Characterizing Viral Exanthems

Joseph M Lam

Disclosures

Pediatr Health. 2010;4(6):623-635. 

In This Article

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]

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]

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 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.

Figure 4.

Sterile nonfollicular pustules with underlying erythema.

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