Why is eczema herpeticum unexpectedly rare?

Abstract

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease of humans, affecting approximately 17% of children. AD patients are especially susceptible to cutaneous bacterial and viral infections, and may develop severe or fatal herpes simplex virus (HSV) infection (eczema herpeticum, EH), requiring intensive antiviral therapy. However, even though a majority of adults show serologic evidence of previous HSV exposure, EH occurs in less than 3% of AD patients. The unexpected rarity of AD patients with EH (ADEH+) suggests that multiple host factors play a role in the clinical expression of this complex phenotype. Recent studies comparing ADEH+ versus ADEH- patients reveal that patients prone to ADEH+ have more severe AD skin disease, biomarkers associated with Th2 helper cell responses (reduced interferon levels, circulating eosinophil counts, increased serum IgE and allergen sensitization) and decreased epidermal expression of filaggrin and antimicrobial peptides. ADEH+ subjects are also more likely to have a history of food allergy or asthma, early onset of AD and a history of other cutaneous infections with Staphylococcus aureus or molluscum contagiosum.

Figure 1

Genes associated with AD in at least 1 published study. Genes are grouped according to how many positive association studies have been reported. The y-axis indicates the number of genes (corresponding to the yellow boxes) for each time that a positive association was reported (From: Barnes, K.C. 2010).

Figure 2

A Child with atopic dermatitis complicated by eczema herpeticum. From Boguniewicz and Leung, 2009.

Figure 3

Boxplot graphs of AD severity scores [EASI (A) and Rajka and Langeland (B)] and biomarkers indicative of Th2 polarity[serum total IgE (C) and total eosinophil counts (D)]. From: Beck, L.A., et al, 2009.

Figure 4

Summary of association tests among European American subjects showing significance for each FLG mutation. The −log10-transformed P values on the y axis for all genotyped markers are plotted against their genomic position in NCBI Build 35 in megabase along the x axis. Red circles indicate associations for ADEH; green circles indicate associations for AD. The horizontal dotted line indicates nominal significance P < .05 (Gao, et al. 2009).