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

Background: Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown.
Objective: We sought to characterize age-related changes in the AD profile.
Methods: 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).
Results: 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 _H 2 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 _H 2 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 _H 22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T _H 1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T _H 17-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 _H 2 downregulation (CCL26; r = -0.32, P < .1) and T _H 1 upregulation (IFN-γ; r = 0.48, P < .01) with age.
Conclusion: The adult AD profile varies with age. Although T _H 1/T _H 17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T _H 2/T _H 22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
(Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)