Dupilumab Therapy Improves Stratum Corneum Hydration and Skin Dysbiosis in Patients With Atopic Dermatitis

Abstract

Purpose We aimed to investigate the effects of dupilumab on 1) the permeability and antimicrobial barrier, 2) the composition of the skin microbiome, and 3) the correlation between changes in skin barrier properties and microbiota in atopic dermatitis (AD) patients. Methods Ten patients with severe AD were treated with dupilumab for 12 weeks. Disease severity was assessed using the Eczema Area and Severity Index (EASI). Skin barrier function was evaluated by measuring transepidermal water loss, stratum corneum (SC) hydration, and pH. The following parameters were analyzed in the pre- and post-treatment SC samples; 1) skin microbiota using 16S rRNA gene sequencing, 2) lipid composition using mass spectrometry, and 3) human β-defensin 2 (hBD-2) expression using quantitative reverse transcription polymerase chain reaction. Results SC hydration levels in the lesional and non-lesional skin increased after 12-week dupilumab therapy (24.2%, P < 0.001 and 59.9%, P < 0.001, respectively, vs. baseline) and correlated with EASI improvement ( r = 0.90, P < 0.001 and r = 0.85, P = 0.003, respectively). Dupilumab increased the long-chain ceramide levels in atopic skin (118.4%, P = 0.028 vs. baseline) that correlated with changes in SC hydration ( r = 0.81, P = 0.007) and reduced the elevated hBD-2 messenger RNA levels (−15.4%, P = 0.005 vs. baseline) in the lesional skin. Dupilumab decreased the abundance of Staphylococcus aureus. In contrast, the microbial diversity and the abundance of Cutibacterium and Corynebacterium species increased, which were correlated with an increase in SC hydration levels (Shannon diversity, r = 0.71, P = 0.027; Cutibacterium , r = 0.73, P = 0.017; Corynebacterium , r = 0.75, P = 0.012). Increased abundance of Cutibacterium species was also correlated with EASI improvement ( r = 0.68, P = 0.032). Conclusions Th2 blockade-induced normalization of skin microbiome in AD patients is associated with increased SC hydration.

Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study

“…Some other studies have also evaluated the impact of dupilumab on skin barrier function [ 46 , 47 , 48 , 49 , 50 ]. They showed that dupilumab reduced TEWL on non-involved and involved skin [ 46 , 47 , 48 , 49 , 50 ]. The impact of dupilumab in SCH differs between studies.…”

Skin barrier defects in atopic dermatitis: From old idea to new opportunity

“… 168 In a small study, 12 weeks of Dupilumab treatment significantly increased SC hydration (L and NL) and this barrier improvement correlated with EASI improvement. 169 These studies suggest that Th2 inflammation is responsible for a number of epidermal abnormalities observed in AD subjects. Future studies will need to investigate how changes seen at early time points may predict later improvement in barrier and disease severity.…”

Immunopathology and Immunotherapy of Inflammatory Skin Diseases

“…Binding of cytokines to type I and type II receptors activates the JAK1/STAT6 pathway in hematopoietic and non-hematopoietic cells ( 37 ). These type 2 cytokines also cause skin barrier damage and increase the colonization of S. aureus ( 38 ). Barrier defects also induce keratinocyte production of IL-23, which leads to the activation of IL-23R expressing DCs triggering the Th22 immune response.…”