3. eksantem (hal.1)

8/28/14, 7:50 PM

Page 1 of 23http://www.medscape.com/viewarticle/734882_print

www.medscape.com

Abstract and IntroductionAbstract

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

Introduction

An exanthem is any eruptive skin rash that may be associated with fever or other systemic symptoms. Causes includeinfectious 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 childhooderuption, formerly referred to as Dukes' disease, is controversial. It may represent misdiagnosed cases of rubella orscarlet fever, rather than a distinct illness.

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

Macular & Maculopapular ExanthemsMeasles

Measles is caused by a ssRNA virus belonging to the Paramyxoviridae family, genus Morbillivirus. It has an incubationperiod of approximately 1012 days, and clinical disease begins with symptoms of fever, conjunctivitis, rhinorrhea,sore throat and a dry cough. Koplik spots (graywhite papules on the buccal mucosa) may be seen during thisprodromal phase. Approximately 34 days after the prodromal symptoms, the typical exanthem of coalescingerythematous macules and papules erupts, beginning behind the ears and in the hairline area, and spreads over therest of the skin over a period of a few days. The eruption typically resolves in the same order as its appearance, andwill 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, acutepostinfectious encephalitis and subacute sclerosing panencephalitis (SSPE). Transient immunosuppression occursduring the illness and lasts for approximately 6 weeks.[1] During this time, an infected individual is at risk for secondary

Characterizing Viral ExanthemsJoseph M LamPediatr Health. 2010;4(6):623-635.

8/28/14, 7:50 PM


bacterial infections, such as otitis media, pneumonia or gastroenteritis. Postinfectious encephalitis occurs inapproximately 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-knownentity, known as measles inclusion-body encephalitis, can affect immunocompromised patients from weeks to monthsafter acute infection.[5] SSPE affects approximately one in 100,000 patients, and manifests as a slow, progressivedisease, which can present months or even years after resolution of the acute infection. The onset of SSPE isinsidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stageof akinetic mutism. In total, 95% of individuals with SSPE die within 5 years of diagnosis.[6] SSPE is caused by apersistent 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 antibodiesand patients on immunoglobulin therapy.[1] In this modified form, the prodrome and exanthem are milder and of shorterduration. However, the disease is just as contagious in these individuals. Diagnosis is based on clinical presentationwith laboratory confirmation, if necessary. Measles IgM can usually be detectable after the first 3 days of theexanthem.

Currently, there is no specific antiviral therapy for measles and treatment is symptomatic. More importantly, thelongstanding availability of the measles vaccine makes the disease easily preventable. Despite, this, there is still pooruptake of the vaccine,[79] owing to, in part, a proposed causal relationship between receipt of the measlesmumpsrubella 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 infectedindividuals become symptomatic. After an incubation period of 23 weeks, symptomatic patients exhibit prodromalsymptoms, which include low-grade fever, headache, sore throat and myalgias. A macular or maculopapular exanthemappears after approximately 25 days and spreads in a cephalocaudal pattern. Symmetrical lymphadenopathy is oftenseen, and often occurs in the postauricular and occipital areas. Arthralgias and arthritis are also common. The mostserious 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 asmeasles, roseola, parvovirus B-19 infection and drug eruptions. The diagnosis of rubella can be made with IgMantibody 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 originalpositive serum sample was labeled (i.e., Row B, Sample 19).[12] It is the only parvovirus that has been linked directlyto disease in humans.[13] Although parovirus B19 infection can have different clinical manifestations (see later), EI isthe most commonly recognized.

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

8/28/14, 7:50 PM


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 cansuppress red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis orcongenital anemia. This is even more likely in patients with illnesses that have already shortened the lifespan oferythrocytes, such as iron-deficiency anemia, HIV, sickle cell disease, thalassemia and spherocytosis. Althoughtreatment 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 viralDNA 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 thesubfamily of Betaherpesvirinae.[19]

Both HHV-6 and -7 are highly prevalent in the healthy population, and establish latency in macrophages and Tlymphocytes. They are frequently shed in saliva of healthy donors, and the pathogenic potential of reactivated virusranges 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

8/28/14, 7:50 PM


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]

In roseola, after an incubation period of 515 days, infected children develop high fevers that last 35 days. This isfollowed by the acute onset of a rosey pink, nonpruritic macular rash, predominantly on the neck and trunk. Owing tothe 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 recoverwithout sequelae. However, approximately 22% of patients with roseola may develop febrile seizures.[24] Thedifferential 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 thelimited availability of antibody tests, problems with antigenic crossreaction and lack of understanding of the clinicalrelevance and epidemiology of these two viruses. However, the development of standardized quantitative real-timePCR, and the use of antibody tests based on recombinant proteins, may aid in the diagnosis of HHV-6 and -7 infectionin the future.[22]

EpsteinBarr Virus & Aminopenicillins

EpsteinBarr virus (EBV) is a member of the Herpesvirus family, belonging to the genus Lymphocryptovirus. Whileonly approximately 510% of children infected with EBV manifest an exanthem,[2] if amoxicillin or ampicillin isadministered, a characteristic bright-red morbilliform eruption almost always occurs.[2527] This eruption begins 59days after exposure to the medication, starting on the trunk before becoming generalized as confluent macules andpapules. The eruption most likely results from ampicillinantibody immune complexes as a consequence of polyclonalB-cell activation. This consistently occurs in adolescents and adults with infectious mononucleosis administeredampicillin, but resolves without specific measures. This reaction is not considered a 'true' drug allergy and, in mostchildren, re-exposure to the antibiotic after the EBV infection will not trigger a similar response. However, sinceantimicrobial therapy is not necessary for infectious mononucleosis, the antibiotic should be discontinued during theacute EBV infection.

Although approximately 7% of mononucleosis-like illnesses are caused by cytomegalovirus (CMV), CMV does notappear to give this drug-related exanthem.[28]

Vesicular & Pustular ExanthemsVaricella & 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 withvesicular lesions, infection of neuronal tissue and latent infection of dorsal root ganglia. Primary infection causesvaricella, after which, the virus becomes latent.

The transmission of VZV does not require skin-to-skin contact, and is more commonly transmitted by respiratorysecretions via an aerosol route.[29] When a susceptible individual is exposed to VZV, the virus initially undergoesprimary replication, beginning 34 days after exposure, and occurring in the oropharynx and regional lymph nodes.This is followed by a primary viremia. A secondary viremia occurs 1021 days after exposure and, during this timeperiod, patients manifest with prodromal symptoms of fever, malaise and myalgias. The exanthem begins soon after aserythematous pruritic macules, which develop into papules and fluid-filled vesicles, described as 'dewdrops on a rosepetal'. The lesions usually begin in the hairline and spread in a cephalocaudal pattern, involving the scalp and mucousmembranes. The vesicles crust over, typically within 45 days of the onset of the initial lesion. The average number oflesions is approximately 300400.[30]

Older lesions crust over as newer lesions form, and so giving a polymorphous appearance to the exanthem. Lesions

8/28/14, 7:50 PM


may heal with hypopigmentation and scarring. The differential diagnosis includes pityriasis lichenoides, arthropodbites, herpes simplex virus (HSV) infection and impetigo. The most common complication of varicella inimmunocompetent children is bacterial superinfection, usually due to group A Streptococcus or Staphylococcusaureus. Neurological complications can also occur, and these include meningitis, meningoencephalitis, cerebellarataxia, transverse myelitis and GuillainBarre syndrome. Other complications include arthritis, glomerulonephritis,myocarditis, thrombocytopenia and purpura fulminans. Immunocompromised patients are at risk for severe andprotracted varicella, multiorgan involvement and hemorrhagic varicella.[31]

The other common clinical manifestation of VZV infection is herpes zoster (shingles) (Figure 2). VZV becomes latent indorsal 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 orpruritic, especially in adults. Zoster generally is a milder disease in children than in adults. Reactivation is probably dueto declining cell-mediated immunity, which explains the increased incidence in the elderly and in immunocompromisedpatients.

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 fordeveloping severe illness, oral ACV should be administered for 5 days, ideally starting within 24 h of the developmentof a varicella rash.[32]

8/28/14, 7:50 PM


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 lesionshave appeared for 48 h.[33] Ideally, therapy should be started within 24 h of onset, but ACV can still be effective up to72 h after the appearance of the skin lesions.

Fever should be controlled with acetaminophen. The use of aspirin may predispose to Reye syndrome, and ibuprofenmay predispose to group A Streptococcus infection. The live-attenuated varicella vaccine has been useful indecreasing the incidence of VZV infection.[34,35] Zoster appears to be less of a problem after immunization than afternatural infection. To avoid breakthrough varicella, individuals should be vaccinated twice, once at an age of 1215months and again at 46 years.[36] The varicella vaccine has been combined with the measlesmumpsrubellavaccine, and was licensed by the US FDA in September 2005 for use in children 12 months through to 12 years ofage..[37]

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

Eczema Herpeticum

Eczema herpeticum (also known as HSV-associated Kaposi varicelliform eruption) is a severe form of disseminatedcutaneous HSV infection, which occurs primarily in individuals with atopic dermatitis and skin diseases, such aspemphigus, Darier disease or traumatic burns. Defective cytokine secretion and decreased cell-mediated immunity inskin 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 inareas of active dermatitis (Figure 3). The upper body is the most common site of infection, with a predilection for thehead 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 bacterialsuperinfection and keratoconjunctivitis. In some cases, it may progress to fulminating life-threatening infection, andmortality 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), afluorescent antibody smear or culture of a vesicular lesion. The treatment involves systemic ACV. More severeinvolvement may require hospitalization and the use of intravenous antivirals. In addition, it is recommended thattopical steroids and moisturizers be continued to repair the skin barrier.

HandFootMouth Disease

Handfootmouth disease (HFMD) is a distinct monomorphous exanthem caused by viruses of the Picornaviridaefamily 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 71appears to be responsible for recent epidemics of HFMD in the AsiaPacific region.[41]

8/28/14, 7:50 PM


The infection has a typical incubation period of 37 days. The main manifestations are fever, lymphadenopathy,followed by the appearance of 28-mm painful oval, gray vesicles on the palmar and plantar skin, buccal mucosa andtongue after 12 days. The vesicles are often arranged parallel to the dermatoglyphs, and may have a surrounding redhalo. Papular and vesicular lesions can also occur on other parts of the body, and the buttocks may often exhibit anonspecific eruption prior to the onset of the vesicular exanthem. The oral enanthem helps to distinguish HFMD fromother causes of childhood exanthems, although cases without oral lesions have been described. In the oral cavity, thehard palate, tongue and buccal mucosa are most commonly affected. The differential diagnosis includes aphthousstomatitis, varicella, HSV infection and herpangina.

Most HFMD cases are self-limiting, and only required supportive treatment. Rarely, there may be a neurological orcardiopulmonary complication, such as meningoencephalitis or myocarditis. Uncomplicated HFMD usually resolves in57 days. The casefatality rate for HFMD ranges from 0.06 to 0.11%.[42] In particular, enterovirus 71 infection hasbeen associated with fatal outcomes.

The diagnosis of HFMD is usually made on clinical grounds. Confirmation is possible via isolating the virus from thevesicles, 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 notpractical, 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 andmultiple nonfollicular pinpoint sterile papulopustules, which overlie the generalized erythroderma (Figure 4). AGEP wasfirst in the literature in 1980, when Beylot et al. described pustular eruptions with the characteristics of acute onsetafter a bout of infection and/or drug ingestion in patients without a history of psoriasis, evolution toward spontaneoushealing after a single attack, and existence of a marked dermal vasculitis in addition to nonfollicular subcornealpustules on histologic examination.[43] Roujeau et al. proposed the following criteria for the diagnosis of AGEP: thepresence of numerous, small, nonfollicular pustules arising on a widespread edematous erythema, fever exceeding38C, pathologic findings of subcorneal and/or intraepithelial spongiform pustules, blood neutrophil count above 7000per mm3 and acute course with spontaneous resolution of the pustules in less than 15 days.[44] Although medicationsare often implicated in adult cases of AGEP, a small series of pediatric patients suggested a viral trigger in 80% ofaffected 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 differentialdiagnosis includes pustular psoriasis, miliaria pustulosa and folliculitis. No definitive treatment exists, but it is importantto recognize AGEP clinically and histologically and remove any potential offending medications.

Figure 4.

Sterile nonfollicular pustules with underlying erythema.

Papular ExanthemsPapular Acrodermatitis of Childhood

Papular acrodermatitis of childhood (PAC), also known as GianottiCrosti syndrome (GCS), is a unique cutaneousdisorder characterized by the abrupt onset of an erythematous papular exanthem found on the extremities, buttocksand face (Figure 5). It is a relatively common dermatosis, seen worldwide, primarily affecting children between 2 and 6years of age.

8/28/14, 7:50 PM


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 monomorphouserythematous papular rash confined to the extensor surfaces of the arms and legs.[48] After finding hepatitis B surface

8/28/14, 7:50 PM


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 theUSA.[50] However, many other viruses and infectious agents have been associated with PAC, and these includehepatitis A virus, CMV, human herpesvirus, Coxsackie virus A16, B4 and B5, rotavirus, parvovirus B19, molluscumcontagiosum (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 diverseinfectious stimuli. Clinically, PAC usually presents with symmetrical monomorphous papular or papulovesicularexanthem over the cheeks, extensor aspects of the extremities and gluteal areas. Occasionally, the papules coalesceinto larger plaques and become hemorrhagic or form scales. The trunk, elbows and knees are usually spared; lesionstypically fade within 34 weeks.

The diagnosis is made clinically, and a recent study proposed clinical criteria for the diagnosis of PAC ().[51,52] Thedifferential diagnosis includes varicella, HenochSchnlein purpura, arthopod bites, scabies and MC. Treatment isusually 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 110 mm in diameter on at least three ofthe following four sites: cheeks, buttocks, extensor surfaces of the forearms, and extensor surfaces of thelegs

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 inchildren. 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% ofpatients, an eczematous reaction may encircle lesions.[53] Patients with immunodeficiency, including AIDS andleukemia, may be more likely to develop extensive disease.[54] MC is transmitted by close physical contact, fomitesand autoinoculation. Shared bathtubs, pools and towels may facilitate spread of the MC virus.

8/28/14, 7:50 PM


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 willreveal characteristic intracytoplasmic inclusions. A Tzanck stain can also be done to highlight the typical pattern of

8/28/14, 7:50 PM


numerous discrete ovoid intracytoplasmic inclusion bodies, known as molluscum bodies.

The differential diagnosis includes juvenile xanthogranuloma, verruca plana, milia and papular urticaria. Lesionsusually resolve spontaneously, but this process may take years, with more prolonged illness in theimmunocompromised 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 stigmaof 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 MCin 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 includecurettage, liquid-nitrogen cryotherapy and peeling agents, such as lactic acid or topical retinoids. Immune-enhancingagents speed up the immune clearance of MC infection, and these include topical imiquimod, oral cimetidine andintralesional Candida antigen.[56] Antivirals, such as cidofovir, have been used in pediatric patients with HIV-1 for thetreatment of disseminated MC recalcitrant to conventional therapy.[57,58]

Other Viral ExanthemsPapular Purpuric Glove & Socks Syndrome & Parvovirus-induced Petechial Syndromes

Papular purpuric glove and socks syndrome (PPGSS) is a distinctive exanthem, which is usually caused byparovovirus B19. While other viruses, such as CMV, EBV, measles and HHV-6, have also been considered ascausative agents for PPGSS,[59] most studies employing seroconversion, viral DNA detection andimmunohistochemistry 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, andedema of the hands and feet that later progresses to a petechial rash. Edema and erythema can be observed on thebuccal and genital mucosa, and on the inner aspect of the thighs (Figure 7). Unlike EI, patients with PPGSS arecontagious when they exhibit the exanthem.

8/28/14, 7:50 PM


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 namessuch as 'bathing suit' and 'acropetechial' syndrome.[60,62,63] Parvovirus B19 has been described recently to causegeneralized petechiae.[6466] The differential diagnosis includes allergic contact dermatitis, rickettsial infections andKawasaki 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-squamouslesions of the trunk and limbs, which usually spares the face, scalp, palms and soles. It is thought to be virally inducedbecause of features such as an associated prodromal symptoms and seasonal clustering of cases. Pityriasis roseaderives its name from pityriasis meaning bran-like, and rosea meaning pink. It has been linked to HHV-6 and HHV-7,[6769] 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 largelesion is commonly 210 cm in diameter, ovoid, erythematous and slightly raised, with a typical collarette of scale at

8/28/14, 7:50 PM


the margin. At times, the herald patch may be absent or overlooked. In one series, only 17% of patients referred to adermatology clinic reported a herald patch.[72] Days to weeks later, numerous smaller scaly papulosquamous plaquesdevelop on the trunk along the lines of skin cleavage with a collarette of scale (Figure 8). The plaques usually sparethe 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 inversepityriasis rosea. In particular, dark-skinned children seem to have more frequent facial and scalp involvement.[67] Inaddition, vesicular, pustular, urticarial and hemorrhagic variants have also been described.[67] The differentialdiagnosis 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% ofpatients.[73] Clearance usually occurs within 6 weeks, and lesions may fade with residual hypopigmetation. Diagnosingpityriasis rosea is nearly always made by history and physical examination alone. In certain atypical cases, a skinbiopsy 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 isgenerally supportive. There is some evidence for narrow-band ultraviolet-B phototherapy.[76,77] Topical steroids maybe used for associated pruritus.[78]

Erythema Multiforme

8/28/14, 7:50 PM


Erythema multiforme (EM) is a relatively uncommon disorder, characterized by the abrupt onset of multiple target skinlesions. It is frequently recurrent, and some individuals have monthly episodes. HSV appears to be responsible forprecipitating most cases of EM episodes in children.[79,80] Other infectious agents and medication have also beenimplicated.[81] The EM skin lesions characteristically occur 110 days after an episode of herpes labialis or genitalis,and appear as 'target' lesions, characterized by a central dusky zone surrounded by an inner ring of pale edema, andan outer ring of erythema. The central area may also be vesicular. The eruption is symmetric and is often seen overthe hands and feet. The individual lesions may remain fixed for approximately 1 week, and the entire episode may lastfor 23 weeks. The differential diagnosis includes annular urticaria, acute hemorrhagic edema of infancy, urticarialvasculitis and StevensJohnson syndrome. The diagnosis can usually be made clinically, and patients are treatedsymptomatically. Childhood HSV-associated EM may be unresponsive to treatment with oral steroids or oral or topicalACV. 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 spreadscentrifugally (Figure 9). It has a prolonged course and usually resolves within 46 weeks. ULTE was first described asa new clinical entity by Bodemer and de Prost in 1992,[83] but, in the past has been described under different namesfrom as early as 1962.[84,85] In the literature, ULTE has other designations, such as asymmetric periflexural exanthemand unilateral mediothoracic exanthem.[86,87]

8/28/14, 7:50 PM


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 aunilateral and localized exanthem, often in the axillary region (Figure 9), which spreads in a centrifugal pattern,

8/28/14, 7:50 PM


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 lackof response to systemic antibiotics and the possibility of familial cases suggest an infectious cause. Infectious agentslinked 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 cutaneousreaction to several infectious agents.

The eruption usually lasts 46 weeks, although some cases can persist for more than 8 weeks.[88,92] The differentialdiagnosis includes pityriasis rosea, papular acrodermatitis of childhood and allergic contact dermatitis. The diagnosis ismade clinically and treatment is supportive.

Nonspecific Viral Exanthem

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

Conclusion & Future Perspective

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

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

SidebarExecutive 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 EpsteinBarr virus is a bright-redmorbilliform 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-threateningcomplications in immunocompetent and immunocompromised hosts. The varicella vaccine is now available in

8/28/14, 7:50 PM


combination with the measlesmumpsrubella vaccine.

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

Handfootmouth disease is a distinct monomorphous exanthem that is most commonly caused by theCoxsackie A16 virus and human enterovirus 71. Meningoencephalitis and myocarditis are rare complications,which occur more commonly with human enterovirus 71.

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

Papular exanthems

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

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

Other viral exanthems

Parovovirus B19 has been linked recently to several petechial and purpuric exanthems, which may be localizedto 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, witha prolonged clinical course.

References

1. Flster-Holst R, Kreth HW: Viral exanthems in childhood infectious (direct) exanthems. Part 2: other viralexanthems. J. Dtsch Dermatol. Ges. 7(5), 414419 (2009).

Excellent review on various viral exanthems.

2. Flster-Holst R, Kreth HW: Viral exanthems in childhood infectious (direct) exanthems. Part 1: classicexanthems. J. Dtsch Dermatol. Ges. 7(4), 309316 (2009).

Excellent review on various viral exanthems.

3. Goodyear HM, Laidler PW, Price EH et al.: Acute infectious erythemas in children: a clinicomicrobiologicalstudy. Br. J. Dermatol. 124(5), 433438 (1991).

4. Rall GF: Measles virus 19982002: progress and controversy. Annu. Rev. Microbiol. 57, 343367 (2003).

Good review that discusses recent advances in the understanding of the measles virus, including measlesreceptor usage, the cellular basis of immunosuppression, the role of measles in 'nonviral' diseases and the

8/28/14, 7:50 PM


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, andapproaches to therapy. Med. Microbiol. Immunol. 99(3), 261271 (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 aRoma population in Pulawy, eastern Poland, June to August 2009. Euro. Surveill. 15(17), 19550(2010).

9. Roggendorf H, Mankertz A, Kundt R et al.: Spotlight on measles 2010: measles outbreak in a mainlyunvaccinated community in Essen, Germany, MarchJune 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),497450 (2010).

11. Morice A, Ulloa-Gutierrez R, Avila-Agero ML: Congenital rubella syndrome: progress and future challenges.Expert Rev. Vaccines 8(3), 323331 (2009)

12. Vafaie J, Schwartz RA: Parvovirus B19 infections. Int. J. Dermatol. 43(10), 747749 (2004).

13. Katta R: Parvovirus B19: a review. Dermatol. Clin. 20, 113 (2002)

14. Dobec M, Kaeppeli F, Cassinotti P et al.: Persistent parvovirus B19 infection and arthralgia in a patientmistakenly treated for Lyme disease. J. Clin. Virol. 43(2), 226229 (2008).

15. Modrof J, Berting A, Tille B et al.: Neutralization of human parvovirus B19 by plasma and intravenousimmunoglobulins. Transfusion 48(1), 178186 (2008).

16. Cao YH, Zhang GY, Zhang GC: Successful treatment with high-dose intravenous immunoglobulin for parvovirusB19 infection associated with acute fulminant hepatitis in a chinese child. Clin. Pediatr. (Phila.) 48(6), 674676(2009).

17. Young NS: Parvovirus infection and its treatment. Clin. Exp. Immunol. 104(Suppl. 1), 2630 (1996).

18. Abuhammour W, Abdel-Haq N, Asmar B: Petechial eruption with parvovirus B19 infection. Arch. Pediatr.Adolesc. Med. 153, 8788 (1999).

19. Caselli E, Di Luca D: Molecular biology and clinical associations of roseoloviruses human herpesvirus 6 andhuman herpesvirus 7. New Microbiol. 30(3), 173187 (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, 768776. (2005).

Nice large series on human herpesvirus-6 in humans, and sheds light on the prevalence of humanherpesvirus-6.

21. Prober C: Sixth disease and the ubiquity of human herpesviruses. N. Engl. J. Med. 352(8), 753755 (2005).

22. Ward KN: The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the

8/28/14, 7:50 PM


immunocompetent. J. Clin. Virol. 32(3), 183193 (2005).

23. Hall CB, Long CE, Schnabel KC et al.: Human herpesvirus-6 infection in children. A prospective study ofcomplications and reactivation. N. Engl. J. Med. 331(7), 432438 (1994).

24. Millichap JG, Millichap JJ: Role of viral infections in the etiology of febrile seizures. Pediatr. Neurol. 35(3), 165172 (2006).

25. Jenson HB: Acute complications of EpsteinBarr virus infectious mononucleosis. Curr. Opin. Pediatr. 12(3),263268 (2000).

26. Pullen H, Wright N, Murdoch JM: Hypersensitivity reactions to antibacterial drugs in infectious mononucleosis.Lancet 2, 11761178 (1967).

27. Patel BM: Skin rash with infectious mononucleosis and ampicillin. Pediatrics 40, 910911 (1967).

28. Hurt C, Tammaro D: Diagnostic evaluation of mononucleosis-like illnesses. Am. J. Med. 120(10), 911.e1911e8(2007).

29. Asano Y: Clinicopathologic understanding and control of varicella-zoster virus infection. Vaccine 26(50), 64876490 (2008).

30. Schleiss MR: Persistent and recurring viral infections: the human herpesviruses. Curr. Probl. Pediatr. Adolesc.Health Care 39(1), 723 (2009).

31. Miller HC, Stephan M: Hemorrhagic varicella: a case report and review of the complications of varicella inchildren. Am. J. Emerg. Med. 11(6), 633638 (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, 15391544 (1991)

33. Arvin AM: Antiviral therapy for varicella and herpes zoster. Semin. Pediatr. Infect. Dis. 13, 1221 (2002).

34. Gershon AA, Katz AL: Perspective on live varicella vaccine. J. Infect. Dis. 197(Suppl. 2), S242S245 (2008).

35. Guris D, Jumaan AO, Mascola L et al.: Changing varicella epidemiology in active surveillance sites: UnitedStates, 19952005. J. Infect. Dis. 197, S71S75 (2008).

36. Marin M, Gris D, Chaves SS et al.: Prevention of varicella: recommendations of the Advisory Committee onImmunization Practices (ACIP). MMWR Recomm. Rep. 56(RR-4), 140 (2007).

37. Zareba G: A new combination vaccine for measles, mumps, rubella and varicella. Drugs Today (Barc.) 42(5),321329 (2006).

38. Gershon A: Varicella-zoster virus infections. Pediatr. Rev. 29, 511 (2008)

39. Schmid DS, Rouse BT: The role of T cell immunity in control of herpes simplex virus. Curr. Top. Microbiol.Immunol. 179, 5774 (1992).

40. Wollenberg A, Wetzel S, Burgdorf W et al.: Viral infections in atopic dermatitis: pathogenic aspects and clinicalmanagement. J. Allergy Clin. Immunol. 112, 667674 (2003).

41. Wong SS, Yip CC, Lau SK: Human enterovirus 71 and hand, foot and mouth disease. Epidemiol. Infect. 138(8),10711089 (2010).

8/28/14, 7:50 PM


Interesting report that demonstrates the complications of handfootmouth disease caused by humanenterovirus 71 in Asia.

42. Chong CY, Chan KP, Shah VA et al.: Hand, foot and mouth disease in Singapore: a comparison of fatal andnon-fatal cases. Acta Paediatrica 92, 11631169 (2003).

43. Beylot C, Bioulac P, Doutre MS: Pustuloses exanthematiques aigues generalisees. A propos de 4 cas. Ann.Dermatol. Venereol. 107, 3748 (1980).

44. Roujeau JC, Bioulac-Sage P, Bourseau C et al.: Acute generalized exanthematous pustulosis. Analysis of 63cases. Arch. Dermatol. 127, 13331338 (1991).

45. Ersoy S, Paller AS, Mancini AJ: Acute generalized exanthematous pustulosis in children. Arch. Dermatol.140(9), 11721173 (2004).

Quite interesting in that it highlights cases of acute generalized exanthematous pustulosis in children that arenot 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, 487491 (1997).

47. Haro-Gabaldon V, Sanchez-Sanchez-Vizcaino J, Ruiz-Avila P et al.: Acute generalized exanthematouspustulosis with cytomegalovirus infection. Int. J. Dermatol. 35, 735 737 (1996).

48. Brandt O, Abeck D, Gianotti R et al.: GianottiCrosti syndrome. J. Am. Acad. Dermatol. 54(1), 136145 (2006).

Very comprehensive review on GianottiCrosti symdrome (papular acrodermatitis of childhood).

49. Gianotti F: Papular acrodermatitis of childhood and other papulo-vesicular acro-located syndromes. Br. J.Dermatol. 100(1), 4959 (1979).

50. Hofmann B, Schuppe HC, Adams O et al.: GianottiCrosti syndrome associated with EpsteinBarr virusinfection. Pediatr. Dermatol. 14, 273227 (1997).

51. Chuh AA: Diagnostic criteria for GianottiCrosti syndrome: a prospective casecontrol study for validityassessment. Cutis 68(3), 207201 (2001).

Interesting attempt to develop diagnostic criteria for papular acrodermatitis of childhood.

52. Chuh A, Lee A, Zawar V: The diagnostic criteria of GianottiCrosti syndrome: are they applicable to children inIndia? Pediatr. Dermatol. 21(5), 542527 (2004).

53. Silverberg NB, Sidbury R, Mancini AJ: Childhood molluscum contagiosum: experience with cantharidin therapyin 300 patients. J. Am. Acad. Dermatol. 43, 503507 (2000).

54. Brown J, Janniger CK, Schwartz RA et al.: Childhood molluscum contagiosum. Int. J. Dermatol. 45(2), 9399(2006).

55. van der Wouden JC, van der Sande R, van Suijlekom-Smit LW et al.: Interventions for cutaneous molluscumcontagiosum. 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

8/28/14, 7:50 PM


molluscum. Pediatr. Dermatol. 25(2), 189192 (2008).

57. Toro JR, Wood LV, Patel NK et al.: Topical cidofovir: a novel treatment for recalcitrant molluscum contagiosumin children infected with human immunodeficiency virus 1. Arch. Dermatol. 136(8), 983985 (2000).

58. Ibarra V, Blanco JR, Oteo JA et al.: Efficacy of cidofovir in the treatment of recalcitrant molluscum contagiosumin an AIDS patient. Acta Derm. Venereol. 80(4), 315316 (2000).

59. Hsieh MY, Huang PH: The juvenile variant of popular purpuric gloves and socks syndrome and its associationwith viral infections. Br. J. Dermatol. 151, 201220 (2004).

Recognizing this manifestation of parovirus B19 helps explain well-appearing children who present withgeneralized petechaie.

60. Huerta-Brogeras M, Avils Izquierdo JA, Hernanz Hermosa JM et al.: Petechial exanthem in "bathing trunk"distribution caused by parvovirus B19 infection. Pediatr. Dermatol. 22(5), 430433 (2005).

61. Harms M, Feldmann R, Saurat JH: Papular-purpuric "gloves and socks" syndrome. J. Am. Acad. Dermatol. 23,850854 (1990).

62. Butler GJ, Mendelsohn S, Franks A: Parvovirus B19 infection presenting as 'bathing trunk' erythema withpustules. Australas J. Dermatol. 47(4), 286288 (2006).

63. Harel L, Straussberg I, Zeharia A et al.: Papular purpuric rash due to parvovirus B19 with distribution on thedistal extremities and the face. Clin. Infect. Dis. 35(12), 15581561 (2002).

64. McNeely M, Friedman J, Pope E: Generalized petechial eruption induced by parvovirus B19 infection. J. Am.Acad. Dermatol. 52(5 Suppl. 1), S109S113 (2005).

65. Foti C, Bonamonte D, Conserva A et al.: Erythema infectiosum following generalized petechial eruption inducedby human parvovirus B19. New Microbiol. 29(1), 4548 (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 parvovirusB19 outbreak. Pediatrics 125(4), e787e792 (2010).

67. Drago F, Broccolo F, Rebora A: Pityriasis rosea: an update with a critical appraisal of its possible herpesviraletiology. J. Am. Acad. Dermatol. 61(2), 303318 (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), 13671368(1997).

70. Kempf W, Adams V, Kleinhans M et al.: Pityriasis rosea is not associated with human herpesvirus 7. Arch.Dermatol. 135(9), 10701072 (1999).

71. Kosuge H, Tanaka-Taya K, Miyoshi H et al.: Epidemiological study of human herpesvirus-6 and humanherpesvirus-7 in pityriasis rosea. Br. J. Dermatol. 143(4), 795798 (2000).

8/28/14, 7:50 PM


72. Tay YK, Goh CL: One-year review of pityriasis rosea at the National Skin Centre, Singapore. Ann. Acad. Med.Singapore 28(6), 829831 (1999)

73. Drago F, Vecchio F, Rebora A: Use of high-dose acyclovir in pityriasis rosea. J. Am. Acad. Dermatol. 54, 8285(2006).

74. Sharma PK, Yadav TP, Gautam RK et al.: Erythromycin in pityriasis rosea: a double-blind, placebo-controlledclinical trial. J. Am. Acad. Dermatol. 42(2 Pt 1), 241244 (2000).

75. Stulberg DL, Wolfrey J: Pityriasis rosea. Am. Fam. Physician 69(1), 8791 (2004).

76. Leenutaphong V, Jiamton S: UVB phototherapy for pityriasis rosea: a bilateral comparison study. J. Am. Acad.Dermatol. 33, 996999 (1995).

77. Valkova S, Trashlieva M, Christova P: UVB phototherapy for pityriasis rosea. J. Eur. Acad. Dermatol. Venereol.18(1), 111112 (2004).

78. Browning JC: An update on pityriasis rosea and other similar childhood exanthems. Curr. Opin. Pediatr. 21(4),481485 (2009).

79. Brice SL, Krzemien D, Weston WL et al.: Detection of herpes simplex virus DNA in cutaneous lesions oferythema multiforme. J. Invest. Dermatol. 93, 183197 (1989).

80. Weston WL, Stockert SS, Jester JD et al.: Herpes simplex virus in childhood erythema multiforme. Pediatrics89, 3234 (1992).

81. Brice SL, Huff JC, Weston WL: Erythema multiforme minor in children. Pediatrician 18(3), 188194 (1991).

82. Weston WL, Morelli JG: Herpes simplex virus-associated erythema multiforme in prepubertal children. Arch.Pediatr. Adolesc. Med. 151(10), 10141016 (1997).

83. Bodemer C, de Prost Y: Unilateral laterothoracic exanthema in children: a new disease? J. Am. Acad. Dermatol.27, 693696 (1992).

84. Brunner MJ, Rubin L, Dunlap F: A new papular erythema of childhood. Arch. Dermatol. 85, 539540 (1962).

85. Taieb A, Megraud F, LeRoy JM et al.: Erythme localis avec adnopathie rgionale de l'enfant: une maladied'inoculation? Ann. Dermatol. Venereol. 113, 10231024 (1986).

86. Taieb A, Mgraud F, Legrain V et al.: Asymmetric periflexural exanthem of childhood. J. Am. Acad. Dermatol.29, 391393 (1993).

87. Chuh AA, Chan HH: Unilateral mediothoracic exanthem: a variant of unilateral laterothoracic exanthema. Cutis77, 2932 (2006).

88. Harangi F, Vrszegi D, Szcs G: Asymmetric periflexural exanthem of childhood and viral examinations.Pediatr. Dermatol. 12, 112115 (1995).

89. Pauluzzi P, Festini G, Gelmetti C: Asymmetric periflexural exanthem of childhood in an adult patient withparvovirus B19. J. Eur. Acad. Dermatol. Venereol. 15, 372374 (2001).

90. Duarte AF, Cruz MJ, Baudrier T et al.: Unilateral laterothoracic exanthem and primary EpsteinBarr virusinfection: case report. Pediatr. Infect. Dis. J. 28(6), 549550 (2009).

8/28/14, 7:50 PM


Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest inor 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, orroyalties.

No writing assistance was utilized in the production of this manuscript.

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

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, 799780 (1993).

93. Flster-Holst R, Kreth HW: Viral exanthems in childhood. Part 3: parainfectious exanthems and thoseassociated with virusdrug interactions. J. Dtsch Dermatol. Ges. 7(6), 506510 (2009).

94. Mancini AJ: Childhood exanthems: a primer and update for the dermatologist. Adv. Dermatol. 16, 337 (2000).

95. Mortureux P, Laut-Labrze C, Legrain-Lifermann V et al.: Acute urticaria in infancy and early childhood: aprospective study. Arch. Dermatol. 134(3), 319323 (1998).

Papers of special note have been highlighted as:

of interest

of considerable interest

Documents

3. eksantem (hal.1)