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Exanthems in Children
A Review and Update
Anthony J. Mancini, M.D., FAAP, FAAD
Professor of Pediatrics and Dermatology
Northwestern University Feinberg School of Medicine
Head Pediatric Dermatology
Head,
Ann & Robert H. Lurie Children’s Hospital of Chicago
Chicago, IL
Disclosures
I have no financial relationships with the
manufacturer(s)
f t
( ) off any commercial
i l product(s)
d t( )
and/or provider of commercial services discussed
in this CME activity.
I do not plan on discussing an unapproved or
investigative use of a commercial product/device
in this presentation.
Objectives
j
At the conclusion of this activity, participants will be
able to …
•
•
•
•
Appreciate several classic and related exanthems
Recognize B19B19-associated exanthems and understand
the epidemiologic significance
Consider enteroviruses as agents in the appropriate
exanthematous
th
t
settings
tti
Diagnose atypical/parainfectious
atypical/parainfectious exanthems
Exanthem
Exanthems
S t
Spectrum
off common and
d uncommon
disorders
Variety of pathogens
Viral, bacterial, rickettsial, drug
drug--induced
Many benign/self
benign/self--limited
Potential for serious complications
Exanthems in Children
P
Prompt
t recognition
iti
Accurate diagnosis
Further evaluation?
Systemic
y
associations?
Epidemiologic concerns?
Approach to the Child
Does the child appear ill?
Presenting history/exposures
More concern:
Purpura,, blisters, mucosal involvement
Purpura
Hi h fevers
High
f
Extracutaneous organ involvement
Pearls in Assessing the Rash
Lesion morphology (blanchable
(blanchable,
blanchable, petechiae
petechiae,,
trailing scale, reticulate, blisters . . .)
Distribution (acral
(acral,, palmoplantar
palmoplantar,, unilateral,
truncal . . .)
g
(centripetal,
(
p
centrifugal,
g
Progression
cephalocaudad . . .)
Pearls in Assessing the Rash
Associated features:
Purpura (parvo
parvo,, entero,
entero, rickettsia, N. men,
men, HSP,
group A strep)
Ed
Edema
(K
(Kawasaki,
ki serum sickness,
i k
drug
d
hypersensitivity)
Enanthem (Kawasaki, drug, measles, rubella,
entero,, parvo,
entero
parvo, adeno,
adeno, group A strep, EBV)
Conjunctivitis (Kawasaki, drug, measles,
adeno
adeno)
d )
Classic exanthems
circa early 1900’s
I.
II.
III.
IV.
V
V.
VI.
Measles ((rubeola
rubeola))
Scarlet fever
German measles (rubella)
Filatow
Filatow--Dukes disease
E th
Erythema
i f ti
infectiosum
Roseola infantum
. . . Varicella, too
Measles
Marked postpost-vaccination era
Recent resurgence:
2008: 140 total U.S. cases
2011 222 cases**
2011:
*90%: importation (Europe/SE Asia)
*86% unvaccinated or unknown status
*32% hospitalized/no deaths
Cough, coryza,
coryza, conjunctivitis
Koplik
p spots
p
Cephalocaudad spread
Risks: encephalitis, pneumonia,
myocarditis, bronchitis
CDC. MMWR 2012;61(15);253.
Measles
Koplik
K lik spots
t pathognomonic?
th
i ?
Prospective
p
data,, 6 months,, London
Clinical observations, IgM (ELISA) or
measles RNA (PCR)
69 patients
ti t with
ith adequate
d
t clinical
li i l info
i f
and lab results
((+)) PV of clinical suspicion:
p
50%
Using KS: 80%
KS a timely tool in diagnosis
Zenner D, et al. J Infect Dev Ctries 2012;6(3):271.
Scarlet fever
GABHS
Fever, pharyngitis, headache, chills
Fine papular erythema,
erythema “sandpaper
sandpaper rash
rash”
Flexural accentuation w/petechiae
w/petechiae (Pastia lines)
Circumoral pallor
Scarlet--fever like?
Scarlet
Mononucleosis
Arcanobacterium haemolyticum
A.
A haemolyticum
Emergency medicine literature mainly
Gram+ bacillus; *culture on 5% human blood agar
Adolescents/young adults
Pharyngitis scarlatiniform exanthem
Pharyngitis,
Rarely soft tissue infections, septicemia ((esp
esp with DM),
thyroid abscess, Lemierre syndrome
M
More
responsive
i to macrolides
lid
Tan TY, et al. J Infect 2006;53(2):e692006;53(2):e69-74.
Therriault BL, et al. Ann Pharmacother 2008;42(11):1697
2008;42(11):1697--702.
Lundblom K, et al. Infection 2010;38:427.
Sayyahfar S, et al. J Infect Chemother 2012;Jan 31 (epub
(epub).
).
Erythema infectiosum
Fifth disease
Parvovirus B19
Fiery--red facial
Fiery
erythema
y
Reticulated lacy
eruption
May wax and wane
for months
Erythema infectiosum
Arthralgias in 88-22%
(more common in adults)
A l i crises
Aplastic
i in
i those
h
predisposed
Fetal infection: self
self-limited, mild anemia,
CHF, hydrops,
hydrops, death (1
(1-9%)
**Non--contagious when
**Non
rash present
p
Nicolay N, et al. Eurosurveillance
2009;14(25):1.
Papular-purpuric gloves and
Papularsocks syndrome
Usually parvo B19
Symmetric swelling of
hands & feet
Erythema, purpura
Sharpp demarcation
Enanthem: soft/hard palate
B19 DNA in skin lesions
** ill viremic
**Still
i
i with
i h rashh
Fretzayas A,
A et al.
al Pediatr Infect Dis J 2009;28: 250.
250
Fruhauf J, et al. J Am Acad Dermatol 2009;60:691.
Smith PT, et al. Clin Infect Dis 1998;27:1641998;27:164-8.
Bathing-trunk eruption/petechiae
Bathing+ B19
A th clinical
Another
li i l presentation
t ti off B19 infection
i f ti
Accentuation in flexures
P
Petechiae
hi prominent
i
feature
f
May have associated petechial enanthem
Kramkimel N, et al. Br J Dermatol 2008;158:405.
Butler GJ, et al. Australas J Dermatol 2006;47(4):286.
McNeely M, et al. J Am Acad Dermatol 2005;52:S109.
Generalized petechial rashes
+B19
Community outbreak of B19,
B19 Dane County,
County WI
17 unexplained petechial rashes
13 confirmed as B19 acute infection ((serology,
gy, PCR))
Fever (85%), mild URI symptoms
Petechiae generalized (100%), locally accentuated
(54%; folds and acral extremities)
Leukopenia (83%)
Edmonson MB, et al. Pediatrics 2010;125(4):e787.
Roseola infantum
Exanthem subitum
HHV--6 and -7
HHV
High seroprevalence by
3-6 years
High fever,
fever then
exanthem
Trunk first: blanchable
macules, peripheral
halo
Nagayama spots: soft
palate, uvula
HHV--6/7 – Other associations
HHV
Fever
Febrile seizures
Otitis media
Meningitis
g
Encephalitis/--opathy
Encephalitis/
Hepatitis
Macrophage activation
syndrome (MAS)
Lymphoproliferative d/o
HIV--1 cofactor
HIV
Pityriasis rosea
Mononucleosis
Multiple sclerosis
Lymphadenopathy
Drug hypersensitivity
(reactivation)
Agut H. J Clin Virol 2011;52:164.
Matsumoto H, et al. Pediatr Infect Dis J 2011;30(11):999.
HHV--6/7 – Other associations
HHV
Fever
Febrile seizures
Otitis media
Meningitis
g
Encephalitis/--opathy
Encephalitis/
Hepatitis
Macrophage activation
syndrome (MAS)
Lymphoproliferative d/o
HIV--1 cofactor
HIV
Pityriasis rosea
Mononucleosis
Multiple sclerosis
Lymphadenopathy
Drug hypersensitivity
(reactivation)
Agut H. J Clin Virol 2011;52:164.
Matsumoto H, et al. Pediatr Infect Dis J 2011;30(11):999.
Breakthrough varicella
U.S. first country to introduce universal varicella
vaccination (1995)
2006: 2nd dose of vaccine added to schedule
Prior to vaccination: 4 million cases/year in U.S. (105
deaths/year)
Breakthrough infection still occurs: 2.1% among >1
million vaccinees in Taiwan (1 dose schedule)
Most often at 55--6 years of age
Marin M, et al. Pediatrics 2008;122:e744.
Huang WC, et al. Vaccine 2011;29:2756.
Varicella
Prodromal symptoms
Rash spreads centrifugally (trunk extremities)
“Dewdrop on a rose petal”
Secondary bacterial infection (GABHS),
(GABHS) pneumonia,
pneumonia
encephalitis
May accentuate at sites of sunburn (“photolocalized
(“photolocalized””
v.),
v ) vaccine sites
sites, dermatitis/abrasions
dermatitis/abrasions, trauma,
trauma burns
Termed “occult varicella”
Nikkels AF, et al. Pediatr Infect Dis J 2009;28(12):1073.
Herpes zoster
zoster, healthy children?
VZV
llatency iin dorsal
d
l
sensory/cranial n. ganglia
Reactivation sensory dermatomal
distribution of vesicles
Greatest risk: acute VZV <1 yr of age
Infant: maternal VZV during pregnancy
Wild--type or vaccine strain VZV
Wild
U ll nott a sign
Usually
i off immunodeficiency
i
d fi i
Post--herpetic neuralgia: rare
Post
Feder HM, et al. Pediatr Infect Dis J 2004;23:451.
Enteroviruses
Include echo, coxsackie,
coxsackie, entero,
entero, (polio)
Majority of infections benign
Potential for severe infection: meningitis,
encephalitis, myocarditis, neonatal sepsis
Peak in summer and fall,
fall but yearyear-round
Oral secretions, respiratory droplets, fecalfecal-oral
Enteroviruses
Most exanthems nonspecific; petechiae common
Hand-ffoot
Handfoot--and
and--mouth disease best recognized
g
1 – 4 years of age
*Elbows, knees, buttocks too
Epidemics of severe disease – enterovirus 71 (EV71)
Taiwan 1998, Malaysia 1997
Aseptic meningitis
meningitis, encephalitis,
encephalitis paralysis,
paralysis pulmonary
edema, heart failure
Chang LY,
LY et al.
al JAMA 2004;291(2):222
2004;291(2):222.
Xu J, et al. Vaccine 2010;28:3516.
Solomon T, et al. Lancet Infect Dis 2010;10:778.
Enterovirus 71 outbreak
176 patients vs 201 case-controls
Hand washing by children &
Hand-washing
caregivers
significant
protective effect
Ruan F, et al. Pediatrics 2011;127(4):e898.
Enteroviruses
EV71
5 genotypes, rapid evolution
Vaccine under development
Xu J, et al. Vaccine 2010;28:3516.
Lee TC, et al. Pediatr Infect Dis J 2009;28:904.
Herpangina – enanthem only, 33--10 years
Echovirus exanthems – variable; may be vesicular,
EM--like,
EM
like roseola
roseola--like; may simulate herpes zoster
Eruptive
pseudoangiomatosis
• Acute onset of
hemangioma--like
hemangioma
lesions
• Resolve over 1 week
• Echovirus 25/32 in
i i i l reports
initial
• May occur in
epidemics
Cherry
C
e y JD,
J , et
e al.. Pediatrics
ed
cs
1969;44(4):498.
Chaniotakis I, et al. Dermatology
2007;215(1):59.
Courtesy Dr. Neil Prose
Courtesy Dr. Andrew Sagan
Recent epidemic
Severe HFMD – June 2012
Fever and atypical
yp
rash
Coxsackie A6 via RTRT-PCR, sequencing
63% <2 years, 24% >18 years
Hospitalization more common
More blisters, perioral involvement; 46% arms/legs
MMWR:
MMWR AL
AL, CT
CT, CA
CA, NV
SPD chat: IL, PA, MA, OR, TX, NY, Toronto
Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly
Rep 2012;Jun 1;61:396.
Enteroviruses
Nail matrix arrest
• May follow HFMD; avg 40 days
• Mechanism unclear
id i nail
il shedding
h ddi
•T
Transverse ridging,
• When assessed: Coxsackievirus
A10, A6, B1, B2
• Most HFMD outbreaks: CV A16,
enterovirus 71, echovirus 4
Wei SH, et al. BMC Infect Dis 2011;11:346.
Davia JL, et al. Pediatr Dermatol 2010;Jun 9 (epub
(epub))
Blomqvist S,
S et al.
al J Clin Virol 2010;48:49.
2010;48:49
Osterback R, et al. Emerg Infect Dis 2009;15:1485.
Clementz GC, Mancini AJ. Pediatr Dermatol 2000;17:7.
Atypical/parainfectious
Atypical/parainfectious
exanthems
- More prolonged course
- Mayy occur in the course of several different viral
infections, rather than representing one distinct
pathogen
Gianotti--Crosti syndrome
Gianotti
Classic: rash, hepatitis,
LAN, hepatitis B
Specific exanthem
URI prodrome
Monomorphous papules –
cheeks, extremities,
buttocks
Primarily children, rarely
adults
Ting PT, et al. J Cutan Med Surg
2008;12(3):121.
Gianotti--Crosti
Gianotti
syndrome
Hepatitis B association – mainly
European/Japanese
Cli i l distinction
Clinical
di i i not possible
ibl
U.S. – Hepatitis B rare;
EBV,, many others
EBV
Vaccines – live, killed &
recombinant; H1N1
Brandt O, et al. J Am Acad Dermatol
2006;54(1):136.
Lam JM.
JM J Am Acad Dermatol 2011;65
(4):e127.
Retrouvey M, et al. Pediatr Dermatol 2012;Feb
22:epub.
Gianotti--Crosti syndrome
Gianotti
Evaluation for GI
symptoms,
hepatosplenomegaly,
hepatosplenomegaly
lymphadenopathy
“Blind”
Blind hepatitis blood
evaluations not
warranted
Resolves: 33--12 weeks
Therapy supportive
Unilateral laterothoracic
exanthem
“Asymmetric
perifle ral
periflexural
exanthem”
1-5 years
Initially unilateral
Axilla trunk,
Axilla,
trunk flank
Initial misdiagnosis:
contact dermatitis
Unilateral laterothoracic
exanthem
In 40%: begins on
extremity
Subsequent
generalization
Maintains unilateral
predominance
Multiple
morphologies
Pruritus in 60%
Unilateral laterothoracic
exanthem
Prodrome in 6060-75%:
rhinitis,, pharyngitis,
p y g ,
GI complaints
Fever in 40
40--65%
P b bl viral,
Probably
i l no agentt
proven
Primaryy EBV?
Resolves over 44--8 weeks
Therapy supportive
Duarte AF, et al. Pediatr Infect Dis J
2009;28(6):549.
Summaryy
• Measles: increasing presence in U.S.; vaccination
education; Koplik spots aid in diagnosis
• A. Haemolyticum
Haemolyticum:: adolescents; scarlet fever
fever--like
illness; macrolides
• Gloves and socks syndrome: B19; purpuric
erythema hands/feet; palatal enanthem
• Diffuse petechial eruption with accentuation in
flexures/acral
flexures/
acral locations: think B19
• Breakthrough varicella occurs, may be “occult”
(s nb rn tra
(sunburn,
trauma,
ma dermatitis)
Summary (continued)
• Zoster in children: greatest risk when acute VZV
<1 year off age; nott a marker
k for
f immunodeficiency
i
d fi i
• Enterovirus
Enterovirus:: petechial exanthems;
exanthems; epidemics of
hand-washingg vital for prevention
p
severe disease;; hand• Nail shedding in otherwise healthy child: review
for HFMD in preceding 22--3 months
• GianottiGi tti-Crosti:
Gianotti
C ti: EBV;
Crosti
EBV monomorphous;
monomorphous
h ;
extensors/face/buttocks; 33-12 weeks
Unilateral
e laterothoracic
e o o c c eexanthem
exanthem:
e : initiallyy
• U
unilateral; generalizes; 44--8 weeks