The differential diagnosis of eczema herpeticum includes impetigo, varicella-zoster virus, and EV.1 A diagnosis of eczema herpeticum should be considered in the presence of multiple umbilicated papules, vesicopustules, or erosions in a patient with underlying skin disease. The presence of herpesvirus infection often can be confirmed by the presence of ballooning degeneration and nuclear cytopathic effect in multinucleated cells seen on a Tzanck test. The characteristic nuclear cytopathic effect includes peripheral margination of nucleoplasm so that it creates a basophilic rim at the edge of the nucleus. When possible, samples should be obtained from the floor of a freshly unroofed vesicopustule.19 More specific identification of the causative agent can be confirmed by viral culture or DFA testing of a smear. Smears for DFA testing generally are obtained with a No. 15 blade from the floor of a fresh vesicle. A round smear requires fewer drops of reagent than a long thin smear and is therefore more cost-effective. DFA results generally can be obtained within 1 to 4 hours.
Biopsy results of eczema herpeticum will show changes characteristic of herpesvirus infection; namely ballooning degeneration of keratinocytes with multinucleated epithelial cells and nuclear cytopathic effect.19 Polymerase chain reaction from tissue or smears may be performed to extract herpes DNA to distinguish among the herpes subtypes. Immunostaining also can be performed using monoclonal antibodies directed against HSV-1 and HSV-2.19
Treatment
The mainstay of therapy for eczema herpeticum is oral therapy with nucleoside analogue antiviral medications such as acyclovir, valacyclovir, and famciclovir (Table). The activation of acyclovir requires a thymidine kinase that is specific for the herpesvirus family. The drug is triphosphorylated to a form that inhibits viral DNA polymerase, resulting in irreversible viral DNA chain termination.20 Absorption of oral acyclovir is unreliable in neonates.
Valacyclovir is an ester prodrug of acyclovir that has a bioavailability 3 to 5 times greater than oral acyclovir. Oral dosing of valacyclovir can result in blood levels similar to those obtained with parenteral acyclovir.20 Valacyclovir generally is dosed twice daily for herpes simplex and 3 times daily for herpes zoster.20 Famciclovir is a prodrug of penciclovir that also must be triphosphorylated to become active. It too has greater bioavailability than acyclovir and generally is dosed 3 times daily. Parenteral therapy may be preferred over oral therapy in the case of immunosuppression or inability to take oral medication. Intravenous acyclovir has been reported to cause phlebitis and reversible renal insufficiency from crystalline nephropathy. This risk can be minimized with intravenous fluid hydration.21 Acyclovir-resistant herpes can be treated with foscarnet, which is not a nucleoside analogue but instead acts by blocking pyrophosphate-binding sites on viral polymerases.20
Secondary bacterial infection is common in eczema herpeticum and should be treated with appropriate antibiotics. Most infections are caused by staphylococcal and streptococcal species. Despite the rare occurrence of herpetic keratitis, some authors recommend that patients with eczema herpeticum be treated with a topical ophthalmic antiviral medication in addition to systemic antiviral therapy; however, oral acyclovir alone has been shown to be beneficial in the treatment of HSV keratitis.8,22
Eczema Vaccinatum
In the early 1970s, the United States ended routine vaccination for smallpox because of the eradication of naturally occurring disease. With the emerging threat of bioterrorism, the issue of vaccination recently has come to the forefront as a public health concern. Smallpox vaccine is made from live vaccinia virus. Immunity induced by vaccinia is protective against the causative agent in smallpox, the variola virus. Although very successful in the campaign against variola, the smallpox vaccine earned the reputation of having one of the highest rates of vaccine-associated adverse events. Dermatologic complications include localized skin reactions without systemic symptoms, generalized skin reactions without systemic symptoms (eg, erythema multiforme minor), and generalized skin reactions with systemic symptoms (eg, EV, generalized vaccinia) (Figures 6 and 7).23 Data from the late 1960s show that adverse events to vaccinia inoculation are 10 times more likely to occur in those receiving the vaccine for the first time compared with those receiving a repeat vaccination. It is estimated that approximately 40% of the current US population are immunologically naive to vaccinia.22
Like eczema herpeticum, EV occurs in the setting of a compromised epidermal barrier. AD, regardless of disease activity, is a risk factor for developing EV. Although many primary care providers do not distinguish between AD and other forms of eczema, AD is a genetic disease with immune defects that may predispose to the spread of the virus.23 To reduce the risk of inadvertent inoculation of a patient with AD, the current recommendations of the Centers for Disease Control and Prevention (CDC) include any history of AD or eczema as a contraindication to receipt of smallpox vaccine.24