrinous or hemorrhagic
▪ Tuberculous and bacterial effusions are usually moderate
to large amount, while effusions secondary to rheumatic
fever are small and serous
CARDIOMYOPATHY
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Most common form of cardiomyopathy
▪ LV dilation + ↓ LV systolic function
▪ Common indication for cardiac transplantation
▪ Most common etiology: idiopathic
▪ Up to 50% are genetic
▪ In 20-50% of cases, DCM is familial with autosomal dominant
inheritance
DILATED CARDIOMYOPATHY
(DCM)
▪ Annual incidence in children <18yo: 0.57 cases per 100,000 per year
▪ Higher in males, blacks, and infants <1yo
▪ Systolic dysfunction and myocyte injury
▪ The resulting myocardial damage, ventricular enlargement, and poor
function likely occur by final common pathways
HYPERTROPHIC
CARDIO-MYOPATHY
▪ ↑ LV wall thickness in the absence of structural heart disease or
hypertension
▪ ↑ Ventricular myocardial wall thickness, N or ↑ systolic function, and
diastolic (relaxation) abnormalities
▪ Heterogenous, relatively common, and potentially life-threatening
form of cardiomyopathy
▪ Genetic disorder frequently occurs because of mutations in
sarcomere or cytoskeletal components of the cardiomyocte
▪ Hypertrophic and fibrotic cardiac muscle demonstrates relaxation
abnormalities (diminished compliance) and LV filling may be impaired
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
▪ Similar to CHF
▪ Include palpitations, syncope, sudden death
▪ Irritability or lethargy, failure to thrive, nausea, vomiting,
abdominal pain
▪ Respiratory symptoms – tachypnea, wheezing, cough or
dyspnea on exertion)
▪ Infrequently, may present acutely with pallor, altered
mentation, hypotension, shock
▪ Tachycardia with narrow pulse pressure
▪ Hepatic enlargement
▪ Rales or wheezing
▪ ↑ Precordial cardiac impulse
▪ Heart may be enlarged to palpation or percussion
▪ Gallop rhythm
▪ Sudden death during physical exertion
▪ Palpitations, chest pain, easy fatigability, dyspnea,
dizziness, syncope
▪ Overactive precordial impulse with a lift or heave
▪ Systolic ejection murmur in the aortic region not
associated with an ejection click
▪ Apical blowing murmur of mitral insufficiency
LABORATORY FINDINGS /
DIFFERENTIAL DIAGNOSIS
TREATMENT / COMPLICATIONS / PREVENTION
ECG
▪ Atrial or ventricular hypertrophy
▪ Nonspecific T-wave abnormalities
▪ Occasionally, atrial or ventricular arrhythmias
ACE inhibitors / ARBs + β-blockers (carvedilol/metop)
▪ Reverse remodeling → improve ventricular size and function
Furosemide
▪ ↓ Symptoms of pulmonary or systemic venous congestion
CXR
▪ Cardiomegaly
▪ Pulmonary vascular prominence
▪ Pleural effusion
Implantable cardiac defibrillators – considered for patients with a high
risk of sudden cardiac arrest
Pacemakers – Improve patients with certain underlying electrical
derangements
2DED
▪ Diagnostic
▪ LV enlargement
▪ ↓ Ventricular contractility
▪ Occ, globular (remodeled) LV contour
▪ Evidence of pulmonary hypertension, MR, or other
structural cardiac or coronary abnormalities
PROGNOSIS
▪ 1- and 5-years freedom from death or transplantation in patients
diagnosed with DCM is 60-70% and 50-60%
▪ Independent factors at DCM diagnosis for subsequent death or
transplantation:
● Older age
● Heart failure
● Lower LV fractional shortening z score
● Underlying etiology
B-blockers (propranolol, atenolol, metoprolol) or calcium channel
blockers (verapamil)
▪ ↓ LVOT obstruction, modify LV hypertrophy, improve ventricular
filling
▪ Has an anti-arrhythmic benefit
▪ Reduce symptoms
ECG
▪ LV hypertrophy
▪ ST segment and T-wave abnormalities (T-wave inversion in
the left precordial leads)
CXR
▪ Normal or mildly ↑ heart size
▪ Prominent LV
2DED
▪ Diagnostic in identifying, localizing and quantifying the
Anti-arrhythmic therapy – if with atrial or ventricular arrhythmias
Indications for implantable cardioverter-defibrillator
▪ Documented, previously aborted sudden cardiac arrest
Batch Clingy
DISEASE
139
(diastolic dysfunction)
▪ Systolic function is preserved or even hyperdynamic but systolic
dysfunction may occur late and is a predictor for death or need for
cardiac transplant
degree of myocardial hypertrophy
▪ Defines, localizes, and quantifies the degree of LVOT
obstruction
▪ Demonstrates and quantifies the degree of mitral
insufficiency and diastolic dysfunction
▪ Interventricular septum is disproportionately involved → asymmetric
septal hypertrophy
▪ Left ventricle is predominantly affected
▪ Cardiac myofibrils and myofilaments demonstrate disarray
▪ Near-normal ventricular chamber size and wall thickness with
preserved systolic function
▪ Dramatically impaired diastolic function → ↑ filling pressures and
atrial enlargement
▪ <5% of cardiomyopathy cases
▪ F>M
RESTRICTIVE CARDIOMYOPATHY
▪ Abnormal ventricular myocardial compliance + high ventricular
diastolic pressure → dramatic atrial dilation
2DED
▪ Diagnostic
▪ Normal-sized ventricles with preserved systolic function
▪ Dramatic enlargement of the atria
▪ Abnormal filling parameters
▪ Fibrofatty infiltration and replacement of the normal RV myocardium
and occasionally the LV → RV (and LV) systolic and diastolic
dysfunction and arrhythmias
▪ Most patients have no symptoms at birth
▪ Rare
▪ Prevalence: 1:5000 in general population
Major clinical findings
▪ Global and regional RV and LV dysfunction
▪ Ventricular tachyarrhythmias
▪ Mutations create problems with intercellular adhesion, intracellular
calcium, intercellular signaling, and combinations thereof
▪ As many of these myocardial structural and functional changes
develop over time, it is important to understand their pathophysiology
to remain attuned to earlier pediatric manifestations
MRI
▪ Thickened or calcified pericardium
▪ Criteria for diagnosis based on the repolarizing and
depolarizing abnormalities
▪ Restrict from competitive sports and strenuous physical activity
▪ Recreational exercise activities should be tailored based on overall
clinical status
▪ Screen first-degree relatives of patients using ECG and 2DED
Cardiac transplantation
▪ Treatment of choice
▪ Results are excellent in those without pulmonary hypertension or
severe CHF
COMPLICATIONS
Atrial tachyarrhythmias, complete heart block, thromboemboli
PROGNOSIS
Generally poor with progressive clinical deterioration
▪ Heart transplantation
▪ Myocardial changes manifest during the pediatric years
▪ In the early phase, no detectable structural abnormalities
in the myocardium – patients are still at ↑ risk of
ventricular arrhythmias and sudden cardiac death (SCD)
▪ Later phase: symptomatic arrhythmias, clinical evidence
of RV or biventricular failure
Batch Clingy
ARRHYTHMOGE-NIC
RIGHT VENTRICULAR
CARDIO-MYOPATHY
(ARVC/D)
▪ Edema, hepatomegaly, ascites – d/t abnormal ventricular
filling (diastolic heart failure)
▪ Cough, dyspnea, or pulmonary edema – d/t elevation of
L-sided filling pressures
▪ Chest pain, shortness of breath, syncope/ near-syncope,
or sudden death during activity
▪ Pulmonary hypertension and pulmonary vascular disease
▪ Prominent gallop rhythm
PROGNOSIS
▪ <1yo or those with inborn errors of metabolism,
malformation syndromes, or a mixed HCM/DCM have a
significantly poorer prognosis
▪ The risk of sudden death in older patients is greater in
those with a personal or family history of cardiac arrest,
Vtach, exercise hypotension, syncope, or excessive
ventricular wall thickness
ECG
▪ Prominent P waves
▪ Normal QRS voltage
▪ Nonspecific ST and T-wave changes
CXR
▪ Normal or
▪ Prominent atrial shadow
▪ Pulmonary vascular redistribution
▪ Strong family history of sudden death
▪ Ventricular wall end-diastolic dimensions of >3cm
▪ Unexplained syncope, non-sustained ventricular tachycardia, or
blunted or hypotensive blood pressure response to exercise
PPS Oral Exam Reviewer 2020
140
Acute
ETIOLOGY / INCIDENCE / PATHOGENESIS
Etiologic Agents
▪
Viruses
(predominant):
Adenovirus,
coronavirus, CMV, EBV, Enteroviruses, HSV,
HIV, human metapneumovirus, influenza,
measles, parainfluenza, RSV, rhinovirus
▪ Bacteria: GABHS (most important),
Acranobacterium
haemolyticum,
F.
necrophorum, C. diphtheriae, N. gonorrhea,
Group C Strep, Group G Strep, mycoplasma, F.
tularensis, C. pneumonia, C. trachomatis
Environmental Exposures
▪ Smoke, air pollutants, allergens
PATHOGENESIS
▪ Colonization in the pharynx
▪ GAS (M Protein)
ACUTE
PHARYNGITIS
PERITONSILLAR
ABSCESS
▪ Commonly seen in adolescents with recurrent
ATP
▪ Group A Strep + mixed oropharyngeal
anaerobes
▪ Bacterial invasion through the tonsillar
capsule → cellulitis/ abscess in surrounding
tissues
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
Viral (General) – conjunctivitis, coryza, cough, diarrhea, hoarseness,
discrete ulcerative stomatitis, viral exanthema
HSV – gingivostomatitis, ulcerating vesicles, high fever, difficulty taking in
fluids
Herpangina – discrete papulovesicular lesions or ulcerations (posterior
pharynx), severe throat pain
HFMD (Coxsakie A16, A6; Enterovirus 71)
▪ Same with herpangina but also involves palms and soles
Adenovirus (Pharyngoconjuctival fever)
▪ Pharyngitis resolves in 7days, conjunctivitis may persist up to 14 days
▪ Swimming pool exposures
Measles
▪ Intense, diffuse pharyngeal erythema, koplik spots
HIV (Acute Retroviral Syndrome)
▪ Non-exudative pharyngitis, fever, arthralgia, myalgia, adenopathy,
maculopapular Rash
GABHS
▪ Sudden onset sore throat
▪ 5-15 years old
▪ Fever, HA, N/V, abdominal pain, tonsillopharyngeal exudates, palatal
petechiae, anterior cervical adenitis (tender nodes)
▪ Winter and early spring presentation
▪ History of exposure to strep pharyngitis
▪ Scarlatiniform rash
Fusobacterium necrophorum
▪ 15-30 years old; toxic looking
▪ Lemierre Syndrome (etiologic agent in 80% of cases)
▪ Internal jugular vein septic thrombophlebitis
Gonococcal
▪ Asymptomatic
▪ Acute ulcerative or exudative pharyngitis, fever, cervical lymphadenitis
Diphtheria
▪ Bull neck, gray pharyngeal pseudomembrane
F. tularensis
▪ Ingestion of water, milk or undercooked meat
▪ Severe throat pain, tonsillitis, cervical adenitis, oral ulcerations,
pseudomembrane formation
▪ Sore Throat, fever, trismus, muffled or garbled voice, dysphagia
▪ Asymmetric tonsillar bulge with displacement of uvula (poorly visualized
because of trismus)
LABORATORY FINDINGS / DIAGNOSIS
▪ Throat Culture – gold standard
▪ Rapid Antigen Detection Tests
● Very high specificity ≥95%; if positive, diagnosis is accurate
● Less sensitive than culture; if negative, must confirm with
culture
▪ Testing should only be done if signs and symptoms point to bacterial
rather than viral etiology
▪ GAS Molecular Tests
● Amplification of specific GAS gene in <1hr
● Sens & Spec ≥98% when compared with standard throat culture
● May not exhibit spectrum bias
● Very sensitive that it may cause unnecessary treatment to
carriers
● Prone to contamination with exogenous GAS DNA from other
swabs
●More expensive than culture
▪ Special culture media
● Done if suspected organism is not GAS
● A. haemolyticum
▪ CBC – atypical lymphocytes and a positive mononucleosis slide
agglutination test → EBV
RECURRENT PHARYNGITIS
● ≥7 episodes in the previous year, or
● ≥5 in each of the preceding 2yrs, Or
● ≥3 in each of the previous 3yrs
▪ CT Scan
▪ Ultrasound – differentiates cellulitis vs. abscess; avoids radiation
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Amoxicillin 50mkday (PO) QD x 10 days
▪ Penicillin V (PO)
● <27 kg: 250mg BID x 10 days
● > 27 kg: 500mg BID x 10 days
▪ Benzathine Penicillin G (IM) once
● < 27 kg: 600,000 IU
● > 27 kg: 1,200,000 IU
▪ Benzathine Penicillin G (900,000 IU) + Procaine Penicillin G (300,000 IU)
per IM for one dose
For Penicillin Allergic Patients:
▪ 1st generation cephalosporins (Varies) x 10 days
● Do not use if with history of anaphylaxis to beta-lactam
▪ Erythromycin Ethylsuccinate 40mkday (Max 1,000 mg/day) BID x 10
days
▪ Erythromycin Estolate 20-40mkday (Max 1,000mg/day) BID x 10 days
▪ Clarithromycin 15mkday (Max 500mg/day) BID x 10 days
▪ Azithromycin
● D1: 12mkday (Max 500mg/day) QD
● D2-5: 6mkday (Max 250mg/day) QD
▪ Clindamycin 20mkday (Max 1800mg/day) TID x 10 days
▪ Tetracyclines, fluoroquinolones, or sulfonamides should not be used to
treat GAS pharyngitis
Supportive Management
▪ Paracetamol or Ibuprofen
▪ Anesthetic spray/lozenges (benzocaine, phenol, menthol)
COMPLICATIONS
▪ AOM, sinusitis, parapharyngeal Abscess
▪ Acute renal failure, PSGN
▪ Poststreptococcal reactive arthritis
▪ Pediatric autoimmune neuropsychiatric disorders associated with
streptococci (PANDAS) or childhood acute neuropsychiatric symptoms
(CANS) or pediatric acute-onset neuropsychiatric syndrome (PANS)
▪ Chronic GAS Carriage
▪ Directed antibiotic therapy
▪ Surgical Drainage – needle aspiration; incision and drainage
▪ Tonsillectomy
COMPLICATIONS
▪ Aspiration Pneumonitis (if abscess ruptures)
▪ Overall, 10% recurrence risk
▪ Recurrence in 5% of s/p needle aspiration → requires I&D
Batch Clingy
DISEASE
141
▪ Epstein-Barr Virus (EBV) – 90%
Type 1/A – more prevalent; induces in vitro
growth transformation of B lymphocytes more
efficiently
▪ 5-10% of cases: CMV, T. gondii, adenovirus,
hepatitis virus, HIV
▪ Socioeconomically disadvantaged societies
▪ Incidence: 20-70 per 100,000 person-years
▪ Young adults: 100 in 100,000 person-years
INFECTIOUS
MONONUCLEOSIS (IM)
TRANSMISSION
▪ Via oral secretions – viral shedding
consistently for > 6mos after acute infection
then intermittently for life
▪ Sexual Contact
▪ Transmission → oral epithelial cells and
tonsillar B lymphocytes → viremia → blood
stream → lymphoreticular system (liver and
spleen)
▪ Malaise, fatigue, acute or prolonged fever (> 1 week), headache, sore
throat (moderate to severe), nausea, abdominal pain, myalgia
▪ Marked tonsillar enlargement
▪ Palatal petechiae
▪ Lymphadenopathy
● Anterior and posterior cervical nodes – most common
● Epitrochlear lymphadenopathy – suggestive of
Mononucleosis
● Axillary, inguinal
▪ Splenomegaly (50%)
▪ Hepatomegaly (10%)
▪ Ampicillin Rash (3-15%)
Infectious
Gianotti-Crosti syndrome
▪ Symmetric rash on the cheeks with multiple erythematous papules or
plaques
▪ 15-50 days
▪ Appears like atopic dermatitis at the extremities or buttocks
▪ Clinical diagnosis
● Consider IM if failure to improve within 48-72 hours of
treatment for strep.
▪ Leukocytosis (10,000-20,000) (90%)
● 2/3 lymphocytes; 20-40% are atypical
▪ Mild thrombocytopenia (50,000 - 200,000) (50%)
▪ Mild elevation of liver enzymes
▪ Monospot (Heterophile antibodies)
● Cross-reactive immunoglobulin M (IgM) antibodies that
agglutinate mammalian erythrocytes but are not EBV-specific
● Very useful if supported by strong clinical manifestations
▪ Detection of Viral DNA
▪ Rest, adequate fluid and nutrition
▪ Symptomatic treatment
▪ Avoidance of contact sports and strenuous athletic activities if with
splenomegaly
▪ Antiviral therapy is not recommended
▪Short course steroids if with airway obstruction
COMPLICATIONS
▪ Splenic Rupture
▪ Airway Obstruction
▪ Seizures
▪ Alice in Wonderland Syndrome
● Metamorphosia
● Perceptual distortions of sizes, shapes and spatial relationships
▪ Hemophagocytic lymphohistiocytosis (HLH)
▪ Burkitt Lyphoma
▪ Hodgkin Lymphoma
▪ Aggressive NK Cell Leukemia
▪ Nasopharyngeal Carcinoma
▪ Gastric Carcinoma
Batch Clingy
▪ Incubation period: 6 weeks
▪ Classic Triad: fatigue, pharyngitis, generalized lymphadenopathy (90%)
▪ Incubation period: 30-50 days
▪ Shorter in children
▪ Clinical presentation may be silent in children and fast in adults
PPS Oral Exam Reviewer 2020
142
Acute Cough (<2 Weeks) | Acute
COMMON COLDS
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Rhinovirus (50%), RSV, Human metapneumovirus, Parainfluenza
viruses, Adenoviruses, Influenza virus, Enteroviruses, Human
Coronavirus
▪ Seasonal prevalence in other countries
▪ Average of 6-8 colds per year
▪ 10-15% of children have at least 12 infections per year →
decreases to 2-3/year by adulthood
▪ Direct hand contact (self-inoculation)
▪ Inhalation of small particles
▪ Deposition of large particles on nasal or conjunctival mucosa
PATHOGENESIS
▪ HRV – large particles
▪ Influenza Virus – genetic drift and shift
▪ Coronavirus – multiple distinct strains can induce short-term
protective immunity
PATHOLOGY
▪ Viral infection of nasal epithelium → destruction → acute
inflammatory response → cytokine release and infiltration of
mucosa by inflammatory cells → symptoms
▪ Peak of viral shedding: 3-5 days after inoculation
▪ Viral shedding may persist for up to 2 weeks
ETIOLOGY
▪ Genetics
▪ Environment – virus, allergen, irritant exposure (cold, dry, air,
exercise)
ASTHMA
WITHOUT
EXACERBATION
EPIDEMIOLOGY (MORE COMMON)
▪ Males, poor
▪ 80% of all asthmatic patients report disease onset before 6 years
old
EARLY CHILDHOOD RF FOR PERSISTENT ASTHMA
Major
▪ Parent asthma
▪ Eczema
▪ Inhalant Allergen Sensitization
Minor
▪ Allergic rhinitis
▪ Wheezing apart from colds
▪ ≥4% Peripheral blood eosinophils
▪ Food allergen sensitization
▪ Allergy in young children with recurrent cough and/or wheeze is
the strongest identifiable factor for the persistence of childhood
asthma.
PATHOGENESIS
▪ Airflow obstruction in asthma is the result of numerous
pathologic processes.
▪ Bronchoconstriction of muscle layer + inflammatory infiltration of
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
Infants: fever, nasal discharge
Older children:
▪ Colds (2-3 days after infection)
▪ Sore or scratchy throat – resolves quickly (2-3 days) then nasal
symptoms predominate
▪ Nasal obstruction, rhinorrhea
▪ Hoarseness
▪ Cough (2/3 of cases) – may persist for 1-2 weeks
DIAGNOSIS
▪ Clinical
▪ Routine laboratory studies are not helpful for the diagnosis and
management of the common cold
▪ Hansel stain – nasal smear for eosinophils to rule out allergic
rhinitis
▪ Cultures and PCR – may be useful if GABHS and Bordetella
pertussis is suspected
Occasional Symptoms:
▪ Headache
▪ Difficulty sleeping
▪ Irritability
▪ Decreased appetite
▪ Vomiting, diarrhea
▪ Increased nasal secretion
▪ Change in color or consistency of mucus
▪ Swollen erythematous nasal turbinates
▪ Anterior cervical lymphadenopathy
▪ Conjunctival injection
▪ Intermittent dry cough and expiratory wheezing – most common
chronic symptoms
▪ Shortness of breath
▪ Chest congestion
▪ Chest tightness
▪ Non focal chest pain – common in younger children
▪ Worse symptoms at night, triggered by physical activities
▪ Usually triggered by environmental changes
▪ Decreased breath sounds in some lung fields (right lower
posterior lung field is common)
▪ Rhonchi and crackles (or rales)
TREATMENT / COMPLICATIONS
Supportive care
▪ Maintain adequate oral hydration (warm liquids)
▪ No use of non-prescription cold and cough medications < 6 years
old
▪ Zinc – reduces duration if given within 24 hours of symptoms
▪ NSAIDs
▪ Decongestants, saline drops
▪ Antihistamines
▪ Honey
Antibacterial therapy
▪ Of no benefit
▪ Should be avoided to minimize possible adverse effects and
antibiotic resistance
▪ Ribavirin – severe RSV infections
▪ Oseltamivir or Zanamivir – influenza
COMPLICATIONS
▪ Acute Otitis Media – most common, 5-30%
▪ Sinusitis
▪ Asthma Exacerbation
Not effective:
▪ Vitamin C, guaifenesin, inhalation of warm, humidified air,
echinacea
▪ Risk factors + clinical presentation
▪ Improvement within 10mins from SABA administration
▪ Pulmonary Function Testing
▪ Forced expiratory airflow
▪ Spirometry – can be done as young as 6yo
Key components of optimal asthma management
▪ Assessment and monitoring of disease activity
▪ Education to enhance patient and family knowledge and skills for
self-management
▪ Identification and management of precipitating factors and
comorbid conditions that worsen asthma
▪ Appropriate selection of medications
▪ Long term goal: asthma control
For Classification See Table 169.7 of Nelson’s 21st
ADOLESCENTS
Preferred reliever: low dose ICS-formoterol or SABA
Preferred controller:
▪ Step 1: ICS-formoterol PRN or low dose ICS with SABA
▪ Step 2: Daily low-dose ICS or low dose ICS-formoterol PRN or
daily LRTA or low dose ICS with SABA
▪ Step 3: Low dose ICS-LABA or medium-dose ICS or low dose
ICS+LTRA
▪ Step 4: Medium dose ICS-LABA; High-dose ICS, add on tiotropium
or LRTA
▪ Step 5: High dose ICS-LABA or low dose OCS
CHILDREN 6-11 YEARS OLD
Preferred reliever: SABA PRN
Preferred controller:
▪ Step 1: No preferred; May give low dose ICS with SABA or daily
low dose ICS
▪ Step 2: Daily low-dose ICS or daily LRTA or low dose ICS with
SABA
Batch Clingy
DISEASE
143
different cell types → epithelial damage and desquamation
▪ Step 3: Low dose ICS-LABA or medium-dose ICS or low dose
ICS+LTRA
▪ Step 4: Medium dose ICS-LABA and refer for expert advice; Highdose ICS, add on tiotropium or LRTA
▪ Step 5: Refer for Phenotypic assessment, High dose ICS-LABA or
low dose OCS
Regular clinic visits every 2-6 weeks for reassessment of asthma
control.
PEF Monitoring
Stepwise Approach *See GINA*
See Table 169.11-13 (Nelsons)
COMPLICATION
Status Asthmaticus
PNEUMONIA
MINIMUM/
LOW RISK
ETIOLOGY
Non-infectious: aspiration (food or gastric acid, foreign body,
hydrocarbons, lipoid substances), hypersensitivity reactions, drugor radiation-induced pneumonitis
Infectious causes:
▪ S. pneumoniae (pneumococcus) – most common in children 3wks
to 4yrs of age
▪ Mycoplasma pneumoniae
▪ C. pneumoniae – most frequent in children age ≥5yo
▪ Group A streptococcus (Streptococcus pyogenes)
▪ Staphylococcus aureus
▪ Viral pathogens – most common cause of LRTIs in 1mo – 5yo
PATHOGENESIS
Viral pneumonia – direct injury of the respiratory epithelium →
swelling and airway obstruction → atelectasis, interstitial edema,
hypoxemia from VQ mismatch
Bacterial pneumonia – colonization of trachea → seeding to the
PPS Oral Exam Reviewer 2020
▪ Preceded by several days of URTI (rhinitis, cough)
▪ Tachypnea – most consistent
▪ Viral – low grade fever, retractions (subcostal, intercostal,
suprasternal), alar flaring, fever, crackles, wheeze
▪ Bacterial
● Fever, cough, chest pain, drowsiness, intermittent periods of
restlessness, rapid respirations, anxiety, delirium
● Early: grunting, diminished breath sounds, scattered crackles,
rhonchi are commonly heard over the affected lung field. A lag in
respiratory excursion often occurs on the affected side.
● Abdominal distention, abdominal pain
▪ Chest Radiograph (PA-Lat)
● Viral – hyperinflation with bilateral interstitial infiltrates and
peribronchial cuffing
● Pneumococcal – confluent lobar consolidation
▪ CBC – high WBC count
▪ ESR, procalcitonin, CRP
Definitive diagnosis: viral genome or antigen detection (for viruses)
and sputum culture (Bacteria)
▪ Blood CS only 10% have yield
▪ Gram Stain
▪ Culture and Sensitivity
Other exams:
▪ Cold agglutinin – Mycoplasma
▪ ASO – Streptococcus
▪ Ultrasound
▪ Amoxicillin 90 mkday q12 (Nelson’s)
▪ Amoxicillin 40-50mkday (Max 1500) divided to 3 doses in low
resistance areas (PAPP)
Alternatives
▪ Cefuroxime, co-amoxiclav
▪ Azithromycin 10mkday QD for 3days, or 10mkday at day 1 then
5mkday for D2-5 (max dose 500 mg)
Suspected Mycoplasma or Chlamydia – macrolide
▪ Azithromycin, Clarithromycin 15mkday in 2 doses x 7 days (Max
1000 mg) or Doxycycline
See Table 428.7 for antibiotic choices in Nelson’s
Antibiotic duration:
▪ Until 72 hours afebrile but not less than 10 days all-in-all
▪ 5-7 days is acceptable for OPD
Adjuncts:
▪ Oral zinc (10mg/day for <12mos, 20mg/day for ≥ 12mos given for
7days)
▪ Bubble CPAP – improves mortality from pneumonia with
hypoxemia compared with standard oxygen therapy in settings
Batch Clingy
▪ Inflammation of the lung parenchyma
▪ Leading cause of death globally
▪ Risk Factors: Poverty
144
lung tissue → infection to the lung parenchyma → properties of
invading organism determines presentation
▪ Vitamin D3
▪ Probiotics
Recurrent pneumonia – ≥2 episodes in a single year or ≥3 episodes
ever with radiographic clearing between occurrences
COMPLICATIONS
▪ Pleural effusion, empyema
▪ Asthma after 5 years in 45% of cases
▪ Pericarditis
▪ Acute Respiratory Failure
▪ Pneumothorax
▪ Lung Abscess
Rarely,
▪ Meningitis, endocarditis
▪ Suppurative arthritis, osteomyelitis
Acute Cough in Distress | Acute
ETIOLOGY / INCIDENCE / PATHOGENESIS
Etiology – RSV (50%), Parainfluenza, Human metapneumovirus, Rhinovirus,
Bocavirus, Adenovirus
▪ Most common diagnosis
▪ More common in males
▪ Only 5-8% of wheezing illness prior to school age develop asthma in
adulthood
BRONCHIOLITIS
RISK FACTORS
▪ Second-hand tobacco smoke
▪ Formula-fed
▪ Crowded conditions
▪ Infants born from mothers who smoked during pregnancy
▪ History of asthma and allergies
PATHOGENESIS
▪ Bronchiolar obstruction with edema, mucus and cellular debris
▪ Increased resistance in smaller airways → expiratory wheezing, air
trapping, and lung hyperinflation
▪ Complete obstruction → atelectasis
CLINICAL MANIFESTATIONS
▪ Sneezing and clear rhinorrhea initially
▪ Diminished appetite
▪ Fever
▪ Respiratory distress ensues, with paroxysmal cough, dyspnea,
irritability
▪ Apnea may precede lower respiratory signs early in the disease,
particularly with very young infants.
▪ Term infants at a postconceptual age of <44wks and preterm infants
at postconceptual age <48wks are at highest risk for apneic events
DIAGNOSIS
▪ Clinical
▪ CXR and labs not routinely indicated
▪ Viral testing (PCR, rapid immunofluorescence) – not
routinely recommended but may be helpful if such testing
prevents more invasive evaluations
▪ If with failure to thrive, consider chronic diseases such as
cystic fibrosis or immunodeficiency
DIFFERENTIAL DIAGNOSIS
Asthma
▪ Tachypnea, wheezing, crackles, rhonchi – 2o to inflammation of the
small airways
▪ Expiratory time may be prolonged
▪ Work of breathing may be markedly increased, with nasal flaring and
retractions
▪ Complete obstruction to airflow can eliminate the turbulence that
causes wheezing thus, the lack of audible wheezing is not reassuring if
the infant shows other signs of respiratory distress
▪ Poorly audible breath sounds – suggest severe disease with nearly
complete bronchiolar obstruction
COMPLICATIONS
▪ Otitis Media
▪ Respiratory Arrest or Failure
▪ Severe dehydration and electrolyte imbalance
▪ A majority of deaths due to bronchiolitis occur in children
with complex medical conditions or comorbidities such as
bronchopulmonary dysplasia, congenital heart disease, or
immunodeficiency
▪ Wheezing with an onset after the first 18-36mos of life is
one of the strongest predictors of eventual asthma in both
cohorts
THREE PATTERNS OF INFANT WHEEZE
▪ Transient early wheezing – 20%, lower lung function at birth which
improves with growth resulting in resolution of wheezing by age 3
▪ Persistent wheezing – 14%, declining lung function and wheezing before
and after age 3
▪ Late-onset wheezing –15%, relatively stable lung function and wheezing
that does not begin until after age 3
PNEUMONIA,
MODERATE RISK
Respiratory Rate
▪ 3-12mos: >60 to <70/min
▪ 1-5yrs: >50/min
▪ >5yrs: >35/min
▪ Intercostal or subcostal retractions
▪ Head bobbing, cyanosis
▪ Irritability
PPS Oral Exam Reviewer 2020
TREATMENT / COMPLICATIONS
▪ Supportive management
o
sPO2 > 90%
o
Fluids via IV or NGT
o
Suction secretions
▪ Admit if with respiratory distress (hypoxia, inability to feed,
apnea, extreme tachypnea)
▪ Chest physiotherapy – no benefit to children with
bronchiolitis
▪ Pharmacologic agents – largely proven ineffective in the
management of bronchiolitis
Same as mild but with focus on assessment of gas exchange:
▪ O2 saturation, ABG
▪ CRP, procalcitonin
▪ CXR PA-Lat
▪ CBC (WBC)
▪ Chest UTZ (Effusion)
▪ Gram Stain, Culture and Sensitivity
May manage as outpatient if the following are NOT present:
▪ Age less than 2 years old
▪ Convulsions
▪ CXR with effusion, lung abscess, air leak, or multilobar
consolidation
▪ O2 Sat <95%
▪ Otherwise, admit to ward
Batch Clingy
DISEASE
145
EPIDEMIOLOGY
▪ Older infants and toddlers
▪ M>F
▪ Most common object: food items (nuts, seeds, hot dogs, hard candy,
gum, bones, raw fruits and vegetables)
FOREIGN BODY
LARYNGOTRACHEITIS
(Croup)
PATHOGENESIS
▪ Young children are more at risk to aspirate a foreign body largely because
of their developmental vulnerabilities and their underdeveloped ability to
swallow food.
▪ An infant is able to suck and swallow and is equipped with involuntary
reflexes (gag, cough, and glottis closure) that help to protect against
aspiration during swallowing.
▪ Despite a strong gag reflex, a child's airway is more vulnerable to
obstruction than an adult's airway
▪ Young children are more likely to experience significant blockage by small
foreign bodies due to their smaller airway diameter.
▪ Mucus and secretions may form a seal around the foreign body, making it
more difficult to dislodge by forced air
▪ In addition, the force of air generated by an infant or young child's cough
is less effective in dislodging an airway obstruction.
ETIOLOGY AND EPIDEMIOLOGY
▪ Parainfluenza virus types 1, 2, and 3 (75%)
▪ Other viruses: influenza A and B, adenovirus, respiratory syncytial virus,
and measles.
▪ 3 months to 5 years old
▪ Peak: 2nd year of life
▪ Males
PATHOGENESIS
▪ Viral infection (invasion) at the glottic and subglottic region
PPS Oral Exam Reviewer 2020
Additional: Serum Na, K
▪ May range from asymptomatic to severe respiratory distress
▪ History taking – most important
▪ Comprehensive PE of the orifices
▪ Radiograph – look for 2o findings (air trapping, asymmetric
hyperinflation,
obstructive
emphysema,
atelectasis,
mediastinal shift, consolidation)
▪ Bronchoscopy – done if clinically suggestive despite
negative imaging
Areas involved:
▪ Larynx – hoarseness, cough, stridor, dyspnea
▪ Trachea – dysphonia, dysphagia, dry cough, biphasic stridor
PRESENTATION IN 3 STAGES
Initial event: Paroxysms of coughing, choking, gagging, and airway
obstruction immediately after aspiration of the FB; the child is
sometimes able to expel the foreign body during this stage.
Asymptomatic interval: The foreign body becomes lodged, reflexes
fatigue, and the immediate irritating symptoms subside.
▪ If with immunization: Penicillin G 100,000 units/kg/day in 4
divided doses
▪ If incomplete or unsure immunization: ampicillin 100mkday
divided to 4 doses.
▪ Oral medications may be given if not O2 requiring
▪ MRSA: Vancomycin + Referral to ID
If clinically suspected or confirmed influenza virus infection:
▪ Oseltamivir (start within 48 hours)
● 3-8mos: 3mkdose BID x 5days
● 9-11mos: 3.5mkdose BID x 5days
● >12mos:
BW <15 kg at 30 mg BID x 5days
>15-23 kg at 45 mg BID x 5days
>23-40 kg at 60 mg BID x 5days
>40 kg at 75 mg BID x 5days
▪ Zanamivir >7yo: 10mg (two 5-mg inhalations) BID x 5days
within 36 hours of onset of influenza-like symptoms
▪ Heimlich Maneuver – If laryngeal foreign body is suspected
▪ Endoscopic removal
COMPLICATIONS
▪ Complete obstruction of airway – most serious complication
▪ Air trapping
▪ Atelectasis
For bronchoscopy
▪ Bronchospasm
▪ Desaturation
▪ Bleeding
▪ Airway edema
Complications: Obstruction, erosion, or infection develops. Patient
may have include fever, cough, hemoptysis, pneumonia, atelectasis
▪ Acute or chronic complications have been reported in almost 15% of
cases of foreign bodies of the airway.
▪ Rhinorrhea, pharyngitis, mild cough, and low-grade fever for 1-3 days
before apparent upper airway obstruction
▪ Barking cough, hoarseness, and inspiratory stridor
▪ Symptoms are worse at night
▪ Prefer to sit up in bed or be held upright
▪ Hoarseness, coryza, inflamed pharynx, slight tachypnea
▪ Nasal flaring, retractions, persistent stridor
▪ Clinical Diagnosis
▪ Radiograph: subglottic narrowing, or steeple sign but not
diagnostic
COMPLICATIONS
▪ Bacterial tracheitis
▪ Otitis media
▪ Pneumonia
▪ Airway management
Nebulized racemic epinephrine – established treatment for
moderate or severe croup
▪ 0.25-0.5 ml of 2.25% racemic epi in 3 mL of normal saline
every 20 mins.
▪ Duration of activity < 2 hours
▪ No rebound effect.
Oral dexamethasone – single dose of 0.6mg/kg, a dose as
low as 0.15mg/kg may be just as effective
Batch Clingy
▪ Choking is a leading cause of morbidity and mortality among children,
especially those <4yo
▪ Convulsions
▪ CRT >3secs
▪ Pallor
▪ Moderately malnourished, unable to drink
▪ CXR: effusion, abscess, air leak or multilobar consolidation
▪ O2 Sat 91-94%
146
EPIGLOTTITIS
BACTERIAL
TRACHEITIS
ASTHMA IN
EXACERBATION
▪ Staphylococcus aureus – most common
▪ S. pneumoniae, S. pyogenes, M. catarrhalis, non-typeable H. influenzae
▪ Mean Age: 5-7 years old
▪ Males
▪ Bacterial infection preceded by a viral respiratory infection (LTB)
▪ More common than epiglottitis in vaccinated populations
▪ Brassy cough, high fever, toxic-looking
▪ Lies flat, no drooling, no dysphagia
▪ Mucosal swelling at the level of the cricoid cartilage, complicated by
copious,
thick,
purulent
secretions,
sometimes
causing
pseudomembranes
▪ Progressive ↑ in symptoms of shortness of breath, cough, wheezing or
chest tightness and progressive ↓ in lung function
▪ Usual Triggers:
● Viral infections
● Allergen, food allergen, outdoor air pollution
● Seasonal changes
● Poor adherence to ICS
▪ Worsen during sleep (midnight – 8 AM)
Mild
Breathless-ness
Can lie down
Sentences
May be agitated
Increased
Increased
Severe
While at rest (stops feeding)
Sits upright
Words
Drowsy or confused
Often > 30 cpm
Usually not
Common
Usual
Pulse Rate (bpm)
Moderate; Often endexpiratory
<100
Pulsus Paradoxus
Absent < 10 mmHg
Loud; throughout
exhalation
100-120
May be present > 10-25
mmHg
Usually loud; throughout
inhalation and exhalation
>120
Often present > 20-40
mmHg (child)
Wheeze
FUNCTIONAL ASSESSMENT
Peak Expiratory Flow
PaO2
PCO2
SaO2 at sea level
PPS Oral Exam Reviewer 2020
> 70%
Normal
< 42 mmHg
> 95%
Hypercapnea
▪ Laryngoscopy under OR-ICU set-up.
▪ Lateral Radiograph – thumb sign
▪ Cultures: blood, epiglottic surface, CSF
10-40% are resistant to ampicillin
▪ Clinical diagnosis – upper airway disease with high fever,
purulent secretions, and absence of epiglottitis features
▪ Incentive Spirometry
▪ Peak Expiratory Flow (PEF)
▪ Forced Expiratory Volume in 1 Second (FEV1)
Moderate
While at rest (difficulty
feeding)
Prefers sitting
Phrases
Usually agitated
While walking
Talks in..
Alertness
SIGNS
RR
Use of accessory
muscles
▪ High fever, sore throat, dyspnea, and rapidly progressing respiratory
obstruction.
▪ Previously healthy child suddenly develops a sore throat and fever →
toxic-looking within a matter of hours: difficulty in swallowing, labored
breathing, drooling, hyperextended neck (tripod position)
▪ Air hunger with restlessness → cyanosis, coma
▪ Stridor is a late finding and suggests near-complete airway
obstruction
▪ The barking cough typical of croup is rare.
~ 40-69% or response lasts
<2 hours
> 60 mmHg
< 42 mmHg
90-95%
< 40%
< 60 mmHg; possible
cyanosis
> 42 mmHg
<90%
▪ Secure airway
▪ Prepare for possible intubation in an OR-ICU set-up
▪ O2 supplementation (unless patient is agitated with mask)
▪ Start on ceftriaxone, cefepime, or meropenem
▪ Complete antibiotics for 10d
▪ Racemic epinephrine and corticosteroids are ineffective
Rifampicin Prophylaxis
▪ 20mkday x 4 days (max dose: 600 mg)
▪ <4yo, incompletely immunized
▪ <12mos old, incomplete primary vaccination
▪ Immunocompromised
COMPLICATIONS
Respiratory arrest or failure
▪ Supplemental oxygen
▪ Antibiotics: Vancomycin or clindamycin and a 3rdgeneration cephalosporin (e.g. ceftriaxone or cefepime)
COMPLICATIONS
▪ Cardiorespiratory Arrest
▪ Toxic Shock Syndrome
▪ Written action plan: medication instructions and when to
come back
▪ Increase controller medications from previous following the
recommended stepwise approach, if:
● Asthma symptoms are interfering with normal activities
● PEF has fallen by >20% for >2days
▪ The need for repeated doses of SABA over more than 1–2
days signals the need to review, and possibly increase,
controller treatment if this has not already been done.
▪ Combination low dose ICS (budesonide or beclometasone)
with formoterol maintenance and reliever regimen
● Effective in improving asthma symptom control
● Reduces
exacerbations
requiring
OCS
and
hospitalizations
● Formoterol max dose: 72 mcg
● Not approved in 4-11 years old
● Do not use with other ICS or ICS-LABA
▪ Leukotriene Receptors Antagonists
▪ Oral Corticosteroids – 6-11yo 1-2mkday x 3-5d (max
40/day), with indications:
● Failure to improve with controller in 2-3d
● Rapid deterioration
● PEF or FEV1 <60%
● With history of severe exacerbations
▪ If with 1-2 exacerbations/year despite Step 4-5 therapy,
refer to specialist
COMPLICATION
▪ Status Asthmaticus
Batch Clingy
▪ H. influenzae type b – most common (pre-vaccination)
▪ Other etiologic agents: S. pyogenes, S. pneumoniae, nontypeable H.
influenzae, S. aureus
▪ Usually seen in 2-4 years old
▪ Some cases in 1st year of life and in 7-year-old children
147
Acute Cough in Distress | Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
PNEUMONIA
HIGH RISK
CLINICAL MANIFESTATIONS
▪ Respiratory Rate
● 3-12mos: >70/min
● 1-5years: >50/min
● >5years: >35/min
▪ Intercostal, subcostal, or suprasternal retractions
▪ Head bobbing, cyanosis
▪ Grunting
▪ Apnea
▪ Lethargic/stupor/coma
▪ Convulsions
▪ Shock
▪ Pallor
▪ Severely malnourished
▪ Unable to drink
DIAGNOSIS
Similar with severe but with focus on assessment of gas
exchange:
▪ O2 Saturation, ABG
▪ CRP, procalcitonin
▪ CXR PA-Lat
▪ CBC (WBC)
▪ Chest UTZ (Effusion)
▪ Gram Stain, Culture and Sensitivity
Additional labs to investigate metabolic derangements
▪ ABG
▪ Serum Na, K
▪ CXR: effusion, abscess, air leak or multilobar consolidation
▪ O2 Sat ≤90%
ARDS
▪ Respiratory failure - oxygenation and ventilation are
insufficient to meet the metabolic demands of the body.
● PaO2 <60 mm Hg when breathing room air
● PaCO2 >50 mm Hg resulting in acidosis
▪ ALI → ARDS
● Onset: within 1 week of insult
● Origin: Not fully explained by cardiac failure or fluid
overload
● Chest imaging: new infiltrate(s) consistent with acute
pulmonary parenchymal disease
▪ Non-invasive MV
● PF Ratio < 300
● SF Ratio < 264
▪ Invasive MV
Hypoxic respiratory failure – intrapulmonary shunting and
venous admixture or insufficient diffusion of O2 from alveoli
into pulmonary capillaries
Hypercarbic respiratory failure – decreased minute
ventilation (i.e. TV x RR)
▪ Asthma exacerbation which does not improve with
standard therapy
STATUS
ASTHMATICUS
PPS Oral Exam Reviewer 2020
▪ Depends on the site involved
● Alar flaring, tachypnea, retractions, grunting, dyspnea
● Wheezing
● Altered sensorium, unresponsiveness, lethargy
● Poor cry, rapid shallow respirations
▪ Pulse oximetry monitoring – keep between 94-96%
▪ Capnography – determine the effectiveness of ventilation and
pulmonary circulation
▪ Clinical diagnosis + Blood Gas
● PaO2 <60 mm Hg when breathing room air
● PaCO2 >50 mm Hg resulting in acidosis
▪ Extreme dyspnea, prolonged exhalation
▪ Anxiety
▪ Upright, leaning forward
▪ Unable to talk, drowsy or confused
▪ Paradoxical breathing
▪ Absent breath sounds
▪ Bradycardia
▪ PEF < 25%
▪ Hypoxia despite O2 supplementation, hypercapnea
▪ Signs of severe exacerbation with no response within 1-2 hours
from administering SABA
▪ Recurrence of exacerbation within 48 hours of administering
oral corticosteroids
TREATMENT / COMPLICATIONS
▪ Refer to specialist
▪ May manage as outpatient if the following are NOT PRESENT:
● Age less than 2 years old
● Convulsions
● CXR with effusion, lung abscess, air leak or multilobar consolidation
● O2 Sat < 95%
▪ Otherwise, admit to ward
▪ If with immunization: Penicillin G 100,000 units/kg/day in 4 divided doses
▪ If incomplete or unsure immunization: ampicillin 100mkday divided to 4 doses
▪ Oral medications may be given if not O2 requiring
▪ MRSA: Vancomycin + Referral to ID
If clinically suspected or confirmed influenza virus infection
▪ Oseltamivir: (start within 48 hours)
● 3-8mos: 3mkdose BID x 5 days
● 9-11mos: 3.5mkdose BID x 5 days
● >12mos:
BW <15 kg at 30 mg BID x 5 days
>15-23 kg at 45 mg BID x 5 days
>23-40 kg at 60 mg BID x 5 days
>40 kg at 75 mg BID x 5 days
▪ Zanamivir: >7yo: 10 mg (two 5-mg inhalations) BID x 5 days, within 36 hours of
onset of influenza-like symptoms.
Goals:
▪ Ensure a patent airway
▪ Adequate oxygenation
▪ Removal of Carbon Dioxide
▪ Oxygen administration
▪ Airway adjuncts (oropharyngeal and NP airway)
▪ Inhaled gases – Helium-oxygen mixtures, nitric oxide
▪ Positive Pressure Respiratory Support – high-flow nasal cannula, CPAP, NIPPV
▪ Intubation – sedated or rapid sequence intubation
● PaO2 <60 mmHg while breathing >60% oxygen
● PaCO2 >60 mmHg
● pH <7.25
▪ ICU Admission
▪ O2 via FM to maintain 94-98% O2 Sat
▪ SABA: 2-6 puffs or 2.5mg diluted in 3 mL NSS; 2-3 puffs per hour may be given.
▪ Systemic Steroids:
● 1-2yo: 1-2mkday (max 20)
● 2-5yo: 30 mg
● IV Methylpred 1mkday q6
▪ Ipratropium Bromide: 2 puffs or 250 mcg/neb q 20 x 1 hour
▪ Magnesium sulfate
Batch Clingy
DISEASE
148
Subacute (2-4 weeks) | Acute
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Nonspecific bronchial inflammation often following a viral
infection
▪ Usually viral in origin: influenza
▪ Common bacterial etiology: pertussis, diphtheria, S. aureus, S.
pneumoniae (not necessarily)
BRONCHITIS
CLINICAL MANIFESTATIONS
▪ Cough is prominent followed by constitutional symptoms (fever and
malaise). Protracted cough may last 1-3 weeks
▪ Nonspecific URTI (rhinitis) → frequent, dry, hacking cough which may
or may not be productive 3-4 days after
▪ Sputum becomes purulent due to leukocyte migration
▪ Emesis of sputum that was swallowed
▪ Chest pain
Early findings: no or low-grade fever, upper respiratory signs –
nasopharyngitis, conjunctivitis, rhinitis, clear BS
Later findings: coarse and fine crackles, scattered high-pitched
wheezing
▪ M. tuberculosis complex: M. tuberculosis, M. bovis, M. africanum, M. microti, M. canetti
CLINICAL STAGES
▪ Exposure – recent contact, TST or IGRA (-), CXR and PE is normal
▪ Tuberculosis infection (TBI) – TST positive (hallmark) or IGRA positive, asymptomatic with normal PE, CXR may show granuloma or
calcifications.
▪ Disease – symptomatic and apparent radiographic evidence.
EPIDEMIOLOGY
▪ Ethnic minorities (Asian, non-Hispanic Black and Hispanic Children)
▪ 3 cases per 100,000 persons
TUBERCULOSIS
PATHOGENESIS
▪ Multiplication of tubercle bacilli in the alveoli → survives in non-activated macrophages and carried to LN → intensifies over 2-12 weeks →
tissue hypersensitivity → fibrosis and encapsulation → enlarging LN → may cause obstruction
▪ Seeding to different organs (RES, brain, kidneys, bones) or dissemination especially in immunocompromised patients
Primary Pulmonary Disease
▪ Hallmark: relatively large size of the regional lymphadenitis compared with the relatively small size of the initial lung focus
▪ Usual sequence: hilar lymphadenopathy → focal hyperinflation → atelectasis
▪ Nonproductive cough and mild dyspnea (most common), fever, night sweats, anorexia, ↓ activity
▪ Infants: failure-to-thrive, poor weight gain, wheezing, ↓ breath sounds
Progressive Primary Pulmonary Disease
▪ High fever, severe cough with sputum production, weight loss, night sweats
▪ Diminished breath sounds, rales, dullness or egophony
Reactivation Tuberculosis
▪ CXR: extensive infiltrates, thick-walled cavities in the upper lobes
▪ Older child and adolescents: fever, anorexia, malaise, weight loss, night sweats, productive cough, hemoptysis, chest pain
Pleural Effusion
▪ Commonly asymptomatic
▪ Tuberculous pleural effusion is uncommon in children <6yo and rare in children <2yo
▪ Sudden onset, low to high fever, shortness of breath, chest pain on deep inspiration, and diminished breath sounds
Pericardial Disease (Pericarditis)
▪ Low-grade fever, malaise, weight loss
▪ Pericardial friction rub, distant heart sounds, pulsus paradoxus
PPS Oral Exam Reviewer 2020
DIAGNOSIS
▪ CXR: Normal or with ↑ bronchial markings
▪ Absence of abnormality of VS (tachycardia, tachypnea, fever) and
a normal physical examination of the chest reduce the likelihood of
pneumonia
TREATMENT / COMPLICATIONS
▪ No specific therapy
▪ No need for antibiotics
▪ Cough suppressants may be used judiciously
Nonprescription cough and cold medicines
▪ Should not be used in children <4yo
▪ Use with caution if 4-11yo
Positive TST or IGRA + abnormal chest radiograph consistent with
TB + history of recent exposure to an adult with infectious TB –
highly suggestive of the clinical diagnosis of TB disease
▪ Isoniazid (H) 10-15mkday (max 300)
▪ Rifampin (R)15-20mkday (max 600)
▪ Pyrazinamide (Z) 30-40mkday (max 2000)
▪ Ethambutol (E) 20mkday (max 2500)
Chest X-ray and other imaging
Tuberculin Skin Testing (TST)
▪ Tuberculin sensitivity develops 3wks to 3mos (often in 4-8wks)
after inhalation of organisms
▪
False
negatives:
Very
young
age,
malnutrition,
immunosuppression by disease or drugs, viral infections (measles,
mumps, varicella, influenza), vaccination with live-virus vaccines,
overwhelming TB, corticosteroid therapy
Interferon-γ Release Assay (IGRA)
▪ Cannot differentiate between TBI and TB disease
▪ Advantages: only one patient encounter (vs two with TST) and
the lack of cross-reaction with BCG vaccination
Mycobacterial Sampling, Susceptibility and Culture
▪ Induced sputum with a jet nebulizer, inhaled saline, and chest
percussion followed by NP suctioning is effective in children as
young as 1yo
▪ Early morning gastric acid as specimen
▪ Negative cultures never exclude the diagnosis of tuberculosis in a
child.
Nucleic Acid Amplification Tests
▪ Sensitivity 25–83%, and specificity has varied from 80–100%.
Gene Xpert MTB/RIF
▪ Real-time PCR assay
▪ Simultaneously detects rifampin resistance – often used as a
proxy for MDR TB
CSF Analysis (CNS TB)
CT Scan
▪ CNS infection
▪ Usual regimen: 6 months: 2 HRZE 4 HR
▪ Bone and Joint: 12 months: 2 HRZE 10 HR
▪ Surgical debridement in bone and joint disease
▪ VP Shunt in CNS disease
▪ HIV-infected children: 6-9mos or 6mos after culture of sputum
becomes sterile; treatment should be daily
▪ Treatment of drug-resistant tuberculosis is successful only
when at least 2 bactericidal drugs are given to which the
infecting strain of M. tuberculosis is susceptible.
Drug-Resistant Tuberculosis
Primary resistance – infected with M. tuberculosis that is
already resistant to a particular drug
Secondary resistance - drug- resistant organisms emerge as the
dominant population during treatment; usually due to poor
adherence
▪ Treatment duration of 9mo with RZE is usually adequate for
isoniazid-resistant tuberculosis
▪ For IR resistance, total duration of therapy must be extended
to 12-24mos, intermittent regimens should not be used
2nd Line Treatment
▪ Bedaquiline – children ≥12yo and >33 kg, with the same
indications specified for delamanid
▪ Delamanid – children ≥6yo and ≥20 kg in whom a 4-drug
regimen plus pyrazinamide cannot be used because of drug
resistance
▪ Have baseline ECG and QTc monitoring for both Bedaquiline
and Delaminid.
▪ Linezolid, clofazimine
Corticosteroids
▪ Indicated in TB meningitis, endobronchial TB, and pericardial
Batch Clingy
DISEASE
149
Lymphohematogenous (Disseminated) Disease
▪ Depends on the burden of organisms released from the primary focus to distant sites and the adequacy of the host's immune response
▪ Indolent and prolonged
▪ Spiking fever
TB
▪ Prednisone 1-2mkday in 1-2 divided doses for 4-6 weeks
Latent Tuberculosis Infection
▪ 6-9 months of isoniazid
▪ 3 months of rifampicin and isoniazid
▪ 4-6 months of rifampicin (daily)
▪ Isoniazid and rifapentine (once weekly) x 12 wks
Miliary tuberculosis
▪ Occurs 2-6 months after initial infection
▪ Most common in infants and young children, malnourished and immunosuppressed patients
▪ Insidious with early systemic signs – anorexia, weight loss, low-grade fever
▪ Generalized lymphadenopathy & hepatosplenomegaly within several weeks
▪ Dyspnea, cough, rales, wheezing
Window Prophylaxis
▪ Isoniazid should be given to children <5yo who have a (-) TST
or IGRA result but who have a known recent exposure to an
adult with potentially contagious TB disease.
▪ TST or IGRA done at 8-10 weeks after exposure
● If positive, complete LTBI treatment
● If negative, stop LTBI treatment
Upper Respiratory Tract Disease
▪ Laryngeal TB: croup-like cough, sore throat, hoarseness, dysphagia
▪ TB of the middle ear: painless unilateral otorrhea, tinnitus, ↓ hearing, facial paralysis, perforated TM
Lymph Node Disease (Scrofula)
▪ Most common form of extrapulmonary tuberculosis in children
▪ Acute, with rapid enlargement, tenderness, and fluctuance of LN, high fever
▪ Lesion is discrete, nontender, and firm but not hard, usually unilateral but may be bilateral, involving multiple nodes and cause matted
nodes
COMPLICATIONS
▪ Respiratory distress
▪ Pneumothorax
▪ TB effusion
▪ Pneumomediastinum
Nontuberculous mycobacteria (NTM)
▪ Cat-scratch disease (Bartonella henselae), tularemia, brucellosis, toxoplasmosis, pyogenic infection
Central Nervous System Disease
▪ Most serious complication; fatal without prompt and appropriate treatment
▪ SIADH
▪ Stage 1: nonspecific symptoms – fever, HA, irritability, drowsiness, malaise. No focal neurologic signs but infants can experience a
stagnation or loss of developmental milestones.
▪ Stage 2: lethargy, nuchal rigidity, seizures, (+) Kernig and Brudzinski, hypertonia, vomiting, CN palsies, and other focal neurologic signs –
encephalitis, disorientation, movement D/O, speech impairment
▪ Stage 3: coma, hemi- or paraplegia, HTN, decerebrate posturing, deterioration of vital signs, death
Bone and Joint Disease (Pott disease)
▪ Vertebrae – most common involvement
▪ May present with gibbus formation (vertebrae)
▪ Sterile polyarticular (large joints)
CHLAMYDIA
PNEUMONIA
▪ TB peritonitis – most often in young
▪ TB enteritis – commonly the jejunum and ileum near Peyer patches and the appendix; shallow ulcers that cause pain, diarrhea or
constipation, weight loss, low-grade fever
▪ Renal TB – sterile pyuria, microscopic/gross hematuria, dysuria, flank, or abdominal pain
▪ Genital tract TB – fallopian tubes (90–100%), endometrium (50%), ovaries (25%), cervix (5%); lower abdominal pain, dysmenorrhea,
amenorrhea
▪ Congenital TB – most common route of infection for the neonate is postnatal airborne transmission from an adult with infectious
pulmonary TB
▪ Perinatal Disease – may be present at birth but usually begins by the 2nd or 3rd week of life; family history of TB; respiratory distress,
fever, hepatic or splenic enlargement, poor feeding, lethargy or irritability, lymphadenopathy, abdominal distention, failure to thrive, ear
drainage, skin lesions
▪ C. pneumoniae, C. trachomatis
▪ Mild to moderate: constitutional symptoms – fever, malaise,
headache, cough, pharyngitis
PPS Oral Exam Reviewer 2020
▪ Isolation of organism in tissue culture (at posterior pharynx)
CXR: diffuse lobar infiltrates with small pleural effusion (appears
▪ Tetracycline
▪ Macrolides
Batch Clingy
Abdominal and Gastrointestinal Disease
▪ Most common lesion is a painless ulcer on the mucosa, palate, or tonsil with enlargement of the regional LNs
150
PATHOGENESIS
▪ Person to person transmission
▪ Elementary body (EB) → attach to host cells via electrostatic
binding → endocytosis → differentiate to Reticulate body (RB) in
36 hours that undergo binary fission → after 48 hours, cytolysis
or exocytosis
▪ Mycoplasma pneumoniae
▪ Complete absence of a cell wall → dependence to host cells for
obtaining essential nutrients; intrinsic resistance to β-lactam
agents
MYCOPLASMA
PNEUMONIA
EPIDEMIOLOGY
▪ ~20% of all CAP in middle and high school children
▪ 5% in < 5 yr
▪ 16% in 5-9 yr
▪ 23% in 10-17 yr
▪ Transmission rates of 40 to > 80% for household adult and
children contacts, respectively.
▪ Incubation period: 2-3 weeks
▪ Severe: pneumonia with pleural effusion and empyema
▪ Symptoms of asthma and acute chest syndrome in sickle cell disease
patients
▪ Rales, wheeze
worse than the clinical status)
CBC: may be elevated with left shift
Microimmunofluorescence (MIF): for acute infection, 4-fold
increase in IgG titer or an IgG titer of ≥16; use of a single elevated
IgG titer was discouraged
▪Tracheobronchitis and atypical pneumonia – most common
▪ Abrupt onset but with gradual development of headache, malaise,
fever, and sore throat
▪ Hoarseness and non-productive cough
▪ Clinical hallmark: worsens during the 1st wk of illness, symptoms
generally resolve within 2 wk; cough up to 4 weeks, may be
accompanied by prolonged wheezing
▪ Auscultation may be normal or dry rales
▪ PCR throat swab
▪ Culture on special media (SP4 Agar media) – mulberry colonies
after 2-3 weeks
▪ ELISA to detect IgM and IgM against M. pneumonia
CXR: interstitial or bronchopneumonic, most commonly involving
lower lobes; bilateral diffuse infiltrates, lobar pneumonia or hilar
lymphadenopathy in up to 30%; may have pleural effusion
CBC: normal
ESR, CRP: elevated
PATHOGENESIS
▪ Attaches to sialic acid receptors in the cilia of respiratory
epithelial cells of the respiratory tract → ciliostasis and sloughing
off of cells and hydrogen peroxide production → biofilm
production → hinders antibiotic penetration and immune system
recognition
▪ Community-Acquired Respiratory Distress Syndrome (CARDS) –
exotoxin involved in severe or even fatal disease
▪ At Lower Respiratory Tract: polyclonal activation of B & T
lymphocytes + CD4+ cells → cytokine production + cold
agglutinins (IgM Ab)
RHINOSINUSITIS
▪ Viral from common colds
▪ S. pneumoniae (~30), nontypeable H. influenzae (~30%), M.
catarrhalis (~10%).
▪ MRSA, α- and β-hemolytic streptococci, coagulase-negative
staphylococci
▪ Nasal congestion, purulent nasal discharge (unilateral or bilateral),
fever, cough
▪ Halitosis, hyposmia, periorbital edema
▪ Headache, facial pain, maxillary tooth discomfort, pain or pressure
exacerbated by bending forward
Predisposing conditions: viral URTI, AR, tobacco smoke exposure,
immune deficiencies, cystic fibrosis, ciliary dysfunction,
abnormalities of phagocyte function, GER, anatomic defects (cleft
palate), nasal polyps, cocaine abuse, nasal foreign bodies
▪ Erythema and swelling of the nasal mucosa with purulent nasal
discharge, sinus tenderness
▪ Transillumination: opaque sinus
▪ Acute <30 days
▪ Subacute 1-3mos
▪ Chronic >3mos
PATHOGENESIS
▪ Viral URTI → viral rhinosinusitis (MRI: mucosal thickening,
PPS Oral Exam Reviewer 2020
Suggestive of sinusitis
▪ Persistence of nasal congestion, rhinorrhea (of any quality), and
daytime cough ≥10d without improvement
▪ Severe symptoms of temperature ≥39°C (102°F) with purulent nasal
discharge for ≥ 3 days
▪ Worsening symptoms: recurrence of symptoms after an initial
improvement or new symptoms of fever, nasal discharge, daytime
▪ Clinical Diagnosis: 2 Major or 1 major with 2 or more minor
▪ Sinus aspirate culture – only accurate method of diagnosing
▪ CT Scan – opacification, mucosal thickening, or presence of an airfluid level
● Erythromycin 40mkday PO BID x 10 days
● Clarithromycin 15mkday PO BID x 10 days
● Azithromycin 10mkday PO on day 1, and then 5mkday PO
on days 2-5
▪ Quinolones
COMPLICATIONS
▪ Acute chest syndrome in Sickle Cell Disease
▪ Acute otitis media
▪ Persistent cough for several weeks
▪ Treatment may be more effective when started within 3-4
days of illness onset
▪ Clarithromycin 15mkday BID x 10 days
▪ Azithromycin 10mkday on D1, 5mkday on D2-5
▪ Doxycycline 100mg BID x 7-14 days – child >8yo
▪ Levofloxacin 750mg QD x 7-14days – not recommended as a
first-line therapy in children
Macrolide-Resistant:
▪ Doxycycline 2-4mkday QD or BID x 10 days (max 200 mg) –
>8yo
▪ Levofloxacin 10mkdose q12 children <5yrs or QD in older
children
COMPLICATIONS
▪ Large pleural effusions with lobar infiltrates and necrotizing
pneumonia in sickle cell disease and immunodeficiencies, Down
Syndrome, and Chronic Cardiopulmonary Disease
▪ Encephalitis, ADEM, transverse myelitis, cerebellar ataxia,
aseptic meningitis, Guillain-Barré syndrome, Bell palsy,
peripheral neuropathy
▪ Maculopapular rash, urticaria, SJS, Gianotti-Crosti syndrome,
erythema nodosum
▪ Thrombocytopenia, aplastic anemia, coagulation defects
▪ Arthritis, cardiac complications (pericarditis, myocarditis, and
rheumatic fever-like syndrome)
▪ Uncomplicated mild to moderate acute bacterial sinusitis:
Amoxicillin 45mkday BID
▪ Penicillin-allergic: cefdinir, cefuroxime axetil, cefpodoxime, or
cefixime, levofloxacin
▪ Children with risk factors (antibiotic treatment in the
preceding 1-3mos, daycare attendance, or age <2yo) for the
presence of resistant bacterial species, and for children who fail
to respond to initial therapy with amoxicillin within 72hrs, or
with severe sinusitis:
● Co-Amoxiclav 80-90mkday of amoxicillin
● Ceftriaxone 50mkday IV or IM
▪ Refer to ENT
COMPLICATIONS
Orbital complications: periorbital cellulitis, orbital cellulitis
▪ CT Scan
▪ Refer to Ophtha and ENT
Batch Clingy
EPIDEMIOLOGY
▪ Affects all ages
▪ 2-19% of CAP
▪ Droplet transmission
151
edema, inflammation)
▪ Nose blowing → propels nasal secretions to sinuses → bacteria
from nasopharynx enters sinuses → inflammation and edema →
blocked sinus drainage, impaired mucociliary clearance of
bacteria
cough
▪ Surgical drainage
▪ IV antibiotics
Intracranial complications: epidural abscess, meningitis,
cavernous sinus thrombosis, subdural empyema and brain
abscess
▪ Cranial CT Scan
▪ IV antibiotics
▪ Surgical drainage (50%)
Pott puffy tumor – osteomyelitis of frontal bone characterized
by edema and swelling of the forehead
Mucoceles
Major Symptoms: purulent anterior nasal discharge, purulent or
discolored posterior nasal discharge, nasal congestion or obstruction,
facial congestion or fullness, facial pain or pressure, hyposmia or
anosmia, fever (For acute sinusitis only)
Minor Symptoms: headache, ear pain, pressure or fullness, halitosis,
dental pain, cough, fever (for subacute or chronic sinusitis), fatigue
Chronic Cough (>4 weeks) | Complex
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ B. pertussis (causes pandemic), B. parapertussis – exclusive
pathogens of humans and some primates which causes the
epidemic
▪ B. holmesii – in immunocompromised hosts without cough
illness; causes pertussis-like cough illness in small outbreaks
in healthy persons
▪ B. bronchiseptica – common animal pathogen
CLINICAL MANIFESTATIONS
Catarrhal Stage
▪ 1-2 weeks
▪ Nasal congestion, rhinorrhea, low-grade fever, sneezing, lacrimation,
conjunctival suffusion
▪ Pertussis transmitted via droplet → hemagglutinin,
agglutinogens, perctactin allows attachment to ciliated
respiratory epithelial cells
▪ Pertussis toxin (major virulence protein) – increases
histamine sensitivity, insulin secretion, leukocyte dysfunction
▪ Tracheal cytotoxin + PT – inhibits the clearance of bacterial
Paroxysmal Stage
▪ 2-6 weeks
▪ Onset of cough – dry, intermittent, irritative hack, → inexorable
paroxysms (hallmark)
▪ Machine-gun burst of uninterrupted cough on a single exhalation,
chin and chest held forward, tongue protruding maximally, eyes
bulging and watering, face purple, until coughing ceases and a loud
whoop
▪ Posttussive emesis, exhaustion
▪ Extremely contagious (100% attack rate) via droplet with
high rates of subclinical infection (80%) in households
▪ Incubation period: 3-12 days
Convalescent Stage
▪ ≥2 weeks
▪ Number, severity, and duration of episodes diminishes
DIAGNOSIS
▪ Clinical: predominant complain of cough with the absence of fever,
malaise/myalgia, exanthem or enanthem, sore throat, hoarseness,
tachypnea, wheezes, rales
Clinical case definition: Cough of ≥14 days duration with at least 1
associated symptom of paroxysms, whoop, or post tussive vomiting
has sensitivity of 81% and specificity of 58%.
CBC: Leukocytosis (15,000-100,000 cells/μL), absolute lymphocytosis
(catarrhal stage)
CXR: perihilar infiltrate or edema and variable atelectasis
PCR via nasopharyngeal wash: test of choice
Culture: nasopharyngeal
TREATMENT / COMPLICATIONS
Hospitalization
▪ <3mos old
▪ 3-6mos old unless paroxysms are not severe or if with
comorbidities
Azithromycin – drug of choice in all age groups for both
treatment and prophylaxis
▪ < 6mos: 10mkday QD
▪ > 6mos: D1 10mkday QD then D2-5 5mkday QD
Erythromycin
▪ May cause infantile hypertrophic pyloric stenosis in neonates
< 14days old
▪ 40-50mkday in 4 doses x 14 days
Serologic tests: most sensitive tests in immunized individuals
PERTUSSIS
In infants <3mos old:
▪ Shorter catarrhal phase (often unnoticed)
▪ Chokes, gasps, gags, and flail extremities
▪ Reddened face, apnea, cyanosis
▪ Lengthy paroxysmal and convalescent stages in young infants
Clarithromycin
▪ >1mos: 15mkday in 2doses x 7days
Trimethoprim-sulfamethoxazole (TMP-SMX)
▪ Alternative for infants >2mos old and children unable to
receive azithromycin
▪ TMP 8mkday in 2doses x 14days
Place on droplet precaution and isolation until 5 days after
initiation of azithromycin therapy.
Batch Clingy
COMPLICATIONS
▪ Apnea
▪ Bradycardia
▪ Otitis Media
▪ Progressive Pulmonary Hypertension
▪ Pneumonia
▪ Seizures, encephalopathy
▪ Death
PPS Oral Exam Reviewer 2020
152
Physiologic GER – retrograde movement of gastric contents
across the LES into the esophagus
Pathologic GERD – reflux produces bothersome symptoms or
impairs nutrition
▪ Associated with OM, sinusitis, lymphoid hyperplasia,
hoarseness, vocal cord nodules, laryngeal edema
▪ Worsens laryngomalacia or BPD if present
▪ Genetic predispositions: family clustering of GERD
symptoms, endoscopic esophagitis, hiatal hernia, Barrett
esophagus, adenocarcinoma
GASTROESOPHAGEAL
REFLUX DISEASE
(GERD)
PATHOPHYSIOLOGY
▪ Factors determining reflux symptoms: duration and
frequency of exposure, causticity of gastric regurgitant,
susceptibility to damage
▪ Frequency of episodes is ↑ by insufficient LES tone,
abnormal frequency of LES relaxations, and hiatal herniation
that prevents the LES pressure from being proportionately
augmented by the crura during abdominal straining
▪ Duration of episodes is ↑ by lack of swallowing (e.g., during
sleep) and by defective esophageal peristalsis
▪ Transient LES relaxation – 1o mechanism allowing reflux
VASCULAR RING
▪ Vascular anomalies that result from abnormal development
of the aortic arch complex
▪ Double aortic arch – most common complete vascular ring,
encircling both the trachea and esophagus, compressing both
▪ Pulmonary artery sling
▪ Left aortic arch with aberrant right subclavian artery – most
common open (incomplete) vascular ring
▪ May have congenital heart disease
TRACHEOMALACIA
▪ Chondromalacia of a central airway → insufficient cartilage
to maintain airway patency throughout the respiratory cycle
▪ Recurrent regurgitation (± vomiting)
▪ Weight loss or poor weight gain
▪ Irritability
▪ Ruminative behavior
▪ Heartburn or chest pain
▪ Hematemesis
▪ Dysphagia or odynophagia
▪ Wheezing, stridor
▪ Cough
▪ Hoarseness, laryngeal/pharyngeal Inflammation
▪ Recurrent Pneumonia
▪ Anemia
▪ Dental Erosion, feeding refusal
▪ Dystonic neck posturing (Sandifer Syndrome)
Infants:
▪ Regurgitation (postprandial)
▪ Signs of esophagitis – irritability, arching, choking, gagging, feeding
aversion
▪ Respiratory symptoms – obstructive apnea, stridor
▪ Failure to thrive
▪ Symptoms resolve spontaneously in most infants by 12-24mos
▪ Thorough history and PE (with use of standardized questionnaires)
– infant GER questionnaire
▪ Extended esophageal pH monitoring –used to diagnose acidic
reflux
▪ Empirical antireflux therapy – trial of PPI treatment, mostly
established in adults
▪ Barium Studies – to rule out other diseases
▪ Endoscopy – usually for complications
▪ Intraluminal impedance – diagnoses GERD and assesses
esophageal function
▪ Laryngotracheobronchoscopy – to establish GERD as cause of
respiratory symptoms
DIFFERENTIAL DIAGNOSIS
▪ Milk and other food allergies
▪ Eosinophilic esophagitis
▪ Pyloric stenosis, intestinal obstruction (especially malrotation with
intermittent volvulus)
▪ Non-esophageal inflammatory diseases
▪ Infections, IEM, hydronephrosis, ↑ ICP, rumination, bulimia
Older children:
▪ Regurgitation
▪ Abdominal or chest pain
▪ Airway manifestations (laryngitis, sinusitis)
Waxing and Waning
▪ Respiratory symptoms
▪ Dysphagia
▪ Barium esophagogram
▪ CT or MRI with angiography
▪ Symptoms appear within the 1st 2wks, increase in severity for up to
6mos
▪ Gradual improvement can begin at any time
▪ Flexible or rigid bronchoscopy
▪ Fluoroscopy – poorly sensitive
▪ MRI or CT Scan – if secondary to vascular ring
AIRWAY ANOMALY
Primary: congenital absence of tracheal-supporting cartilages
Secondary: EA, TEF, vascular rings (double aortic arch),
tracheal compression from an aberrant innominate artery,
tracheal compression from mediastinal mases, abnormally
soft tracheal cartilages associated with connective tissue
disease, prolonged mechanical ventilation, chronic lung
disease
▪ M:F = 2:1
▪ 45% to 75% of congenital causes of stridor
LARYNGEAL CLEFT
▪ Deficiency in the midline of the posterior larynx
PPS Oral Exam Reviewer 2020
▪ Stridor especially with crying, agitation, or feeding
▪ Low-pitched monophonic wheezing predominantly during expiration
– most prominent over the central airways
▪ Wheezing – loudest at trachea
Conservative therapy and lifestyle modification
▪ Normalization of abnormal feeding techniques, volumes,
frequencies
● Thickening feeds
● Hypoallergenic diet
● Avoidance of smoke exposure
● Avoid acidic or reflux-inducing food and beverages:
tomatoes, chocolate, mint, juices, carbonated and caffeinated
drinks, alcohol
● Weight reduction
● Positioning measures
▪ Antacids
▪ H2RA: cimetidine, famotidine, nizatidine, and ranitidine
▪ PPI: omeprazole, lansoprazole, pantoprazole, rabeprazole,
esomeprazole
▪ Prokinetic agents: metoclopramide (dopamine-2 and 5-HT3
antagonist), bethanechol (cholinergic agonist), erythromycin
(motilin receptor agonist)
▪ Surgery: fundoplication
COMPLICATIONS
▪ Esophagitis, esophageal stricture, barrett
adenocarcinoma of the esophagus
▪ Failure to thrive
▪ Aspiration
▪ Laryngeal penetration
▪ Apnea in infants
▪ Reflux Laryngitis
▪ Dental erosions
▪ Surgery
esophagus,
▪ Postural drainage
▪ Nebulized ipratropium bromide
▪ CPAP via tracheostomy (if severe)
▪ Surgery (aortopexy and bronchopexy) if symptomatic or
cyanotic
COMPLICATIONS
▪ Prolonged recovery from common respiratory infections
▪ Prolonged bacterial bronchitis
▪ Prognosis for secondary causes varies with the comorbidity
▪ Aspiration (frequent)
▪ Recurrent respiratory infections
▪ Larygoscopy and bronchoscopy with palpation of posterior larynx
– gold standard
▪ Stabilize airway
▪ Control GERD
Batch Clingy
▪ Most common esophageal disorder in children of all ages
153
▪ Associated with tracheal agenesis, TEF, and multiple
congenital anomalies (G syndrome, Opitz-Frias syndrome,
Pallister-Hall syndrome)
4 Types:
Type I – mild; interarytenoid notch extends to the true vocal cords; 60% asymptomatic with no surgery needed
Type II – extends beyond the vocal cords to, but not through, the cricoid cartilage
Type III – extends through cricoid into cervical trachea
Type IV – extends inferiorly into the cervical or thoracic trachea; no separation between the trachea and esophagus →
laryngotracheoesophageal cleft
BRONCHIECTASIS
▪ Cough and copious purulent sputum – most common
▪ Etiology, as complications of:
▪ Hemoptysis
● Cystic Fibrosis, primary ciliary dyskinesia
▪ Fever
● Foreign body aspiration
▪ Anorexia
● Aspiration of Gastric Contents
▪ Crackles and wheezing
● Immune Deficiency Syndromes
▪ Digital Clubbing
● Infections
▪ Severe: Hypoxemia
● Williams-Campbell Syndrome (absence of annular
bronchial cartilage)
Prebronchiectasis – chronic or recurrent endobronchial infection with
●
Marnier-Kuhn
syndrome
(congenital
nonspecific HRCT changes; may be reversible
tracheobronchomegaly)
HRCT bronchiectasis – clinical symptoms with HRCT evidence of
bronchial dilation; may persist, progress, or improve and resolve
▪ Lower lobes – most commonly affected
Established bronchiectasis – like the previous but with no resolution
▪ Irreversible abnormal dilation and anatomic distortion of
within 2yrs
the bronchial tree
▪ Common end stage of many nonspecific and unrelated
Exacerbations
antecedent events
▪ 1 Major + 1 Lab Criteria; 2 Major; 1 major + 2 minor
▪ Major Criteria: wet cough >72hrs, increased cough frequency > 72hrs
Incidence
▪ Laboratory Criteria: CRP > mg/L, serum IL-6 >2 ng/L, serum amyloid A
▪ Low- and middle-income countries
>5mg/L, ↑ neutrophil percentage
▪ Females > Males
▪ Minor Criteria: change in sputum color, breathlessness, chest pain,
crackles/crepitations, wheeze
PATHOGENESIS
Three Mechanisms
1.
Obstruction
2.
Infections
3.
Inflammation:
inflammatory
factors
activate
neutrophils → destruction of cells and induction of
goblet cell hyperplasia
▪ Early stages: bronchiolar wall thickening and destruction of
elastin → bronchial dilatation
▪ Later stages: bronchial walls develop cartilage destruction
with associated pulmonary artery/ arteriole vascular
remodeling → pulmonary HTN
▪ May have microorganisms in the isolate: S. pneumoniae, H.
influenzae non–type b, M. catarrhalis, M. pneumoniae
Psychogenic Cough
▪ Abrupt & loud cough – harsh, honking, barking quality
▪ Tic Cough/Somatic Cough Disorder/Habit Cough
▪ Absent if the physician listens outside the examination room and
▪ May be preceded by an URTI
reappears upon direct attention to child.
▪ Esophagogram
▪ FEES
▪ Type I – endoscopic surgery
▪ Type II and up – open procedure
▪ Pulmonary function studies: obstructive, restrictive, or mixed
▪ Investigate possible cause (sweat test, immunologic work-up
▪ Thin-section HRCT scanning – gold standard
▪ “tram lines”, “signet ring appearance”, varicose (bronchi with
beaded contour), cystic (cysts in strings and clusters)
▪ Airway clearance techniques (e.g., gravity-assisted drainage,
active cycle of breathing, positive expiratory pressure [PEP],
acapella, high-frequency chest wall oscillation)
▪ Antibiotics for 2-4wks depending on isolate:
Amoxicillin/clavulanic acid (22.5mkdose BID)
▪ Bronchodilators
▪ Long-term prophylactic macrolide antibiotics or nebulized
antibiotics
▪ Inhaled hypertonic saline
▪ Inhaled corticosteroids
▪ Lung transplantation
Forms:
▪ Cylindrical – regular, diffuse dilation of the bronchial unit
▪ Varicose – Irregular, greater dilatation with local constrictions
▪ Saccular (cystic) bronchial dilation progresses; ballooning of
bronchi; most severe
COMPLICATIONS
▪ Recurrent pulmonary illness
▪ Stunted growth
▪ Osteopenia
▪ Osteoporosis
▪ Cough lasting weeks-months
▪ Refractory to treatment
▪ Disappears with sleep or distraction
▪ Assurance that a pathologic lung condition is absent, and
child may resume full activity
▪ Speech therapy techniques
▪ Self-hypnosis
Batch Clingy
TRACHEOESOPHAGEAL FISTULA
PPS Oral Exam Reviewer 2020
154
Acute
DISEASE
COMMON COLDS
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Rhinoviruses – 50%
▪ RSV
▪ Human Metapneumovirus
▪ Parainfluenza virus
▪ Adenovirus
▪ Influenza virus
▪ Nonpolio enterovirus
▪ Human coronaviruses
▪ Direct hand contact
▪ Inhalation of small particle aerosol
▪ Deposition of large particle aerosols
▪ Viral infection of the nasal epithelium →
destruction of epithelial lining → acute inflammatory
response
2 factors for expression of AR:
▪ Sensitivity to allergen
▪ Presence of allergen in the environment
Early Phase: degranulation of mast cells, release of
preformed and newly generated inflammatory
mediators
Late Phase: 4-8hrs after allergen exposure,
inflammatory cells infiltrate the nasal mucosa
LABORATORY FINDINGS / DIAGNOSIS
▪ Clinical
▪ Routine lab tests – not helpful
▪ Sore or scratchy throat
▪ Nasal obstruction
▪ Rhinorrhea
▪ Cough
▪ Swollen, erythematous nasal turbinates
▪ Abnormal middle ear pressure
▪ Anterior CLAD
▪ Conjunctival injection
▪ Change in the color and consistency of nasal
secretion → accumulation of PMNs
▪ Allergic salute
▪ Nasal crease
▪ Nasal congestion
▪ Itching, sneezing
▪ Clear rhinorrhea
▪ Conjunctival irritation
▪ Allergic gape – open mouth breathing
▪ Allergic shiners
▪ Skin test
▪ Prep: Withhold montelukast for 1 day, most
sedating antihistamine for 3-4 days, and
nonsedating antihistamines for 5-7 days
▪ Serum IgE
DIFFERENTIAL DIAGNOSIS
▪ Nonallergic rhinitides – no sIgE elevation
▪ Vasomotor rhinitis
▪ Rhinitis medicamentosa
▪ Structural problems – nasal polyps, septal
deviation
TREATMENT
▪ Mainly supportive
▪ Antiviral treatment if indicated (Oseltamivir,
Zanamivir) – should be started within 48hrs of
symptom onset
▪ Nonprescription cough and cold products → not
used for infants and <6yo
▪ Zinc – reduces symptom duration if given within
24hrs
▪ Topical adrenergic agents
● Oxymetazoline, phenylephrine
● Avoid prolonged use to prevent Rhinitis
Medicamentosa
● Not used for <6yo
▪ 2nd gen antihistamine – anticholinergic effect
▪ Honey (5-10ml) – for children >1yo to relieve
nocturnal cough
▪ Antihistamines (second-generation)
▪ +/- pseudoephedrine
▪ Intranasal decongestants
▪ Intranasal corticosteroids – most effective therapy
▪ Immunotherapy
COMPLICATIONS / PROGNOSIS
▪ AOM – most common complication
▪ Sinusitis – rhinorrhea or daytime cough without
improvement for 10-14 days
▪ Exacerbation of asthma
▪ Antibiotic resistance
▪ Chronic sinusitis
▪ Eustachian tube obstruction
▪ Middle ear effusion
▪ OSA
▪ Up to 78% of patients with asthma have AR, and
38% of patients with AR have asthma
Batch Clingy
ALLERGIC RHINITIS
CLINICAL MANIFESTATIONS
Infants: fever and nasal discharge predominate
PPS Oral Exam Reviewer 2020
155
Acute
DISEASE
ETIOLOGY / PATHOLOGY / PATHOGENESIS
▪ Spongiosis – marked intercellular edema
CLINICAL MANIFESTATIONS
▪ Severely dry skin – hallmark
LABORATORY FINDINGS / DIAGNOSIS
Labs: Nonspecific
▪ Chronic lichenified AD: hyperplastic epidermis with
hyperkeratosis and minimal spongiosis
Cardinal features:
▪ Intense pruritus
▪ Cutaneous reactivity
DIFFERENTIAL DIAGNOSIS
▪ Seborrheic Dermatitis
▪ Nummular Dermatitis
▪ Irritant Contact Dermatitis
▪ Allergic Contact Dermatitis
▪ Lichen Simplex Chronicus
▪ Asteatotic Eczema
▪ Dermatophyte infection
▪ Scabies, Impetigo, HIV
▪ Icthyosis vulgaris
▪ Acrodermatitis enterohepatica (zinc)
▪ Biotin deficiency, Pellagra (niacin)
▪ Kwashiorkor, PKU
▪ Cutaneous T-cell lymphoma
▪ Langerhans cell histiocytosis
▪ Atopic eczema (IgE mediated)
▪ Nonatopic eczema
▪ Increased expression of IL4 & IL13
▪ Genetic mutations in Filaggrin gene
▪ Lichenification & fibrotic papules – chronic AD
ATOPIC DERMATITIS
Atopic Eczema
TREATMENT / COMPLICATIONS / PROGNOSIS
▪ Moisturizers – first line of therapy
▪ Topical corticosteroids – cornerstone of therapy
▪ Topical Calcineurin Inhibitors (>2yo)
▪ Topical PDE-4 Inhibitor (Crisaborole)
▪ Antihistamine
▪ Systemic Corticosteroids
▪ Cyclosporine
▪ Dupilumab
▪ Antimetabolites (MMF, MTX, Azathioprine)
▪ Phototherapy
COMPLICATIONS
Eczema Herpeticum
Exfoliative Dermatitis
Allergic Keratoconjunctivitis
Keratoconus
PREVENTION
Avoid triggers
Chronic (>6 weeks)
▪ Not physical urticaria or recurrent urticarial with repeated
exposures to a specific agent
URTICARIA
(Hives)
And
ANGIOEDEMA
Hives – erythematous, pruritic raised wheal that blanches
with pressure, transient and resolves without residual
lesions
Urticarial vasculitis – lesions that burn more than itch, last
>24 hours, does not blanch, heal with scarring or associated
with bleeding into the skin (purprura)
PHYSICAL URTICARIA
Cold Dependent Disorders
▪ Localized pruritus, urticarial/angioedema after exposure to a cold
stimulus
▪ Due to the presence of cryoproteins
Cholinergic Urticaria
▪ Associated with exercise, hot showers and sweating
DIFFERENTIAL DIAGNOSIS
▪ Cutaneous or systemic mastocytosis
▪ Hereditary angioedema
▪ Urticaria pigmentosa
▪ Exercise induced anaphylaxis
Dermatographism/Urticaria Factitia
▪ Ability to write on skin
Pressure Induced Urticaria/Angioedema
▪ Occurs 4-6 hours after pressure has been applied
Solar Urticaria
▪ Occurs within minutes of sun exposure
▪ Disappears within 1-3 hours after cessation of sun exposure
PPS Oral Exam Reviewer 2020
Clinical diagnosis
Batch Clingy
Acute (<6 weeks)
▪ IgE mediated
▪ Non IgE mediated
PROGNOSIS
▪ Severe and persistent in young children
▪ Spontaneous resolution after age 5 (40-60%)
▪ Adults: Hand dermatitis
Poor prognostic factors:
▪ Widespread AD during childhood
▪ FLG null mutations
▪ Concomitant AR and asthma
▪ Family history of AD in parents and siblings
▪ Early age at onset of AD
▪ Only child
▪ Very high serum IgE levels
▪ Antihistamines – hydroxyzine & diphenhydramine
▪ Avoidance of triggers
▪ Epinephrine – seldom required
▪ Short course oral corticosteroids – for severe episodes
▪ Leukotriene Modifiers
156
Aquagenic Urticaria
▪ Occurs after contact with water regardless of termperature
▪ Latex Allergy - most common cause occurring in the
hospital setting
▪ Food Allergy – community
▪ Mostly results from activation of mast cells and basophils
via cell-bound allergen-specific IgE molecules
ANAPHYLAXIS
Principal pathologic features:
▪ Bronchial obstruction with pulmonary hyperinflation
▪ Pulmonary edema
▪ Intraalveolar hemorrhage
▪ Visceral congestion
▪ Laryngeal edema
▪ Urticaria
▪ Angioedema
CHRONIC IDIOPATHIC URTICARIA/ANGIOEDEMA
▪ Does not appear to result from an allergic reaction
▪ Non necrotizing, perivascular, mononuclear cellular infiltration
▪ Associated with anti-thyroid antibodies
▪ 35-40% have (+) autologous serum skin test
▪ Ingested allergens have delayed onset (minutes to 2hrs) compared to
injected allergens
Initial symptoms
▪ Pruritus of the mouth and face
▪ Flushing, urticarial and angioedema
▪ Sensation of warmth, weakness and apprehension (sense of doom)
▪ Tightness in the throat, dry staccato cough, hoarseness
▪ Periocular pruritus
▪ Nasal congestion, sneezing
▪ Dyspnea, deep cough, wheezing
▪ Nausea, abdominal cramps, vomiting
▪ Uterine contractions (lower back pain)
▪ Faintness and loss of consciousness
Labs are nonspecific
▪ Plasma histamine
▪ Plasma tryptase
MEDICAL EMERGENCY!
Epinephrine
▪ Most important
▪ IM on the lateral thigh
▪ 1:1000, 0.01mg/kg max 0.5mg
▪ Biphasic Anaphylaxis – occur within 4 hours of treatment
Batch Clingy
▪ Cutaneous manifestations are absent in 10% of cases & the acute
onset of severe bronchospasm in a previously well person with asthma
should suggest the diagnosis of anaphylaxis
PPS Oral Exam Reviewer 2020
157
Complex
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Chronic autoimmune disease of multisystem inflammation & (+)
circulating autoAb directed against self Ag
▪ Genetic predisposition
▪ Women of reproductive age – due to hormones
● 90% are female
● Female sex – strongest risk factor (9:1)
● Estrogen → exposure promotes B-cell autoreactivity
● Estrogen containing OCPs do not appear to induce flares in
quiescent SLE, risk of flares may be in in postmenopausal
receiving hormone replacement therapy
▪ Viral infections, EBV may play a role
▪ UV light exposure – trigger disease activity
▪ Prevalence: 1-6/100,0000
▪ Factors influencing risk and severity of disease: genetics,
hormonal milieu, environmental exposures
▪ Genetic predisposition associated with specific genetic
abnormalities:
● Congenital deficiencies of C1q, C2 and C4
● Polymorphism (IFN regulatory factor 5, protein tyrosine
phosphatase N22)
▪ Human leukocyte antigen (HLA) types occur with ↑ frequency
in patients with SLE (HLA-B8, HLA-DR2, HLA-DR3)
SYSTEMIC LUPUS
ERYTHEMATOSUS
PATHOGENESIS
▪ Hallmark: generation of autoAb against self-antigens
(particulartly nucleic acid)
▪ Cell necrosis by apoptosis → antigens released
▪ ↑ Levels of apoptosis or significantly impaired ability to clear
cell debris → prolonged exposure to nucleic acid antigens in the
bloodstream → recognition by immune cells → B-cell stimulation
and autoantibody production
▪ Circulating autoAb may form immune complexes and deposit in
tissues → local complement activation, initiation of
proinflammatory cascade and tissue damage
▪ Ab to double-stranded (ds) DNA form immune complexes →
deposit in glomeruli → inflammation → glomerulonephritis
CLINICAL MANIFESTATIONS
▪ Hallmark – multiorgan disease
▪ Most common presenting complaints in children: fever, fatigue,
hematologic abnormalities, arthralgia, arthritis
▪ Renal disease – asymptomatic, monitor BP and urinalysis
4/11 ACR 1997 Criteria
simultaneously or cumulative over time
▪ Malar rash
▪ Discoid rash
▪ Photosensitivity
▪ Oral or nasal ulcers
▪ Arthritis (non-erosive, > 2joints)
● Present in the 1styr of diagnosis
● Painful or painless swelling, stiffness in the morning
● Symmetric polyarthritis (large & small joints)
▪ Serositis – pleurisy, pericarditis, peritonitis
▪ Renal manifestations
● Proteinuria or casts
● Renal biopsy (dx and stage disease)
▪ Seizure or psychosis
● Neuropsychiatric complications may occur w/ or w/o
apparently active SLE
▪ Hematologic manifestations
● Hemolytic anemia
● Leukopenia (<4000)
● Lymphopenia (<1500)
● Thrombocytopenia (<100,000)
▪ Immunologic abnormalities
● (+) anti ds DNA or anti-Smith AB
● False positive RPR test
● Positive lupus anticoagulant test
● Elevated anticardiolipin Ig or IgM Ab
(+) ANA is not required for diagnosis, but (-) ANA in SLE is rare
SLICC 2012 Criteria
▪ Inclusion of hypocomplementemia
▪ Addition of nonscarring alopecia
▪ Additional cutaneous and neurologic manifestations of lupus
▪ Positive direct Coombs test in the absence of hemolytic anemia
LABORATORY FINDINGS / DIAGNOSIS
ANA – 95-99% Sn; poor Sp (50%), poor screening tool
TREATMENT
Sunscreen and avoid direct sun exposure
anti dsDNA Ab
▪ More specific (98%)
▪ May correlate with disease activity especially in nephritis, (Sn
40-64%)
Hydroxychloroquine <6.5mkday (max 400mg daily)
▪ Recommended for all SLE patients if tolerated
▪ Prevents flares, improves lipid profiles, improve mortality and
renal outcomes
▪ Side effects: retinal pigmentation, impaired color vision (ophtha
q6-12mos)
Anti-Smith
▪ Specific (98%)
▪ Does not correlated with disease activity
↓ C3 and C4 in active disease
Hypergammaglobulinemia – common; nonspecific
Elevated inflammatory makers
▪ ESR
▪ CRP – elevation often correlates with infection, where chronic
mild elevation may indicate ↑ CV risk
Antiphospholipid Ab
▪ Indicate presence of anticardiolipin Ab, prolonged phospholipid
depended coagulation tests, and circulating lupus anticoagulant
▪ If it occurs, clotting + Antiphospholipid antibody → APAS (may
occur ± SLE)
Discoid rash biopsy: hyperkeratosis, follicular plugging,
infiltration of mononuclear cells into dermal-epidermal junction
(DEJ)
Lupus-band test: deposition of immune complexes with the DEJ
DIFFERENTIAL DIAGNOSIS
▪ Infections – sepsis, EBV, parvovirus B19, endocarditis
▪ Malignancies – leukemia, lymphoma
▪ Other rheumatic conditions – JIA, vasculitides
▪ Nephrotic Syndrome, PSGN
▪ Pleural or pericardial effusion
▪ Cardiopulmonary abnormalities
▪ New onset psychosis; movement/seizure disorder
MONITORING AND PREVENTION
▪ Monitor cholesterol, BP, and BMI
▪ Smoking prevention
▪ Immunization
● Annual flu
● PCV 13 for SLE >6yo → PPSV 23 after 2 months
NSAIDS – for arthralgia and arthritis
Corticosteroids – mainstay
▪ Limit dose and length of exposure
▪ SE: growth disturbance, weight gain, striae, acne, hyperglycemia,
HTN, cataracts, avascular necrosis, osteoporosis
▪ Severe disease: high dose IV Methylprednisone (30mkday,
max1g/day) for 3d sometimes ffd by a period of weekly pulses
and/or high dose oral prednisone 1-2mkday tapered overtime
Steroid sparing immunosuppressive agents
MTX, Leuflonamide, Azathioprine, MMF
▪ For persistent moderate disease – ↑ arthritis, significant
cutaneous or hematologic involvement and pleural disease
Cyclophosphamide, MMF, Azathioprine
▪ For lupus nephritis
MMF and Rituximab
▪ For significant hematologic manifestations – leukopenia, hemolytic
anemia, thrombocytopenia
Cyclophosphamide
▪ Reserved for severe renal, neuro and cardiopulmonary disease
▪ Hydrate to prevent hemorrhagic cystitis
▪ Other SE: cytopenia, premature gonadal failure, ↑ risk for
malignancy
CARRA Treatment Plan
▪ 6mos induction Tx 500-1000mg/m2 IV monthly or MMF
(600mg/m2 – 1500mg BID), + 1 of 3 standardized glucocorticoid
regimens
Lupus Nephritis maintenance
▪ Cyclophosphamide q3mos, or MMF or Azathioprine for 36mo after
induction therapy
Belimumab
▪ Monoclonal Ab vs Blys/BAFF FDA-approved for adult SLE →
improved markers of disease severity
Long-term anticoagulation
▪ SLE with APAS, with history of clot
PPS Oral Exam Reviewer 2020
Batch Clingy
Calcium and Vitamin D to prevent osteoporosis
158
▪ Circulating antihistone Ab – detected in only 20% of patients
with SLE
▪ Not likely to be (+) in antidsDNA, hypocomplementemia and
renal or neuro disease
▪ Hepatitis more common in drug-induced lupus
▪ Annular/macular rash (face) – often appears at birth or within
first 6-8 weeks of life, after exposure to UV light and lasts 3-4
months
▪ 25% may have cytopenia and hepatitis
Arthritis (>6wks) present
▪ Intraarticular swelling or presence of >2:
▪ Limitation of range of motion
▪ Tenderness/pain on motion
▪ Increased heat or erythema
Initial symptoms – subtle and acute
▪ Morning stiffness w/ a limp or gelling after inactivity
▪ Joints swollen, warm to touch, and painful on movement or
palpation with ↓ ROM but not erythematous yet
▪ Arthritis in large joints (knees) accelerates linear growth causing
limb length discrepancy
▪ Rapid and premature closure of the growth plate→ shortened
bones
▪ Recovery takes several months to years
COMPLICATION
Congenital Heart Block
▪ Most feared complication
▪ Diagnosed in utero: fetal echo at 16 weeks, period of greatest
vulnerability 18-24 weeks
▪ Fetal bradycardia from heart block → hydrops fetalis
▪ Mom with anti-RO/LA → treat with HCQ, steroids, or IVIg
JIA is a clinical diagnosis without any diagnostic laboratory test
Early x-ray findings
▪ Soft tissue swelling
▪ Periarticular osteoporosis
▪ Periosteal new bone apposition
Late
▪ Subchondral erosions
▪ Loss of cartilage with bone destruction
Changes in cervical spine
▪ C2-C3 may progress to atlantoaxial subluxation
DIFFERENTIAL DIAGNOSIS
▪ SLE, JD, sarcoidosis, vasculitic syndromes
▪ Scleroderma – limited ROM because of sclerotic skin overlying a
joint
▪ Acute rheumatic fever – exquisite joint pain and tenderness,
remittent fever, migratory polyarthritis
Goals: achieve disease remission, prevent joint damage, foster
normal growth
Other Management:
▪ Periodic slit lamp examinations to monitor for asymptomatic
uveitis; treatment: mydriatics and corticosteroids
▪ Dietary evaluation and counseling to ensure proper calcium,
vitamin D, protein, and caloric intake
▪ PT and OT
PROGNOSIS
Oligoarticular disease (OD)
Persistent OD – majority achieve remission
Extended OD – poorer prognosis
▪ OD in girls who are (+) ANA and onset of arthritis is <6yo →
greatest risk for chronic uveitis
▪ Uncontrolled uveitis – posterior synechiae, cataracts, glaucoma,
Batch Clingy
JUVENILE
IDIOPATHIC
ARTHRITIS
DRUG INDUCED LUPUS
▪ SLE manifestations triggered by exposure to minocycline,
anticonvulsants, sulfonamides, antiarrhythmic agents
▪ Procainamide and hydralazine – promote lymphocyte
hypomethylation causing lupus-like syndrome
▪ May trigger true SLE
▪ M=F
NEONATAL LUPUS
▪ Not an autoimmune disease of the fetus
▪ Passively acquired autoimmunity – maternal IgG autoAb cross
the placenta → fetal circulation
▪ Associated with maternal anti-RO (anti-SSA) and anti-LA (antiSSB) Ab or anti-RNP (antiribo-nucleoprotein) auto Ab
▪ 2% of offspring born to mothers (+) antiRO/LA develop neonatal
lupus
▪ Most common rheumatic disease in children
▪ Peak age of onset
● Oligoarticular: 2-4yo
● Polyarthritis (bimodal): 2-4yo, 10-14yo
● sJIA: 1-5yo
▪ Unknown etiology and pathogenesis → immunogenetic
susceptibility and external trigger – autoimmune, associated with
alterations in both humoral and cell mediated immunity
▪ T lymphocytes release proinflammatory cytokines (TNF-α, IL6,
IL1)
▪ B cell activation, immune complex formation, complement
activation → inflammation
▪ sJIA – dysregulation of the innate immune system with a lack of
autoreactive T cells and autoAb → inflammatory synovitis (villous
hypertrophy and hyperplasia with hyperemia and edema of the
synovial tissue)
▪ To prevent thrombotic events
ASA 81mg/day
▪ SLE with APAS, no history of clot
▪ HCQ, NSAIDS, steroids
▪ Resolves with removal of drug
PPS Oral Exam Reviewer 2020
159
▪ Autoimmune hepatitis – may have acute arthritis
▪ Transient arthritis cause by infections – Parvovirus B19, Rubella,
EBV, Hep B, HIV, Lyme disease
▪ Septic arthritis – fever with painful erythematous hot joint
▪ Isolated hip pain with limited motion: suppurative arthritis,
osteomyelitis, toxic synovitis, Legg Calve Perthes, slipped capital
femoral epiphysis
▪ ERA – tenderness over insertion of ligaments, tendons, and LE
extremity arthritis (esp if boy)
▪ Psoriatic arthritis – limited joint involvement (small joints of
hands and ankle)
▪ IBD – oligoarthritis, usually LE, with GI symptoms, elevations in
ESR and microcytic anemia
▪ Growing pains – 4-12yo leg pain in the evenings with normal
studies and no morning symptoms
▪ Leukemia or neuroblastoma – bone pain from infiltration of the
bone, synovium or bone marrow, nocturnal pain awakens child
from sleep (malignancy)
blindness
ORTHOPEDIC COMPLICATIONS
▪ Leg length discrepancy
▪ Flexion contractures (knees, hips, wrists)
▪ Psychosocial adaptations and problems may warrant counseling
*high ESR with leukopenia and low normal platelet count may be
a clue to underlying leukemia
SYSTEMIC JIA
▪ Arthritis + fever + prominent visceral
(hepatosplenomegaly, lymphadenopathy, and
pericarditis)
PPS Oral Exam Reviewer 2020
involvement
serositis –
▪ Partial response to NSAIDS
▪ If no or only partial response after 4-6 weeks, or with functional
limitations
(joint
contracture/leg-length
discrepancy)
→
intraarticular steroids (triamcinolone)
▪ Others require DMARDS like MTX or TNF inhibitors
PROGNOSIS
Polyarticular JIA – prolonged course of active joint inflammation,
requiring early aggressive Tx
Predictors of severe disease
▪ Young age at onset
▪ RF seropositivity or Rheumatoid nodules
▪ (+) Anti-cyclic citrullinated peptide antibodies
▪ Many affected joints (hand, hip, and wrist poorer prognosis)
Macrophage activation syndrome
▪ Secondary hemophagocytic syndrome or HLH
▪ Rare but fatal complication of sJIA
▪ sJIA/MAS and HLH share similar functional defects in granule-
▪ ↑ Inflammatory markers, WBC & PC
▪ ↓ Hgb (7-10), indices like anemia of chronic disease
▪ ↑ ESR (except in MAS)
▪ ANA and RF uncommon
Polyarticular or sJIA
▪ DMARDS (MTX) – oldest, least toxic adjunctive treatment; 6-12
weeks to see effect
▪ Failure of MTX monotherapy, add biologic DMARD → inhibit
cytokines like TNFα (Etanercept, adalimumab), IL-1, IL-6
▪ Early aggressive Tx w/ MTX + TNFα antagonist may result in earlier
achievement of clinically inactive disease
▪ Abatacept (selective inhibitor of T cell activation) & Tocilizumab
(IL-6 antagonist) effective and approved for polyarticular JIA
SJIA w/ dominant systemic symptoms
▪ Systemic steroids → IL-1 or IL-6 antagonist – dramatic, rapid
response
▪ Anakinra may be used for severe ds activity
Batch Clingy
OLIGOARTHRITIS (<4 joints)
▪ Often involves single joint, affects large joints of LE (knee,
ankles)
▪ Isolated involvement of the hip is almost never a presenting sign
(suggests Enthesitis-Related Arthritis)
▪ (+) ANA seropositivity – ↑ risk for chronic uveitis
POLYARTHRITIS (>5 joints)
▪ Both UE and LE
▪ RF (+) polyarthritis resembles the symmetric presentation of
adult RA
▪ Presence of rheumatoid nodules almost exclusively occur in RF
(+), associated with more severe course
▪ Micrognathia reflects chronic TMJ disease
160
▪ Most common inflammatory myositis in children, distinguished
by proximal muscle weakness and characteristic rash
▪ Genetic disposition (transfer of maternal chimeric cells) and
unknown environmental trigger (hx infection, URTI or GI, 3mos
before commonly reported)
▪ Peak onset 4-10yo
▪ Incidence 3/1 million/year
JUVENILE
DERMATOMYOSITIS
PATHOGENESIS
▪ Upregulation of gene products controlled by Type I interferon
(IFN)
▪ Inc susceptibility to JDM assoc with HLA alleles B8, DRB1*0301,
DQA1*0501, DQA1*0301 → may have prolonged exposure to
maternal chimeric cells and/or an unk environmental trigger →
upregulation of MHC class I expression and maturation of
dendritic cells
▪ Overexpression of MHC class I upregulates adhesion molecules
→ migration of lymphocytes → inflammatory infiltration of
muscle
dependent cytotoxic lymphocyte activity
▪ Acute onset of profound anemia, thrombocytopenia, or
leukopenia with high spiking fever, lymphadenopathy, and
splenomegaly
▪ Purpura and mucosal bleeding, prolonged PT and PTT, ↑ liver
enzymes, LDH, ferritin, TG
▪ ESR falls because of hepatic dysfunction
▪ BM biopsy: hemophagocytosis
▪ ↓ WBC and/or platelet with active SJIA
▪ Treatment: high dose IV Methylprednisolone, cyclosporine or
anakinra
Criteria for sJIA-associated MAS
▪ Hyperferritinemia (>684ng/mL) + any 2 of the ffg:
▪ Thrombocytopenia (<181x109)
▪ ↑ Liver enzymes (AST >48U/L)
▪ Hypertriglyceridemia (>156mg/dL)
▪ Hypofibrinogenemia (<360mg/dL)
▪ Rash, insidious onset of weakness, or both
▪ Fever, dysphagia or dysphonia, arthritis, muscle tenderness,
fatigue
Rash
▪ 1st symptom in 50% cases
▪ Extreme photosensitivity to UV light exposure with generalized
erythema in sun exposed areas (shawl sign → chest, neck)
▪ Erythema over knees and elbows
▪ Heliotrope rash – blue violet discoloration of eyelids associated
with periorbital edema
▪ Facial erythema crossing nasolabial folds (contrast to SLE, w/o
nasolabial)
▪ Gottron papules – bright pink or pale, shiny thickened atrophic
plaques over PIP and DIP joints, occasionally on knees, elbows,
ankle malleoli
▪ Mechanic’s hands (rare) – thickened erythematous and scaly
rash over palms and soles
▪ Telangiectasia, cutaneous ulcers
Weakness
▪ Insidious and difficult to differentiate from fatigue
▪ Symmetric, affecting proximal muscles (neck flexors, shoulder
girdle, or hip flexors)
▪ Difficulty climbing stairs, combing hair, getting out of bed,
inability to perform a sit up, head lag after infancy and Gower
sign
PPS Oral Exam Reviewer 2020
▪ ↑ Ferritin (>10,000ng/mL)
▪ Canakinumab (IL-B inhibitor) & Tocilizumab – for children >2yo
with sJIA
PROGNOSIS
sJIA’s poorer prognosis is related to:
▪ Polyarticular distribution of arthritis
▪ Fever >3mos
▪ ↑ Inflammatory markers (PC, ESR for >6mos)
Standardized consensus 4 Treatment Plan for sJIA
▪ Glucocorticoids, MTX, Anakinra/tocilizumab with optional GC use
in the latter 3 plans as indicated clinically
COMPLICATIONS
▪ Bone mineral metabolism and skeletal maturation affected in all
types JIA
▪ ↓ Bone mass (osteopenia), associated with ↑ disease activity
▪ Systemic steroids must be given only in severe systemic illness, as
bridge therapy while waiting for therapeutic response to DMARDS,
control uveitis.
▪ Oral Janus Kinase (JAK) inhibitors (tofacitinib, ruxolitinib) inhibit
JAK signaling pathways involved in immune activation and
inflammation.
Diagnostic Criteria
▪ Classic rash (heliotrope rash of the eyelids, Gottron papules)
▪ Plus 3 of the ff:
● Symmetric and proximal weakness
● Muscle enzyme elevation (>1) (CK, AST, LDH, Aldolase)
● EMG changes – myopathy, denervation, fibrillations, bizarre
discharges
● Muscle biopsy – necrosis and inflammation
▪ Some children present with classic rash but not apparent muscle
weakness or inflammation → AMYOPATHIC JDM or
dermatomyositis sine myositis – risk of progression to more
severe muscle involvement with long-term sequelae if untreated
(calcinosis and lipodystrophy)
LABS
▪ ↑ CK, aldolase, AST, ALT, LDH – reflect muscle inflammation
▪ ALT usually ↑ on initial presentation, CK level may be normal
▪ ESR usually N, RF usually negative
▪ CBC: anemia consistent with chronic disease
▪ ANA (+) in >80%
Myositis-associated antibodies (MAA)
▪ Ab to SSA, SSb, Sm, ribonucleoprotein (RNP) and dsDNA
negative
▪ May ↑ likelihood of overlap disease or connective tissue
myositis
Esophageal and respiratory muscles also affected (aspiration and
respiratory failure)
▪ Assess for dysphonia, nasal speech, palatal elevation with gag,
dysphagia, GERD
Myositis-specific antibodies (MSA)
▪ Positive results for anti-Jo-1, anti-Mi2, anti-p155/140, anti-NXP2
▪ More significant, help define distinct clinical subsets, may
predict development of complications
Lipodystrophy and calcinosis
▪ Associated with longstanding or undertreated disease
▪ Dystrophic deposition of calcium in SC plaques or nodules
MRI
▪ Identifies active sites of disease
▪ Increases sensitivity of muscle biopsy and EMG (both are
Corticosteroids – mainstay
▪ Stable – oral prednisone 2mkday (max 60mg/day)
▪ Severe, with resp or oropharyngeal weakness – high dose pulse
methylprednisolone (3omg/kg/day) for 3 days, max 1g/day with
ongoing weekly or monthly IV dosing along w/ daily oral steroids
prn
▪ Tapered over 12-24 months
Methotrexate
▪ Decreases length of treatment with steroids
▪ Weekly oral, IV, or SC (the lesser of 1mg/kg or 15mg/m2, max
40mg)
▪ Given with Folic acid
▪ SE: immunosuppression, blood count dyscrasia, chemical hepatitis,
pulmonary toxicity, side effects of folate inhibition (oral ulcers,
nausea, anemia)
Hydroxychloroquine
▪ Little toxicity, reduce rash, maintain remission
▪ 4-6mg/kg/day
▪ Monitor retinal toxicity q6mos
▪ SE – hemolysis with G6PD, GI intolerance, skin/hair discoloration
IVIg – adjunct treatment for severe disease, given at 2g/kg (max
70g) every 2 weeks for 3 doses then every 4 weeks PRN
For severe unresponsive disease: IVIg, MMF, cyclosporine and
cyclophosphamide
▪ OGT or NGT to avoid aspiration for those with pharyngeal
weakness
▪ PT and OT – integral; passive stretching → direct muscle
reconditioning for strength and range of motion
▪ Avoid sun exposure and apply sunscreen
▪ Vitamin D and calcium supplements – prevent osteoporosis
Batch Clingy
▪ Heat can evoke rash
▪ Koebner phenomenon – cutaneous hypersensitivity to
superficial trauma
▪ Arthritis usually polyarticular and destructive and includes hip,
cervical spine, and TMJ involvement
161
▪ Lipodystrophy (face and upper body), associated with metabolic
syndrome similar to PCOS with insulin resistance, hirsutism,
acanthosis, hypertriglyceridemia, and abnormal glucose tolerance
Vasculitis GI tract (rare)
▪ Crampy abdominal pain, pancreatitis, GI bleeding and potential
for intestinal perforation or infarction
nondiagnostic if not directed by MRI)
Muscle biopsy
▪ Evidence of disease activity and chronicity
Contrast swallow study
▪ Palatal dysfunction & risk of aspiration
PFT – respiratory weakness, restrictive
Radiographs – calcinosis along the fascial planes and within
muscles
COMPLICATIONS
▪ Due to prolonged and severe weakness
▪ Aspiration pneumonia and respiratory failure
▪ Bowel wall vasculitis
▪ Pathologic calcifications
▪ Draining lesions and nodules – cellulitis or osteomyelitis
PROGNOSIS
▪ Mortality rate less than 1%
DIFFERENTIAL DIAGNOSIS
If weakness w/o rash
▪ Polymyositis
▪ Infection related myositis (influenza A and B, coxsackie and
other viruses)
▪ Infections with prominent muscular symptoms: Trichinosis,
Bartonella, toxoplasmosis, staphylococcal pyomyositis
▪ Muscular dystrophies (duchenne and becker)
▪ Myasthenia gravis, GBS
▪ Endocrinopathies (hyper/hypothy)
▪ Mitochondrial myopathies
▪ Metabolic disorders (glycogen and lipid storage diseases)
▪ TNF receptor associated periodic syndrome (TRAPS)
▪ Transient rhabdomyolysis w/ myoglobinuria in blunt trauma and
crush injuries
▪ Myositis assoc w/ vaccinations, drugs, growth hormone and
GHVD
2 categories:
Juvenile localized scleroderma (JLS / morphea) – more common
in children (>95%), largely limited to the skin
Juvenile systemic sclerosis (JSSc) with multisystem organ
involvement
Linear scleroderma
▪ Predominantly a pediatric condition
▪ <8yo, F>M, after 8yo F=M
SCLERODERMA
▪ Combination of vasculopathy,
activation, and fibrosis
autoimmunity,
immune
▪ Triggers (trauma, infection, possibly subclinical GVH reaction
from persistent maternal cells) injure vascular endothelial cells →
increased expression of adhesion molecules → entrap platelets
and inflammatory cells → vascular changes (Raynaud
phenomenon and pulmonary hypertension)
▪ Inflammatory cells infiltrate area of vascular damage →
thickened artery walls → reduction in capillary numbers →
migration of macrophages and other inflammatory cells into
PPS Oral Exam Reviewer 2020
LOCALIZED
▪ Insidious erythema or bluish hue around an area of waxy
induration, → indurated hyper/ hypopigmented atrophic lesions
▪ Subtle erythema may be the only presenting sign
▪ Linear scleroderma – varies in size (from few cm to entire length
of extremity)
▪ Sometimes with arthralgias, synovitis, or flexion contractures
▪ Limb length discrepancies as result of growth impairment of
muscle and bone
▪ En coup de sabre – seizures, hemifacial atrophy, ipsilateral
uveitis, learning/behavioral changes
▪ 25% have extracutaneous symptoms
SYSTEMIC
▪ Insidious onset with prolonged course, periods of remission or
chronic disability/death
▪ Skin – early phase of edema spreads from dorsum of hands and
fingers then face
▪ ↓ Edema → induration and fibrosis of skin, loss of SC fat, sweat
glands, hair follicles
▪ Atrophic skin become shiny and waxy, flexion contractures
develop at elbows, knees and hips with secondary muscle
weakness and atrophy
▪ Skin ulceration –with subcutaneous calcification
Table 185.2 Provisional Criteria for Classification of JSSc
Major (Required)
▪ Proximal skin sclerosis/induration of the skin proximal to MCP
or MTP joints
Minor (At least 2 Required)
Cutaneous
Sclerodactyly
Raynaud phenomenon, nail fold capillary
Peripheral
abnormalities (telangiectasias), digital tip
vascular
ulcers
GI
Dysphagia, GER
Cardiac
Arrhythmias, heart failure
renal crisis, new onset arterial
Renal
hypertension
Pulmonary fibrosis (HRCT/ radiography),
Respiratory
↓ diffusing capacity for carbon monoxide,
pulmonary arterial HTN
Neurologic
Neuropathy, carpal tunnel syndrome
MSK
Serologic
Tendon friction rubs, arthritis, myositis
Antinuclear Ab—SSc – selective autoAb
▪ Superficial morphea – topical steroid or UV therapy
▪ Deeper structures – systemic therapy
JLS
▪ Methotrexate and steroids – prevent lesion extension → skin
softening, improved ROM of joints
Treatment plan:
● Weekly SC MTX at 1mg/kg (max 25mg)
● Weekly SC MTX at 1mg/kg (max 25mg) + either 3mo high-dose
IV CS (30mg/kg, max 1000mg) for 3 consecutive days a month or
weekly CS (same dose) for 3mo OR
● High-dose daily oral CS (2mkday, max 60mg) w/ slow taper
over 48 wk
▪ MMF – 2nd line agent for recalcitrant disease
▪ OT/PT
JSSc – target specific disease manifestation
▪ CCBs – Nifedipine 30-60mg SR daily, amlodipine 2.5-10mg daily
▪ ACEi – HTN with renal disease
▪ MTX and MMF – for skin manifestations
▪ Cyclophosphamide and MMF for pulmonary alveolitis and prevent
fibrosis
▪ Cautious use of CS in JSSc bec of association with renal crisis
Batch Clingy
▪ Presence of fibrosis on skin
Rash
▪ Confused with eczema, dyshidrosis, psoriaris, malar rash from
SLE
▪ Biopsy helpful to confirm diagnosis
▪ New classification major PLUS 2 of 20 minor criteria
162
Autoimmunity key process in pathogenesis of both types → (+)
ANA in 42% of children with localized disease, 47% of these have
antihistone Ab
(+) ANA in 80.7% of children with JSSc, 34% of these have anti-Scl70 Ab
Prevalence: 1/100,000
LS > JSSc (10:1 ratio, linear scleradema m/c type)
▪ Sclerodactyly – severe Raynaud phenomenon ulceration of the
fingertips with loss of tissue pulps and tapered fingers
▪ Acro osteolysis – resorption of the distal tufts of distal
phalanges
▪ Hyperpigmented post inflammatory changes with atrophy—salt
and pepper appearance
▪ Pulmonary disease – most common visceral manifestation, both
arterial and interstitial involvement (alveolitis)
▪ Asymptomatic to exercise intolerance, dyspnea at rest, right
sided heart failure
▪ Pulmonary HTN – poor prognostic sign
▪ Cardiac fibrosis → arrhythmia, ventricular hypertrophy & ↓
cardiac function
▪ GIT – esophageal and intestinal dysmotility – dysphagia, reflux,
dyspepsia, gastroparesis, bacterial overgrowth, dilated bowel
loops, malabsorption and FTT
▪ Renal – arterial disease can cause chronic or severe episodic
hypertension
Raynaud Phenomenon
▪ Most frequent initial symptom in pediatric systemic sclerosis,
70% of children months or years before other symptoms
▪ Classic triphasic sequence of:
● Blanching (initial arterial vasoconstriction)
● Cyanosis (venous stasis)
● Erythema of the digits (reflex vasodilation from factors
released from ischemia)
▪ Caused by cold weather or emotional stress, associated with
pain and paresthesia (immerse hands in cold water), may involve
thumbs, toes and ears
▪ Independent of Raynaud disease, connected to SLE, Scleroderma
▪ Begins in adolescence, symmetric occurrence, no tissue necrosis
and absence of periungal telangiectasia
▪ vs Acrocyanosis – vasospastic d/o resulting in cool, painless,
bluish discoloration in the hands and sometimes feet despite
normal tissue perfusion
▪ vs. Chilblains – episodic color changes and devt of nodules
related to severe cold exposure and spasm-induced vessel and
tissue damage; assoc w/ SLE
ANKYLOSING
SPONDYLITIS
And
OTHER
SPONDYLOARTHRITIDES
(Psoriatic Arthritis,
Arthritis of IBD)
▪ May be familial, HLA-B27 strongly associated with JAS (90%) and
50% of ERA patients, 7% healthy individuals
▪ Onset in older child, boy, oligo arthritis affecting hips, knees,
ankles, feet, with enthesitis, with inability to touch toes
PATHOGENESIS
▪ Susceptibility is largely genetically determined
▪ 30% heritability identified
▪ HLA-B27 responsible for 2/3 of the total and >100 additional
PPS Oral Exam Reviewer 2020
Raynaud disease
▪ Begins in adolescence
▪ Symmetric occurrence, absence of tissue necrosis and gangrene
and lack of manifestations of an underlying rheumatic disease
Distinguishing clinical manifestations in spondyloarthritis:
▪ Arthritis of the axial skeleton, sacroiliac joints, hips, enthesitis,
symptomatic eye inflammation (uveitis) and GI inflammation
(even in the absence of IBD)
▪ Enthesitis – inflammation at the sites of attachments of
ligaments, tendons, or joint capsule to bone
(anticentromere, antitopoisomerase I Scl70), antifibrillarin, anti-PM/Scl, antifibrillin,
or anti-RNA plumerase I or III
LABS
▪ No labs diagnostic for both types
▪ CBC, Serum Chem and UA usually normal
▪ May have ↑ ESR, Eosinophilia, hypergammaglobulinemia
▪ ↑ Muscle enzymes (aldolase) with muscle involvement
▪ JSSc – anemia, leukocytosis, eosinophilia, (+) ANA and anti-SCL
70 Ab
▪ Imaging – delineate affected area and can be used to follow
disease progression
MRI – en coup de sabre and Parry-Romberg syndrome (facial
hemiatrophy) to determine CNS/Orbital involvement
▪ PAH – pulmo testing (↓ VC), bronchioalveolar lavage, high
resolution chest CT (basilar ground glass opacities, reticular linear
opacities, honeycombing and mediastinal adenopathy → for
monitoring visceral involvement in JSSc
Tx for Raynaud phenomenon
▪ Cold avoidance
▪ Use hand and foot warmers
▪ Avoid carrying bags by their handles
▪ Nifedipine (10-20mg TID adult dose) reduces episodes
▪ Topical nitrates for digital vasodilation
PROGNOSIS
▪ LS – self-limited, ave period of stabilization 3-5yr → active disease
up to 20 years
▪ Prolonged diseases – disfigurement, disability with linear and deep
ds subtypes
▪ SSC – some rapidly progressive with early organ failure and death
▪ Most common cause of death – heart failure due to myocardial
and pulmonary fibrosis
DIFFERENTIAL DIAGNOSIS
▪ Differentiate LS from SSc
▪ Juvenile arthritis –with contractures, no skin changes
▪ Diabetic cheiroarthropathy
▪ Pseudoscleroderma – patchy or diffuse cutaneous fibrosis
without the other manifestations of sclerederma
▪ PKU, syndromes of premature aging, localized idiopathic fibrosis
▪ Scleredema – transient, self-limited after febrile illness (strep)
with patchy sclerodermatous lesions on neck and shoulders
▪ ↑ ESR and or CRP is variable and may or may not be present at
the onset of disease
▪ Mild increase in WBC and PC
▪ RF (-) in spondyloarthropathies
▪ ANA (-) except in psoriatic arthritis (50%)
▪ HLAB27 (+) in ~90% of Px w/ JAS
Conventional radiograph
▪ Detects chronic bony changes & damage but not active
inflammation
Goals
▪ Control inflammation, minimize pain, preserve function, prevent
ankylosis
▪ Anti-inflammatory meds + PT + education
SpA
▪ Monotherapy or combination with NSAIDS, DMARDS or biologic
agents
Batch Clingy
affected tissues → secretion of cytokines that induce fibroblasts
to reproduce and synthesize excessive amount of collagen =
fibrosis, lipoatrophy, loss of sweat glands and hair follicles
163
▪ Early changes in sacroiliac joint – distinct margins and erosions
→ joint space widening
▪ Sclerosis starts on iliac side of joint
▪ Bamboo spine – squaring of the corners of the vertebral bodies
and syndesmophyte formation in advanced disease
MRI
▪ Gold standard for early visualization of sacroiliitis – bone
marrow edema adjacent to the joint (Short T1 inversion recovery)
DIFFERENTIAL DIAGNOSIS
Reactive Arthritis
▪ Onset of arthritis after recent hx of diarrhea or symptoms of
urethritis or conjunctivitis
See Table 181.2 Etiologic Microorganisms of Reactive Arthritis
Lower back pain can be caused by any of the ff:
▪ Suppurative arthritis of the sacroiliac joint
▪ Osteomyelitis of the pelvis or spine
▪ Osteoid osteoma of the posterior elements of the spine
▪ Malignancies – osteogenic sarcoma, Ewing, or leukemia
Mechanical conditions:
Scheuermann disease
spondylolysis,
spondylo-listhesis,
Fibromyalgia
▪ Pain usually affecting soft tissue of the upper back in symmetric
pattern
▪ Well-localized tender points and sleep disturbance
ENTHESITIS-RELATED ARTHRITIS (ERA)
▪ 60% are males > females
▪ 20% have FHx of HLA-B27 associated disease (reactive arthritis,
AS, or IBD with sacroiliitis)
▪ Sacroiliac joint arthritis clinically or radiographically – in up to
40% of children
▪ 20% have evidence of sacroiliac joint arthritis at diagnosis
▪ Risk of sacroiliac joint arthritis is highest in children who are
HLA-B27(+) and ↑ CRP
PSORIATIC ARTHRITIS
▪ 5% of JIA
▪ Onset peaks at
● Preschool – F>M, ANA (+), at risk for asymptomatic ocular
inflammation
● Early adolescent years – M=F, arthritis is asymmetric, affects
<4 joints at presentation
▪ Enthesitis detectable in 20-60% of patients, more frequent in
older age
PPS Oral Exam Reviewer 2020
▪ 1st 6mos of disease – arthritis is asymmetric, involves <4 joints
(knees, ankles, hips)
▪ Tarsitis/inflammation of small joints of foot – highly suggestive
of ERA
▪ Enthesitis usually symmetric, affecting lower limbs
▪ Sacroiliac/axial joint involvement: inflammatory back pain, hip
pain, alternating buttock pain
▪ Pain with palpation of lower back or with pelvic compression
▪ Nail pitting, onycholysis, dactylitis
▪ DIP joint involvement uncommon but highly suggestive of
diagnosis when present
NSAIDS
▪ Naproxen 15-20mkday
▪ May slow progression of structural damage (syndesmophyte
formation and growth)
Intraarticular CS
▪ Triamcinolone hexacetonide
▪ Helps control peripheral joint inflammation
For moderate disease and JAS
▪ Add DMARDS (Sulfasalazine up to 50mkday, max 3g/day or MTX
10mg/m2) – may be beneficial for peripheral arthritis
▪ TNF inhibitors (etanercept, infliximab, adalimumab) – ↓
symptoms, improves function
▪ PT and Low impact exercise
PROGNOSIS
▪ Ongoing disease activity for >5yrs in juvenile spondyloarthritis
predicts disability
▪ Disease remission in <20% of children with SpA 5 years after
diagnosis
Factors affecting disease progression:
▪ Tarsitis
▪ HLA-B27 positivity
▪ Hip arthritis within the 1 st 6 months
▪ Disease onset after 8yo
Legg Calve Perthes disease (avascular necrosis of femoral head),
slipped capital femoral epiphysis, chondrolysis
▪ Pain over inguinal ligament and loss of internal rotation of the
hip joint but without SpA features (like involvement of enthuses
and/joints)
Children with either arthritis and enthesitis OR
arthritis OR enthesitis,
with at least 2 of the ff:
▪ Sacroiliac joint tenderness/inflammatory LS pain
▪ Presence of HLA-B27
▪ Onset of arthritis in a male >6yo
▪ Acute anterior uveitis
▪ FHx of an HLA-B27-assoc disease (ERA, sacroilitis w/ IBD,
reactive arthritis, or acute anterior uveitis) in a 1st deg relative
*Excluded: Patient with psoriasis (or FHx of psoriasis in a 1st deg
relative), (+) RF, systemic arthritis
Arthritis and psoriasis OR arthritis and at least 2 of the ff:
▪ Dactylitis
▪ Nail pitting or onycholysis
▪ Psoriasis in a 1st deg relative
▪ HLA-B27 positivity – highest risk of axial arthritis
Batch Clingy
genetic loci accounting for only 1/3
▪ HLA-B27 → tendency to misfold and form abnormal cell surface
structures.
▪ Infection with certain GI/GU pathogen can trigger reactive
arthritis
▪ Altered gut microbiota and abnormal immune response to
normal microbiota may play a role
▪ Inflamed joints & entheses in spondyloarthritis contain T & B
cells, macrophages, osteoclasts, proliferating fibroblasts and
osteoblasts w/ activation of the IL-23/IL-17 pathway
164
REACTIVE
and
POSTINFECTIOUS
ARTHRITIS
ARTHRITIS WITH IBD
▪ Presence of erythema nodosum, pyoderma gangrenosum, oral
ulcers, abdominal pain, diarrhea, fever, weight loss, anorexia in a
child with chronic arthritis → suspect IBD
REACTIVE ARTHRITIS
▪ Following enteropathic or urogenital infections
▪ Variable course
▪ May remit or progress to a chronic spondyloarthropathy
(ankylosing spondylitis)
PATHOGENESIS
▪ Follows enteric infection (Salmonella, Shigella, Yersinia,
Campylobacter or GU infection with C. trachomatis or E. coli and
C. difficile)
▪ 75%are HLA-B27 positive (RA represents autoimmune response
involving molecular mimicry
▪ Those HLA (+) have ↑ frequency of uveitis and extraarticular
features
▪ Incomplete elimination of bacteria and bacterial products such
as DNA
▪ Risk factor for persistent GI inflammation → ↑ risk that
individual will develop chronic spondyloarthritis
POSTINFECTIOUS ARTHRITIS
▪ Occurs after illnesses not in reactive arthritis group (Group A
strep, viruses), N gonorrhea, N meninigitidis, Hib type B,
Mycoplasma pneumonia
▪ Pain or joint swelling transient, <6 weeks
▪ Direct infection or generation and deposition of immune
complexes
PATHOGENESIS
▪ Viruses (rubella, varicella, herpes simplex, CMV) have been
isolated in joints of patients
▪ Antigens from Hep B and adenovirus have been identified in
immune complexes from joint tissue
Transient Synovitis (toxic synovitis)
▪ Affects hip, often after an URTI
▪ Boys 3-10yo
▪ Acute onset of severe pain in hip with referred pain to thigh or
knee (lasts one week)
▪ ESR and WBC usually normal
▪ Radio – widening of joint space 2o to effusion
▪ Aspiration of joint fluid often necessary to r/o septic arthritis
▪ Trigger presumed to be viral
PPS Oral Exam Reviewer 2020
▪ Arthritis usually lower extremities (often hips)
▪ Axial disease and inflammatory back pain less frequent at
disease onset
▪ Enthesitis and peripheral arthritis more common
2 patterns of arthritis in IBD
▪ Polyarthritis – large and small joints, reflects activity of intestine
inflammation
▪ Arthritis of the axial skeleton – ↑ sacroiliac joints
▪ Presents 3 days to 6 weeks after infection
▪ Reiter syndrome – arthritis, urethritis, conjunctivitis;
uncommon in children
▪ Arthritis is asymmetric, oligo, with LE predilection
▪ Dactylitis (inflammation of entire digit) may occur and enthesitis
(inflammation of tendons, ligmaents and joints attached to bone)
common
▪ Cutaneous manifestations – circinate balanitis, ulcerative
vulvitis, oral lesions, keratoderma blenorrhagica
▪ Systemic – fever, malaise, and fatigue
▪ Less common: conjunctivitis, optic neuritis, aortic valve
involvement, sterile pyuria, polyneuropathy
Modified New York criteria
▪ Radiographic changes in the sacroiliac joints – takes many years
to develop
▪ Clinical sequelae of axial disease – lags further behind
Criteria for axial spondyloarthritis (SpA)
▪ ≥3mos back pain and sacroiliitis on imaging PLUS
▪ 1 feature of SpA: inflammatory back pain, arthritis, enthesitis
(heel), uveitis, dactylitis, psoriasis, Chron disease/UC, good
response to NSAIDs, FHx of SpA, HLA-B27, or ↑ CRP
▪ (+) HLA-B27 – risk factor for the development of axial disease
▪ Diagnosis: history of recent GU or GI infection
▪ No specific test
▪ Trigger organism not typically found at the time arthritis is
present
▪ Imaging may be nonspecific or normal
▪ R/o other causes of arthritis
▪ ASO and anti-DNAse B (to document previous strep infection)
may help in Dx of postinfectious arthritis
▪ ↑ ESR and/ CRP is variable and may or may not be present at
the onset of disease
Radiology: Bamboo spine
▪ ESR and CRP may be markedly elevated
▪ Rubella and Hep B – affect small joints (esp knees)
▪ Mumps and Varicella involves large joints (knees)
▪ Hepatitis B arthritis-dermatitis syndrome – urticarial rash,
symmetric migratory polyarthritis, resembling serum sickness
▪ Rubella associated arthropathy – may follow natural rubella
infection or immunization, common in young women, arthralgia
of hands and knees within 7d of onset or rash or 10-28d after
immunization
▪ Parvovirus – arthralgia, symmetric joint swelling, morning
stiffness (older women)
▪ Varicella – may be complicated by suppurative arthritis,
secondary to Group A strep infection
▪ Post streptococcal arthritis
● Follow infection with Group A or Group G Strep
● Oligoarticular, affecting LE joints, mild sxs can persist for
months
● Differs from rheumatic fever – painful migratory arthritis of
brief duration
● Sometimes with valvular lesions on 2DED so considered an
incomplete form of RF
● HLADRB1*16 may predispose children to dev post-strep
arthritis or ARF
DIFFERENTIAL DIAGNOSIS
▪ Rheumatic fever – Group A streptococcus
▪ Non-suppurative arthritis
● Adolescent boys with severe truncal acne
● Fever, persistent infection of pustular lesions
● Pyogenic (sterile) arthritis, pyoderma gangrenosum, acne
(cystic) syndrome
● Autosomal dominant, mutation in PSTPIP1 gene
● Recurrent episodes may be associated with sterile myopathy
and may last for several months
▪ Infective endocarditis – associated with arthralgia, arthritis, with
signs of vasculitis (Osler nodes, Janeway lesions and Roth spots)
▪ Septic arthritis – acute arthritis affecting single joint
▪ Osteomyelitis – pain and effusion in adjacent joint, focal bone
pain and tenderness at the site of infection
▪ Infectious of autoimmune hepatitis – arthritis assoc with GI sx or
abn liver func tests
PROGNOSIS
▪ Disease progresses to involve joints of spine and sacroiliac joints
and may cause fusion and disability
▪ Usually unnecessary
▪ NSAIDS for pain and functional limitation
▪ Treating offending organism not warranted unless ongoing
Chlamydia infection is suspected
▪ Intraarticular steroids for refractory/severely injured joints may
be given once infection ruled out
▪ Physical activity and PT – may be added
▪ If postinfectious due to Strep – Penicillin prophylaxis for at least 1
year
PROGNOSIS
▪ Usually resolves w/o complication unless associated with other
organ involvement such as encephalomyelitis
▪ Reactive arthritis
● Uveitis, carditis
● May progress to chronic spondyloarthritis
▪ Persistent arthritis > 6 weeks → chronic rheumatic disease – JIA
or SLE
Batch Clingy
JUVENILE ANKYLOSING SPONDYLITIS (JAS)
▪ Onset <16yo
▪ Begins with oligoarthritis and enthesistis
165
Palpable purpura – hallmark
▪ Pink macules or wheals → petechiae, raised purpura or
ecchymoses, occasionally bullae and erosions develop
▪ Occur in gravity dependent areas
▪ Last 3-10d, may recur up to 4mos after initial presentation
▪ 90% cases in children between 3-10 years old
▪ M>F (1.2-1.8:1)
▪ Follow a documented URTI
PATHOGENESIS
▪ Unknown but common finding is IgA deposition, suggests IgA
mediation by IgA complexes
▪ Infectious triggers: GABHS, S. aureus, Mycoplasma, adenovirus
▪ Occasionally clusters in families → genetic component (HLA-B34
and HLA-DRB1*01)
▪ Subcutaneous edema – dorsum of hands and feet, periorbital
area, lips, scrotum, or scalp
▪ Musculoskeletal involvement – arthritis and arthralgias common
(75%); self-limited and oligoarticular (more of LE)
▪ Gastrointestinal (80%)
● Abdominal pain, vomiting, diarrhea, paralytic ileus, melena,
intussusception and mesenteric ischemia or perforation
● Purpura of intestinal tract
▪ Renal involvement (30%)
● Hematuria, proteinuria, HTN, frank nephritis, nephrotic
syndrome, acute or chronic renal failure
● ESRD uncommon
● Manifestations can be delayed for several months after the
initial illnsss → close ffup, serial UA
▪ Neurologic
● Due to HTN or CNS vasculitis
● Intracerebral hemorrhage, seizures, headaches, behavior
changes
▪ Others – orchitis, carditis, inflammatory eye disease, testicular
torsion, pulmonary hemorrhage
HENOCHSCHONLEIN
PURPURA
TAKAYASU
ARTERITIS
▪ Pulseless disease
▪ Chronic large vessel vasculitis of unknown etiology, involves
aorta and major branches
▪ 10-40yo, Asians, females (2-4:1)
Prepulseless phase (early)
▪ Fever, malaise, weight loss, HA, HTN, myalgia, arthralgias,
dizziness, abdominal pain
▪ HTN and Headache – most common presenting symptom
PATHOLOGY
▪ Inflammation of vessel wall → damaged elastic lamina and
media → blood vessel dilation and aneurysm formation
▪ Progressive scarring and proliferation→ stenotic vessels
▪ Subclavian, renal, carotid arteries m/c involved
▪ Pulmonary, coronary, and vertebral arteries also affected
▪ Some report no systemic symptoms and present with vascular
complications
PATHOGENESIS
▪ Etiology unknown
▪ Presence of abundant T cells with a restricted repertoire of
cellular immunity in TA vascular lesions → importance of cellular
PPS Oral Exam Reviewer 2020
Later manifestations
▪ Diminished pulses, asymmetric BP, claudication, Raynaud
phenomenon, renal failure, symptoms of pulmonary or vascular
ischemia
▪ Other findings: pericardial effusion, pericarditis, pleuritis,
splenomegaly, arthritis
▪ Inflammation of aortic valve – valvular insufficiency
▪ Clinical diagnosis → presence of typical rash
▪ No lab diagnostic
▪ Leukocytosis, thrombocytosis, mild anemia, elevations of CRP,
ESR
▪ Platelet count normal in HSP
▪ Occult blood (+) frequently
▪ Serum albumin may be ↓ due to renal or intestinal protein loss
▪ Renal assessment: BP, UA, creatinine
UTZ
▪ For GIT complaints
▪ Bowel wall edema or intussusception → barium enema (dx/tx)
Skin biopsy – leukocytoclastic vasculitis of dermal capillaries and
postcapillary venules
Renal biopsy
▪ Endocapillary proliferative glomerulonephritis (focal segmental
process to extensive crescentic involvement
▪ IgA deposition, deposition of C3, fibrin and IgM in a lesser
extent
DIFFERENTIAL DIAGNOSIS
▪ Other small vessel vasculitis, infection, acute PSGN, HUS,
coagulopathy, other acute intraabdominal processes
▪ Papular purpuric glove and sock syndrome
▪ SLE, other vasculitides (urticarial, hypersensitivity) and
thrombocytopenia
▪ Infantile acute hemorrhagic edema (AHE)
● Resembles HSP
● Cutaneous leukocytolastic vasculitis affecting infants <2yo
● Fever, tender edema of the face, scrotum, hands & feet,
ecchymosis on the face & extremities
● Trunk spared
● Petechiae in mucous membranes
● PC normal or elevated
● UA abnormal
● Biopsy may help in differentiating it with HSP
Table 192.5 proposed Classification Criteria for Pediatric-Onset
Takayasu Arteritis
Angio abnormalities (CT, MRI) of aorta and main branches and at
least ONE of the ff:
▪ ↓ Peripheral artery pulse and claudication
▪ BP diff bet arms and legs >10mmHg
▪ Bruits over aorta and major branches
▪ HTN (based on childhood normative data)
▪ Elevated acute phase reactant (ESR or CRP)
LABS
▪ Nonspecific
▪ ↑ ESR and CRP
▪ Other nonspecific markers of inflammation: leukocytosis,
thrombocytosis,
anemia
of
chronic
inflammation,
hypergammaglobulinemia
▪ Supportive
▪ Adequate hydration, nutrition, analgesia
Steroids – to treat significant GIT involvement or other lifethreatening manifestations
▪ IV methylprednisolone for 1-2 weeks → taper → reduce
abdominal pain and joint pain but does not alter overall prognosis
▪ Empiric use of Prednisone 1mkday for 1-2wks tapered
▪ Chronic HSP renal disease – azathioprine, cyclophosphamide,
mycophenolate mofetil
COMPLICATIONS
▪ GIT perforation
▪ ESRD <5% HSP nephritis
▪ Serial monitoring of BP and UA for 6mos after dx if presenting with
HTN or urine abnormalities
PROGNOSIS
▪ Excellent, acute self-limited course for an average of 4 weeks
▪ 15-60% with ≥1 recurrence within 4-6mos after dx
▪ Milder in each relapse
▪ Severe initial course higher risk for relapse
▪ Chronic renal disease develops in 1-2%
▪ <5% of those with HSP nephritis go on to have ESRD
Glucocorticoids
▪ Mainstay of treatment
▪ High doses (1-2mkday prednisone or MP IV) → gradual dose
tapering
▪ If TA progresses or recurs: MTX, Azathioprine
▪ Cyclophosphamide – for severe or refractory disease
▪ AntiHTN → control BP caused by renovascular disease
COMPLICATIONS
▪ Arterial stenosis, aneurysms, occlusions → ischemic symptoms →
life threatening
▪ Stroke, MI, renal impairment, limb threatening arterial disease
PROGNOSIS
▪ 20% has monophasic course with sustained remission
Batch Clingy
▪ Most common vasculitis in childhood
▪ Leukocytoclastic vasculitis and immune deposition in the small
vessels (skin), joints, GIT, and kidney
▪ IgA vasculitis – presence of vasculitis and predominance of IgA
deposits in small vessels
166
immunity → existence of specific but unknown aortic tissue
antigen
▪ Expression of IL1, IL6, TNFα higher in patients with TA
Subdiaphragmatic (aortic arch) disease
▪ CNS (stroke, transient ischemic attack) and cardiac (heart
failure, palpitations) symptoms
Infradiaphargmatic (mid-aortic syndrome) disease
▪ HTN, abdominal bruit, pain
Radiology
▪ To establish large vessel arterial involvement
▪ Gold standard – Arteriography of the aorta and major branches
including carotid, subclavian, pulmonary, renal, and mesenteric
branches → ID luminal defects, dilatation, aneurysm, stenoses
▪ MRA and CT angio also accepted
▪ 2DED for assessing aortic valvular involvement
▪ Serial vascular imaging necessary to assess response to
treatment
▪ Most suffer relapses
▪ Overall survival: 93% at 5yrs, 87% at 10yrs
▪ High risk for accelerated atherosclerosis
Batch Clingy
DIFFERENTIAL DIAGNOSIS
▪ Giant Cell Arteritis (temporal arteritis) – large vessel vasculitis in
older adults, rare in childhood
▪ Systemic infections, autoimmune conditions, malignancies
▪ Non inflammatory conditions causing large vessel compromise –
Fibromuscular dysplasia, Marfan syndrome and Ehler Danlos
PPS Oral Exam Reviewer 2020
167
Acute
Can be painful or painless
▪ Painful – stance phase is shortened as child decreases time on painful extremity
▪ Painless –underlying proximal muscle weakness or hip instability, stance phase is equal but the child leans or shifts the center of gravity over the involved extremity for balance
Bilateral disorder produces a waddling gait
Trendelenburg gait – weak abnormal hip adductors, in a single leg stance can be elicited when abductors are weak
DISEASE
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
Trauma – leading cause of death and disability in children >1yo →
r/o fracture
TRAUMA
LABORATORY FINDINGS / DIAGNOSIS
TREATMENT
*See Fracture*
CHILD ABUSE
▪ Suspected in non-ambulatory children with LE long bone
fractures
▪ Transverse fractures in long bones – most prevalent
▪ Corner fractures in metaphysic – most classic
S. aureus most common in all age groups
Fractures that suggest non accidental injury:
▪ Femur fractures in non-ambulatory children (<18mos)
▪ Distal femoral metaphysical corner fractures
▪ Posterior rib fractures
Scapular spinous process fractures
proximal humeral fractures
Full skeletal survey – demonstrates multiple fractures in various
stages of healing
▪ Subtle, non-specific → dependent on patient age
▪ Clinical suspicion
▪ Blood CS should be performed in all suspected cases
▪ ↑ WBC and differential, ESR, CRP
▪ Leukocyte and ESR may be normal during 1st few days of
infection and does not preclude diagnosis
Neonates
▪ Group B Strep & gram neg (E. coli) also common), Group A Strep
(<10%)
Neonates
▪ Pseudoparalysis or pain with movement
▪ Half do not have fever and might not appear ill
>6yo
▪ S. aureus, Strep, or Pseudomonas (puncture wounds of foot,
direct inoculation from foam padding of the shoe into
bone/cartilage → osteochondritis)
Older infants and children
▪ Fever, pain, localizing signs (edema, erythema and warmth)
▪ Limp or refusal to walk
Sickle cell patients – Salmonella and S. aureus
▪ Sickle cell <24mos - S. pneumoniae (declined incidence due to
PCV vaccine)
▪ Focal tenderness over a long bone
▪ Local swelling and redness – infection has spread out of
metaphysis into subperiosteal space
▪ Long bones involved – femur and tibia equally affected, UE (1/4
cases)
Bartonella henselae – osteomyelitis in pelvic & vertebral bones
OSTEOMYELITIS
Kingella kingae – 2nd most common cause in <4yo, esp in
subacute presentation, difficult to detect (PCR)
Atypical mycobacteria (also S. aureus and pseudomonas) in
penetrating injuries, implanted materials (orthopedic hardware)
Fungal infections as part of multisystem disseminated disease
(Candida osteomyelitis complicateting fungemia in neonates w/ or
w/o indwelling catheters)
-Blastomycosis in endemic areas
(+) Confirmed microbial etiology in 60% of cases of osteomyelitis,
blood culture (+) in 50% of patients
▪ Median age 6yo, boys>girls (boys’ behavior predisposing them to
traumatic events)
▪ Healthy children – hematogenous
▪ Minor closed trauma (30%) – common preceding event
▪ Infection of bone following penetrating injuries or open
PPS Oral Exam Reviewer 2020
Pelvic osteomyelitis – subtle findings like hip, thigh, or abdominal
pain
Vertebral osteomyelitis – back pain ± tenderness to palpation
overlying the vertebral processes
▪ Usually single site affected except neonates (2 or more bones)
Brodie abscess – children with subacute symptoms and focal
finding in metaphyseal area (usually tibia)
▪ Radiographic lucency and surrounding reactive bone
▪ Contents are usually sterile
▪ Some patients with osteomyelitis (S.aureus) develop DVT
adjacent to affected bone which can produce septic pulmonary
emboli
▪ Mandatory reporting to social welfare agencies
Radiographic findings on some systemic disease that mimic signs
of child abuse: Osteogenesis imperfecta, Osteomyelitis, Caffey
disease, fatigue fractures
Xray
▪ Initial evaluation to exclude trauma and foreign bodies
▪ Within 72hrs, can show displacement of deep muscle planes
from adjacent metaphysis caused by deep tissue edema
▪ Lytic bone changes not seen until 30-50% bony matrix destroyed
▪ Tubular long bones do not show lytic changes 7-14 days after
onset of infection
CT
▪ Can demonstrate osseous and soft tissue abnormalities, ideal for
detecting gas in soft tissues
▪ Poor sensitivity for detecting osteomyelitis
MRI
▪ Most Sn and Sp
▪ Best for identifying abscess and differentiating bone from soft
tissue infection
▪ Provides precise anatomic detail of subperiosteal pus and
accumulation of purulent debris (bone marrow and metaphysis)
for possible surgical intervention
Acute osteomyelitis – purulent debris and edema appear dark with
↓ signal intensity on T1 weighted images, fat appear bright
Cellulitis and sinus tract – areas of high signal intensity on T-2
weighted images
Short tau inversion recovery (STIR) MRI – rapid imaging for
osteomyelitis
Radionuclide
Neonates
▪ MSSA, Group B strep, Gram neg bacilli
▪ Nafcillin or Oxacillin (150-200mkday q6 IV) + Cefepime (100150mkday q12)
▪ If MRSA – Vancomycin 45mkday q8 (gold standard for invasive
MRSA)
▪ If preterm or with vascular catheter – cover for nosocomial
(gram neg enteric, Pseudomonas or S. aureus, fungal (Candida)
Older infants and children
▪ S. aureus, K. kingae, group A step
▪ MSSA – nafcillin or Cefazolin (150mkday q6) - parenteral
treatment of choice, backbone of empirical treatment for acute
hematogenous osteomyelitis
▪ Critically ill, high local prevalence of CA-MRSA infection, add
Vancomycin to a beta-lactam
▪ Clindamycin (40mkday q6) alternative to susceptible MRSA and
MSSA when beta-lactam cannot be used (allergy), anaerobic
coverage
▪ S. pneumonia – Penicillin first line
▪ If resistant to penicillin, cefotaxime or ceftriaxone
Sickle cell with osteomyelitis
▪ Salmonella, S. aureus
▪ Cefepime (150mkday q8) + Vancomycin/ Clindamycin
Immunocompromised
▪ Vancomycin + Ceftazidime,
Aminoglycoside
▪ K. kingae – Cefazolin (<4yo)
Cefepime
or
Pip-tazo
±
▪ Duration of antibiotic individualized, based on clinical
improvement, culture growth/ isolates
Batch Clingy
Fractures – 2nd most common manifestation of child abuse (after
skin injury e.g. bruises, burns, abrasions)
168
fractures, or surgery
▪ In suspected bone infections esp in early course, alternative to
MRI (esp if multiple foci suspected)
▪ Technetium 99 methylene diphosphonate accumulates in areas
of ↑ bone turnover
▪ Increased uptake, 3 phase imaging
▪ Sn 84-100%, Sp 70-96% in hematogenous osteomyelitis and can
detect osteomyelitis within 24-48h after onset of symptoms
▪ Sn in neonates lower bec of poor mineralization
▪ Advantage: infrequent need for sedation, can image entire
skeleton for detection of multiple foci
▪ Disadvantage: radiation exposure, inability to image surrounding
soft tissues, overall lack of detail
PATHOGENESIS
▪ Anatomy and circulation of long bones – localization of blood
borne bacteria
▪ Metaphysis has low velocity blood flow predisposing to bacterial
invasion → bacterial focus, phagocyte migration → inflammatory
exudate (metaphyseal abscess) → ↓ O2 tension, ↓ pH, osteolysis,
tissue destruction → pressure ↑ spread via haversian system and
Volkmann canals into subperiosteal space
▪ Purulence = impairment of blood supply to cortex and
metaphysis
NB – transphyseal blood vessels connect metaphysis and
epiphyses → pus from metaphysis may enter joint space →
potential for abnormal growth and bone or joint deformity
Late childhood more adherent → pus decompresses through
periosteum
Late adolescent – hematogenous osteomyelitis begins in the
diaphysis → entire intramedullary canal
▪ Septic arthritis + osteomyelitis may be seen in older children w/
S.aureus osteomyelitis → simultaneous hematogenous
inoculation of bone and joint space
SEPTIC ARTHRITIS
▪ Pain in groin, anterior thigh, or knee, which may be referred
from the hip
▪ Able to bear weight on affected limb, usually ambulatory with
antalgic gait with foot externally rotated
▪ Afebrile or with low grade fever
If with venous thrombosis – anticoagulant
Surgery – drainage when there is frank pus, removal of sinus tract
or sequestrum in chronic osteomyelitis if present
PT – preventive, start 2-3days after pain decreases, cast when
there is potential for pathologic fracture
PROGNOSIS
▪ CRP normalizes within 7 days after treatment starts
▪ ESR drops after 10-14 days
▪ On ff up, monitor ROM and bone length
▪ Symptomatic treatment
▪ Activity limitation and relief of weight bearing
▪ Anti-inflammatory agents and analgesics can shorten duration of
pain
▪ Recovery usually within 3-6 weeks
▪ Prevalent in 3-8yo (but present in all age groups)
▪ 70% with recent URTI 7-14 days before symptoms
▪ S. aureus – most common cause in all age groups
▪ MRSA (>25%), Group A Strep, Strep pneumonia (10-20%, most
likely in <2 yrs old)
▪ Kingella kingae in <4yo (culture and PCR detection)
▪ Gonococcus – sexually active adolescents, septic arthritis, and
tenosynovitis usually of small joints or as monoarticular infection
of a large joint (knee)
▪ N. meningitides may occur on the first few days of illness, or a
reactive arthritis several days after antibiotic initiation
▪ Neonates – Group B Strep
▪ Fungal infection as part of multisystem disseminated disease
Candida arthritis can complicate systemic infection in neonates
with or without indwelling vascular catheters
▪ Primary viral infections of joints are rare, arthritis may
accompany viral syndromes (parvovirus, mumps, rubella live
PPS Oral Exam Reviewer 2020
▪ CRP and WBC normal
▪ May have mild elevation of ESR
▪ Monoarticular
▪ Signs and symptoms depend on age of patient
Neonates and infants – subtle, septic arthritis can be caused by
adjacent osteomyelitis, transphyseal spread
vs osteomyelitis – pseudoparalysis or pain limiting voluntary
movement of affected extremity (diaper changes)
Older infants and children – fever and pain
▪ Localizing signs – swelling erythema, warmth of affected joint
▪ Limp or refusal to walk
▪ Erythema and edema – seen earlier in SA than osteo because
synovium more superficial, metaphyses deeper (except SA of hip,
because hip joint deep)
Lyme arthritis – more prominent joint swelling, disproportionate
Xray (AP and Lauenstein (frog leg) lateral) of pelvis, usually normal
Hip UTZ -preferred to xrays, demonstrates joint effusion
▪ ↑ WBC, differential, ESR, CRP
▪ Most children will have normal leukocyte counts and ESR at
presentation → do not preclude dx of SA
▪ Blood cultures in all cases, positive in 20%
▪ Obtain cervical, anal and throat cultures when gonococcus is
suspected
UTZ-guided aspiration of joint fluid/pus for GS/CS – best
specimen for bacteriologic culture
PCR – best method to determine K. kingae in synovial fluid
Synovial fluid analysis – >50k-100k cells/mm3 indicate infectious
process
CRP monitoring – assessment of response to treatment
▪ CRP >10-13mg/dL seen in adjacent infections complicating septic
arthritis
XRAY – widening of joint capsule, soft tissue edema, obliteration
Neonates
▪ S. aureus, GBS, Gram neg: Nafcillin or Oxacillin (150-200mkday
q6 IV) + Cefepime (100-150mkday q12)
▪ If MRSA, Vancomycin (15mkday q6)
▪ If preterm or with vascular catheter – consider Pseudomonas or
fungal coverage
Older children
▪ Empiric treatment (S. aureus, Strep, K. kingae): Cefazolin (100150mkday q8) or Nafcillin (150-200mday q6)
▪ Ill appearing, suspected to be bacteremic, local clindamycin
resistance is 10-15% – Vancomycin
▪ CA-MRSA – Clindamycin (40mkday q6)
▪ Immunocompromised – Vancomycin + Ceftazidime, Cefepime,
or Piptazo ± aminoglycoside
Batch Clingy
TRANSIENT
MONOARTICULAR
SYNOVITIS
(Toxic Synovitis)
▪ Reactive arthritis that affects the hip, one of most common
causes of hip pain in young children
▪ Etiology unknown
▪ Nonspecific inflammatory condition
▪ Postviral immunologic synovitis
DIFFERENTIAL DIAGNOSIS
▪ Cellulitis and trauma (accidental or abuse) most common
▪ Myositis or pyomyositis –fever, warm swollen extremities and
limping, tenderness more diffuse
▪ Pyomyositis – pelvis common site, distinguish from pelvic
osteomyelitis, do MRI, often caused by S.aureus and group A strep
● Any child with (-) xray, (-) hip aspiration, with fever, limp and
↑ inflammatory markers should be evaluated for pyomyositis
▪ Iliopsoas abscess – thigh pain, limp, fever
▪ Pelvic osteomyelitis vs appendicitis, UTI and gynecologic disease
▪ Leukemia – bone pain and joint pain early sx
▪ Neuroblastoma – if with bone involvement can be mistaken for
osteo
▪ Ewing sarcoma – no fever
▪ Diagnosis is clinical
▪ r/o Septic arthritis first! –appear more systematically ill, more
severe pain, child refuses to walk or move their hip at all → high
fever, ↑ CRP or ESR, WBC → UTZ-guided aspiration of the hip
joint
▪ S. aureus – 21-28 days if with improvement in 5-7 days, if not
total of 4-6 weeks (slower resolution of symptoms or
normalization of CRP)
▪ IV to oral antibiotics if afebrile >48-72hrs, resolved bacteremia
▪ Cephalexin (100-150mkday q8) or Clindamycin (30-40mkday q8)
169
vaccines) → immune mediated pathogenesis
▪ Microbial etiology confirmed in 65% of cases
▪ Common in young children, 2-5yrs old
▪ Adolescents and neonates at risk for gonococcal septic arthritis
PATHOGENESIS
▪ Most are hematogenous
▪ Hematogenous seeding of synovial space (rich vascular supply)
→ bacterial products within joint space stimulates cytokine
production (TNF-a, IL-1) → inflammatory cascade → destruction
of cartilage and synovium → ↑ pressure compromise vascular
supply → necrosis
▪ Less common → follow penetrating injuries, arthroscopy,
prosthetic joint surgery, intraarticular steroid injection,
immunocomp pxs with rheuma joint disease
to the relatively lesser degree of pain and limited range of motion
when compared with suppurative arthritis
▪ Predilection for large joints (knees, hips), monoarticular or
pauciarticular at presentation
▪ Joints of LE (75% of SA)
▪ Elbow wrist and shoulder (25%)
of normal fat lines
▪ Hip – medial displacement of obturator into pelvis (obturator
sign)
UTZ – highly sensitive in detecting joint effusion and fluid in soft
tissue and subperiosteal regions, help in aspiration of hip
CT/MRI – useful to check joint fluid, MRI used to exclude adjacent
osteomyelitis/pyomyositis
Radionuclide – more sensitive than x-ray, may be positive 2d
before onset of symptoms, useful for sacroiliac joint
DIFFERENTIAL DIAGNOSIS
Hip
▪ Toxic synovitis
▪ Legg Calve Perthes disease
▪ Slipped capital femoral epiphyses
▪ Psoas abscess
▪ Proximal femoral, pelvic osteomyelitis
Knee
▪ Distal femoral or tibial osteomyelitis
▪ Pauciarticular JRA
▪ Usually 10-14 days for Streptococci, K. kingae
Longer (3 weeks) for S. aureus and gram neg infections
▪ 4 weeks if with concomitant osteomyelitis, extensive disease,
slow response to treatment
▪ Plain radiograph of joint before completing tx can provide
evidence (periosteal new bone) of a previously unappreciated
contiguous site of osteomyelitis → prolong antibiotic tx
▪ Shift to oral antibiotics for completion of tx once afebrile for 4872 hours and clearly improving
Surgical
▪ Infection of hip – surgical emergency (vulnerable blood supply
head of femur)
▪ Other joints – daily aspiration synovial fluid
▪ Arthrotomy or video assisted arthroscopy
PROGNOSIS
▪ Recurrence and devt of chronic infection after treatment occur
in <10% of patients
▪ Long term squelae (<5%): leg-length discrepancy, angular
deformity from growth arrest, limitation of ROM (chrondral
damage and avascular necrosis of the femoral head from septic
arthritis of the hip)
▪ Long term ff up, ROM and bone length
Batch Clingy
▪ r/o trauma, cellulitis, pyomyositis, Sickle cell disease, hemophilia
and HSP
▪ Several joints involved – collagen vasc diseases, HSP, RF, reactive
arthritis, IBD
Dexamethasone for 4 days – adjunct tx w/ antibiotics to ↓
duration of fever and promote more rapid decline in inflammatory
markers – not routine
PPS Oral Exam Reviewer 2020
170
Complex
ETIOLOGY / INCIDENCE / PATHOGENESIS
CLINICAL MANIFESTATIONS
Classification
Acetabular dysplasia – abnormal morphology and development of
acetabulum
▪ Hip sublaxation – partial contact between the femoral head &
acetabulum
▪ Hip dislocation – hip w/o contact between the articulating surfaces of
the hip
Neonate
▪ Asymptomatic, use maneuvers
▪ Barlow – assess dislocation, adduct flexed hip push posteriorly, if
positive- hip will slide out of acetabulum
▪ Ortolani – abduct flexed hip, if (+) femoral head will slip into pocket
▪ Hip click – high pitched sound at end of abduction after Barlow &
Ortolani
2 groups
▪ Typical – normal pxs w/o syndromes or genetic conditions
▪ Teratologic – identifiable causes like arthrogryposis & genetic
syndrome & occur before birth
Infants
▪ 2nd & 3rd month—tighter tissues
▪ Limited hip abduction, shortening of thigh, proximal location of greater
trochanter, asymmetry of gluteal folds, positioning of the hip
▪ Limitation of abduction – most reliable sign of dislocated hip
▪ Galeazzi sign – shortening of the thigh, both hips in 90 o of flexion vs.
height of the knees, asymmetry
▪ Klisic test – place 3rd finger over the greater trochanter and index finger
on the ASIS → (+) if trochanter elevated, line projects halfway between
umbilicus and pubis
▪ Etiology remains unknown
▪ ↑ Laxity of joint, fails to maintain a stable femoroacetabular
articulation → affected by hormonal, mechanical & genetic factors
▪ FHx of DDH in 12-33%
▪ More common in females (80%, & their greater susceptibility to
maternal hormone relaxin)
DEVELOPMENTAL
DYSPLASIA OF THE HIP
SKELETAL DYSPLASIAS
RISK FACTORS
▪ Any condition that leads to a tighter intrauterine space
(oligohydramnios, large BW, first pregnancy)
▪ High association w/ intrauterine molding abnormalities (torticollis,
metatarsus adductus) → crowding phenomenon has a role in the
pathogensis
▪ Left hip commonly affected
PATHOGENESIS
▪ Fatty tissue in the depths of the socket (pulvinar) & the ligamentum
teres can hypertrophy → blocked reduction of femoral head
▪ Transverse acetabular ligament thickens → narrows opening of
acetabulum
▪ Shortened iliopsoas tendon becomes taut across the front of the hip →
hourglass shape to the hip capsule → limited access to acetabulum
▪ Dislocated femoral head places pressure on the acetabular rim and
labrum→ infolds & becomes thick
▪ Longer time hip spends dislocated → abnormal devt of acetabulum →
progressively shallow, oblique acetabular roof and a thickened medial
wall
Genetic skeletal disorders
▪ Chondroosteodysplasias – skeletal/bone dysplasia
▪ Metabolic bone conditions – rickets, hyopophosphatasia
▪ Dysostoses – affect single bone (craniosynostosis)
▪ Other skeletal malformation
Chondroosteodysplasias
▪ 1 in 4000 births
▪ Mutations of chondrodysplasia genes
▪ Types:
● Chondroosteodysplasia – genetic d/o of cartilage, deficient linear
PPS Oral Exam Reviewer 2020
LABORATORY FINDINGS / DIAGNOSIS
Ultrasound
▪ Diagnostic modality of choice for DDH before
appearance of femoral head ossifies (4-6oms)
▪ Neonates – PE better than UTZ ( incidence of false (+)
▪ Used to monitor acetabular devt in infants in Pavlik
harness
▪ Most authors recommend screening in infants at risk
(breech, family hx, torticollis), regardless of clinical
findings
X-ray (AP) recommended at 4-6mos (after ossification)
COMPLICATIONS
▪ Avascular necrosis of the femoral head – most feared
▪ Abnormal growth & devt can occur
▪ Others: redislocation, residual subluxation, acetabular
dysplasia, post op complications (wound infections)
TREATMENT
▪ Obtain & maintain concentric reduction of femoral head
for normal devt
Newborns & infants <6mos
▪ Pavlik harness as soon as dx is made
▪ Significant proportion normalize within 3-4 weeks →
need to reexamine
▪ Pavlik harness manages acetabular dysplasia,
subluxation, or dislocation
▪ Hip instability resolves in approx. 75% of cases if
maintained on Ortolani-positive hip in a Pavlik harnesss
on a full-time basis for 6 wk
▪ After 6mos Pavlik not effective anymore, >50% failure
rate
▪ Set to maintain hips in flexion, if not reduced in 3-4
weeks → d/c harness
Children 6mos to 2 years old
▪ Goals of treatment in late-dx dysplasia: obtain &
maintain reduction of the hip w/o damaging the femoral
head
▪ Closed reductions – OR under GA
▪ Maintained after in a well molded spica cast in
moderate flexion and abduction
▪ Removal of cast after 12 weeks
▪ If unsuccessful → open reduction
The walking child
▪ Limp or waddling gait, or leg length discrepancy
▪ Affected side shorter, child toe walks on affected side
▪ Trendelenburg sign (+) – abductor lurch observed when child walks
▪ Galeazzi sign – limited hip adduction on affected side, knees at
different levels when hips are flexed
▪ Excessive lordosis – common & often presenting complaint
Children > 2 years old
▪ Require open reduction
▪ Concomitant femoral shortening osteotomy performed
to reduce pressure off femur and minimize risk of
osteonecrosis
▪ Post op, immobilized in spica cast for 6-12 weeks
Metaphyseal dysplasia – short stature, bowing of the legs and waddling
gait, normal serum Ca, PO4, ALP activity and Vit D metabolites
Jansen type – cupped and ragged metaphyses → mottled calcification at
the distal ends of bone overtime
Schmid type – less severe, radiograph resembles signs seein in familial
hypophosphatemia; defects in collagen type X, alpha 1 and hip abnormal
more debilitating
▪ History, PE matched with disproportionate clinical
features and clinical phenotypes of well-documented d/o
▪ Radiographs → skeletal survey
▪ Molecular genetic testing – FGFR mutation in
achondroplasia; used for prenatal diagnosis as well for
future pregnancy planning
▪ Once correct Dx is established → prognosis and
anticipation of medical and surgical problems
▪ Lifesaving measures discussion over poor prognosis
cases (thanatophoric dysplasia or achondrogenesis types
Ib or II)
▪ Mgt directed at preventing and correcting skeletal
deformities,
treating
nonskeletal
complications,
providing genetic counseling and helping patients and
families learn to cope.
Batch Clingy
DISEASE
171
growth → achondroplasia; generalized skeletal abnormal with nonskeletal tissue
● Osteodysplasia – abnormal bone structure → OI
Table 714.2 Major Problems Associated with Skeletal Dysplasias
Table 714.4 Lethal neonatal dwarfism
▪ Avoidance of contact sports or activities that cause
injury or stress to joints
PATHOPHYSIOLOGY
Chrondrodysplasia mutations act through cartilage matrix proteins →
dominant negative mechanism (protein products of mutant allele
interfere w/ assembly and function of multimeric molecules containing
protein products of both normal and mutant allele)
▪ Type II collagen gene COL2A1 forms the mutant & normal chains
▪ Mutations disrupt endochondral ossification affecting linear growth of
skeleton
Disorders involving cartilage matrix protein
▪ Spondyloepiphyseal dysplasia/type 2 collagenopathies
● Lethal spondyloepiphyseal dysplasia
● Spondyloepiphyseal dysplasia congenita – head & face normal, cleft
palate common, short neck, barrel chest, club foot & hypotonia
▪ Kniest Dysplasia – flat face, prominent eyes, enlarged joints, cleft
palate, club foot, hearing loss, myopia, retinal detachment common
complication
▪ Late onset Spondyloepiphyseal dysplasia – mild epiphyseal & vertebral
abnormality on x-ray
▪ Aggrecan-related spondyloepiphyseal dysplasias
▪ Stickler syndrome/dysplasia - associated with Pierre Robin anomaly
▪ Schmidt metaphyseal dysplasia
▪ Pseudoachondroplasia and multiple epiphyseal dysplasia
▪ Controversial on surgical limb lengthening, human
growth hormone, C-natriuretic peptite to promote linear
bone growth
Table 714.5 Nonlethal dwarfing conditions Recognizable
at Birth or within 1st few mos of life
Growth
▪ Disproportionate short stature (limbs vs trunk; lt/ht below 3rd
percentile)
▪ Shortening of limbs: UE do not reach mid-pelvis in infancy or upper
thigh after infancy
▪ Rhizomelic shortening –greatest in proximal segments
▪ Mesomelic shortening – involves hands and feet
▪ Shortening of trunk: short neck, small chest, protruberant abdomen
Non-growth-related manifestations
▪ Abn joint mobility, protruberence at and around joints and angular
deformities (symmetric)
▪ Spinal cord compression in achondroplasia, shor ribs reduce thoracic
volume → breathing compromise (chondrodysplasia)
▪ Cleft palate common → defective palatal growth
▪ Retinal detachment (spondyloepiphyseal dysplasia congenita), sex
reversal (campomelic dysplasia), congenital heart malformations (Ellisvan Crevald Syndrome), immunodeficiency (cartilage-hair hypoplasia),
renal dysfunction and asphyxiating thoracic dysplasia
Family and Reproductive History
▪ Mendelian inheritance pattern
▪ Attention to mild degrees of short stature, disproportion, deformities
& others (precocious osteoarthritis) that may have been overlooked
▪ Previous stillbirths, fetal losses, other abn pregnancy outcomes from
skeletal dysplasia, polyhydramnios, reduced fetal movt
▪ Mostly genetic, but common to have no FH of the d/o
Batch Clingy
Disorders involving Transmembrane Receptors
Mutations in FGFR3 & PTHR1
Achondroplasia
▪ Thanatophoric dysplasia
● Large head very short limbs, polyhydramnios, premature delivery
● Kleeblattschadel – cloverleaf skull
● Severe respiratory distress due to small thorax, poor prognosis
▪ Achondroplasia
● Short limbs, long narrow trunk, large head w/ midfacial hypoplasia,
prominent forehead
● Delayed motor milestones (hypotonia, mechanical difficulty
balancing → exaggerated lumbar lordosis, intelligence normal)
▪ Hypochondroplasia
● Milder than achondroplasia, not apparent until childhood, stocky
build, slight frontal bossing, may have learning disability
Jansen Metaphyseal dysplasia
▪ Rare, severe shortening of limbs, unusual facial appearance,
sometimes with clubfoot and hypercalcemia (serum 13-15mg/dL)
▪ Normal epiphyses, enlarged joints, limited mobility → flexion
contractures, bent over posture
▪ Normal intelligence, ± hearing loss
▪ Diet preventing obesity
▪ Dental care to minimize crowding and malalignment of
teeth
▪ Participation in Support Groups
PPS Oral Exam Reviewer 2020
172
Disorders involving transcription factors
Campomelic dysplasia
▪ Bowing of long bones, short bones, respi distress, anomalies of cervical
spine, Pierre-Robin sequence, CNS, heart, kidneys anomalies
▪ Karyotyping in females, SOX9 importance in gonadal differentiation
Cleidocranial dysplasia – drooping shoulders, open fontanelles,
prominent forehead
Nail-patella syndrome
▪ Nail dysplasia, patellar hypoplasia, elbow abnormalities, spurs →
osteo-onychodysostosis
▪ 30% with chronic glomerulonephritis (proteinuria ± hematuria) →
ESRD (5%)
Disorders involving defective bone resorption
Osteopetrosis – macrocephaly, hepatosplenomegaly, deafness,
blindness, severe anemia, diffuse bone sclerosis and hypocalcemia
▪ X-ray: bone within bone appearance
▪ FTT, psychomotor delay, cranial neuropathies, anemia
Pyknodysostosis
Osteoporosis – fragility of the skeletal system & susceptibility to
fractures of the long bones / vertebral compressions from mild or
inconsequential trauma
Osteogenesis imperfecta – brittle bone disease
▪ Most common genetic cause of osteoporosis
▪ Structural or quantitative defects in type I collagen (1o component of
extracellular matrix of bone and skin) cause full spectrum of OI
OSTEOGENESIS
IMPERFECTA
ETIOLOGY
▪ Molecular defect in type 1 collagen
▪ Overmodified collagen due to recessive null mutations in any of the 3
components of the collagen (coded by LEPRE1 gene on chromosome
1p34.1) or its assoc protein CRTAP or cyclophilin B
▪ Defective genes w/ protein products that interact w/ type 1 collagen
▪ Rare mutations in enzyme that processes the C-propeptide of type 1
collagen causes recessive form of OI → involved in osteoblast
differentiation, collagen synthesis and cross linking
▪ 1/20, 000 incidence
PPS Oral Exam Reviewer 2020
Other Inherited disorders of Skeletal Development
Ellis-van Creveld Syndrome
▪ Chondroectodermal dysplasia, ciliopathy
▪ Short limbs, postaxial polydactyly, knock-knee deformity, nail dysplasia, dental anomalies, ASD, CHD
▪ AR, common in Amish
▪ EVC1 or EVC2 gene mutation
▪ 30% die of cardiac or respi problems during infancy
Asphyxiating thoracic dystrophy
▪ AR, Jeune syndrome, ciliopathy
▪ Long narrow thorax & respi insufficiency (pulmo hypoplasia) → death
Short-rib Polydactyly Syndromes
Cartilage-hair Hypoplasia-anauxetic Spectrum disorders
▪ Flaring lower rib cage, prominent sternum, bowed legs, immunodefiency, malabsorption, celiac disease, hirschprung
Metatorophic dysplasia – tail like appendage base of the spine, odontoid hypoplasia, kyphoscoliosis compromising cardiopulmo function
Spondylometaphyseal dysplasia, Kozlowski Type
Disorders involving Filamins
Juvenile Osteochondroses
▪ Localized pain and tenderness: Freiberg disease, Osgood-Schlatter disease etc)
▪ Painless limitation of joint movt (Legg-Calve-Perthes disease)
Caffey Disease (infantile cortical hyperostosis)
▪ Sudden irritability, swelling of contiguous soft tissue preceding cortical thickening of bones, fever, anorexia, painful swelling w/ wood-like induration but minimal warmth & redness, no
suppuration (clavicle, mandible, ulna)
Fibrodysplasia ossificans progressive
▪ Progressive extraskeletal heterotopic bone formation in muscles, tendons, ligaments, fascia
▪ Normal at birth, large toe deformity w/ episodes of soft tissue swelling & inflammation
Osteogenesis imperfecta
Marfan Syndome
Metabolic bone disease
▪ Hypophosphatasia
▪ Hyperphosphatasia
▪ Osteoporosis
TRIAD: fragile bones + blue sclera + early deafness
OI Type I (mild)
▪ Blue sclerae, recurrent fractures & presenile hearing loss (30-60%)
▪ Easy bruising, hyperextensible joints, thin skin, joint laxity, scoliosis,
Wormian bones, henia & mild short stature
OI Type II (Perinatal lethal)
▪ Stillborn or die in 1st year of life
▪ SGA, bones, and CT extremely fragile
▪ Multiple intrauterine fracture of long bones, large skull and fontanels,
micromelia, & bowing of extremities, multiple rib fractures (beaded
appearance), small thorax, dark blue gray sclerae
▪ Multiple neuronal defects on cerebral cortex (agyria, gliosis, PVL)
Osteogenesis Imperfecta Type III (Progressive Deforming)
▪ Most severe nonlethal form → significant physical disability
▪ BW & BL low normal, fractures in utero, macrocephalic & triangular
facies
▪ Disorganized bone matrix – popcorn appearance at metaphyses
▪ Pectal deformity, scoliosis & vertebral compression, extremely short
DNA sequencing – test for dominant & recessive OI
*mutation identification to determine type, family
screening, prenatal dx
-Type VI screened by determination of severe reduction
in serum pigment epithelium derived factor
-obtaining dermal fibroblasts can be useful for
determining level of transcripts of candidate gene for
collagen biochemical testing →(+) in types I-IV, IX, VII/VIII
LABS
-collagen biochemical studies using cultured dermal
fibroblasts
-must be differentiated from thanatophoric dysplasia
Prenatal determination of Severe OI
-detected as early as 16 wks AOG by UTZ
-chorionic villus biopsy for molecular or biochemical
studies
Normal to elevated alkaline phosphatase in neonatal
period → distinguish it OI from hypophosphatasia
▪ No cure
▪ For severe nonlethal OI – active physical rehab in early
years → to attain higher functional level
▪ Type I and some type IV – spontaneous ambulators
▪ Type III, IV, V, VI and XI – benefit from gait aids and
swimming and conditioning
Orthopedic management – fracture management and
correction of deformity to enable function
Bisphosphonates (IV pamidronate or oral olpadronate or
risedronate) given for several years have some benefits
→  bone resorption by osteoclasts →  bone volume
but still contain defective collagen
▪ No effect on mobility scores, muscle strength or bone
pain
▪ SE: abnormal long-bone remodeling,  incidence of Fx
non-union, osteoperotic brittleness to bone
Genetic counseling
▪ AD → 50% risk of passing to offspring
▪ Empirical recurrence risk to an unaffected couple of
Batch Clingy
Disorders involving ion transporters
Loss of sulfate ion transporter DTDST
AR Mutiple epiphyseal dysplasia
▪ Normal stature in childhood but final height slightly decreased, 50%
have clubfeet & external ear abnormality
▪ Diastrophic dysplasia – very short ext, clubfoot, short hands, proximal
displacement of thumb (hitchhiker), cauliflower ear deformity
▪ Achondrogenesis Type 1B and Atelosteogenesis Type 2 – rare
recessive lethal dysplasias; extremely short limbs, soft head, hypoplastic
pelvis, short ribs
173
PATHOGENESIS
▪ Collagen structural mutations → abnormal bone
▪ Bone matrix w/ abnormal type 1 collagen fibrils & relatively  levels of
types III & V collagen
▪ Abnormal osteoblast differentiation & ↑ # of active bone resorbing
osteoclast
▪ Hypermineralization of the bone
▪ Classical OI (Sillence types I-IV & type V) autosomal dominant
▪ Recessive OI (7-10%) caused by null mutations in genes coding for the
collagen in the ER
Types of collagen structural defects
▪ Point mutation (80%) – substitution of helical glycine residues or
crucial residues in the C-propeptide by other AA
▪ Single exon splicing defects (20%) – clinically mild OI type 1 – null
mutations in 1 a1(I) allele → reduced collagen
stature
▪ Scleral hue (white to blue)
▪ Dentinogenesis imperfecta, hearing loss & kyphoscoliosis may be
present/develop
OI Type IV (moderately severe)
▪ In utero fractures, bowing of bones, require ortho & rehab but can
attain community ambulation skills
▪ Osteoporotic w/ metaphyseal flaring & vertebral compressions, mod
short stature, sclera (blue/white)
OT Type V (Hyperplastic Callus) and Type VI Hyperosteoidosis
(Mineralization Defect)
▪ Similar in skeletal severity to types IV & III but have distinct bone
histology
▪ Type V (<5%) – hyperplastic callus, calcification of interossesous
membrane of forearm & radiodense metaphyseal band
▪ (+) Ligamentous laxity, no blue sclera/dentinogenesis imperfecta
▪ Type VI – progressive deforming that doesn’t manifest at birth.
▪ Broad osteoid seams & fish-scale lamellation under polarized light
(pigment epithelium derived factor deficiency)
COMPLICATIONS
▪ Cardiopulmonary M&M
▪ Recurrent pneumonias, ↓ pulmo function
▪ Cor pulmonale – adults
▪ Neuro: basilar invagination, brainstem compression,
hydrocephalus & syringomyelia
having a second child with OI is 5-7% (when one parent
has germline mosaicism)
▪ If parent is a mosaic carrier, risk of recurrence may be
50%
▪ AR → recurrence risk is 25% per pregnancy
▪ No known patient with severe nonlethal recessive OI
has had a child
PROGNOSIS
▪ OI type I usually die within months to 1 year of life
▪ Occasional child w/ type II & extreme growth deficiency
survives to the teen years
▪ OI type III reduced life span w/ mortality from
pulmonary causes in early childhood, teen & 40s
▪ Types I, IV & V are compatible with full life span
▪ OI Type III often wheelchair dependent → aggressive
rehabilitation (transfer skills & household ambulation)
▪ OI Type IV attain community ambulation skills
independently or with gait aids
OI Type VII, VIII and IX (Autosomal Recessive)
▪ Overlap II & III but have distinct features: white sclerae, rhizomelia,
small to normal head circumference
▪ Severe osteochondrodysplasia w/ extreme short stature
▪ Type IX (very rare, only 8 cases reported) lethal to mod severe, white
sclera but no rhizomelia
OI Types X and XI (AR)
▪ Defects in serine-type endopeptidase inhibitor of HSP47 that helps
maintain folded state of procollagen heterotrimers responsible for
collagen synthesis
▪ Type XI, more prevalent, mod to severe, white sclera, normal teeth,
congenital contracture of large joints
▪ Kuskokwim syndrome – deletion of single tyrosine residue w/ very mild
vertebral findings and osteopenia
High Bone Mass OI
▪ Mutations in cleavage of procollagen C-propeptide
▪ Normal stature, white sclera & teeth, mild to moderate OI
▪ Null mutations in BMP1 → severe skeletal phenotype w/ short stature,
scoliosis & bone deformity
PPS Oral Exam Reviewer 2020
→
Radiographs
▪ Surgery is required only in 4-5% of pediatric fractures
Indications for Operative treatment in children &
adolescents
▪ Displaced physical fracture
Batch Clingy
FRACTURES
Pediatric skeletal system vs adults predisposing them to injuries:
▪ (+) Periosseous cartilage
▪ Physes
▪ Thicker, stronger, more osteogenic periosteum that produces new
bone (callus), more rapidly & in greater amounts
▪ Pediatric bone less dense, more porous
OI Types XIII-XVIII
▪ Affects osteoblast differentiation & bone formation
▪
Impaired
collagen
posttranslational
modification
underhydroxylation of collagen helix
Upper extremity
▪ Phalangeal fractures
▪ Forearm fractures
▪ Distal humeral fractures
▪ Proximal humerus fractures
▪ Clavicular fractures – most common site, middle and lateral third
LE fractures
174
Pediatric Fracture Patterns
Plastic Deformation
▪ Unique to children, commonly seen in the forearm & occasionally the
fibula
▪ Fracture from force that produces microscopic failure on the tensile
side of bone & does not propagate to the concave side
Buckle or Torus Fracture
▪ Failure in compression of the bone at the junction of the metaphysic &
diaphysis
▪ Inherently stable, heals in 3-4wks w/ simple immobilization
Greenstick Fracture
▪ Occurs when the bone is bent, & failure in the tensile (convex) side of
the bone
▪ Concave side shows evidence of microscopic failure with
plasticdeformation
Complete Fractures
▪ Propagate completely through the bone
▪ Classified as: spiral, transverse, or oblique depending on the direction
& shape of fracture lines
Epiphyseal Fractures
▪ Involves epiphysis, often growth plate → potential for growth
disturbance leading to deformity & discrepancy
▪ Distal radial physic - m/c injured physics
▪ Salter & Harris Classification
I and II – closed reduction, tend to remodel with growth
III and IV – involves articular surface, require anatomic alignment
(<2mm displacement)
V – not diagnosed initially, manifest later with growth disturbance
▪ “Twisted neck”, not a Dx but rather a clinical manifestation
TORTICOLLIS
Congenital muscular torticollis (CMT) most common Dx during infancy,
etiology unknown
▪ Muscle biopsies & MRI show in utero muscle compression & or stretch
resulting in localized ischemia & intramuscular compartment syndrome
▪ Contracture of left SCM results in tilt to left & rotation to right
▪ Hypothesized to result from intrauterine deformation or compression
PPS Oral Exam Reviewer 2020
▪ Hip fracture
▪ Toddler fracture
▪ Tibula and fibula shaft fractures – most commonly fractured
▪ Femoral shaft fractures
▪ Triplane and tillaux fractures
▪ Metatarsal fractures
▪ Toe phalangeal fractures
Hip Fracture
▪ Result from high-energy trauma, can be assoc to injury to the chest,
head, or abdomen
▪ Treatment entails complication rate of up to 60%, avascular necrosis
rate 50%, malunion rate 30%
Femoral shaft fracture
▪ Urgent atomic reduction (open/closed), spica casting for younger
AP and Lateral Xray of femur, pelvis
children
Femoral Shaft Fractures
Tibia and Fibula Shaft Fractures
▪ Low energy twisting type injuries to high-velocity injuries in vehicular
AP and lateral radiograph of the knee and ankle
accidents
▪ Femur fx in <2y/o raise concern for child abuse
Metatarsal fractures
Proximal Tibia Fractures
AP, lateral, oblique radiographs of the foot
▪ Can be physical injuries, metaphysical injuries, or avulsion injuries of
the tibial spine or tubercle
Toddler fracture
▪ Careful neuromuscular exam warranted (pre & post-reduction)
AP and lateral views of tibia and fibula showing
▪ Proximal tibial metaphysical fracture (cozen fracture) common in 3-6
nondisplaced spiral fracture of the distal tibial
y/o → can cause valgus deformity
metaphysis
Tibia and Fibula Shaft Fractures
▪ Tibia – m/c fractured bone of the LE in children
▪ Inflammatory markers may be requested to rule out
▪ Direct injury
infectious process in dx is in doubt
▪ Most assoc with fibular fracture, mean age 8 y/o
▪ Pain, swelling, deformity of affected leg and is unable to bear weight
Toddler fracture
▪ In young ambulatory children (1-4 y/o)
▪ Injury after seemingly harmless twist or fall often unwitnessed
▪ Result of torsional injury
▪ Dx by physical exam, no fracture on X-ray
▪ Refusal to bear weight (pulling up affected extremity or florid display of
protest, point tenderness at the site of fracture
Triplane and Tillaux Fractures
▪ Occur at the end of growth period
▪ Based on relative strength of the bone-physics junction & asymmetric
closure of the tibial physis
Metatarsal fractures
▪ Direct trauma to the dorsum of the foot
▪ High energy trauma or multiple fx of the metatarsal base → swelling
Toe phalangeal fractures
▪ Secondary to direct blows → barefoot child
▪ Swollen, ecchymotic and tender
▪ Tilting of head & neck ipsilaterally toward the side of the contracted muscle w/ head rotation contralaterally
DIFFERENTIAL DIAGNOSIS
CONGENITAL
Muscular torticollis, Positional deformation
Hemivertebra (cervical spine), unilateral atlanto-occipital fusion
Klippel-Feil syndrome
Unilateral absence of sternocleidomastoid, pterygium colli
TRAUMA
▪ Displaced intraarticular fracture
▪ Unstable fractures
▪ Multiple injuries
▪ Open fractures
▪ Failure to achieve adequate reduction in older children
▪ Failure to maintain an adequate reduction
▪ Certain pathologic fractures
Proximal Tibia Fractures
▪ Anatomic reduction and pin fixation, preferred with
unstable fractures or displaced SH III or IV fractures
Tibia and Fibula Shaft Fractures
▪ Closed reduction and immobilization
▪ Open fracture → irrigation, debridement, and antibiotic
treatment
▪ Any suspicion of compartment syndrome → emergent
fasciotomy
Toddler fracture – below knee cast for 3-4w
Triplane Fracture – anatomic reduction, stabilized by
internal fixation
Tillaux Fractures – closed reduction; open reduction only
if residual intraarticular step-off persists
Metatarsal fractures
▪ Closed method (below-knee cast)
▪ Closed/open reduction e/ internal fixation for displaced
fractures (using smooth Kirschner wires)
Toe phalangeal fracture – buddy taping of the fractured
toe
*See table 703.3 common indications for External
Fixation in Pediatric Fractures
CMT
▪ Stretching, stimulation & positioning measures,
supervised by PT
▪ Resolution in 95% cases, when tx started 1st 4mos of life
Surgery
▪ If diagnosed late, surgical release of SCM
Batch Clingy
Unique characteristics of pediatric fractures
Fracture remodeling
▪ 3rd & final phase in fracture healing, preceded by inflammatory and
reparative phases
▪ 3 major factors affecting angular correction: skeletal age, distance to
the physis, orientation to the joint axis
▪ Remodeling best when fx occurs close to the physics
▪ Skeletal maturity: Girls 13-15, boys 15-17 years
Overgrowth – physical stimulation from the hyperemia assoc w/ fracture
healing
175
▪ Hip disorder of unknown etiology
▪ Temporary interruption of blood supply to proximal femoral
epiphyses→ osteonecrosis and femoral head deformity
▪ Etiology obscure, disruption of the vascular supply to the femoral
epiphysis → ischemia & osteonecrosis
▪ More common in boys, 4-8yrs old
PATHOGENESIS
▪ Ischemia & necrosis of femoral head → changes during repair process
▪ Infection, trauma, & transient synovitis are unsubstantiated causative
factors
▪ Thrombophilia, Factor V Leyden mutation, protein C and S deficiency,
lupus anticoagulant, anticardiolipin antibodies, antitrypsin and
plasminogen might play a role in the abnormal clotting mechanism
LEGG-CALVE-PERTHES
DISEASE
4 stages of disease
Initial stage
▪ 6mos
▪ Synovitis, joint irritability, early necrosis of femoral head
▪ Revascularization → resorption of necrotic segement
▪ Necrotic bone replaced by fibrovascular tissue (not bone) which
comprises structural integrity of femoral epiphysis
Fragmentation stage
▪ 8mos
▪ Femoral epiphyses begin to collapse, laterally and extrudes from
acetabulum
Healing stage
▪ 4yrs
▪ New bone formation in subchondral region, reossification begins
▪ Deformity depends on severity of collapse and amount of remodeling
that occurs
Residual stage
▪ After entire head has ossified
▪ Mild amount of remodeling until child reaches skeletal maturity
PPS Oral Exam Reviewer 2020
Muscular injury (cervical muscles), atlanto-occipital sublaxation
Atlantoaxial sublaxation, C2-3 sublaxation
Rotary sublaxation, fractures (clavicle fracture or brachial plexopathy)
INFLAMMATION
Cervical lymphadenitis
Retropharyngeal abscess, cervical vertebral osteomyelitis
Rheumatoid arthritis, Grisel syndrome (nontraumatic subluxation of the atlantoaxial joint d/t local inflammation), upper lobe
pneumonia
NEUROLOGIC
Visual disturbances (nystagmus, superior oblique or lateral rectus paresis)
Dystonic drug reaction (phenothiazines, haloperidol, metoclopramide)
Cervical cord tumor, posterior fossa brain tumor, syringomyelia, Wislon disease
Dystonia muscularum deformans
OTHER
Acute cervical disk calcification
Sandifer syndrome (GERD, hiatal hernia), benign paroxysmal torticollis
Bone tumors (eosinophilic granuloma), soft tissue tumor, psychogenic
▪ Most common presenting symptom is LIMPING
X-ray – 1O diagnostic tool (Lauenstein/frog leg lateral)
▪ Pain if present is activity related, localized in groin or referred to thigh
or knee
▪ Initial – ↓ size of ossification center, lateralization of
femoral head w/ widening of medial joint space,
▪ Antalgic gait – limp characterized by shortening of gait phase on the
subchondral fracture and physeal irregularity
injured side to alleviate weight bearing pain, prominent after strenuous
▪ Fragmentation – fragmented epiphyses, scattered areas
activity
of increased radiolucency and radiodensity
▪ Reossification – bone density returns to normal by new
▪ Hip motion – limited internal rotation and abduction; initially due to
bone formation
synovitis but later becomes permanent
▪ Residual stage – reossification of femoral head,
▪ Mild hip flexion contracture – 10-20 degrees
remodeling of acetabulum
▪ Atrophy of muscles of thigh, calf, or buttock from disuse
Associated with poor prognosis when seen on radiograph:
▪ Leg length inequality – adduction contracture of true shortening on
▪ Lateral extrusion of the epiphysis, horizontal physis,
involved side from femoral head collapse
calcification lateral to the epiphysis, subluxation of the
hip and a radiolucent horizontal V in the lateral aspect of
the physics (Gage’s sign)
Radionuclide bone scan – can reveal avascularity early
MRI – sensitive in detecting early infarction and
determine degree of impaired perfusion but cannot
portray stages of healing
Arthrography – assess shape of femoral head and
diagnose hinge abduction
Catteral Classification based on involved femoral
epiphysis and a set of radiographic “head at risk” signs
▪ Group I 25% involved, no sequestrum, no metaphysial
abnormality
▪ Group II 50% involved, clear demarcation b/n involved
and uninvolved segments, metaphyseal cyst may be
present
▪ Group III 75% involvement and a large sequestrum
▪ Group IV entire femoral head involved
Herring lateral pillar classification
▪ Determine treatment and prognosis during active stage
of disease
▪ Based on several radiographs during fragmentation
stage
▪ Some say delay until 18mos some say 1-4yo
Goal of treatment – preserve well covered femoral head
and maintain hip range close to normal
Non-surgical
▪ Activity limitation, protected weight bearing, NSAIDS,
and PT
▪ Severe pain – bedrest
▪ Petrie casts – 2 long leg casts help hips in abduction and
internal rotation (best position)
Surgical
▪ Varus osteotomy of proximal femur most common
procedure
▪ Pelvic osteomies (acetabular rotational osteotomyies,
shelf procedures and medical displacement or Chiari
osteotomyies
▪ Post op → containment to manage residual deformity
PROGNOSIS
▪ If sxs develop <5yo, good prognosis, remodeling
potential higher in children
Batch Clingy
problem & is more common in first pregnancies
▪ Fibrotic mass palpable within the muscle and disappears in first few
months of life
▪ Part of molded baby syndrome – DDH, plagiocephaly, facial asymmetry
& foot deformities (metatarsus adductus)
▪ Facial findings – flattening on affected side, recessed eyebrow &
inferior orbital displacement
Paroxysmal torticollis of infancy - uncommon & may be due to vestibule
dysfunction
Neurogenic torticollis – uncommon, results from tumors of the
posterior fossa or brainstem, syringomyelia and Arnold-Chiari
malformation
176
▪ Occurs during period of accelerated growth, late childhood, or
adolescence (10-15yrs) more common in boys, esp in athletes, due to
repetitive trauma
▪ Localized soft tissue swelling, along with an eventual firm & fixed 
prominence at the tibial tubercle
▪ Pain aggravated by sports activities and persist with regular daily
activities and even at rest
▪ Diagnosis is clinical
▪ Xray: fragmentation of tibial tubercle & soft tissue
swelling
▪ Usually self-limited, resolves with rest
▪ Restriction of activities and occasionally knee
immobilizer necessary with restricted weight bearing +
isometric and flexibility exercise program
▪ Advise that tibial tubercle welling will not likely resolve
COMPLICATIONS
▪ Rare
▪ Early closure of the tibial tubercle w/ recurvatum or
hyperextension, deformity, and, rarely, patellar tendon
rupture or avulsion fracture of the tibial tubercle
Batch Clingy
OSGOOD-SCHLATTER
DISEASE
PATHOGENESIS
▪ Irritation of the patellar tendon at its insertion into the tibial tubercle
or a traction apophysitis of the tibial tubercle growth plate
▪ Anterior knee pain, very specifically localized point tenderness over the
tibial tubercle & the distal portion of the patellar tendon
PPS Oral Exam Reviewer 2020
177
Acute
ETIOLOGY / INCIDENCE/ PATHOGENESIS
▪ EA: S. pneumoniae (30%), nontypeable H. influenzae (30%), M.
catarrhalis (10%), S. aureus
▪ Occur at any age
Sinuses
Ethmoid
Maxillary
Sphenoid
Frontal
BACTERIAL SINUSITIS
Present
At birth
At birth
5yo
7-8yo
Pneumatized
At birth
4yo
Risk Factors
▪ Viral URTI (associated with out-of-home daycare or a school-age
sibling; 0.5-2%)
▪ Allergic rhinitis, tobacco smoke exposure
▪ Immunodeficiencies, cystic fibrosis, ciliary dysfunction,
abnormalities of phagocyte function
▪ GER, cleft palate, nasal polyps, cocaine abuse, nasal foreign
bodies
▪ Nasotracheal intubation or NGT → sinus ostia obstruction →
sinusitis with MDR organisms of the ICU
▪ Acute sinusitis – <30 days
▪ Subacute sinusitis – 1-3mos
▪ Chronic sinusitis – >3 months
▪ Viral infection → viral rhinosinusitis → inflammation and edema
→ blocked sinus drainage and impaired mucociliary clearance of
bacteria → bacterial overgrowth
CLINICAL MANIFESTATIONS
▪ Nonspecific – nasal congestion, purulent nasal discharge (unior bilateral), fever, cough
▪ Halitosis, hyposmia (↓ sense of smell), periorbital edema
▪ Headache and facial pain are rare in children
▪ Maxillary tooth discomfort, pain or pressure exacerbated by
bending forward
▪ Erythema and swelling of the nasal mucosa with purulent nasal
discharge
▪ Sinus tenderness in adolescents and adult
▪ Transillumination – opaque sinus that transmits light poorly
LABORATORY FINDINGS / DIAGNOSIS
▪ Sinus aspirate culture – only accurate method of diagnosis but is
impractical; may be necessary for the immunosuppressed
▪ Rigid nasal endoscopy – less invasive for obtaining culture
material; detects a great excess of positive cultures compared with
aspirates
▪ Radiographic studies (plain film, CT) – opacification, mucosal
thickening, air fluid level; not diagnostic and not recommended for
healthy children; can confirm the presence of inflammation but
cannot differentiate among viral, bacterial, or allergic causes
TREATMENT
▪ Antimicrobial treatment for those with severe onset of a
worsening course to promote resolution of symptoms and
prevent suppurative complications
▪ 50-60% recover without antimicrobial therapy
*See Table 408.2 below
▪ If with risk factors for the presence of resistant bacterial
species (antibiotic treatment in the preceding 3mos, daycare
attendance, or <2yo), and with failure to respond to initial
therapy with amoxicillin within 72h, or with severe sinusitis,
give high-dose Co-Amox (80-90mkday)
▪ If vomiting or at risk for poor compliance, give IV Ceftriaxone
followed by a course of oral antibiotics
▪ If still with treatment failure, refer to an ENT
▪ Duration of therapy: individualized; minimum of 10 days or 7
days after resolution of symptoms
DIFFERENTIAL DIAGNOSIS
▪ Viral URTI – clear and usually non purulent discharge, cough,
initial fever; symptoms do not usually persist beyond 10-14days
▪ Allergic Rhinitis – seasonal; nasal secretions have significant
eosinophilia
▪ Persistence of nasal congestion, rhinorrhea (of any quality) and
daytime cough ≥10 days,
▪ Severe symptoms of temp ≥39C with purulent nasal discharge for
≥3days, and
▪ Worsening symptoms either by recurrence of symptoms after an
initial improvement or new symptoms of fever, nasal discharge, and
daytime cough (double sickening)
▪ Frontal sinusitis – can rapidly progress to serious intracranial
complications, hence, initiate IV Ceftriaxone until substantial
clinical improvement
▪ Decongestants, antihistamines, mucolytics, intranasal
corticosteroids – not enough studies hence, not recommended
▪ Saline nasal wash or nasal sprays – help liquefy secretions
and act as a mild vasoconstrictor
COMPLICATIONS
▪ Serious orbital/intracranial complications – due to the
proximity of the paranasal sinuses to the brain and eyes
▪ Periorbital and orbital cellulitis
● Often 2o to acute bacterial ethmoiditis
● Infection spreads directly through the lamina papyracea –
thin bone that forms the lateral wall of the ethmoidal sinus
● Do CT scan of the orbits and sinuses with Ophtha and ENT
consults
● Treat with IV antibiotics
● Orbital cellulitis may require surgical drainage
▪ Intracranial Complications
● Epidural abscess, meningitis, cavernous sinus thrombosis,
subdural empyema, brain abscess
● Altered mental status, nuchal rigidity, severe HA, focal
neurologic findings, signs of ↑ ICP
● Do CT scan of the brain, orbits, and sinuses
● Treat with broad-spectrum IV antibiotics (cefotaxime or
ceftriaxone combined with vancomycin) pending culture
results
● In 50%, infection is polymicrobial
PPS Oral Exam Reviewer 2020
Batch Clingy
DISEASE
178
● Abscesses require surgical drainage
▪ Osteomyelitis of the frontal bone (Pott puffy tumor) – edema
and swelling of the forehead
▪ Mucocele – chronic inflammatory lesions in the frontal
sinuses; can expand → displacement of the eye → diplopia; do
surgical drainage
LEPTOSPIROSIS
▪ Zoonosis caused by aerobic, motile spirochetes of the genus
Leptospira
▪ Worldwide distribution, most human cases occur in tropical and
subtropical countries
▪ Asymptomatic infection to severe disease (5-10%) with
multiorgan dysfunction and death
▪ Abrupt; may have a mono- or biphasic course
▪ Incubation period: 2-30 days
Lepstospires
▪ Survive for days to weeks in warm and damp environmental
conditions – water & moist soil
▪ Infect rats, mice, moles, livestock (cattle, goats, sheep, horses,
pigs), wild mammals (raccoons, opossums), domestic dogs →
ANICTERIC LEPTOSPIROSIS
Septicemic phase
▪ Lasts 2-7 days
▪ Leptospires can be isolated from the blood, CSF, and other
tissues
PPS Oral Exam Reviewer 2020
Immune phase
▪ CSF abnormalities
● Modest ↑ in pressure
● Pleocytosis
● Early PMN leukocytosis → mononuclear predominance
● N or slightly ↑ CHON levels
● N glucose values
Weil Syndrome
▪ UA – hematuria, proteinuria, casts
▪ Direct and indirect hyperbilirubinemia, modestly ↑ hepatic
▪ Initiate treatment before the 7th day to shorten the clinical
course and decrease the severity of the infection
▪ Parenteral penicillin G (6-8 million U/m2/day) every 4hrs for
7days
▪ If penicillin-allergic, give doxycycline (2mkday) BID (maximum
of 100mg twice daily)
▪ Cefotaxime, ceftriaxone, azithromycin – alternative if
doxycycline is contraindicated
▪ If mild illness, may give oral doxycycline, amoxicillin, and
ampicillin
Batch Clingy
PREVENTION
▪ Frequent handwashing
▪ Avoid persons with colds
▪ Yearly influenza vaccine
179
excrete spirochetes in urine for prolonged periods
▪ Most human cases occur from exposure to water or soil
contaminated with rat urine
▪ Enter human hosts through mucous membranes (1o eyes, nose,
mouth), transdermally through abraded skin, or by ingestion of
contaminated water → bloodstream → endothelial damage of
small blood vessels → 2o ischemic organ damage
▪ Flulike signs – fever, shaking chills, lethargy, severe HA, malaise,
n/v, severe debilitating myalgia (most prominent in the LE, LS
spine, abdomen)
▪ Bradycardia and hypotension can occur
▪ Conjunctival suffusion with photophobia and orbital pain, (-)
chemosis and purulent exudate
▪ Generalized lymphadenopathy
▪ Hepatosplenomegaly
▪ Transient (<24h) erythematous maculopapular, urticarial,
petechial, purpuric, or desquamating rash (10%)
Immune phase
▪ Recurrence of fever and aseptic meningitis
▪ 80% have abnormal CSF findings but only 5% have clinical
meningeal manifestations
▪ Self-limited unilateral or bilateral uveitis – rarely results in
permanent visual impairment
▪ CNS symptoms resolve spontaneously within 1wk, with almost
no mortality
enzymes (returns to N after recovery)
▪ Transient thrombocytopenia (50%)
▪ Diagnosis is confirmed by serologic testing
▪ Microscopic agglutination test – gold standard diagnostic method;
≥4x increase in titer in paired sera
▪ Agglutinins appear by the 12th day of illness, reach a maximum
titer by the 3rd week, and low titers can persist for years
▪ Unlike other spirochetes, leptospires can be recovered from the
blood or CSF during the 1st 10 days of illness and from the urine
after the 2nd week by repeated culture of small inoculum (1 drop of
blood or CSF in 5mL of medium)
▪ The inoculum in clinical specimens is small and growth can take up
to 16 weeks
▪ If severe, give specific attention to cardiopulmonary status,
renal function, coagulopathy, and fluid and electrolyte
imbalance
PREVENTION
▪ Rodent control measures
▪ Avoidance of contaminated water and soil
▪ Immunization of livestock and domestic dogs
▪ Use protective clothing (boots, gloves, goggles) if at risk for
occupational exposure
▪ If admitted, observe contact precaution
▪ If adult and travelling to highly endemic areas for short
periods, give prophylactic doxycycline 200mg PO once a week.
No specific pediatric data.
ICTERIC LEPTOSPIROSIS (Weil Syndrome)
▪ Severe form more commonly seen in adults (>30yo)
▪ Initial manifestations similar to anicteric leptospirosis
▪ Immune phase – jaundice, acute renal dysfunction,
thrombocytopenia → pulmonary hemorrhage, CV collapse
▪ Hepatic involvement → RUQ pain, hepatomegaly
▪ Azotemia, oliguria/anuria
▪ Acute kidney failure in 16-40%
▪ Abnormal ECG (90%)
▪ Epistaxis, hemoptysis, pulmonary, GI, and adrenal hemorrhage
VIRAL SYNDROMES
DENGUE FEVER
TYPHOID FEVER
URI
BRONCHIOLITIS
PNEUMONIA
OTITIS MEDIA
UTI
*see Common Viral Illnesses*
*see Common Bacterial Infections*
*see Cough*
*see Ear Pain*
*see Renal Disorders*
OCCULT
BACTEREMIA
PFAPA SYNDROME
ETIOLOGY / INCIDENCE/ PATHOGENESIS
▪ Positive blood culture for a pathogen in a well-appearing child
without an obvious source of infection
▪ Prevalence: <1% in febrile, well-appearing young children
▪ At risk: Unimmunized and incompletely immunized because of
pneumococcus
▪ Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis
▪ Most common recurrent fever syndrome in children
▪ Between 2-5yo
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS
▪ Recurring episodes of fever, malaise, exudative-appearing
tonsillitis
with
negative
throat
cultures,
cervical
lymphadenopathy, oral aphthae
▪ Less often, has HA, abdominal pain, arthralgia
LABORATORY FINDINGS / DIAGNOSIS
▪ CBC, blood culture
TREATMENT
▪ Give IV Ceftriaxone if leukocytosis is present while awaiting
blood culture results
▪ Mild leukocytosis
▪ Elevated acute-phase reactants
▪ Single oral dose of prednisone (0.6-2mg/kg) – does not
prevent recurrence; shorten the interval between flares
▪ Cimetidine (20-40mkday) – effective at preventing
recurrences in 1/3 of cases
Batch Clingy
Complex
DISEASE
180
▪ Etiology and pathogenesis are unknown
▪ Episodes last 4-6 days, regardless of antipyretic or antibiotic
treatment
▪ Occur with clock-like regularity on 3-to-6-week cycles
▪ Colchicine – may extend the time between flares
▪ Complete resolution has been reported after tonsillectomy
▪ Medical management should be the first approach
▪ Mild hepatosplenomegaly
▪ Temp >38C documented by a healthcare provider and for which
the cause could not be identified after at least 8days of evaluation
(see Table 204.1 below)
▪ Most result from atypical presentation of common diseases
*see Table 204.2 – Diagnostic considerations for FUO*
▪ JIA and SLE – CTDs most often associated with FUO
▪ IBD, Kawasaki Disease
▪ FUO >6mos – uncommon in children; suggests granulomatous,
autoinflammatory, or autoimmune disease
▪ 90% have an identifiable cause – 50% infectious, 10-20% collagen
vascular, 10% oncologic
Fever without a source
▪ Source has not yet been identified
▪ Can progress to FUO if no cause is elicited after 7days of
evaluation
Drug Fever
▪ Fever is sustained with no accompanying symptoms
▪ Discontinuation of the drug = resolution of the fever, generally
within 72h
Factitious Fever
▪ Inoculation of pyogenic material or manipulation of the
thermometer by the patient or parent
Pseudo-FUO
▪ Successive episodes of benign, self-limited infection with fever
that the parents perceive as 1 prolonged episode
▪ Often starts with a well-defined infection (often viral) that
resolves but is followed by other viral illnesses that may be less
well-defined
*see Table 204.4 – examples of potential diagnostic clues to
infections presenting as FUO*
▪ Do a thorough history and PE
Fever History: repetitive chills and spikes – septicemia
Age
▪ If >6yo, respiratory of GUT infection, localized infection
(abscess/osteomyelitis), JIA, leukemia
▪ If adolescent, IBD, autoimmune processes, lymphoma, TB
Animal exposure – if domestic animals, ask for vaccines
Pica: ingestion of dirt – Toxocara canis (VLM) or Toxoplasma gondii
(toxoplasmosis)
Medication History: Including nonprescription and topical meds
(eyedrops may be associated with atropine-induced fever)
Family History: Familial dysautonomia (recurrent hyperthermia;
common among Jews), familial Mediterranean fever
▪ Ultimate treatment is tailored to the underlying diagnosis
▪ Antimicrobial agents should only be used when there is
evidence of infection, with avoidance of empirical trials of
medication
▪ After a complete evaluation, may give antipyretics to
control fever
PROGNOSIS
▪ Better than FUO in adults
▪ Outcome depends on the primary disease process
▪ In many cases, no diagnosis can be established, and fever
abates spontaenously
▪ CBC
● ANC >5000/μL – against indolent bacterial infection other than
typhoid fever
● PMN >10,000/μL or a non-segmented PMN >500/μL – severe
bacterial infection is highly likely
▪ Urinalysis
▪ ESR >30mm/hr – inflammation; low ESR does not eliminated the
possibility of infection or JIA
▪ Blood culture (aerobic)
▪ TST – if child is >2yo, request for IGRA
▪ Imaging studies – indicated by specific history/PE findings
Batch Clingy
FEVER OF
UNKNOWN ORIGIN
▪ The frequency and intensity of the episodes diminish with
increasing age
*see Table 204.3 below*
PPS Oral Exam Reviewer 2020
181
*see Seizures*
Batch Clingy
CNS INFECTIONS
PPS Oral Exam Reviewer 2020
182
Acute
DISEASE
ETIOLOGY / INCIDENCE/ PATHOGENESIS
▪ Acute and potentially severe illness
▪ TSS toxin – 1 – producing and some enterotoxin – producing
strains of S. aureus
▪ Highest rate in menstruating women 15-25yo
▪ 1-2 cases per 100,000 menstruating women
Nonmenstrual TSS
▪ Associated with S. aureus infected nasal packing and wounds,
sinusitis, tracheitis, pneumonia, empyema, abscesses, burns,
osteomyelitis, primary bacteremia
CLINICAL MANIFESTATIONS
CLASSIC TSS:
▪ Abrupt onset
▪ High fever, vomiting, diarrhea, sore throat, HA, myalgia
▪ Diffuse erythematous macular rash (sunburn-like or scarlatiniform)
appears within 24hrs + hyperemia of the pharyngeal, conjunctival, and
vaginal mucous membranes
LABORATORY FINDINGS / DIAGNOSIS
▪ No specific laboratory tests
▪ Diagnosis is based on clinical manifestations
▪ Strawberry tongue
▪ Altered LOC, oliguria, hypotension → if severe, shock and DIC
TSST-1
▪ Act as superantigens, triggers cytokine release → massive fluid
loss from the intravascular space → end-organ cellular injury
▪ Selectively produced in an environment of neutral pH, high PCO2,
and an anaerobic PO2 – found in abscesses and the vagina with
tampon use during menstruation
TREATMENT
▪ Identify and drain/remove any focal source of infection –
abscess, tampon, nasal packing
▪ β-lactamase-resistant antistaphylococcal antibiotic
(nafcillin, oxacillin, cefazolin) + clindamycin
▪ If with high rates of MRSA, when hospital acquired MRSA
is suspected, or when the clinical picture overlaps with
staphylococcal sepsis, use vancomycin instead of a βlactam
▪ Often requires intensive supportive care
● Aggressive fluid replacement – prevent/ treat
hypotension, renal failure, CV collapse
● Inotropes – treat shock
● Corticosteroids and IVIg – if severe
▪ Recovery within 7-10 days
● Associated with desquamation of the palms and soles
● Hair and nail loss after 1-2mos
▪ Recurrences can occur – inadequate antibiotic treatment
and/or recurrent tampon use
TOXIC SHOCK
SYNDROME
COMPLICATIONS
▪ ARDS, myocardial dysfunction, renal
commensurate with the degree of shock
failure
–
PROGNOSIS
▪ Overall mortality rate of treated patients – 3-5% if with
early treatment
KAWASAKI
DISEASE
(Mucocutaneous
LN syndrome)
▪ Highest incidence in Asian children
▪ Leading cause of acquired heart disease in children in most
developed countries
▪ Disease of early childhood (highest in those <5yo); boys > girls
▪ Cause is unknown, some say infectious in origin
3-PHASE PROCESS TO KD ARTERIOPATHY
1) Neutrophilic necrotizing arteritis – 1st 2wks of illness; begins in the
PPS Oral Exam Reviewer 2020
Fever
▪ Highly spiking (≥38.3C), remitting, unresponsive to antipyretics
▪ If without treatment, lasts for 1-2wks, but may be as short as 5days
or persist for 3-4wks
Conjunctival Injection with limbal sparing
Rash of various forms – maculopapular, erythema multiforme,
scarlatiniform, psoriatic-like, urticarial, or micropustular
Perineal desquamation – acute phase
Periungual desquamation – begins 2-3wks after onset of the illness;
fingers and toes → entire hand and foot
Arthritis – small or large joints; may occur early in the illness or may
develop in the 2nd or 3rd week
▪ Symptoms other than the principal criteria are common in the 10d
▪ 2DED – most useful test to monitor CAA development
● CA dimensions may be increased in the 1st 5wks after
presentation
● Small Aneurysms – ≤4mm internal diameter (ID)
● Medium – >4 to ≤8mm ID
PREVENTION
▪ Change tampons at least every 8 hours
▪ If (+) fever, rash, or dizziness during menstruation, remove
tampon immediately and seek consult
▪ Avoidance of tampon use in subsequent menstrual cycles
to reduce recurrence risk
▪ IVIG should be given within 10d of disease onset, ideally
ASAP after diagnosis
▪ ASA high dose (anti-inflammatory) → low dose
(antithrombotic) – continued for 6-8wks after illness onset
then discontinued if normal 2DED throughout the entire
course of the illness. If with CAA, continue indefinitely.
▪ Do not give other NSAIDs together with ASA
Batch Clingy
▪ Systemic inflammatory disorder manifesting as vasculitis with a
predilection for the coronary arteries (CA)
▪ Predominantly affects the medium-sized areteries (CA, axillary,
subclavian, femoral, popliteal, brachial)
DIFFERENTIAL DIAGNOSIS
▪ Streptococcal TSS – caused by GAS; severe streptococcal sepsis or a
focal streptococcal infection (cellulitis, necrotizing fasciitis,
pneumonia)
▪ Kawasaki Disease – resembles TSS but not as severe or rapidly
progressive
▪ Scarlet fever, Rocky Mountain spotted fever, Leptospirosis, TEN,
sepsis, measles
▪ No diagnostic test but have characteristic lab findings (see Table
191.1 in the next pages)
▪ Platelet is N in the 1st week → rapid ↑ by the 2nd-3rd week
(sometimes >1million/mm3)
▪ Normocytic, normochromic anemia
▪ ESR may remain elevated for weeks
▪ KD is unlikely if the ESR, CRP, and platelet counts are normal after 7
days of fever
183
endothelium → coronary wall; saccular aneurysms may form
2) Subacute/chronic vasculitis – driven by lymphocytes, plasma cells,
eosinophils; lasts weeks to years; results in fusiform aneurysms
3) Progressive Stenosis – the vessels affected in the 2nd phase
develop smooth muscle myofibroblasts → stenosis → thrombi
formation → blood flow obstruction
before the diagnosis of KD
▪ GI symptoms – >60% of patients
▪ Respiratory symptoms – at least 1 in 35%
Cardiac Involvement – most important manifestation of KD;
myocarditis manifests as tachycardia disproportionate to fever + ↓ LV
systolic function; pericarditis with a small effusion; mild MR (10-25%)
Node-first KD
▪ Initially presents with only fever and lymphadenopathy
▪ Older (4yo)
▪ Have more days of fever and higher CRP levels
▪ Many also have retropharyngeal and peritonsillar inflammation on CT
scans
KD SHOCK SYNDROME
▪ Greatly ↓ LV function
▪ Higher risk for CA dilation
▪ Diagnosis should be made within 10 days, ideally within 7 days, of
fever onset to improve coronary artery outcome
ATYPICAL OR INCOMPLETE KD
▪ Persistent fever + <4 of the 5 characteristic clinical signs
▪ Labs and 2DED assist in the diagnosis
▪ Occur most frequently in infants (highest likelihood of CAA
development)
Any infant <6mos old with unexplained fever ≥7days
should undergo 2DED to assess the coronary arteries.
DIFFERENTIAL DIAGNOSIS
▪ Adenovirus – exudative pharyngitis & conjunctivitis
▪ Scarlet Fever – GAS; rapid clinical response to appropriate antibiotic
therapy; rarely have ocular findings
▪ Measles, cervical lymphadenitis, rocky mountain spotted fever
▪ Leptospirosis – biphasic, few asymptomatic days between an initial
period of fever and HA; late phase has renal and hepatic failure
▪ JIA – diffuse lymphadenopathy & hepatosplenomegaly
▪ Annual influenza vaccination – for patients on long-term
ASA therapy to ↓ risk of Reye syndrome
▪ MMRV vaccination – defer until 11mos after IVIG
administration (IVIG may interfere with the immune
response to live virus vaccines d/t specific antiviral
antibody)
IVIG-RESISTANT KD (15%)
▪ Persistent or recrudescent fever 36h after completion of
the initial IVIG infusion
▪ Increased risk for CAA
Batch Clingy
3 CLINICAL PHASES
1) Acute febrile phase – fever and other acute signs of illness; lasts 1-2
weeks
2) Subacute phase – desquamation, thrombocytosis, development of
CAA; highest risk of death in those who develop aneurysms; lasts 3
weeks
3) Convalescent phase – begins when all clinical signs have
disappeared until the ESR returns to normal; 6-8 weeks after the onset
of the illness
● Giant – >8mm ID
● Performed at diagnosis then at 1-2wks of illness
- If normal, repeat 6-8wks after onset of illness
- If with abnormalities or patient has recurrent fever or
symptoms, more frequent 2DED
- If without CAA at any time during the illness, do 2DED and lipid
profile after 1year then CV follow up every 5yrs
PPS Oral Exam Reviewer 2020
184
▪ Treatment (Table 191.4): 2nd dose of IVIG (2g/kg), tapering
course of corticosteroids, and/or infliximab
COMPLICATIONS
▪ MI, angina, sudden death
▪ 2/3 have a history of URTI several weeks prior
▪ Almost always have serologic evidence of a recent GAS (S.
pyogenes) infection
▪ Annual incidence of >50 per 100,000 children in some developing
countries
▪ RHD is the most common form of acquired heart disease in all age
groups worldwide
▪ 5-15yo – age of greatest risk for GAS pharyngitis
ACUTE
RHEUMATIC
FEVER
PPS Oral Exam Reviewer 2020
MIGRATORY POLYARTHRITIS (75%)
▪ Large joints – knees, ankles, wrists, elbows
▪ Hot, red, swollen, exquisitely tender joints that is dramatically
responsive to even low dose salicylates
▪ Pain can precede and can appear to be disproportionate to the
objective findings
▪ A severely inflamed joint can become normal within 1-3 days without
treatment
▪ If suspecting RF, hold salicylates and observe for migratory
progression
▪ Almost never deforming
CARDITIS (50-60%)
▪ Subclinical carditis – (-) murmur of valvulitis but (+) echo evidence of
valvulitis (see table 465.1)
▪ Clinical carditis – (+) murmur of valvulitis
▪ Carditis & chronic RHD – most serious manifestations of acute RF;
account for all associated morbidity and mortality
▪ Pancarditis – active inflammation of the myo-, peri-, and
endocardium
▪ Endocarditis (valvulitis) – universal finding in rheumatic carditis
▪ Myo- and/or pericarditis without evidence of endocarditis is almost
never is rheumatic carditis
▪ Most RHD is isolated MV disease or combined AV and MV
▪ Valvular insufficiency – acute & convalescent stages
▪ MV and/or AV stenosis – years/decades after the acute illness; in
*See table 210.2 below
▪ Synovial fluid: 10,000-100,000 WBC/μL with neutrophil
predominance; 4g/dL CHON; N glucose; forms a good mucin clot
▪ 2DED – pericardial effusion, ↓ ventricular contractility, aortic
and/or mitral regurgitation
▪ Circumstances when the diagnosis of acute RF can be made without
strict adherence to the Jones Criteria:
● Chorea occurs as the only major manifestation
● Indolent carditis is the only manifestation in patients who first
come to medical attention only months after the apparent onset of
acute RF
● Recurrence of acute RF in particularly high-risk populations
▪ The diagnosis of acute RF should not be made in those with elevated
or increasing streptococcal antibody titers who do not fulfill the Jones
Criteria
Recent GAS Infection
▪ Absolute requirement for the diagnosis of acute RF
▪ Acute RF develops 10-21 days after an acute GAS pharyngitis –
clinical findings of pharyngitis are no longer present
▪ Evidence is based on an elevated or rising serum antistreptococcal
antibody titers – ASO, anti-DNAse B, antihyaluronidase
PREDICTORS OF POOR OUTCOME
▪ Young age, male gender
▪ Persistent fever, poor response to IVIG
▪ Labs – neutrophilia, thrombocytopenia, transaminitis,
hyponatremia, hypoalbuminemia, ↑ CRP and N-terminalbrain-natriuretic protein
▪ Bed rest – allowed to ambulate only when the signs of
acute inflammation have improved
▪ Penicillin or Amoxicillin PO for 10days OR Benzathine
Penicillin G per IM for 1 dose – to ensure complete
eradication of GAS from the URT
▪ Erythromycin PO for 10days OR Azithromycin for 5days
OR Clindamycin for 10days if penicillin-allergic
▪ Withhold anti-inflammatory agents (salicylates,
corticosteroids) if the only manifestation of presumed RF is
arthralgia or atypical arthritis. May give acetaminophen to
control pain and fever.
▪ Oral salicylates
● 50-70mkday QID for 3-5 days followed by
● 50mkday QID for 2-3wks → 25mkday QID for 2-4wks
● Give if (+) migratory polyarthritis and carditis, (-)
cardiomegaly or congestive heart failure (CHF)
▪ Corticosteroids
● Prednisone 2mkday QID for 2-3wks → 1mkday for 23wks → taper by 5mg/day every 2-3days
● Give if (+) carditis, minimal cardiomegaly and/or CHF
● When being tapered, start ASA 50mkday QID for 6wks
– to prevent rebound of inflammation
▪ Supportive therapy for mod to severe carditis: Digoxin,
fluid and salt restriction, diuretics, oxygen
▪ Sedatives for Sydenham chorea – phenobarbital (16-32mg
q6-8h PO) is the drug of choice; haloperidol,
Batch Clingy
PROGNOSIS
▪ Majority return to normal health
▪ Recurs in 1-3% of cases
▪ 20-25% of untreated children (and those treated with ASA
alone) develop CA abnormalities (CAA) – aneurysms; 2nd-3rd
week of illness; often asymptomatic, diagnosed by 2DED
▪ <5% treated with IVIG & ASA within the 1st 10 days of
illness develop CAA
▪ 50% of CAA regress to N lumen diameter by 1-2y after the
illness
▪ Almost all the morbidity and mortality occur in those with
large or giant artery aneurysms (z score ≥10 or an absolute
dimension of ≥8mm) – less likely to regress; greatest risk of
thrombosis, stenosis, angina, MI
185
developing countries, may occur sooner
▪ Presents with tachycardia and cardiac murmurs → cardiomegaly,
heart failure, hepatomegaly, peripheral & pulmonary edema
▪ Mitral regurgitation – high pitched holosystolic murmur radiating to
the axilla
▪ Aortic insufficiency – high pitched decrescendo diastolic murmur at
the left sternal border
chlorpromazine
COMPLICATIONS
▪ Arthritis and chorea resolve without sequelae
▪ Chronic, progressive valvular disease
consequence of acute rheumatic carditis
CHOREA (10-15%)
▪ Isolated, frequently subtle, movement disorder
▪ Emotional lability, incoordination, poor school performance,
uncontrollable movement, facial grimacing, exacerbated by stress,
disappears with sleep
Clinical Maneuvers to elicit features of chorea
▪ Milkmaid’s grip – irregular contractions & relaxations of muscles of
the fingers while squeezing the examiner’s fingers
▪ Spooning and pronation of the hands when the arms are extended
▪ Wormian darting movements of tongue on protrusion
▪ Examine the handwriting to evaluate fine motor movements
ERYTHEMA MARGINATUM (1%)
▪ Characteristic rash of acute RF
▪ Erythematous, nonpruritic, serpiginous, macular lesions with pale
centers
▪ Trunk and extremities; not on the face
▪ Accentuated by warming the skin
major
PROGNOSIS
▪ Depends on the initial manifestations, severity of the
initial episode, presence of recurrences
▪ 50-70% of those with carditis recover with no residual
heart disease – the more severe the involvement, the
higher risk for residual
▪ Those without carditis in the initial episode are less likely
to have carditis with recurrent attacks
▪ Those with acute RF are susceptible to recurrent attacks
following reinfection of the URT with GAS – 50% risk with
each GAS pharyngitis. Thus, requires long-term continuous
chemoprophylaxis
▪ The risk of recurrence is highest in the 1st 5yrs after the
initial episode and decreases with time
▪ 20% of those who present with pure chorea not given 2o
prophylaxis develop RHD within 20 years
PRIMARY PREVENTION
▪ Depends on identification and eradication of GAS causing
acute pharyngitis
▪ Appropriate antibiotic therapy before the 9th day of
symptoms of acute GAS pharyngitis
SECONDARY PREVENTION
▪ Preventing acute GAS pharyngitis in patients at substantial
risk of recurrent acute RF
▪ Continuous antibiotic prophylaxis beginning at the
diagnosis of acute RF and immediately after a full course of
antibiotic therapy has been completed
Batch Clingy
SUBCUTANEOUS NODULES (≤1%)
▪ Firm nodules 0.5-1cm in diameter along the extensor surfaces of
tendons near bony prominences
▪ (+) Correlation with significant RHD
MINOR CRITERIA
▪ CRP at least 3mg/dL in mod/high risk populations
▪ Prolonged P-R interval on ECG unless carditis is a major criterion; not
an evidence of carditis nor predict long-term sequelae
–
PPS Oral Exam Reviewer 2020
186
*see Common Viral Illnesses*
*see Common Bacterial Infections*
*see Collagen and Vascular Disorders*
Batch Clingy
VIRAL
EXANTHEMS
MENINGOCOCCE
MIA
HENOCHSCHONLEIN
PURPURA
PPS Oral Exam Reviewer 2020
187
Acute
ETIOLOGY/INCIDENCE/ PATHOGENESIS
▪ Humans only host
▪ Most important proteins in induction of immunity:
1) Hemagglutinin (H) Protein: neutralizing Ab are directed against
2) Fusion (F) protein: Ab limit proliferation of the virus during
infection
INCUBATION PERIOD
▪ 8 – 12 days
▪ Shed virus 7d after exposure to 4-6d after onset of rash
▪ Immunocompromised – shed measles during duration of
disease
TRANSMISSION
Portal of entry
▪ Respiratory tract or conjunctivae following contact with large
droplets or small droplet aerosols w/ virus
▪ Virus may remain suspended in air for an hour
▪ Infectious from 3 days before up to 4-6 days after onset of the
rash
MEASLES
Rubeola
PATHOLOGY
▪ Necrosis of resp tract epithelium and lymphocytic infiltrate
▪ Produces small vessel vasculitis on the skin and on the oral
mucous membranes
▪ Rash histology: intracellular edema and dyskeratosis with
formation of syncytial giant cells
▪ Fusion of infected cells → multinucleated giant cells: WARTHIN
FINKELDEY GIANT CELLS (pathognomonic)
4 PHASES
▪ Incubation Phase
● Virus migrates to regional LN
● 10 viremia: spreads to RES
● 20 viremia: spreads to body surfaces
▪ Prodromal Illness
● Begins after 20 viremia
● Epithelial necrosis and giant cell formation
● Virus shedding begins
▪ Exanthematous
● With onset of rash antibody production begins, viral
replication and symptoms subside
▪ Recovery Phase
MUMPS
▪ Humans are the only natural host
▪ Surface glycoproteins stimulate production of protective Ab
● Hemagglutinin-neuraminidase (HN) Protein: mediate
absorption of the virus to host cells
● Fusion (F) Protein: mediate penetration of virus into cells
▪ Incidence has decreased after MMR 2 dose vaccine
PPS Oral Exam Reviewer 2020
CLINICAL MANIFESTATIONS / FINDINGS / DIAGNOSIS
Prodrome: Mild fever, conjunctivitis w/ photophobia, coryza, cough
and increasing fever
Koplik Spots – enanthem
▪ Pathognomonic
▪ Appears 1-4 days prior to onset of rash
▪ Initially appears as discrete red lesions with bluish white spots in
the center on the inner aspects of the cheeks at the level of
premolars
▪ Symptoms ↑ in intensity for 2-4d until D1 of rash (maculopapular)
▪ Symptoms subside with onset of rash
▪ Rash appears in a cephalocaudal fashion, fades over 7 days with
fine desquamation
▪ Cough lasts longest (up to 10 days)
▪ Severe: generalized LAD with prominent cervical and occipital LN
MODIFIED MEASLES INFECTION
▪ Passively acquired Ab: infants & recipients of blood products →
subclinical form of measles may occur
▪ Rash: indistinct, brief, or rarely, entirely absent
▪ Some who received vaccines, when exposed, may have rash but
few other symptoms
▪ Not contagious
DIAGNOSTICS
Acute Phase: leukopenia w/ lymphocytopenia
neutropenia)
If without bacterial co-Infection: normal ESR & CRP
(absolute
Serologic Confirmation
Serum IgM Ab
▪ Appears 1-2 days after onset of rash
▪ Detectable for a month
▪ If collected <72 hrs after onset of rash and (-) for measles Ab, a 2nd
specimen may be obtained
IgG Ab:
▪ 4-fold rise in acute and convalescent specimens collected 2-4
weeks apart
▪ Viral isolation from blood, urine, resp secretions by culture or
molecular detection by PCR
▪ Prodrome lasts 1-2 days: fever, HA, vomiting, achiness → parotitis
(unilateral → bilateral)
▪ Tenderness enhanced by ingestion of sour or acidic foods or
liquids
▪ Ipsilateral ear pain, swelling obscuring the angle of jaw, earlobe
lifted upward and outward; peaks in 3 days, subsides over 7 days
MANAGEMENT
▪ Supportive
VITAMIN A – QD x 2 days at
● > 12mos: 200,000 IU
● 6 – 11mos: 100,000 IU
● <6mos: 50,000 IU
▪ If with SSx of vit. A deficiency, a 3rd dose is given 2-4 weeks after
2nd dose
MEASLES VACCINE (SC)
Given at 9mos but may be given as early as 6mos of age in
cases of outbreaks
If monovalent measles vaccine is not available, then
MMR/MR vaccine may be given as substitute for infants <12
months old/. In such cases, the recipient should receive 2
more MMR vaccines starting at 1 year of age, following
recommended schedules.
MMR (SC)
Minimum age of 12mos
2 doses of MMR are recommended
The 2nd dose is usually given at 4 - 6 years of age but may
be given at an earlier age with minimum of 4 weeks interval
between doses.
MMRV (SC)
Minimum age: 12 mos; Maximum age: 12 years
May be given as an alternative to separately administered
MMR and Varicella vaccines.
The recommended minimum interval between doses is 3
months but a 2nd dose given 4 weeks from the first dose, is
considered VALID.
COMPLICATIONS / PROGNOSIS
▪ Morbidity & mortality highest in <5yo
▪  Serum retinol concentrations
▪ Higher rate of activation of PTB in populations infected with
MTB then exposed to measles
▪ Measles during pregnancy: fetal wastage, stillbirths, congenital
malformations (3%)
Acute Otitis Media
▪ Most common complication
Pneumonia
▪ Most common cause of death
▪ May manifest as giant cell pneumonia or as superimposed
bacterial infection (S. pneumonia, S. aureus, H. influenza)
▪ Fatal outcome: bronchiolitis obliterans
▪ Infants/toddlers: croup, tracheitis, bronchiolitis
Measles Encephalitis
▪ Post infectious, immune mediated
▪ Clinical onset begins during exanthem and manifests as
seizures, lethargy, coma, irritability
▪ CSF: lymphocytic pleocytosis,  protein
▪ Immune compromised- occurs 1-10 months after. Seen as
seizures, myoclonus, stupor, and coma.
PROGNOSIS
Pneumonia and encephalitis were the complications in most of
deaths
AE (MMR):
▪ Fever (after 6-12 days), rash, transient thrombocytopenia
▪ Febrile seizure
▪ Do not give to pregnant, immunosuppressed or immunodeficient
(except asymptomatic HIV-infected patients)
POSTEXPOSURE PROPHYLAXIS
Vaccine
▪ Effective if given within 72 hours of exposure
Immunoglobulin
▪ May be given up to 6 days after exposure
▪ Indicated for susceptible household contacts of measles patients
(<6mos old, pregnant and immunocompromised)
▪ Immunocompetent: 0.5ml/kg (max: 15 mL/kg)
▪ Supportive, antipyretics, isolate for 5 days after onset of parotid
swelling
MMR
▪ 2-dose series starting at 12-15 mos then 4-6 y/o
▪ 3rd MMR dose during outbreaks for at-risk population
Most common: Meningitis + encephalitis, Gonadal involvement
Meningitis + Meningoencephalitis
▪ Neurotropic, enters CNS via choroid plexus
▪ May occur before, with or after (most commonly 5 days after
parotitis)
Batch Clingy
DISEASE
188
TRANSMISSION
▪ Via respiratory droplets
▪ Virus is present in saliva 7 days before to 7 days after parotid
swelling
▪ Infectious 1-2 days before to 5 days after parotid swelling
PATHOLOGY
▪ Initial viral replication: epithelium of upper resp tract, spreads to
adjacent LN, viremia ensues spreading to targeted tissues (e.g.
salivary glands, CNS, pancreas, testes)
▪ SALIVARY GLAND DUCTS: lined with necrotic epithelium
▪ TESTES: swelling of tissues may result in focal ischemic infarcts
▪ CSF: mononuclear pleocytosis
▪ Humans are the only known host
▪ Sensitive to heat, UV light, pH extremes
▪ Highest in pre-school & school age
INCUBATION PERIOD: 14 – 21 days
TRANSMISSION
▪ Period of highest communicability from 5 days before to 6 days
after appearance of the rash
▪ Viral shedding from nasopharynx: 10 days after infection and up
to 2 weeks of onset of rash
▪ Children with CRS excrete virus in respiratory secretions up to
1yo
RUBELLA
German measles
3-DAY measles
PATHOLOGY
Non-specific findings:
▪ Lymphoreticular inflammation, mononuclear perivascular,
meningeal infiltration
▪ Virus replicates in respiratory epithelium → regional LN →
viremia, most intense from 10-17 days after infection
CONGENITAL RUBELLA SYNDROME (CRS)
Congenital infection occurs during maternal viremia
Risk for congenital defects for the ff AOG:
▪ <11 weeks: high risk
▪ >16 weeks: uncommon
85% during 1st 12 weeks of gestation
50% during 1st 13 – 16 weeks of gestation
PPS Oral Exam Reviewer 2020
▪ Opening of Stensen duct: red and edematous
▪ Submandibular salivary glands may be involved
▪ Edema over sternum as a result of lymphatic obstruction
▪ Contraindications: pregnant women, severely ID or
immunosuppressed; HIV not severely immunocompromised may be
given
DIAGNOSTICS
▪ In highly prevalent areas: hx of exposure, appropriate incubation
period, typical clinical findings (parotitis is demonstrated by 
serum amylase; leukopenia + relative lymphocytosis is common)
PROGNOSIS
Nearly always excellent even with encephalitis, although fatal cases
CNS involvement or myocarditis have been reported
▪ In highly immunized populations w/ parotitis lasting longer than 2
days and of unknown cause: r/o mumps by cell culture, direct IF or
rt-PCR
▪ SPECIMENS: buccal or oropharyngeal mucosa, CSF or urine
● PCR from OP mucosa should be run within 3 days (becomes
negative quickly in immunized individuals)
▪ Serologic testing more convenient and available:
●  serum mumps IgG b/w acute and convalescent serum
specimens
● Mumps IgM (EIA): recent infection
▪ Low-grade fever, sore throat, red eyes + pain, HA, malaise,
anorexia, suboccipital, postauricular, anterior CLAD
▪ 1st manifestation in children is rash: variable; beginning on the
face and neck as small irregular pink macules → spreads
centrifugally; fades from the face as it extends; duration: 3 days
then fades without desquamation
▪ Forchheimer spots: rose colored spots or petechiae on soft
palate; occurs at onset of rash
DIAGNOSTICS
▪ Leukopenia, neutropenia, mild thrombocytopenia
▪ Most common test: Rubella IgM enzyme immunosorbent assay
(present 4 days after appearance of rash)
▪ Confirmation: IgM capture assay, rt-PCR or viral culture
For diagnosis of congenital infection:
▪ Viral isolation by culture of NP secretion, cord blood or placenta
▪ PCR of amniotic fluid during pregnancy
▪ CSF: normal or mild pleocytosis and/or  protein, virus is rarely
isolated
▪ Most common finding: nerve deafness
▪ Most common finding apparent at birth: IUGR
▪ Most common ocular finding: salt and pepper retinopathy
▪ Most serious ocular finding: cataracts
▪ Most freq. reported cardiac abnormality: PDA ff. by lesions of the
pulmonary arteries and valvular disease
▪ 10-20% have active meningoencephalitis at birth (e.g. full anterior
fontanelle, irritability, hypotonia, seizures, lethargy)
▪ Supportive
▪ Severe non-remitting thrombocytopenia: IVIg or corticosteroids
▪ Isolated for 7 days after onset of rash, standard and droplet
precaution
Exposed Pregnant Women
Obtain blood specimen for rubella IgG-specific Ab testing, then save
1 frozen aliquot
▪ If (+), mother is immune
▪ If (-), obtain 2nd specimen after 2-3 weeks and test with saved
frozen aliquot
▪ If both (-): obtain 3rd specimen 6 weeks after exposure and test
with the saved frozen aliquot
▪ If 2nd and 3rd (-), infection has not occurred
▪ If (+) in either 1 – RECENT INFECTION
● Routine Ig (0.55 mL/kg IM) is considered only if termination of
pregnancy is not an option
VACCINE
▪ Postexposure prophylaxis within 3 days
▪ Contraindications: pregnant women, severely ID or
immunosuppressed; HIV not severely immunocompromised may be
given
▪ Ig may inhibit serologic response to vaccine
▪ MMR AE: fever, rash, arthralgia & arthritis (adults), peripheral
neuropathies, transient thrombocytopenia
▪ Evaluate cardiac, audio, ophthalmic, and neurologic systems
▪ Contact precaution until 1yo
▪ Infants: fever, malaise, lethargy; older: headache and
meningeal signs
▪ Sxs resolve 7-10 days
Orchitis
▪ 2nd most common finding in adolescent and adult males
▪ Begins days ff onset of parotitis
▪ Fever, chills, exquisite pain, and swelling testes (30% bilateral)
→ atrophy may occur but sterility is rare
Oophoritis: uncommon
Pancreatitis: fever, epigastric pain, vomiting
Arthritis: arthralgia, mono or migratory polyarthritis, within 3
weeks of parotid swelling
Others: myocarditis, thyroiditis, conjunctivitis, optic neuritis,
pneumonia, nephritis, mastitis, thrombocytopenia, transverse
myelitis, ADEM, aqueductal stenosis, facial palsy, SNHL
▪ Pregnancy:  fetal wastage, perinatal mumps
Thrombocytopenia
▪ 2w after onset of rash – petechiae, epistaxis, GI bleeding,
hematuria
▪ Self-limiting
Arthritis
▪ Within 1 week of rash, self-limiting
▪ Small joints of hands
Encephalitis – most serious; 2 forms
Post-infectious syndrome
▪ Within 7d rash onset, HA, seizures, confusion, coma, focal
neurological signs, ataxia
▪ Non-infectious pathogenesis
Progressive Rubella Panencephalitis
▪ Rare, similar to SSPE, virus isolated in brain tissue
▪ Infectious pathogenesis
▪ Death after 2-5 years onset
Others: GBS, peripheral neuritis, myocarditis
PROGNOSIS
▪ Post-natal: excellent
RE-INFECTION
▪ Significant increase in IgG and/or an IgM response in an
individual with documented preexisting rubella-specific IgG
above an accepted cut-off
▪ Miscarriage, fetal death, constellation of congenital anomalies
▪ CRS is one of the few known causes of autism
PROGNOSIS
▪ Less favorable
Batch Clingy
INCUBATION PERIOD
Range: 12 – 25 days
Usual: 16 – 18 days
189
▪ Tissue necrosis due to vascular insufficiency, ↓ cellular
multiplication time, chromosomal breaks, production of protein
inhibitor causing mitotic arrest
▪ Distinctive feature is CHRONICITY: once infected early in
gestation, it persists beyond delivery
▪ dsDNA HHV-6 (6A & 6B) and HHV7
▪ Major cause: 6B
EPIDEMIOLOGY
Peak of infection
▪ HHV 6B: 6-9 months old (after maternal Ab wane)
▪ HHV 7: later in childhood
ROSEOLA
INFANTUM
Exanthem
subitum/
Sixth disease
TRANSMISSION
HHV6
▪ Saliva or respiratory droplets of asymptomatic adults or older
children
▪ Congenital infection via vertical transmission (transplacental
infection and chromosomal integration)
HHV7- saliva of asymptomatic individuals
Both: sexual or perinatal (as seen in cervical secretions)
▪ caused by Parvovirus B19
▪ Rash and transient aplastic crisis: most prevalent in school –
aged (5-15yo)
ERYTHEMA
INFECTIOSUM
Fifth Disease
INCUBATION PERIOD
Range: 4 – 28 days
Average: 16 – 17 days
▪ Transient aplastic crisis: shorter period of incubation
TRANSMISSION
▪ Respiratory route – large droplet spread from NP viral shedding
▪ Blood and blood products
▪ Fomite – due to resistance to solvents but not yet established
PATHOLOGY
▪ 1o target: erythroid cell line (erythroid precursors near the
pronormoblast stage) → cell lysis → transient arrest in
erythropoiesis
PPS Oral Exam Reviewer 2020
▪ Later neurologic manifestations: behavioral disorders,
microcephaly, mental retardation
▪ Other findings: interstitial pneumonitis, dermal erythropoiesis
(blueberry muffin rash), DM, thyroid dysfunction, glaucoma,
hepatosplenomegaly, thrombocytopenia
▪ All infants with evidence of IUGR or stigmata suggesting CRS
should undergo virologic (viral culture or PCR) and serologic study
for rubella (serum IgM > 21 mg/dL during the 1 st week of life
strongly indicate congenital infection)
▪ Abrupt onset of high fever (mean 39.7C) + fussiness→ resolves
after 3 days (crisis) or may fade over a day (lysis) coincident with
appearance of faint blanching pink or rose-colored nonpruritic
morbilliform rash that lasts for 1-3 days
▪ Mild injection of pharynx, palpebral conjunctiva, or tympanic
membranes (TM), enlarged suboccipital nodes,
rhinorrhea,
congestion, GI complaints and encephalopathy
▪ Nagayama spots: ulcers at uvulopalatoglossal junction
▪ Mean duration: 6 days
▪ Supportive
▪ Unusual/severe manifestations: ganciclovir, foscarnet, cidofovir
DIAGNOSTICS
▪ Characteristic:  Mean of WBC, lymphocytes, neutrophils
▪ Sporadically noted:  Serum transaminase,  platelet, atypical
lymphocytes
Encephalitis:
▪ CSF: normal or minimal pleocytosis, mild  protein
▪ MRI: hyperintense signal on T2-weighted and FLAIR images of the
hippocampus, uncus, and amygdala
▪ PET scan:  metabolism within hippocampus
▪ 3 day hx of high fever in an otherwise nontoxic infant with a
blanching maculopapular rash suggest the diagnosis
▪ Specific dx is not usually necessary except if manifestations are
severe or atypical and might benefit from antiviral therapy
● Viral culture (gold standard); if not possible, detection of viral
DNA by PCR or rt-PCR
▪ Prodrome: low grade fever, headache, URTI, LAD
▪ Hallmark: characteristic rash that occurs in 3 stages
● Slapped cheek: erythematous facial flushing
● Diffuse macular erythema spreading to trunk and proximal
extremities
● Lacy and reticulated (central clearing) prominent on extensors,
sparing palms and soles
● Resolves spontaneously without desquamation
● Waxes and wanes for 1-3 weeks
▪ Lymphadenopathy and atypical papular, purpuric, vesicular
rashes are also described
Arthritis/Arthralgia
▪ Older adolescents, F>M, self-limited (resolves in 2-4 weeks)
▪ Diffuse polyarthralgia with AM stiffness to frank arthritis; affects
hands, wrists, knees, and ankles
Transient Aplastic Crisis
▪ Most common complication: convulsions
▪ Higher frequency of partial seizures, prolonged seizures,
postictal paralysis and repeated seizures
▪ Other complications: ADEM, autoimmune encephalitis, acute
cerebellitis, hepatitis, myocarditis
▪ Reactivation occurred in approx. 50% of immunocompromised
hosts 2-4 wks after HSCT
Post-transplant acute limbic encephalitis (PALE): short-term
memory dysfunction, confusion, insomnia with seizures or
prolonged EEG described primarily in pts. Ff. HSCT
PROGNOSIS
▪ Self-limiting
PALE:
▪ Associated with increased mortality
▪ Long term neurocognitive sequelae
FINDINGS / DIAGNOSIS
Diagnosis of erythema infectiosum is clinical
Serologic tests:
▪ B19-specific IgM: develops rapidly after infection, persists for 6-8
weeks
▪ Anti-B19 IgG: past infection or immunity
▪ Anti B19 IgM: recent/ acute infection
▪ To confirm recent infection: seroconversion of anti-B19 IgG Ab in
paired sera
In immunocompromised:
▪ Serologic diagnosis is unreliable
▪ Requires methods to detect viral DNA
If maternal infection suspected
▪ Fetal ultrasound and peak systolic flow velocity of MCA
▪ Detection of viral DNA in fetal blood or amniotic fluid
MANAGEMENT
Arthropathy
▪ Arthralgias/ arthritis may persist after resolution of rash
Neurologic
▪ Aseptic meningitis, encephalitis, peripheral neuropathy
▪ Stroke in children w/ SCD ff. B19V-induced transient aplastic
crisis
PREVENTION
For (+) erythema infectiosum only, no isolation needed
(+) B19V induced RBC aplasia (w/ transient aplastic crisis):
▪ Isolate for 1 week and until fever has resolved, avoid contact
with pregnant women
Batch Clingy
25% during the end of 2 nd trimester
190
Patients with chronic hemolytic anemia: when infected →
transient arrest in RBC production → fall in Hgb (requiring
transfusion) & reticulocyte count (lysis of infected erythroid
precursors) → development of IgM 1-2 days after infection ff. by
anti-B19 IgG → control of infection & resolution of s/sx
Patients with impaired humoral immunity
serious/persistent
infection,
chronic
RBC
thrombocytopenia, neutropenia, marrow failure
–
more
aplasia,
Crosses placenta → profound fetal anemia and high output
cardiac failure
INCUBATION PERIOD: 10 – 21 days
TRANSMISSION
▪ Contagious 24-48 hrs before the rash is evident until vesicles are
crusted (usually 3-7d after onset of rash)
▪ Direct contact: aerosolization in cutaneous lesions
▪ Oropharyngeal secretions
Primary Infection
▪ Virus inoculates in the mucosa of URT and tonsillar lymphoid
tissue → replicates in lymphoid tissue, spread to T lymphocytes →
skin: innate immunity controls VZV replication → cutaneous
lesions
VARICELLA ZOSTER
Latent Infection
▪ Develops during incubation period or the disease itself
▪ Occurs only in the ganglionic neurons
▪ Virus is transported back to sensory axons to the dorsal root
ganglion throughout the spinal cord and to CN ganglia
▪ Can be established by attenuated VZV in varicella vaccine like
Oka strain (similar to natural or wild type) however the risk is
lower after vaccination than natural infection
HERPES ZOSTER (shingles)
▪ Milder in children
PPS Oral Exam Reviewer 2020
▪ Occurs in patients with chronic hemolytic conditions (e.g. sickle
cell disease, thalassemia, hereditary spherocytosis, pyruvate kinase
deficiency)
▪ Fever, malaise, lethargy, ss/x of profound anemia, vasooclusive
pain crisis (in px w/ SCD); rash is rarely present
Immunocompromised
▪
Chronic
anemia
(most
common)
+
thrombocytopenia, complete marrow suppression
▪ No specific antiviral therapy
▪ IVIg sometimes used
▪ In patients with AIDS, HAART has been reported to clear B19V
infection
▪ Infected fetus: intrauterine RBC transfusions
neutropenia,
Fetal Infection
▪ Associated with nonimmune fetal hydrops and IUFD, 2nd trimester
most sensitive period
Myocarditis
▪ Fetal myocardial cells express P Ag (receptor for virus)
Papular purpuric gloves-and-socks syndrome (PPGSS)
▪ Fever, pruritus, painful edema, and erythema localized to distal
extremities (gloves-and-socks distribution) → acral (or generalized)
petechiae and oral lesions
▪ Self-limited, resolves within a few weeks
▪ Begins 14-16 days after exposure
▪ Prodrome: fever (mean: 37.8-38.9OC; may be as high as 41OC),
malaise, anorexia, headache, mild abdominal pain occurs 24-48 hrs
before rash appears
▪ Systemic symptoms resolve within 2-4 days after rash onset
▪ Exanthem first at scalp, face, or trunk (CENTRAL)
▪ Simultaneous lesions in various stages of evolution: intensely
pruritic erythematous macules → papules → clear fluid-filled
vesicles → 24-48 hrs: clouding and umbilication of lesions →
crusting
FINDINGS
▪ Leukopenia (1st 72 hours) after onset of rash → Lymphocytosis
▪ Mildly  LFT
▪ CSF: mild lymphocytic pleocytosis, slight to mod  protein, N
glucose
DIAGNOSTICS
▪ Direct fluorescence assay of cells from cutaneous lesions vesicular
fluid
▪ PCR (vesicular fluid and crusts): most sensitive
▪ Rapid culture with IF staining
▪ Tzanck smear: multinucleated giant cells w/ nonspecific stains,
poor sensitivity
▪ Genotyping: strain identification
VZV IgG Ab
▪ > 4-fold rise is confirmatory of acute infection
▪ To determine immune status if hx of varicella is unknown or
equivocal
▪ Vesicular lesions clustered within 1-2 adjacent dermatomes; rash
is mild, symptoms of acute neuritis are minimal, complete
Acyclovir: not routinely recommended
▪ 20mkdose QID x 5 days (max 800mg)
▪ Give within 24 hours of rash onset
▪ IV form for severe or IC: 500 mg/m2 Q8 x 7-10 days until no new
lesions x 48 hours
If resistant (HIV-infected): IV Foscarnet or Cidofovir
For older children that can tolerate tablets: Famciclovir or
Valacyclovir
▪ 2 to <18yo: 20mkdose TID x 5 days (max1000 mg/dose)
▪ AE: neuro and GI illness
Secondary bacterial infections
▪ S. aureus and GAS
▪ Recurrence of fever 3 days after rash
Encephalitis and Cerebellar ataxia
▪ Highest: <5yo - >20yo
▪ Nuchal rigidity, altered LOC, seizures
▪ Gradual onset of gait disturbance, nystagmus, slurred speech
▪ Begins 2-6 days after onset of rash
▪ Complete clinical recovery within 24-72 hours
Pneumonia: 1-6 days after onset of rash; higher risk in smokers
VARICELLA VACCINE
▪ given SC for 2 doses at a minimum age of 12 mos. (12-15 mos.)
and 2nd dose given at 4-6 y/o (to prevent breakthrough varicella)
▪ contraindications similar to MMR vaccine
Postexposure prophylaxis
▪ vaccine given to healthy children within 3-5 days after exposure
▪ high-titer anti-VZV Ig is recommended for immunocompromised
children, pregnant and newborns (dose: 1 vial per 10kg BW) given
ASAP up to 10 days after exposure
▪ Anti-viral treatment is not always necessary in otherwise healthy
children
Progressive Varicella: severe, fatal disease
▪ Visceral organ involvement, coagulopathy, severe hemorrhage,
continued vesicular lesion development after 7 days
▪ Abdominal pain: involvement of mesenteric LN or the liver
▪ Risk factors: congenital cellular ID disorders, malignancy, after
organ transplant, high dose steroids, HIV
PROGNOSIS
▪ Low case fatality rate in children 1-9 y/o; infants have 4x
greater risk, adults have 25x greater risk
▪ Causes: pneumonia, CNS complications, 2O infections, and
hemorrhagic conditions
▪ Immunocompromised children may have more severe herpes
zoster similar to adults (including postherpetic neuralgia)
Batch Clingy
▪ Aplastic crisis: direct result of virus
▪ Exanthem and arthritis: post-infectious phenomena (immune
response)
191
▪ Unusual in healthy children <10yo
▪ Lifetime risk of zoster for individuals w/ hx of varicella: 30%; 75%
occurring after age 45 y/o
▪ Severe in immunocompromised children
▪ Reactivation of latent infection
▪ Exposure to varicella with prior infection will ↓ reactivation
▪ Suppression of cell mediated immunity to VZV will increase risk
NEONATAL VARICELLA
▪ Transplacental
▪ Maternal viremia occurs up to 48hr prior to onset of maternal
rash
CONGENITAL VARICELLA SYNDROME
▪ High risk in moms infected <13wks AOG and 13-20wks AOG
resolution within 1-2 wks
▪ Zoster sine herpete: unilateral dermatomal pain without rash
▪ Septic meningitis, enteric zoster: GI illness
▪ A large rise in VZV IgG titer in convalescent titer in atypical zoster
rash is confirmatory
VARICELLIFORM RASHES IN VACCINATED INDIVIDUALS
▪ Within 1-2wks after vacination: likely wild-type virus
▪ 14-42 days: either wild-type virus or vaccine strains
▪ >42 days: Breakthrough varicella caused by wild-type virus
▪ Atypical rash, <50 lesions, shorter duration, fewer complications,
and little or no fever, less contagious than wild-type virus
▪ Rash appears 2 days – end of 1st wk of life
▪ Fatal if the mother has varicella 5 days prior to 2 days after
delivery (no maternal antibodies formed yet)
▪ If >5 days prior to delivery and >30 weeks AOG: attenuated form
of varicella
▪ Zigzag cicatricial skin scarring, dermatomal distribution, limb
hypoplasia, LBW
▪ Neurologic – microcephaly, cortical atrophy, seizures, MR
▪ Eye – chorioretinitis, microphthalmia, cataracts
▪ Renal – hydroureter, hydronephrosis
▪ ANS – neurogenic bladder, swallowing dysfunction, aspiration
pneumonia
▪ Oral acyclovir can shorten duration but does not prevent postherpetic neuralgia
▪ If with disseminated disease: give IV acyclovir 500mg/m2 or 10mk
Q8
▪ If immunocompromised but uncomplicated zoster (low risk for
visceral dissemination): give PO acyclovir, famciclovir, or
valacyclovir
▪ Steroids are not recommended
PROGNOSIS
▪ Excellent
▪ Self-limited
▪ Give VZIG to NB if mother had varicella 5d prior to 2d after
delivery, preterm <28wks born to mother with active varicella at
delivery (even if maternal rash >1wk), hospitalized exposed preterm
+ mother has no evidence of immunity
▪ If no VZIG, give IVIG
▪ Symptomatic NB: Acyclovir (10 mk q8 IV)
▪ Susceptible mother exposed to varicella: give VZIG
▪ Mother with severe varicella: treat with acyclovir (class B)
▪ Although neonatal varicella may occur in about half of these
infants despite administration of VZIG, it is milder than in the
absence of VZIG administration
DIAGNOSTICS
▪ Hx of gestational varicella combined with characteristic
abnormalities in the NB
▪ Viral DNA by PCR in tissue (vesicular fluid or scabs)
▪ VZV specific IgM antibody in cord blood sample
▪ Persistently (+) VZV IgG Ab at 12-18 months old: prenatal infection
▪ Ultrasound for limb atrophy
HEPATITIS
TRANSMISSION
▪ Person-to-person through fecal – oral route
● Fecal excretion of virus starts late in incubation period
● Peak: just before the onset of symptoms
● Resolves by 2 weeks after onset of jaundice
● Travel to endemic areas; contact with contaminated food or
water (shellfish, frozen berries, raw vegetables)
▪ Highly contagious 2wks before & 7 days after jaundice
▪ Perinatal – rare
PPS Oral Exam Reviewer 2020
Serology (adapted from Nelson’s 21 st Ed., Table 385.3)
Acute/Active
Past/Recovered
Chronic
Vaccine Response
(+) anti-HAV IgM, remains for 4-6 mos
after infection
(+) anti-HAV IgG
N/A
(+) Anti-HAV IgG
COMMON BIOCHEMICAL PROFILES IN ACUTE INFECTION
▪ Altered synthetic function: most important marker of liver injury; prolonged PT, ↑ INR, ↓ serum albumin, hypoglycemia, lactic
acidosis, ↑ NH3
▪ Cytopathic injury: rapid ↑ AST/ALT
▪ Cholestasis: ↑ serum bilirubin, ALP, 5NT, GGT
▪ Supportive
▪ ALF (rare)
▪ Anti-pruritic agents and fat-soluble vitamins
▪ Prolonged cholestatic syndrome
▪ Handwashing
▪ Pruritus
▪ Contact and standard precautions
▪ Fat malabsorption
Pre-Exposure Prophylaxis
PROGNOSIS
Vaccine
▪ Excellent
Minimum age of 12 months
Hep A Vaccine
2 doses series
Inactivated (IM)
Minimum interval between 1 st and 2nd
dose is 6 months
Minimum age of 18
Live (SC)
Single dose
Immunoglobulin
▪ Provides protection x 2 months
▪ Suitable for <12mo old, allergic to a vaccine component, those
Batch Clingy
PATHOGENESIS
▪ Direct cytopathic and/or immune mediated injury: centrilobular necrosis, bile duct proliferation, diffuse Kupffer cell hyperplasia in
sinusoids
▪ Liver morphology returns to normal within 3 months after recovery from acute infection
▪ If chronic hepatitis develops, inflammatory infiltrates settle in the periportal areas → progressive scarring
HEPATITIS A
▪ Causes acute hepatitis only
▪ Most prevalent
▪ Duration: 7-14 days
▪ Heat stable, limited hosts: human & other primates
▪ In young children: anicteric illness; s/sx similar to viral AGE
▪ Older adolescent or adults, underlying liver disorders, IC: acute
INCUBATION PERIOD: 15- 19 days (mean 3wks)
febrile illness, anorexia, nausea, malaise, vomiting, jaundice
192
who elect not to receive vaccine
HAV + Ig: for older patients, immunocompromised, (+) chronic liver
disease who plans to travel in endemic areas in < 2wks
INCUBATION PERIOD: 45-160 days (mean: 120 days)
TRANSMISSION
▪ Parenteral, sexual, perinatal
▪ Concentrations
● High: blood, serum, serous exudates
● Moderate: saliva, vaginal fluid, semen
● Inconsistent: Breast milk
Risk Factors:
▪ IV drugs or blood products, contaminated needles, sex,
institutional care, intimate contacts w/ carrier
▪ Most important RF: perinatal exposure to (+) HBsAg mother;
high maternal HBV viral load + delivery of prior infant who
developed HBV despite prophylaxis
▪ HBV is predominantly noncytopathogenic
● Causes injury mostly by immune-mediated processes
● Expression of viral antigens (i.e. HBcAg and HBeAg) + class I
MHC proteins on cell surface makes it a target for cytotoxic T-cell
lysis
▪ Mechanism for chronic HBV infection is less well understood
● possible non-recognition of core protein or MHC class I
protein, non-activation of cytotoxic lymphocytes
ACUTE HBV INFECTION
▪ Most are asymptomatic
▪ 6-8 weeks after exposure: serum ALT levels ↑ ff. by fatigue,
anorexia, malaise or serum sickness like prodrome: arthralgia and
skin lesions, papular acrodermatitis (Gianotti Crosti syndrome) →
extrahepatic conditions may occur
▪ Jaundice – begins 8wks after exposure, lasts for 4wks
▪ Symptoms persist for 6-8 wks then resolves but some enters a
chronic carrier sate
CHRONIC HBV INFECTION (3 PHASES)
▪ Immune tolerant – majority; spontaneous HBeAg seroconversion
(development of anti-HBe and loss of HBeAg)
▪ Immune active – active inflammation, elevated AST/ALT,
progressive fibrosis
▪ Inactive
HBsAg: early marker of infection, falls during recovery before s/sx
wane
Anti-HBc IgM: rises early after infection, remains (+) for months,
replaced by Anti-HBc IgG (persists for years)
Ant-HBs: marker of recovery and protection
HBeAg: present in active acute or chronic infection, marker of
infectivity
Serology (adapted from Nelson’s 21 st Ed., Table 385.3)
Acute/Active
Past/Recovered
Chronic
Vaccine Response
(+) Anti-HBc IgM
(+) HBsAg
(-) Anti-HBs
(+) HBV DNA (PCR)
(+) Anti-HBs
(+) Anti-HBc IgG
(+) Anti-HBc IgG
(+) HbsAg
(-) Anti-HBs
(+) PCR
(+) Anti-HBs
(-) Anti-HBc
Treatment
▪ Indicated for immune-active form (evidenced by ↑ AST/ALT or
fibrosis on liver biopsy)
▪ Not for immune-tolerant patients (normal AST/ALT, (+) HBeAg
with ↑ viral load)
IFN α2b: immunomodulatory and antiviral effects; viral resistance
does not develop; given SQ x 24 wks, SE: flu-like s/sx, marrow
suppression, depression; C/I: decompensated cirrhosis
Lamivudine: oral synthetic nucleoside analog; inhibits reverse
transcriptase
Adefovir: purine analog; inhibits viral replication
Entecavir: nucleoside analog; inhibits replication
Tenofovir: nucleotide analog; inhibits replication
Peginterferon-α2: same MOA as IFN
Hepatitis B Vaccine (IM)
3 doses series
Administer the 1st dose of monovalent HBV to all newborns >2
kgs within 24 HOL
A 2nd dose is given 1-2 months after the birth dose
Final dose: administered not earlier than 24 weeks of age.
Another dose is needed if the last dose was given at age <24
weeks.
(see Nelson’s 21st Ed., Table 385.5 for Typical Interpretation of Test
Results for HBV Infection)
HEPATITIS C
▪ Most common cause of chronic liver disease in adults
PPS Oral Exam Reviewer 2020
▪ Acute: mild, insidious in onset
▪ Chronic (evidence of active viral infection with detectable HCV
RNA for at least 6 months): clinically silent until with complication
▪ Acute HCV infection: due to high rate of spontaneous clearance
and AE of currently available therapy, tx is not routinely given
▪ Chronic HCV infection
▪ ALF with coagulopathy, encephalopathy, cerebral edema
● Risk increased by coinfection or superinfection with HDV or
in immunosuppressed host
● Liver transplant is the only effective intervention
▪ Chronic Hepatitis (HBsAG (+) for >6mos) → cirrhosis then
ESLD; HCC
▪ Extrahepatic (immune mediated): PAN, GN (membranous or
MPGN),
aplastic
anemia,
polymyalgia
rheumatica,
leukocystoclastic vasculitis, GBS
PROGNOSIS
▪ Acute: favorable
● Mortality from ALF: >30%
▪ Chronic: HCC was the most prevalent cancer-related death in
young adults in Asia
PREVENTION
▪ Mothers HBV DNA >200,000 IU/mL: give antiviral during 3 rd
trimester
▪ Not spread by breastfeeding, kissing, hugging, or sharing water
or utensils
▪ Exclude children who are prone to biting
▪ HBIG: temporary protection (3-6mo), give at separate
anatomical site from vaccine
Infants born to HBsAg positive mothers (preterm or term
infants regardless of weight):
- Administer HBV* and HBIG (0.5 mL) within 12 hours of
birth.
- HBIG should be administered not later than 7 days of age,
if not immediately available.
Infants born to mothers with unknown HBsAg status
(preterm or term infants regardless of weight)
- BW >2 kg, administer HBV within 12 hours of birth and
determine the mother’s HBsAg as soon as possible.
If HBsAg (+) administer also HBIg not later than 7 days of
age.
- BW <2 kgs, administer HBIG in addition to HBV* within 12
HOL
*For those <2 kgs, the 1st dose received at birth is not
counted as part of the vaccine series. Additional 3 HBV
doses are needed.
▪ Highest risk of chronic hepatitis
▪ Cirrhosis, liver failure and primary HCC (within 20-30yo)
● Yearly liver UTZ and serum AFP
Batch Clingy
HEPATITIS B
▪ Risk of chronic infection ↑ in younger patients
Ig Post-Exposure Prophylaxis
▪ Not effective if given > 2 weeks after exposure
▪ Preferred in <12 months old and older > 40 y/o, IC, (+) chronic liver
disease or in whom vaccine is contraindicated
▪ Acute HBV infection: supportive
▪ Chronic HBV infection (goal): ↓ viral replication (undetectable
HBV DNA and development of Anti-HBe)
193
Risk Factors: blood transfusion, illegal drug use, multiple sexual
partners, occupational
INCUBATION PERIOD: 2-24 weeks (mean: 7-9 wks)
TRANSMISSION
▪ Parenteral
▪ Sexual – rare
▪ Perinatal – 5-15%, most prevalent MOT in children
● Serum aminotransferase fluctuates (sometimes normal)
● Liver fibrosis progresses slowly
(see Nelson’s 21st Ed., Fig. 385.5 for Natural history of hepatitis C
virus infection)
Acute/Active
Past/Recovered
Chronic
(+) Anti-HCV IgG‡*
(+) HCV RNA PCR*
(+) Anti-HCV
(-) Blood PCR
(+) Anti-HCV IgG‡
(+) Blood PCR
● Goal: achieve a sustained viral response (absence of viremia at
a variable period after stopping meds; assoc. w/ improved histology
& ↓ risk of morbidities)
● Tx should be considered for pts w/ evidence of advanced
fibrosis or injury on liver biopsy
● Peginterferon, IFN-α2b, Ribavirin are FDA-approved for
children > 3yo; (24-48 wks of peginterferon and ribavirin)
● Sofosbuvir ± Ledipasvir has FDA approval for > 12-17yo
● Side effects: influenza-like symptoms, anemia, neutropenia, lag
in height
▪ Chronic HCV infection can be associated with small vessel
vasculitis (Ab to smooth muscle, ANA, ↓ TH may be sometimes
present)
▪ Supportive
▪ No specific HDV targeted treatments
▪ Small studies: IFN
PREVENTION
▪ Immunize against HBV
PROGNOSIS
▪ Children are believed to have a higher rate of spontaneous
clearance (up to 45% by age 19)
● Viral titers should be checked yearly to document
spontaneous remission
‡One
INCUBATION PERIOD
▪ Co-infection – same as HBV
▪ Superinfection – 2 to 8 weeks
TRANSMISSION
▪ Parenteral, sexual, perinatal
▪ Direct injury by cytopathic mechanisms; liver damage is usually
severe
HEPATITIS E
INCUBATION PERIOD: 15-60 days (mean: 40 days)
TRANSMISSION
▪ Fecal-oral (water-borne)
▪ Cytopathic virus; pathology similar to other hepatitis viruses
ROTAVIRUS
▪ Classified by serogroup and subgroup
● Group A includes the common human pathogens; Groups B &
C occassionaly reported
● Strains are species specific
▪ Disease tends to be severe in 3-24mos of age
● < 3mos old are protected by transplacental Ab and BF
PPS Oral Exam Reviewer 2020
(+) Anti-HDV IgM
(+) Blood PCR
(+) HBsAg
(-) Anti-HBs
(+) Anti-HDV IgG
Past/Recovered
(-) Blood PCR
(+) Anti-HDV IgG
(-) Blood PCR
Chronic
(+) HBsAg
(-) Anti-HBs
▪ Similar to HAV but more severe
▪ Chronic illness does not occur except in immunosuppressed
patients
▪ Affects older patients (15-34yo)
Acute/Active
(+) Anti-HEV IgM (1 week)
(+) Blood PCR
(+) Anti-HEV IgG
Past/Recovered
(-) Blood PCR
▪ Mild to moderate fever, vomiting → frequent, loose watery stools
● Vomiting & fever abate on the 2 nd day of illness
● Diarrhea continues for 5-7 days
▪ Most severe disease: 4-36 mos. of age
▪ Major pathogen in pregnant women
● causes ALF with a high fatality incidence
▪ Decompensation of pre-existing chronic liver disease
PREVENTION
▪ Recombinant vaccine is highly effective in adults
Acute/Active
DIAGNOSTICS
▪ Diagnosis of viral AGE is clinical
▪ Avoid & treat dehydration
▪ Maintenance of nutritional status
● Breastfeeding should be continued even during rehydration
● Hypocaloric diets (↓ CHON & fat) such as BRAT (bananas, rice,
cereal, applesauce, toast) diet have not been shown to be superior
to a regular diet
▪ No routine role for antivirals or antibiotics
Rare:
▪ Mild encephalopathy with reversible splenium lesions →
cerebellitis
▪ Necrotizing enterocolitis
PROGNOSIS
▪ Subsequent reinfection decreases in severity during the 1 st 5
yrs of life
Batch Clingy
HEPATITIS D
▪ cannot cause infection on its own
● Co-infection: same time as initial HBV
● Superinfection: already infected with HBV
disadvantage of the antibody-based tests is that they cannot
distinguish acute from chronic infection; anti-HCV IgM is not useful
for distinguishing b/w acute & chronic HCV infection and measuring
HCV IgM is not recommended (2012 NASPGHAN Practice
Guidelines)
*anti-HCV IgG antibodies are usually negative during the acute
phase and HCV infection during this time frame can only be
determined by serum HCV RNA (2012 NASPGHAN Practice
Guidelines)
▪ Symptoms are similar but more severe than those of other
hepatotropic viruses
● Co-infection – acute hepatitis is more severe than HBV alone;
risk of developing chronic hepatitis is low
● Superinfection – acute illness is rare, chronic hepatitis is
common; risk of ALF is higher
194
INCUBATION PERIOD: <48hrs (range: 1-7 days)
TRANSMISSION
▪ Fecal-oral – ↑concentration in stool before and for days after
the clinical illness
▪ Isotonic dehydration with acidosis
▪ FA: no blood or WBC
▪ CBC: WBC may be moderately elevated 2O to stress (marked left
shift seen with invasive bacterial enteritis is absent)
PREVENTION
RV (PO)
Human RV1 (oral liquid formulation): 2 dose series with
minimum age of 6 weeks and minimum interval of 4 weeks.
The last dose should be administered not later than 24 weeks
of age.
▪ Gastric mucosa is not affected
▪ Nonstructural protein 4 (NSP4) functions as an enterotoxin
▪ Infect and destroy villus tip cells in small intestine leads to
● ↓ Absorption of salt and water and an imbalance in the ratio
of intestinal fluid absorption to secretion,
● Diminished disaccharidase activity and malabsorption of
complex carbohydrates, particularly lactose
▪ Most common cause in older children and adults
▪ Large explosive outbreaks among older children and adults
(schools, cruise ships, hospitals)
▪ Source: shellfish or water in food preparation
▪ Winter infantile AGE
NORWALK
(Norovirus)
Human-Bovine live-attenuated reassortant (RV5) (oral liquid
formulation): 3 dose series, the 1st dose is given at age 6 – 12
weeks, with minimum interval of 4 weeks. The last dose
should not be administered beyond 32 weeks of age.
Human-Bovine live-attenuated reassortant (RV5) (oral freezedried formulation): 3 dose series, recommended at 2, 4, and
6 months. Given at a minimum age 6 weeks and minimum
interval of 4 weeks. The last dose should not be administered
beyond 12 months of age.
▪ Good hygiene
▪ Vomiting and nausea tend to predominate; lasting 1-3 days
▪ Resembles food poisoning from S. aureus or B. cereus
▪ Laboratory findings similar to other viral AGE
INCUBATION PERIOD: 12 hours
TRANSMISSION: Fecal – oral
RABIES
INCUBATION PERIOD
▪ 1-3 months
▪ In severe wounds to the head, s/sx may occur w/in 5 days after
exposure
TRANSMISSION & PATHOGENESIS
▪ Inoculation of saliva through bite or scratch from an infected
vector
● Transmission rate is higher if multiple bites and inoculation in
highly innervated parts (hand or face)
▪ May enter intact mucous membranes
▪ Virus replicates slowly in muscle or skin → enters peripheral
motor nerve, uses nicotinic Ach receptor
▪ Axonal transport: crosses synapses q12hrs → rapid
dissemination in brain and spinal cord
PPS Oral Exam Reviewer 2020
2 FORMS:
Encephalitic/Furious
▪ Fever, sore throat, malaise, HA, n/v, weakness
▪ Paresthesia and pruritus at or near the site of bite → extend to
the affected limb
▪ Encephalitis: agitation, sleep disturbance or depressed mentation,
orofacial dyskinesias, myoclonus, seizures
▪ Periods of lucidity alternating with profound encephalopathy
▪ Cardinal sx: Hydrophobia and aerophobia (phobic spasms)
▪ Death occur in almost 100% of cases; 73% die w/in 3 days of
onset; 84% die w/in 24hrs of admission (2019 DOH NRPCP)
Paralytic/Dumb
▪ Uncommon
▪ Fever & ascending motor weakness involving both limbs and CN;
encephalopathy (occasional)
POSTEXPOSURE PROPHYLAXIS (PEP)
▪ Cell Culture & Embryonated Egg-based Vaccine (CCEEV)
● Purified Vero Cell Rabies Vaccine (PVRV)
● Purified Chick Embryo Cell Vaccine (PCECV)
PREVENTION
▪ Vaccinate domestic animals
▪ Education
PRE-EXPOSURE PROPHYLAXIS (PrEP)
▪ Persons traveling to a rabies-endemic region
(2018 WHO Position Statement on Rabies)
▪ Regimens for individuals of all ages:
● 2-site ID vaccine (0.1 mL) on days 0 & 7
● 1-site IM (1 vial) on days 0 & 7
PEP SCHEDULE FOR PREVIOUSLY IMMUNIZED ANIMAL BITE
PATIENTS
DIAGNOSTICS
▪ Often based on clinical manifestations & exposure to a rabid
animal
(2019 DOH National Rabies Prevention and Control Program)
▪ Fluorescent Antibody Testing (FA) – gold standard; tissue samples
from brainstem, thalamus, cerebellum and the hippocampus are
Batch Clingy
PATHOGENESIS
Similar to RV; may also cause delayed gastric emptying
▪ True animal reservoirs: terrestrial carnivores, bats
▪ Rare in small animals (mice, squirrels, rabbits)
▪ Species Affected by Rabies 2018 (2019 DOH National Rabies
Prevention and Control Program)
● 96% of positives are from canines ff. by felines
● 72% of rabies cases are owned; 88% of rabies cases were
either free-roaming or occasionally roaming
195
● Histopathology: limited damage, inflammation, or apoptosis
● Pathologic hallmark: Negri bodies – cytoplasmic inclusions
▪ Virus concentrates on brainstem (autonomic dysfunction and
relative sparing of cognition)
▪ Virus travels anterograde into PNS (exacerbating dysautonomia)
→ innervated organs → salivary glands
recommended; may also be detected on skin biopsies taken from
the nuchal area with hair follicles containing nerve endings
▪ rt-PCR – most sensitive; uses saliva, urine or skin
▪ Serologic (antibody) testing – only 50% will give (+) results among
rabies cases; more useful to ascertain immune status of immunized
animals & humans
PROGNOSIS
▪ Fatal
▪ Once with symptoms, vaccine and Ig are contraindicated
▪ Presence of normal Ab response by 7d: clearance of salivary
viral load and survival
● Schedule (may use either)
1-site IM, days 0-3-7 then 4th dose b/w days 14 to 28
2-site IM on day 0 and 1-site IM on days 7 and 21
TRANSMISSION
▪ Respiratory
▪ Fecal – oral: can be shed from GIT for prolonged periods
ADENOVIRUS
INFLUENZA
▪ Damage to epithelial mucosa → sloughing of cell debris →
inflammation
▪ Host response: recruit neutrophils, macrophages, and NK cells
▪ Three genera (or types): A, B, and C
● A & B: 1o human pathogens causing seasonal epidemics
● C: sporadic
▪ Influenza A subtypes are based on 2 surface proteins:
● HA (hemagglutinin), NA (neuraminidase)
PPS Oral Exam Reviewer 2020
▪ Acute Respiratory Disease: Bronchiolitis, pneumonia (may
present features more typical of bacterial disease), coryza, sore
throat, fever
▪ Ocular: follicular conjunctivitis (self-limiting), epidemic
keratoconjunctivitis (severe), pharyngoconjunctival fever
▪ GI: often asymptomatic but can cause acute diarrhea, mesenteric
adenitis
▪ Hemorrhagic cystitis: sudden onset of hematuria, dysuria,
frequency, urgency w/ (-) urine CS; resolves 1-2 weeks
▪ Myocarditis, hepatitis, meningoencephalitis
▪ Abrupt onset
▪ Predominance of systemic symptoms (i.e. fever, myalgia, chills,
HA, malaise, anorexia); coryza, pharyngitis, dry cough are also
usually present
● Duration of febrile illness: 2-4 days; cough may persist longer
▪ Organ failure in immunocompromised persons (esp. transplant
recipients)
▪ Respiratory failure, chronic lung disease, bronchiolitis
obliterans 2o to severe HAdV pneumonia
▪ Epidemic keratoconjunctivitis is vision-threatening
▪ Refractory severe anemia in hemorrhaging cystitis
PROGNOSIS
▪ Risk for severe/fatal disease
▪ Reactivation in a transplant recipient
MANAGEMENT
▪ Supportive care
▪ Bacterial superinfections are common; should be appropriately tx
▪ Give antivirals to those who are:
● Hospitalized
PREVENTION
▪ Hygiene: handwashing and cleaning
▪ Vaccines: live attenuated HAdV-4 & HAdV-7 (for military)
▪ OM and pneumonia: most common in young children
▪ Acute myositis or rhabdomyolysis particularly calf muscles,
myoglobinuria, ARF, myocarditis, sepsis
▪ CNS: encephalitis, myelitis, GBS, Reye syndrome with salicylate
use, bacterial co-infection
Batch Clingy
▪ Immunocompetent hosts
▪ Outbreaks: schools and military setting
▪ Rabies Ig (RIG)
● Human RIG (150 IU/mL) – Dose: 20 IU/kg
● Equine RIG (200 IU/mL) – Dose: 40 IU/kg
● Total computed dose shall be infiltrated around and into the
wound as much anatomically feasible (may be diluted with NSS to
increase volume)
● Given only once during the PEP course
▪ Supportive
▪ For epidemic keratoconjunctivitis: Cidofovir (highly nephrotoxic) +
topical steroids or immunosuppressive agents
196
INCUBATION PERIOD: 1-4 days (average 2 days)
TRANSMISSION
▪ Respiratory droplets
▪ Contact with secretions and small-particle aerosols
▪ Infectious day before until 5-7 days after onset of symptoms
▪ Children with 1o infection: higher viral loads and more prolonged
viral shedding
▪ Community transmission: rapid with highest incidence within 2-3
weeks of introduction
▪ Infect respiratory epithelium → HA attaches to sialic acid →
replication (10-14 days) → lytic infection of epithelium, loss of
ciliary function,  mucus, desquamation → permit 2O bacterial
infection
▪ Enterovirus
▪ 3 serotypes (types 1, 2 and 3)
● type 1 has greatest propensity for natural polio
● type 3 has a predilection for VAPP
▪ Acute paralytic disease can be caused by:
● wild poliovirus
● vaccine-associated paralytic poliomyelitis (VAPP) – OPV
viruses that cause illness in vaccine recipients (rare cause);
consider if symptoms occur 7-14 days after receiving OPV
● vaccine-derived polioviruses – either OPV viruses that
continuously replicate in immunodeficient persons (iVDPV) or
circulating vaccine-derived polioviruses (cVDPV) that have
acquired virulence properties resulting from sustained person-toperson circulation in the absence of adequate population
immunity
▪ Family members/close contacts experience similar illness
▪ Abdominal pain, vomiting, diarrhea may also occur
▪ Less common: parotitis, rash
▪ Severe: underlying cardiopulmonary disease
▪ High Risk: pregnant, adolescent female, child on chemotherapy,
immunodeficient
DIAGNOSTICS
▪ Diagnosis is clinical in the context of an epidemic
● However, presentation is indistinguishable from other
respiratory viruses
▪ Confirmation is not required for decision to prescribe antivirals
(see Nelson’s 21st Ed., Table 285.2 for Influenza Virus Testing
Methods)
▪ Paralysis – 3-8d after the initial symptom with extent of
involvement obvious within 2-3 days possibly affecting respiration
and circulation system
▪ Inapparent infection, abortive poliomyelitis and nonparalytic
poliomyelitis are more commonly seen with wild type poliovirus
infection
POSSIBLE COURSE OF INFECTION
Inapparent Infection (90-95%) – no disease/sequalae
Abortive Poliomyelitis (5%)
▪ Non-specific influenza-like syndrome 1-2 wks after infection,
lasting 2-3 days with complete recovery
▪ Prominent: fever, malaise, anorexia, HA, sore throat, abdominal or
muscular pain, irregular vomiting
POLIOVIRUS
▪ the last case of WILD poliovirus in the Philippines was in 1993;
polio-free since 2000 however outbreak was declared last Sept.
2019
▪ as of Jun 15, 2020, the Philippines is affected by both cVDPV1
and cVDPV2 (UNICEF WHO Philippines Polio Outbreak Situation
Report 22)
INCUBATION PERIOD: 8-12 days (range: 5-35 days)
TRANSMISSION
▪ Fecal – oral
▪ GIT → CNS
▪ Infectivity is for several days at room temp.
▪ Human: only known reservoir
▪ ↑ risk of acquisition of paralysis: tonsillectomy & IM injections
PPS Oral Exam Reviewer 2020
Nonparalytic Poliomyelitis (1%)
▪ Signs of abortive polio present + more intense HA, n/v; soreness
and stiffness of the posterior muscles of the neck, trunk, and limbs;
fleeting paralysis of bladder and constipation
● 1st phase: minor illness
● 2nd phase: CNS disease or major illness
▪ Nuchal and spinal rigidity (basis for nonparalytic polio diagnosis)
● Nuchal rigidity is present as well as head drop (normally, head
follows plane of the trunk when lifting up)
▪ Changes in reflexes precede weakness by 12-24 hrs
● 1st to diminish: spinal, gluteal, abdominal, cremasteric,
superficial reflexes
● Changes in DTR occur 8-24h after superficial reflex are
depressed → impending paresis
● Complicated or progressive illness
● At high risk for complications (< 2yo, chronic pulmo, cardio,
renal, hepa, hema, metabolic, neuro, neurodevelopmental D/O,
immunosuppressed, pregnant, postpartum (2wk), < 19yo w/ longterm aspirin or salicylate medication, BMI ≥ 40, residents of long
term facilities)
▪ Can also be considered for any previously healthy, symptomatic
patient not at high risk if tx can be initiated within 48 hrs of onset
(uncomplicated influenza)
● Oseltamivir BID x 5 days
● Clinical benefit is greatest when antiviral is given within 2 days
Post exposure Prophylaxis
▪ Routine use not recommended; consider for:
● unvaccinated persons at high risk of influenza complications
● persons for whom vaccine is CI
● residents/patients in care facilities
▪ May use oseltamivir (PO) & zanamivir
▪ Can be started within 48h of exposure up to 7 days after the last
known exposure
▪ CDC/IDSA: minimum 2wks – 1wk after the last known case is
identified whichever is longer
▪ Chemoprophylaxis with antiviral is not a substitute for vaccination
▪ No specific antiviral
▪ Mgt is supportive and aimed at limiting progression of disease,
preventing skeletal deformities and preparing the child & family for
prolonged tx
▪ All IM injections & surgical procedures are contraindicated during
acute phase of illness (1st wk) to prevent progression of disease
▪ Abortive Poliomyelitis – supportive, rest x 2wks, do check-up 2
months later
▪ Nonparalytic Poliomyelitis – analgesic + hot pack compress 15-30
min Q2-4hr, hot tub baths, firm bed, footboard or splint, gentle PT;
check-up 2mos after recovery
▪ Paralytic Poliomyelitis
● Suitable body alignment, change position Q3-6hr, active and
passive movement, opiates and sedatives, bethanecol (bladder
paralysis) or bladder compression, catheter
● Head-low prone position with face to 1 side to prevent
aspiration in those with bulbar polio
● Pts w/ pure bulbar polio may require tracheostomy because of
vocal cord paralysis or constriction of the hypopharynx
● Impaired ventilation must be recognized early
PREVENTION
Polio Eradication and Endgame Strategic Plan 2013-2018
▪ Withdrawal of trivalent OPV (tOPV) with bivalent (bOPV) in all
countries by 2016 and addition of 1 dose of IPV
● risk of VDPV was highest w/ type 2 strain → switch from tOPV
to bOPV
● IPV will protect against type 2
▪ replacement of bOPV with IPV in all countries by 2019 (to prevent
PROGNOSIS
▪ Excellent if uncomplicated; fatal if severe
PREVENTION
INFLUENZA VACCINE
▪ Trivalent (IM or SC) Quadrivalent (IM)
▪ Minimum age: 6 months
For pediatric dose, follow the manufacturer’s
recommendation:
▪ 6mos-8yo receiving vaccine for the 1st time should
receive 2 doses separated by at least 4 weeks
▪ If only one dose was given during the previous influenza
season, give 2 doses of the vaccine then 1 dose yearly
thereafter
▪ 9-18yo should receive one dose of the vaccine yearly
▪ Annual vaccination should begin in February by may be
given throughout the year
Bulbar Poliomyelitis
▪ Hypertension and dysautonomia → associated
irregular/failed respiratory effort, delirium, coma
w/
Immobilized for long periods:
▪ Atrophy of the limb, failure of growth, deformity, pneumonia,
renal stones (hypercalcemia/hypercalciuria sec to bone
resorption)
▪ Acute gastric dilation, melena from superficial intestinal
erosions (rare: perforation), HTN, cardiac irregularities,
myocarditis, acute pulmonary edema,
PROGNOSIS
▪ Good in inapparent, abortive and aseptic meningitis syndrome
▪ Severe bulbar poliomyelitis – 60% fatal
▪ Paralysis
● Maximum: 2-3 days after onset of paralytic phase (PP)
● Recovery: w/in 6mos (If persistent > 6mos, permanent
paralysis)
POSTPOLIO SYNDROME
▪ 30-40% who survived paralytic polio
▪ Occurs after 30-40yo
▪ Common in prev. wild type infection
▪ Muscle pain & exacerbation of weakness or development of
new weakness or paralysis
▪ Risk: Female, presence of permanent residual impairment after
recovery,  length of time since acute infection
POLIO OUTBREAK RESPONSE
▪ DOH initiated a Supplemental Immunization Activity to at-risk
Batch Clingy
Antigenic Variation
▪ Antigenic Drift – minor change within subtype → new strains of
same type (influenza A & B); contributes to annual epidemics
▪ Antigenic Shift – major change in subtype → new influenza A
subtype with little or no immunity (influenza A)
● Reassortment: proteins in non-human hosts could be
introduced to humans → pandemic
197
PATHOGENESIS
▪ Adsorb on poliovirus receptor (CD155) mostly on the epithelial
cells lining the tonsil follicle and small intestine → penetrates cell
& releases viral RNA → translated to produce proteins for RNA
replication & shuts off host protein synthesis
▪ Mature virus is produced in 6-8 hours
▪ Wild type virus accesses the CNS thru peripheral nerves
● primarily affects the anterior horn cells (SC) and the cranial
nerve nuclei (brainstem)
▪ Perineuronal inflammation & mixed inflammatory reaction →
extensive neuronal destruction
● >50% motor neurons destroyed: Limb weakness
● involvement of the reticular formation (containing vital
centers) → poor outcome
Paralytic Poliomyelitis (0.1%)
VDPV with continued OPV use)
Spinal Paralytic Poliomyelitis
▪ 2nd phase after abortive poliomyelitis
● Pt recovers for 2-5 days but followed by severe HA, fever with
exacerbation of previous systematic symptoms
▪ Severe muscle pain, paresthesia, hyperesthesia, fasciculation,
spasms
▪ Spotty distribution of paralysis → w/n 1-2 days asymmetric flaccid
paralysis or paresis occurs (proximal > distal), nuchal stiffness,
hyperactive DTRs → diminution of reflexes → paresis or flaccid
paralysis
▪ Weakness of some muscle of neck, abdomen, trunk, diaphragm,
thorax, or extremities
▪ Bowel & bladder dysfunction often accompany paralysis of lower
limbs
National Immunization Program
▪ 3 doses bOPV given starting at 6 weeks, 4 weeks apart (6-10-14)
with 1 dose IPV given together with the 3 rd dose of bOPV
regions using bOPV and mOPV2
▪ No new polio cases reported after Feb 15, 2020 (UNICEF WHO
Philippines Polio Outbreak Situation Report 22, June 15 2020)
IPV only schedule
▪ given in combination with DPT-containing vaccines
▪ 3 doses starting at 6 weeks, 4 weeks apart
▪ 2 booster doses (either OPV or IPV): between 12-18 mos and 4-6
yo
Provocation Paralysis (subset of spinal paralytic polio)
▪ occurs in 50-60% after IM injection
▪ Initially present with fever and paralysis
● Most have abrupt flaccid paralysis
● Some have spasm, ↑ muscle tone with transient ↑ DTR
▪ Once temperature is normal, progression of paralysis stops
▪ Recovery is within 6 months.
● The lack of improvement within 1st several weeks or months
after → permanent paralysis
▪ CSF is often normal during minor illness; pleocytosis with PMN
predominance early in the course then shift to mononuclear, CSF
CHON normal to slightly elevated
Bulbar Poliomyelitis
▪ Dysfunction of CN and medullary centers (CN involvement is
seldom permanent)
▪ Paralysis of facial, extraocular, masticatory muscles (+) respiratory
difficulty 1) nasal twang to voice/cry 2) inability to swallow
smoothly 3) accumulated pharyngeal secretions 4) absence of
effective coughing 5) nasal regurgitation of saliva 6) deviation of
palate, uvula, tongue 7) involvement of vital centers in Medulla 8)
paralysis vocal cord/s 9) rope sign: acute angulation b/w chin and
larynx (weakness of hyoid muscles)
▪ HTN & other autonomic disturbances are common
▪ No apparent involvement of the SC but bulbar disease may
culminate in an ascending paralysis (Landry type); uncommon
Paralytic Poliomyelitis w/ Ventilatory Insufficiency
▪ Components that contribute to respiratory insufficiency: anxiety,
fear → overventilation → respiratory alkalosis
PPS Oral Exam Reviewer 2020
Batch Clingy
Polioencephalitis
▪ Rare with higher centers of the brain severely involved
▪ Seizures, coma, spastic paralysis, increased reflexes, irritability,
disorientation, drowsiness, coarse tremor, peripheral or CN
paralysis
▪ Hypoxia and hypercapnia due to respiratory insufficiency
198
▪ Pure spinal polio: tightness, weakness, or paralysis of respiratory
muscles (cervical, thoracic)
▪ Pure bulbar polio: paralysis of motor CN nuclei ± vital centers (9 th,
10th, 12th → airway obstruction
▪ Virus is isolated from water sources, sewage, wet soil,
contaminants from drinking water, swimming pools, ponds,
hospital water reservoirs
INCUBATION PERIOD: 3-6 days
▪ Acute Hemorrhagic Conjunctivitis (AHC) 1-3 days
NONPOLIO
ENTEROVIRUSES
TRANSMISSION
▪ Fecal – oral
▪ Respiratory
▪ Airborne & eye-hand-fomite-eye transmission (AHC)
▪ Mother to neonate (vertical perinatally, peripartum,
breastfeeding, intrafamilial, sporadic/epidemic transmission from
nurseries)
▪ Fomites, tickborne
Risk:
▪ Water contamination, diaper change
▪ Symptomatic/asymptomatic shed virus from:
● Respiratory tract <1-3wks
● Feces 7-11wks
● Mucosal sites for longer periods
PATHOGENESIS
▪ Initial replication in pharynx/ intestine (w/in mucosal M cells) →
multiplication in lymphoid tissue (tonsils, Peyer patches, regional
LN) → minor viremia (liver, spleen, BM, distant LN) → replication
is limited by host response (subclinical infection) OR proceeds →
major viremia (CNS, heart, skin)
▪ Tropism to target organs is determined in part by the infecting
serotype
▪ At risk for severe/chronic infection:
● Hypo/ agammaglobulinemia
● Perinatally infected neonates lacking maternal type-specific
Ab to infecting virus
PPS Oral Exam Reviewer 2020
Hand-Foot-and-Mouth Disease (Coxsackie A, B, Echo)
▪ Mild illness ± low-grade fever
▪ Inflamed oropharynx with scattered painful vesicles → ulcerate,
4-8 shallow lesions with surrounding erythema
▪ 3-7 mm tender maculopapular, vesicular, and/or pustular lesions
on hands>feet, buttocks and groin that resolve within a week
▪ Eczema coxsackium: disseminated vesicular rashes which may
complicate preexisting eczema
▪ Coxsackie A6: severe, atypical HFMD and herpangina – fever, gen
rash, pain, dehydration, desquamation of palms and soles,
onychomadesis (nail shedding)
Herpangina (Enterovirus, Coxsackie A)
▪ Sudden fever (up to 41OC, higher in younger age, lasts 1-4 days)
▪ Sore throat, dysphagia, painful lesions in the PP, HA, backache,
vomiting, abdominal pain, vesicles, and ulcers on the mouth →
enlarge 2-3 days, 1-15 lesions → resolution of symptoms in 3-7d
Respiratory
▪ Sore throat, coryza, wheezing, apnea, resp distress, pneumonia,
OM, bronchiolitis, croup, parotitis, exudative tonsillopharyngitis
▪ Pleurodynia/Bornholm disease (coxsackie B and echovirus) –
paroxysmal thoracic pain due to myositis of chest and abdominal
wall muscles, malaise, myalgia, HA, sudden fever. The pain subsides
w/in 3-6 days but can persist in weeks. May be assoc. with
meningitis, orchitis, myocarditis or pericarditis.
Ocular
▪ AHC (enterovirus D70 & coxsackie A24/A24 variant) - sudden
severe eye pain, photophobia, blurred vision, lacrimation,
conjunctival erythema and congestion, lid edema, preauricular LAD,
▪ Supportive
▪ Milrinone: may be used in severe enterovirus A71
cardiopulmonary disease
▪
Ig:
IV
and
intraventricular
infusion
to
treat
hypogammaglobulinemic patients w/ chronic enterovirus
meningoencephalitis
▪ IV Ig + corticosteroids: enterovirus (A71, D68) neurologic disease
▪ IF α and IF β: enterovirus myocarditis
COMPLICATIONS
▪ HFMD: encephalitis, AFP, myocarditis, pericarditis, shock
▪ Herpangina: dehydration, meningitis
▪ Respiratory infection:
Enterovirus A71 brainstem encephalitis
→ noncardiogenic pulmonary edema, hemorrhage and/or
interstitial pneumonitis
▪ Ocular infection: uveitis → destruction of iris, cataracts,
glaucoma
▪ Myopericarditis: sudden death (SIDS)
▪ Neurologic infection: seizures, obtundation, ICP, SIADH,
ventriculitis, transient cerebral arteriopathy and coma
▪ Neonatal infections
● Endothelitis, veno-occlussive disease, placentitis
● CNS necrosis and gen or focal neurologic compromise,
coagulopathy w/ intracranial or other bleeding; DIC
● Arrhythmias, CHF, MI, pericarditis,
● Hepatic necrosis, failure
● Adrenal necrosis and hemorrhage
● Rapidly progressing pneumonitis and pulmonary HTN
● Involvement of pancreas
● Rare: myositis, arthritis, NE, SIADH, HLH-like presentation,
BM failure, sudden death
● Fetal demise, nonimmune hydrops
PROGNOSIS
▪ Majority: excellent
▪ Morbidity and mortality assoc. w/ myocarditis, neurologic
disease, severe neonatal infections, infections in IC hosts
PREVENTION
▪ Good hygiene
▪ Chlorination of water
▪ Contact precaution in the hospital
▪ Droplet precaution if with respiratory syndromes
▪ Prophylactic Ig or convalescent plasma for nursery epidemic
▪ Pregnant (near term): avoid contact with ill individuals; if w/
suggestive illness, extend pregnancy to passively acquire
protective Ab
▪ Maintenance of high dose IVIg hypogammaglobulinemic
Batch Clingy
▪ e.g. Coxsackie virus & Echovirus/Parechovirus
▪ Humans only known natural reservoir
▪ Increased severity: young age, male, exp. to children, poor
hygiene, overcrowding, low socioeconomic status
DIAGNOSTICS
▪ in suspected cases of acute flaccid paralysis, 2 stool specimens
should be collected 24-48 hrs apart ASAP
● Poliovirus concentrations are high in the stool in the 1 st wk
after onset of paralysis
● Rectal swab may be done in children w/ constipation 2O to
paralysis
▪ Once poliovirus is isolated, it is sent to CDC or WHO to distinguish
b/w wild-type & vaccine-type strains
Nonspecific febrile illness
▪ most common symptomatic manifestation
▪ Duration: 4-7 days (range: 1 day to >1wk)
▪ Abrupt fever (38.5-40OC) – lasts a mean of 3 days, occ. biphasic
▪ Malaise, irritability, lethargy, anorexia, diarrhea, N/V, abdominal
discomfort, rash, sore throat, respiratory symptoms, mild
conjunctivitis, pharyngeal injection, CLAD, meningitis
▪ Older children: HA and myalgia
199
● Young age; immunosuppression
● Specific HLA Ag genes
● Immune response gene polymorphisms, ↓ vit A
subconjunctival hemorrhages (hallmark of eD70), superficial
punctate keratitis, eye discharge (serous → mucopurulent), fever,
HA. Recovery complete w/n 1-2 wk.
▪ Uveitis, chorioretinitis, uveoretinitis, optic neuritis, unilateral
acute idiopathic maculopathy
patients
Myocarditis and Pericarditis (25-35% enterovirus)
▪ CXR: cardiac enlargement
▪ 2DED: ventricular dilation, ↓ contractility, pericardial effusion
▪ ECG: ST segment, T wave & rhythm abnormality,  serum
myocardial enzymes
GIT and GU
▪ Diarrhea, hematochezia, pneumatosis intestinalis, NEC in
prematures
▪ Acute/chronic gastritis, intussusception, chronic intestinal
inflammation in hypogammaglobulinemic patients, sporadic
hepatitis (severe in neonates), pancreatitis (→ transient exocrine
pancreatic insufficiency), nephritis, IgA nephropathy
▪ Coxsackie B is second only to mumps as a cause of orchitis
Neurologic (coxsackie B, echo, entero D70 & A71)
▪ Enteroviruses are the most common cause of meningitis in
mumps immunized population
● Common in < 3mos old
● Most are mild and lack meningeal signs, but nuchal rigidity is
apparent in >1-2yo. Fever resolves in 3-5d and other symptoms
within a week
▪ Enteroviruses are also responsible for ≥ 10-20% of encephalitis
● Nonspecific symptoms → encephalopathy
● Seizures, hemichorea, acute cerebellar ataxia, aphasia,
extrapyramidal symptoms
▪ Chronic Enterovirus Meningoencephalitis: high risk in pts with Ab
or combined immunodeficiencies & pts who are receiving anti-CD20 Ab therapy; presents as insidious intellectual and/or personality
deterioration, altered mental status, seizures, motor weakness, 
ICP.
▪ Enteroviral infections may also present as acute flaccid myelitis
Infections in Transplant Recipients and Patients with Malignancies
▪ Progressive pneumonia, severe diarrhea, pericarditis, heart
failure, meningoencephalitis, disseminated disease
PPS Oral Exam Reviewer 2020
Batch Clingy
Myositis and Arthritis
Neonatal Infections
▪ Majority are asymptomatic
▪ Fever, hypothermia, irritability, lethargy, anorexia, rash (MP),
jaundice, respiratory symptoms, apnea, hepatomegaly, abdominal
distention, emesis, diarrhea, decreased perfusion
▪ Benign course with fever resolution in 3d and other symptoms in 1
week.
▪ Some have severe disease dominated by a combination of sepsis,
meningoencephalitis, mypcarditis, hepatitis, coagulopathy and/or
pneumonitis
200
▪ Bronchiolitis is a clinical diagnosis
▪ rhinorrhea: 1st sign which persists throughout the illness
→ 1-3 days ff by cough w/ sneezing and intermittent low-grade
fever (fever is an inconsistent sign of RSV infection)
▪ PE: diffuse fine inspiratory crackles and expiratory wheezes
▪ progression of illness → air hunger, tachypnea, IC and SC
retractions, hyper expansion of chest, restlessness, peripheral
cyanosis
● signs of severe, life-threatening illness: central cyanosis, RR>70
bpm, listlessness, apneic spells, significantly hyper expanded chest,
silent auscultation (poor air movement)
▪ Presence of ileus or other abdominal signs, high temperature and
circulatory collapse → consider bacterial etiology; initiate antibiotic
treatment
INCUBATION PERIOD: 3-5 days
DIAGNOSTICS
▪ CXR: often normal in the initial phase; 70% of hospitalized infants
show hyperexpansion of the chest, peribronchial thickening,
interstitial infiltrates; consolidation (unusual); pleural effusion (rare)
● Lobar consolidation without other signs or w/ PE should be
considered of bacterial etiology until proved otherwise
▪ WBC normal or  w/ neutrophilic or mononuclear predominance
● Neutrophilia, neutropenia in the presence of severe disease:
consider bacterial etiology
▪ Hypoxemia via pulse oximeter or ABG
▪ Definitive diagnosis: viral culture, PCR or antigen testing
TRANSMISSION:
▪ Droplet or through fomites inoculated in the nasopharynx
PATHOGENESIS
Bronchiolitis
▪ airway narrowing caused by virus-induced necrosis of
bronchiolar epithelium, hypersecretion of mucus, round cell
infiltration and edema of surrounding submucosa → mucus plug
formation obstructing bronchioles → hyperinflation or collapse of
distal lung tissue during expiration
Pneumonia
▪ generalized infiltration, epithelial shedding extends to bronchi &
alveoli
▪ smooth muscle hyperreactivity contributes to airway narrowing
in older subjects but less typical in young infants
▪ largest of the human herpesviruses
▪ exists as genetically diverse forms w/in an individual → virus
persists for a lifetime while inducing chronic immune activation
INCUBATION PERIOD: highly variable
CYTOMEGALO
VIRUS
TRANSMISSION
Community
▪ horizontal (direct person to person) by intermittent shedding
from mucosal surfaces (saliva, genital secretions, urine)
● CMV is considered a sexually transmitted infection;
presumed cause for  spike in infection for adolescents and
young adults
▪ vertical (perinatal): genital secretions upon birth and
breastfeeding (most common route in early childhood; 60% rate
of infection)
● Infants infected through breast milk excrete virus in the saliva
and urine for prolonged periods thus serve as CMV reservoir for
spread to others
Nosocomial
PPS Oral Exam Reviewer 2020
▪ Most common: asymptomatic
Normal Host
▪ mononucleosis-like syndrome, fatigue, occ. CLAD, mild increase
transaminases, thrombocytopenia
Immunocompromised
▪ depends on the magnitude of the immunodeficiency
● profoundly immunocompromised hosts such as HSCT
recipients can present with disseminated infection
●in less immunocompromised patients (i.e. solid organ
transplant recipients), CMV infection can present with fever,
hematological abnormalities and mild hepatocellular dysfunction
▪ clinical disease develops 30-60 days post-transplantation (prior to
widespread antiviral prophylaxis use)
Congenital Infection
▪ 90% of infected infants will have no clinical manifestations in the
NB period; 10% will be symptomatic
● IUGR, hepatosplenomegaly, petechial rashes, jaundice,
microcephaly, chorioretinitis
▪ Symptomatic treatment for uncomplicated bronchiolitis
▪ IV or tube feeding when suckling is difficult due to tachypnea
▪ Humidified O2 and suctioning for hypoxic infants
● high-flow nasal cannula (mostly useful for pressure support)
● nCPAP for infants w/  WOB; mechanical ventilation if with
respiratory failure
▪ Heliox (helium + O2) for infants with severe respiratory distress
but do not require large amount of O2
▪ Limited use of α and β2 agonist and corticosteroids (2014 AAP
Bronchiolitis Clinical Practice Guideline)
● Corticosteroid is indicated only in older children with
established diagnosis of asthma (its use is assoc. with prolonged
virus shedding and is of no proven clinical benefit)
▪ Ribavirin has no clear beneficial effect; no longer used for routine
therapy of RSV disease
▪ Recurrent wheezing in 30-50% of children with severe RSV
bronchiolitis in infancy
● Likelihood of the recurrence is increased in the presence of
an allergic diathesis
PROGNOSIS:
▪ Almost all deaths occur among young, premature infants or
infants with underlying disease
PREVENTION
▪ Contact precaution isolation to prevent nosocomial spread
▪ transplacentally acquired anti-RSV maternal IgG serum Ab
appear to provide partial protection for the neonate during 1st 46 weeks of life
● Breastfeeding also provide protection on severe RSV but
seen in female infants only
PASSIVE IMMUNOPROPHYLAXIS
▪ Palivizumab (15 mg/kg IM monthly): neutralizing humanized
murine monoclonal Ab is recommended to protect high-risk
children against serious complications such as:
(1) infants born < 29 wk in the 1 st year of life (2) born < 32 wk w/
hx of chronic lung disease of prematurity in the 1st yr of life
(3) < 1 yo w/ significant CHD ff. cardiac transplantation (children
< 2 yr old)
(4) < 2 yr old w/ profound IC conditions during RSV season
(5) 1 yo w/ congenital abn in airway or NM disease that
compromises the handling of respiratory secretions
(6) Administration in the 2nd yr of life for children who required
≥ 28 days O2 support after birth and ongoing tx for chronic
pulmonary disease
Immunocompromised
▪ treatment has been shown to limit both the morbidity and the
mortality
▪ drugs: ganciclovir, foscarnet, cidofovir
▪ heart-lung and lung transplant recipients are at a high risk for
severe manifestations
▪ most common long term sequelae in congenital infection:
SNHL
Congenital
▪ ganciclovir (could limit hearing loss and possibly improve
developmental outcome)
▪ monitor development, NM function, audiologic, and
ophthalmologic system
PREVENTION
Immunoprophylaxis
▪ Passive: passive transfer of anti-CMV Abs have been utilized to
limit disease but not infection in allograft recipients
▪ Active: vaccine trials show that protection was very short lived,
effectiveness not convincing
Perinatal
▪ severe infection ff. breast milk ingestion w/ end-organ disease has
been successfully treated w/ ganciclovir
▪ children who are shedding do not require exclusion or
isolation; apply standard precaution and hand hygiene
▪ Prevention of transmission in blood transfusion: freezing RC in
glycerol before administration, remove buffy coat or filtration to
remove WBC
▪ Prevention in human milk: pasteurization will inactivate CMV,
but freezing milk will only decrease viral titers
Batch Clingy
RESPIRATORY
SYNCITIAL
VIRUS
▪ Major cause of bronchiolitis and viral pneumonia in < 1 yo
▪ peak incidence of severe LRTI: 6 wks to 7 mos.
▪ infection is nearly universal by 2 yo
● reinfection occurs at least 10-20% per epidemic throughout
childhood
● reinfection may occur as early as a few weeks after recovery
● severity of illness during reinfection is usually lower than in
first infection (partial acquired immunity, more robust airway
physiology, increased age)
▪ Medical factors associated with higher risk:
● Chronic lung disease of prematurity
● CHD
● Immunodeficiency
● Prematurity
201
▪ blood products, allograft transplantation
Congenital
▪ in-utero
▪ CMV is thought to be transferred to the developing fetus
following hematogenous spread to the placenta
(see Nelson’s 21st Ed., Table 282.1 for Findings in Infants with
Symptomatic Congenital Cytomegalovirus Infection)
▪ Prevention in transplant recipients: prophylactic antiviral
therapy
▪ Lab findings consistent with congenital infection: direct
hyperbilirubinemia,  hepatic transaminases, thrombocytopenia,
abn. cUTZ/CT findings (periventricular calcifications)
Perinatal Infection
▪ not been assoc. w/ any clinical manifestations or assoc. w/ long
term sequelae
▪ in rare cases, breast milk transmission of CMV to extremely
premature infants or infants born to nonimmune women can result
in severe, disseminated infections assoc. w/ end-organ disease and
death
DIAGNOSTICS
▪ Serologic reactivity for CMV is lifelong ff. primary infection
● presence of IgG Ab to CMV does not provide evidence of acute
infection
● IgM reactivity for CMV can be detected for prolonged periods
after acute infection; cannot be used reliably to estimate duration
of infection
▪ Recovery of virus from body fluids does not permit diagnosis of
CMV infection (d/t persistent intermittent shedding)
Congenital Infection
▪ Diagnosis of congenital CMV infections require recovery of
replicating virus and/or viral nucleic acids w/in first 2-3 wks of life
● NBS using saliva ff. by confirmation of positive screens using
urine assay
INCUBATION PERIOD: 2 days – 2 weeks
PPS Oral Exam Reviewer 2020
▪ Herpes gingivostomatitis
● most often affect 6 mo-5 yr
● sudden extreme pain in the mouth, drooling, refusal to eat or
drink, fever (up to 40.6OC), swollen gums, vesicles throughout the
oral cavity, ulcers – may be covered w/ yellowish-gray membrane,
tender submandibular, submaxillary, CLAD, foul breath, in the initial
phase there may be tonsillar exudates suggestive of bacterial
pharyngitis
● in older patients: tonsillitis, pharyngitis rather than herpes
gingivostomatitis
● untreated, symptoms resolve in 7-14 days; LAD persists for
several weeks
▪ Herpes Labialis
● fever blisters/cold sores: most common in recurrent HSV1
DIAGNOSTICS
▪ Culture: highest yield from ruptured herpetic vesicle and
vigorously rubbing base of lesion to collect fluid and cells
▪ PCR: test of choice in CSF for suspected HSV encephalitis
▪ Serology:
● HSV IgM: unreliable
● HSV IgG: ≥ 4-fold rise between acute & convalescent sample is
useful in retrospect
▪ Neonate:
● culture of suspicious lesions; eye and mouth swabs PCR of both
CSF & blood
● elevation of liver enzymes as indirect evidence of
dissemination
▪ Acute Genital Herpes:
● culture or Ag detection
● HSV-2 type specific Ab testing for sexually experienced
adolescents or young adults with unexplained recurrent nonspecific
urogenital s/sx
▪ Tzanck test should not be performed due to low sensitivity
PROGNOSIS:
▪ most: self-limiting except in IC and newborns
▪ recurrent oral-facial herpes s/p dermobrasion or laser
resurfacing can be severe and lead to scarring
▪ life-threatening: neonatal herpes, herpes encephalitis, HSV in
IC and burn patients
▪ Recurrent ocular infections → blindness
PREVENTION
▪ good hygienic practices, contact precaution
▪ Decreases risk: male circumcision, daily oral A, V, or F during
the last 4 wk of gestation for pregnant w/ a hx of genital herpes,
delivery by CS for pregnant women with active genital herpes at
the time of delivery
▪ There is NO concern of transmission through milk: (+) active
lesions on the breasts can feed expressed milk, but no part of
pump should come in contact w/ lesions during expression
Batch Clingy
HERPES SIMPLEX
VIRUS
▪ 2 closely related HSVs (HSV-1 & HSV-2); contains the ff.
● 12 glycoproteins: target for humoral immunity
● other nonstructural proteins: target for cellular immunity
● 2 proteins (viral DNA polymerase and thymidine kinase):
target of antiviral drugs
▪ HSV 1 and 2 differ in glycoprotein G genes
● used in serologic tests to discriminate whether a patient has
been infected with HSV-1, HSV-2 or both
▪ Humans are the only natural host
▪ Both viruses are equally capable of causing initial infection at any
anatomic site but differ in their capacity to cause recurrent
infections
● HSV-1 → recurrent oral infections
●HSV-2 → recurrent genital infections
▪ HSV is the leading cause of sporadic, fatal encephalitis in children
and adults
Noncongenital Infections
▪ Demonstration of CMV-specific IgG seroconversion or the
presence of CMV-specific IgM Abs represent evidence of a newly
acquired CMV infection
▪ Hallmarks: skin vesicles and shallow ulcers (small, 2-4 mm vesicles
surrounded by erythematous base → shallow minimally
erythematous ulcers)
202
Perinatal:
▪ in utero, during delivery, or neonatal period
▪ during delivery, it can enter thru conjunctiva, mucosal
epithelium of nose and mouth, breaks in skin w/ scalp electrode
or forceps use
▪ documented also via CS
PATHOGENESIS
▪ Primary infection: HSV seronegative and have no preexisting
immunity that tends to be severe
▪ Nonprimary first infection: prev. infected HSV-1 who have
become infected for the 1st time with other type of HSV (less
severe due to cross-protection)
▪ Recurrent infection: reactivated latent infection in regional
sensory ganglion neurons (less severe and shorter duration)
▪ viral infection begins at a cutaneous portal of entry → replicates
in skin and mucous membranes → spreads to neural tissue
(sensory ganglia)
▪ virus replicates in some sensory neurons → progeny virions sent
back to periphery → replicate further in skin or mucosal surfaces
● movement of virus through this neural arc is responsible for
the development of characteristic herpetic lesions
▪some infected neurons do not support viral replication → latent
infection w/ undefined changes that trigger virus to replicate
▪ Viremia/hematogenous spread: occur in neonates, individuals
with eczema and severely malnourished children
● most common site: vermillion border of lip, it may also occur
on nose, chin, cheek, oral mucosa
● burning, tingling, itching or pain 3-6 hr (rarely up to 2 days)
before development of herpes lesion (small group of erythematous
papules → vesicle → ulcers or pustules)
● lesions completely heal in 6-10 days
▪ Cutaneous Infections
● contact sports: wrestling (herpes gladiatorum), rugby
(scrumpox)
● skin trauma w/ exposure to infectious secretions → herpes
labialis-like lesions that completely heal 6-10 days
● regional LAD may occur; systemic symptoms are uncommon
● recurrences are assoc. w/ local edema or local neuralgia
▪ Herpes whitlow
● HSV of paronychia (fingers or toes) in infants and toddlers due
to thumb sucking, adolescents due to genital secretions
● (+) LAD, lymphangitis, neuralgia
● Onset is 2-7 days after exposure (itching, pain & erythema),
persists x 10 days, complete recovery x 18-20 days
● life-threatening in patients with eczema (eczema herpeticum),
pemphigus, burns, Darier disease, and ff. laser skin resurfacing
▪ Genital herpes
● genital-genital (HSV-2) or oral-genital (HSV-1)
● local burning and tenderness → vesicles on genital mucosal
surfaces, keratinized skin around anus, buttocks, & thighs
● urethritis, dysuria
● women may experience watery vaginal discharge; males: clear
mucoid urethral discharge
● Systemic s/sx are common: fever, headache, myalgia →
aseptic meningitis (15%)
● complete healing: 2-3 weeks, may recur (sometimes
asymptomatic)
● For young children: consider abuse or autoinoculation
▪Ocular Infections
● kerato/conjunctivitis: usually unilateral, assoc. w/ blepharitis &
tender preauricular LAD
● vesicles may be seen on the lid margins and periorbital skin
● untreated infection generally resolves in 2-3 wks
● corneal involvement is rare; retinal infections are rare, more
likely in neonatal herpes & IC w/ disseminated HSV
▪ HSV Encephalitis
● Acute necrotizing infection affecting frontal/temporal cortex
and limbic system.
● The cause beyond neonatal period is almost always HSV-1.
● Fever, headache, nuchal rigidity, nausea, vomiting, gen
seizures, alteration of consciousness
● anosmia, memory loss, peculiar behavior, expressive aphasia,
change in speech, hallucinations, focal seizure
● untreated: 75% → coma and death
PPS Oral Exam Reviewer 2020
TREATMENT
▪ Acyclovir (A): poorest bioavailability, more frequent dosing
▪ Better oral bioavailability: Valaciclovir (V) prodrug of acyclovir and
Famciclovir (F) prodrug of penciclovir
Acute Oropharyngeal infections
▪ Gingivostomatitis: A (start within 72 hours)
▪ Herpes labialis: oral > topical; recurrence lesions in adolescents:
oral A, V & F shortens duration; frequent or severe recurrences:
long term use of A or V
Cutaneous infections
▪ Keratitis: topical trifluridine and ganciclovir
▪ Herpes gladiatorum: oral A or V at 1st signs of outbreak can
shorten the course of recurrence; if w/ hx of recurrence: chronic
daily prophylaxis w/ V
▪ Herpetic whitlow: no clinical trials assessing the benefit of
antiviral, high dose A started 1st signs of illness abort some
recurrences and reduce duration of others in adults.
▪ Eczema herpeticum: clinical trial A (effective in adults)
▪ Oral-facial HSV: V & F in adults for prevention since HSV can
reactivate after cosmetic facial laser resurfacing → extensive
disease and scarring,
▪ HSV infections in burn pts: Intravenous A
▪ Daily prophylactic use of antiviral can prevent reoccurences of
erythema multiforme for herpes labialis
Genital Herpes
▪ A, V, or F for initial infection: reduce severity and duration but has
no effect in frequency of subsequent recurrent infections
▪ Recurrences: 3 options (no treatment, episodic or long-term
suppressive therapy)
Ocular Infections: seek consult with an ophthalmologist
CNS infections: older than neonate: IV A (10 mk Q8 over an hour for
14-21 days)
Immunocompromised
▪ Intravenous A: Severe or disseminated:
▪ oral A, V or F: Less severe or suppression of recurrences during
episodes of significant immunosuppression
▪ Resistance to A and Penciclovir → Foscarnet & Cidofovir
Perinatal Infections
▪ proven or suspected: high-dose IV A (60mkday q8 x 14 days for
SEM and 21 days for CNS or disseminated)
▪ suppressive oral A x 6 mo after completion of IV therapy improves
the neurodevelopment of infants with CNS infection and prevent
cutaneous recurrences, measure absolute neutrophil count at week
2, week 4 and monthly
▪ Regardless of disease classification, pxs should have an
ophthalmologic exam and neuroimaging to establish baseline brain
Batch Clingy
TRANSMISSION:
▪ direct contact between mucocutaneous surfaces
● HSV 1: oral secretions
● HSV 2: anogenital contact
▪ all infected harbor latent infection & experience recurrent
infections w/c may be symptomatic or unrecognized and thus
periodically contagious
203
▪ HIV-1 and HIV-2 are members of the Retroviridae family
▪ HIV-1 genome:
● contains 2 copies of ssRNA
● has long terminal repeats (for regulation and expression of
HIV genes)
● other major regions (encodes viral part): GAG (core
proteins), POL (enzymes), ENV (envelope proteins)
▪ HIV-2 genome:
● Subtypes A & B: major causes of infection in humans (rare in
child)
● most prevalent in West Africa but with increasing number of
cases reported in Europe and South Asia
HUMAN
IMMUNODEFICIENCY
VIRUS
▪ Difference of HIV-2 from HIV-1:
● accessory genes: vpx gene compared to vpu gene in HIV-1
● more difficult to dx due to major difference in genetic
sequences
● longer asymptomatic stage
● slower declines in CD4+,
● less transmission perinatally
▪ HIV tropism determined by envelope glycoprotein (Env) and
chemokines as co-receptors:
● gp120: contains the highly variable V3 loop which is
immunodominant for neutralizing Ab; carries binding site for CD4
● gp41: immunogenic; used to detect HIV-1 Ab in diagnostic
assays
● CXCR-4: co-receptor for attachment to lymphocyte
● CCR-5: facilitates entry to the macrophages
EPIDEMIOLOGY
▪ majority of HIV infections in childhood: vertical transmission
▪ 13-24 yr old constitute the growing population of newly infected
(81% MSM)
HIV and AIDS Estimates (UNAIDS Country Fact Sheet: Philippines,
2019)
▪ Adults and children living with HIV: 97,000 (81,000-110,000)
▪ Adults and children newly infected with HIV: 16,000 (13,00018,000)
▪ HIV incidence per 1000 population (all ages): 0.14 (0.12-0.17)
PPS Oral Exam Reviewer 2020
▪ Perinatal Infections
● INTRAUTERINE INFECTION: skin vesicles or scarring,
chorioretinitis, keratoconjunctivitis, microcephaly or
hydranencephaly
● POSTPARTUM INFECTION: either (1) disease localized to the
skin, eyes or mouth, (2) encephalitis with or without skin, eye and
mouth involvement, (3) disseminated infection
▪ At birth: PE is normal
▪ Initial s/sx: LAD, hepatosplenomegaly, FTT, chronic or recurrent
diarrhea, respiratory symptoms, oral thrush
▪ S/sx commonly seen in children: recurrent bacterial infection,
early onset of progressive neurologic deterioration, chronic
parotid swelling & lymphocytic interstitial pneumonitis
▪ CDC Surveillance Case Definition for HIV infection is based on the
age-specific CD4+ T-lymphocyte percentage of total lymphocytes
● EXCEPT when a stage 3-defining opportunistic illness
supersedes the CD4 data
(see Nelson’s 21st Ed., Table 302.2 for Stage 3-Defining
Opportunistic Illnesses in HIV Infection)
Infection
▪ 20% of AIDS-defining illnesses are recurrent bacterial infections
caused by encapsulated organisms (S. pneumoniae, Salmonella) &
most common serious infection: bacteremia, sepsis, pneumonia
▪ Opportunistic: usually a primary infection with a more fulminant
course
● Pneumocystis jiroveci pneumonia presents as ± fever,  RR,
dyspnea, hypoxemia w/ CXR: int. infiltrates or diffuse alveolar
disease
▪ Nontuberculous mycobacteria (NTM): most commonly caused by
Mycobacterium avium-intracellulare complex (MAC)
● disseminated MAC: fever, malaise, weight loss, night sweats,
diarrhea, abd. pain, rarely intestinal perforation or jaundice, focal
(lymphadenitis, osteomyelitis, tenosynovitis, and pulmonary
disease)
▪ Fungal: oral candidiasis as the most common that can progress to
esophagus char. by anorexia, dysphagia, vomiting, & fever
▪ Parasitic: intestinal cryptosporidiosis and microsporidiosis pres. as
chronic diarrhea → malnutrition
anatomy (MRI: most sensitive)
DIAGNOSTICS
▪ HIV Ab tests cannot be used to make a diagnosis of HIV infection in
infants younger than 24 mos.
● viral diagnostic assays (i.e. HIV DNA or RNA PCR) are more
useful in young infants, allowing definitive dx in most infected
infants by 1-4 mos.
▪ In any child older than 24 mos., demonstration of IgG Ab to HIV by
a repeatedly reactive enzyme immunoassay and confirmatory HIV
PCR establishes the diagnosis
▪ Breastfed infants should have Ab testing performed 12 wk ff.
cessation of BF to identify those who became infected at the end of
lactation by the HIV-infected mother
▪ Testing should be done within the first 12-24 HOL for high-risk
infants
● If negative at first 1-2 DOL, rpt. at 2-3 wks. of age, 4-8 wks. of
age and 4-6 mos.
● for higher risk infants, additional virologic testing should be
considered at 2-4 wks after cessation of ARV prophylaxis
▪ positive virologic assay should be confirmed by a rpt test on a 2nd
specimen ASAP (exclude false positive)
▪ Confirmed diagnosis: 2 positive virologic test results obtained
from different blood samples
▪ Presumptive exclusion (non-BF infants): 2 or more negative
virologic test or 1 negative virologic test at ≥ 8 wks or 1 negative HIV
Ab test at age ≥ 6 mos.
▪ Definitive exclusion (non-BF infants): 2 or more negative virologic
tests with one obtained at ≥1 mo and one at age ≥ 4 mos or 2
negative HIV Ab tests from separate specimens obtained ate age ≥ 6
mos.
TREATMENT
▪ to suppress the virus for extended periods of time and changes the
course to a chronic process
▪ Basis of combination antiretroviral therapy (cART)
● uninterrupted HIV replication progresses to AIDS
● magnitude of viral load predicts rate of disease progression
● at least 3 drugs with at least 2 diff. MOA: restricts the selection
of ART-resistant mutants
● sustainable suppression of HIV replication is best achieved by
COMPLICATIONS
▪ For IRIS: continuation of ART ± NSAIDS or corticosteroids
▪ Virologic failure: repeated plasma viral load ≥ 200 copies/mL
after 6 mo of therapy
PROGNOSIS
▪ Best prognosis: sustained suppression of plasma viral load and
restoration of normal CD4 count
▪ Worst prognosis: opportunistic infections, encephalopathy,
regressing development milestones, wasting syndrome
▪ Poor outcome:
Persistent fever, oral thrush, serious bacterial infection,
hepatitis, persistent anemia,  platelet
PREVENTION
▪ All pregnant women should be tested for HIV and if (+), treat
w/ cART irrespective of viral load or CD4 count
▪ All infants born to HIV-infected mother should receive
zidovudine prophylaxis for 4-6 weeks
▪ HIV-infected mothers living in resource-limited settings should
breastfeed their infants until at least 12 mos. of age, with
exclusive BF for the first 6 mos and cART should continue
▪ All HIV-exposed and HIV-infected children should receive
standard pediatric immunization
● Live OPV & BCG should NOT be given
▪ Do TST or IGRA once a year (>5 mm positive)
▪ All infants b/w 4-6 wks and 1 y/o who are proven to be HIVinfected should receive prophylaxis to prevent P. jiroveci
pneumonia regardless of the CD4 count or percentage
▪ Prophylaxis:
● P.jiroveci: TMP SMX or dapsone/ atovaquone/ aerosolized
pentamidine
● MAC: azithromycin, clarithromycin, rifabutin
▪ To reduce incidence of opportunistic infections: good
handwashing, avoid raw or undercooked food, drinking,
swimming in lake or river water or being in contact with young
farm animals, risk of playing w/ pets
▪ For sexually active: condoms, male circumcision, 1% vaginal gel
formulation of tenofovir, for MSM: once daily dosing of
coformulated tenofovir and emtricitabine
Batch Clingy
▪Immunocompromised
● The most common: mucositis & esophagitis, atypical lesions
slowly enlarge, ulcerate → necrotic
● tracheobronchitis, pneumonitis, anogenital infection
● disseminated infection: sepsis-like, liver and adrenal
involvement, DIC and shock
204
INCUBATION PERIOD
AIDS: 8-12 yr
TRANSMISSION:
▪ Sexual contact
▪ Parenteral exposure to blood: 3-6% of all pediatric AIDS cases
▪ Vertical transmission: 3 routes
(1) Intrauterine:
● 20-30% detectable in culture or PCR as early as 10 wk AOG up
to 1st wk of life
● most occurs in late gestation when the vascular integrity of
the placenta weakens and microtransfusion across the maternalfetal circulation occurs
(2) Intrapartum:
● higher percentage of HIV-infected children acquire the virus
this way (70-80% of infected infants do not demonstrate
detectable virus until after 1 st week of life)
● via mucosal exposure to infected blood and cervicovaginal
secretions and intrauterine contractions causing late
microtransfusions
(3) Postpartum:
● accounts for 40% of perinatal infections in resource-limited
countries
● risk of transmission through BF is increased by viremia during
primary infection
PATHOGENESIS
▪ Attach to dendritic cells, reach lymphatic tissue and binds to cells
expressing CD4
▪ within 3-6 weeks after infection: acute retroviral syndrome
(acute HIV infection) - burst of plasma viremia that occurs
when HIV replication reaches a threshold; presents like flu or
mononucleosis (fever, rash, pharyngitis, LAD, malaise,
arthralgia, fatigue,  liver enzymes)
▪ within 2-4 months, clinical latency:
● cellular & humoral immune response established
● viral load declines, CD4 return to mod decreased levels
● asymptomatic
● very high turnover of virus and marked depletion of CD4 cells
● HIV virions and their immune complexes migrate through the
LN→immune activation → promoting viral replication &
depletion of CD4 cells
For children, there are 3 distinct patterns:
▪ Rapid progression (15-24% of HIV-infected NB)
● onset 1st few months of life,
● median survival time 6-9 months
● most have detectable virus in the plasma in the 1st 48 HOL→
peak 2-3 mo of age→stay high at least 1st 2 years of life
● occurs if intrauterine infection coincides with the rapid
expansion of CD4 cells in the fetus
▪ Slower progression (60-80%)
PPS Oral Exam Reviewer 2020
▪ Viral: HSV (recurrent gingivostomatitis), VZV, disseminated CMV,
measles, molluscum contagiosum, RSV, adenovirus, HPV
▪ Immune reconstitution inflammatory syndrome (IRIS)
● increased inflammatory response from the recovered immune
system to subclinical opportunistic infections
● may occur after appropriate ARV therapy; more commonly
observed in pts. with progressive disease and severe CD4 + Tlymphocyte depletion
● fever + worsening CM of the opportunistic infection or new
CM w/n 1st few weeks after initiation of ART
CNS involvement
▪ subtle developmental delay to progressive encephalopathy,
cognitive deterioration, impaired brain growth, attention problems,
psychiatric disorders
▪ cerebellar atrophy,  ventricular size, basal ganglia calcifications,
leukomalacia
▪ focal signs and tumor may imply comorbidities: CNS tumor
(lymphoma), opportunistic (toxoplasmosis, CMV, JC, HSV), stroke
Respiratory
▪ recurrent OM and sinusitis → invasive sinusitis and mastoiditis
▪ Lymphocytic Interstitial Pneumonia (LIP): most common chronic
process with nodular lymphoid hyperplasia leading to progressive
alveolar capillary block; CXR: chronic diffuse reticulonodular pattern
(lymphoproliferative response to EBV infection)
▪ Pneumonia secondary to S. pneumoniae, End-stage: P. aeruginosa
& other gram negative, TB
Cardiovascular - pre-cART era: LVH, LV dilation,  LV fractional
shortening, and/or HF; currently, cART has been shown to have a
cardioprotective effect
GI and Hepatobiliary
▪ Oral manifestations: candidiasis, periodontal disease, salivary
gland disease, and rarely, ulceration or oral hairy leukoplakia
▪ GIT involvement is common and a variety of pathogens can cause
GI disease; most severe & protracted: MAC and protozoa (Giardia,
Crypto, Isospora, Microsporidia)
▪ Most common symptoms: chronic or recurrent diarrhea w/
malabsorption, abdominal pain, dysphagia, FTT (less common:
wasting syndrome - loss of >10% BW w/ grave prognosis)
▪ AIDS enteropathy: syndrome of malabsorption with partial villous
atrophy not assoc. w/ specific pathogen (direct HIV infection)
▪ Chronic liver inflammation ± cholestasis, cryptosporidial
cholecsytitis
combinations of ART that px has not been exposed prev. and not
cross-resistant to drugs w/c the px. has been tx. previously
● drug interactions and toxicities should be minimal
● adherence to regimen is crucial
Initiation of Therapy
▪ < 1 yo: as soon as HIV diagnosis is confirmed
Age
1-6 yo
> 6 yo
Urgent
Stage 3 opportunistic infection or
Treatment
CD4
<500
<200
Treatment
strongly
recommended
Treatment
recommended
CD4
Moderate HIV symptoms or
500-999
200-499
Asymptomatic or w/ mild symptoms with
CD4
>1000
>500
Mechanisms of Action
▪ preventing viral entrance into CD4+ T cells
● Fusion inhibitors either bind to viral gp41 causing
conformational change (enfuvirtide) or blocks viral attachment to
CCR5 (maraviroc) which is an essential process in the viral binding
and fusion to the CD4+ cells
▪ inhibiting HIV reverse transcriptase or protease enzymes
● Nucleoside (or nucleotide) reverse transcriptase inhibitors
(NRTI): act like chain terminators and block further incorporation of
nucleosides preventing DNA synthesis
● Nonnucleoside reverse transcriptase inhibitors (NNRTI):
attach to reverse transcriptase and cause a conformational change,
reducing the activity of the enzyme
● Protease inhibitors (PI): bind to the site where the viral long
polypeptides are cut into individual, mature, and functional core
proteins that produce infectious virions before they leave the cell
▪ inhibiting integration of the virus into the human DNA
● Integrase inhibitors (INSTI): block the enzyme that catalyzes
the incorporation of the viral genome into the host’s DNA
Combination Therapy
▪ by targeting different points in the viral life cycle and stages of cell
activation and by delivering drug to all tissue sites, maximal viral
suppression is feasible:
● thymidine analog NRTI
● nonthymidine analog NRTI: to suppress replication in both
active and resting cells
● ritonavir-boosted PI, an NNRTI, or an INSTI: to produce
prolonged suppression of the virus
Renal disease
▪ focal glomerulosclerosis, segmental necrotizing GN & minimal
change
▪ Nephrotic syndrome: most common manifestation
Skin Manifestations
▪ early nonspecific signs: severe & unresponsive seborrheic
Batch Clingy
▪ Adult and child deaths due to AIDS: 1600 (1000-2400)
205
Immune changes in children:
▪ absolute CD4 cell depletion is less dramatic in infants (due to
normal relative lymphocytosis)
▪ lymphopenia: rare but usually found in older children or with
end-stage disease
▪ cutaneous anergy is common in HIV but also frequent in healthy
children (< 1 year old)
▪ polyclonal activation occurs early (Ab response to vaccination
may be abnormal)
▪ two distinct types: EBV-1 and EBV-2
● EBV-1 more prevalent worldwide; EBV-2 more common in
Africa
▪ both types lead to persistent, lifelong, latent infection
INCUBATION PERIOD: 30-50 days in adolescents; shorter for
children
EPSTEIN-BARR
VIRUS
TRANSMISSION
▪ Oral secretions
● shed consistently for >6 mo after acute infection then
intermittently for life
▪ Sexual contact
● penetrative sexual intercourse (esp type II), oral secretions
(kissing) and sharing water bottles
PATHOGENESIS
▪ after transmission, infects oral epithelial cells & tonsillar B
lymphocytes → viral replication → viremia & dissemination of
infected B lymphocytes into peripheral blood & lymphoreticular
system (atypical CD8 T lymphocytes activation)
▪ Latent infection:
● persists in memory B lymphocytes
● EBV-determined nuclear Ag (EBNA) are produced – important
in maintaining the viral episome
● reactivation is unlikely to be accompanied by distinctive
clinical symptoms
PPS Oral Exam Reviewer 2020
dermatitis
▪ recurrent or chronic episodes of HSV, herpes zoster, molluscum
contagiosum, flat warts, anogenital warts, candidal infections,
allergic drug eruptions (rare: SJS)
▪ Epidermal hyperkeratosis with dry scaling skin + sparse hair or hair
loss
Hematologic and Malignant Diseases
▪ Anemia (chronic infection, autoimmune factors, virus-associated:
hemophagocytic syndrome, parvovirus B19 red cell aplasia or drug
effect: zidovudine)
▪ Leukopenia and neutropenia (drug effect: TMP-SMX, ganciclovir,
zidovudine) → treatment w/ gCSF may be necessary
▪ Thrombocytopenia (immunologic, drug toxicity or idiopathic) →
cART may reverse thrombocytopenia in ART-naïve patients; IVIg in
severe thrombocytopenia
▪ deficiency of F2, 7, 9 → Vitamin K
▪ most commonly reported neoplasms: NHL, primary CNS
lymphoma, leiomyosarcoma (EBV associated); Kaposi sarcoma is
uncommon in HIV-infected children in resource-rich countries
▪ Anterior mediastinal multilocular thymic cysts: novel disease of
the thymus in a few HIV-infected children; cART may result in
resolution or spon. Involution
▪ Infectious Mononucleosis (>90%)
● majority of primary EBV infection are clinically silent in infants
and young children; in older patients, onset is insidious and vague
● classic triad of primary EBV infection: fatigue, pharyngitis,
generalized LAD
● malaise, fatigue, acute or prolonged (> 1 wk) fever, HA, sore
throat, nausea, abd. Pain, myalgia
● prodrome: 1-2 wks
● sore throat is often accompanied by moderate to severe
pharyngitis with marked tonsillar enlargement, occ. with exudates
(similar to Strep infection)
● classic PE findings: generalized LAD (90%; ant. & post. cervical,
submandibular > axillary, inguinal & epitrochlear), splenomegaly
(50%; 2-3 cm below costal margin), hepatomegaly (10%;  liver
enzymes, symptomatic hepatitis or jaundice is uncommon)
● rashes are maculopapular; reported in 3-15%; ampicillin rash:
patients with IM who are tx. w/ ampicillin or amoxicillin,
morbiliform, vasculitic rash, prob. immune-mediated, resolves w/o
specific tx.)
DIAGNOSTICS
▪ presumptive dx can be made by presence of classical clinical s/sx
with atypical lymphocytosis
● majority have leukocytosis (10,000-20,000) w/ at least 2/3
lymphocytes (20-40% atypical)
▪ Serologic testing: for heterophile Ab or specific EBV antibodies
(EBNA, EA and VCA systems)
● Heterophile Ab: cross reactive IgM Ab that agglutinate
mammalian erythrocytes but are not EBV-specific (monospot test);
(+) in 90% of EBV-assoc. IM in adolescent and adults; can remain
positive up to 12 months
▪ No specific treatment
▪ Supportive: rest, adeq. fluid and nutrition intake, symptomatic
treatment
▪ Antiviral is not recommended
● have not been shown to provide consistent clinical benefit
▪ Adoptive immunotherapy (infusion of EBV-specific cytotoxic T
lymphocytes): for transplant recipients and for other patients with
EBV-assoc. malignancies
▪ Splenic rupture: mild trauma or spontaneous
● avoid contact sports
▪ Airway obstruction: swelling of oropharyngeal lymphoid tissue
▪ Neurologic:
● Headache, uncommon: meningitis or encephalitis
● seizure, ataxia, Alice in Wonderland syndrome
(metamorphopsia)
● some assoc. with MS
▪ Hematologic:
● mild hemolytic anemia,  plt & neutrophils
● rare: aplastic anemia, severe low plt and neutrophils
▪ Other (rare): myocarditis, interstitial pneumonia, pancreatitis,
parotitis & orchitis
▪ Oncogenesis
● HL, aggressive NK cell leukemia, T- & NK-cell
lymphoproliferative disorder, epithelial cell malignancies (NPCA,
gastric CA)
● Endemic Burkitt lymphoma: in areas endemic with P.
falciparum infection and EBV
● Numerous congenital and acquired immunodeficiency
syndromes are assoc. with an increased incidence of EBV-assoc.
B-lymphocyte lymphoma, esp CNS lymphoma and
leiomyosacroma
PROGNOSIS:
▪ gradual recovery w/in 2 months of symptom onset
▪ prolonged and debilitating fatigue and malaise may wax and
wane for several weeks to 6 months
Batch Clingy
● median survival: 6 yrs
● (-) PCR in the 1st wk of life→viral load rapidly
increases→peaks by 2-3 mos→slowly declines over a period of
24 mos.
● probably partially d/t immaturity of the immune system in
NBs and infants
▪ Long-term survivors/ non-progressors:
● normal CD4 &  viral loads >8 yr old
● effective humoral immunity and/or CTL responses, host
genetic factors, and infection with an attenuated virus
206
● EBV-specific Ab: if heterophile test result is (-) but EBV
infection is suspected; measurement of Abs to EBV proteins (viral
capsid Ag, EBV nuclear Ag, early Ag)
Clinical Status
VCA
VCA
EA
EBNA
IgM
IgG
IgG
IgG
Susceptible
Acute Primary
Infection
Recent Primary
Infection
Past
+
+
+/-
-
+/-
+
+/-
+/-
-
+
+/-
+
PREVENTION
- No EBV vaccine yet
VCA: Viral Capsid Ag, EBNA: EB Nuclear Ag, EA: early Ag
INCUBATION PERIOD: 1-7 days (Nelsons); 3 -14 days (PIDSP)
TRANSMISSION:
▪ bite of vector mosquito from viremic humans
▪ Vector: Aedes aegypti (daytime mosquito); Less commonly:
Aedes albopictus
DENGUE FEVER
PATHOLOGY
▪ incompletely understood; DHF may be assoc. with second
heterotypic infections with dengue types 1-4 or in infants born to
mothers who have had two or more lifetime dengue infections
● circulation of infection-enhancing Abs at the time of infection
is the strongest risk factor for development of severe disease
▪ dengue virus immune complexes attach to
monocyte/macrophage Fc receptors
→ suppress innate immunity and enhance viral production
▪ early in the acute stage of secondary dengue infections, there is
rapid activation of the complement system
● NS1: viral toxin that attaches to toll receptor 4 & activates
myeloid cells, contributes to  vascular permeability
▪ Mechanism of bleeding is not known but a mild degree of DIC,
liver damage and thrombocytopenia may operate synergistically
PHASES OF DENGUE
▪ Febrile: 2-7 days accompanied by gen. body ache, muscle, joint
pains, headache, retroorbital pain, facial flushing, sore throat,
hyperemic pharynx, macular or MP rash, petechiae and mild
mucosal membrane bleeding
▪ Critical: During fever defervescence, D3-7 of illness, increase in
capillary permeability in parallel w/  Hct levels
- significant plasma leakage 24-48 hours
▪ Convalescent: Gradual improvement and stabilization of
hemodynamic status
PPS Oral Exam Reviewer 2020
▪ Dengue with warning signs
● Lives in or travels to dengue-endemic area, with fever lasting
for 2- 7 days PLUS ANY of the ff:
● abdominal pain or tenderness, persistent vomiting, clinical
signs for fluid accumulation, mucosal bleeding, lethargy,
restlessness, liver enlargement, AND laboratory test: increase in Hct
and/ or decreasing platelet count.
● Confirmed diagnosis: Viral culture isolation, PCR
▪ Severe dengue
● Dengue (with/without warning signs) PLUS ANY of the
following:
● severe plasma leakage, leading to: shock, fluid accumulation
with respiratory distress
● severe bleeding
● severe organ impairment (liver: AST or ALT >1000, CNS:
seizures, impaired consciousness, heart: myocarditis, kidneys: renal
failure)
▪ Dengue Without Warning Signs:
● oral rehydration if not admitted; sports drinks should not be
given
● isotonic solutions for patients who are admitted but without
shock
▪ Dengue With Warning Signs/Severe Dengue:
● admit for close monitoring
● cyanotic/ labored breathing: supplemental O2
● rapid IV replacement of fluids and electrolytes (if in
compensated shock: 10-15 mL/kg/hr over 1 hr; if in hypotensive
shock: 20 mL/kg in 15 mins)
● may give glucose containing IVF in the ff. conditions: HGT < 80
mg/dL; if HGT is not available and pt. is unable to eat and is weaklooking
● Transfusion to control bleeding (do not give if w/
hemoconcentration): FWB (10-20 mL/kg) or pRBC (5-10 cc/kg, if w/
fluid overload) are preferable because stored blood loses 2,3 DPG,
low levels of w/c impede the O2-releasing capacity of Hgb resulting
in functional tissue hypoxia
● Prophylactic platelet transfusion: do not reduce the risk of
hemorrhaging or improve low platelet counts unless with significant
bleeding or DIC
● Vasopressors, if necessary
DISCHARGE CRITERIA
▪ No fever for at least 48-hours
▪ Improvement in clinical status
▪ Increasing trend in platelet count, stable hematocrit without IVF
▪ Hypervolemia during fluid reabsorptive phase is life
threatening ( Hct & wide PP)
▪ Infants and young:
● fluid & electrolyte losses, hyper-pyrexia, febrile convulsion
● uncommon: epistaxis, petechiae, purpuric lesions
● after febrile phase: prolonged asthenia, mental depression,
bradycardia, ventricular extrasystoles
PROGNOSIS:
▪ Dengue Fever: Good
▪ DHF: 40-50% in shock → death but with ICU <1%
PREVENTION
▪ avoid daytime mosquito using insecticides, repellents (use EPAapproved), body covering clothes, screening of house,
destruction of vector breeding sites
● there is insufficient evidence to say that use of citronellabased repellents is more effective than DEET-based repellents in
reducing dengue transmission (PPS PIDSP Clinical Practice
Guidelines on Dengue in Children, 2017)
▪ Dengue vaccine (Dengvaxia)
● a mixture of 4 chimeras: DENV + yellow fever 17D
● 3-dose series given 6 months apart for 9-45yo in highly
endemic areas
● in 2015: completed phase III w/c offered poor protection of
seronegatives, good protection of seropositives w/ reduction of
hospitalization and severe disease in vaccinated 9-year-old
● seronegative who were incompletely protected were
sensitized to the enhanced disease of hospitalized dengue
(Further reading : PPS PIDSP Clinical Practice Guidelines on
Dengue in Children, 2017)
DIAGNOSTICS
Dengue Fever
▪ After 3-4 days → pancytopenia (neutropenia may persist), WBC
<2000 µ/L, platelets rarely fall (<100 000)
Batch Clingy
▪ caused by several arthropod-borne viruses
● four distinct antigenic types of dengue virus (dengue 1,2,3,
and 4); members of the family Flaviviridae
● EBV DNA via PCR: Not necessary in immunocompetent
patients;
used
for
surveillance
for
posttransplant
lymphoproliferative disease (PTLD), screen and determine
prognosis for some EBV-ass malignancies (NPCA and HL)
REVISED DOH/PPS CLASSIFICATION AND LEVELS OF SEVERITY 2011
▪ Dengue without Warning Signs
● Lives in or travels to dengue-endemic area with fever PLUS
ANY TWO of the ff:
● headache, body malaise, myalgia, arthralgia, retro-orbital pain,
anorexia, nausea, vomiting, diarrhea, flushed skin, rash AND
laboratory test, at least CBC (leucopenia with or without
thrombocytopenia) and/or dengue NS1 Ag or dengue IgM Ab test
(optional)
● Confirmed diagnosis: Viral culture isolation, PCR
207
▪ (+) tourniquet test, mild acidosis, hemoconcentration, 
transaminase,  protein
▪ ECG: sinus bradycardia, ectopic ventricular foci, flattened T waves,
prolongation of P-R interval
DHF/DSS
▪  20% of Hct,  plt, prolonged BT, mod.  PT level (seldom <40%
control), subnormal Fibrinogen,  fibrin split-products, mod 
serum transaminase, consumption of C’, mild metabolic acidosis, 
Na,  alb, CXR: pleural effusion (R>L)
▪ Signs of  vascular permeability: thickening of GB wall, presence
of perivascular fluid
Batch Clingy
▪ Serology:
● NS1 (acute) requested D1-5 of illness, detectable from the
beginning of febrile phase until D7-10 of illness
● IgM (recent): detectable 3-5 days after illness, disappears after
6-12 wk
● IgG (past infection), detectable 3-7 days ff infection and
remain up to 6 months
▪ PCR (blood or tissue): for confirmation
PPS Oral Exam Reviewer 2020
208
ETIOLOGY / INCIDENCE / PATHOGENESIS
▪ Acute toxic infection
▪ Gram (+) bacilli, aerobic, non-encapsulated, nonspore forming nonmotile, pleomorphic
Corynebacterium diphtheriae
▪ Exclusive inhabitant of human mucous
membranes and skin
C. ulcerans
▪ Animal sources that can cause human disease, (+)
Urease
INCUBATION PERIOD: 1-10 days
DIPHTERIA
TRANSMISSION
▪ Airborne respiratory droplets
▪ Direct contact w/ respiratory secretions of
symptomatic individuals or exudate from infected
skin lesions
▪ For endemic areas, 3-5% of healthy individuals can
carry toxigenic organisms but carriage is rare
▪ Skin infection and skin carriage are silent
reservoirs of C.d.
▪ Organisms remain viable in dust or fomites up to 6
months
▪ Contaminated milk and infected food handler
PATHOGENESIS
▪ Both toxigenic and non-toxigenic C. diphteriae
cause skin and mucosal infection
Potent polypeptide exotoxin
▪ the ability to produce diphtheritic toxin results
from acquisition of a lysogenic corynebacteriophage
which encodes the diphtheritic toxin gene
▪ Major virulence
▪ Inhibits protein synthesis and causes local tissue
necrosis and resultant local inflammatory response
▪ Within first few days of RTI (pharynx) → WHITE
dense necrotic coagulum of organisms, epithelial,
fibrin, WBC, & RBC → gray-brown, leather-like
adherent PSEUDOMEMBRANE (removal reveals
bleeding edematous submucosa)
▪ Early effect of toxin: paralysis of palate and
hypopharynx
PPS Oral Exam Reviewer 2020
Acute
CLINICAL MANIFESTATIONS / FINDINGS / DIAGNOSIS
MANAGEMENT
Respiratory tract
▪ Specific antitoxin: mainstay of therapy; should be
▪ Sites: tonsils, pharynx, nose, or larynx
administered on the basis of clinical diagnosis
▪ After 2-4 days: local SSx of inflammation
▪ Antimicrobial therapy: to halt toxin production, treat localized
▪ ½ fever, fewer dysphagia, hoarseness, malaise, or infection, and prevent transmission to contacts
headache
● Penicillin, erythromycin (E>P for eradication of NP
▪ Anterior nares infection:
carriage) x 14 days, cutaneous x 7 days
● more common in infants
▪ Elimination should be documented by 2 successive (-) cultures
● Serosanguinous, purulent, erosive rhinitis w/ from nose and throat (or skin), 24-hour apart AFTER completion
membrane formation
of therapy
● Shallow ulceration of external nares and upper lip
▪ Antibiotic therapy is not a substitute for antitoxin therapy
▪ Tonsillar and pharyngeal diphtheria
▪ Supportive care
● Universal early symptom: sore throat
● droplet and contact precautions
● Mild pharyngeal injection → uni-/bilateral tonsillar
● bed rest >2wks until risk for symptomatic cardiac damage
membrane formation → uvula (may cause toxin- has passed
mediated paralysis), soft palate, post. oropharynx, ▪ Vaccine
DTaP (IM)
hypopharynx, or glottis
3 doses series with minimum age of 6 weeks and minimum interval
● Bull neck appearance: underlying soft tissue edema
of 4 weeks
and enlarged lymph nodes
Cutaneous diphtheria
▪ Nonprogressive, superficial, ecthyma-like, nonhealing
ulcer with a gray-brown membrane
▪ Pain, tenderness, erythema, or exudate
▪ Can coexist w/ strep or staph impetigo
▪ Extremities > trunk or head
▪ Assoc. with more prolonged mucosal shedding, greater
contamination of environment,  transmission to
pharynx & skin of close contacts
Other sites
▪ Ear (OE), eye (purulent and ulcerative conjunctivitis),
genital (vulvovaginitis)
▪ Endocarditis (sporadic) among IV drug users, strains:
nontoxigenic
▪ Pyogenic arthritis (sporadic), septicemia (rare)
▪ Diphtheroid isolated from sterile body sites should not
be routinely dismissed as contaminants without careful
consideration of the clinical setting
DIAGNOSTICS
▪ Culture: nose, throat, mucocutaneous lesion
DIFFERENTIAL DIAGNOSIS
▪ S. pyogenes, EBV
3 BOOSTER DOSE series at: 12 – 23 months, 4 – 7 years, 9 – 15 years
Minimum interval between booster doses: 4 years
Full dose DTP should preferably be used only until 7 years, but
package inserts should be consulted for maximum age indications of
specific products.
Unvaccinated
5
▪ For 1o immunization w/ 1st and 2nd doses
9-18 yrs old
doses
interval of 4 weeks, and the 2 nd and 3rd
doses with an interval of at least 6
months
▪ 1st booster given at least 1yr after 3 rd
dose, 2nd booster at least 1yr from 1st
booster
Rcvd 1 dose
4
0, 1, 2, 6 months
With 2 doses
3
0, 1, 6 months
With 3 doses
2
0, 6 months
Fully
1
1 dose Td/Tdap every 10 years
vaccinated
Booster
▪ Adult preparation of Tdap at 11-12yo
▪ For 13-18 yo who missed Td/Tdap booster at 11-12yo OR >5y
since Td booster should receive a single dose of Tdap if they
completed the DTP/DTaP series.
▪ Contraindication: hx of neurologic or severe hypersensitivity
reaction after a prior dose
COMPLICATIONS / PROGNOSIS
COMPLICATIONS
▪ Laryngeal diphtheria: suffocation – local soft tissue edema,
airway obstruction
▪ Toxic cardiomyopathy
● 10-25% of patients with respiratory diphtheria
● Occurs 2nd-3rd week of illness as pharyngeal disease
improves
●  HR out in proportion to fever
● ECG: prolonged PR interval, changes in ST-T wave, single
or progressive dysrhythmias (1st-3rd degree heart block), AV
dissociation and Vtach
● 2DED: dilated/hypertrophic cardiomyopathy
● Acute or insidious HF
●  AST ∝ myonecrosis
▪ Toxic Neuropathy
● Acutely or 2-3wks after onset of oropharyngeal
inflammation
● Hypesthesia and local paralysis of soft palate
● Weakness of post. pharyngeal, laryngeal & facial nerves
(nasal voice, difficult swallowing, risk for aspiration)
● Cranial neuropathies (5th wk) → oculomotor and ciliary
paralysis (strabismus, blurred vision, difficult accommodation)
● Symmetric demyelinating polyneuropathy (10d-3mos
after oropharyngeal infection) causing motor defects
w/diminished DTR
● Paralysis of diaphragm
● DDX: GBS – indistinguishable nerve conduction velocity &
CSF
PROGNOSIS
▪ Depends on virulence of organism (gravis – highest fatality
rate)
▪ Age, immunization status, site of infection or speed of
administration of antitoxin
▪ Mechanical obstruction from laryngeal diphtheria or bullneck diphtheria and the complications of myocarditis account
for most deaths
▪ Toxic Cardiomyopathy
● Complete recovery but if it occurs at 1st week, poor
prognosis, may have permanent conduction defects
▪ Toxic Neuropathy
● Complete recovery
● Rare: vasomotor center dysfunction 2-3wks after onset of
illness→  BP or HF
Batch Clingy
DISEASE
209
Clostridium tetani
▪ Gram (+), motile, spore-forming obligate anaerobe
▪ Natural habitat: soil, dust, alimentary tracts of
various animals
INCUBATION PERIOD: 2-14 days, may be months
after injury
TETANUS
TRANSMISSION
▪ Neonatal: umbilical
▪ Maternal: postpartum, postabortal, post-surgical
wound infection
▪ Non-neonatal: trauma, illicit drug injection, animal
bites, abscesses (also dental), body piercing, chronic
skin ulceration, burns, compound fractures,
frostbite, gangrene, intestinal surgery, ritual
scarification, infected insect bites, female
circumcision
PATHOGENESIS
▪ Toxin mediated process
▪ Forms spores resembling drumstick or tennis
racket appearance
▪ Traumatic injury → spores germinate, multiply,
vegetable cells produce toxin
▪ Toxin binds at NMJ and enters motor nerve by
endocytosis, → retrograde axonal transport →
enters spinal inhibitory neurons, prevents release of
GABA and glycine → blocks normal inhibition of
antagonistic muscles on which voluntary movement
depends → affected muscles sustain max
contraction & cannot relax (lock jaw)
PPS Oral Exam Reviewer 2020
▪ Vincent angina, Lemierre syndrome, mucositis
▪
Bacterial
epiglottitis,
severe
viral
staph/streptococcal tracheitis
POSTEXPOSURE PROPHYLAXIS
Asymptomatic case contacts
▪ Monitor for 7d, do culture, give antimicrobial prophylaxis
regardless of immunization status
▪ Toxoid vaccine given in age-appropriate form to immunized
individuals who have not received a booster dose within 5yrs
LTB,
Generalized
▪ Patient is conscious and in extreme pain
▪ Trismus: masseter muscle spasm (lock jaw)
▪ Headache, restless, irritability → stiffness, difficulty
chewing, dysphagia, neck muscle spasm, sardonic smile
(risus sardonicus)
▪ Opisthotonos: arched posture of extreme
hyperextension of the body
▪ Laryngeal and respiratory muscle spasm → airway
obstruction and asphyxiation
▪ Seizures: sudden, severe tonic contractions of the
muscle w/ fist clenching, flexion and adduction of the
arms and hyperextension of the legs
▪ Fever (as high as 400C): caused by metabolic energy
consumed by spastic muscles
▪ Dysuria, urinary retention from bladder sphincter
spasm, forced defecation
▪ Autonomic: HR, dysrhythmias, labile HTN, diaphoresis,
cutaneous vasoconstriction
▪ The smallest disturbance by sight, sound or touch may
trigger a tetanic spasm
▪ Paralysis is more severe in 1 st wk, stabilizes 2nd wk,
ameliorates gradually in 1-4 wk
Neonatal
▪ Manifests within 3-12 days of birth
▪ Progressive difficulty in feeding, paralysis or diminished
movement, stiffness, and rigidity to touch & spasms, ±
opisthotonos
Localized: painful spasms of muscles adjacent to wound;
may precede generalized tetanus
▪ Surgical wound excision and debridement: to remove foreign
body or devitalized tissue that created the anaerobic growth
● performed promptly after administration of human
tetanus Ig (HTIg)
▪ HTIg
● goal: neutralize toxin that diffuses from the wound into the
circulation before the toxin can bind at distant muscle groups
● optimal dose has not been determined: 500 U/IM (range:
3,000-6,000 U)
● If unavailable:
- Human IVIg (4-90 U/mL of TIG) but no optimal dose and
not approved for this indication
- Equine-derived tetanus antitoxin (TAT) 1,500-3,000 U,
administered after appropriate testing for sensitivity and
desensitization (up to 15% experience serum sickness)
▪ Antibiotic: to decrease the number of vegetative forms
● DOC: Metronidazole 30mkday q6 (max 4g/day)
● Alternative: Pen G 100,000 U/kg/day q4-6 (max 12M
U/day)
▪ Muscle Relaxants: Diazepam, Midazolam, MgSO4,
Chlorpromazine, Dantrolene, Baclofen (ICU setting),
vecuronium, pancuronium
▪ Morphine: for autonomic instability
▪ Meticulous supportive care in a quiet, dark secluded room,
sedation, ET/ tracheostomy, prophylactic SQ heparin,
Enoxaparin (DVT)
Asymptomatic carriers
▪ Antimicrobial prophylaxis for 10-14 days
▪ Toxoid vaccine given in age-appropriate form to immunized
individuals who have not received a booster dose within 1yr
▪ Droplet or contact precautions until 2 (-) successive cultures
24hrs apart after cessation of therapy → repeat after 2 wks. If
(+) → 10 days Erythromycin
COMPLICATIONS
▪ Airway obstruction and asphyxiation
▪ Aspiration, pneumothorax, mediastinal emphysema
▪ Seizures: lacerations of the mouth and tongue, IM
hematomas, rhabdomyolysis w/ myoglobinuria, renal failure,
long bone, or spinal fractures
▪ Venous thrombosis, pulmonary embolism, gastric ulceration
± hemorrhage, paralytic ileus, decubitus ulcers
▪ Excessive use of muscle relaxants → iatrogenic apnea
▪ Autonomic NS: cardiac arrhythmias, asystole, unstable BP &
labile temperature regulation
▪ Hypoxic brain injury → CP, diminished mental abilities,
behavioral difficulties
PROGNOSIS
▪ Recovery occurs through regeneration of synapses in spinal
cord → muscle relaxation
▪ Mortality is highest: extremes of age
▪ Favorable prognosis: long incubation period, absence of
fever, localized disease
▪ Unfavorable prognosis: trismus <7d after injury, gen. tetanic
spasms <3 days after onset of trismus
▪ Cephalic tetanus: poor prognosis due to breathing and
feeding difficulties
▪ Vaccine
● follow DTaP schedule
● For pregnant: give 1 dose of Tdap during each pregnancy
Batch Clingy
▪ Toxin absorption → kidney tubule necrosis, 
platelet, cardiomyopathy, demyelination of nerves.
Because the latter 2 occur 2-10 weeks after
mucocutaneous infection, the pathophysiology is
suspected to be immunologically mediated
210
● Cephalic: rare form of localized; involves bulbar
musculature, from wounds or foreign bodies in head,
nostril, face, assoc. w/ chronic OM; Retracted eyelids,
deviated gaze, trismus, risus sardonicus, spastic paralysis
of tongue and pharyngeal musculature
DIAGNOSTICS
▪ C. tetani is not always visible on GS, isolated in culture
in only 30% of cases
▪ Usual setting: unimmunized patient/mother injured or
born w/in the past 2 weeks presents w/ trismus,
dysphagia, gen. muscle rigidity, spasm, and clear
sensorium
▪  WBC: maybe d/t 2O bacterial infection or stressinduced
▪  CK and aldolase
▪ EMG: continuous discharge of motor subunits &
shortening, or absence of the silent interval normally
observed after an action potential
▪ Spatula test: touch the oropharynx w/ spatula or
tongue blade (high Sn and Sp); if tetanus is present, (-)
gag reflex (+) reflex spasm of masseter and bite the
spatula
PERTUSSIS
▪ usually caused by Bordetella pertussis &
occasionally B. parapertussis
● Gram negative coccobacilli, small, fastidious
▪ B. holmesii: cause of bacteremia in IC w/o cough,
pertussis-like cough illness in healthy persons
▪ B. bronchiseptica: common animal pathogen w/
occasional human reports in IC and young
INCUBATION PERIOD: 3-12 days
TRANSMISSION
PPS Oral Exam Reviewer 2020
DIFFERENTIAL DIAGNOSIS
▪ Rabies – hydrophobia, marked dysphagia, chronic
seizures, pleocytosis
▪ Strychnine poisoning
● Tonic muscle spasms & gen seizure, general
relaxation occurs between spasms
● White, odorless, bitter crystalline powder –
ingested, inhaled, or mixed in a solution → IV
● Found in Strychnos nux-vomica plant, given as
“street drugs” or pesticide
▪ Hypocalcemia (no trismus) epileptic seizures, narcotic
withdrawal
CATARRHAL (1-2wks)
▪ Congestion, rhinorrhea, low grade fever, sneezing,
lacrimation, conjunctival suffusion
PAROXYSMAL (2-6wks)
▪ Dry, intermittent, irritative hack → inexorable
paroxysms (hallmark)
▪ Well appearing toddler → anxious aura → machine-gun
uninterrupted cough on a single exhalation – chin and
chest held forward, tongue protruding maximally, eyes
bulging and watering, face purple → coughing ceases
with a loud whoop that follows as inspired air traverses
Wound Management
History of
absorbed
TT
Uncertain
or <3
doses
>3 doses
Clean Minor Wounds
All Other Wounds
DTaP, Tdap or Td
TIG
DTaP, Tdap or Td
TIG
Yes
No
Yes
Yes
No if <10 yr since
last dose of
tetanuscontaining
vaccine
Yes, if >10 yr
since last dose of
tetanuscontaining
vaccine
No
No
No if <5 yr since
last dose of
tetanuscontaining
vaccine
Yes, if >5 yr since
last dose of
tetanuscontaining
vaccine
No
No
▪ Should always be given after a dog or other animal bite
▪ If not available → IVIg or equine-derived TAT
▪ Do not give Td more frequently if with previous Arthus
reaction after a dose of TT containing vaccine
▪ Hospitalized: < 3mos old suspected case, severe paroxysms,
complications
● Room: quiet, dim, undisturbed, comforting environment
● Avoid large feedings
▪ Antibiotics
● Azithromycin – drug of choice; risk for fatal heart rhythms
to those at risk for CV events (esp. prolonged QT interval)
● Erythromycin – risk for infantile hypertrophic pyloric
stenosis
● Alternatives: Clarithromycin & TMP-SMX
▪ Discharge Criteria:
COMPLICATIONS
▪ Apnea, 2o infections (OM & pneumonia), physical sequalae
of forceful coughing
▪ Acute neurologic events – 2o to hypoxemia & hemorrhage
▪ Apnea or bradycardia
▪ Seizures (hypoxemia)
▪ Hyponatremia – excessive secretion of ADH during
pneumonia
▪  Intrathoracic and intraabdominal pressure: conjunctival
and scleral hemorrhages, petechiae on the upper body,
epistaxis, pneumothorax, SQ emphysema, umbilical or
Batch Clingy
Tetanospasmin
▪ 2nd most poisonous substance known (after
botulinum toxin)
▪ Lethal dose 10-5mg/kg
211
PATHOGENESIS
▪ Only colonizes ciliated epithelium
▪ Only B. pertussis expresses pertussis toxin – major
virulence protein → histamine sensitivity, insulin
secretion, leukocyte dysfunction
▪ Aerosol acquisition → attach to resp. ciliated cells
via filamentous hemagglutinin, agglutinogens, &
pertactin → clearance is inhibited by tracheal
cytotoxin, adenylate cyclase, PT → local epithelial
damage → respiratory sx, facilitates absorption of
PT
the partially closed airway; post tussive emesis
▪ At the peak of the stage: 1 episode hourly
CONVALESCENT (>2wks)
▪ Number, severity, duration of episode diminishes
DO NOT DISPLAY THE CLASSIC STAGES:
Infants < 3 months
▪ Catarrhal phase is unnoticed, cough may not be
prominent, apnea and cyanosis follow coughing
paroxysm or apnea as the only symptom
▪ “Exacerbations” can occur throughout the 1 styr (not a
recurrence or reactivation)
Adolescents & prev. immunized
▪ Foreshortening of all stages
▪ Sudden feeling of strangulation → uninterrupted
coughs, feeling of suffocation, bursting headache,
diminished awareness → gasping breath without a
whoop
▪ 30% have nonspecific illness distinguished by duration
of >21 days
● Over 48 hours, disease severity is unchanged or diminished
● Intervention is not required during paroxysms
● Nutrition is adequate
● No complication has occurred
● Parents are adequately prepared for care at home
▪ Droplet precaution & isolate immediately until 5 days after
azithromycin
inguinal hernia, hemorrhage in CNS & retina, laceration of
lingual frenulum
▪ Severe and usual causes of death: progressive pulmonary
HTN & 2O bacterial pneumonia
▪ Rare: Bronchiectasis after pertussis
▪ Children <2yo may have abnormal pulmonary function in
adulthood
▪ Vaccine
● follow DTaP schedule
● Acellular pertussis vaccine: less reactogenic compared to
whole-cell pertussis vaccine
PROGNOSIS
▪ Severe course/Death: rapid rise and extreme leukocytosis &
thrombocytosis, prematurity, pulmonary HTN & cardiogenic
shock
▪ < 6mo old: excessive morbidity and mortality
● < 4mo old: 90% of cases of fatal pertussis (as well as
preterm and young maternal age)
● < 2mo old: highest rates of pertussis assoc. hospitalization,
pneumonia, seizures, encephalopathy, death
DIFFERENTIAL DIAGNOSIS
▪ Mycoplasma – protracted episode continuous cough w/ hx of
fever, systemic sx, PE: rales
▪ Adenovirus – fever, sore throat, conjunctivitis
▪ Chlamydia (staccato cough), Parainfluenza, influenza,
enterovirus, RSV, FB Aspiration
Typical Paroxysms that are not life threatening:
▪ duration <45 sec, red but not blue color change, HR,
HR (not <60 in infants), or O2 desaturation that
spontaneously resolves, whooping or strength for brisk
self-rescue at the end of rescue, self-expectorated mucus
plug, post tussive exhaustion but not unresponsiveness
ENTERIC FEVER
Typhoid Fever
Salmonella enterica serovar typhi
▪ Gram negative
PPS Oral Exam Reviewer 2020
DIAGNOSTICS
▪ Should be suspected in any individual who has a pure or
predominant complaint of cough
▪ Clinical case definition: cough ≥ 14 days + paroxysm,
whoop, or post tussive vomiting
▪ Suspect in:
● Older child whose cough is escalating at 7-10d and
comes in bursts
● < 3mos old with gagging, gasping, apnea, cyanosis
▪ Leukocytosis caused by absolute lymphocytosis is
characteristic in the catarrhal stage
▪ CXR: mildly abnormal
▪ PCR testing on NP wash specimens is the laboratory test
of choice for B. pertussis identification
▪ Results from PCR & culture are expected (+) in
unimmunized & untreated during catarrhal and early
paroxysmal stage
▪ More dramatic presentation in < 5yo
Primary Bacteremia: asymptomatic, blood CS (-)
▪ Adequate rest, hydration, antipyretic therapy, soft easily
digestible diet
POSTEXPOSURE PROPHYLAXIS
Care of Household and Other Close Contacts
▪ Azithromycin should be given to ALL contacts
▪ < 7yo who had < 4 doses DTaP: give DTaP & complete
recommended series
▪ < 7yo who received 3rd DTaP > 6mos before exposure or 4th
dose ≥ 3yrs before exposure: give booster dose
▪ ≥ 9yo: give Tdap
COMPLICATIONS
▪ Infancy – DIC
Batch Clingy
▪ Extremely contagious
▪ 100% attack rate exposed to aerosol droplets at
close range
▪ Rate of sub-clinical infection is high as 80% in fully
immunized or previously infected
▪ No chronic carrier documented
▪ Does not survive for prolonged periods in the
environment
212
INCUBATION PERIOD: 4-14 days (depending on the
inoculating dose of viable bacteria)
TRANSMISSION
▪ Direct or indirect contact with infected person
(sick or chronic carrier)
▪ Most common: ingestion of food or water
contaminated with S. typhi from human feces
▪ Water-borne outbreaks (poor sanitation or
contamination): oysters, shellfish, use of night soil
as fertilizer
PATHOGENESIS
▪ Infective dose: 105-109
▪ Orally ingested salmonellae survive low pH of
stomach, evade SI defenses, enter epithelium (M
cells)
▪ In contrast to NTS, expresses virulence factors that
allows to downregulate the pathogen recognition
receptor mediated host inflammatory response,
colonize deeper tissues, lymphoid cells in Peyer
Patches → hyperplasia, pass thru the intestinal
mucosa enter the mesenteric lymphoid system then
thru the blood stream causing PRIMARY
BACTEREMIA → enter macrophages → disseminate
in RES → necrosis and sloughing of overlying
epithelium → SECONDARY BACTEREMIA →
systemic symptoms is from the release of proinflammatory cytokines (IL-6, IL-1β, TNFα) from
infected cells
NON
TYPHOIDAL
SALMONELLA
Typhoid toxin
▪ CdtB cytothelial distending toxin (a DNase that
causes double-strand breaks in host cell DNA)
▪ PltA pertussis-like toxin
▪ Salmonellosis: a common and widely distributed
food-borne disease; global major public health
problem
▪ 2 most important serotypes for salmonellosis
transmitted from animals to humans
PPS Oral Exam Reviewer 2020
Secondary Bacteremia
▪ Onset of symptoms
▪ Marks the end of incubation period
▪ High-grade fever, coated tongue, anorexia, vomiting,
hepatomegaly, diarrhea, toxicity, abdominal pain, pallor,
splenomegaly, constipation, HA, jaundice, obtundation,
ileus, intestinal perforation
▪ Initially, iarrhea (pea-soup) → constipation
▪ D7-10: rose spots – crops of 10-15 on the lower chest &
abdomen lasting for 2-3 days
▪ No complication, resolves within 2-4 weeks
DIAGNOSTICS
▪ Mainstay of diagnosis: positive culture from the blood
or another anatomic site
● during the 1st week: blood and bone marrow
● after the 1st week: stool and urine
● over the 3 rd week, BM culture could remain (+)
despite (-) blood CS; difficult to obtain/invasive
▪ Widal test: measures Ab O and H antigens of S typhi
but lacks Sn and Sp in endemic areas
▪ Other serologic tests (i.e. Typhidot) have not been
proven sufficiently robust in large-scale evaluations in
community settings
▪ Leukocytosis: common in younger children
▪ Thrombocytopenia: marker of severe illness (DIC)
▪ Liver function test may be deranged, but sig.
dysfunction is rare
DIFFERENTIAL DIAGNOSIS
▪ Early: dengue fever or malaria
▪ Sepsis, TB, brucellosis, tularemia, leptospirosis,
rickettsia, acute hepatitis
Acute Enteritis
▪ most common presentation
▪ abrupt N/V, crampy abdominal pain (periumbilical
area/RLQ) → watery diarrhea, sometimes w/ blood and
mucus
▪ Antibiotic therapy is critical to minimize complications;
influenced by the prevalence of antimicrobial resistance
Uncomplicated
1st Line
Sensitive
MDR
FLQ
resistant
Amox
(DOH)
Chloram
Cipro
Cefixime
Azith
Ceftri
Alternative
14 d
14-21 d
5-7 d
7-14 d
7d
10-14 d
Severe
1st Line
Sensitive
FLQ
(Cipro)
Ceftri
(DOH)
10-14 d
10-14 d
MDR
FLQ
10-14 d
FLQ
Resistant
Ceftri
Cefotax
10-14 d
10-14 d
Ampi
(DOH)
Cipro
Azith
5-7 d
7d
Cefixime
7-14 d
14 d
Alternative
Chloram
14-21
Amox
Ceftri
Cefotax
Azith
FLQ
10-14 d
10-14 d
7
7-14
▪ Use of 2nd line should be reserved for suspected or proven
multi-drug resistant typhoid fever: resistant to first line
(Chloramphenicol, Ampicillin and TMP-SMX)
▪ Should be suspected in ANY of the following situations:
● Failure to respond after 5-7 days treatment with a first line
antibiotic
● Household contact w/ documented case or during an
epidemic of MDRTF and/or
● Clinical deterioration or development of complications
during conventional antibiotic treatment
▪ Adults – CNS, GI bleeding
▪ GI: intestinal hemorrhage and perforation
▪ CNS: encephalopathy, cerebral edema, subdural empyema,
meningitis, GBS, ventriculitis, ataxia, seizures, psychosis
▪ CV: toxic myocarditis (arrythmias, sinoatrial block,
cardiogenic shock)
▪ Pulmonary: pneumonia, empyema, broncho-pleural fistula
▪ Bone and Joint: Osteomyelitis, septic arthritis
▪ Hepatobiliary system: cholecystitis, hepatitis, hepatic
abscesses, splenic abscess, peritonitis
▪ GUT: UTI, renal abscess, pelvic infections, testicular abscess
▪ SSI: psoas abscess, gluteal abscess, cutaneous vasculitis
▪ Hematologic: Hemophagocytosis syndrome
PREVENTION
▪ Most important risk: contamination of water supplies with
sewage
PROGNOSIS
▪ Depends on rapid diagnosis and treatment, age, general
state of health, causative serotype, appearance of
complications
▪ 2-4% can have relapse despite treatment
▪ Chronic carriers: > 3months secretion of S typhi.
● Risk increases with age
● A chronic urinary carrier state can develop in children w/
schistosomiasis
▪ Vaccine
● Oral live attenuated Ty21a strain, efficacy 5 years
● IM Vi capsular polysaccharide for ≥ 2yo, booster q2 years,
efficacy 70-80%
▪ Antibiotics are not generally recommended for the treatment
of isolated uncomplicated Salmonella gastroenteritis due to
● Disruption normal intestinal flora
● Prolonged excretion with ↑ risk as a chronic carrier
▪ Give antibiotics until culture is available to:
COMPLICATIONS
▪ Acute dehydration can be assoc. with Salmonella
gastroenteritis
▪ Osteomyelitis (in children w/ sickle cell disease)
▪ Reactive arthritis (especially in adolescents with HLA-B27 Ag)
Batch Clingy
▪ other etiologies: S. enterica var paratyphi A, B, C
▪ Age-specific incidence highest in < 5yo
▪ notable for emergence of drug resistance
▪ S. typhi is highly adapted to infection of humans;
lost ability to cause transmissible disease in animals
▪ Associated with malnutrition
213
INCUBATION PERIOD: 6-72 hours
TRANSMISSION
▪ Food contaminated by contact w/ an infected
animal product or a human carrier
▪ Contact with infected animals (e.g. domestic pets,
amphibians)
▪ Animal-derived pet foods and treats
PATHOGENESIS
▪ Infective dose: 106-108
▪ Gastric acidity inhibits multiplication of
salmonellae
● Achlorhydria, buffering meds, rapid gastric
emptying after gastrectomy or gastroenterostomy
and a large inoculum enable viable organisms to
reach the SI
▪ After an infection, excreted in feces for 5 weeks
▪ During excretion, it may be transmitted by fecaloral route or indirect contamination of food
▪ Enterocolitis w/ diffuse mucosal inflammation &
edema (sometimes erosions and micro abscesses)
→ penetrate the intestinal mucosa → lymphoid
tissue and mesenteric LN enlargement & necrosis
→ hyperplasia of the RES → bacteremia → localized
infection and suppuration to any organ
▪ Gram positive, coagulate positive
▪ Most common cause of pyogenic infection of skin
and soft tissue
S. AUREUS
Strains that protect organism from host defenses:
▪ Produce biofilm or loose polysaccharide capsule:
interfere w/ opsonophagocytosis
▪ Clumping factor interferes w/ phagocytosis
▪ Coagulase causes plasma to clot (abscess
formation)
▪ Protein A: prevents antibacterial Ab from acting as
opsonins → inhibit phagocytosis
PPS Oral Exam Reviewer 2020
▪ febrile
▪ symptoms last 2-7 days
Bacteremia (1-5%)
▪ Transient bacteremia
▪ NB & young infants present with minimal symptoms
▪ Older infants, typically follows AGE; associated with
fever, chills, septic shock
▪ Fever is present in 95% of cases but may have no
apparent focus; diarrhea is NOT a prominent feature
Extraintestinal Focal Infections
▪ occurs following bacteremia
▪ Most common: skeletal system, meninges (peak in
infancy), intravascular sites and sites of pre-existing
abnormalities
Chronic Salmonella Carriage
▪ Asymptomatic, w/ colonization in the gall bladder pres.
w/ intermittent (+) stool CS
● < 3 months old (risk of bacteremia)
● High risk groups w/ immune compromise
▪ Choice of antibiotics (Nelsons’ DOH NAG)
● Cefotaxime 100-200mkday q6-8 x 5-14 days or
● Ceftriaxone 75mkday QD x 7days
● Ampicillin 100mkday q6-8 x 7 days
● Cefixime 15mkday x 7-10 days
▪ AIDS: multisystem involvement, septic shock and death
▪ IBD: toxic megacolon, bacterial translocation, sepsis
▪ Schistosomiasis: may lead to chronic infection
▪ Neonates, <6mos old, children w/ 1o or 2o ID may have
symptoms that lasts for weeks
▪ RES dysfunction: prolonged, intermittent bacteremia assoc.
low-grade fever, anorexia, weight loss, diaphoresis, myalgia
▪ IF antimicrobial therapy in a well child with NTS gastroenteritis
with no disseminated disease is initiated, give single dose of
ceftriaxone → discharge with oral azithromycin pending blood
CS results (alternatives: ampicillin, TMP SXT or FLQ, if
susceptible) (AAP Red Book, 2018)
PROGNOSIS
▪ Most recover fully
▪ Malnourished children and those with suboptimal
supportive treatment: prolonged diarrhea and complications
▪ Young infants, IC: systemic involvement, prolonged course
and extraintestinal foci
▪ Prolonged carrier state seen in children with biliary tract
disease & cholelithiasis after chronic hemolysis
PREVENTION
▪ Control transmission in the animal reservoir
▪ Judicious use of antibiotic in dairy and livestock
▪ Prevent contamination of food prepared from animals
▪ Vaccine: some are used in animals, but no human vaccine is
available yet
DIAGNOSTICS
▪ definitive diagnosis is based on clinical correlation of
the presentation and culture from feces or other body
fluids
● in children with AGE, stool CS > rectal swabs
▪ Mild leukocytosis
▪ Stools: moderate PMN and occult blood
(see Nelson’s 21st Ed., Table 225.1, for Host Factors and
Conditions Predisposing to Development of Systemic Disease with
NTS strains)
Newborn
▪ Cutaneous: omphalitis, cellulitis, mastitis, subcutaneous
abscesses
▪ Staphylococcal pustulosis: large pustule filled lesions
1mm in dm and scattered around the umbilicus
▪ DDX: HSV
Skin
▪ Impetigo, ecthyma, hidradenitis, folliculitis, furuncles,
carbuncles, SSSS, cellulitis, necrotizing fasciitis
▪ Recurrent skin and soft tissue infections: MRSA
Respiratory
▪ OM, sinusitis, suppurative parotitis
DIAGNOSTICS
Culture
▪ Diagnosis depends on the isolation of the organism in culture
from nonpermissive sites
▪ Best: tissue samples or fluid aspirates
▪ Obtain culture of any potential focus of infection as well as
blood culture
PCR identify genetic patterns ass. w/ methicillin resistance
Food Poisoning
▪ food may be cultured & test for exotoxin
COMPLICATIONS
▪ Omphalitis → abdominal wall cellulitis or necrotizing fasciitis
▪ Osteomyelitis → DVT → septic pulmonary emboli
▪ Endocarditis → perforation of heart valves, myocardial
abscesses,
HF,
conduction
disturbances,
acute
hemopericardium, purulent pericarditis, sudden death
PREVENTION
▪ Hand hygiene, handwash w/ chlorhexidine or alcohol
▪ Hospitals: Isolate until treated adequately
▪ Decolonization for recurrent infections
● Decontaminating baths (hypochlorite, 1 tsp common
Batch Clingy
● S. enterica var enteritidis and S. typhimurium
▪ Practices that promote antibiotic-resistant
bacteria
● Subtherapeutic concentration of antibiotics in
animal feeds to promote growth (can also be
contaminated with Salmonella)
● Previous antibiotic use among the child in the
previous month
214
Strains that cause local tissue destruction:
▪ Hemolysins causes tissue necrosis
▪
Panton-Valentine
leucocidin
(PVL):
↑
permeability and eventual death of the cell
▪ Exfoliatin A & B: exotoxins; produce localized
(bullous impetigo) or generalized (SSSS, scarlet
fever) dermatologic manifestations
Toxins:
▪ Enterotoxin (types A-V): ingestion of preformed
enterotoxin A & B results to food poisoning
▪ Toxic shock syndrome toxin-1 (TSST-1) superantigen that induces production of IL-1 & TNF;
assoc. w/ TSS, related to menstruation and focal
infection (nasal packing)
Expression of proteins that mediate resistance
▪ Penicillinase or ß-lactamase: produced universally
by all isolates; inactivates ß-lactams
▪ Altered penicillin-binding proteins: mediates
resistance to penicillinase resistant antibiotics
INCUBATION PERIOD: 2 – 7 hours
TRANSMISSION
▪ Person to person
▪ Autoinoculation or direct contact w/ hands of
other colonized individuals
● Effective disseminators: nasal carriers
▪ Rare: Fomites (shared towels in football team)
Risk factors: disruption of intact skin,
corticosteroids, malnutrition, azotemia, viral
infections, congenital defects in chemotaxis &
phagocytosis, HIV, poor mucous clearance (cystic
fibrosis)
▪ Membranous tracheitis (complication of viral croup) –
high fever, leukocytosis, upper airway obstruction
▪ Pneumonia
● hematogenous pneumonia may be 2o to septic
emboli from R-sided endocarditis or septic
thrombophlebitis
● Inhalation Pneumonia: high fever, abdominal pain,
RR, dyspnea, localized or diffuse bronchopneumonia or
lobar disease
● Necrotizing pneumonitis: assoc. w/ empyema,
pneumatocele, pyopneumothorax, bronchopulmo-nary
fistulas
Sepsis
▪ onset may be acute; nausea, vomiting, myalgia, fever,
chills
▪ Organism may localize to heart valves, lungs, joints,
bones muscles and deep tissue abscesses
▪ Disseminated S. aureus disease: fever, persistent
bacteremia despite antibiotics, focal involvement of ≥ 2
separate tissue sites; usually have an endovascular nidus
of infection
Pyomyositis: localized abscess in muscle w/ out
septicemia (prior trauma)
Bones and joints
▪ Osteomyelitis, suppurative arthritis: pseudo paralysis
(neonates) or pain w/ movement of affected extremity;
older: pain, fever, localizing signs (edema, erythema,
warmth, limp, or refusal to walk)
CNS
▪ Meningitis (uncommon) – assoc. penetrating cranial
trauma,
neurosurgical
procedures,
endocarditis,
parameningeal foci, complicated sinusitis, DM, or
malignancy
Heart: Acute endocarditis on native valves
Kidneys: renal and perinephric abscess
Intestinal Tract
▪ Enterocolitis, diarrhea + blood and mucus, peritonitis
from long-term peritoneal dialysis
▪ Food poisoning: 2-7 hours after ingestion of preformed
enterotoxins, sudden, severe vomiting, watery diarrhea,
absent to low fever. Symptoms persist >12-24 hours.
Toxic Shock Syndrome
▪ characterized by fever, hypotension, erythematous rash
with subsequent desquamation on the hands and feet,
multisystem involvement
(see Nelson’s 21st Ed., Table 208.2 for Diagnostic Criteria of
PPS Oral Exam Reviewer 2020
DIFFERENTIAL DIAGNOSIS
▪ Skin: GAS (rapid spread)
▪ Fluctuant skin & soft tissue: MTB, atypical mycobacteria, B.
henselae, F. tularensis, fungi
▪ Cavitary pneumonia: K. pneumonia, MTB
▪ Bone and joint infection: GAS, Kingella kingae
▪ TSS: Kawasaki disease
MANAGEMENT
▪ Incision and drainage
▪ Remove foreign bodies
Initial Empiric Therapy
▪ If life threatening, Vancomycin + nafcillin or oxacillin
▪ If non-life threatening,
● No signs of severe sepsis, vancomycin or clindamycin
● Low likelihood of MRSA, cefazolin or nafcillin
bleach solution per gallon of water or chlorhexidine 4% soap
used weekly)
● Appropriate oral antibiotic
● Nasal mupirocin BID x 1 week
● Cleaning of household linens in hot water
▪ Food poisoning
● Exclude individuals w/ infection of the skin from
preparation and handling of the food
● Prepared foods should be eaten immediately or
refrigerated appropriately to prevent multiplication of S.
aureus that may have contaminated the food
PROGNOSIS
▪ Untreated septicemia: high fatality rate
▪ Pneumonia: fatal at any age
▪ Factors affecting prognosis: nutrition, immunologic
competence, presence of other debilitating disease
MSSA
▪ Nafcillin*
▪ Cefazolin
▪ Clindamycin – if with serious Pen allergy & susceptible strain
▪ Vancomycin – if Pen and Cephalosporin allergic
▪ AmpiSul – if broader gram (-) coverage is needed
▪ Less severe: Dicloxacillin, cephalexin, co-amox
MRSA
▪ Vancomycin*
▪ Clindamycin (if susceptible)
▪ Daptomycin, Linezolid, TMP SXT
*Add gentamycin or rifampin for endocarditis and CNS infection
Batch Clingy
▪ Catalase: inactivates H2O2 for intracellular survival
215
PATHOGENESIS
Staphyloccocal TSS)
▪ recovery occurs w/in 7-10 days; recurrences can occur
N. GONORRHEA
INCUBATION PERIOD
▪ Genital: 2-5 days in men, 5-10 days in women
▪ Peripartum: 2-5 days after birth
TRANSMISSION
▪ Sexual: sustained by asymptomatic people and
hyperendemic, high risk core group (CSW, MSM,
adolescents w/ multiple sexual partners)
▪
Peripartum:
neonates;
inoculation
or
autoinoculation from a genital site
PATHOGENESIS
▪
Gonococcal
adaptations:
sialylation
of
lipooligosaccharides (endotoxin), ↑ catalase
production and high-frequency antigenic variations
of surface proteins
▪ Gonococcus infects columnar epithelium → attach
to host cells, adhere by pili → after 24h, invaginate
epithelial cell surface → phagocytosed by
neutrophils and suppress activation on CD4 + T
lymphocytes → phagocytic vacuoles release
gonococci → local disease or dissemination through
the bloodstream and lymphatics → inguinal LAD;
perineal; perianal; ischiorectal, periprostatic
abscesses and disseminated gonococcal infection
(DGI)
PPS Oral Exam Reviewer 2020
Asymptomatic Gonorrhea
▪ Isolated in oropharynx of young children (sexually
abused)
▪ Urogenital gonorrheal infection (80% female, 10% male)
▪ Rectal carriage: 26-68% females w/ urogenital infection
Uncomplicated, localized gonorrhea
▪ Urethritis – males; purulent discharge & dysuria, (-)
urgency/frequency, resolve spontaneously or progress
▪ Vulvovaginitis – pre-pubertal female; purulent vaginal
discharge, swollen, erythematous, tender excoriated
vulva, dysuria
▪ Cervicitis and urethritis – post-pubertal female;
purulent
discharge,
suprapubic
pain,
dysuria,
intermenstrual bleeding, dyspareunia
▪ Rectal gonorrhea – asymptomatic; may cause proctitis
with anal discharge, pruritus, bleeding, pain, tenesmus,
constipation
● In MSM, the rectal mucosa is painless w/
mucopurulent discharge and scant rectal bleeding to
overt proctitis w/ rectal pain and tenesmus
▪ Ophthalmitis – uni/bilateral, any age group
● Ophthalmia neonatorum – 1-4 d after birth; mild
inflammation and serosanguinous discharge → within 24
hours, thick purulent discharge with tense edema of
eyelids and chemosis
Disseminated Gonococcal Infection (DGI)
▪ 1-3% (asymptomatic>symptomatic); M>F
▪ Most common initial symptom: acute onset of
polyarthralgia with fever
▪ Asymmetric arthralgia, petechial, or postural acral skin
lesions, tenosynovitis, suppurative arthritis, carditis,
meningitis, osteomyelitis
▪ Painful discrete 1-20mm pink or red macules → MP,
vesicular, bullous, pustular, or petechial lesions and
necrotic pustule on an erythematous base unevenly
DIAGNOSTICS
▪ Gram stain: gram negative intracellular diplococci within
leukocyte in urethral discharge
▪ NAAT
● Less stringent transport, more rapid turnaround time,
flexibility in sampling; however, cannot provide antimicrobial
susceptibility
● Endocervical swabs, vaginal swabs, male urethral swabs,
female/male 1st catch urine
● For women, Sn is lower in urine specimen
● For MSM: annual rectal and pharyngeal sites
▪ Culture
● Swab endocervix & rectum in ALL females, regardless of
history of anal intercourse; swab urethra and rectum in males
● in a suspected case of child abuse, culture remains the
recommended method of detection of N. gonorrhoeae
● DGI: culture blood, pharynx, rectum, urethra, cervix, and
synovial fluid
● Used to evaluate treatment failure and monitor developing
resistance to current regimen
MANAGEMENT
▪ Test for co-infection (syphilis, HIV, chlamydia)
● Neonates: treat for both if chlamydia results are not
available or (-) in non-NAAT test
● Sexually active: abstain for 7d after treatment and until all
partners are adequately treated. Sexual partners exposed in the
preceding 60d should be examined, specimens collected, and
presumptive treatment started
● Ophthalmia: lavage of the infected eye with saline solution
once
▪ Neo: Ceftriaxone (WOF hyperbilirubinemia) or Cefotaxime
▪ Children < 45 kg: Ceftriaxone
▪ > 45 kg, adolescent and adult: Ceftriaxone + Azithromycin 1g
PO (1 dose)
COMPLICATIONS
▪ Ophthalmia: corneal ulceration, rupture, blindness
▪ Endometritis → salpingitis, peritonitis, tuboovarian abscess
(PID)
▪ PID: vaginal discharge, suprapubic pain, cervical tenderness,
fever, leukocytosis, ↑ ESR, adnexal tenderness
▪ Fitz-Hugh-Curtis syndrome/perihepatitis ± signs of salpingitis
→ hydrosalpinx, pyosalpinx, tuboovarian abscess, sterility
▪ Urogenital infection during the 1st trimester – high risk for
septic abortion
▪ After 16wks AOG: chorioamnionitis → PROM and premature
delivery
▪ Epididymitis → overt urethritis
▪ Unusual: penile edema ass. dorsal lymphangitis or
thrombophlebitis, periurethral abscess or fistulas, seminal
vasculitis, and balanitis (uncircumcised)
PREVENTION
▪ Education
▪ Barrier protection (condoms)
▪ Screening of high-risk populations
Gonococcal ophthalmia neonatorum
▪ Give erythromycin (0.5%) ophthalmic ointment
▪ If unavailable and at risk, give Ceftriaxone 25-50mg/kg IV or
IM (max: 250 mg) single dose
PROGNOSIS
▪ Good if w/ early appropriate therapy
▪ Treatment failure
● No resolution within 3-5d of treatment + no sex during tx
● (+) Culture > 72h or NAAT ≥ 7d after treatment + no sex
during tx
Batch Clingy
Gonorrhea: infection of the GUT mucous
membranes, mucosa of the rectum, oropharynx &
conjunctiva
▪ Nonmotile anaerobic, non-spore forming, gram
negative diplococcus w/ flattened adjacent surface,
pili
▪ Oral sex (MSM) provided pool of asymptomatic
pharyngeal infections
● account for as much as 1/3 of symptomatic
gonococcal urethritis
216
Increased Risk for DGI:
▪ Asymptomatic carriers
▪ Menstruation, pregnancy & postpartum – d/t
maximal endocervical shedding and ↓ peroxidase
bactericidal activity
▪ Neonates due to lack of bactericidal IgM Ab
▪ Persons with terminal complement component
deficiencies are at considerable risk for
development of recurrent episodes
N.
MENINGITIDIS
Meningococcus
▪ Commensal of the human nasopharynx
▪ Rarely enters the blood stream (meningitis,
meningococcemia)
▪ Gram negative, fastidious, encapsulated, oxidasepositive, aerobic diplococcus
▪ Endemic disease is caused by genetically
heterogenous strains
▪ Outbreaks are usually clonal, caused by a single
strain
▪ Carriage peaks during adolescence and young
adulthood
▪ Most cases are sporadic
▪ Highest rate: <1yo due to immunologic
inexperience, immaturity of alternative and lectin
complement pathway & poor response to bacterial
polysaccharides
INCUBATION PERIOD: 1 – 14 days
TRANSMISSION
▪ Droplet: close contact thru aerosol droplets
▪ Person to person: exposure to respiratory
secretions (kissing)
▪ Enhanced rates of mucosal colonization and ↑
PPS Oral Exam Reviewer 2020
distributed sparing face and scalp
▪ 2 syndromes
Tenosynovitis – dermatitis syndrome
● More common
● Fever, chills, skin lesions, polyarthralgia (wrists,
hands, fingers)
● (+) Blood culture 30-40%, (-) Synovial fluid cultures
Suppurative arthritis syndrome
● Systemic signs less prominent
● Monoarticular arthritis common (knee); for
neonates, polyarticular.
● (-) Blood culture (+) Synovial fluid cultures 45-55%
consistent w/ septic arthritis
Acute endocarditis: uncommon but fatal; rapid
destruction of aortic valve
Acute pericarditis: rare
Meningitis: SSx similar to acute bacterial meningitis
▪ Most common form: asymptomatic carriage of
organism in the nasopharynx
Acute meningococcal septicemia
▪ Fever, irritability, lethargy, respiratory symptoms,
refusal to drink, vomiting, diarrhea, sore throat, chills
▪ 7%: limb pain, myalgia, refusal to walk
▪ 10%: maculopapular rash
▪ Cold hands/feet, abnormal skin color, prolonged CRT,
non-blanching, or petechial rash in > 80%
▪ Fulminant: progress rapidly over hours to septic shock –
prominent petechia and purpura (purpura fulminans),
poor peripheral perfusion,  HR,  RR, BP, confusion,
coma, coagulopathy, electrolyte disturbance (hypoK),
acidosis, adrenal hemorrhage, RF, myocardial failure
Meningococcal meningitis
▪ Indistinguishable from other bacterial meningitis
▪ Rapidly progressive cerebral edema → death
Occult meningococcal bacteremia
▪ Fever ± symptoms that suggest minor viral infection;
spontaneous resolution can occur
▪ Sustained bacteremia → meningitis 60% and distant
infection of other tissues
▪ If allergic to cephalosporin and uncomplicated: Gentamicin
240 mg IM + Azithromycin 2g PO
▪ If allergic to Azithromycin: Doxycycline 100mg PO BID x7d
▪ If Ceftriaxone unavailable: oral Cefixime 400mg PO,
Ceftizoxime, Cefoxitin + probenecid or Cefotaxime
Duration of Ceftriaxone treatment
▪ One dose – pharyngeal, anorectal, urogenital, ophthalmia
neonatorum
▪ 7 days – scalp abscess, septic arthritis
▪ 10-14 days – meningitis
▪ Min. of 28 days – endocarditis
▪ If DGI, continue 24-48h after clinical improvement begins. If
no organism is isolated and diagnosis is secure, continue for at
least 7days
▪ Follow-up test-of-cure is not recommended for uncomplicated
urogenital or rectal gonorrhea receiving recommended or
alternative regimens
● Pharyngeal gonorrhea treated with alternative regimen:
patient should return after 14d for CS, NAAT
▪ Once suspected, start third-generation cephalosporin until
diagnosis is confirmed
▪ Once diagnosis of β lactam sensitive meningococcal disease is
confirmed → switch to Penicillin
Pen G
300,000
u/kg/day
Q4-6
Does not
clear carriage
& prophylaxis
is required at
the end
Ampicillin
200400mkday
Q6
Cefotaxime
200300mkday
Q6-8
Neonate
Ceftriaxone
100mkday
Q1224
↓ Skin
complications
▪ Supportive care: assess and correct glucose, K, Ca, Mg, PO4,
clotting factors, anemia
Vaccine
▪ 2 preparations
● Tetravalent (ACYW-135) conjugate vaccine: MCV4-D,
MCV4-TT, MCV4-CRM; all given IM
● Tetravalent meningococcal polysaccharide vaccine:
MPSV4; given IM or SQ; poorly immunogenic in infants, do not
induce immunologic memory, assoc. w/ immunologic
hyporesponsiveness (IH) that is why conjugated vaccines were
COMPLICATIONS
▪
Acute:
adrenal
hemorrhage,
endophthalmitis,
endo/peri/myocarditis, pneumonia, lung abscess, peritonitis,
renal infarcts
▪ Pre-renal failure → renal insufficiency (dialysis)
▪ Reactivation of latent herpes simplex
▪ Waterhouse-Friderichsen syndrome: adrenal insufficiency
resulting from adrenal necrosis or hemorrhage 2O to severe
meningococcal sepsis
▪ Immune complex vasculitis – fever, rash, iritis, carditis,
pericarditis; self-limiting, occurs 1st 10 days after infection
● Arthritis: mono or oligoarticular, large joints, sterile
effusions
Meningococcal Meningitis
▪ Most frequent sequela: deafness
▪ Severe: cerebral arterial & venous thrombosis → infarction
▪ Subdural effusion, brain abscess, ataxia, seizures, blindness,
CN palsies, hemi- or quadriparesis, obstructive hydrocephalus
(3-4wks after onset)
Meningococcal septicemia
▪ Most common: focal skin infarction → scarring, require skin
grafting
▪ Distal tissue necrosis in purpura fulminans may require
amputation
Batch Clingy
▪ IgA protease inactivates IgA1 for colonization or
invasion of host mucosal surfaces
▪ Estrogen-induced cornification of the vaginal
epithelium of neonates and mature females resist
infection
217
Chronic meningococcemia
▪ Fever, nontoxic appearance, arthralgia, headache,
splenomegaly, MP or petechial rash
▪ Intermittent symptoms for 6-8 weeks
▪ May spontaneously resolve
▪ If untreated may lead to meningitis
PATHOGENESIS
Colonization of the nasopharynx (carriage or
invasive disease) → host epithelial cells (mediated
by pili) → 1st line of defense avoided by Ig A1
protease that degrades secretory IgA → close
adhesion, internalization, transcytosis to the
basolateral tissue → dissemination into the blood
stream → resistance to complement-mediated lysis
& phagocytosis is mediated by polysaccharide
capsule and LPS → Multiply to high levels to cause
meningococcemia → ↑ vascular permeability
(hypovolemia), capillary leak syndrome (pulmonary
edema & respiratory failure), pathologic
vasoconstriction (pallor & cold extremities) and
vasodilation (warm shock: warm extremities,
bounding pulses), DIC, profound myocardial
dysfunction (direct negative cytokine effect IL-6) →
impairment of microvascular blood flow →
multiorgan failure
DIAGNOSTICS
▪ CBC:  or WBC, neutrophils, bands, anemia,  plt
▪ Proteinuria, hematuria, ESR & CRP
▪ If rapid onset: findings may be normal
▪ Diagnosis more likely: CRP, fever, petechiae
▪ Confirmation: isolation of organism from normal sterile
body fluid (blood, CSF, synovial fluid)
● GS/CS: petechial or purpuric skin lesion or buffy coat
of centrifuged blood sample.
● Culture <50% positive and isolation from the NP is
not diagnostic of invasive disease
▪ PCR: High sensitivity & specificity (blood & CSF)
▪ CSF analysis: findings are the same as bacterial
meningitis and showing gram negative diplococci.
▪ Meningococcal septicemia:  Alb, Ca, K, Mg, PO4,
glucose, met. acidosis,  lactate
DIFFERENTIAL DIAGNOSIS
▪ Gram (-) causing sepsis & meningitis (S. pneumonia, S.
aureus, epidemic typhus)
▪ Bacterial endocarditis
▪ Petechial rash: enterovirus, influenza, measles, EBV,
CMV, parvovirus
▪ Protein C or S deficiency, platelet disorders, HSP,
connective tissue disorders, drug eruptions, trauma
Following invasion of circulation, may enter CSF →
stimulate proinflammatory cascade, upregulation of
specific adhesion molecules, recruitment of
leukocytes → damage directly by meningeal
inflammation & indirectly by circulatory collapse →
cerebral edema → herniation
SHIGELLOSIS
▪ 4 species: S. dysenteriae (group A), S. flexneri
(group B), S. boydii (group C), S. sonnei (group D)
▪ Gram negative bacilli, facultative, aerobic
▪ Acute invasive enteric infection
▪ Endemic to temperate and tropical climates
▪ Highest incidence: < 10yo
▪ 70% of all episodes & 60% of Shigella-related
deaths occur in < 5yo
▪ Infection in the 1st 6mos of life is rare
● partially may be d/t breastmilk (contains Ab to
PPS Oral Exam Reviewer 2020
▪ Bacillary dysentery (bloody diarrhea, fever, abdominal
cramps, rectal pain, mucoid stools)
● clinically similar regardless of infecting serotype
▪ Diarrhea: large volume, watery → frequent smallvolume, bloody mucoid stools (most never progress to
bloody stools)
▪ High fever, severe abdominal pain, emesis, anorexia,
generalized toxicity, urgency, painful defecation,
dehydration
● Fever distinguishes shigellosis from EHEC
invented.
▪ Indications: those at high risk for invasive disease
● persistent complement component deficiencies
● anatomic functional asplenia (including sickle cell dse)
● HIV
● Travelers to/resident of areas where it is hyper/endemic
including countries in the African meningitis belt or the Hajj,
● Belonging to a defined risk group during a community or
institution meningococcal outbreak
▪ Dose and Schedule
CONJUGATE:
● MCV4-D - For children 9-23 months, give 2 doses 3 months
apart; For children 2 yrs and above, give one dose except in
cases of asplenia, HIV, persistent complement component
deficiency where 2 doses given 8 weeks apart are
recommended
● MCV4-TT- Infants 6-12 weeks old, give first 2 doses at least
2 months apart, the 3rd (booster) dose is at age 12 months; For
children from 12 months of age to adolescence: 1 dose only
● MCV-CRM - given to children 2 years and above as single
dose; revaccinate with a MCV4 Q5 years as long as the person
remains at increased risk of infection
POLYSACHARRIDE:
● MPSV4 - given to children 2 years and above as a single
dose. if used for high risk as the 1st dose, a 2nd dose using MCV4
should be given 2 months later. No booster.
(see PPS PIDSP PFV Childhood Immunization Schedule 2020 Annotations
for Vaccines for High-Risk/Special Groups for further reading)
▪ Fluid and electrolyte correction and maintenance
▪ Nutrition: high protein and caloric diet enhances growth in
6mos after infection
▪ Do not use drugs that impair intestinal motility (e.g.
loperamide) → can prolong the illness
▪ single dose Vitamin A 200,000 IU
▪ Zinc 20mg x 2wks
▪ Antibiotics
● 1st line: Ciprofloxacin (WHO DOC for all patients with
bloody diarrhea regardless of age); Ceftriaxone (if parenteral
▪ DIC → avascular necrosis of epiphyses & epiphysealmetaphyseal defects → growth disturbance and late skeletal
deformities
PROGNOSIS
▪ Case fatality is 5-10% for invasive meningococcal dse
▪ Delayed initiation of supportive therapy: poor outcome
▪ Poor prognostic factors: hypothermia or extreme
hyperpyrexia, hypotension/shock, purpura fulminans,
seizures,  WBC,  plt, DIC, acidosis,  endotoxin & TNF α;
petechiae <12h before admission, absence of meningitis,  or
N ESR → rapid, fulminant progression → poor prognosis
PREVENTION
▪ Droplet precaution x 24 hours after initiation of therapy
POSTEXPOSURE PROPHYLAXIS
▪ Indications
● Household contact esp. < 2yo
● Childcare or preschool contact at any time during 7d
before onset of illness
● Direct exposure to index patient (kissing, sharing
toothbrush) during 7d before onset of illness
● Medical personnel w/ exposure to aerosols of resp.
secretions (mouth to mouth resuscitation, intubation,
suctioning ≤24hr after antibiotic therapy) during 7d before
onset of illness
● Frequently slept in same dwelling as index px during 7d
before onset of illness
● Passengers seated directly next to index case during
airline flights >8hrs
▪ Most effective: Ceftriaxone 125-250mg IM x 1dose +
Ciprofloxacin 20mg/kg (max 500 mg) PO x 1dose
▪ Most widely used: Rifampin 5-10mg/kg Q12 x 2days but fails
to eradicate colonization in 15% of cases
▪ Alternative (not recommended routinely): Azithromycin
10mg/kg (max 500 mg) PO x 1dose
COMPLICATIONS
Intestinal
▪ Rectal prolapse, toxic megacolon, pseudomembranous
colitis
▪ Rare: intestinal obstruction and appendicitis ± perforation
Extraintestinal
▪ Most common complication: dehydration
▪ Severe hypoNa (<126), hypoglycemia, focal infections
(osteomyelitis, arthritis, splenic abscess, vaginitis – typically
Batch Clingy
disease risk: ↑ likelihood of exposure to new strain
or ↑ proximity to a carrier (kissing, bar patronage,
binge drinking, night clubs, MSM, living in freshman
college dorm)
▪ Risk of carriage: damage of NP mucosa – smoking,
respiratory viral infection
218
INCUBATION PERIOD: 12h to several days
TRANSMISSION
▪ Fecal – oral
● Vector: contaminated food (extensive handling
of ingredients) and water
PATHOGENESIS
▪ Shigella can survive the acid in the stomach →
colon (target organ) w/ changes most intense in the
distal part
▪ In the colon, it crosses the epithelium by
transcytosis through M cells → encounters & kills
macrophages by activating inflammasome inducing
pyroptosis, apoptosis, & proinflammatory signaling
→ move to the basolateral side, cytoplasm and
adjacent cells → activates immune response
attracting NK cells and PMNs → disintegrates
epithelial lining facilitating more invasion of
bacteria but ultimately, phagocytosed and killed by
PMNs
E. COLI
Shiga toxin
▪ Produced by S. dysenteriae serotype 1, Shiga
toxin-producing E. coli & occ. other Shigella spp.
▪ Inhibits protein synthesis to injure vascular
endothelial cells and trigger severe complications of
HUS
▪ Gram negative, facultative, anaerobic, bacilli
▪ Commensal & ubiquitous among humans starting
1st mo of life, normal fecal flora
▪ Categorized by serogroup O (serotype) & H
(flagellar antigen)
▪ Cause frequent infections in 1st yr of life
▪ 30-40% of all diarrheal cases worldwide
▪ Warm months in temperate climates & rainy
seasons on tropical climates
TRANSMISSION
▪ Fecal-oral – contaminated food or water, contact
w/ infectious person, fomite, or carrier animal and
its environment
PPS Oral Exam Reviewer 2020
▪ Untreated diarrhea can last 7-10 days
▪ 10% persists > 10 days (AIDS, malnourished, occ.
normal children)
▪ PE: Abdominal distention and tenderness, hyperactive
bowel sounds, tender rectum (DRE), rectal prolapse (esp.
for malnourished)
▪ Extraintestinal findings: neurologic (convulsions, HA,
lethargy, confusion, nuchal rigidity, hallucinations before
or after the onset of diarrhea)
therapy is warranted)
DIAGNOSTICS
▪ Presumptive data supporting dx of bacillary dysentery
● Stool: leukocytes (>50-100/hpf, confirms colitis),
fecal blood
● Blood: leukocytosis with shift to left, usually 500015000cells/µL, leukopenia, leukemoid reaction >40 000/
µL may occur
▪ Culture: stool & rectal swab
▪ Quantitative PCR
(see Nelson’s 21st Ed., Fig. 226.1 for Management algorithm: guidelines
for treatment of shigellosis)
● 2nd line: Azithromycin, Cefixime or TMP-SMX (if known to
be susceptible)
● Treatment should be reserved for moderate to severe
disease, IC, or to prevent or mitigate outbreaks (childcare or
food handling)
● A child with typical dysentery who responds to initial
treatment should be continued x 5d even if stool culture is (-)
DIFFERENTIAL DIAGNOSIS
▪ Enteroinvasive E. coli (EIEC), C. jejuni, Salmonella spp.,
Shiga toxin-producing E. coli (O157:H7), Yersinia
enterocolitica, Clostridium difficile, E. histolytica
▪ IBD
PATHOGENESIS
▪ Pathogenicity: virulence characteristics (adherence
factors & toxins)
▪ To produce diarrhea, adherence to glycoprotein or
glycolipid receptor on intestinal cell → injure or disturb
the function of intestinal cell
Post-infectious
▪ HUS, reactive arthritis, IBS, protein losing enteropathy
▪ Cholestatic hepatitis, conjunctivitis, iritis, corneal ulcers,
pneumonia (2-5wks after), cystitis, myocarditis
▪ Neonates: septicemia, meningitis, dehydration, colonic
perforation, toxic megacolon
PREVENTION
▪ Control measure: After cessation of symptoms, should avoid
recreational water activities for 1 additional week
▪ Encourage breastfeeding
▪ Proper handwashing
▪ Children should be excluded in child-care facilities
▪ No vaccine, but measles immunization can reduce the
incidence and severity of diarrheal disease including
Shigellosis
▪ CSF: pleocytosis with minimally ↑ protein levels can be
seen but meningitis caused by shigellae is rare
▪ Vertical transmission (neonatal sepsis), UTI (ascending),
epididymitis (sex in men who practice insertive anal sex),
pneumonia (nosocomial by aspiration or hematogenous
spread)
with blood-tinged discharge assoc. S. flexneri)
▪ Sepsis (malnourished or IC), leukemoid reaction
▪ Ekiri syndrome/lethal toxic encephalopathy: severe toxicity,
convulsions, extreme hyperpyrexia, HA, brain edema, rapidly
fatal outcome without sepsis or significant dehydration
▪ Uncommon: DIC (malnourished), bacteremia (girls or women
w/ HIV, malnourished)
PROGNOSIS
▪ 20% mortality: sepsis
▪ Severity of illness and risk of death greatest with S.
dysenteriae type 1 and least with S. sonnei
GENERAL MANAGEMENT
▪ Appropriate fluid and electrolyte therapy
▪ Early refeeding – within 6-8hours of initiating rehydration
▪ Oral zinc
▪ Other than for a child recently returning from travel in the
developing world, empirical treatment of severe watery
diarrhea with antibiotics is seldom appropriate
DIFFERENTIAL DIAGNOSIS
▪ Presumptive diagnosis of intussusception, appendicitis, IBD,
ischemic colitis
PREVENTION
▪ Prolonged breastfeeding
▪ Personal hygiene
▪ Proper food and water handling
▪ Standard and contact precautions
● Outbreak in childcare center: child should not be
permitted to reenter until 2 (-) stool cultures obtained at least
48h after antimicrobial therapy has been discontinued, stools
contained in the diaper or if child is continent, stool frequency
is ≤ 2 stools above normal
Batch Clingy
both virulence plasmid-coded Ag and LPS)
▪ In endemic areas, 75% of family members have
asymptomatic infection
▪ In developed countries: most common cause is S.
sonnei ff. by S. flexneri
219
PPS Oral Exam Reviewer 2020
▪ Acute 3-7 days
▪ Explosive watery, nonmucoid, nonbloody diarrhea, abdominal pain, n/v,
little or no fever
DIAGNOSTICS
▪ Detection of enterotoxins by EIA or PCR
▪ Self-limited
▪ Resolves in 3-5 days but occ. >1 week
SPECIFIC MANAGEMENT
▪ 1st line: Azithromycin 12mg/kg (day1) → 6mg/kg QD (day2-3)
(AAP Red Book 2018)
▪ Acute
▪ Watery diarrhea or dysentery
syndrome with blood, mucus
▪ Fever, systemic toxicity, crampy
abdominal pain, tenesmus, urgency
DIAGNOSTICS
▪ ↑ Peripheral blood PMN w/ left shift
▪ Fecal leukocyte examination of the stool is often positive
▪ Detection of invasion plasmid antigen of Shigella (ipaH) by PCR
SPECIFIC MANAGEMENT
▪ Often initially tx as Shigellosis prior to culture
▪ If susceptible, TMP-SMX is appropriate
▪ Acute or prolonged (>7d), persistent
(>14d)
▪ Profuse watery, non-bloody diarrhea
with mucus, vomiting, low-grade fever
DIAGNOSTICS
▪ Detection of intimin gene (eae) ± bundle-forming pili (bfpA) by
PCR
▪ Absence of Shiga toxins
▪ Tissue culture assay: Hep-2 cells adherence assay (LA, LLA)
▪ Complication: Malnutrition
▪ Toxins: EspF, Map, EAST1, SPATEs
SPECIFIC MANAGEMENT
▪ TMP-SMX may be effective in speeding resolution but lack of a
rapid diagnostic test in resource-poor setting makes treatment
decisions difficult
▪ Acute 4-7 days
▪ May be asymptomatic
▪ Mild diarrhea to severe hemorrhagic
colitis
▪ Abdominal pain w/ watery diarrhea,
→ bloody in 1-4d
▪ Infrequent fever (unlike Shigella and
EIEC)
▪ Toxins: Shiga toxins (Stx1, Stx2 & var
STx2)
▪ Acute, prolonged, or persistent
▪ Watery, mucoid, secretory diarrhea
▪ Low grade fever and little or no
vomiting
DIAGNOSTICS
▪ ↑ Peripheral blood PMN w/ left shift
▪ Detection of Shiga toxins by EIA or PCR (Stx1, Stx2)
▪ Stool culture to detect E. coli O157
▪ Simultaneous culture for O157 and nonculture assays to
detect Shiga toxin
▪ Confirmation: latex agglutination tests
SPECIFIC MANAGEMENT
▪ Do not give antibiotics – higher risk for HUS
● antibiotics induce bacterial stress → toxin production →
phage-mediated bacterial lysis with toxin release
DIAGNOSTICS
▪ Detection of AggR, AA (aggregative adherence) plasmid, and
other virulence genes by PCR
▪ Tissue culture assay: HEp-2 cells adherence assay
▪ Most recover without complications
▪ HUS: develops in 5-10%; acute kidney failure,  plt, MAHA
(microangiopathic hemolytic anemia)
● at risk: young children w/ bloody diarrhea & neutrophilic
leukocytosis
▪ Older: can also develop HUS or TTP
● HUS: MAHA, ARF,  plt, mild CNS symptoms
● TTP: MAHA, Renal dysfunction,  plt, severe CNS, fever
▪ Growth retardation, malnutrition in infants of developing
world
Batch Clingy
ENTEROTOXIGENIC (ETEC)
▪ At risk: >1yo and travelers
▪ Most common cause of traveler’s diarrhea
Watery Bloody
▪ Incubation Period: 1-5 days
▪ Secrete heat-labile enterotoxin (LT) and/or heat+++
stable enterotoxin (ST) → induces ion and water
secretion into the intestinal lumen
▪ Produces type IV pilus/ longus: colonization factor
ENTEROINVASIVE (EIEC)
▪ At risk: >1yo
▪ Occurs in outbreaks, endemic in developing
countries
▪ Incubation: 3-4 days (range: 1-8 days)
+
++
▪ Mucosal invasion and inflammation of large bowel
▪ Shares virulence genes w/ Shigella spp (+) LPS,
nonmotile (lack H or flagellar antigens), not lactose
fermenting
ENTEROPATHOGENIC (EPEC)
▪ At risk: <2yo
▪ Occ. cause of outbreaks in pediatric wards &
daycare
▪ Small bowel adherence and effacement →
blunting of villi, local inflammatory changes,
sloughing of superficial mucosal cells (duodenum
+++
+
through the colon)
▪
Characteristic
attaching
and
effacing
histopathologic lesion: intimate attachment of
bacteria to epithelial surface and effacement of
host cell microvilli encoded by locus of enterocyte
effacement
SHIGA TOXIN-PRODUCING (STEC)/
ENTEROHEMORRHAGIC (EHEC)/
VEROTOXIN-PRODUCING (VTEC)
▪ At risk: 6mos-10yo & elderly
▪ E. coli O157:H7 – most virulent; most freq. assoc.
with HUS
+
+++
▪ Incubation Period: 1-9 days (often 3-4 days)
▪ Affects the colon → adhere to intestinal cells →
produces Shiga toxins → systemic circulation →
damage of vascular endothelial cells → activation
of coagulation cascade, formation of microthrombi,
intravascular hemolysis, ischemia
ENTEROAGGREGATIVE (EAEC OR EGGEC)
▪ At risk: < 2yo, HIV
▪ 2nd most common cause of travelers’ diarrhea
+++
+
▪ Forms characteristic biofilm on intestinal mucosa
→ shortening of villi, hemorrhagic necrosis,
220
inflammatory responses
▪ 3 phases of pathogenesis
● Adherence to intestinal mucosa by fimbriae
● Enhanced production of mucus
● Production of toxins that result in damage to
mucosa
DIFFUSELY ADHERENT (DAEC)
▪ At risk: >1 yo & travelers (adults)
▪ Express diffuse adherence pattern phenotype
▪ Loss of microvilli and decrease in the expression
and enzyme activities of functional brush-borderassociated proteins
ENTEROAGGREGATIVE HEMORRHAGIC E. COLI /
SHIGA-TOXIN PRODUCING EAEC
▪ E. coli O104:H4
▪ hybrid pathogen: colonization mechanisms similar
to EAEC; toxin prod. typical of STEC
● stronger adherence allowing more toxin
delivery to target cells
▪ Tightly spiraled motile spirochete w/ finely
tapered ends
▪ Asymptomatic for years or do not recognize the early
signs
Pathogenic genus subspecies
▪ Venereal species – T. pallidum subsp pallidum
▪ Yaws – T. pallidum subsp pertenue
▪ Bejel or endemic syphillis – T. pallidum subsp
endemicum
▪ Pinta - T. pallidum subsp carateum
PRIMARY SYPHILIS
▪ Chancre: painless papule at the site of entry (usually
genitals, occ. mouth or other extragenital sites) → clean,
painless, highly contagious ulcer w/ raised borders, heals
spontaneously w/in 4-6 weeks → thin scar
▪ Regional lymphadenitis (enlarged and nontender)
ACQUIRED SYPHILIS
SECONDARY SYPHILIS
▪ Untreated 1o syphilis related to spirochetemia 2-10
weeks after chancre heals
▪ Generalized non-pruritic MCP rash on the palms and
soles (pustules can develop)
▪ Condyloma lata – gray white to erythematous wart-like
papules in moist areas: anus, scrotum and vagina
TRANSMISSION
▪ Sexual
▪ Transfusion of contaminated blood or direct
contact with infected tissues
PPS Oral Exam Reviewer 2020
-
SPECIFIC MANAGEMENT
▪ For travelers: Ciprofloxacin or Rifaximin
▪ Acute
▪ Toxins: SPATEs (Sat)/serine-protease
autotransporters
of
Enterobacteriaceae expresses Afa
DIAGNOSTICS
▪ Detection of Dr adhesins (daaC or dad) and Dr-associated
genes by PCR
▪ Tissue culture assay: Hep2-cells adherence assay
▪ Hemorrhagic colitis; some developd
HUS
DIAGNOSTICS
▪ Serologic testing for syphilis remains the principal means for
diagnosis; involves a 2-step screening process
NON-TREPONEMAL Venereal Disease Research Laboratory
(VDRL) & Rapid plasma reagin (RPR)
▪ Sensitive
▪ Detects Ab against phospholipid Ag on the treponeme surface
that cross react with cardiolipin-lecithin-cholesterol antigens of
damaged host cells
▪ Titers increase with active disease, decline with active
treatment; becomes nonreactive within 1 year of adequate
therapy for 1o and within 2 years for 2o
▪ 15-25% becomes serofast (prolonged persisting low levels of
titer)
▪ Mucus patches – white plaques in mucous membrane
▪ Flu-like illness w/ renal, hepatic, and ophthalmologic,
neurologic symptoms
▪ Even w/o treatment, becomes latent 1-2 months after
onset of rash
▪ Relapses occur during 1 st year latency (early latent
period) → late syphilis follows & maybe asymptomatic
(late latent) or symptomatic (tertiary)
TREPONEMAL
▪ Traditionally used to confirm diagnosis
▪ Measures specific T. pallidum Abs
▪ (+) soon after initial infection; positive for life even with
adequate therapy
▪ Titers do not correlate with disease activity
TERTIARY SYPHILIS
(see Nelson’s 21st Ed., Fig. 245.8 A, for Traditional laboratory testing
MANAGEMENT
▪ Test all pregnant women, selective testing of adolescents
based on lesions and risk factors
▪ Test ALL (+) SYPHILIS for HIV
▪ Pregnant women treated in the past do not require
additional therapy unless w/ reinfection (4-fold ↑ in titer)
▪ Desensitize if allergic to penicillin
▪ Sexual partners should be treated if person exposed for
● ≤ 90d before the diagnosis even if seronegative
● > 90d before the diagnosis IF seropositive or if serologic
tests are not available
For 1O, 2O, early latent
▪ Benzathine Pen G 50,000 U/kg (pedia) up to 2.4M U (adult;
max. dose) per IM x 1 dose
▪ If allergic & not pregnant: Doxycycline 100mg PO BID x14d
For late latent
▪ Benzathine Pen G 50,000 U/kg (pedia) per IM x 3 doses at 1week intervals; 2.4 M U (adult) per IM each buttock x 3 doses
at 1-week intervals
▪ 2nd line: Doxycycline 100mg PO BID x 4wks
For tertiary: Benzathine Pen G 7.2M total administered as 3
doses of 2.4M U/IM at 1-week interval; if allergic, consult ID
specialist
For neurosyphilis:
▪ Pedia: Aqueous crystalline Pen G 200,000–300,000 U/kg/day
Batch Clingy
INCUBATION PERIOD: 2-6 weeks
TREPONEMA
PALLIDUM
++
▪ Toxins: SPATEs (Pic, Pet), ShET1,
EAST1
221
NEUROSYPHILIS
▪ Can occur at any stage
▪ Syphilitic meningitis, uveitis, seizures, optic atrophy,
dementia
▪ CSF: pleocytosis and ↑ protein
▪ CSF VDRL test is poorly sensitive
CONGENITAL SYPHILIS
TRANSMISSION
▪ Transplacental or intrapartum contact with
infectious lesions
▪ Can occur at any stage of pregnancy – highest
during the 1st 4 years of primary infection,
secondary infection and early latent disease
▪ Vasculitis → necrosis and fibrosis
▪ Untreated during pregnancy results in vertical
transmission (100%) → symptoms appear w/n
weeks or months
Early signs (1st 2 years of life)
▪ Most are asymptomatic at birth
▪ Hepatosplenomegaly, jaundice, elevated LFT
▪ Liver involvement: bile stasis, fibrosis, extramedullary
hematopoiesis
▪ Diffuse LAD resolves spontaneously (shotty nodes
persist)
▪ Osteochondritis, periostitis, erythematous MP or VB →
desquamation hands & feet
▪ Osteochondritis: painful → irritability and refusal to
move the involved extremity (Pseudoparalysis of Parrot)
▪ Mucous patches, persistent rhinitis, condyloma
▪ FTT, nephritis, NS, HTN, hematuria, proteinuria,
hypoproteinemia,
hypercholesterolemia,
hypocomplementemia
▪ Less common: AGE, peritonitis, pancreatitis,
pneumonia, glaucoma, chorioretinitis, non-immune
hydrops, testicular masses
▪
Labs:
Coombs-negative
hemolytic
anemia,
thrombocytopenia
▪ Bone: Wimberger lines – demineralization medical
prox. tibial metaphysis; multiple osteochondritis (wrists,
elbows, ankles, knees), periostitis of the long bones and
skull (rare)
Late sign (1 st 2 decades, rare)
▪ Skeletal changes: persistent or recurrent periostitis and
thickening of the involved bone.
▪ Hutchinson teeth: can lead to repeated caries → tooth
destruction
PPS Oral Exam Reviewer 2020
algorithm for syphilis and B, for Suggested alternate testing algorithm)
▪ Darkfield or direct fluorescent Ab microscopy of scrapings
from primary lesions, congenital or secondary lesions can reveal
T. pallidum (confirmatory) but are usually not available in
clinical practice
DIFFERENTIAL DIAGNOSIS
▪ Beyond early infancy, consider ABUSE
▪ Oral lesions: aphthous ulcers, herpes
▪ Nipple: cellulitis or eczema
▪ (+) CSF VDRL warrants treatment for neurosyphilis
DIAGNOSTICS
▪ For infants with proven or highly probable disease or abnormal
findings
● RPR, VDRL, CBC, LFT, long-bone radiographs,
ophthalmologic examination, ABR and others, as indicated
▪ Serological tests (nontreponemal and treponemal)
● In congenital infection, VDRL/RPR can become NR within a
few mos. after adequate treatment
● Neonatal tests can be confounded by maternal IgG Ab
transferred to fetus
● Passively acquired Ab is suggested by titer at least 4-fold
less than maternal titer; can be verified by decline in Ab in the
infant (undetectable 3-6mos of age)
(see Nelson’s 21st Ed., Fig. 245.10 for Algorithm for evaluation and
treatment of infants born to mothers with reactive serologic tests for
syphilis)
▪
Examine
placenta
grossly
&
microscopically:
disproportionately large placenta with focal proliferative villitis,
endovascular and perivascular arteritis, focal or diffuse
immaturity of the placenta villi
▪ For infant (+) VDRL or RPR, normal PE, mothers are
inadequately treated: further evaluation is not necessary if 10
days of parenteral therapy is administered
IV q4-6 x 10-14 days, not to exceed adult dose
▪ Adults: Aqueous crystalline Pen G 18-24M U/day
administered as 3-4M U/IV q4 x 10-14 days or Pen G procaine
2.4M U/IM + Probenecid x 10-14days
▪ If allergic, desensitization most reliable strategy
Jarisch Herxheimer Reaction
▪ Transient acute systemic febrile reaction caused by massive
release of endotoxin like antigens in 15-20% of syphilis
▪ Do not discontinue penicillin
PREVENTION
▪ Early diagnosis
▪ Timely treatment
▪ Routine prenatal screening
▪ Stillborn ≤ 20 week: test for syphilis
▪ Maternal status should be documented at least once
MANAGEMENT
(from DOH National Antibiotic Guidelines 2018)
▪ Aqueous Pen G 100,000-150,000 units/kg/day per IV
administered as 50 000U/kg Q12 during the first 7 days of life
and Q8 thereafter for a total of 10-15 days OR
▪ Procaine Pen G 50,000 units/kg/dose IM x 1 dose for 10-15
days
▪ Ff. up every 2-3 months to confirm 4-fold decrease in
nontreponemal titer
▪ If (+) neurosyphilis: ff. up clinically w/ CSF evaluation every 6
months; at 2 yo: assess neurodevelopment
COMPLICATIONS
▪ Obliterating endarteritis, 40% fetal or perinatal death,
prematurity delivery
PREVENTION
▪ Adequate maternal treatment at least 30 days prior to
delivery
Batch Clingy
▪ 1/3 untreated case: neurologic, cardiovascular &
gummatous lesions (nonsuppurative granulomas of the
skin, bone, liver; from host cytotoxic T-cell response)
222
▪ Saddle nose: assoc. w/ perforated nasal septum
▪ Rare: soft tissue gummas & paroxysmal cold
hemoglobinuria
▪ Other ocular: choroiditis, retinitis, vascular occlusion,
optic atrophy
(See Nelson’s 21st Ed., Table 245.1, for Late Manifestations of
Congenital Syphilis)
INCUBATION PERIOD Invasive: variable
H. INFLUENZAE
TRANSMISSION
▪ Direct contact or inhalation of respiratory droplets
▪ Neonates: intrapartum by aspiration of amniotic
fluid or by contact with genital tract secretions
PATHOGENESIS
▪ Hib: adherence to respiratory epithelium →
colonization of the NP → once in bloodstream, Hib
resists intravascular clearance mechanisms
▪ Noninvasive H. influenzae: gain access to sites by
direct extension causing OM, sinusitis, and
bronchitis
Antibiotic Resistance
▪ 1/3 produces β-lactamase
▪ β-lactamase-negative ampicillin-resistant isolates
manifest resistance by production of a β-lactaminsensitive cell wall synthesis enzyme (PBP3)
Immunity
▪ Host defense: Ab against type b capsular
polysaccharide polyribosylribitol phosphate (PRP)
▪ Unimmunized >6mos & young children lacked an
PPS Oral Exam Reviewer 2020
MENINGITIS
▪ clinically similar with meningitis caused by other
organisms
CELLULITIS
▪ often have antecedent URTI – seeding to soft tissues
during bacteremia
▪ Most common sites: head, neck (cheek & preseptal eye)
▪ Buccal
● Erythematous ± violaceous hue
● Dx: aspirate lead edge (seldom performed) & blood
culture, consider diagnostic LP (<18mos)
▪ Preseptal
● Uncomplicated preseptal cellulitis does not imply a
risk for visual impairment or direct CNS extension;
However, concurrent bactermemia may be assoc. w/
meningitis
● Fever, edema, tenderness, warm lid, occ. purple
discoloration
● Dx: Do blood culture & LP
● DDX: S. pneumoniae, S. aureus & GAS (latter 2: no
fever & interrupted integument)
▪ Orbital
● Complications of acute ethmoid or sphenoid
sinusitis
● Lid edema, proptosis, chemosis, impaired vision,
limited EOM, ↓ mobility of globe or pain on movement
● Dx: CT, to delineate from preseptal cellulitis
CONJUNCTIVITIS
▪ most commonly caused by nontypeable isolates
Respiratory
SUPRAGLOTTITIS/ACUTE EPIGLOTTITIS
PNEUMONIA
OTITIS MEDIA
● 29% H. influenzae
SINUSITIS
▪ Initial for invasive disease: parenteral extended-spectrum
cephalosporin effective in sterilizing all foci & effective against
ampicillin-resistance strains
▪ DOC for susceptible isolates: Ampicillin (IV)/ Amoxicillin (oral)
● if resistant to ampicillin: ceftriaxone; if resistant to
amoxicillin: amox + clavulanate or 2 nd or 3rd gen cephalosporin
COMPLICATIONS
▪ Sequelae of meningitis: behavior problems, language
disorders, impaired vision, mental retardation, motor
abnormalities, ataxia, seizures, hydrocephalus
● 6% are left with hearing impairment (inflammation of the
cochlea and labyrinth) →
▪ Meningitis
● IV antibiotics x 7-14 days
● Dexamethasone (0.6 mkday q6 x 2d) – to decrease
incidence of hearing loss
▪ Buccal Cellulitis
● Parenteral antibiotic until afebrile x then switch to oral to
complete 7-10 days
▪ Preseptal Cellulitis
● Parenteral antibiotics (also active against MSSA, MRSA, S.
pneumoniae, GABHS) x 5d until fever & erythema have abate;
complete for total of 10 days
▪ Orbital Cellulitis
● Parenteral x at least 14 days; if with sinusitis or orbital
abscess, may require surgical drainage ± prolonged antibiotic
POSTEXPOSURE PROPHYLAXIS
▪ Indications
● Household with at least 1 contact younger than 4 yo who
is unimmunized or incompletely immunized
● Household w/ child <12mos who did not complete the
primary Hib series
● Household w/ contact who is an IC child, regardless of
that child’s immunization status or age
● Preschool and childcare center contact when ≥ 2 have
occurred w/in 60 days
● For index patient, if < 2yo or member of a household w/
a susceptible contact and treated w/ a regimen other than
cefotaxime or ceftriaxone, chemoprophylaxis at the end of
therapy for invasive infection
▪ Rifampin, orally QD x 4d (CI: pregnant)
● 0 – 1 month old: 10mkdose
● >1 month old: 20mkdose (max: 600 mg/dose)
▪ Epiglottitis
● 1st line: Ceftriaxone x 7-10 days; 2nd line: Ampi-sul x 10 days
(DOH National Antibiotic Guidelines 2018)
▪ Pneumonia
● < 12 mos. whom H. influenza is suspected, give parenteral
antibiotics because of increased risk of bacteremia
● older children not severely ill: oral antimicrobial
treat x 7-10 days
▪ Suppurative Arthritis
● Uncomplicated – parenteral 5-7d x ≥ 3wks until CRP is
normal
● If GS shows G(-) organism: cefotaxime 100-200mkday or
ceftriaxone 100mkday (DOH National Antibiotic Guidelines 2018)
▪ AOM
● Amoxicillin 80-90 mkday (<2yo: 10d, 2-5yo: 7d, >5yo: 5-7d)
or Ceftriaxone (single dose)
● If (+) anaphylaxis: Clarithromycin 15mkday Q12
PROGNOSIS
▪ Presence of SIADH or FND during meningitis are poor
prognostic features
▪ Supraglottitis is a MEDICAL EMERGENCY; potentially lethal
Batch Clingy
▪ Fastidious, gram negative, pleomorphic
coccobacillus
● requires Factor X (hematin) and Factor V
(phosphopyridine nucleotide) for growth
▪ > 90% in children < 5yo; majority < 2yo
▪ Humans are the only natural hosts (normal flora in
60-90%)
▪ Unvaccinated infants are at increased risk of
recurrence
▪ Among age-susceptible household contacts
exposed to invasive Hib, increase risk for secondary
cases in the 1st 30 days
▪ Most remain colonized during 1 st 24 hours of
therapy
223
DIAGNOSTICS
▪ Presumptive: Gram staining (difficult to visualize)
▪ Culture: should not be exposed to drying or
extreme temperatures
▪ Serotyping: slide agglutination with type specific
antisera
▪ NAAT, PCR
SUPPURATIVE ARTHRITIS (3%)
▪ Single large joints (knee, hip, ankle, elbow), 6%
multijoint
PERICARDITIS
▪ Antecedent URTI
▪ Fever, respiratory distress, tachycardia
▪ Dx: recover from blood or pericardial fluid, GS, or
detection of PRP in pericardial fluid, blood or urine
BACTEREMIA WITHOUT AN ASSOCIATED FOCUS
▪ Fever without any apparent focus of infection
▪ Risk factors: fever ≥ 39OC & leukocytosis ≥ 15 000
cells/µ
▪ If untreated: 25% developed meningitis
▪ Dx: reevaluate focus of infection, 2 nd blood culture, LP,
CXR
MISCELLANEOUS INFECTION
▪ Rare: UTI, epididymo-orchitis, cervical adenitis, acute
glossitis, infected thyroglossal duct cysts, uvulitis,
endocarditis, endophthalmitis, primary peritonitis,
osteomyelitis & periappendiceal abscess
INVASIVE DISEASE IN NEONATES
▪ Bacteremia w/ sepsis, pneumonia, RDS + shock,
conjunctivitis, scalp abscess or cellulitis, meningitis,
mastoiditis, septic arthritis, congenital vascular eruption
GROUP B
STREPTOCOCCUS
Streptococcus agalactiae
▪ Major pathogen for neonates, pregnant women
and nonpregnant adults
▪ Facultative anaerobic gram (+) cocci (chains or
diplococci)
▪ 10 distinct GBS capsular polysaccharides identified
(types Ia, Ib, II-IX)
● important virulence factors and stimulators of
antibody-assoc. immunity
▪ Incidence of neonatal GBS disease is higher in
premature and LBW infants although most cases
occur in full-term infants
▪ Vaginal or rectal colonization in 30% of pregnant
women
● maternal intrapartum chemoprophylaxis led
PPS Oral Exam Reviewer 2020
▪ Two syndromes of neonatal GBS disease
Early Onset
Late Onset
Age at onset
0-6 days
7-90 days
↑ risk after
OB
Yes
No
complications
Common
Bacteremia,
Sepsis,
clinical
meningitis,
pneumonia,
manifestations
osteomyelitis, other
meningitis
focal infections
Common
1a, 1b, II,
III predominates
serotypes
III, V
Case fatality
4.7%
2.8%
rates
● Amoxicillin-clavulanic acid: for treatment failure or if β
lactamase producing isolate (tympanocentesis or drainage fluid)
▪ Sinusitis
● Amoxicillin, Amoxicillin – Clavulanic Acid x 10d
▪ Conjunctivitis
● Tobramycin or Levofloxacin 2 drops QID x 5-7 days (DOH
National Antibiotic Guidelines 2018)
● Avoid topical FQ (broad spectrum, cost, emerging
resistance)
Vaccine
Hib Conjugate Vaccine (IM)
3 doses series with minimum age of 6 weeks and minimum interval
of 4 weeks
Booster dose: 12-15 mos. of age, interval of 6 mos. from the 3rd dose
High Risk:
- Chemotherapy recipients, anatomic/ functional asplenia including
SCD, HIV, Ig or early component complement deficiency
Children 12-59 months
- Unimmunized * or w/ one vaccine dose received <12 months, give 2
additional doses 8 weeks apart
- w/ >2 vaccine received <12 month, give 1 additional dose
- <5 yrs old who received a vaccine dose during or w/in 14d of
starting chemotherapy or RT, rpt the dose at least 3 months after
completion
- (+) Hematopoietic stem cell transplant recipients, revaccination w/ 3
doses, 4 weeks apart starting 6-12 months after transplant is
recommended, REGARDLESS of vaccination history
- Unimmunized* >15 months of age and undergoing elective
splenectomy should be given 1 dose of Hib-containing vaccine at
least 14d before the procedure
- Unimmunized* 5-18 yr + anatomic or functional asplenia (SCD) or
HIV, should be given 1 dose
* Unimmunized: without primary series and booster those or those
w/o at least one dose of vaccine after 14 months of age
▪ Drug of choice: Penicillin G
Neonatal Sepsis
▪ Empiric therapy: Ampicillin + Aminoglycoside (Nelson’s) /
Cefotaxime or Ceftriaxone (avoid ceftri in jaundiced NB) +
Genta or Amik ± Oxacillin or Vanco (if w/ SSTI) (DOH National
Antibiotic Guidelines 2018)
● once identified as GBS & with good clinical response,
therapy may be completed with penicillin alone
▪ Treat for 10 days
Uncomplicated meningitis
▪ High dose of Penicillin or Ampicillin (Nelson’s) / Ampicillin or
Cefotaxime (may use Ceftriaxone if cefotaxime is not available
and NB is not jaundiced) + Amik or Genta (DOH National Antibiotic
COMPLICATIONS
▪ Bacteremia, SSI, bone and joint infections, endocarditis,
pneumonia, meningitis
▪ Meningitis: developmental delay, spastic quadriplegia,
microcephaly, seizure disorder, cortical blindness, or deafness,
PVL
▪ Shock in premature infants
PREVENTION
▪ Chemoprophylaxis – effective only during labor
▪ Vaginorectal GBS screening of all pregnant women at 35-37
wks AOG, except for those w/ GBS bacteriuria during current
or a previous infant w/ invasive GBS disease
▪ Intrapartum prophylaxis: (+) prenatal screening culture, GBS
bacteriuria during pregnancy or previous infant w/ invasive
Batch Clingy
anti-PRP Ab conc. reflecting maturational delay in
the immunologic response to thymus-independent
type 2 Ag such as unconjugated PRP → increased
susceptibility to disease
224
INCUBATION PERIOD
▪ Early onset <7 days, Late-onset & late-late onset:
unknown
TRANSMISSION
▪ Early onset: ascending infection or during passage
through the birth canal, fetal aspiration of infected
amniotic fluid
▪ Late onset: vertical transmission, horizontal
acquisition from nursery or other community
sources
PATHOGENESIS
▪ Type specific capsular polysaccharide (CP):
protects from opsonophagocytosis in the nonimmune host and downregulates leukocyte
activation
● also contains sialic acid w/c prevents activation
of the alternative complement pathway in the
absence of type-specific Ab; also dampen
inflammatory gene activation
▪ Type specific virulence attributes:
● Type III strains are implicated in most cases of
late-onset neonatal GBS disease and meningitis
(taken up by brain endothelial cells more efficiently
vs. other serotypes)
● also produces hypervirulent GBS adhesin
(HvgA): adherence to intestinal and endothelial cells
and mediates invasion to CNS
▪ GBS surface proteins: adhesion to host cells
▪ C5a peptidase: inhibit recruitment of PMN
▪ β hemolysin: cell injury in vitro
▪ Hyaluronidase: spreading factor
ENTEROCOCCUS
▪ Invasive disease: GBS gain access into the
bloodstream by invasion from alveolar space ff.
aspiration of infected fluid
● Except Type III: induce TNF α release in vitro
▪ formerly classified as Lancefield group D
streptococci
PPS Oral Exam Reviewer 2020
Early Onset:
▪ In utero → septic abortion or immediate distress after
birth
▪ Non-specific signs, prominent respiratory signs,
persistent fetal circulation may develop
Late Onset:
▪ Focal: bone and joints, SSI, UTI, lungs, cellulitis &
adenitis (submandibular or parotid regions)
▪ Invasive GBS disease beyond early infancy is
uncommon
● Bacteremia without a focus is the most common
syndrome
DIAGNOSTICS
▪ Isolation from blood, urine, or CSF
● GS (CSF, pleural or joint fluid): (+) in cocci in pairs or
short chains
● Culture (CSF, blood, suppurative focus)
● Latex agglutination: Lancefield group B CHO Ag
● PCR: CSF, DNA probe assays, NAAT
▪ CBC: ↑ or ↓ neutrophil, ↑ band count, ↑ ratio of
bands to total neutrophils or leukopenia
▪ CRP: potential early marker for sepsis (unreliable)
▪ CXR: indistinguishable from RDS
Guidelines 2018)
▪ Start immediately after LP or if delayed, after blood culture
▪ Suggest doing additional CSF sample at 24-48h to determine
when sterility is achieved
▪ Persist GBS: unsuspected intracranial focus or an insufficient
antibiotic dose
▪ Treat for 14 days
● Ventriculitis: at least 4 weeks
Recurrent neonatal GBS disease
▪ standard IV antibiotics ff. eradiation of mucosal colonization
● Rifampin is freq. used for eradication
Septic arthritis or osteomyelitis:
▪ Vancomycin + Cefotaxime or Ceftriaxone (DOH National
Antibiotic Guidelines 2018)
▪ Treat for 3-4 weeks
Pneumonia
▪ Ampicillin or Pen G; add Aminoglycosides (for severe
infections) (DOH National Antibiotic Guidelines 2018)
UTI
▪ Cefotaxime + Amikacin (DOH National Antibiotic Guidelines
2018/PNSP Consensus on UTI in Children 2018)
▪ Treat for 10-14 days
GBS disease
● give prophylaxis as well to those with unknown culture
and who deliver prematurely, PROM, intrapartum fever ≥
38OC, (+) NAAT
▪ Preferred agent: Penicillin (alternative: Ampicillin)
● if w/ amnionitis: broad spectrum with activity against
GBS
▪ Cefazolin for PCN-intolerant but if at high risk for
anaphylaxis, may give Clindamycin
▪ Vancomycin for resistant isolates
Maternal immunization
▪ Transplacental transfer of naturally acquired maternal Ab to
the GBS capsular polysaccharide protects NB from invasive
GBS and that efficient transplacental passage of vaccine
induced GBS Ab occurs
▪ Conjugated vaccines (type III polysaccharide coupled to
tetanus toxoid): protective in >90% of recipients
▪ GBS vaccine: to induce specific Ab both in the serum and at
mucosal surfaces
▪ 2 levels of protection: 1) passive immunity 2) prevent
colonization in the reproductive tract that would protect the
neonate in utero or childbirth
▪ Due to antigenic variation – trivalent (1a, 1b, III)
polysaccharide- protein conjugate vaccine has been
developed & under human trials in early phase
PROGNOSIS
▪ Mortality is higher in premature infants
▪ Meningitis: 19% neurologic impairment, 25% mild to
moderate impairment at long term follow-up
▪ Favorable prognosis: bone or soft tissue infections
Neonatal Infections
▪ Early onset: <7d, mimicking early-onset GBS septicemia
ANTIMICROBIAL RESISTANCE
▪ Beta-lacmtams
PREVENTION
▪ Removal of urinary and IV catheters, debridement of
Batch Clingy
to a decrease in incidence of early-onset neonatal
GBS
▪ Risk factors for early onset sepsis: prematurity,
LBW, PROM, intrapartum fever, maternal
bacteriuria during pregnancy or previous delivery
with GBS
225
▪ Members
● Enterococcus faecalis: predominant organism;
accounts for 80% of infections; colonization in 1st
week of life
● Enterococcus faecium: colonization less
consistent (25% in adults); accounts for the rest of
infections
● E. gallinarum & casseliflavus: rare causes
however notable for their low-level intrinsic
vancomycin resistance
▪ Disruption of normal intestinal microbiota by
antibiotic exposure or HSCT greatly enriches for
fecal enterococcal abundance and dramatically
increases risk for subsequent blood stream infection
TRANSMISSION
▪ Person to person or from contaminated medical
devise (e.g. nurseries, NICU)
▪ Contiguous spread (NTD, or in assoc.
intraventricular shunt)
PATHOGENESIS
▪ Cause disease in children w/ damaged mucosal
surfaces or impaired immune response
▪ Hospital-associated enterococci: lack CRISPR
(clustered regularly interspaced short palindromic
repeat) elements
→ diverse antimicrobial
resistance
▪ Adhesion promoting factors likely account for the
propensity of these organisms to cause endocarditis
& UTI
▪ Can also form biofilms, facilitating colonization of
urinary and vascular catheters)
▪ Other virulence factors: cytolysin, aggregation
substance, gelatinase, & extracellular superoxide
PPS Oral Exam Reviewer 2020
but milder, often occurring in healthy full-terms
▪ Late onset: ≥ 7d; Risk factors: prematurity, (+)
intravascular catheter, NEC, or s/p intraabdominal
surgery
▪ More severe: apnea, bradycardia, deteriorating
respiratory function, ass. focal infection (scalp abscess &
catheter infection)
Infections in older children
▪ nosocomial infections (i.e. UTI, bacteremia)
● Risk factors: (+) indwelling catheter, intestinal
perforation or s/p surgery, immunodeficiency,
cardiovascular
abnormalities,
residence
on
Hematology/Oncology
unit,
prolonged
MV,
immunosuppression, recent broad-spectrum antibiotic
exposure
▪ CLABSI: catheter-associated bloodstream infections
DIAGNOSTICS
▪ CSF: minimal abnormality
▪ Culture: sterile body sites or abscess w/ appropriate
biochemical and serologic analysis
▪ Rapid automated molecular assay: for direct detection
of vanA
● Highly resistant to cephalosporins and semisynthetic
penicillins (e.g. nafcillin, oxacillin, methicillin)
● Moderately resistant to extended-spectrum penicillins
(e..g ticarcillin, carbenicillin)
● Ampicillin, imipenem, penicillin: most active against these
organisms
● Some strains have decreased resistance due to mutations
in PBP5
● Some strains produce a plasmid-encoded B-lactamase →
completely resistant to penicillins (thus, use penicillin + Blactamase inhibitor or imipenem or vancomycin)
▪ Aminoglycosides
● all have intrinsic low-level resistance (d/t poor transport
across cell wall) → combination of cell wall active agent plus
aminoglycoside results in synergestic killing
▪ Vancomycin
● resistance to this and ampicillin prevalent among E.
faecium
▪ Resistance to almost all other antibiotic classes warrant
individual susceptibility testing
necrotic tissue
▪ Decolonization are generally ineffective in eradicating skin or
GI carriage of VRE
▪ Standard & Contact precautions: discontinue if with 3
consecutive negative cultures from multiple sites (stool or
rectal swab, perineal area, axilla or umbilicus, wound,
indwelling urinary catheter or colostomy sites)
▪ Culture obtained after cessation of antimicrobial therapy w/
each culture 1 week apart
▪ Proper diet, oral health, (dental sealants, adequate fluoride),
prevention or cessation of smoking)
PROGNOSIS
Mortality: 6% early-onset, 15% late onset + NEC
(see Nelson’s 21st Ed., Table 213.1 for Intrinsic Resistance Mechanisms
Among Enterococci and Table 213.2 for Acquired Resistance Mechanisms
Among Enteroccoci)
MANAGEMENT
▪ Ampicillin – minor localized infection
▪ Nitrofurantoin – uncomplicated UTI
▪ PCN or Ampicillin – invasive (sepsis, meningitis, endocarditis),
if susceptible
● Vancomycin + aminoglycoside – PCN substitutes
▪ Endocarditis – may relapse after prolonged therapy due to
high level of aminoglycoside resistance
▪ Catheter-associated enterococcal bacteremia – remove
catheter, Ampicillin or Vancomycin + Aminoglycoside
VANCOMYCIN- RESISTANT ENTEROCOCCI:
Oxazolidinone (e.g. linezolid, tedizolid)
▪ Inhibits protein synthesis, bacteriostatic E. faecium & E.
faecalis; Linezolid preferred agent for VRE
▪ Causes reversible BM suppression after prolonged use &
assoc. rare lactic acidosis & irreversible peripheral neuropathy
▪ Tedizolid – better in vitro activity, favorable pharmacokinetic
& toxicity profiles compared to linezolid
Daptomycin
▪ cyclic lipopeptide; rapidly bactericidal VS gram positives
Quinupristin-Dalfopristin
▪ Streptogramin; inhibits bacterial protein synthesis at 2
Batch Clingy
▪ Gram (+), catalase (-), facultative anaerobes that
grow in pairs & short chains
▪ Non-hemolytic (γ-hemolytic), some have α & β
hemolysis
▪ Normal inhabitants of GIT in humans & animal
kingdom
● also colonize: oral secretions, dental plaque,
URT, skin, vagina
226
INCUBATION PERIOD: 3 days (1-7 days)
CAMPYLOBACTER
JEJUNI
TRANSMISSION
▪ Food borne: consumption of raw or undercooked
meat, cross contamination w/ food (chicken –
classic source); ingestion of raw (unpasteurized)
milk
▪ Water borne: shedding of animals contaminating
water & food
▪ Airborne droplets: poultry workers (antimicrobials
in animal foods, ↑ the prevalence of antibioticresistance)
▪ C.jejuni: person to person (fecal-oral), perinatally,
childcare centers (diapered toddlers), shed for
weeks – months
▪ Fecal shedding in untreated lasts for 2-3wks (daysmonths)
▪ Nosocomial infection in nurseries
PATHOGENESIS
▪ Transit stomach → adhere to intestinal mucosal
cells → initiate intestinal lumen fluid accumulation
(direct damage to mucosal cells from invasion,
enterotoxin and other cytotoxins)
▪ Differ from other enteric pathogens: presence of
N- (surface) & O- (flagellae) linked glycosylation
▪ Slipped-strand mispairing in glycosylation loci:
antigenic variation
PPS Oral Exam Reviewer 2020
Acute Gastroenteritis
▪ Fever, HA, dizziness, myalgias → 1-3 days later,
cramping periumbilical pain, loose watery stools, or
mucus + bloody stools, n/v
▪ Severe: bloody stools 2-4 days after onset of the
symptoms
▪ >1yo: fever may be the only manifestation
▪ Diarrhea lasts 7d & resolves spontaneously
▪ DDx: appendicitis, colitis, or intussusception, IBD
(persistent C. jejuni infection)
▪ (+) C. jejuni s/p appendectomy: acute appendicitis,
mesenteric lymphadenitis & ileocolitis
Bacteremia
▪ Transient asymptomatic to rapidly fatal, prolonged
bacteremia (lasting 8-13wk)
▪ Fever, HA, malaise, abdominal pain
▪ Relapsing or intermittent fever, night sweats, chills,
weight loss
▪ Lethargy, confusion, but focal neurologic signs are
unusual w/o CVD or meningitis
Focal Extraintestinal
▪ mostly caused by C. jejuni; rare, mainly neonates and IC
▪ Meningitis, pneumonia, thrombophlebitis, pancreatitis,
cholecystitis, UTI, arthritis, peritonitis, pericarditis,
endocarditis
Perinatal
▪ Maternal C. fetus & C. jejuni: asymptomatic →
abortion, stillbirth, premature delivery or neonatal
infection with sepsis and meningitis.
▪ C. jejuni rare: severe type
▪ C. jejuni associated with diarrhea that may be bloody
COMPLICATIONS
▪ Most common: GBS, reactive arthritis
▪ Severe prolonged infection in patients with ID (i.e.
hypogammaglobulinemia, malnutrition, AIDS)
DIFFERENTIAL DIAGNOSIS
▪ Shigella, Salmonella, E. coli, Y. enterocolitica, Aeromonas, V.
parahaemolyticus, amebiasis
GBS
▪ Acute demyelinating disease of PNS – acute flaccid paralysis
▪ Miller-Fischer variant: affects CN; ataxia, areflexia,
ophthalmoplegia, cross-reacting Ab to the GQ1b ganglioside
found in CN myelin
MANAGEMENT
Acute gastroenteritis
▪ Fluid replacement, correction of electrolyte imbalance,
supportive care
▪ Antibiotics
● may result in shortened duration of symptoms and
shedding
● Recommended: bloody stools, high fever, severe course,
immunosuppressed, or have underlying disease, high risk for
developing severe (pregnant), extra intestinal infections
● DOC: Azithromycin 10mkday PO x 3days, Erythromycin
40mkday q6 x 5days
Sepsis
▪ parenteral meropenem or imipenem ± aminoglycoside
GBS
▪ supportive care, IVIg, and plasma exchange
Reactive Arthritis (3%)
▪ Adolescents & adults esp. (+) HLA B27
▪ Appears 1-2wks (5-40 days) after the onset of diarrhea
▪ Migratory, large joints, afebrile, resolves without sequelae
▪ Responds to NSAIDS, resolved after 1wk – months
▪ Less common: conjunctivitis, urethritis, & rash (erythema
nodosum)
Other
▪ IgA nephropathy, immune complex GN
▪ Hemolytic anemia, HUS
PREVENTION
▪ Cook meat thoroughly, prevent recontamination
▪ Avoid unpasteurized dairy products
▪ Prevent contamination of water (chlorination)
▪ Avoid infected animals
▪ Breastfeeding – ↓ symptoms but does not ↓ colonization
▪ Standard precaution, in hospital: contact precaution
PROGNOSIS
▪ Self limited
▪ Protracted or severe: immunosuppressed (AIDS)
▪ Poor: septicemia in NB, IC (mortality 30-40%)
▪ GBS: more in axonal form; worse prognosis with slow
recovery and more neurologic disability Mortality rate: 2%,
Batch Clingy
▪ Gram negative, non-spore-forming rods,
microaerophilic, anaerobic, oxidase positive
▪ One of the most common causes of human
intestinal infections; a leading cause of acute
diarrhea
▪ Peak in early childhood and young adulthood (1544 yr)
▪ Repeated infection → increased immunity & rare
in adulthood
different stages
Tigecycline
▪ Inhibits protein synthesis by binding to the 30S ribosome,
bacteriostatic
▪ Broad: gram (+/-), anerobic, MRSA, VRE
▪ Avoid <8 yr old
Ceftarolline
▪ 5th generation cephalosporin VS MRSA
▪ Highly synergistic w/ daptomycin w/ poor activity vs E. facium
DIAGNOSTICS
▪ CBC: moderate leukocytosis with left shift
▪ Stool: leukocytes 75%, blood 50%
▪ Gram stain: less sensitive
▪ Stool culture >90% sensitive, apparent 1-2 days
▪ Blood culture: not apparent until 5-14 days – can grow more
slowly which can result to failure due to overgrowth of other
enteric bacteria → selective culture media for C. jejuni
▪ To confirm campylobacter enteritis: rectal swabs or stool
culture
▪ Rapid diagnosis: direct carbolfuschin test, indirect
fluorescence Ab, dark field microscopy, latex agglutination, PCR
▪ Do drug sensitivities: unresponsive, invasive, extraintestinal
227
YERSINIA
ENTEROCOLITICA
INCUBATION PERIOD : 4-6 days (range 1-14d)
TRANSMISSION
▪ Food, water, animal contact, contaminated blood
products
▪ Mother to newborn
▪ Excreted in stool for 1-4 weeks
PATHOGENESIS
▪ Adherence, invasion, and toxin production
▪ Enter alimentary tract → mucosal ulcerations in
the ileum → necrotic lesions of Peyer patches and
mesenteric lymphadenitis → septicemia
▪ Suppurative lesions can trigger reactive arthritis
and erythema nodosum
▪ Gram negative envelope, obligate intracellular
▪ Most significant human pathogens encode
proteins forming a pathway for synthesis of
peptidoglycan, including PBP
▪ Military recruits & nursing homes
INCUBATION PERIOD: 21 days
CHLAMYDIA
PNEUMONIAE
TRANSMISSION
▪ Person to person through respiratory droplets
▪ NP shedding occurs for months even after
treatment
PATHOGENESIS
▪ All has major outer membrane protein, but it is the
major determinant for C. trachomatis & C. psittaci
isolates
▪ Elemental body and reticulate body
PPS Oral Exam Reviewer 2020
20% has neurologic sequelae
Enterocolitis
▪ Diarrhea, fever, abdominal pain, pharyngitis (20%)
▪ Younger children: Acute enteritis
▪ Older: mesenteric lymphadenitis
▪ Watery stools ± WBC, frank blood, mucus
▪ Duration: 12-22 days
Septicemia
▪ Less common
▪ <3mos and immune compromised
▪ Splenic & hepatic abscesses, osteomyelitis, septic
arthritis, meningitis, endocarditis & mycotic aneurysms
▪ Infrequent: exudative pharyngitis, pneumonia,
empyema, lung abscess, ARDS
▪ Antibiotic for systemic infection and very young children:
TMP-SMX, aminoglycosides, 3rd generation cephalosporin,
quinolones
▪ Enterocolitis: TMP SXT x 5 days
▪ Severe infections: 3rd generation cephalosporin ±
aminoglycosides x 3wks
▪ If on deferoxamine, discontinue iron chelation therapy esp.
complicated GI and extraintestinal infection
COMPLICATIONS
▪ Erythema nodosum, reactive arthritis, erythema multiforme,
hemolytic anemia, thrombocytopenia, systemic dissemination
of bacteria, rarely uveitis
▪ Younger: septicemia
▪ Older: reactive arthritis,
PREVENTION
▪ Reduce contact with environmental sources
▪ Break or sterilize chain from animal reservoirs to humans
PROGNOSIS
▪ Self-limiting disease
DIAGNOSTICS
▪ Stool: leukocytes, mucus, blood
▪ Culture: normal sterile sites but if stool (CIN, cefsulodinirgasan-novobiocin)
▪ PCR
DIFFERENTIAL DIAGNOSIS
▪ Salmonella, Shigella, Campylobacter, C. difficile, EIEC, Y.
pseudotuberculosis, Vibrio-related diarrheal disease
▪ Amebiasis, appendicitis, Crohn disease, ulcerative
colitis, diverticulitis, pseudomembranous colitis
CLINICAL MANIFESTATIONS
▪ Cannot be differentiated w/ M. pneumoniae
▪ Atypical pneumonia:
● Mild: pertussis-like
● Mild to Moderate: fever, malaise, HA, cough, and
pharyngitis
● Severe pneumonia + pleural effusions and
empyema
● PE: rales, wheezing, nonexudative pharyngitis
● CXR: worse than the clinical status – mild diffuse or
lobar infiltrates with small pleural effusions
▪ Trigger asthma exacerbations
▪ Acute chest syndrome + SCD
● CXR: New consolidation + ≤1 of the following: fever,
hypoxia, tachypnea, ↑ work of breathing, chest pain,
wheezing, new cough
▪ showed In vitro activity: Tetracycline (not <8yo), macrolides,
and quinolones; resistant to sulfonamides
▪ Optimum dose and duration: uncertain because of
recrudescent symptoms; usually 2 wks or longer d/t persistent
positive cultures ff. 2wks erythromycin & 30d of tetracycline &
doxycycline
▪ Studies for eradiation of nasopharynx in 80%:
● Erythromycin 40mkday PO BID x10d,
● Clarithromycin 15mkday PO BID x10d,
● Azithromycin 10mg/kg D1, 5mkday D2-5
● Duration 10-14d (except Azithromycin x5d)
PREVENTION
▪ Standard & Droplet Precaution
PROGNOSIS
▪ Clinical response varies
▪ Coughing persists even after therapy
Batch Clingy
▪ Complications such as GBS, reactive arthritis,
erythema nodosum are due to molecular mimicry
▪ Most common Yersinia sp. causing human disease
▪ Large, gram negative coccobacillus, ferments
glucose & sucrose but not lactose, oxidase negative,
reduces nitrate to nitrite, motile
▪ Relies on other bacteria for iron uptake and
conditions associated with iron overload
▪ Cold months, M>F
▪ Natural reservoirs: pigs, rodents, rabbits, sheep,
cattle, horses, dogs, cats (undercooked pork,
chitterlings/pig
intestines/
“chitlins”),
an
occupational threat to butchers
228
▪ AOM (co-infection w/ other bacteria)
▪ Asymptomatic respiratory infection 2-5% and persists
for a year
TRACHOMA
▪ Most important preventable cause of blindness
▪ Primarily caused by serotypes A, B, Ba, C; in areas
endemic for trachoma, it can also be caused by
serotypes for genital infections (D – K)
▪ Poverty and lack of sanitation
INCUBATION PERIOD
▪ Variable depending on the type of infection,
usually 1 week
▪ Azithromycin
COMPLICATIONS
▪ Blindness
▪ Bacterial superinfection
▪ 1st line for uncomplicated infections in men & nonpregnant
women: Azithromycin or Doxycycline
COMPLICATIONS
▪ Inclusion conjunctivitis
▪ Proctocolitis (rectal infection, LGV strain)
▪ Perihepatitis, salpingitis
▪ PID: chronic pelvic pain, 17% infertility, 9% ectopic
pregnancy
▪ 50% neonates born to mother with untreated infection will
DIAGNOSTICS
▪ Culture & staining during active stage: Confirmation
▪ Serologic: not helpful due to long duration & high
seroprevalence
TRANSMISSION
▪ Eye to eye (common vector: flies)
PATHOGENESIS
▪ Follicular conjunctivitis → heal → scar →
entropion (eyelid turning inward w/ lashes abrading
cornea) → corneal ulceration → scarring &
blindness
GENITAL TRACT INFECTIONS
▪ Major cause of epididymitis
▪ Co-infection: N. gonorrhea
TRANSMISSION
▪ Perinatally acquired rectal and vaginal
▪ Autoinoculation from the genital tract to the eyes
PPS Oral Exa