July 2015 Dermatology Clinic
A 16-year-old Hispanic male with a history of well-controlled moderate-to-severe atopic dermatitis presents to the emergency room complaining of a one-day history of a painful facial rash. He reports that the initial lesion started on the cheek and quickly spread from there. He has been applying triamcinolone ointment twice daily to the lesions, but the lesions have continued to spread. Physical examination reveals diffuse punched-out, eroded vesicles on the face and anterior neck. You notice his mother has a small shallow ulceration on her right lower lip.
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Eczema herpeticum develops in patients with underlying atopic dermatitis whose eczematous areas become infected with herpes simplex virus (HSV). Eczema herpeticum is also known as Kaposi’s varicelliform eruption, which is the term typically used to describe cases of cutaneous disseminated herpes simplex virus in conditions with an impaired skin barrier other than atopic dermatitis. These conditions include allergic and photoallergic contact dermatitis, cutaneous T-cell lymphoma, Darier disease, Hailey-Hailey disease, ichthyosis vulgaris, mycosis fungoides, pemphigus, pemphigoid, scabies, severe seborrheic dermatitis, Sézary syndrome, thermal burns, and Wiskott-Aldrich syndrome.1
Eczema herpeticum initially presents as an eruption of painful monomorphic vesicles on an erythematous base that evolve into “punched-out” erosions that often have a hemorrhagic crust. The lesions typically have an active vesicular border and a scalloped periphery. In severe cases, hundreds of umbilicated vesicles may be present. Lesions begin on eczematous skin and may later extend peripherally to normal-appearing skin. Confluent erosions may result in large areas of epithelial denudation.2 Untreated erosive lesions typically resolve gradually, but in rare cases, the lesions may become papular or vegetative.
The lesions are often widespread and may occur anywhere on the body. However, they commonly occur on the face, neck, and trunk. Eczema herpeticum may be associated with fever, malaise, lymphadenopathy, and irritability.3 The lesions are more commonly due to viral infection with HSV-1, as opposed to HSV-2, although either can be the causative agent.2 Eczema herpeticum is more common in infants and children and can be transmitted to a child with atopic dermatitis from a parent with herpes labialis.2,4
Individuals with atopic dermatitis are more prone to developing skin infections such as eczema herpeticum due to their impaired skin barrier. Mutations in the gene encoding filaggrin result in an increased risk for eczema herpeticum.4 In addition, patients with severe atopic dermatitis, early-onset atopic dermatitis, asthma, food and environmental allergies, elevated levels of immunoglobulin E, and a high eosinophil count have an increased risk for eczema herpeticum.5,6 Use of topical calcineurin inhibitors such as tacrolimus or pimecrolimus have also been associated with eczema herpeticum.1,7 The use of physiologic lipid mixtures to repair the epidermal lipid barrier is thought to reverse some negative effects of topical calcineurin inhibitors and reduce the risk of eczema herpeticum.8
Patients with eczema herpeticum are also more likely to have secondary bacterial infections with Staphylococcus aureus and Streptococcus pyogenes or the viral infection molluscum contagiosum and may suffer from complications including herpetic keratoconjunctivitis and meningoencephalitis.9
The clinical diagnosis of eczema herpeticum is confirmed by cultures for HSV from the margin of the ulcer and direct fluorescent antibody (DFA) testing for HSV, which is specific and provides results rapidly. In rare cases, a skin biopsy will reveal typical herpetic changes even when cultures and DFA are negative for HSV.1S. aureus infection should also be ruled out due to common secondary infection.2
HSV vesicles are intraepidermal. Leukocytes can be found in the affected epidermis and adjacent inflamed dermis, and serous exudate containing dissociated cells accumulates to create the vesicle. Acantholysis occurs as a result of the ballooning degeneration of the affected epidermal cells.10 Histologically, multinucleated giant cells are characteristic of HSV infection. A steel-gray-colored nucleus and peripheral condensation of the nucleoplasm can act as markers of HSV infection when multinucleated giant cells are not seen.1 In addition, immunoperoxidase stains can detect HSV infection in paraffin-fixed tissue.
The differential diagnosis for eczema herpeticum includes herpes zoster; however, zoster presents with clusters of lesions along a dermatome, and zoster lesions are usually more painful than herpetic lesions and can be differentiated with DFA testing.1 Bullous impetigo may also be on the differential. The blisters of bullous impetigo are typically flaccid and unilocular and occur at the edge of a crust, whereas herpetic lesions are widespread, small, tense vesicles.1 Primary HSV infection may also be considered, but, in eczema herpeticum, the lesions are not grouped but disseminated within the eczematous areas.
In the treatment of eczema herpeticum, it is recommended that antiviral therapy be initiated immediately while confirmatory testing is pending due to the limited toxicity of that treatment. Intravenous or oral antiviral treatment can be used, depending on the severity of the disease. Oral treatment regimens include 400 mg of acyclovir three times per day, 500 mg of famciclovir twice per day, or 1 g of valacyclovir twice per day. A 5- to 10-day course of antiviral medication is recommended, and treatment should be continued until all lesions are healed. In hospitalized patients or cases of severe infection, intravenous acyclovir dosed at 5 mg/kg to 10 mg/kg every 8 hours initially is recommended to control the infection.1 Due to possible ocular involvement, an emergent ophthalmology consult is recommended when lesions are present on the face.1 Long-term suppressive therapy with acyclovir, famciclovir, or valacyclovir should be considered in patients with chronic immunosuppression or acquired immune deficiency syndrome (AIDS).
Eczema herpeticum is typically self-limited in healthy patients. Mild cases with only a few lesions are much more common than severe cases and often go untreated. Patients may be concerned by the appearance of the vesicles, but even when left untreated, lesions usually resolve in two to six weeks.2
After initial infection, the virus remains latent in the nerve ganglia, and recurrent episodes are typically milder and not accompanied by systemic symptoms. Kaposi’s varicelliform eruption can be fatal in patients with systemic immunosuppression and an impaired epidermal barrier, such as those with pemphigus or cutaneous T-cell lymphoma. This morbidity is typically due to S. aureus septicemia, but may be secondary to visceral dissemination of HSV.1
The patient in this case was hospitalized and intravenous acyclovir was initiated. His skin lesions began to improve after the first 24 hours of this treatment. After two days of intravenous acyclovir, he was transitioned to oral acyclovir and discharged from the hospital. At one-week and one-month outpatient follow-up, he had no recurrences of the rash.
Megan Trainor, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.
- James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011:Chap. 11.
- Wolff K, Johnson RA, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, N.Y.: McGraw Hill Education; 2013: Sec. 27.
- Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007;57(5):737-763.
- Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2012: Chap. 12, 80.
- Howell MD, Wollenberg A, Gallo RL, et al. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006;117(4):836-841.
- Beck LA, Boguniewicz M, Hata T, et al. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum. J Allergy Clin Immunol. 2009;124(2):260-269.
- Lübbe J, Sanchez-Politta S, Tschanz C, Saurat JH. Adults with atopic dermatitis and herpes simplex and topical therapy with tacrolimus: What kind of prevention? Arch Dermatol. 2003;139(5):670-671.
- Kim M, Jung M, Hong SP, et al. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability, and antimicrobial barrier function. Exp Dermatol. 2010;19(6):501-510.
- Wollenberg A, Wetzel S, Burgdorf WH, Haas J. Viral infections in atopic dermatitis: Pathogenic aspects and clinical management. J Allergy Clin Immunol. 2003;112(4):667-674.
- Rapini RP, ed. Practical Dermatopathology. 2nd ed. New York, N.Y.: Elsevier Saunders; 2012: Chap. 14.