Pediatrics
FEVER and RASH
Lan-fang Tang
Dept. Pediatric Pulmonology
Rash appearance
Skin lesions evolve over time, but the characteristic
distribution and appearance provide important clues
to the diagnosis
 Macular or Maculopapular Rash
 Diffuse Erythroderma
 Urticarial Rash
 Vesicular, Bullous, Pustular
 Petechial-Purpuric
 Erythema Nodosum
Differential Diagnosis of Fever and Rash
Macular or Maculopapular Rash -- virus:
Measles
Rubella
Roseola (HHV-6 or HHV-7)
Others: Erythema infectiosum (fifth disease,
parvovirus B19), Epstein-Barr virus,
Echoviruses, HBV, HIV
Differential Diagnosis of Fever and Rash
Macular or Maculopapular Rash--bacteria
Scarlet fever (group A streptococcus)
Others: Secondary syphilis, Leptospirosis,
Pseudomonas, Meningococcal infection (early),
Salmonella typhi (typhoid fever), Lyme disease
(erythema migrans), Mycoplasma pneumoniae
Measles
Etiology
Measles virus

genus Morbillivirus

family Paramyxoviridea
Only one serotype
Week vitality in vitro
Measles virus
Epidemiology
Source of infection
Route of transmission
Susceptible population
Source of infection
 patients as the main source
 infectivity from prodromal period to the
time of 5~10 days after the rash appears
 respiratory secretions as the main media
Route of transmission
Direct respiratory transmission by droplet spray
Indirect transmission by contact with the
contaminated articles.
Susceptible population
 Peak incidence: 8m~5yr
Pathogenesis
Virus inhalation
incubation
Local proliferation
First viremia
Proliferation in endoreticular system
Second viremia
prodromal
All parts of the body
eruption
Clearance of virus
convalescence
Clinical Manifestation
Typical measles
Incubation stage
Prodromal stage
Eruptive stage
Convalescent stage
Stage 1: Incubation stage
6~18 days
No symptoms or low fever, malaise
Stage 2: Prodromal stage (Catarrhal stage)
Lasts 3~4 days
Low-grade to moderate fever
Mucosal catarrh: conjunctivitis,
coryza
hacking cough
Stimson line: transverse line of inflammation
along the eyelid margin
Koplik spots: a pathognomonic sign
Koplik spots
—a pathognomonic sign of measles
Appear 2-3 days after fever develops
Tend to occur over the buccal mucosa opposite
the lower molars
A grayish white dots(as small as grains of sands)
with slight reddish areola
Increase and disappear 1-2d after eruption
Stage 3: Eruptive stage
Lasts 3~4 days
Characterized by the eruption of the rash
The temperature rises abruptly as rash
develops (usually >40℃)
Exacerbated mucosal catarral symptoms:
cough, vomitting and diarrhea, anorexia,
a few rales on auscultation
The order of eruption
 Usually starts on the upper lateral parts of the neck,
behind ears, along the hairline and on the posterior parts
of the cheek;
 Spreads rapidly over entire face, neck, upper arms and the
upper parts of the chest within the first 24hr;
 Over the back, abdomen, entire arm and thighs during the
succeeding 24hr;
 Finally reaches the feet on the 2nd~3rd day.
The features of the rash
Faint macules initially
Pink maculopapular, 1-3mm in diameter
Sparse to confluent or even fused with each
other to form patches, but the normal skin can
be found.in between.
Begins to fade as the rash reaches the feet.
Stage 4: Convalescent stage
The symptoms resolve rapidly
The rash fades downwards in the same
sequence in which it appeared.
Branny desquamation and brownish
pigmentation occur and disappear within 710days
Atypical Measles
Atypical measles

Mild measles (modified measles)

Severe measles

Measles without rash

Hemorrhagic measles (black measles)

Atypical measles syndrome
Laboratory examination
A laboratory confirmation is rarely needed
Leukopenia , with a relative lymphocytosis
Multinucleated giant cells in smear of nasal
mucosa (Warthin-Finkeldey cells)
Serum antibody(sIgM or double serum IgG)
Virus isolation or virus antigen/RNA detection
Complications
 Pneumonia ( fatal giant cell (Hecht) pneumonia
in patients with impaired cell-mediated
immunity)
 Laryngo-bronchitis
 Myocarditis
 Encephalitis
 Reactive tuberculosis
 Subacute sclerosing panencephalitis
Basis of diagnosis
Evidence of epidemiology
Koplik spots
The order and features of the rash
Branny desquamation and brownish
discoloration
Therapy
No specific antiviral therapy
Supportive treatment
antipyretics, bed rest,
maintenance of an adequate fluid intake
Management of complication
Vitamine A supplement
IVIG
Vitamin A and measles: evidence
Hyporetinemia is present in over 90% of measles
cases in Africa and 22-70% in USA.
There is an apparent inverse correlation between
retinol concentration and the severity of measles.
Oral Vitamin A supplement reduces the morbidity
and mortality of severe cases.
Indication for Vit A supplement
(American Academy of Pediatrics)
 Hospitalized children 6mo~2yr of ages
 Children >6mo with

immunodeficiency

ophthalmologic evidence of Vit A deficiency

impaired intestinal absorption

moderate to severe malnutrition

recent immigration from areas with a high
mortality from measles
Prevention
Isolation
Block the route of transmission
Vaccine
Post-exposure prophylaxis
Prevention: Isolation
Isolation precautions should be maintained from
the 7th day after exposure until 5 days after the
rash develops.
Until 10 days after the rash develops for severe
cases with pneumonia
Contact with susceptibility be isolated for 21
days (28days for passive immunity receiver)
Prevention: active immunization(Vaccine)
Measles attenuated vaccine , or Measles- MumpsRubella vaccine(MMR)
Initial immunization: 8mo
A second immunization is recommended
routinely(7y).
Urgent vaccination for measles postexposure and
outbreak prophylaxis
Prevention:
Passive immunization(post-exposure
prophylaxis)
Passive immunization with Ig within 5 days of
exposure is effective for the prevention and
attenuation of measles.
Susceptible children <12mo should receive Ig
(0.25ml/kg, <=15ml,IM)
Differential Diagnosis of Fever and Rash
Macular or Maculopapular Rash -- virus:
Measles
Rubella
Roseola (HHV-6 or HHV-7)
Others: Erythema infectiosum (fifth disease,
parvovirus B19), Epstein-Barr virus,
Echoviruses, HBV, HIV
Rubella
also known as German measles and 3-day
measles;
congenital rubella syndrome (infection in
utero )
Etiology and epidemiology
 a single-stranded, positive-sense RNA virus ( a
member of the togavirus family)
 Humans as the only host
 Spread either by oral droplet or transplacentally to
fetus causing congenital infection
 Virus recovered from the nasopharynx 7d before
exanthem and 7-8 d after its disappearance.
 Peak incidence in children 5~14 yr of age
Clinical manifestations
Incubation (14 to 21 d)
Prodromal phase
 Mild catarrhal symptoms with shorter period
 Low-grade fever (1~3d) with meager systemic
symptoms.
 About 2/3 are subclinical.
Clinical manifestations
The most characteristic sign：
 Enlarged post-occipital, retroauricular and
posterior cervical lymph nodes with tender.
 Be evident 24h before rash and remain for 1
week or more
Clinical manifestations
Exanthem more variable even no rash
 first appear on face
 rapid evolution, usually cover the entire body in 24 h
 Usually clears by the 3rd day
 Discrete maculopapules with large flushing, or pinpoint
appearance, or may be confluent on face
 Mild itching and minimal desquamation
Clinical manifestations
Enanthem in 20% patients
 Just before rash
 Discrete rose spots on the soft palate (Forchheimer
spots)
 May coalesce into a red blush and extend over the
fauces
 Slightly inflamed pharyngeal mucosa and conjunctivae
without photophobia
Clinical manifestations
Congenital rubella (syndrome)
 Affects virtually all organ systems
 The most common manifestation is intrauterine growth
retardation
 Other common findings: cataracts (microphthalmia,
myocarditis, PDA); “blueberry muffin” skin lesions;
hearing loss; meningoencephalitis.
Diagnosis
Apparent diagnosis based on clinical symptoms
and signs
 Laboratory findings non-specific and generally do not
aid in diagnosis
 confirmed by serology or virus culture
Congenital rubella: serum sIgM or virus culture
Prenatal diagnosis: cord blood sIgM or virus
culture from amniotic fluid
Treatment and prognosis
There is no specific antiviral therapy
 Entirely supportive, and antipyretics
The prognosis is excellent, but congenital rubella
syndrome may have sequalae such as intrauterine
growth retardation, cataracts, deafness, and a
patent ductus arteriosus.
Prevention
Live rubella vaccine recommended as MMR for
children( initial at 12-15m and second 4-6y)
It is important for girls to have immunity before
they reach childbearing age
Differential Diagnosis of Fever and Rash
Macular or Maculopapular Rash -- virus:
Measles
Rubella
Roseola (HHV-6 or HHV-7)
Others: Erythema infectiosum (fifth disease,
parvovirus B19), Epstein-Barr virus,
Echoviruses, HBV, HIV
Etiology
Roseola was first established as a distinct illness
at the turn of 20th century;
No causative pathogens were consistently
identified until recent 10 years;
It appears now that primary infection of human
herpesvirus type 6 (HHV-6) and less frequently
HHV-7 causes the majority of the cases of roseola.
Epidemiology
Primary HHV-6 infection occurs early in life with
peak acquisition from 6-15 months of age.
Rarely report contact with other infected children
and outbreak uncommon.
 Most adults excrete HHV-6 and HHV-7 in saliva
and may serve as primary sources for virus
transmission.
HHV-6 can be transmitted in utero.
Cinical manifestations
Incubation period: 5-10d
Prodromal period:
 Usually asymptomatic
 Mild URT signs
 Mild cervical lymphadenopathy
Cinical manifestations
 Clinical illness heralded by high fever
 37.9~40.0 with an average of 39℃
 Persists for 3-5 days and then resolves rather abruptly
(crisis). Occasionally fever diminish over 24-36h
gradually (lysis).
 May be irritable and anorexia but most behave
normally
 Seizures in 5~10%
 Infrequent : rhinorrhea, sore throat, abdominal pain,
vomiting and diarrhea.
Cinical manifestations
Eruption and fever
 A rash appears within 12~24 hours of fever
resolution
 Eruption during defervescence or within a
few hours of fever resolution
Cinical manifestations
Characteristic rash
 Rose colored rash ( discrete, small
(2~5mm),slightly raised pink lesions)
 appears trunk , neck, behind ears, face and
proximal extremities
 No pruritic, no vesicles
 Fade in 1~3 days
Treatment and prevention
There is no specific therapy
 HHV-6 is inhibited by ganciclovir but the
benign nature preclude consideration of
antiviral therapy.
Excellent prognosis in majority
no guidelines for prevention of roseola.
Varicella
Etiology
Chickenpox (varicella) is the manifestation of
primary infection of varicella-zoster virus (VZV).
Zoster (shingles) is the manifestation of reactivated
latent infection of endogenous VZV.
Clinical manifestation
Incubation period: 10~21d
Subclinical varicella is rare
Prodromal symptoms
 Usually moderate fever
 malaise, headache, anorexia and occasionally
mild abdominal pain
 precede the rash by 24~48h
Clinical manifestation
The characteristic rash
 initially as small red papules
 rapidly progress to nonumbilicated, oval,
"teardrop" vesicles on an erythematous base.
 The fluid progresses from clear to cloudy, and the
vesicles ulcerate, crust, and heal.
 New crops appear for 3 to 4 days, usually
beginning on the trunk followed by the head, the
face, and, less commonly, the extremities.
Clinical manifestation
Pruritus, mucous membrane lesions,
lymphadenopathy
Hypopigmentation or hyperpigmentation persists
for days to weeks in some
Scarring unusual unless secondarily infected
Clinical manifestation
 Progressive varicella
 usually in immunocompromised children
 Neonatal chickenpox
 delivery within 1 week before or after the onset of
maternal varicella frequently results in severe varicella
in neonates
 Congenital varicella
 when pregnant women (especially between 8-20 weeks)
contract chickenpox, 25%of the fetuses may become
infected.
Complication
Complications are common
 secondary infection of skin lesions by streptococci
or staphylococci, Thrombocytopenia and
hemorrhagic lesions or bleeding, pneumonia ,
myocarditis, pericarditis, orchitis, hepatitis,
ulcerative gastritis, glomerulonephritis, and
arthritis , Reye syndrome, encephalitis, cerebellar
ataxia, nystagmus, and tremor
Therapy
Symptomatic therapy
Antivirals (acyclovir, famciclovir, or valacyclovir )
are effective in preventing severe complications
 the routine oral administration of acyclovir is not
recommended in otherwise healthy children because of
the marginal therapeutic benefit, the lack of difference in
complications, and the cost of acyclovir treatment.
Thank you!
Email: tanglanfangzju@163.com