Pathobiology of atopic dermatitis and association with disease severity after acute oral steroid treatment

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.

We sought to evaluate the association between clinical severity and skin inflammation in AD.

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.

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_H17/proinflammatory cytokines (IL-17A, IL-1β, and TGF-α) in allergen-challenged skin, reduced T_H2 (IL-5, IL-9, IL-10, and IL-13) and T_H1 (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.

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.