HIGH-DOSE UVA(1) RADIATION-THERAPY FOR LOCALIZED SCLERODERMA

Background: Fibrotic skin lesions in patients with localized scleroder ma can cause muscle atrophy, disfigurement, and flexion contractures. There is no effective therapy for this disease. Skin fibrosis is thoug ht to be caused by decreased collagenase activity. Collagenase activit y can be induced in dermal fibroblasts by UVA(1) irradiation. Objectiv e: Our purpose was to assess whether UVA(1) radiation therapy is effec tive for patients with localized scleroderma. Methods. Patients with l ocalized scleroderma (n = 17) were exposed 30 times to 130 J/cm(2) UVA (1) (high-dose UVA(1) therapy; n = 10) or 20 J/cm(2) UVA(1) (low-dose UVA(1) therapy; n = 7). Therapeutic effectiveness was assessed by eval uation of (1) clinical features, (2) thickness of sclerotic plaques, a nd (3) cutaneous elastometry. Sequential biopsy specimens from treated lesions were analyzed for collagenase I messenger RNA (mRNA) expressi on by semiquantitative reverse transcriptase-polymerase chain reaction . Results: In all patients, high-dose UVA(1) therapy softened scleroti c plaques, and complete clearance was observed in four of 10 patients. High-dose UVA(1) therapy significantly reduced thickness and increase d elasticity of plaques, These changes could not be detected in unirra diated control plaques and were still present in 9 of 10 patients 3 mo nths after cessation of therapy, For all factors assessed, high-dose U VA(1) was superior to tow-dose UVA(1) therapy (p = 0.001). High-dose U VA(1) therapy increased collagenase I mRNA expression about 20-fold in treated plaques. Conclusion: High-dose UVA(1) therapy is effective in the treatment of localized scleroderma. Effectiveness is UVA(1) dose dependent and is associated with induction of collagenase I expression .