Suggested mechanisms of action of UVA phototherapy in morphea: a molecular study.
BACKGROUND
Ultraviolet A (UVA) phototherapy proved to be an efficient line of treatment of scleroderma. The mechanism through which it acts is still not clear.


OBJECTIVE
To detect the mechanism of action of UVA phototherapy in morphea through measuring its effect on the levels of different parameters related to collagen metabolism.


METHODS
Twenty-one cases of morphea were treated with low-dose broad-band UVA for 20 sessions. Twelve cases received 20 J/cm(2)/session with a cumulative dose of 400 J/cm(2) and nine cases received 10 J/cm(2)/session with a cumulative dose of 200 J/cm(2). The response was assessed clinically every week. Two skin biopsies were taken from the lesional skin of each patient before starting and after the end of therapy. Paraffin sections were examined for quantitative polymerase chain reaction measurement of collagen I, collagen III, collagenase, transforming growth factor-beta (TGF-beta) and interferon gamma (IFNgamma).


RESULTS
Eighteen patients reported remarkable softening of the skin lesions, with variable degrees ranging from moderate in 57.1% of them good in 19% to very good response in 9.5%. After treatment, all the studied parameters revealed statistically significant changes. There was a significant decrease in collagen I, collagen III and TGF-beta and a significant increase in collagenase (MMP-1) and IFNgamma. The relative change was found to be greatest in collagenase, followed by IFNgamma then TGF-beta and finally collagen I. The changes in collagen I, collagenase, IFNgamma and TGF-beta were found to increase gradually with the degree of clinical response. In all the parameters studied the relative change was significantly higher in cases treated with 20 J/cm(2)/session in contrast to those treated with 10 J/cm(2)/session although no statistically significant difference could be detected in the clinical response to those doses.


CONCLUSIONS
The efficacy of low-dose UVA phototherapy in the treatment of localized scleroderma is mainly obtained by the increased production of MMP-1 and IFNgamma, and to a lesser extent by decreasing TGF-beta and collagen production. Concerning the use of 10 or 20 J/cm(2)/session those effects are dose dependent, but the clinical response does not significantly differ.
El-Mofty
M
M
Department of Dermatology, Phototherapy Unit, Faculty of Medicine, Cairo University, Egypt.
Mostafa
W
W
Esmat
S
S
Youssef
R
R
Bousseila
M
M
Nagi
N
N
Shaker
O
O
Abouzeid
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002648:Child; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012594:Scleroderma, Localized / Q000473:pathology / Q000532:radiotherapy*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014467:Ultraviolet Therapy / Q000379:methods*
D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D003094:Collagen; D017364:Collagenases