Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis

Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown.

We sought to characterize age-related changes in the AD profile.

We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years).

Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b⁺ and FcεRI⁺, P < .05) decreased with age. T_H2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T_H2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T_H22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T_H1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T_H17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T_H2 downregulation (CCL26; r = -0.32, P < .1) and T_H1 upregulation (IFN-γ; r = 0.48, P < .01) with age.

The adult AD profile varies with age. Although T_H1/T_H17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T_H2/T_H22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.