Phenotype of atopic dermatitis subjects with a history of eczema herpeticum

Abstract

Background: A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum.

Objective: This National Institute of Allergy and Infectious Diseases-funded multicenter study was performed to establish a database of clinical information and biologic samples on subjects with AD with and without a history of eczema herpeticum (ADEH(+) and ADEH(-) subjects, respectively) and healthy control subjects. Careful phenotyping of AD subsets might suggest mechanisms responsible for disseminated viral infections and help identify at-risk individuals.

Methods: We analyzed the data from 901 subjects (ADEH(+) subjects, n = 134; ADEH(-) subjects, n = 419; healthy control subjects, n = 348) enrolled between May 11, 2006, and September 16, 2008, at 7 US medical centers.

Results: ADEH(+) subjects had more severe disease based on scoring systems (Eczema Area and Severity Index and Rajka-Langeland score), body surface area affected, and biomarkers (circulating eosinophil counts and serum IgE, thymus and activation-regulated chemokine, and cutaneous T cell-attracting chemokine) than ADEH(-) subjects (P < .001). ADEH(+) subjects were also more likely to have a history of food allergy (69% vs 40%, P < .001) or asthma (64% vs 44%, P < .001) and were more commonly sensitized to many common allergens (P < .001). Cutaneous infections with Staphylococcus aureus or molluscum contagiosum virus were more common in ADEH(+) subjects (78% and 8%, respectively) than in ADEH(-) subjects (29% and 2%, respectively; P < .001).

Conclusion: Subjects with AD in whom eczema herpeticum develops have more severe T(H)2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. They are also much more likely to experience cutaneous infections with S. aureus or molluscum contagiosum.

Figure 1

Boxplots of EASI (A) and Rajka-Langeland (B) severity scores and serum total IgE (C) and total eosinophil counts (D). The statistics are reported for all datapoints (as shown in these graphs) as well as age-adjusted cohorts.

Figure 2

Correlations between the log₁₀-transformed EASI scores and (A) serum IgE and (B) log₁₀-transformed total eosinophil counts in AD subjects. [(A) n=117 for ADEH+ (filled diamond) and n=407 for ADEH- (open square); (B) n=128 for ADEH+ (filled diamond) and n=408 for ADEH- (open square)].

Figure 3

Percentage of AD subjects or caregivers who self-report a history of or current food allergy or asthma.

Figure 4

Six allergen-specific ImmunoCAPs^® performed on AD subjects were depicted as a Gaussian distribution with ADEH+ (red) curves shifted to the right compared to ADEH- (orange) subjects are shown in A-E. On the far left of each graph is the proportion of ADEH- (orange) and ADEH+ (red) with values ≤ 0.35 kU_A/L. When ImmunoCAP^® results [(including SEA, SEB and TSST-1 (not shown)] were treated as a binary trait, a greater proportion of ADEH+ had positive results than ADEH- subjects with the exception of Grass (D). *p-value<0.001 for ADEH+ vs ADEH- on binary outcome (≤0.35, >0.35 kU_A/L).

Figure 5

Percentage of subjects (ADEH+, ADEH- and CTL) who self-report a history of ocular infections with herpes simplex virus (A), S. aureus skin infections (B), Human papilloma virus skin infections (C) and molluscum contagiosum virus infections (D).

Figure 6

Boxplots of serum CTACK (CCL27; A) and TARC (CCL17; B) levels in age- and gender-matched ADEH+ and ADEH- cohorts. Correlations between the log₁₀-transformed EASI scores and the (C) serum levels of CTACK and (D) TARC in AD subjects. [n=34 for ADEH+ (filled diamond) and n=34 for ADEH-(open square)].