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You are called to the emergency room to see an ill-looking, 13-year-old boy with a severe flare of his atopic dermatitis associated with fever, malaise, and chills, which started a week ago.
You are called to the emergency room to see an ill-looking, 13-year-old boy with a severe flare of his atopic dermatitis associated with fever, malaise, and chills, which started a week ago. What’s your diagnosis?
Eczema herpeticum (EH) is a disseminated herpes simplex virus (HSV) infection usually affecting patients suffering from atopic dermatitis (AD), contact dermatitis, or other widespread primary dermatoses.1 Although most patients show serologic evidence of HSV exposure, EH affects only about 3% of patients with AD.2
Predisposing factors may include compromised host defenses such as those seen in severe AD, leukemia, lymphoma, bone marrow transplantation, chemotherapy, and previous topical corticosteroid use.1 However, recent studies have shown little evidence to substantiate the latter, and in many children with AD, their skin disease may be relatively well controlled when EH erupts.3,4 A recent study by Aronson and colleagues confirmed this and found that use of oral corticosteroids increased average length of hospitalization in patients with EH by 18%.5
Classic findings of primary infection include fever; lymphadenopathy; exquisite pain in the affected area; and clusters of disseminated, monomorphic, vesicular, and dome-shaped vesicles, pustules, and crusts. The most commonly affected areas are the head, neck, and upper trunk.3 Unlike other primary or recurrent HSV eruptions, lesions in EH are usually disseminated, but if the clinician looks carefully, he or she may still be able to define clustering of discrete and confluent lesions.
Patients with head, neck, or large body-surface-area involvement, or early-onset AD, have higher risks of EH.6,7 Although unusual, more serious systemic involvement occurs particularly in patients with primary infection and immunosuppression.1 Rarely, patients can develop keratoconjunctivitis, meningoencephalitis,8 disseminated intravascular coagulation, bronchial hemorrhage, and even adrenal hemorrhage.9 The infection typically resolves within 2 to 3 weeks, but recurrences are common. Although recurrences tend to be milder than primary disease,1 they can disrupt normal day care, school, and sports activities.
Eczema herpeticum may resemble varicella, disseminated varicella zoster virus (VZV) infection, and impetigo. Varicella tends to be uniformly disseminated on skin and mucous membranes. In disseminated VZV in the immunocompromised host, one can usually identify more than 20 vesicles outside the area of primary or adjacent dermatomes.10 In bullous impetigo, the clustered initial vesicles tend to expand and vary in size. The typical appearance of characteristic lesions as well as a history of AD or other cutaneous dermatoses should raise the clinical suspicion for EH. Because secondary bacterial infection complicating EH is common, bacterial and viral cultures should be sent when both are suspected.6
More recently, enteroviral infection with coxsackievirus A6 has been recognized as a trigger of a disseminated eruption similar to EH. However, at the time of diagnosis, affected children are usually afebrile and clinically appear well, and the eruption tends to be symmetric with a predilection for involvement of the distal extremities, diaper area, and perioral skin. Cultures for HSV are negative.11
In severe EH, particularly in those who are immunocompromised, early diagnosis is critical. Mortality in the latter as high as 50% has been reported, although between 6% to 10% is the more accepted number.4,6 Studies before the use of acyclovir quoted mortality rates upward of 10% to 50%.12 Although the current mortality rate of EH has not been reported, the mortality rate of hospitalized children with EH is low.13
Eczema herpeticum is a clinical diagnosis that can be confirmed from blister fluid by polymerase chain reaction for viral DNA.3 The diagnosis is supported by Tzanck test, which also may be done on blister fluid. A less sensitive method is viral culture, and a less specific method is serologic testing.
Herpes simplex virus is responsible for causing EH. Current evidence suggests that the susceptibility of patients with AD to develop EH stems from innate and adaptive immune response deficiencies commonly seen in these patients. Reduced levels of plasmacytoid dendritic cells and antimicrobial peptides in patients’ skin also have been reported.14 These same factors may contribute to the well-documented susceptibility to superinfection with Staphylococcus aureus or Streptococcus pyogenes in these patients.8,13
Patients suspected of having EH should be cultured for HSV and treated with acyclovir (Zovirax) or valacyclovir (Valtrex) immediately because there is a statistically significant, time-dependent increase in hospitalization duration with every day of delay in initiating acyclovir therapy.13 Empiric antibiotic therapy was not associated with a shorter hospitalization overall, but was associated with a shorter admission in patients with a bloodstream infection.15 Hence, for these patients, empiric antiviral and antibiotic treatment is both prudent and cost effective.
When involvement of the eyes is suspected, consultation to ophthalmology should be of the highest priority. Herpetic keratoconjunctivitis is extremely dangerous and can result in permanent blindness.4 Recurrent infection may be treated with prophylactic acyclovir or valacyclovir (eg, valacyclovir 500 mg/day).1
Given the severity of his condition at the time of presentation, the patient was started on parenteral acyclovir and vancomycin (Vancocin) therapy. The following day, a positive viral culture confirmed the diagnosis. During the first 2 days, his symptoms improved dramatically and completely resolved after 7 days of therapy. He was discharged on day 10. Because this was his first episode of EH, prophylaxis was not prescribed and close monitoring was arranged.
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2. Leung DY. Why is eczema herpeticum unexpectedly rare? Antiviral Res. 2013;98(2):153-157.
3. Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B. Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J Am Acad Dermatol. 2003;49(2):198-205.
4. Hasegawa K, Obermeyer Z, Milne LW. Eczema herpeticum. J Emerg Med. 2012;43(5):e341-e342.
5. Aronson PL, Shah SS, Mohamad Z, Yan AC. Topical corticosteroids and hospital length of stay in children with eczema herpeticum. Pediatr Dermatol. 2013;30(2):215-221.
6. Liaw FY, Huang CF, Hsueh JT, Chiang CP. Eczema herpeticum: a medical emergency. Can Fam Physician. 2012;58(12):1358-1361.
7. Jen M, Chang MW. Eczema herpeticum and eczema vaccinatum in children. Pediatr Ann. 2010;39(10):658-664.
8. Bieber T, Bussman C. Atopic dermatitis. In: Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. Vol. 1. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:211-212.
9. Sanderson IR, Brueton LA, Savage MO, Harper JI. Eczema herpeticum: a potentially fatal disease.Br Med J (Clin Res Ed). 1987;294(6573):693-694.
10. Mendoza N, Madkan V, Sra K, Willison B, Morrison LK, Tyring SK. Human herpesviruses. In: Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. Vol. 1. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:1328-1333.
11. Mathes EF, Oza V, Frieden IJ, et al. “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132(1):e149-e157.
12. Wheeler CE Jr, Abele DC. Eczema herpeticum, primary and recurrent. Arch Dermatol. 1966;93(2):162-173.
13. Aronson PL, Yan AC, Mittal MK, Mohamad Z, Shah SS. Delayed acyclovir and outcomes of children hospitalized with eczema herpeticum. Pediatrics. 2011;128(6):1161-1167.
14. Bussmann C, Peng WM, Bieber T, Novak N. Molecular pathogenesis and clinical implications of eczema herpeticum. Expert Rev Mol Med. 2008;10:e21.
15. Aronson PL, Yan AC, Mohamad Z, Mittal MK, Shah SS. Empiric antibiotics and outcomes of children hospitalized with eczema herpeticum. Pediatr Dermatol. 2013;30(2):207-214.
DR SANTOS-ARROYO is a second-year dermatology resident, University of Puerto Rico School of Medicine, San Juan. MR NEVARES-POMALES is a fourth-year medical student, University of Puerto Rico School of Medicine, San Juan. DR COHEN, section editor for Dermcase, is professor of pediatrics and dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The authors and section editor have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Vignettes are based on real cases that have been modified to allow the authors and editor to focus on key teaching points. Images also may be edited or substituted for teaching purposes.