Open label trial of tamoxifen in scleroderma.

BACKGROUND Previous reports have suggested that treatment with the selective estrogen antagonist tamoxifen may be effective in diminishing primary and secondary Raynaud's vasospasm, including cases occurring in the setting of scleroderma. Tamoxifen treatment has also been associated with improvement of retroperitoneal fibrosis and desmoid tumors, conditions also associated with abnormal fibroblast proliferation. Tamoxifen increases production of the immunosuppressive cytokine TGF beta which modulates fibroblast activity. The potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised questions about its utility as a therapeutic agent in scleroderma. OBJECTIVE To determine the utility of tamoxifen therapy in scleroderma. METHODS Open label preliminary, prospective, proof of concept study of tamoxifen. RESULTS Fifteen patients (3 male, 12 female) with scleroderma were enrolled (10 diffuse disease, 5 CREST). Mean age was 55 (34-75) years. Mean duration of scleroderma was 9.3 (1-25) years. Two patients were excluded. For 13 patients, mean duration of treatment was 7 (1.5-32) months. Two of 13 patients treated with tamoxifen experienced transient improvement. They did not appear to have clinical features that identified them as a unique subset. Both patients subsequently relapsed, in one case 12 months, and in the other 24 months after treatment. CONCLUSION Based on these results, we would not recommend tamoxifen for further large scale studies in scleroderma.