Reversal of Atopic Dermatitis with Narrow-Band UVB Phototherapy and Biomarkers for Therapeutic Response

Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/T22 immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/T22-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the inside-out hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus.

35

Tintle S, Shemer A, Suárez-Fariñas M, Fujita H, Gilleaudeau P, Sullivan-Whalen M, Johnson-Huang L, Chiricozzi A, Cardinale I, Duan S, Bowcock A, Krueger JG, Guttman-Yassky E