PEM|BRS: Heme/Onc & Allergy/Immunology
Anaphylaxis is an immunoglobulin E (IgE)-mediated, immediate hypersensitivity
reaction to a protein antigen.
Initial exposure to the antigen is required to generate allergen-specific antibodies;
anaphylaxis follows a subsequent re-exposure to the allergen. The usual causes of
anaphylaxis are foods (eg, nuts, shellfish), insect stings (eg, Hymenoptera), or
medications (eg, penicillin). Latex allergy can occur in health-care workers and patients
who undergo multiple surgeries, especially those who have spina bifida. Although many
cases of anaphylaxis seem initially to be idiopathic, an allergist may be able to identify
the specific allergen with skin testing or serum antibody tests.
The diagnosis of anaphylaxis is clinical. Symptoms typically develop rapidly (within
minutes to a few hours) after exposure. Patients present with a combination of
cardiovascular (eg, dysrhythmias, hypotension), cutaneous (eg, angioedema, urticaria),
gastrointestinal (eg, cramps, vomiting), neurologic (eg, diminished mental status,
seizure), and respiratory (eg, stridor, wheezing) manifestations of variable severity.
Approximately 10% to 20% of patients lack cutaneous findings, which may result in
misdiagnosis. A minority of patients experience biphasic reactions (a recurrence of
symptoms after apparent initial resolution), generally within 72 hours of onset.
Approximately 1% to 2% of anaphylactic reactions are fatal. Nuts, particularly peanuts,
cause death from anaphylaxis more than any other food in the United States.
Because of its dual alpha- and beta-adrenergic effects, epinephrine is the drug of choice
for anaphylaxis and should be administered intramuscularly as soon as possible.
Intramuscular administration is preferred over subcutaneous because of more rapid
absorption and attainment of higher peak values. The dose of intramuscular epinephrine
for the treatment of anaphylaxis is 0.01 mg/kg (1:1,000 solution) to a maximum of 0.5
mg/dose. Epinephrine administration within the first 30 minutes of a reaction is
associated with decreased fatalities. Corticosteroids (eg, methylprednisolone), H1 and H2
histamine receptor blockers (eg, diphenhydramine and ranitidine, respectively), inhaled
bronchodilators (eg, albuterol), intravenous saline, and oxygen are important additional
emergency therapies.
All patients who experience anaphylaxis should be referred to an allergist for further
evaluation. For causes such as insect stings, prophylactic immunotherapy may be
warranted.
Anaphylactoid reactions have similar clinical presentations, but they are not IgEmediated. Pathophysiologic mechanisms of anaphylactoid reactions include complement
activation by immune complexes (eg, blood products), probable complement activation
(eg, radiocontrast media), abnormal leukotriene metabolism (eg, aspirin, nonsteroidal
anti-inflammatory drugs), and direct release of mediators by physical factors or
medications (eg, exercise, morphine). An anaphylactoid reaction may occur upon initial
exposure to the agent, in contrast to anaphylaxis, which requires prior exposure.
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The most likely cause of cyanosis in a 7 wk old child with acute gastroenteritis is
methemoglobinemia. Acquired methemoglobinemia occurs when the iron molecules in
hemoglobin are oxidized from the ferrous (Fe2+) to the ferric (Fe3+) state. In the ferric
state, hemoglobin is unable to bind oxygen, but any other iron molecules in the same
hemoglobin moiety that still are in the ferrous state have an increased oxygen affinity
(hemoglobin dissociation curve is shifted to the left) and are unable to release oxygen
molecules, leading to impaired oxygen transport and tissue hypoxia.
Methemoglobin (MHb) is produced normally in the body and usually accounts for about
1% to 1.5% of a child's total hemoglobin. Most of the MHb is reduced back to the ferrous
state by the actions of cytochrome b5 or MHb reductase. In the first few postnatal
months, infants are relatively lacking in this enzyme, making them more susceptible to
oxidant stresses that may lead to the formation of increased amounts of MHb. Multiple
causes of oxidant stress can precipitate an episode of methemoglobinemia in infants.
Exogenous sources of oxidants often are related to the ingestion of nitrites or nitratecontaining compounds that may be converted to nitrites in the gastrointestinal tract of
infants by normal gut flora. Such conversion of nitrates to nitrites also may be
exacerbated by the relatively high pH of the infant gastrointestinal tract. Well water that
contains high concentrations of nitrites or nitrates (often due to agricultural runoff),
certain foods (including carrot juice), and specific medications can be the cause of
methemoglobinemia in infants. The most common medications associated with
methemoglobinemia in infancy are local topical anesthetics, especially benzocaine
(which frequently is used in teething gels). Other implicated medications include
dapsone, metoclopramide, quinones, and sulfonamides.
In very young infants, especially those of low weight for their age, methemoglobinemia
may occur during diarrheal illnesses. The exact mechanism of this development is not
completely understood. Acidosis, especially hyperchloremic acidosis, may be enough of
an oxidant stress to cause oxidation of hemoglobin to the ferric state. Changes in gut flora
during the illness may lead to an increased production of nitrites, causing increased
production of MHb. Escherichia coli and Campylobacter jejunii have been implicated in
some case series. Whatever the initial cause of increased MHb, the low concentrations of
MHb reductase cause the child to develop high concentrations of MHb.
Methemoglobinemia should be considered whenever cyanosis in a child does not respond
to oxygen, and blood co-oximetry should be obtained. Pulse oximetry readings are
inaccurate and may be misleading in patients who have methemoglobinemia.
Failure to recognize this diagnosis can lead to continued hypoxia, worsening acidosis,
seizures, coma, and even death. Treatment involves removal of the oxidant stress (in this
case, rehydration) and treatment of acidosis, if needed, and 1 to 2 mg/kg of intravenous
methylene blue for patients who are symptomatic or who have MHb concentrations
greater than 30%. Methylene blue should not be administered to patients who have
glucose–6–phosphate dehydrogenase (G6PD) deficiency because it can precipitate acute
hemolysis. Exchange transfusion or hyperbaric oxygen therapy may be useful in patients
who have G6PD disease or in those who do not respond to methylene blue.
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If an infant has been exclusively breastfed, well water contamination with nitrates or
nitrites would not be responsible for their symptoms. Passage of medication through
human milk has not been implicated as a cause of methemoglobinemia. In children who
have cyanosis due to congenital heart disease or pneumonia, the degree of cyanosis
should correlate with the pulse oximetry reading.
The signs and symptoms of cerebellar involvement and increased intracranial pressure
described for an alert, afebrile, previously well child suggest the presence of an
infratentorial space-occupying lesion. The most likely cause of the space-occupying
lesion is a brain tumor in the posterior fossa. Early morning headache that is relieved by
vomiting is a sign of increased intracranial pressure, which could be due to mass effect or
to hydrocephalus created by pressure on the fourth ventricle. The patient's alertness and
normal vital signs suggest that there is no immediate danger of herniation. Specifically,
hypertension, bradycardia, and irregular respiratory patterns (Cushing triad) should alert
the physician to the possibility of critically increased intracranial pressure that requires
emergent interventions such as osmotic agents, high-dose corticosteroids, relative fluid
restriction, head elevation, controlled hyperventilation, and possible neurosurgical
intervention.
The initial evaluation of suspected brain tumors depends on presenting signs and
symptoms and available resources. If available, magnetic resonance imaging (MRI) with
and without contrast (gadolinium) is the diagnostic test of choice. Fluid–attenuated
inversion recovery (FLAIR) sequences often are useful in determining tumor infiltration
or peritumor edema. Diffusion-weighted imaging can differentiate cysts from solid
tumors and identify areas of necrosis.
In many settings, obtaining an urgent computed tomography (CT) scan may be more
realistic than MRI because MRIs are less commonly available and require sedation. CT
scans allow accurate evaluation of ventricle size and detection of hemorrhage or stroke as
well as some tumors with calcifications. However, CT scan does not demonstrate
posterior fossa pathology as well as MRI. In relatively stable patients, such as the child
described in the vignette, obtaining an MRI is ideal.
Primary pediatric brain tumors are the second most common cancers in children after
hematologic malignancies and the most common solid tumors in the pediatric population.
Brain tumors are a heterogenous group of cancers that can be classified according to
location or histologic appearance. Supratentorial tumors typically present with focal
seizures or motor weakness (tumors in the cerebral hemispheres), visual field defects
(optic chiasm), endocrine abnormalities (hypothalamic or pituitary tumors), or signs of
increased intracranial pressure. Infratentorial tumors present with ataxia (cerebellar
involvement) or signs of increased intracranial pressure due to mass effect and
obstruction of cerebrospinal fluid flow.
Causes of prolonged fever and bone or joint pain can be divided into three broad
categories: 1) Infectious disorders such as mononucleosis, cytomegalovirus infection,
subacute bacterial endocarditis, occult abscess, and zoonotic infections; 2) Immunologic
conditions such as juvenile idiopathic arthritis and systemic lupus erythematosus; and 3)
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Neoplastic diseases such as hematologic malignancies.
The history and laboratory findings suggest the diagnosis of acute lymphoblastic
leukemia (ALL) for the boy in the vignette. Specifically, the depressed platelet count,
markedly elevated white blood cell count, and severe neutropenia all point to this
diagnosis. The immediate concern in this ill-appearing patient who has tachycardia and
neutropenia is bacterial sepsis. The risk of sepsis is markedly increased in patients whose
absolute neutrophil counts are less than 0.5x103/mcL (0.5x109/L).
Neutropenia results from replacement of normal hematopoiesis by malignant cells. Gramnegative organisms that colonize the skin, mouth, and gastrointestinal tract are the
primary pathogens. It is important to treat with broad-spectrum antimicrobial agents
effective against gram-positive and gram-negative pathogens, particularly methicillinresistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. A combination
of vancomycin and ceftazidime is an appropriate choice.
Approximately 95% of cases of ALL involve at least single cytopenia. For the child
described in the vignette, the absolute neutropenia, low platelet count, and mild anemia
strongly suggest new-onset leukemia. Juvenile idiopathic arthritis is not likely because
acute-phase reactants, including platelets, generally are elevated in this condition.
Ganciclovir is used in patients who have severe immunodeficiency and suspected viral
infection, but is not first-line therapy for a febrile patient who has neutropenia in the
emergency department. Severe elevations in white blood cell count are common with
infections caused by Bordetella pertussis, but this patient has no symptoms consistent
with this diagnosis, and pertussis typically is not associated with severe neutropenia. The
severity of this patient's presentation warrants further evaluation and management in an
inpatient setting.
In ALL, blasts typically are seen on the peripheral smear, but in 1% of cases, results of
the complete blood count may be normal. The white blood cell count is greater than
50.0x103/mcL (50.0x109/L) in 20% of patients, between 10.0 and 50.0x103/mcL (10.0
and 50.0x109/L) in 30% of patients, and less than 10.0x103/mcL (10.0x109/L) in 50% of
patients. A widened mediastinum on chest radiograph due to enlarged lymph nodes may
be noted in some T-cell ALLs.
The diagnostic evaluation of those in whom ALL is suspected is performed best in
consultation with hematology to confirm that the atypical lymphocytes are, indeed, blasts
and to coordinate the diagnostic evaluation. The evaluation usually involves obtaining a
large volume of blood for diagnostics that include lactic dehydrogenase, uric acid, blood
typing and screening, prothrombin time, and partial thromboplastin time.
The pre-existing diagnosis of systemic lupus erythematosus (SLE) combined with obesity
and steroid therapy places a patient at particular risk for PE.
The D-dimer test is a sensitive screening test for PE. Although results of a complete
blood count (CBC), erythrocyte sedimentation rate (ESR), or antinuclear antibody (ANA)
test can be abnormal and suggest “active” lupus, they are not specific for PE. Common
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findings on a CBC in a patient who has SLE include leukopenia, thrombocytopenia, and
anemia of chronic disease. The ESR usually is elevated and can be a marker of active
disease. The ANA is part of the panel of tests used to diagnose SLE. The presence of an
A-a gradient [150 – 1.2{Pco2}-Pao2] derived from the arterial blood gas could suggest
ventilation-perfusion mismatch as the underlying physiologic mechanism of low oxygen
saturation, which may be helpful, but this is not a sensitive test for diagnosing PE and can
give normal results in 25% of cases.
Other predisposing conditions for PE include trauma, presence of a central venous
catheter, prolonged immobilization, malignancy, use of oral contraceptives, sickle cell
disease, kidney diseases (particularly nephrotic syndrome), congenital heart disease, and
thrombophilic disorders such as Factor V Leiden mutation and Protein C or S deficiency.
The clinical presentation of PE often is subtle or masked by the underlying predisposing
condition. Dyspnea and pleuritic chest pain are the most common presenting symptoms;
other signs and symptoms include cough, hemoptysis, syncope, unexplained tachypnea or
tachycardia, clinical signs of deep vein thrombosis, or a sudden increase in oxygen
requirements in those receiving mechanical ventilation. The diagnosis often is made
postmortem in the setting of unexplained sudden death.
Chest radiographs in PE usually appear normal. It is helpful to exclude other causes of
chest pain such as pneumonia or pneumothorax. A well-described radiographic finding of
PE is the Westermark sign, which represents an abrupt localized cutoff of central
pulmonary vasculature and usually is seen in conjunction with massive PE.
Nonspecific ST-T wave changes are the most common electrocardiography (ECG)
findings of PE. A large pulmonary embolism may demonstrate evidence of right
ventricular strain on an ECG. The classically described S1Q3T3 pattern on ECG is seen
in 12% of cases.
An elevated value for D-dimer, a breakdown product of cross-linked fibrin, has shown
high sensitivity (~95%) but is not specific. The value may be elevated in other conditions
such as disseminated intravascular coagulation, sepsis, postsurgical state, or cancer.
Threshold values are dependent on the type of assay being used and can vary between
institutions. The negative predictive value of a D-dimer by rapid enzyme-linked
immunosorbent assay of less than 500 units/mL, performed in adult patients, ranged from
87% to 97%.
When the pretest probability of PE is low-to-moderate an elevated D-dimer value
prompts additional diagnostic testing. If the pretest probability is high, based on the
Wells criteria, D-dimer is not required because even a negative result does not rule out
PE. Definitive tests should be undertaken for all of these patients.
Four radiographic modalities are available to confirm the diagnosis of PE:
Ventilation-perfusion (V-Q) scan
Computed tomography angiography (CTA)
Pulmonary angiography (PA)
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Magnetic resonance angiography
A V-Q scan can be performed rapidly and is helpful if results are clearly normal or show
“high” probability of PE. The presence of prior lung disease or congenital heart disease
with differential pulmonary blood flow can lead to false-positive results on the perfusion
scan. Helical or spiral CTA has become the test of choice. Although it involves
significant radiation, it is noninvasive and readily available. CTA also is helpful in ruling
in alternate diagnoses. Although PA is the gold standard for diagnosing PE, it is invasive
and expensive. Magnetic resonance angiography does not involve radiation and,
therefore, does not expose the breasts, thyroid, and gonads of the pediatric patient to
long-term effects of ionizing radiation. However, it is not readily available, takes longer
to accomplish, and frequently requires sedation or anesthesia.
Treatment of PE involves prompt anticoagulation with intravenous heparin or
subcutaneous low-molecular weight heparin. For massive PE in an unstable patient or
when anticoagulation is contraindicated, open surgical or transcatheter embolectomy may
be considered.
Because the patient described in the vignette has already had PE diagnosed by computed
tomography scan, ventilation/perfusion scan or pulmonary artery angiography is not
indicated. PE originates from thrombi in proximal deep veins of the pelvis and lower
extremity in 90% of the cases, which makes Doppler ultrasonography of the lower
extremities the test of choice. In fact, a deep vein thrombosis is detected in 20% to 50%
of cases of PE with this noninvasive test. If ultrasonography does not reveal a thrombus,
contrast venography or computed tomography scan of the pelvis would be indicated.
Echocardiography is appropriate for measuring cardiac function, but it rarely localizes the
source of the embolus.
The incidence of DVT is estimated at 4.9 per 100,000 children per year. DVT is more
common in African Americans and children younger than 2 years and older than 15 years
of age. The pathogenesis for thrombus formation can be explained by the Virchow triad
of hypercoagulability, stasis, and endothelial injury. Risk factors known to induce one or
more of the Virchow conditions are:
Immobilization for longer than 3 days
Trauma
Vasculitis (systemic lupus erythematosus)
Intravenous drug use
Presence of indwelling catheters
Pregnancy
Major surgery in the past 4 weeks
Sepsis
Use of oral contraceptives
Hypercoagulable states (inherited prothrombotic disorders or acquired prothrombotic
states such as nephrotic syndrome)
The use of oral contraceptives increases the incidence of DVT by a factor of 10 due to the
alteration of procoagulant and fibrinolytic systems. Recent data suggest that women who
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are taking oral contraceptives and have a genetic predisposition to thrombosis, such as the
presence of factor V Leiden or a prothrombin gene mutation (G20210A); increased
plasma lipoprotein A concentrations; or deficiencies of antithrombin, protein C, or
protein S are at a higher risk for developing DVT. Research suggests that a positive
family history is the only significant predictor for a congenital thrombotic disorder.
Many patients who have DVT can be asymptomatic or present for the first time with
complications such as PE. Classic signs and symptoms of DVT include local swelling,
edema, erythema, pain on forced dorsiflexion of the foot (Homans' sign), fever, and
discoloration of the extremity. Although contrast venography is the gold standard for
diagnosis, this diagnostic tool may not be reliable in 5% to 10% of patients and is
associated with the risks of contrast reaction, extravasation of contrast causing skin
irritation or sloughing, and renal failure. Therefore, the use of Doppler ultrasonography
(duplex Doppler compression) to demonstrate the inability to compress the vein walls
when pressure is applied to the overlying skin is recommended. Ultrasonography with
angiography has been suggested for upper extremity thrombosis, and gadoliniumenhanced magnetic resonance venography has been used recently to detect thrombosis in
chest veins.
The primary goals of treatment of DVT are to reduce morbidity by preventing further clot
formation, acute PE, and recurrence of thrombosis. Treatment also prevents the
development of late complications such as postphlebitic syndrome and chronic
thromboembolic pulmonary hypertension. Anticoagulation is initiated with lowmolecular weight heparin. Low-molecular weight heparin is preferred over unfractionated
heparin because of its better bioavailability, pharmacokinetic properties that permit single
daily subcutaneous dosing, lack of necessity for laboratory monitoring, and lower risk of
heparin-induced thrombocytopenia. Warfarin is administered simultaneously and
continued for 3 to 6 months. Heparin administration is discontinued in a few days.
Because the child described in the vignette is afebrile, well-appearing, and has no other
signs of chronic illness but has easy bruising and a platelet count of 5, he most likely has
acute idiopathic thrombocytopenic purpura (ITP). However, malignancies and other
potential causes of thrombocytopenia must be considered in the differential diagnosis.
Awaiting the results of the counts of other cell lines and carefully examining the
peripheral blood smear are important steps before verifying the diagnosis of ITP. A blood
smear in a child who has ITP should show a reduced number of platelets, which are
normal, or larger than normal, in size as well as normal white blood cell and red blood
cell morphologies. Intravenous immune globulin or other therapies should be
administered only after consultation with a hematologist and the diagnosis of
malignancies has been excluded. Bone marrow aspiration is somewhat controversial in
children who have presumed ITP and should not precede a careful examination of the
peripheral blood smear. Computed tomography scan of the head should be obtained only
in children who have signs and symptoms of intracranial bleeding, a rare complication of
ITP. Platelet transfusion is not indicated for patients who have ITP and are not actively
bleeding.
ITP is the most common form of acquired thrombocytopenia in the pediatric patient.
Similar to the child in the vignette, children who have acute ITP usually present with
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increased bruising and bleeding from mucosal surfaces, mouth, vagina, and
gastrointestinal tract. Otherwise, the children usually appear well, without
lymphadenopathy or hepatosplenomegaly. As the platelet count decreases, the risk of
bleeding increases, especially after trauma. Life-threatening complications such as
intracranial hemorrhage are extremely rare (<1%), but they are associated with a very
high mortality rate (46%).
Proposed mechanisms responsible for the pathophysiology of ITP involve autoimmunity
against glycoproteins on the surfaces of platelets. The autoantibodies coat the platelets
that then are destroyed by the spleen and other organs of the reticuloendothelial system.
As with some diseases with proposed autoimmune mechanisms, the antibodies are
believed to arise from the immune response to a mild bacterial or viral infection, and
subsequently cross-react with platelet antigens. In addition, platelet production in ITP
may be decreased by immune mediators.
A minority of children who have acute ITP eventually progress to chronic ITP. Such a
progression is more common in older children. Occasionally, such children are resistant
to pharmacologic treatments (including rituximab) and require splenectomy.
For most children who have ITP, the thrombocytopenia resolves within 6 months without
any treatment. However, depending on the platelet count and the clinical symptoms,
treatment may include:
Restriction of physical activities
Wearing protective head-gear
Intravenous immune globulin
Corticosteroids
Anti-Rho antibody (for patients who are Rh-positive)
The threshold for pharmacologic treatment in the child who does not have acute bleeding
is unclear, although a platelet count of 20x103/mcL (20x109/L) traditionally has been
used.
Epistaxis is common between the ages of 2 and 10 years. It is rare in infancy and
becomes less prevalent after puberty. Most children have “benign” epistaxis that requires
no further evaluation. Patients who have benign epistaxis have single or occasional
episodes of epistaxis that last for a few minutes (usually less than 15 minutes) and are
associated with a small amount of blood loss. History or physical examination findings
suggestive of allergic rhinitis, upper respiratory tract infection, obvious trauma, or
epistaxis digitorum strongly suggest the diagnosis. Benign epistaxis tends to occur more
often in winter, when indoor heating dries the mucosae, leading to bleeding from fragile
superficial vessels.
Benign epistaxis typically emanates from the anterior nasal septal mucosa, an area also
referred to as Kiesselbach plexus. This highly vascular area is within reach of a child’s
finger during nose picking or rubbing. Examination may reveal a prominent anterior
septal blood vessel.
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More profuse bleeding or recurrent bleeding lasting more than 20 minutes, as described
for the boy in the vignette, requires further evaluation. Initial assessment should include
complete blood count, peripheral blood smear, platelet count, and coagulation studies.
Most epistaxis can be terminated with the use of controlled pressure, ice, or topical
instillation of vasoconstrictor medications such as phenylephrine. Pressure is applied to
the outside of the nose in a forward leaning position. Another method is to pinch the
nostrils and compress the upper lip, which occludes the labial artery. If bleeding persists
and no anatomic site or foreign body is identified, nasal packing may be indicated.
If the initial laboratory results show no abnormality, referral to a hematologist to evaluate
for von Willebrand disease is recommended. von Willebrand disease is the most common
coagulopathy, with a prevalence of 1% in childhood. von Willebrand factor (VWF) is a
multimeric protein that helps platelets bind to the vessel wall and serves as a carrier
protein for factor VIII. Therefore, in its severe form, patients exhibit prolonged
prothrombin time and partial thromboplastin time. However, many patients who have von
Willebrand disease do not exhibit abnormalities in one or both of these tests.
Concentrations of the heat-labile VWF protein may be elevated by stress, trauma,
medication, or difficult venipuncture. von Willebrand disease is assessed using a panel
that includes VWF antigen concentration, ristocetin cofactor for functional testing of
VWF activity, and factor VIII concentrations.
Examination of the bone marrow is not warranted in a child who has recurrent epistaxis
and a normal platelet count. It may be useful if the complete blood count indicates an
abnormality in bone marrow production, such as thrombocytopenia, aplastic anemia, or
leukemia. Factor IX is much less important as an initial study in this child because
children who have clinically significant disorders of factor IX activity usually exhibit a
prolonged partial thromboplastin time. Platelet aggregation studies are complex to
perform but may be considered when results of initial studies, including evaluation for
von Willebrand disease, are normal. Fibrin split products are a specific marker of
disseminated intravascular coagulation, which is not a consideration in this child.
If the epistaxis is consistently unilateral, otorhinolaryngology evaluation may be
indicated to exclude an unrecognized foreign body, abnormal vessel, polyp, or rarely, a
neoplastic lesion such as angiofibroma. Vascular disorders such as hypertension or
hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) are among the
nonhematologic disorders that can result in epistaxis. Nonaccidental trauma should be
considered in children younger than 2 years of age who have unexplained epistaxis.
Typhlitis is a type of necrotizing enterocolitis seen almost exclusively in neutropenic
patients with leukemia or lymphoma. Presenting signs and symptoms include abdominal
pain and tenderness to palpation, diarrhea, and fever. Plain films may reveal, paucity of
air, ileus, thickened bowel, and air in the bowel wall. CT may show an intraluminal
abscess. Fluids and broad spectrum ABX coverage, including anaerobic coverage should
be initiated quickly. Medical management is the primary treatment (non-surgical).
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Tumor Lysis Syndrome: high potassium, high phosphorus, high uric acid, low calcium.
Tx: Allopurinol and D5 0.25 NS with NaHCO3 or D5 0.5NS at 2xm can help to alleviate
the phosphate load on the kidneys without elevating the K further; TLS may cause high
K, causing peaked T-waves on EKG. NOTE: In treating high K in TLS, DON’T USE
Calcium (in an effort to protect the heart) because you run the risk of precipitating
calcium phosphate crystals. Albuterol, Sodium bicarbonate, and insulin/dextrose are
faster ways to redistribute K from the extracellular space. Slower, but more permanent
ways of extracting K from the body are furosemide and sodium polystyrene sulfonate
enemas. Aluminum hydroxide lowers serum phosphate levels; Allopurinol reduces uric
acid.
Steroids have a role in the management of malignancy-associated hypercalcemia.
Antibiotics are appropriate for febrile patients with new leukemia diagnoses, and
transfusion is recommended for Hgb <8,
VZIG, given within 72 hours of a cancer patient’s (without documented immunity)
exposure to Varicella may prevent or lessen the severity of illness. Acyclovir is indicated
for patients with evidence of disease. The varicella vaccine is a live vaccine and is
contraindicated in an immunosuppressed individual under any circumstances.
HD and NHL are the most common malignancies presenting with mediastinal masses.
An indolent presentation of chronic cough or wheeze is a common presentation of a slowgrowing anterior mediastinal mass. Germ cell tumors (teratoma), thyroid malignancies,
HD and NHL may all present in the anterior mediastinum. However, 10% of HD patients
can have night sweats, weight loss and intractable pruitus.
Anthracyclines (adriamycin, idarubicin, daunomycin), used in the treatment of ALL have
cardiotoxic effects, including acute or delayed rhythm disturbances, carditis-pericarditis
syndrome, cardiomyopathy, and cardiac failure. Patients on these meds who present in
fluid-refractory shock without evidence of sepsis should be managed with afterload
reduction and inotropic agents such as dobutamine or amrinone.
In the absence of hemorrhage, a child with severe anemia from bone marrow failure is at
risk of heart failure from too large or too rapid a transfusion. Therefore, 3-5 cc/kg of
PRBC’s should be transfused over 4 hours if the hemoglobin is < 5.
Spinal cord compression is a true neurosurgical emergency. It presents as back pain,
radicular pain, difficulty with urination, paresis, or paralysis. In the ED, administration
of dexamethasone can decrease acute inflammation. For neuroblastoma, emergent
chemotherapy is indicated while other tumors may require surgical decompression and
radiation. MRI with gadolinium is the most appropriate test for confirmation; when MRI
is not available, CT should be performed (though it is less sensitive than MRI for
detecting spinal cord compression.) Plain films are of NO USE and are a WASTE.
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Delayed transfusion reactions (presenting with pallor and severe anemia in patients
having previously received matched blood that had undetectable incompatible antigens)
occur on day 3-14 following the repeat transfusion and are less likely to progress to end
organ failure than acute reactions due to the less rapid destruction of RBC’s. The direct
antiglobulin test will be positive and the antibody will now be discernable in the crossmatch, making transfusion of compatibility tested RBC’s safe.
Factor V Leiden mutation analysis should be unaltered by clot presence or treatment for
DVT’s. Other heme tests (Protein C, Protein S, Antithrombin III, and Activated
prothrombin complex concentrate—aPCC) will all be altered by heparin and warfarin
treatment.
Factor IX has NO ROLE in the treatment of Factor VIII Deficiency. In a patient with
inhibitors and a severe bleed, factor VIIa or aPCC would be the therapy of choice. If
unavailable, patients with low inhibitor levels may respond to high doses of Factor VIII.
Anti-factor antibodies can be removed from the blood by plasmapheresis in refractory
cases.
ITP with severe anemia secondary to bleeding should be treated with IVIG in a Rh+
patient, because, while normally you would give Win-rho to such a person, they wouldn’t
be able to tolerate the mild decrease in hemoglobin from the capture in the spleen of the
Rh+ RBC’s resulting from Win-rho.
Even with Plt < 10k, don’t do platelet transfusion because anti-platelet antibodies from
ITP would quickly destroy them—instead do IVIG or Win-rho.
If a child has a normal PaO2 but a low pulse ox following the ingestion of a sulfacontaining antibiotic, it is likely the child has methemoglobinemia. Treatment should
initially be attempted with methylene blue. Failure of treatment is frequent in patients
with G6PD, and may require ascorbic acid or exchange transfusion.
Initial treatment of an acute chest crisis should include O2, IVF, analgesics, and a third
generation cephalosporin. Overly aggressive hydration is contraindicated outside the
context of shock due to the risk of edema from pulmonary vessel permeability. Steroids,
macrolides, and exchange transfusion (or transfusion if anemic) are all considerations in
severe or refractory cases.
An aplastic crisis is typically from parvovirus, and presents with progressive pallor
without jaundice. The Hgb and retic are both low until BM recovery and symptomatic
children respond well to small volumes of transfused PRBC’s.
Normally, sickle cell associated priapism is treated with hydration, aspiration of the
corpora and instillation of an epinephrine-type solution, and transfusion/exchange
transfusion. Exchange transfusion is recommended if the Hgb >10 as routine transfusion
could increase blood viscosity. If these modalities do not lead to improvement in 72
hours, a shunting procedure is considered.
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In a well-appearing febrile child with HIV and low viral load, standard work-up includes
CBC, blood culture, and U/A, UCx. CXR and pulse ox measurements are indicated if the
WBC is elevated or a left shift is present.
Acute pancreatitis is a common side effect of several HIV medications including
didanosine, amivudine, and stauvidine.
Bleomycin (treats HD) can cause pulmonary fibrosis.
Pneumocystis Carinii Pneumonia (PCP) typically afflicts infants between ages 2-6
months with symptoms of fever, wheezing, tachypnea, and decreased breath sounds.
CXR shows diffuse bilateral infiltrates. A high A-a gradient on ABG and elevated LDH
(above 500) are typical lab findings.
Treatment initiated in the ED for anaphylaxis should be continued for at least 48 hours
following discharge and may include antihistamines, steroids, and H2 blockers. For
patients who experience upper airway obstruction or shock, an overnight admission is
indicated for monitoring due to the possibility of a biphasic reaction.
Intubating Asthmatics: Ketamine at 1-2 mg/kg is an ideal induction agent for RSI due to
its bronchodilatory effects. Mechanical ventilation of ashmatics places them at high-risk
for barotraumas, and should be used only in the most extreme situations. When done,
allowance of permissive hypercapnia, a short I/E ratio to allow expiration, and
minimizing sedation when possible helps to reduce this risk.
In addition to albuterol, Epi would be an appropriate first-line treatment for an asthmatic
near respiratory failure.
NSAIDS are appropriate therapy for fevers and myalgias seen in serum sickness, an
immune complex mediated activation of the complement pathway due to injection of
foreign serum proteins. Antihistamines are indicated in this condition if pruitis, urticaria,
or angioedema are present. Steroids are reserved for severe cases or those refractory to
more conservative measures. The inciting protein should be discontinued if possible.
In children with severe and refractory eczema, one consideration is Wiskott-Aldrich, an
X-linked recessive disorder characterized by low platelets, often small in size,
immunodeficiency, and refratory eczema.
Another immunodeficiency associated with severe eczema is hyper-IgE syndrome.
Low sodium may be seen in RMSF.
An elevated CRP can be seen in meningococcemia.
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The signs and symptoms of serum sickness are fever, arthralgia, skin eruptions,
lymphadenopathy, nephritis, edema, and neuritis. The signs and smptoms of serum
sickness-like reactions, in contrast, may include fever and lymphadenopathy, but are
otherwise confined to the skin and joints.
Antibiotics are the most common medications to cause serum sickness-like reactions
(often with cefaclor, and prior sensitization is not necessary). A latent period of 2-17
days is expected between antigen exposure and the onset of serum sickness-like
reactions.
Unlike serum sickness (Type III hypersensitivity reaction), serum sickness-like reactions
are not associated with circulating immune complexes. Therefore, palpable purpura,
nephritis, edema, and neuritis are not expected in cases of serum sickness-like reactions.
Measles vaccine, DTP, and Hep B are the most commonly identified vaccine-related
causes of anaphylaxis.
Measles vaccine is derived from chick embryo fibroblast tissue and contain egg protein—
so children with egg allergy are at increased risk of having an allergic reaction to these
immunizations—but the risk is exceedingly small.
In contrast, the Influenza vaccine contains a greater amount of egg protein and places
children at such a great risk for allergic reactions that it is recommended that this vaccine
be withheld from children with egg allergies.
IPV contains trace amounts of neomycin, streptomycin, and polymyxin B.
MMR and Varicella vaccines contain trace amounts of neomycin and gelatin.
Yeast protein is present in Hep B, and children with yeast allergies can have reactions to
this vaccine.
The vaccines most associated with rashes are Varicella and MMR. Most Varicella
vaccine rashes appear 9-16 days post immunization. The MMR rash and fever appears 710 days post immunization and can be associated with transient lymphadenopathy.
Fever occurs within 2 days for Hep B, Influenza, Hib, and pneumococcal vaccines.
Joint symptoms like arthralgias and arthritis are associated with the rubella component of
MMR.
MMR is associated with thrombocytopenia within 2-6 weeks.
Wounds at higher risk for tetanus include contaminated wounds (with dirt, feces, soil, or
saliva), puncture wounds, avulsions, wounds resulting from missiles, crush injuries,
burns, frostbite, and those with neurovascular compromise.
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Tdap is not recommended in pregnant patients.
Withhold Td until the second trimester of pregnancy. You may give TIG any time.
You give TIG only if it is a high-risk wound and the person has had <3 Td doses or their
vaccine history is unknown.
Bites from raccoons, skunks, bats, foxes, bobcats, coyotes, woodchucks, beavers, and
mongooses are considered high-risk for rabies transmission.
Domestic animal bites (dogs, cats, ferrets, and livestock) are generally considered lowrisk. Low risk bites also include mice, squirrels, rabbits, chipmunks, rats, hamsters,
gerbils, guinea pigs.
If you are going to use prophylaxis, use BOTH RIG and Rabies vaccine.
Raccoons are the most commonly encountered rabid wild animal—then skunks, bats, and
foxes.
The majority of rabies cases in the USA are due to bat rabies—in most of these cases, no
knowledge of a bite existed.
Nonbite exposures include contamination from open wounds (abrasions, scratches) or
mucous membranes with the saliva or neuronal tissue of a rabid animal. You can also get
it from inhaling large amounts of bat guano in a bat cave.
RPEP should be initiated for patients in whom there is apparent or reasonable probability
of a bat bite, scratch, or mucous membrane exposure. It is also given if a bat is found in
the room of an individual who is incapable of attesting to absence of direct contact (has
been sleeping and awakes to find a bat in the room; or a bat found in the room of an
unattended child, a mentally or physically disabled child or an intoxicated individual.)
The only exception is when the bat is captured and immediate brain testing is available.
Rabies is exclusively seen in mammals. Nonmammalian bites do not pose a risk of rabies
transmission (birds, reptiles).
Rabies vaccine is given on days 0, 3, 7, 14, and 28.
People who have already been vaccinated and are exposed, only should receive the
vaccine on days 0 and 3 (and they DO NOT need RIG).
Rabies vaccine and RIG are OK to give in pregnancy.
You can observe domestic animals for 10 days (dogs, cats, ferrets only) and defer
immunization (unless animal acts rabid while in captivity).
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Often, the first episode of vaso-occlusive pain occurs in infants and toddlers as acute
swelling of the hands and feet (dactylitis). Hand-foot syndrome typically occurs
symmetrically, involving the metacarpals and/or metatarsals. If fever is present,
osteomyelitis may be difficult to exclude and may require a bone scan or MRI.
For sickle cell patients, risk of chest syndrome is higher if: they are younger, have a
lower Hb F, have a higher steady state Hb concentration, or have a higher steady state
leukocyte count. Findings may include fever, cough, chest pain, dyspnea, productive
cough or hemoptysis, hypoxia, leukocytosis, and new pulmonary infiltrates on CXR.
Infection is more likely a cause in children than in adults—mostly due to Chlamydia,
Mycoplasma, and RSV.
Treatment of Acute Chest Syndrome: Admit to PICU, difficult to distinguish from
pneumonia, so give ceftriaxone and a macrolide. Patients typically have a Hb 1-2g below
their baseline and respond well to a simple transfusion of PRBC’s. In more severe cases,
a partial exchange transfusion should be considered—indications include: multilobar
disease, rapidly progressive disease, marked respiratory distress, PO2 < 70 or a fall of
25% in baseline PO2.
Strokes occur in 10% of patients with Hb SS by the age of 20 years. CVA’s are managed
with expeditious exchange transfusion. The goal is to limit further sickling by acutely
decreasing the proportion of Hb S to < 30%. Avoid hyperviscosity by keeping the Hct
around 35%. Treat seizures as per normal.
Biliary cholic and acute cholecystitis are always possible etiologies for Sickle Cell
patients with abdominal pain. Sickled RBC’s undergo chronic hemolysis, leading to
hyperbilirubinemia and formation of bilirubin containing gallstones.
Acute splenic Sequestration occurs in patients between 6 mo and 2 years of age. The
patient has a precipitous drop in Hb in signs of circulatory collapse, requiring prompt
intervention to reverse hypovolemic shock. This can occur in the liver as well so always
check for an enlarged liver OR spleen. Transfusion of PRBC’s is lifesaving—you should
give a fluid bolus prior to the blood arriving.
Parvovirus B19, toxins, folate deficiency or other infections can cause marrow
suppression, and thus an acute aplastic crisis since the RBC’s in HbSS last only 30 days
as opposed to the normal 120 days. Pallor and tachycardia are common features of an
Aplastic Crisis—you’ll see anemia with a low reticulocyte count (<3%).
Pitfall: DO NOT attribute tachycardia to baseline anemia in HbSS patients as they
should have long compensated and have a normal heart rate.
When using parenteral narcotics, morphine is preferred to meperidine (Demerol) which
has a metabolite (normeperidine) that causes seizures and is poorly metabolized in
patients with Sickle Cell Disease.
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Sickle Cell Disease and Fever: all children who appear ill and all infants < 6 months of
age require IV Ceftriaxone even before the return of lab results, and admission to the
hospital. Well-appearing infants and children > 6 months of age who meet specific
criteria, may be treated as outpatients with close follow-up. Criteria:
 Normal mental status
 Normal vitals and cap refill
 Temp under 40 (104)
 No prior pneumococcal sepsis
 Mild pain only
 No evidence of pneumonia
 WBC 5-30K
 Hemoglobin > 5
 Platelets > 100,000
 No allergy to ceftriaxone (able to administer)
 Reliable 24 hour follow-up
Treatment in the ED of newly diagnosed ALL: D5 1/2NS OR D51/4NS + 30 mEq/L
NaHCO3 at twice maintenance; If antibiotics if febrile and neutropenic; PRBC
transfusion for Hb < 8; Platelet transfusion for Plt < 20,000; Allopurinol OR
Rasburicase.
Neuroblastomas arise in the adrenal glands (40%), abdominal (25%) or thoracic (20%)
sympathetic ganglia. These tumors occur in children less than 5 years of age and present
with a large abdominal mass (potentially causing respiratory distress) or metastatic
lesions to the orbits “raccoon eyes”, bones, bone marrow, or lymph nodes. Dumbbell
shaped tumors involving the intervertebral foramina may compress the spinal cord,
causing paraplegia. Tumors involving the cervical sympathetic chain may produce
Horner’s Syndrome (miosis, ptosis, enophthalmos, and anhydrosis). 90% of tumors
produce HVA or VMA, and may require anti-hypertensives. 5% of tumors produce
cerebellar dysfunction.
Wilm’s Tumor: most children are less than 8 years old. Aniridia, Hemihypertrophy,
Urinary tract malformations, and Beckwith-Wiedemann Syndrome (neonatal
hypoglycemia, ophalocele, macroglossia, and visceromegaly) are highly associated with
Wilm’s Tumor. Patients may present with a large abdominal mass, acute abdominal pain
(due to tumor hemorrhage or necrosis), constipation, hypertension, microscopic
hematuria, anemia, and rarely polycythemia. Lung mets occur in 15% of cases.
Nephrectomy is necessary for all tumors. 90% of children are cured with surgery +
chemotherapy. First screening test is abdominal ultrasound, then CT scan.
Hepatoblastoma: present under 2 years of age; occur in association with BeckwithWiedemann Syndrome or extreme prematurity. Present with a large abdominal mass.
Lungs are a common metastatic site. Most tumors produce alpha fetoprotein, which
confirms the diagnosis. Most patients are cured with chemo followed by tumor resection.
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Osteosarcoma is the most common bone cancer. Disease peaks between 10-18 years of
age. Most tumors occur near the knee and some in the humerus. Typical presentations
include localized pain with or without physical findings and pathologic fractures. A plain
radiograph would show poorly defined tumor margins, bone destruction, periosteal
reaction, and calcification (reflecting new bone formation). In contrast, bengin tumors
are round, smooth, and well-circumscribed, without cortical destruction or periosteal
reaction. W/u includes MRI of the entire extremity to exclude skip lesions, bone scan to
detect mets, and Chest CT to detect lung mets. Diagnosis confirmed by open biopsy.
Treatment is preoperative chemo followed by surgery (en bloc tumor resection and
endoprosthesis placement).
Ewing’s Sarcoma (PNET): small round cell tumors of neuronal origin. Arises in the
diaphyses of long or flat bones and in soft tissues. Presentation similar to osteosarcoma.
Hodgkin’s Lymphoma: presents as painless cervical, supraclavicular, or mediastinal
lymphadenopathy, which progresses over several months. Tx: chemo +/- Rad
All patients with fever and neutropenia need cultures, IV ABX and admission.; PRBC
transfusion at 15cc/kg over 2 hr improves tissue perfusion, if necessary.
Median age of childhood ITP is 3-5 years; It is the sudden onset of profound
thrombocyctopenia in an otherwise healthy child. Cancer would be suspected if there
was lymphadenopathy, hepatomegaly, splenomegaly, bone or joint pain, fever,
neutropenia, and anemia. Platelets in ITP are typically large, reflecting fresh platelets,
the rest of the CBC should be normal. Patients with Plt<20 AND active severe bleeding
are at risk for life-threatening hemorrhage and should be admitted, and treated with highdose steroids AND IgG/WinRho. If meningitis suspected, ABX should be administered
and the LP deferred until the Plts are >50.
Normal PT/PTT excludes a clinically significant coagulation factor deficiency (including
hemophilias)
Factor VIII deficiency (Hemophilia A) and Factor IX Deficiency (Hemophilia B):
Prolonged aPTT, low Factor VIII, IX, respectively; PT and TT are normal.
vWD: aPTT is abnormal in severe VWD; Platelet Function Analyzer (PFA) has
replaced bleeding time as the test of choice; Tx: DDAVP; fluid restriction is
recommended during and immediately following DDAVP due to the risk of
hyponatremic seizures.
HUS is characterized by the acute onset of nonimmune microangiopathic hemolytic
anemia (circulating RBC fragments, hemoglobinemia, and hemoglobinuria), consumptive
thrombocytopenia, and renal insufficiency or failure. Mainly affects children from 7mo5 years old. Usually follows 2-14 days after an acute infectious hemorrhagic colitis
caused by EColi; Positive Coombs indicates autoimmune hemolytic anemia and NOT
HUS; Prolonged clotters suggest DIC and NOT HUS; Avoid fluid overload; HTN
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treated with IV agents, avoid plt transfusions, patients with seizures require emergent
imaging to exclude increased ICP or bleeding.
Antibody screening test= Indirect antiglobulin (coombs) Test=IAT
Transient erythroblastopenia of childhood (TEC) is the most common cause of acquired
isolated RBC aplasia in children. TEC typically occurs between 6 months and 3 years of
age, with most affected children older than 1 year at the time of diagnosis. A transient
immunologic suppression of erythropoiesis following a nonspecific viral illness is
responsible for the severe anemia. Although the clinical and laboratory picture is similar
to DBA, the presence of a normal MCV and normal RBC adenosine deaminase (ADA)
concentrations (in TEC) help to distinguish these two conditions.
Severe anemia, reticulocytopenia, macrocytosis, a normal white blood cell count, and a
normal platelet count, which suggest pure red blood cell (RBC) aplasia. In the presence
of congenital skeletal abnormalities (the hypoplastic thumb), these findings point to the
diagnosis of Diamond-Blackfan anemia (DBA), also known as congenital RBC aplasia.
Aplastic anemia also includes the findings of leukopenia and thrombocytopenia.
Sickle Cell Disease Acute Chest Crisis: Immediate care involves oxygen administration,
intravenous (IV) access, laboratory assessment (including complete blood count, blood
cultures, chemistry and renal function tests, and a blood gas analysis), and chest
radiography. Antibiotics should be administered, as should IV fluids to address shock and
dehydration. Pain medication and bronchodilators may be required. Admission to the
hospital, preferably a pediatric intensive care unit, and involvement of hematology
specialists would be prudent. Assistance of airway support and ventilation may need to be
addressed if the boy does not improve or deteriorates, and transfusion may need to be
considered to replace sickled cells with normal red blood cells.
Filariasis is common in West Africa and usually presents with adenopathy and intense
pruritus; overwhelming sepsis is not a common complication. Cocaine intoxication is
unlikely for this child due to his normal blood pressure and sensorium. Having
thalassemia minor does not increase the risk of medical complications, and thalassemia
has a lower prevalence than sickle cell disease on the African continent. Carbamate
toxicity is likely to present with cholinergic symptoms (salivation, lacrimation, urination,
defecation, gastrointestinal cramping, emesis, miosis, and muscle fasciculations), none of
which are present in this boy.
Sickle cell disease includes a number of potential
disorders, from homozygous SS disease to heterozygous conditions such as hemoglobin
SC, SD, SO, S/beta-thalassemia, and S/fetal hemoglobin. Sickle cell anemia (HbSS) is
the most common, with HbS/beta-thalassemia having similar complications but less
severe anemia
Management for potentially life-threatening complications should be determined in
conjunction with experts and awareness of national guidelines. Anemia is evident in
patients who have homozygous disease (after the first few postnatal months, when the
protective fetal hemoglobin has disappeared), increasing from approximately 6% of 618
month-old infants to 96% of patients by the time they reach 8 years of age. Young
children often present with dactylitis (swollen hands), vaso-occlusive episode (painful
crisis), splenic sequestration (before splenic fibrosis due to multiple episodes of splenic
infarction noted in older children), or acute chest syndrome. Meningitis is seen more
often in infants and young children. Older children may demonstrate cerebrovascular
accident, priapism, or splenic dysfunction due to infarction. In the United States,
sickle trait is evident in approximately 8% of African Americans and 0.05% of
Caucasians. Within the various expressions of sickle trait are variable amounts of
hemoglobin S. Although hemoglobin values and life spans are similar in patients with
and without sickle trait, complications still can lead to significant morbidity and
mortality. Reported complications in children who have sickle cell trait include renal
medullary carcinoma, hematuria, hyposthenuria (loss of urinary concentrating ability),
renal papillary necrosis, splenic infarction, rhabdomyolysis, and unexpected exerciserelated sudden death. There may be a relationship as well with venous thromboembolic
events, pregnancy-related complications, hyphema, retinopathy, acute chest syndrome,
and asymptomatic bacteriuria.
Juvenile rheumatoid arthritis (now termed juvenile idiopathic arthritis [JIA]): younger
than 16 years of age, arthritis in one or more joints, duration of 6 weeks or longer, and
absence of any other cause of arthritis. The cause of JIA is unknown, although both
genetic and environmental factors are believed to play roles. Children who have an
exaggerated histamine response would be expected to show evidence of degranulated
mast cells, such as urticaria, angioedema, and wheezing. Clinical characteristics of
symptomatic lead toxicity include lethargy, abdominal pain, and encephalopathy. The
child has no fever or rash to suggest infection with common spirochetes. Leukemia might
be associated with arthralgia or bone pain but not arthritis. In addition, the normal results
of the complete blood count point away from this diagnosis.
JIA is subdivided based on the type of disease present during the first 6 months of illness.
Oligoarthritis (pauciarticular JIA) (50% of cases) is defined as involvement of fewer than
five joints, as in this child. Affected patients typically have mild-to-moderate pain and
joint inflammation. Pauciarticular JIA is subdivided into early onset (before 5 years of
age) and late onset (5 years or older). Early-onset pauciarticular JIA (as seen in the
patient in the vignette) has a female predominance, positive antinuclear antibody (ANA)
titer in up to 60% of cases, rare hip or sacroiliac joint involvement, and association with
chronic iridocyclitis in nearly 50% of cases. Late-onset pauciarticular JIA has a male
predominance, negative ANA titer, frequent involvement of the hip and sacroiliac joints,
and occasional association with uveitis. The joint involvement in pauciarticular disease
frequently is asymmetric.
Polyarticular JIA (35% of cases) is defined as involvement of five or more joints within
the first 6 months of symptoms and is subdivided into rheumatoid factor (RF)-positive
and RF-negative disease. Polyarticular disease may be associated with fever, rash, and
other systemic symptoms, particularly early in the course. RF-positive polyarticular JIA
has a female predominance, generally occurs after 8 years of age, is associated with a
positive ANA in up to 75% of patients, is not associated with uveitis, but is associated
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with severe and destructive arthritis. Subcutaneous rheumatoid nodules, particularly over
extensor surfaces such as the elbows, are seen frequently in RF-positive disease. This
form of JIA is closest in symptomatology to adult rheumatoid arthritis. RF-negative
polyarticular JIA also has a female predominance, typically presents before 8 years of
age, is associated with a positive ANA in only 25% of patients, rarely is associated with
uveitis, and progresses to severe arthritis in approximately 10% of patients. The joint
involvement in polyarticular JIA is typically symmetric and more severe than that seen in
pauciarticular disease.
Systemic JIA (15% of cases) (also know as Still disease) presents with spiking fevers
(often twice daily), an evanescent salmon-pink rash, hepatosplenomegaly, myalgias, and
serositis. The arthritis may not be present during the initial disease onset, making the
diagnosis difficult. Cardiac involvement, including pericarditis or myocarditis, is most
common in the systemic form of the disease. Patients who have systemic JIA more
frequently are male, typically present before the age of 5 years, have negative ANA and
RF status, do not develop uveitis, and develop severe arthritis in approximately 25% of
cases. A feared and potentially fatal complication of systemic JIA is macrophage
activation syndrome, which can present with unrelenting fevers, hepatosplenomegaly,
pancytopenia, hepatic dysfunction, elevated ferritin values, and disseminated
intravascular coagulation.
Radiographs of involved joints reveal soft-tissue swelling, periarticular osteopenia,
progressive narrowing of joint spaces and bony erosions, and ultimately subluxation and
ankylosis in severe cases. Systemic inflammation is evidenced by elevated white blood
cell counts, mild-to-moderate anemia, elevated inflammatory markers, elevated
complement and immunoglobulin concentrations, and variable elevation of ANA and RF
values, as outlined previously. Because there are no specific markers for JIA and many of
the serum markers vary according to disease duration and severity as well as subtype, the
diagnosis is largely based on clinical factors.
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