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.


METHODS
Before-and-after trial of UV-A1 irradiation of sclerotic skin; in vivo biochemical analyses after UV-A1 irradiation of normal skin.


METHODS
Academic referral center.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00129415.
Wang
Frank
F
Department of Dermatology, University of Michigan Medical School, 1618 A. Alfred Taubman Healthcare Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA. frawang@med.umich.edu
Garza
Luis A
LA
Cho
Soyun
S
Kafi
Reza
R
Hammerberg
Craig
C
Quan
Taihao
T
Hamilton
Ted
T
Mayes
Maureen
M
Ratanatharathorn
Voravit
V
Voorhees
John J
JJ
Fisher
Gary J
GJ
Kang
Sewon
S
D000328:Adult; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011829:Radiation Dosage; D012594:Scleroderma, Localized / Q000473:pathology / Q000532:radiotherapy*; D012720:Severity of Illness Index; D012867:Skin / Q000528:radiation effects*; D016896:Treatment Outcome; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy / Q000009:adverse effects*
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases