Eczema Herpeticum

Etiology

Eczema herpeticum is due to cutaneous superinfection with herpes simplex virus (HSV), usually HSV-1, in patients with atopic dermatitis. Cases due to reactivation of HSV are more common than primary infection.[4] Individuals with this condition are prone to recurrent bacterial and viral skin infections due to impaired epidermal barrier function and immune dysregulation.[5] Disseminated cutaneous HSV infection can also occur in patients with other forms of dermatitis that impair the skin barrier, which is known as Kaposi varicelliform eruption (KVE). KVE has been reported in patients with Darier disease, Hailey–Hailey disease, immunobullous diseases, burns, irritant contact dermatitis, mycosis fungoides, Sézary syndrome, ichthyoses, and pityriasis rubra pilaris.[6][7] 

Risk factors associated with developing eczema herpeticum are more severe atopic skin disease, decreased epidermal expression of filaggrin, and decreased production of cathelicidin and other antimicrobial peptides.[8] Affected patients exhibit biomarkers associated with T-helper type 2 (Th2) cell responses, such as reduced interferon levels, elevated eosinophil count, and increased serum immunoglobulin E levels.[5] The Th2 shift of the immune system in patients with eczema herpeticum is associated with decreased antimicrobial peptides in the epidermis and reduced defense against cutaneous HSV infection.

Eczema herpeticum patients are more likely to have food and environmental allergies, asthma, early onset of atopic dermatitis before age 5, and a history of Staphylococcus aureus and molluscum contagiosum infections.[5] The HLA-B7 allele is associated with an increased risk of eczema herpeticum.[9] Increased interleukin (IL)-10 and local IL-25 expression are found in eczema herpeticum patients and may play a role in developing eczema herpeticum.[10] 

Epidemiology

Eczema herpeticum occurs in <3% of patients with atopic dermatitis, affecting infants and children more than adults.[5] Atopic dermatitis is the most common chronic inflammatory skin disease in the world, affecting 10% to 20% of children in developed countries and 7% to 10% of adults in the United States (US).[11][12] Given the prevalence of HSV exposure, the comparative rarity of eczema herpeticum in those with atopic dermatitis suggests many host factors play an important role in the development of eczema herpeticum.

Results from a study of pediatric patients with eczema herpeticum in Canada found that predictors of hospitalization included male sex, age younger than 1 year, fever, and systemic symptoms at presentation.[13] Results from a study conducted in the US found that the average age of hospitalized pediatric patients with eczema herpeticum was 3.26 +/- 0.1 years, and 41.8% of patients were girls. Results from this study also reported higher prevalence, length of hospital stay, and cost of care in Asian pediatric patients.[13] The epidemiology of eczema herpeticum in nonhospitalized and adult patients is not well-defined.

Pathophysiology

The pathophysiology of eczema herpeticum involves a compromised epidermal barrier and dysfunctional immune responses inherent to atopic dermatitis, which predispose the skin to HSV entry and proliferation.[14] In atopic dermatitis, filaggrin deficiency and cytokine-mediated inflammation weaken the skin's structural integrity, allowing HSV to penetrate more easily. The impaired skin barrier, coupled with dysregulated T-cell responses and decreased production of antimicrobial peptides, diminishes the host's ability to control viral replication. This results in widespread vesiculopustular eruptions, often accompanied by systemic symptoms such as fever and malaise.[15]

Histopathology

Histological examination of eczema herpeticum reveals multinucleated giant cells with intranuclear inclusion bodies, known as Cowdry type A inclusions, within the epidermis. These inclusions are indicative of an HSV cytopathic effect. The epidermis shows extensive ballooning degeneration of keratinocytes and intraepidermal vesicle formation. There is often spongiosis and acantholysis, leading to the formation of intraepidermal and subepidermal blisters. The dermis typically exhibits a perivascular lymphocytic infiltrate, sometimes with the presence of eosinophils due to the underlying atopic dermatitis. Additionally, there may be necrosis of keratinocytes and evidence of viral replication within the lesions. These histopathological features are crucial for diagnosing and differentiating eczema herpeticum from other similar vesiculobullous disorders.[10][16]

History and Physical

Eczema herpeticum presents as a sudden onset eruption of monomorphic, dome-shaped, grouped, 2 mm to 3 mm vesicles on an erythematous base. Lesions are superimposed on areas of preexisting atopic dermatitis, most commonly on the face, neck, and upper trunk (see Image. Eczema Herpeticum). The lesions are pruritic and painful and may spread to involve normal skin over 7 to 10 days.[17] 

Within 2 weeks, the vesicles rupture and form characteristic "punched-out" erosions with the hemorrhagic crust. Small erosions may coalesce to form a larger erosion or ulceration with a scalloped border. Numerous vesicles may appear in successive crops, and multiple morphologies may be present simultaneously. Lesions that are secondarily impetiginized may have an overlying honey-colored crust.

In patients with severe or poorly controlled atopic dermatitis, the characteristic morphology may be difficult to recognize and can be misdiagnosed as an exacerbation of eczematous dermatitis.[18] Patients may have systemic symptoms like fever, malaise, and lymphadenopathy.[3] Eczema herpeticum lesions generally heal without scarring within 6 weeks.[19]

Evaluation

The diagnosis of eczema herpeticum can be made clinically if characteristic morphology is present. Viral polymerase chain reaction (PCR) can be performed on vesicle fluid to confirm the diagnosis and determine the type of herpesvirus with high sensitivity and specificity. If PCR is not available, a Tzank smear, direct fluorescent antibody (DFA) testing, and viral cultures can confirm HSV infection. Bacterial culture should be done if there is a concern for impetiginization. If the clinical presentation is atypical, a skin biopsy may be indicated. Laboratory tests may reveal lymphopenia and an increased erythrocyte sedimentation rate.[17]

Treatment / Management

Patients with eczema herpeticum should be treated promptly with systemic acyclovir or valacyclovir to minimize the risk of complications and prevent progression to severe disease.

• Mild cases can be treated with oral acyclovir or valacyclovir for 7 to 21 days or until all lesions are crusted over.[20] The recommended dosage for oral acyclovir is 30 mg/kg/d to 60 mg/kg/d, divided into 3 doses per day in children and 400 mg 3 times per day in adults.[19][21] The dosage for oral valacyclovir is 20 mg/kg/d in children and 500 mg 3 times per day in adults.[4]                                                                                                  
• Severe cases or those who are immunocompromised should be hospitalized for intravenous acyclovir (5 mg/kg to 10 mg/kg every 8 hours). Once clinical improvement occurs and the lesions start to crust over, patients can be transitioned to oral acyclovir.[18] Supportive care with gentle emollients and cool compresses can provide symptomatic relief.                                                                                                                                           
• Those who are critically ill may need intravenous fluids, electrolyte repletion, wound care, pain control, and nutritional support. Patients should be counseled about the risk of autoinoculation, and frequent handwashing should be encouraged. Eczema herpeticum lesions are considered infectious until crusted over.
• Contact precautions should be initiated for those who are hospitalized, including patient isolation and the use of face masks and gowns for healthcare professionals.[21] Patients should be monitored for the development of secondary bacterial infections and treated with systemic antibiotics according to culture and susceptibility results.[21]
(B2)

Differential Diagnosis

The differential diagnosis for eczema herpeticum includes the following:

• Impetigo
• Hand-foot-and-mouth disease
• Eczema coxsackium
• Primary varicella infection
• Disseminated herpes zoster
• Disseminated molluscum contagiosum
• Acute generalized exanthematous pustulosis
• Dermatitis herpetiformis
• Cellulitis
• Erysipelas

Misdiagnosis of eczema herpeticum can lead to delayed initiation of antiviral treatment and subsequent complications. Diagnostic clues that favor eczema herpeticum are painful lesions, monomorphic size of the lesions, and characteristic "punched-out" erosions in areas of preexisting atopic dermatitis. Unlike herpes zoster, eczema herpeticum does not respect dermatomal boundaries.

Prognosis

Eczema herpeticum is a potentially life-threatening disease with mortality risk due to complications of systemic viremia, bacteremia, and fungal infection leading to multiorgan failure.[22] Before using acyclovir, mortality rates in patients with eczema herpeticum were reportedly 10% to 50%.[23] Since the widespread implementation of systemic antiviral treatment, mortality rates have decreased significantly.

Results from a 2011 study of 1331 pediatric eczema herpeticum patients hospitalized in the US found no deaths and concluded that the mortality rate of hospitalized patients is low. The median length of hospital stay was 3 days, with 9.2% of patients requiring hospitalization longer than 1 week and 3.8% requiring intensive care unit admission.[24] 

Results from a study conducted in 2018 showed that 4655 hospitalized children with eczema herpeticum had a mortality rate of 0.1%, and 98.1% of patients were classified as having a minor mortality risk. Only 4.5% of patients were classified as having a major loss of function, while 33.1% had moderate, and the majority had a minor loss of function.[13]

Complications

Potential complications of eczema herpeticum include cutaneous superinfection with Staphylococcus aureus, Streptococcus pyogenes, and molluscum contagiosum virus.[25][26] Results from a study by Aronson et al found S aureus infection in 30.3% of patients who were pediatric and hospitalized with pediatric eczema, with 9.2% due to methicillin-resistant S aureus and 3.9% with bacteremia. Eighty-six percent of patients were treated with oral or intravenous antibiotics.[24] Additional complications include meningoencephalitis and herpetic keratoconjunctivitis, which can result in scarring and blindness.[4] Disseminated systemic infections of HSV leading to bone marrow suppression, disseminated intravascular coagulation, and death have been reported.[18]