Effect of increased pigmentation on the antifibrotic response of human skin to UV-A1 phototherapy.

OBJECTIVE To investigate the efficacy, potential limitations, and biological mechanisms of UV-A1 phototherapy for skin sclerosis due to collagen deposition disorders. DESIGN Before-and-after trial of UV-A1 irradiation of sclerotic skin; in vivo biochemical analyses after UV-A1 irradiation of normal skin. SETTING Academic referral center. PARTICIPANTS Patients with morphea/scleroderma or sclerodermoid graft-vs-host disease and volunteers without skin disease. Intervention Sclerotic skin was treated with high-dose (130 J/cm(2); n = 12) or medium-dose (65 J/cm(2); n = 6) UV-A1 phototherapy 3 times per week for 14 weeks; normal skin was treated with UV-A1 irradiation at various doses and frequencies, with biopsies performed afterwards. MAIN OUTCOME MEASURES In sclerotic skin, induration was clinically assessed using a scoring scale. In normal skin, quantitative polymerase chain reaction was used to assess antifibrotic responses, defined as decreased type I and type III procollagen and increased matrix metalloproteinase levels. RESULTS In patients with sclerotic skin treated with high-dose UV-A1 irradiation, clinical scores for induration modestly decreased. To investigate what factors prevented further improvement (ie, complete clearance), normal skin with light pigmentation was exposed to UV-A1 irradiation (70-150 J/cm(2)) and was assessed for antifibrotic responses. A single high-dose exposure (110-150 J/cm(2)) elicited substantial antifibrotic responses and induced skin darkening. This skin darkening attenuated responses to subsequent UV-A1 exposures and was dose dependent. Thus, to minimize skin darkening, additional patients with sclerotic skin were treated with medium-dose UV-A1 phototherapy, which was no less effective than high-dose therapy. CONCLUSION Clinical responses of sclerotic skin to UV-A1 phototherapy were modest because of UV-A1-induced skin darkening, which is photoprotective and attenuates antifibrotic responses. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00129415.