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Joseph M Lam
Pediatr Health. 2010;4(6):623-635.

Abstract and Introduction

Abstract

An exanthem is any eruptive skin rash that may be associated with fever or other systemic symptoms. Causes include
infectious pathogens, medication reactions and, occasionally, a combination of both. In children, exanthems are most often
related to infection and, of these, viral infections are the most common. Some exanthems have very specific morphologies
that help identify and characterize the eruption. In this article, we describe common and uncommon viral exanthems, based
on their morphology, and review current advancements in understanding and treatment of these exanthems.

Introduction

An exanthem is any eruptive skin rash that may be associated with fever or other systemic symptoms. Causes include
infectious pathogens, medication reactions and, occasionally, a combination of both.

Over 100 years ago, a group of characteristic childhood eruptions were described and numbered from one to six:[1,2]
measles, scarlet fever, rubella, erythema infectiosum and roseola infantum. The origin of the fourth classic childhood
eruption, formerly referred to as Dukes' disease, is controversial. It may represent misdiagnosed cases of rubella or scarlet
fever, rather than a distinct illness.

Viral exanthems are common in childhood. The words 'exanthema' and 'anthos' mean 'breaking out' and 'flower' in Greek,
respectively. Similarly, a child breaking out with a viral exanthem may be likened to a flower bursting into bloom. In children,
exanthems are most often related to infection[3] and, of these, viral infections are the most common. Determining the cause
of an exanthem is based on the characteristic morphology, distribution and time course of the eruption, as well as a careful
assessment of infectious contacts, immunization status and aspects of the physical examination. Although not always
diagnostic, the morphology and configuration of cutaneous lesions are of considerable importance to the classification and
diagnosis of viral exanthems. For the purpose of this article, we will characterize common and uncommon viral exanthems,
based on their morphology, and will discuss current advancements in understanding and treatment of these viral diseases.

Macular & Maculopapular Exanthems

Measles

Measles is caused by a ssRNA virus belonging to the Paramyxoviridae family, genus Morbillivirus. It has an incubation
period of approximately 10–12 days, and clinical disease begins with symptoms of fever, conjunctivitis, rhinorrhea, sore
throat and a dry cough. Koplik spots (gray–white papules on the buccal mucosa) may be seen during this prodromal phase.
Approximately 3–4 days after the prodromal symptoms, the typical exanthem of coalescing erythematous macules and
papules erupts, beginning behind the ears and in the hairline area, and spreads over the rest of the skin over a period of a
few days. The eruption typically resolves in the same order as its appearance, and will often desquamate.

The differential diagnosis includes other maculopapular exanthems, such as rubella, toxic shock syndrome, roseola,
parvovirus B-19 infection and drug eruptions. Complications of measles include transient immunosuppression, acute
postinfectious encephalitis and subacute sclerosing panencephalitis (SSPE). Transient immunosuppression occurs during
the illness and lasts for approximately 6 weeks.[1] During this time, an infected individual is at risk for secondary bacterial
infections, such as otitis media, pneumonia or gastroenteritis. Postinfectious encephalitis occurs in approximately one in
1000 patients, and manifests approximately 1 week after the onset of the exanthem.[4] Symptoms present during, or shortly
after, acute infection, and include headache, fever and seizures. A lesser-known entity, known as measles inclusion-body
encephalitis, can affect immunocompromised patients from weeks to months after acute infection.[5] SSPE affects
approximately one in 100,000 patients, and manifests as a slow, progressive disease, which can present months or even

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years after resolution of the acute infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent.
Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. In total, 95% of individuals with SSPE die
within 5 years of diagnosis.[6] SSPE is caused by a persistent infection of the CNS with the virus, and early childhood
infection with measles is a risk factor for SSPE.

An unusual variant of measles can be seen in previously vaccinated individuals, infants with maternal IgG antibodies and
patients on immunoglobulin therapy.[1] In this modified form, the prodrome and exanthem are milder and of shorter duration.
However, the disease is just as contagious in these individuals. Diagnosis is based on clinical presentation with laboratory
confirmation, if necessary. Measles IgM can usually be detectable after the first 3 days of the exanthem.

Currently, there is no specific antiviral therapy for measles and treatment is symptomatic. More importantly, the longstanding
availability of the measles vaccine makes the disease easily preventable. Despite, this, there is still poor uptake of the
vaccine,[7–9] owing to, in part, a proposed causal relationship between receipt of the measles–mumps–rubella vaccine and
autism, a claim that has been convincingly scientifically refuted.[10]

Rubella

Rubella, or German measles, is caused by an RNA virus in the Togaviridae family. Approximately 50% of infected individuals
become symptomatic. After an incubation period of 2–3 weeks, symptomatic patients exhibit prodromal symptoms, which
include low-grade fever, headache, sore throat and myalgias. A macular or maculopapular exanthem appears after
approximately 2–5 days and spreads in a cephalocaudal pattern. Symmetrical lymphadenopathy is often seen, and often
occurs in the postauricular and occipital areas. Arthralgias and arthritis are also common. The most serious complication of
rubella is congential rubella syndrome, which classically presents with the triad of deafness, cataracts and cardiac
disease.[11] The differential diagnosis includes other maculopapular exanthems, such as measles, roseola, parvovirus B-19
infection and drug eruptions. The diagnosis of rubella can be made with IgM antibody titers. Patients are contagious 1 week
prior to the eruption of the rash until a week after the rash resolves. The treatment of rubella is supportive.

Erythema Infectiosum

Erythema infectiosum (EI) is a common childhood exanthematous illness caused by parvovirus B19 – a nonenveloped,
ssDNA virus belonging to the Parvoviridae family. The name B19 comes from the bloodbank code, where the original
positive serum sample was labeled (i.e., Row B, Sample 19).[12] It is the only parvovirus that has been linked directly to
disease in humans.[13] Although parovirus B19 infection can have different clinical manifestations (see later), EI is the most
commonly recognized.

Erythema infectiosum manifests in three overlapping stages. After an incubation period of 1–2 weeks, patients present with
fiery-red facial erythema, which has been described as having a 'slapped cheeks' appearance (Figure 1). In the second
stage, patients develop a reticulate macular or urticarial exanthem 1–4 days after the slapped cheek eruption, and this
second rash is mainly seen over the proximal extremities. In the third stage, the exanthem recurs intermittently in response
to stimuli, such as local irritation, high temperatures and emotional stress.[12] Arthropathy may occur in up to 60% of adults
with EI,[14] whereas it will only occur in approximately 10% of children with joint symptoms. In children, the arthropathy
affects larger joints, such as the knees, wrists and ankles, and in an asymmetric pattern.[12]

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Figure 1.

A child with the classic 'slapped cheek' appearance of erythema infectiosum.

The differential diagnosis includes a drug reaction, measles, rubella and enterovirus infection, and roseola infantum.
Complications of EI are owing to the affinity of parvovirus B19 for erythroid precursors. Parvovirus B19 infection can
suppress red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis or congenital
anemia. This is even more likely in patients with illnesses that have already shortened the lifespan of erythrocytes, such as
iron-deficiency anemia, HIV, sickle cell disease, thalassemia and spherocytosis. Although treatment is supportive, at-risk
patients may require transfusions or intravenous immunoglobulin therapy.[15,16]

The diagnosis of EI is usually made clinically. An ELISA is commercially available with high sensitivity, although false-
positive results may recur owing to crossreaction to other viruses or the rheumatoid factor.[17] PCR can detect viral DNA in
clinical samples of urine, respiratory secretions, body tissues and serum.[18]

Roseola Infantum

Roseola infantum is caused by human herpesvirus (HHV) types 6 and 7, and belongs to the Roseolovirus genus in the
subfamily of Betaherpesvirinae.[19]

Both HHV-6 and -7 are highly prevalent in the healthy population, and establish latency in macrophages and T lymphocytes.
They are frequently shed in saliva of healthy donors, and the pathogenic potential of reactivated virus ranges from
asymptomatic infection to severe diseases in transplant recipients. By the end of the second year of life, approximately 75%
of all children are seropositive for HHV-6 and approximately 24% of all children with HHV-6 infection will manifest clinical
symptoms of roseola.[20,21] HHV-7 infection usually occurs later, with approximately 65% of British children infected by the
age of 3 years.[22]

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In roseola, after an incubation period of 5–15 days, infected children develop high fevers that last 3–5 days. This is followed
by the acute onset of a rosey pink, nonpruritic macular rash, predominantly on the neck and trunk. Owing to the presence of
high fevers, patients are often worked up for an occult bacterial infection.

Roseola infection can cause leukopenia[23] and, rarely, thrombocytopenia and hepatitis.[22] Patients generally recover
without sequelae. However, approximately 22% of patients with roseola may develop febrile seizures.[24] The differential
diagnosis includes measles, rubella and other viral exanthems.

The diagnosis of roseola is made clinically. Laboratory diagnosis of HHV-6 and -7 infections is difficult owing to the limited
availability of antibody tests, problems with antigenic crossreaction and lack of understanding of the clinical relevance and
epidemiology of these two viruses. However, the development of standardized quantitative real-time PCR, and the use of
antibody tests based on recombinant proteins, may aid in the diagnosis of HHV-6 and -7 infection in the future.[22]

Epstein–Barr Virus & Aminopenicillins

Epstein–Barr virus (EBV) is a member of the Herpesvirus family, belonging to the genus Lymphocryptovirus. While only
approximately 5–10% of children infected with EBV manifest an exanthem,[2] if amoxicillin or ampicillin is administered, a
characteristic bright-red morbilliform eruption almost always occurs.[25–27] This eruption begins 5–9 days after exposure to
the medication, starting on the trunk before becoming generalized as confluent macules and papules. The eruption most
likely results from ampicillin–antibody immune complexes as a consequence of polyclonal B-cell activation. This consistently
occurs in adolescents and adults with infectious mononucleosis administered ampicillin, but resolves without specific
measures. This reaction is not considered a 'true' drug allergy and, in most children, re-exposure to the antibiotic after the
EBV infection will not trigger a similar response. However, since antimicrobial therapy is not necessary for infectious
mononucleosis, the antibiotic should be discontinued during the acute EBV infection.

Although approximately 7% of mononucleosis-like illnesses are caused by cytomegalovirus (CMV), CMV does not appear to
give this drug-related exanthem.[28]

Vesicular & Pustular Exanthems

Varicella & Herpes Zoster

Varicella is caused by varicella-zoster virus (VZV), an enveloped dsDNA virus responsible for varicella (chickenpox) and
herpes zoster (shingles). VZV is one of eight herpesviruses known to infect humans, and is associated with vesicular
lesions, infection of neuronal tissue and latent infection of dorsal root ganglia. Primary infection causes varicella, after which,
the virus becomes latent.

The transmission of VZV does not require skin-to-skin contact, and is more commonly transmitted by respiratory secretions
via an aerosol route.[29] When a susceptible individual is exposed to VZV, the virus initially undergoes primary replication,
beginning 3–4 days after exposure, and occurring in the oropharynx and regional lymph nodes. This is followed by a primary
viremia. A secondary viremia occurs 10–21 days after exposure and, during this time period, patients manifest with
prodromal symptoms of fever, malaise and myalgias. The exanthem begins soon after as erythematous pruritic macules,
which develop into papules and fluid-filled vesicles, described as 'dewdrops on a rose petal'. The lesions usually begin in the
hairline and spread in a cephalocaudal pattern, involving the scalp and mucous membranes. The vesicles crust over,
typically within 4–5 days of the onset of the initial lesion. The average number of lesions is approximately 300–400.[30]

Older lesions crust over as newer lesions form, and so giving a polymorphous appearance to the exanthem. Lesions may
heal with hypopigmentation and scarring. The differential diagnosis includes pityriasis lichenoides, arthropod bites, herpes
simplex virus (HSV) infection and impetigo. The most common complication of varicella in immunocompetent children is
bacterial superinfection, usually due to group A Streptococcus or Staphylococcus aureus. Neurological complications can
also occur, and these include meningitis, meningoencephalitis, cerebellar ataxia, transverse myelitis and Guillain–Barre
syndrome. Other complications include arthritis, glomerulonephritis, myocarditis, thrombocytopenia and purpura fulminans.
Immunocompromised patients are at risk for severe and protracted varicella, multiorgan involvement and hemorrhagic
varicella.[31]

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The other common clinical manifestation of VZV infection is herpes zoster (shingles) (Figure 2). VZV becomes latent in
dorsal root ganglia cells until reactivation, at which time, the virus travels back to the skin along the sensory nerve,
manifesting as a unilateral vesicular skin eruption involving one to three dermatomes. Skin vesicles may be painful or
pruritic, especially in adults. Zoster generally is a milder disease in children than in adults. Reactivation is probably due to
declining cell-mediated immunity, which explains the increased incidence in the elderly and in immunocompromised patients.

Figure 2.

A child with vesicles on an erythematous base in a dermatomal pattern

Since varicella is usually a benign, mild, self-limiting disease in most immunocompetent individuals, oral acyclovir (ACV) is
not routinely recommended. However, since adolescents and young adults are at a moderately high risk for developing
severe illness, oral ACV should be administered for 5 days, ideally starting within 24 h of the development of a varicella
rash.[32]

Intravenous ACV is used for patients at serious risk for, or who have, a severe or potentially severe VZV infection, such as
immunocompromised patients. The recommended duration of ACV therapy is 7 days, or until no new lesions have appeared
for 48 h.[33] Ideally, therapy should be started within 24 h of onset, but ACV can still be effective up to 72 h after the
appearance of the skin lesions.

Fever should be controlled with acetaminophen. The use of aspirin may predispose to Reye syndrome, and ibuprofen may
predispose to group A Streptococcus infection. The live-attenuated varicella vaccine has been useful in decreasing the
incidence of VZV infection.[34,35] Zoster appears to be less of a problem after immunization than after natural infection. To
avoid breakthrough varicella, individuals should be vaccinated twice, once at an age of 12–15 months and again at 4–6
years.[36] The varicella vaccine has been combined with the measles–mumps–rubella vaccine, and was licensed by the US
FDA in September 2005 for use in children 12 months through to 12 years of age..[37]

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The diagnosis of VZV infection is usually made by history and clinical findings. Laboratory confirmation can be conducted by
demonstrating the presence of specific viral antigens in skin scrapings by immunofluorescence using a commercial
monoclonal antibody to VZV conjugated to fluorescein, or by PCR. These diagnostic methods are highly sensitive and
rapid.[38] Serological testing is unreliable to detect acute infection but can confirm the diagnosis retrospectively.[38]

Eczema Herpeticum

Eczema herpeticum (also known as HSV-associated Kaposi varicelliform eruption) is a severe form of disseminated
cutaneous HSV infection, which occurs primarily in individuals with atopic dermatitis and skin diseases, such as pemphigus,
Darier disease or traumatic burns. Defective cytokine secretion and decreased cell-mediated immunity in skin affected by
atopic dermatitis appear to play a role in the pathogenesis of eczema herpeticum[39]

Patients present with monomorphic umbilicated vesiclulopustules, which progress to form punched-out erosions in areas of
active dermatitis (Figure 3). The upper body is the most common site of infection, with a predilection for the head and neck.
Fever and malaise are often present.

Figure 3.

A child with clustered vesiculopustules and punched-out erosions.

The differential diagnosis includes varicella, zoster and impetigo. Complications include viremia, secondary bacterial
superinfection and keratoconjunctivitis. In some cases, it may progress to fulminating life-threatening infection, and mortality
rates were as high as 75% before antiviral drugs were available.[40]

The diagnosis is made clinically, but may be confirmed by a Tzanck smear (looking for multinucleated giant cells), a
fluorescent antibody smear or culture of a vesicular lesion. The treatment involves systemic ACV. More severe involvement
may require hospitalization and the use of intravenous antivirals. In addition, it is recommended that topical steroids and

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moisturizers be continued to repair the skin barrier.

Hand–Foot–Mouth Disease

Hand–foot–mouth disease (HFMD) is a distinct monomorphous exanthem caused by viruses of the Picornaviridae family in
the Enterovirus genus. Although the enteroviruses can cause an assortment of virus-mediated exanthems, HFMD is a
recognizable and common clinical manifestation. The most common pathogen is the Coxsackie A16 virus, but other
Coxsackie viruses and enteroviruses have been implicated as well. In particular, human enterovirus 71 appears to be
responsible for recent epidemics of HFMD in the Asia–Pacific region.[41]

The infection has a typical incubation period of 3–7 days. The main manifestations are fever, lymphadenopathy, followed by
the appearance of 2–8-mm painful oval, gray vesicles on the palmar and plantar skin, buccal mucosa and tongue after 1–2
days. The vesicles are often arranged parallel to the dermatoglyphs, and may have a surrounding red halo. Papular and
vesicular lesions can also occur on other parts of the body, and the buttocks may often exhibit a nonspecific eruption prior to
the onset of the vesicular exanthem. The oral enanthem helps to distinguish HFMD from other causes of childhood
exanthems, although cases without oral lesions have been described. In the oral cavity, the hard palate, tongue and buccal
mucosa are most commonly affected. The differential diagnosis includes aphthous stomatitis, varicella, HSV infection and
herpangina.

Most HFMD cases are self-limiting, and only required supportive treatment. Rarely, there may be a neurological or
cardiopulmonary complication, such as meningoencephalitis or myocarditis. Uncomplicated HFMD usually resolves in 5–7
days. The case–fatality rate for HFMD ranges from 0.06 to 0.11%.[42] In particular, enterovirus 71 infection has been
associated with fatal outcomes.

The diagnosis of HFMD is usually made on clinical grounds. Confirmation is possible via isolating the virus from the vesicles,
nasopharyngeal secretions, cerebrospinal fluid, blood or biopsy materials. Therapy is primarily supportive. Children are
particularly infectious until the blisters have disappeared. Exclusion from school or childcare is not practical, as the virus may
be present in the feces for several weeks.

Acute Generalized Exanthematous Pustulosis

Acute generalized exanthematous pustulosis (AGEP) is an eruption characterized by the acute onset of fever and multiple
nonfollicular pinpoint sterile papulopustules, which overlie the generalized erythroderma (Figure 4). AGEP was first in the
literature in 1980, when Beylot et al. described pustular eruptions with the characteristics of acute onset after a bout of
infection and/or drug ingestion in patients without a history of psoriasis, evolution toward spontaneous healing after a single
attack, and existence of a marked dermal vasculitis in addition to nonfollicular subcorneal pustules on histologic
examination.[43] Roujeau et al. proposed the following criteria for the diagnosis of AGEP: the presence of numerous, small,
nonfollicular pustules arising on a widespread edematous erythema, fever exceeding 38°C, pathologic findings of subcorneal
and/or intraepithelial spongiform pustules, blood neutrophil count above 7000 per mm3 and acute course with spontaneous
resolution of the pustules in less than 15 days.[44] Although medications are often implicated in adult cases of AGEP, a small
series of pediatric patients suggested a viral trigger in 80% of affected patients.[45] Viral infections found to be associated
with AGEP include enterovirus,[44,46] adenovirus,[44] EBV,[44] CMV[44,47] and hepatitis B virus.[44] The diagnosis is made
clinically, and therapy is supportive. The differential diagnosis includes pustular psoriasis, miliaria pustulosa and folliculitis.
No definitive treatment exists, but it is important to recognize AGEP clinically and histologically and remove any potential
offending medications.

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Figure 4.

Sterile nonfollicular pustules with underlying erythema.

Papular Exanthems
Papular Acrodermatitis of Childhood

Papular acrodermatitis of childhood (PAC), also known as Gianotti–Crosti syndrome (GCS), is a unique cutaneous disorder

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characterized by the abrupt onset of an erythematous papular exanthem found on the extremities, buttocks and face (Figure
5). It is a relatively common dermatosis, seen worldwide, primarily affecting children between 2 and 6 years of age.

Figure 5.

Lichenoid monomorphic papules on the extensor upper extremity.

Papular acrodermatitis of childhood was first described by Gianotti in 1953, in a young child with a monomorphous
erythematous papular rash confined to the extensor surfaces of the arms and legs.[48] After finding hepatitis B surface

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antigen in the serum of affected children, it was believed that PAC was solely a manifestation of hepatitis B infection.[49]
However, subsequently, EBV has become recognized as the most common viral agent associated with GCS in the USA.[50]
However, many other viruses and infectious agents have been associated with PAC, and these include hepatitis A virus,
CMV, human herpesvirus, Coxsackie virus A16, B4 and B5, rotavirus, parvovirus B19, molluscum contagiosum (MC),
respiratory syncytial virus, mumps virus, and parainfluenza virus type 1 and 2.[48]

The pathogenesis of GCS is still unclear but probably reflects a recognizable reactive pattern in response to diverse
infectious stimuli. Clinically, PAC usually presents with symmetrical monomorphous papular or papulovesicular exanthem
over the cheeks, extensor aspects of the extremities and gluteal areas. Occasionally, the papules coalesce into larger
plaques and become hemorrhagic or form scales. The trunk, elbows and knees are usually spared; lesions typically fade
within 3–4 weeks.

The diagnosis is made clinically, and a recent study proposed clinical criteria for the diagnosis of PAC ().[51,52] The
differential diagnosis includes varicella, Henoch–Schönlein purpura, arthopod bites, scabies and MC. Treatment is usually
unnecessary as the disease is self-limiting.

Box 1. Proposed diagnostic criteria for papular acrodermatitis of childhood.

Positive clinical features

Monomorphous, flat-topped, pink-brown papules or papulovesicles 1–10 mm in diameter on at least three of

the following four sites: cheeks, buttocks, extensor surfaces of the forearms, and extensor surfaces of the legs

Symmetrical distribution

Duration of at least 10 days

Negative clinical features

Extensive truncal lesions

Scaly lesions

Data taken from [52].

Molluscum Contagiosum

Molluscum contagiosum is a highly contagious viral infection of the mucous membranes and skin, commonly seen in
children. It is caused by a poxvirus of the genus Molluscipoxvirus. It usually presents as pearly umbilicated skin-colored
dome-shaped papules, which usually range from 2 to 8 mm in size (Figure 6). In approximately 30% of patients, an
eczematous reaction may encircle lesions.[53] Patients with immunodeficiency, including AIDS and leukemia, may be more
likely to develop extensive disease.[54] MC is transmitted by close physical contact, fomites and autoinoculation. Shared
bathtubs, pools and towels may facilitate spread of the MC virus.

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Figure 6.

Pearly umbilicated skin-colored dome-shaped papules over the posterior leg.

The diagnosis is made clinically, but Wright or Giemsa staining of cells expressed from the central core of lesions will reveal
characteristic intracytoplasmic inclusions. A Tzanck stain can also be done to highlight the typical pattern of numerous
discrete ovoid intracytoplasmic inclusion bodies, known as molluscum bodies.

The differential diagnosis includes juvenile xanthogranuloma, verruca plana, milia and papular urticaria. Lesions usually

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resolve spontaneously, but this process may take years, with more prolonged illness in the immunocompromised patient.
Reasons for actively treating MC may include alleviating discomfort and itching, limitating spread to other areas and people,
preventing scarring and superinfection, and eliminating the social stigma of visible lesions. No single intervention has been
shown to be convincingly effective in the treatment of MC.[55] Treatment options include destructive, immune-enhancing or
antiviral modalities.

Gentle local destruction is the typical approach for treating MC, and cantharidin is a safe and effective therapy for MC in
children; it is extremely effective and well tolerated, with high parental satisfaction if used in experienced hands.[53] Benefits
include painless application and high efficacy rates of up to 90%.[54] Other destructive therapies include curettage, liquid-
nitrogen cryotherapy and peeling agents, such as lactic acid or topical retinoids. Immune-enhancing agents speed up the
immune clearance of MC infection, and these include topical imiquimod, oral cimetidine and intralesional Candida
antigen.[56] Antivirals, such as cidofovir, have been used in pediatric patients with HIV-1 for the treatment of disseminated
MC recalcitrant to conventional therapy.[57,58]

Other Viral Exanthems

Papular Purpuric Glove & Socks Syndrome & Parvovirus-induced Petechial Syndromes

Papular purpuric glove and socks syndrome (PPGSS) is a distinctive exanthem, which is usually caused by parovovirus B19.
While other viruses, such as CMV, EBV, measles and HHV-6, have also been considered as causative agents for
PPGSS,[59] most studies employing seroconversion, viral DNA detection and immunohistochemistry still strongly support
parvovirus B19 as the main etiologic agent of PPGSS.[60]

In 1990, Harms et al. first described PPGSS.[61] Clinically, it is characterized by symmetric, painful erythema, and edema of
the hands and feet that later progresses to a petechial rash. Edema and erythema can be observed on the buccal and
genital mucosa, and on the inner aspect of the thighs (Figure 7). Unlike EI, patients with PPGSS are contagious when they
exhibit the exanthem.

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Figure 7.

Petechiae coalescing into purpura over the upper thighs.

Other distinctive localized forms of parvovirus-related petechiae and purpura have been described, and given names such
as 'bathing suit' and 'acropetechial' syndrome.[60,62,63] Parvovirus B19 has been described recently to cause generalized
petechiae.[64–66] The differential diagnosis includes allergic contact dermatitis, rickettsial infections and Kawasaki disease.
Treatment is symptomatic, and diagnosis can be made clinically or serologically.

Pityriasis Rosea

Pityriasis rosea is an acute self-limiting and distinctive exanthem, characterized by oval erythematous-squamous lesions of
the trunk and limbs, which usually spares the face, scalp, palms and soles. It is thought to be virally induced because of
features such as an associated prodromal symptoms and seasonal clustering of cases. Pityriasis rosea derives its name
from pityriasis meaning bran-like, and rosea meaning pink. It has been linked to HHV-6 and HHV-7,[67–69] but this
association has been disputed.[70,71]

Classically, pityriasis rosea begins as an erythematous, scaly patch on the trunk, known as a herald patch. This large lesion
is commonly 2–10 cm in diameter, ovoid, erythematous and slightly raised, with a typical collarette of scale at the margin. At
times, the herald patch may be absent or overlooked. In one series, only 17% of patients referred to a dermatology clinic
reported a herald patch.[72] Days to weeks later, numerous smaller scaly papulosquamous plaques develop on the trunk

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along the lines of skin cleavage with a collarette of scale (Figure 8). The plaques usually spare the face, scalp and distal
extremities.

Figure 8.

Pink papulosquamous plaques with a collarette of scale over the trunk.

In children, pityriasis rosea may affect the face and extremities other than the trunk, and this is referred to as inverse
pityriasis rosea. In particular, dark-skinned children seem to have more frequent facial and scalp involvement.[67] In addition,
vesicular, pustular, urticarial and hemorrhagic variants have also been described.[67] The differential diagnosis includes tinea
corporis, guttate psoriasis, pityriasis lichenoides and syphilis.

The rash of pityriasis rosea typically lasts approximately 5 weeks, and resolves by 8 weeks in more than 80% of patients.[73]
Clearance usually occurs within 6 weeks, and lesions may fade with residual hypopigmetation. Diagnosing pityriasis rosea is
nearly always made by history and physical examination alone. In certain atypical cases, a skin biopsy may prove useful in
differentiating pityriasis rosea from other exanthems.

Although some studies have shown improvement with systemic erythromycin and systemic ACV,[74,75] treatment is generally
supportive. There is some evidence for narrow-band ultraviolet-B phototherapy.[76,77] Topical steroids may be used for
associated pruritus.[78]

Erythema Multiforme

Erythema multiforme (EM) is a relatively uncommon disorder, characterized by the abrupt onset of multiple target skin
lesions. It is frequently recurrent, and some individuals have monthly episodes. HSV appears to be responsible for
precipitating most cases of EM episodes in children.[79,80] Other infectious agents and medication have also been
implicated.[81] The EM skin lesions characteristically occur 1–10 days after an episode of herpes labialis or genitalis, and

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appear as 'target' lesions, characterized by a central dusky zone surrounded by an inner ring of pale edema, and an outer
ring of erythema. The central area may also be vesicular. The eruption is symmetric and is often seen over the hands and
feet. The individual lesions may remain fixed for approximately 1 week, and the entire episode may last for 2–3 weeks. The
differential diagnosis includes annular urticaria, acute hemorrhagic edema of infancy, urticarial vasculitis and Stevens–
Johnson syndrome. The diagnosis can usually be made clinically, and patients are treated symptomatically. Childhood
HSV-associated EM may be unresponsive to treatment with oral steroids or oral or topical ACV. Frequent recurrences of EM
may be treated with prophylactic ACV.[82]

Unilateral Laterothoracic Exanthem

Unilateral laterothoracic exanthem (ULTE) is an eruption that begins unilaterally in the axillae or groin, and spreads
centrifugally (Figure 9). It has a prolonged course and usually resolves within 4–6 weeks. ULTE was first described as a new
clinical entity by Bodemer and de Prost in 1992,[83] but, in the past has been described under different names from as early
as 1962.[84,85] In the literature, ULTE has other designations, such as asymmetric periflexural exanthem and unilateral
mediothoracic exanthem.[86,87]

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Figure 9.

Erythematous papules over the left axillae and upper left trunk.

Clinically, ULTE is usually preceded by an upper respiratory or gastrointestinal prodrome, and is characterized by a unilateral
and localized exanthem, often in the axillary region (Figure 9), which spreads in a centrifugal pattern, sometimes reaching
the contralateral side. The mucous membranes, face, palms and soles are generally spared.

The etiology is unknown, but the frequent early age of onset, the seasonal pattern, the associated prodrome, the lack of

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response to systemic antibiotics and the possibility of familial cases suggest an infectious cause. Infectious agents linked
with the eruption of ULTE include parainfluenza 2 and 3, adenovirus,[88] parvovirus B19,[89] and HHV-6 and -7.[90] Recently,
primary EBV infection has been linked with ULTE.[90,91] ULTE probably represents a distinct cutaneous reaction to several
infectious agents.

The eruption usually lasts 4–6 weeks, although some cases can persist for more than 8 weeks.[88,92] The differential
diagnosis includes pityriasis rosea, papular acrodermatitis of childhood and allergic contact dermatitis. The diagnosis is
made clinically and treatment is supportive.

Nonspecific Viral Exanthem

A number of viruses can cause an exanthem associated with an upper respiratory or gastrointestinal infection. These include
the nonpolio enteroviruses in the summer months, and rhinovirus, adenovirus, parainfluenza virus, respiratory syncytial virus
and influenza virus in the winter.[93] The exanthem usually consists of erythematous macules and papules, but may be
urticarial.[94,95]

Conclusion & Future Perspective

Our understanding of certain viral exanthems has expanded significantly since the original description of the classic
exanthems of childhood. Many viral diseases, such as measles, rubella and varicella, are now preventable with vaccination.
However, our understanding and recognition of new viral-associated exanthems continues to expand. In the case of papular
acrodermatitis of childhood, what was once thought to be a manifestation of hepatitis B is now recognized to be a
manifestation of a number of infectious agents, including viruses. In the case of acute generalized exanthematous
pustulosis, what was once thought to be a drug-induced exanthem is now recognized to have viral triggers. In the case of
parvovirus B19, the ability to detect the virus in seronegative patients using PCR has been useful in linking the virus to
erythema infectiousum, as well as other manifestations, such as PPGSS and generalized petechiae.

There are still cases of exanthematous disease where the roles of viruses have yet to be fully elucidated. These include the
association of HHV-6 and -7 reactivation in drug hypersensitivity syndrome, the role of viral triggers in Kawasaki syndrome
and the role of viruses in dermatological conditions with seasonal clustering, such as lichen striatus. Improving laboratory
testing in combination with continual clinical sleuthing may provide clues to the role of viruses in these and other
exathematous disease in childhood.

Sidebar
Executive Summary

Macular & maculopapular exanthems

Measles, rubella, erythema infectiousum and roseola infantum are part of the six classic childhood exanthems, and
have very distinct and recognizable features.

The eruption when aminopenicillins are administered to patients with Epstein–Barr virus is a bright-red morbilliform
eruption that does not preclude future use of aminopenicillins.

Vesicular & pustular exanthems

Varicella infection is benign and self-limiting, but has the potential to cause life- and limb-threatening complications in
immunocompetent and immunocompromised hosts. The varicella vaccine is now available in combination with the
measles–mumps–rubella vaccine.

Eczema herpeticum is a severe form of disseminated cutaneous herpes simplex virus infection that morphologically
presents as monomorphic umbilicated vesiclulopustules, which progress to form punched-out erosions.

Hand–foot–mouth disease is a distinct monomorphous exanthem that is most commonly caused by the Coxsackie
A16 virus and human enterovirus 71. Meningoencephalitis and myocarditis are rare complications, which occur more

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commonly with human enterovirus 71.

Although acute generalized exanthematous pustulosis usually occurs following drug ingestion, cases in children may
be caused by viral infections.

Papular exanthems

Papular acrodermatitis of childhood is characterized by the abrupt onset of erythematous papules over the
extremities, buttocks and face, with relative sparing of the abdomen and chest. It appears to occur as a response to a
number of infectious stimuli.

Therapy for molluscum contagiosum ranges from destructive techniques to observation, as lesions will eventually
resolve spontaneously.

Other viral exanthems

Parovovirus B19 has been linked recently to several petechial and purpuric exanthems, which may be localized to
particular areas of the body. Recently, it has also been implicated in outbreaks of generalized petechiae.

Pityriasis rosea in children may present atypically by involving the face and extremities.

Erythema multiforme is often triggered by herpes simplex virus in children.

Unilateral laterothoracic exanthem is a distinct exanthem, which preferentially affects one side of the body, with a
prolonged clinical course.

References

1. Fölster-Holst R, Kreth HW: Viral exanthems in childhood – infectious (direct) exanthems. Part 2: other viral
exanthems. J. Dtsch Dermatol. Ges. 7(5), 414–419 (2009).
•• Excellent review on various viral exanthems.

2. Fölster-Holst R, Kreth HW: Viral exanthems in childhood – infectious (direct) exanthems. Part 1: classic exanthems.
J. Dtsch Dermatol. Ges. 7(4), 309–316 (2009).
•• Excellent review on various viral exanthems.

3. Goodyear HM, Laidler PW, Price EH et al.: Acute infectious erythemas in children: a clinico–microbiological study. Br.
J. Dermatol. 124(5), 433–438 (1991).

4. Rall GF: Measles virus 1998–2002: progress and controversy. Annu. Rev. Microbiol. 57, 343–367 (2003).
•• Good review that discusses recent advances in the understanding of the measles virus, including measles receptor
usage, the cellular basis of immunosuppression, the role of measles in 'nonviral' diseases and the controversy
surrounding measles vaccine safety.

5. Gutierrez J, Issacson RS, Koppel BS: Subacute sclerosing panencephalitis: an update. Dev. Med. Child Neurol. DOI:
10.1111/j.1469-8749.2010.03717.x (2010) (Epub ahead of print).

6. Reuter D, Schneider-Schaulies J: Measles virus infection of the CNS: human disease, animal models, and
approaches to therapy. Med. Microbiol. Immunol. 99(3), 261–271 (2010).

7. Siegfried N, Wiysonge CS, Pienaar D: Too little, too late: measles epidemic in South Africa. Lancet 376(9736), 160
(2010).

8. Orlikova H, Rogalska J, Kazanowska-Zielinska E et al.: Spotlight on measles 2010: a measles outbreak in a Roma
population in Pulawy, eastern Poland, June to August 2009. Euro. Surveill. 15(17), 19550(2010).

18 of 23 7/21/2015 6:34 AM
 http://www.medscape.com/viewarticle/734882_print

9. Roggendorf H, Mankertz A, Kundt R et al.: Spotlight on measles 2010: measles outbreak in a mainly unvaccinated
community in Essen, Germany, March–June 2010. Euro Surveill. 15(26), 19605(2010).

10. Chatterjee A, O'Keefe C: Current controversies in the USA regarding vaccine safety. Expert Rev. Vaccines 9(5),
497–450 (2010).

11. Morice A, Ulloa-Gutierrez R, Avila-Agüero ML: Congenital rubella syndrome: progress and future challenges. Expert
Rev. Vaccines 8(3), 323–331 (2009)

12. Vafaie J, Schwartz RA: Parvovirus B19 infections. Int. J. Dermatol. 43(10), 747–749 (2004).

13. Katta R: Parvovirus B19: a review. Dermatol. Clin. 20, 1–13 (2002)

14. Dobec M, Kaeppeli F, Cassinotti P et al.: Persistent parvovirus B19 infection and arthralgia in a patient mistakenly
treated for Lyme disease. J. Clin. Virol. 43(2), 226–229 (2008).

15. Modrof J, Berting A, Tille B et al.: Neutralization of human parvovirus B19 by plasma and intravenous
immunoglobulins. Transfusion 48(1), 178–186 (2008).

16. Cao YH, Zhang GY, Zhang GC: Successful treatment with high-dose intravenous immunoglobulin for parvovirus B19
infection associated with acute fulminant hepatitis in a chinese child. Clin. Pediatr. (Phila.) 48(6), 674–676 (2009).

17. Young NS: Parvovirus infection and its treatment. Clin. Exp. Immunol. 104(Suppl. 1), 26–30 (1996).

18. Abuhammour W, Abdel-Haq N, Asmar B: Petechial eruption with parvovirus B19 infection. Arch. Pediatr. Adolesc.
Med. 153, 87–88 (1999).

19. Caselli E, Di Luca D: Molecular biology and clinical associations of roseoloviruses human herpesvirus 6 and human
herpesvirus 7. New Microbiol. 30(3), 173–187 (2007).

20. Zerr DM, Maier AS, Selke SS et al.: A population-based study of primary human herpesvirus 6 infection. N. Engl. J.
Med. 352, 768–776. (2005).
• Nice large series on human herpesvirus-6 in humans, and sheds light on the prevalence of human herpesvirus-6.

21. Prober C: Sixth disease and the ubiquity of human herpesviruses. N. Engl. J. Med. 352(8), 753–755 (2005).

22. Ward KN: The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the
immunocompetent. J. Clin. Virol. 32(3), 183–193 (2005).

23. Hall CB, Long CE, Schnabel KC et al.: Human herpesvirus-6 infection in children. A prospective study of
complications and reactivation. N. Engl. J. Med. 331(7), 432–438 (1994).

24. Millichap JG, Millichap JJ: Role of viral infections in the etiology of febrile seizures. Pediatr. Neurol. 35(3), 165–172
(2006).

25. Jenson HB: Acute complications of Epstein–Barr virus infectious mononucleosis. Curr. Opin. Pediatr. 12(3), 263–268
(2000).

26. Pullen H, Wright N, Murdoch JM: Hypersensitivity reactions to antibacterial drugs in infectious mononucleosis. Lancet
2, 1176–1178 (1967).

27. Patel BM: Skin rash with infectious mononucleosis and ampicillin. Pediatrics 40, 910–911 (1967).

28. Hurt C, Tammaro D: Diagnostic evaluation of mononucleosis-like illnesses. Am. J. Med. 120(10), 911.e1–911e8
(2007).

19 of 23 7/21/2015 6:34 AM
 http://www.medscape.com/viewarticle/734882_print

29. Asano Y: Clinicopathologic understanding and control of varicella-zoster virus infection. Vaccine 26(50), 6487–6490
(2008).

30. Schleiss MR: Persistent and recurring viral infections: the human herpesviruses. Curr. Probl. Pediatr. Adolesc. Health
Care 39(1), 7–23 (2009).

31. Miller HC, Stephan M: Hemorrhagic varicella: a case report and review of the complications of varicella in children.
Am. J. Emerg. Med. 11(6), 633–638 (1993).

32. Dunkel L, Arvin A, Whitley R et al.: A controlled trial of oral acyclovir for chickenpox in normal children. N. Engl. J.
Med. 325, 1539–1544 (1991)

33. Arvin AM: Antiviral therapy for varicella and herpes zoster. Semin. Pediatr. Infect. Dis. 13, 12–21 (2002).

34. Gershon AA, Katz AL: Perspective on live varicella vaccine. J. Infect. Dis. 197(Suppl. 2), S242–S245 (2008).

35. Guris D, Jumaan AO, Mascola L et al.: Changing varicella epidemiology in active surveillance sites: United States,
1995–2005. J. Infect. Dis. 197, S71–S75 (2008).

36. Marin M, Güris D, Chaves SS et al.: Prevention of varicella: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm. Rep. 56(RR-4), 1–40 (2007).

37. Zareba G: A new combination vaccine for measles, mumps, rubella and varicella. Drugs Today (Barc.) 42(5),
321–329 (2006).

38. Gershon A: Varicella-zoster virus infections. Pediatr. Rev. 29, 5–11 (2008)

39. Schmid DS, Rouse BT: The role of T cell immunity in control of herpes simplex virus. Curr. Top. Microbiol. Immunol.
179, 57–74 (1992).

40. Wollenberg A, Wetzel S, Burgdorf W et al.: Viral infections in atopic dermatitis: pathogenic aspects and clinical
management. J. Allergy Clin. Immunol. 112, 667–674 (2003).

41. Wong SS, Yip CC, Lau SK: Human enterovirus 71 and hand, foot and mouth disease. Epidemiol. Infect. 138(8),
1071–1089 (2010).
• Interesting report that demonstrates the complications of hand–foot–mouth disease caused by human enterovirus
71 in Asia.

42. Chong CY, Chan KP, Shah VA et al.: Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal
cases. Acta Paediatrica 92, 1163–1169 (2003).

43. Beylot C, Bioulac P, Doutre MS: Pustuloses exanthematiques aigues generalisees. A propos de 4 cas. Ann.
Dermatol. Venereol. 107, 37–48 (1980).

44. Roujeau JC, Bioulac-Sage P, Bourseau C et al.: Acute generalized exanthematous pustulosis. Analysis of 63 cases.
Arch. Dermatol. 127, 1333–1338 (1991).

45. Ersoy S, Paller AS, Mancini AJ: Acute generalized exanthematous pustulosis in children. Arch. Dermatol. 140(9),
1172–1173 (2004).
• Quite interesting in that it highlights cases of acute generalized exanthematous pustulosis in children that are not
caused by medication use.

46. Feio AB, Apetato M, Costa MM et al.: Acute generalized exanthematous pustulosis due to Coxsackie B4 virus. Acta
Med. Port. 10, 487–491 (1997).

47. Haro-Gabaldon V, Sanchez-Sanchez-Vizcaino J, Ruiz-Avila P et al.: Acute generalized exanthematous pustulosis

20 of 23 7/21/2015 6:34 AM
 http://www.medscape.com/viewarticle/734882_print

with cytomegalovirus infection. Int. J. Dermatol. 35, 735 737 (1996).

48. Brandt O, Abeck D, Gianotti R et al.: Gianotti–Crosti syndrome. J. Am. Acad. Dermatol. 54(1), 136–145 (2006).
•• Very comprehensive review on Gianotti–Crosti symdrome (papular acrodermatitis of childhood).

49. Gianotti F: Papular acrodermatitis of childhood and other papulo-vesicular acro-located syndromes. Br. J. Dermatol.
100(1), 49–59 (1979).

50. Hofmann B, Schuppe HC, Adams O et al.: Gianotti–Crosti syndrome associated with Epstein–Barr virus infection.
Pediatr. Dermatol. 14, 273–227 (1997).

51. Chuh AA: Diagnostic criteria for Gianotti–Crosti syndrome: a prospective case–control study for validity assessment.
Cutis 68(3), 207–201 (2001).
• Interesting attempt to develop diagnostic criteria for papular acrodermatitis of childhood.

52. Chuh A, Lee A, Zawar V: The diagnostic criteria of Gianotti–Crosti syndrome: are they applicable to children in India?
Pediatr. Dermatol. 21(5), 542–527 (2004).

53. Silverberg NB, Sidbury R, Mancini AJ: Childhood molluscum contagiosum: experience with cantharidin therapy in 300
patients. J. Am. Acad. Dermatol. 43, 503–507 (2000).

54. Brown J, Janniger CK, Schwartz RA et al.: Childhood molluscum contagiosum. Int. J. Dermatol. 45(2), 93–99 (2006).

55. van der Wouden JC, van der Sande R, van Suijlekom-Smit LW et al.: Interventions for cutaneous molluscum
contagiosum. Cochrane Database Syst. Rev. 4, CD004767 (2009).

56. Maronn M, Salm C, Lyon V et al.: One-year experience with candida antigen immunotherapy for warts and
molluscum. Pediatr. Dermatol. 25(2), 189–192 (2008).

57. Toro JR, Wood LV, Patel NK et al.: Topical cidofovir: a novel treatment for recalcitrant molluscum contagiosum in
children infected with human immunodeficiency virus 1. Arch. Dermatol. 136(8), 983–985 (2000).

58. Ibarra V, Blanco JR, Oteo JA et al.: Efficacy of cidofovir in the treatment of recalcitrant molluscum contagiosum in an
AIDS patient. Acta Derm. Venereol. 80(4), 315–316 (2000).

59. Hsieh MY, Huang PH: The juvenile variant of popular purpuric gloves and socks syndrome and its association with
viral infections. Br. J. Dermatol. 151, 201–220 (2004).
• Recognizing this manifestation of parovirus B19 helps explain well-appearing children who present with generalized
petechaie.

60. Huerta-Brogeras M, Avilés Izquierdo JA, Hernanz Hermosa JM et al.: Petechial exanthem in "bathing trunk"
distribution caused by parvovirus B19 infection. Pediatr. Dermatol. 22(5), 430–433 (2005).

61. Harms M, Feldmann R, Saurat JH: Papular-purpuric "gloves and socks" syndrome. J. Am. Acad. Dermatol. 23,
850–854 (1990).

62. Butler GJ, Mendelsohn S, Franks A: Parvovirus B19 infection presenting as 'bathing trunk' erythema with pustules.
Australas J. Dermatol. 47(4), 286–288 (2006).

63. Harel L, Straussberg I, Zeharia A et al.: Papular purpuric rash due to parvovirus B19 with distribution on the distal
extremities and the face. Clin. Infect. Dis. 35(12), 1558–1561 (2002).

64. McNeely M, Friedman J, Pope E: Generalized petechial eruption induced by parvovirus B19 infection. J. Am. Acad.
Dermatol. 52(5 Suppl. 1), S109–S113 (2005).

65. Foti C, Bonamonte D, Conserva A et al.: Erythema infectiosum following generalized petechial eruption induced by

21 of 23 7/21/2015 6:34 AM
 http://www.medscape.com/viewarticle/734882_print

human parvovirus B19. New Microbiol. 29(1), 45–48 (2006).

• Recognizing parovirus B19 as a cause of generalized petechiae helps explain.

66. Edmonson MB, Riedesel EL, Williams GP et al.: Generalized petechial rashes in children during a parvovirus B19
outbreak. Pediatrics 125(4), e787–e792 (2010).

67. Drago F, Broccolo F, Rebora A: Pityriasis rosea: an update with a critical appraisal of its possible herpesviral etiology.
J. Am. Acad. Dermatol. 61(2), 303–318 (2009).
• Comprensive review on pityriasis rosea.

68. Drago F, Rebora A: Pityriasis rosea: one virus, two viruses, more viruses? Br. J. Dermatol. 144(5), 1090 (2001).

69. Drago F, Ranieri E, Malaguti F et al.: Human herpesvirus 7 in pityriasis rosea. Lancet 349(9062), 1367–1368 (1997).

70. Kempf W, Adams V, Kleinhans M et al.: Pityriasis rosea is not associated with human herpesvirus 7. Arch. Dermatol.
135(9), 1070–1072 (1999).

71. Kosuge H, Tanaka-Taya K, Miyoshi H et al.: Epidemiological study of human herpesvirus-6 and human herpesvirus-7
in pityriasis rosea. Br. J. Dermatol. 143(4), 795–798 (2000).

72. Tay YK, Goh CL: One-year review of pityriasis rosea at the National Skin Centre, Singapore. Ann. Acad. Med.
Singapore 28(6), 829–831 (1999)

73. Drago F, Vecchio F, Rebora A: Use of high-dose acyclovir in pityriasis rosea. J. Am. Acad. Dermatol. 54, 82–85
(2006).

74. Sharma PK, Yadav TP, Gautam RK et al.: Erythromycin in pityriasis rosea: a double-blind, placebo-controlled clinical
trial. J. Am. Acad. Dermatol. 42(2 Pt 1), 241–244 (2000).

75. Stulberg DL, Wolfrey J: Pityriasis rosea. Am. Fam. Physician 69(1), 87–91 (2004).

76. Leenutaphong V, Jiamton S: UVB phototherapy for pityriasis rosea: a bilateral comparison study. J. Am. Acad.
Dermatol. 33, 996–999 (1995).

77. Valkova S, Trashlieva M, Christova P: UVB phototherapy for pityriasis rosea. J. Eur. Acad. Dermatol. Venereol. 18(1),
111–112 (2004).

78. Browning JC: An update on pityriasis rosea and other similar childhood exanthems. Curr. Opin. Pediatr. 21(4),
481–485 (2009).

79. Brice SL, Krzemien D, Weston WL et al.: Detection of herpes simplex virus DNA in cutaneous lesions of erythema
multiforme. J. Invest. Dermatol. 93, 183–197 (1989).

80. Weston WL, Stockert SS, Jester JD et al.: Herpes simplex virus in childhood erythema multiforme. Pediatrics 89,
32–34 (1992).

81. Brice SL, Huff JC, Weston WL: Erythema multiforme minor in children. Pediatrician 18(3), 188–194 (1991).

82. Weston WL, Morelli JG: Herpes simplex virus-associated erythema multiforme in prepubertal children. Arch. Pediatr.
Adolesc. Med. 151(10), 1014–1016 (1997).

83. Bodemer C, de Prost Y: Unilateral laterothoracic exanthema in children: a new disease? J. Am. Acad. Dermatol. 27,
693–696 (1992).

84. Brunner MJ, Rubin L, Dunlap F: A new papular erythema of childhood. Arch. Dermatol. 85, 539–540 (1962).

22 of 23 7/21/2015 6:34 AM
 http://www.medscape.com/viewarticle/734882_print

85. Taieb A, Megraud F, LeRoy JM et al.: Erythème localisé avec adénopathie régionale de l'enfant: une maladie
d'inoculation? Ann. Dermatol. Venereol. 113, 1023–1024 (1986).

86. Taieb A, Mégraud F, Legrain V et al.: Asymmetric periflexural exanthem of childhood. J. Am. Acad. Dermatol. 29,
391–393 (1993).

87. Chuh AA, Chan HH: Unilateral mediothoracic exanthem: a variant of unilateral laterothoracic exanthema. Cutis 77,
29–32 (2006).

88. Harangi F, Várszegi D, Szücs G: Asymmetric periflexural exanthem of childhood and viral examinations. Pediatr.
Dermatol. 12, 112–115 (1995).

89. Pauluzzi P, Festini G, Gelmetti C: Asymmetric periflexural exanthem of childhood in an adult patient with parvovirus
B19. J. Eur. Acad. Dermatol. Venereol. 15, 372–374 (2001).

90. Duarte AF, Cruz MJ, Baudrier T et al.: Unilateral laterothoracic exanthem and primary Epstein–Barr virus infection:
case report. Pediatr. Infect. Dis. J. 28(6), 549–550 (2009).

91. Scheinfeld N: Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr virus reactivation:
exploration of a possible link. Dermatol. Online J. 13(3), 13 (2007).

92. Laur WE: Unilateral laterothoracic exanthema in children. J. Am. Acad. Dermatol. 29, 799–780 (1993).

93. Fölster-Holst R, Kreth HW: Viral exanthems in childhood. Part 3: parainfectious exanthems and those associated with
virus–drug interactions. J. Dtsch Dermatol. Ges. 7(6), 506–510 (2009).

94. Mancini AJ: Childhood exanthems: a primer and update for the dermatologist. Adv. Dermatol. 16, 3–37 (2000).

95. Mortureux P, Léauté-Labrèze C, Legrain-Lifermann V et al.: Acute urticaria in infancy and early childhood: a
prospective study. Arch. Dermatol. 134(3), 319–323 (1998).

Papers of special note have been highlighted as:

• of interest
•• of considerable interest

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies,
honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Pediatr Health. 2010;4(6):623-635. © 2010 Future Medicine Ltd.

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