Abstract
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with complex immune dysregulation. Acute oral corticosteroids relieve measures of AD severity during flares; however, the association of disease severity with anti-inflammatory effects in skin remains unclear. OBJECTIVE: We sought to evaluate the association between clinical severity and skin inflammation in AD. METHODS: Sixteen patients with moderate to severe AD were randomized 1:1 to prednisolone (0.75-0.25 mg/kg tapered over 15 days) or placebo following an 8-day run-in without systemic anti-inflammatory medications. Clinical scores were measured and biopsies from lesional and allergen-challenged skin were collected and analyzed by histology, immunofluorescence microscopy, and ELISA for cells and cytokine levels. RESULTS: Posttreatment day 8, prednisolone improved clinical scores for Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Investigator's Global Assessment (IGA), suppressed eosinophils, basophils, and select T(H)17/proinflammatory cytokines (IL-17A, IL-1β, and TGF-α) in allergen-challenged skin, reduced T(H)2 (IL-5, IL-9, IL-10, and IL-13) and T(H)1 (TNF-α) cytokines, and reduced chemokines (MIP-1β and TARC) in skin lesions (P < .05). IL-13, TNF-α, IFN-γ, and MCP-1 levels positively associated with the EASI, SCORAD, and IGA (r > 0.5; P < .05) in both allergen-challenged and lesional skin. CONCLUSIONS: Prednisolone modulated a broad range of inflammatory pathways in acute versus chronically inflamed AD skin. Furthermore, identification of positive associations between inflammation and clinical outcomes supports the development of therapeutics beyond type 2 inflammation.