Effect of Increased Pigmentation on the Antifibrotic Response of Human Skin to UV-A1 Phototherapy

Abstract

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 highdose (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 highdose 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.

Update on morphea

“…Forty-seven of the patients had morphea, and again, no difference in efficacy of therapy was noted across the five skin types. 42 This is in contrast to a 2008 molecular-based prospective trial carried out by Wang et al 43 Wang et al 43 made several interesting observations. First, skin type was predictive of the amount of decline of type 1 and type 3 collagen and the increase of matrix metalloproteinases after treatment with high dose UVA1 (ie, the lighter the skin type, the more dramatic the changes and the darker the skin type, the less dramatic the changes).…”

“…First, skin type was predictive of the amount of decline of type 1 and type 3 collagen and the increase of matrix metalloproteinases after treatment with high dose UVA1 (ie, the lighter the skin type, the more dramatic the changes and the darker the skin type, the less dramatic the changes). 43 Secondly, they noted a statistically significant reduction in collagen 1 and 3 production after one treatment of high dose UVA1, that was not seen in patients treated with three high dose UVA1 sessions before measurement. 43 These findings lead them to suggest that UVA1 be provided in pulse therapy, to prevent tanning and increase efficacy, as well as in low doses, for similar reasons.…”

“…What is lacking is agreement on the correct dosing regimen or frequency, total exposure, and whether UVA1 is effective in patients with darker skin tones (ie, Fitzpatrick skin types $ IV). 42,43 Since 1995, 121 patients with morphea treated prospectively with UVA1 have been reported in the literature. 10,17,18,27,28,37,[44][45][46] These patients ranged in age from 3 to 73 years and had morphea based on clinical and histologic findings with a range of duration from 6 months to 20 years.…”

Natural and Sun-Induced Aging of Human Skin

“…2). Because melanin pigments are photoprotective (Kollias et al 1991), the biological effects of UV irradiation are more pronounced in individuals with light versus dark skin Wang et al 2008). In lightly pigmented human skin in vivo, transcripts encoding MMP-1, -3, and -9 are induced within 8 h after UV irradiation (Fisher et al 1996) and enzyme activities are observed 24 h postirradiation in human skin in vivo (Fisher and Voorhees 1998).…”

Phototherapy for sclerosing skin conditions

“…This led the authors to conclude that UVA1 phototherapy should be considered a reasonable therapeutic option in patients with darker skin type. Another report was published shortly thereafter by Wang et al which demonstrated rapid UVA1-induced pigmentation and concomitant abrogation of induction of matrix metalloproteinases in normal buttock skin [33]. This suggests that increased pigmentation, both pre-existing (constitutional) and UVA1-induced (facultative), attenuated responses to UVA1 phototherapy.…”