A mild topical steroid leads to progressive anti-inflammatory effects in the skin of patients with moderate-to-severe atopic dermatitis

Abstract

Topical glucocorticosteroids are considered an efficient treatment option for atopic dermatitis (AD), but a global assessment of glucocorticosteroid responses on key disease circuits upon weeks to months of treatment is currently lacking. We sought to assess short (4weeks) and long-term (16weeks) application of topical glucocorticosteroids on AD skin and define response biomarkers. The effects of triamcinolone acetonide cream 0.025% were assessed based on gene expression and immunohistochemistry studies at baseline, 4weeks, and 16weeks in biopsy specimens from 15 patients with moderate-to-severe AD. At 16weeks, only 3 patients were clinical responders (by using SCORAD50 criteria), but 6 patients qualified as responders based on histologic criteria. Baseline characteristics indicated more severe disease in nonresponders. While 3 of 15 patients experienced only transient benefit after 4weeks, others showed progressive improvements toward 16weeks. Topical glucocorticosteroid use in patients with AD resulted in improvements of the AD genomic signature of 25.6% at 4weeks and 71.8% at 16weeks, respectively, and even 123.9% in the histologic responder group. Cytokines (IL-12p40, IL-13, IL-22, CCL17, CCL18, peptidase inhibitor 3 [PI3]/elafin, and S100As) showed consistent decreases from baseline toward 16weeks with corresponding improvements in epidermal disease hallmarks (keratin 16 and loricrin) in lesional skin from responders (P<.05). Nonresponders largely showed lesser/nonsignificant reductions in key inflammatory and barrier markers (keratin 16, IL-13, IL-22, CCL17, CCL18, PI3/elafin, S100As, and loricrin). The combination of IL-21 and IFN-γ baseline expression closely predicted individual clinical glucocorticosteroid responses at 16weeks of treatment. Our study indicates that even low-potency glucocorticosteroids can broadly affect immune and barrier responses in patients with moderate-to-severe AD, associating higher baseline severity with increased steroid resistance in patients with AD.