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Pediatric Dermatologic Emergencies: A Case-Based Approach for the Pediatrician

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 Pediatric Dermatologic Emergencies: A Case-Based Approach for the Pediatrician
Paul L. Aronson, MD; and Todd A. Florin, MD
Pediatric Annals, Volume 38, Issue 2, February 2008
CM E EDUCATIONAL OBJECTIVES
1. Explain the clinical presentation, evaluation, and treat-
ment of pediatric dermatologic conditions that are
medical emergencies.
2. Describe the differential diagnosis of emergent dermato-
logic conditions that present as erythroderma or purpura.
3. Report the significance of dermatologic manifestations in
a child with prolonged fever.
ABOUT THE AUTHOR
Paul L. Aronson, MD; and Todd A. Florin, MD, are with De-
partment of Pediatrics, The Children’s Hospital of Philadelphia,
University of Pennsylvania School of Medicine, Philadelphia, PA
19104.
Address correspondence to: Paul L. Aronson, MD, Department
of Pediatrics, The Children’s Hospital of Philadelphia, 34th Street
and Civic Center Boulevard, Philadelphia, PA 19104; fax: 215-590-
2768; or e-mail: aronsonp@email.chop.edu.
Dr. Aronson and Dr. Florin have disclosed no relevant financial
relationships.
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claim credit commensurate with the extent of my participation.
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Please rate the degree to which the content presented in this
activity was free from commercial bias. No bias Significant bias
5 4 3 2 1
Comments regarding commercial bias: ______________________________
______________________________________________________________
3802AronsonCS.indd 2
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 HOW TO O BTA I N C M E C R E DI TS B Y RE A D I N G T H I S I S S U E

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Essential Areas and policies of the Accreditation Council for Continuing Medical
Education through the joint sponsorship of Vindico Medical Education and
PEDIATRIC ANNALS. Vindico Medical Education is accredited by the ACCME to provide
continuing medical education for physicians.
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with the extent of their participation in the activity.
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activity audience the relevant financial relationships of the planners, teachers, and
authors involved in the development of CME content. An individual has a relevant financial
relationship if he or she has a financial relationship in any amount occurring in the last 12
months with a commercial interest whose products or services are discussed in the CME
activity content over which the individual has control. Relationship information appears at
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approved by the FDA for use in the United States. The faculty members have been
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EDUCATIONAL OBJECTIVES OVERVIEW

This issue of Pediatric Annals features reviews of topics in pediatric dermatology to dispel myths and update the practicing pediatrician.
To earn CME credits for this issue, go online to take the quiz at PediaticSuperSite.com.

TABLE OF CONTENTS
84 Food Allergies and Atopic Dermatitis: Differentiating Myth from Reality
Lisa R. Forbes MD; Rushani W. Saltzman MD; and Jonathan M. Spergel, MD, PhD

91 Common Genodermatoses: What the Pediatrician Needs to Know

Julianne A. Mann, MD; and Dawn H. Siegel, MD

99 Contact Dermatitis: From Basics to Allergodromes

Rajiv I. Nijhawan, BS; Catalina Matiz, MD; and Sharon E. Jacob, MD

109 Pediatric Dermatologic Emergencies: A Case-Based Approach for the Pediatrician

Paul L. Aronson, MD; and Todd A. Florin, MD

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Copyright © 2009 by SLACK Incorporated. All rights reserved. No part of this publication may be reproduced without prior written consent of the publisher.

3802AronsonCS.indd 3 2/3/2009 2:28:37 PM

 Pediatric Dermatologic Emergencies:
A Case-Based Approach for the Pediatrician
Paul L. Aronson, MD; and Todd A. Florin, MD

P
atients with dermatologic com-
plaints frequently visit the pe-
diatric office and emergency
department. Many of these conditions
are managed safely on an outpatient ba-
sis; however, several situations require
prompt and aggressive intervention. It is
essential to recognize those dermatolog-
ic presentations that warrant emergent
action, and potentially hospitalization, to
minimize morbidity and mortality. This
review presents a case-based approach
to pediatric dermatologic emergencies.
CASE PRESENTATION
A 12-year-old boy with a history of
epilepsy presents to your office with 6
days of fever and 1 day of rash. The rash
is characterized by red patches on the
trunk that rapidly generalized. There is
now redness all over the patient’s body
and his face has become swollen. Upon
questioning, you discover that the pa-
tient was changed 2 weeks ago to car-
bamazepine to control his seizures more
effectively. On physical examination, the
patient is ill-appearing, though not toxic.
There is mild facial edema with no mu-
cous membrane involvement. You note
significant cervical lymphadenopathy.
There is a diffuse erythroderma (see Fig-
ure 1, page 110). There are no papules,
pustules, or bullae. The skin does not
blister with pressure. Complete blood
count reveals a white blood cell count
of 9.7 x 109/L, with a differential of 6%
atypical lymphocytes, 10% eosinophils,
40% neutrophils, 10% monocytes, and
34% lymphocytes. Serum transaminases
are elevated uniformly. Creatinine and
blood urea nitrogen are normal. Skin
biopsy by a dermatology consultant re-
veals perivascular lymphocytes with few
eosinophils. What is the diagnosis, and
how should this patient be managed?
Differential Diagnosis
Erythroderma, though uncommon in
children, can indicate a potentially life-
threatening condition; prompt identifica-
tion, evaluation, and treatment are essen-
tial. The differential diagnosis is broad
and includes immunologic, infectious,
metabolic disorders, and drug reactions.
Immunologic conditions should be
considered in the infant who presents
with erythroderma and systemic symp-

CM E EDUCATIONAL OBJECTIVES

1. Explain the clinical presentation, evaluation, and treat-
ment of pediatric dermatologic conditions that are medi-
cal emergencies.
2. Describe the differential diagnosis of emergent dermatologic
conditions that present as erythroderma or purpura.
3. Report the significance of dermatologic manifestations in a
child with prolonged fever.
Paul L. Aronson, MD; and Todd A. Florin, MD, are with Depart-
ment of Pediatrics, The Children’s Hospital of Philadelphia, Univer-
sity of Pennsylvania School of Medicine, Philadelphia, PA 19104.
Address correspondence to: Paul L. Aronson, MD, Department of
Pediatrics, The Children’s Hospital of Philadelphia, 34th Street and
Civic Center Boulevard, Philadelphia, PA 19104; fax: 215-590-2768; or
e-mail: aronsonp@email.chop.edu.
Dr. Aronson and Dr. Florin have disclosed no relevant financial re-
lationships.

PEDIATRIC ANNALS 38:2 | FEBRUARY 2009 www.PediatricSuperSite.com | 109

3802AronsonCS.indd Sec1:109 2/3/2009 2:28:38 PM

 SIDEBAR 1.
Centers for Disease Control Criteria
of Toxic Shock Syndrome28
1. Temperature ≥ 38.9°C
2. Hypotension
3. Rash
4. Desquamation of rash 1 to 2 weeks after illness onset
5. Abnormalities in three or more organ systems:
a. Central nervous system: Alterations in consciousness without focal neurological
signs when fever and hypotension are absent
b. Hematological: Platelet count < 100,000/mm3
c. Hepatic: Total bilirubin, ALT or AST at least twice the upper limit of normal
d. Renal: BUN or creatinine at least twice the upper limit of normal or pyuria (≥ 5
leukocytes/HPF) without urinary tract infection
e. Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
f. Muscular: severe myalgia or creatine kinase at least twice the upper limit of normal
g. Gastrointestinal: vomiting or diarrhea at onset of illness
6. Laboratory criteria: negative blood, CSF, or throat cultures (blood culture may be positive
for S. aureus), and negative titres to rickettsial infection, leptospirosis, or measles
marrow transplantation are potentially
effective therapies. Similar findings are
found in hypogammaglobulinemia and
graft-versus-host disease. In infants,
congenital ichthyoses may also present
as erythroderma. These children have
a genetically-determined primary skin
barrier dysfunction that may predispose
them to immunologic inflammatory skin
responses. These children often present
with a collodion membrane notable at
birth. Diagnosis is made by history and
skin biopsy.
The etiology of Kawasaki disease is
unknown, although its origins are poten-
tially infectious or immunologic. As de-
Figure 1. Erythroderma secondary to drug reac-
tion with eosinophilia and systemic symptoms scribed in more detail below, Kawasaki
(DRESS) syndrome disease should be suspected in patients
with at least 5 days of fever, in addition
toms. Omenn’s syndrome, a form of to extremity changes, conjunctivitis,
severe combined immunodeficiency lips/oral changes, cervical lymphade-
(SCID), presents with erythroderma, nopathy, and a polymorphic rash that
failure to thrive, lymphadenopathy, and can be erythrodermic.
recurrent infection. Diagnosis is sug- Infectious emergencies that present
gested by leukocytosis, eosinophilia, with erythroderma with or without ex-
and anemia, and is confirmed by skin foliation include toxic shock syndrome
biopsy. Although fatal in nearly all af- (TSS) and staphylococcal scalded skin
fected patients, cyclosporine and bone syndrome (SSSS). Clinical symptom-
atology in these entities is thought to be
caused by toxins produced by Staphylo-
coccus aureus or Group A Streptococcus
acting as superantigens. The clinical cri-
teria for TSS are found in Sidebar 1. The
profound hypotension and toxin effects
result in rapid multiple organ system
failure within 8 to 12 hours after onset of
symptoms. The rash is typically a wide-
spread blanching erythroderma develop-
ing within hours of initial symptom ap-
pearance (see Figure 2, see page 111),
and hyperemia of the mucous mem-
branes may be present. Desquamation of
the skin on the hands and feet occurs 10
to 21 days after disease onset. Common
laboratory findings include elevated cre-
atinine, serum transaminases, and biliru-
bin. S. aureus is cultured from the blood
in less than 5% of cases of TSS, though
Streptococcus is more frequently cul-
tured if it is the etiologic agent.1 Thus,
TSS remains largely a clinical diagno-
sis. Treatment for TSS includes prompt
referral to an emergency department
for aggressive repletion of intravascu-
lar volume loss, oxygen, and initiation
of intravenous anti-staphylococcal (and
anti-streptococcal) antibiotic therapy,
typically oxacillin or vancomycin and
clindamycin together. Oxacillin is bac-
tericidal and inhibits cell wall synthesis,
and the addition of clindamycin, which
targets ribosomes, can help reduce toxin
production and provide synergy. Vanco-
mycin should be used in areas with high
rates of MRSA organisms. In adults, each
hour of delay of antibiotics over the first
6 hours after onset of hypotension has
been associated with an approximately
8% decrease in survival.2 Use of cortico-
steroids and intravenous immunoglobu-
lin (IVIG) in TSS is controversial.1
Staphylococcal scalded skin syn-
drome (SSSS) can occur as localized
bullous impetigo or generalized tender
erythroderma. Bullous impetigo pres-
ents typically as discrete areas of fluid-
filled bullae that easily rupture to leave
behind an erythematous base with mini-

110 | www.PediatricSuperSite.com PEDIATRIC ANNALS 38:2 | FEBRUARY 2009

3802AronsonCS.indd Sec1:110 2/3/2009 2:28:38 PM

 mal crust. Generalized SSSS begins with
malaise and fever that progresses to dif-
fuse erythroderma, worse in the flexural
areas. Typically, mucous membranes are
not involved, although the areas around
the eyes and mouth are often affected,
showing crinkled skin and desquama-
tion. A positive Nikolsky’s sign (denuda-
tion of normal-appearing skin after gen-
tle friction) is characteristic (see Figure
3). Generalized SSSS can resemble tox-
ic epidermal necrolysis (TEN, discussed
below) and is differentiated clinically
by the lack of drug exposure, mucous
membrane or respiratory involvement in
SSSS. Complete blood counts are not es-
pecially useful in SSSS. Blood cultures
should be drawn prior to antibiotic ini-
Generalized SSSS begins
with malaise and fever
that progresses to diffuse
erythroderma, worse in the
flexural areas
tiation; however, they are usually nega-
tive. Cultures from the affected skin are
sterile, though the causative organism
sometimes may be obtained by naso-
pharyngeal culture. Skin biopsy can be
performed if the diagnosis is uncertain,
and reveals superficial separation within
the epidermis just beneath the stratum
corneum, differentiating it from TEN
in which cleavage occurs between the
epidermis and dermis. In the majority
of cases, SSSS is a self-limited disorder,
but use of antibiotics may shorten the
disease course. Corticosteroids should
be avoided; they may exacerbate the
dermatitis. Children younger than 1 year
should be hospitalized and treated with
intravenous antistaphylococcal antibiot-
ics. Older children should be admitted if
toxic-appearing or if there is significant
denudation or severe skin involvement,
PEDIATRIC ANNALS 38:2 | FEBRUARY 2009
3802AronsonCS.indd Sec1:111
with close attention to fluid and electro-
lyte status. Those older than 1 year with
mild disease and nontoxic appearance
can be managed as outpatients using oral
antistaphylococcal antibiotics with close
follow-up. Silver sulfadiazine should be
used topically on denuded areas.3
Considering the patient’s recent medi-
cation change, a drug reaction is high on
the differential diagnosis. Drug reactions
can be potentially fatal, and expedient
identification and therapy are paramount.
Stevens-Johnson syndrome (SJS) and
toxic epidermal necrolysis appear to be
different points on the same spectrum of
disease. Medications are most common-
ly implicated, but infections, systemic
diseases, foods, and physical agents have Figure 2. Erythroderma secondary to toxic shock
syndrome.
been reported as etiologies. Drugs com-
monly implicated include antibiotics,
analgesics, nonsteroidal anti-inflamma-
tory drugs (NSAIDs), and anticonvul-
sant agents. Typical clinical features of
SJS include fever with associated non-
specific headache, malaise, and upper
respiratory symptoms, along with target
lesions followed by skin denudation of
less than 10% of the body surface (see
Figure 4, page 112). Mucous membranes
are almost always involved, differentiat-
ing SJS from erythema multiforme. Vis- Figure 3. Staphylococcal scalded skin syndrome.
Note area of denudation on forehead (Nikolsky’s
ceral involvement of the gastrointestinal sign). Courtesy of the Walter W. Tunnessen Pe-
tract, kidneys and/or liver may occur. diatric Image Library, The Children’s Hospital of
Philadelphia.
Supportive care is the only universally
accepted therapy for SJS. Some studies and severe disease than SJS. TEN is the
have demonstrated that brief periods of result of a drug reaction in the majority
high-dose corticosteroids have improved of cases, with reactions to similar medi-
outcomes in SJS, although others have cations for SJS. The clinical presentation
been inconclusive, demonstrated no ben- of TEN begins with a nonspecific febrile
efit, or shown worse outcomes when cor- prodrome appearing 2 to 3 days prior to
ticosteroids have been used.4 A handful the development of mucous membrane
of studies and case series have explored involvement and generalized epidermal
the use of intravenous immunoglobulin sloughing. Painful, tender skin with tox-
(IVIG) in SJS and TEN. Most seem to icity is a hallmark of the disease. The
demonstrate a favorable outcome; how- epidermis sloughs off in large sheets that
ever, further study is required to confirm reveal a tender diffuse erythroderma. As
benefit due to the paucity and variability in SSSS, there is a positive Nikolsky’s
of existing studies.4,5 sign. Typically, skin recovery occurs
Toxic epidermal necrolysis (TEN) is in 1 to 3 weeks, though mucositis may
more likely to present with erythroderma last for months. Because of the poten-
www.PediatricSuperSite.com | 111
2/3/2009 2:28:39 PM
 SIDEBAR 2. for mechanical ventilation and blood
pressure support. Fluid resuscitation and
Agents Associated nutrition are essential considering the
with Drug Rash with extent of epidermal loss in TEN. There
Eosinophilia and Systemic is a high risk for infection, and thus iso-
Symptoms (DRESS) lation precautions should be used. Some
have advocated that silver sulfadiazine
Aromatic anticonvulsants
should be avoided due to the associa-
Phenytoin
tion of sulfonamides with TEN. Ocular
Phenobarbital
involvement should be evaluated and
Carbamazepine
treated promptly with ophthalmologic
Non-aromatic anticonvulsants
consultation. Pharmacologic therapy for
Lamotrigine
TEN is controversial. A recent Cochrane
Allopurinol
review concluded that there is no reli-
Non-steroidal anti-inflammatory drugs
able evidence to support the use of cor-
Captopril
ticosteroids, IVIG, or cyclosporine A,
Calcium channel blockers
although all three agents are still com-
Mexiletine
monly used in clinical practice to treat
Fluoxetine
TEN.6 Complications from TEN can be
Dapsone
severe affecting respiratory, gastrointes-
Terbinafine
tinal, hepatic, and renal systems. There
Metronidazole
is a high risk of mortality, with rates
Minocycline
ranging from 10% to 70%.
Antiretroviral agents
Case Diagnosis
DRESS syndrome (drug rash with
eosinophilia and systemic symptoms)
is a severe drug reaction consisting of
skin rash, fever, lymphadenopathy, and
visceral involvement, in this case the re-
sult of carbamazepine. Formally known
as a “drug hypersensitivity syndrome,”
DRESS typically presents 1 to 8 weeks
after initiation of the offending agent.
Typical clinical manifestations include
persistent fever, facial edema, lymph-
adenopathy and diffuse morbilliform
patches that may progress to bullae,
vesicles and erythroderma (see Figure 1,
page 110). Unlike SJS or TEN, mucous
membranes erosions are usually not a
manifestation in DRESS. A Nikolsky’s
Figure 4. Target lesions with bullae of Stevens- sign is not present, thus differentiating it
Johnson syndrome
from SSSS and TEN. Visceral involve-
ment in DRESS may include hepatitis,
tial for severe illness, patients with TEN interstitial nephritis, thyroiditis, pneu-
are best cared for in an experienced in- monitis, and carditis.
tensive care unit or burn center. Care is The most common etiologic agents
generally supportive, including aggres- for DRESS include aromatic anticon-
sive wound care, and the potential need vulsants (carbamazepine, phenobarbital,
112 | www.PediatricSuperSite.com
3802AronsonCS.indd Sec1:112
phenytoin), nonaromatic anticonvul-
sants (lamotrigine), and sulfonamides,
although several other agents have also
been associated with the syndrome. (see
Sidebar 2). If suspected, complete blood
count, serum transaminases, creatinine
and urinalysis should be obtained. He-
matologic abnormalities include eo-
sinophilia and atypical lymphocytosis.
Serum transaminases are frequently el-
evated. Skin biopsy is usually nonspe-
cific, revealing findings ranging from
perivascular eosinophilic infiltrates to an
infiltrate of atypical lymphocytes mim-
icking mycosis fungoides.
The hallmark of therapy for DRESS
is prompt withdrawal of the offending
agent, which has been associated with
lower mortality in other serious drug
reactions.7 Supportive therapies include
antipyretics for fever and aggressive
wound care for exfoliated areas of skin.
Systemic corticosteroids can provide
dramatic improvement in clinical and
laboratory findings of DRESS.8 If ini-
tiated, corticosteroids should be given
with an appropriate taper throughout 6
to 8 weeks to prevent relapse or progres-
sion to further systemic involvement.
Despite many cases reporting success,
there are no randomized controlled tri-
als of corticosteroid use in DRESS, and
their use remains somewhat controver-
sial. Some of this controversy may re-
late to confusion between DRESS and
SJS/TEN, entities mediated by entirely
different mechanisms. Furthermore, cor-
ticosteroids may lead to reactivation of
viruses, such as human herpesvirus-6,
which is thought to be involved in the
pathogenesis of some cases of DRESS.
IVIG and plasmapheresis have been
used with success; however, they are not
current standard of care.9 Other agents
that focus on accelerating elimination of
the causative drug, such as N-acetylcys-
teine, are being explored.10 Patients with
DRESS should be followed closely for
several months with attention to hemato-
logic, liver, thyroid, and renal function.
PEDIATRIC ANNALS 38:2 | FEBRUARY 2009
2/3/2009 2:28:40 PM
 CASE PRESENTATION
A 3-year-old girl presents to the
emergency department with refusal to
walk for 2 days and a rash involving her
lower extremities. The patient’s mother
reports that the patient had a “cold” 1
week prior. On physical examination,
the patient is well-appearing but uncom-
fortable, and has palpable purpura on
both lower extremities (Figure 5). Her
ankles are swollen, and she has tender-
ness to palpation of her abdomen with
guaiac positive stool. A complete blood
count is normal. What is the most likely
diagnosis, and how you would you man-
age this patient?
Differential Diagnosis
Purpura and petechiae represent
hemorrhage into the skin. Finding them
on a child is often frightening, as they
can be a sign of life-threatening illness.
Familiarity with the various diseases
that present with purpura or petechiae
is important for both diagnosis and
acute management.
In approaching a child with purpura,
as with any child, it is critical to first rule
out life-threatening disease. While pur-
pura can result from disseminated intra-
vascular coagulation (DIC) secondary to
multiple bacterial pathogens, the leading
and most rapidly fatal condition is acute
infectious purpura fulminans, which oc-
curs in 15% to 25% of individuals with
meningococcemia, or disseminated in-
fection with Neisseria meningitidis.11
Skin manifestations progress rapidly
from scattered petechiae to purpura,
and ultimately to necrosis12 (see Figure
6, see page 114) The distal extremities
are generally the most severely affected,
usually in a symmetric fashion.11 Sys-
temic signs of sepsis are present, initial-
ly manifesting as tachycardia, widened
pulse pressure, and bounding peripheral
pulses, followed by circulatory collapse.
Meningitis, DIC, and acute respiratory
distress syndrome (ARDS) are frequent
complications. Prompt initiation of ag-
PEDIATRIC ANNALS 38:2 | FEBRUARY 2009
3802AronsonCS.indd Sec1:113
gressive fluid resuscitation and antibiotic
therapy is critical for survival. Adjunct
therapies for hemodynamic support in-
clude vasopressors, hydrocortisone for
refractory hypotension, and respiratory
support. The mortality rate of meningo-
coccemia is approximately 10%.12
Another important infectious cause
of a petechial rash is Rocky Mountain
spotted fever (RMSF), a tick-borne in-
fection caused by Rickettsia rickettsii.
RMSF has been reported across the
United States but is most common in the
southeastern and south-central United
States, occurring mostly between April
and September.13,14 The classic triad of
fever, headache, and rash occur togeth-
er in less than two-thirds of patients;
Delay in diagnosis has been
associated with fatal outcome.
patients can also present with myal-
gia, malaise, and gastrointestinal com-
plaints, as well as conjunctival injection
and neurologic symptoms.13 One to 5
days after the onset of fever, the classic
rash develops in approximately 90% to
97% of patients.13,14 The rash begins as
small macules on the wrists and ankles,
spreads distally to involve the palms
and soles before spreading centrally,
and progresses to petechiae by the end
of the first week of illness (see Figure
7, see page 114). Laboratory abnormali-
ties include thrombocytopenia, elevated
transaminases, and hyponatremia. The
gold standard diagnostic test is serologic
testing using the indirect fluorescent
antibody test.13 Delay in diagnosis has
been associated with fatal outcome. Be-
cause laboratory confirmation of infec-
tion may take several days, appropriate
antimicrobial therapy should be initiated
promptly for any patient with fever and a
suspicious rash. Doxycycline is the drug
of choice for children of all ages and
Figure 5. Palpable purpura on the lower extremi-
ties in Henoch-Schönlein purpura. Courtesy of
the Walter W. Tunnessen Pediatric Image Library,
The Children’s Hospital of Philadelphia.
should be continued until the patient is
afebrile for 2 or 3 days.15 Even in appro-
priately treated patients, mortality rates
are as high as 5%.13
Petechiae and purpura may also be
manifestations of thrombocytopenia,
and several diagnoses should be emer-
gently addressed in this setting. The triad
of acute renal insufficiency, microangio-
pathic hemolytic anemia, and throm-
bocytopenia defines hemolytic uremic
syndrome (HUS). HUS usually affects
infants and young children. “Typical”
HUS accounts for 95% of cases, and oc-
curs days to weeks following a diarrheal
illness caused by Shiga-toxin producing
bacteria, most commonly Escherichia
coli O157:H7 and Shigella dysenteriae.16
“Atypical” HUS can occur in association
with various etiologies, including virus-
es, Streptococcus pneumoniae, and bone
marrow transplantation. HUS should be
considered in any child presenting with
petechiae and jaundice (indicating he-
molysis), especially when accompanied
by physical exam findings concerning
for volume overload, such as periorbital
edema or hypertension. Treatment for
HUS is supportive therapy — correct-
ing electrolyte imbalance, treating fluid
overload and hypertension, and dialysis
if necessary. Randomized controlled tri-
als evaluating interventions such as an-
ticoagulation, corticosteroids, plasma-
pheresis, and Shiga-toxin binding agents
have not demonstrated any added benefit
to supportive therapy alone.16,17 Antibi-
otics are not recommended in Esch-
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2/3/2009 2:28:41 PM

Figure 6. Meningococcemia. Courtesy of the
Walter W. Tunnessen Pediatric Image Library, The
Children’s Hospital of Philadelphia.
Figure 7. Rocky Mountain spotted fever. Courtesy
of the Walter W. Tunnessen Pediatric Image Li-
brary, The Children’s Hospital of Philadelphia.
erichia coli O157:H7 infection, as they
do not prevent HUS and may increase
the risk of its development.17 The major-
ity of children with Shiga-toxin associ-
ated HUS recover completely, although
some do have persistent renal dysfunc-
tion. The prognosis is more guarded
with atypical HUS.
Two other etiologies to rule out in a
child with petechiae and thrombocyto-
penia are immune thrombocytopenic
purpura (ITP) and acute leukemia. The
clinical hallmark of ITP is isolated throm-
bocytopenia, without hepatospenomega-
ly or lymphadenopathy, resulting from
the destruction of autoantibody-coated
platelets. The idiopathic disorder usual-
ly develops in young children following
an upper respiratory infection, and most
patients recover a normal platelet count
within several weeks to 6 months of ini-
tial presentation.18 The goal of therapy
for ITP is to accelerate platelet recovery
to prevent the life-threatening complica-
tion of intracranial hemorrhage which
occurs in approximately 0.2% to 1% of
children with ITP, usually when plate-
let counts are less than 20,000/mm3.19
114 | www.PediatricSuperSite.com
3802AronsonCS.indd Sec1:114
Treatment options for ITP include IVIG,
corticosteroids, and anti-Rh (D) immune
globulin. Randomized trials have shown
that treatment with IVIG results in more
rapid platelet count recovery above
20,000/mm3 when compared with the
other treatment modalities.19,20 However,
many practitioners choose observation
alone, as treatment has not been shown
to prevent intracranial hemorrhage.18
If the thrombocytopenia is associated
with anemia or neutropenia, or physical
examination findings such as hepato-
splenomegaly or lymphadenopathy are
present, the diagnosis of acute leukemia
should be ruled out with bone marrow
aspiration and biopsy.
Case Diagnosis
In a well-appearing child with pur-
pura and normal blood counts, as in the
case vignette, the most likely diagnosis
is Henoch-Schönlein purpura (HSP), an
idiopathic small vessel vasculitis that
usually follows an upper respiratory
tract infection. The hallmark of the dis-
ease is palpable purpura, usually located
on the lower extremities (see Figure 5,
page 113) and buttocks, and often ac-
companied by polyarthralgia involving
the knees and ankles, abdominal symp-
toms, and renal disease.21 Abdominal
complaints can be mild, such as pain
and heme-positive stools, but more se-
vere complications such as intussuscep-
tion and gastrointestinal hemorrhage can
occur. Similarly, renal disease can range
from hematuria and proteinuria to rap-
idly progressive glomerulonephritis and
end-stage renal disease.22 As a result of
the acute onset of purpura, children with
HSP are sometimes misdiagnosed as
having meningococcemia. HSP is gen-
erally a self-limited illness, although a
minority of patients develop persistent
renal abnormalities. A recent meta-anal-
ysis demonstrated that corticosteroids
reduce the mean resolution time of ab-
dominal pain and the odds of developing
persistent renal disease.22 Pain control
for arthralgias includes non-steroidal
anti-inflammatory medications.
CASE PRESENTATION
A 2-year-old boy presents to the
emergency department with 6 days of fe-
ver and “irritability.” On physical exam,
the patient has bilateral conjunctival in-
jection without exudate, fissured lips, an
erythematous confluent macular rash,
and swelling of the dorsum of the hands
and feet (Figure 8, see page 115). What
diagnostic test is warranted for therapeu-
tic and prognostic consideration?
Differential Diagnosis
Persistent fever in a child raises sev-
eral diagnostic possibilities, and the
presence and timing of dermatologic
manifestations aid in narrowing the dif-
ferential diagnosis. Human herpesvirus
type 6 (HHV6) causes roseola infantum
or exanthem subitum, characterized by
spiking fever classically followed by
... children with HSP are
sometimes misdiagnosed as
having meningococcemia ...
acute defervescence and the appear-
ance of a non-pruritic erythematous
macular rash that begins on the trunk
before spreading to the extremities and
face. Adenovirus can cause prolonged
fever associated with conjunctivitis,
pharyngitis, upper respiratory tract
and gastrointestinal symptoms, and a
macular or papular rash. Parvovirus
B19 infection classically causes ery-
thema infectiosum, with a character-
istic “slapped-cheek” facial rash and a
reticular, lacy rash on the trunk and ex-
tremities. Scarlet fever caused by group
A beta-hemolytic streptococcus pres-
ents with fever, strawberry tongue, exu-
dative pharyngitis, and a scarlatiniform
PEDIATRIC ANNALS 38:2 | FEBRUARY 2009
2/3/2009 2:28:42 PM
 SIDEBAR 3.

Clinical Criteria for Kawasaki Disease25

(also see Figure 8)

At least 5 days of fever, plus at least four out of five of the following:
• Bilateral non-exudative bulbar conjunctival injection
• Changes in the lips and oral cavity (erythema, fissuring of the lips, strawberry tongue)
• Cervical lymphadenopathy with at least one lymph node > 1.5 cm in diameter
• Extremity changes (erythema or edema of the hands and feet, periungal peeling
of fingers and toes) Figure 8. Kawasaki disease: bulbar conjunctival
injection with limbic sparing. Courtesy of the
• Polymorphous rash Walter W. Tunnessen Pediatric Image Library, The
Children’s Hospital of Philadelphia.

rash described as having a “sandpaper” Case Diagnosis

texture. As described previously, toxic
shock syndrome presents with fever,
erythroderma, conjunctivitis, and hy-
potension; staphylococcal scalded skin
syndrome also presents with fever and
an exfoliative rash. Systemic-onset ju-
venile idiopathic arthritis often presents
with quotidian fever associated with a
salmon-colored macular rash (Figure
9), with variable polyarthritis. Onco-
logic processes such as leukemia can
present with prolonged fever and pete-
chiae resulting from thrombocytopenia,
as described above.
In an adolescent patient, dissemi-
nated Neisseria gonorrhoeae infection
is an important cause of fever and a
polymorphous rash. The classic clini-
cal findings include a migratory, asym-
metric polyarthritis, tenosynovitis, and
a polymorphous rash that can be macu-
lar, papular, pustular, vesicular, pete-
chial, or necrotic, and can involve the
palms and soles.23,24 (see Figure 10).
Neisseria gonorrhoeae is recovered
from synovial fluid or blood in dis-
seminated infection in 20% to 30% of
cases; specimens for nucleic acid am-
plification should be obtained from the
genital tract and often from the rectum
or pharynx. Recommended treatment
consists of ceftriaxone or cefotaxime
for 7 days, plus simultaneous presump-
tive therapy for Chlamydia trachomatis
with azithromycin or doxycycline.24
Prolonged fever is the hallmark of
Kawasaki disease, a systemic vasculitis
of uncertain etiology with significant
potential morbidity. Diagnosis of clas-
sic Kawasaki disease requires at least 5
days of fever associated with at least 4 of
5 clinical criteria.25 (see Sidebar 3). An
algorithm has been developed for chil-
dren with at least 5 days of fever who
meet only 2 or 3 of the clinical criteria,
so-called “incomplete” or “atypical”
Kawasaki disease. The algorithm begins Figure 9. Salmon-colored macular rash in system-
with measuring C-reactive protein and ic-onset juvenile idiopathic arthritis. Courtesy of
the Walter W. Tunnessen Pediatric Image Library,
erythrocyte sedimentation rate. The Children’s Hospital of Philadelphia.
If > 3.0 mg/dL or 40 mm per hour, re-
spectively, the diagnosis of Kawasaki dis-
ease is confirmed if the patient meets 3 out
of 6 supplementary criteria: leukocytosis,
anemia for age, thrombocytosis, low al-
bumin, elevated alanine aminotransferase,
and sterile pyuria.25 If the patient meets the
criteria for classic or incomplete Kawasaki
disease, an echocardiogram should be ob-
tained and treatment initiated. Echocardio-
gram should also be obtained in patients in Figure 10. Disseminated gonococcal infection
involving the palms. Courtesy of the Walter W.
whom the diagnosis of incomplete Kawa- Tunnessen Pediatric Image Library, The Children’s
saki disease is being considered but who Hospital of Philadelphia.
do not fulfill three supplemental labora-
tory criteria. Morbidity and mortality in dition, cardiac function and the presence
Kawasaki disease are primarily caused by of valvular abnormalities and pericardial
vasculitic coronary artery abnormalities. effusion can be evaluated.25 Treatment
Echocardiogram at diagnosis establishes should not be delayed while awaiting
a baseline of coronary artery morphology, echocardiography.
on which long-term treatment, follow-up, First-line therapy for Kawasaki dis-
and prognosis can be established. In ad- ease consists of aspirin and IVIG. Be-

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3802AronsonCS.indd Sec1:115 2/3/2009 2:28:43 PM

 cause of its anti-inflammatory properties
at high doses, aspirin is administered at
doses of 80 to 100 milligrams per kilo-
gram divided four times per day until the
patient is afebrile for 48 to 72 hours, al-
though some practitioners continue high-
dose aspirin until day 14 of illness.25 The
dose is then reduced to 3 to 5 milligrams
per kilogram per day and continued for
6 to 8 weeks, when follow-up echocar-
diography is usually obtained. If coro-
nary artery abnormalities are detected at
follow-up, aspirin is continued and other
platelet inhibitors (clopidogrel) or anti-
coagulants (warfarin) may be indicated
for large coronary aneurysms. The other
mainstay of treatment for Kawasaki dis-
ease is IVIG, administered at a dose of
2 grams per kilogram as a single infu-
sion, which in combination with aspirin
reduces the incidence of coronary aneu-
rysms.26,27 Treatment should be given
within 10 days of the onset of fever, and
within 7 days if possible.25 Approximate-
ly 10% of children do not respond to the
initial IVIG infusion, defined as persis-
tence of fever 36 hours after treatment.
For these refractory patients, a second
dose of IVIG is recommended, though
corticosteroids or infliximab may also
be used.25 With appropriate treatment,
the risk of coronary artery aneurysms is
less than 5%.25
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