Treatment of Generalized Morphea with Oral 1.25-Dihydroxyvitamin D₃

Abstract

Scleroderma is a chronic connective tissue disease characterized by excessive collagen synthesis and its deposition in the skin and various internal organs. Immune system abnormalities and disturbances of connective tissue metabolism have been suggested to play a central role in the pathogenesis of scleroderma. 1.25-Dihydroxyvitamin D₃ (1.25(OH)₂ D₃ causes inhibition of fibroblast growth, has a role in controlling collagen synthesis and deposition and has numerous immunoregulatory activities. We assessed the effects of oral 1,25 (OH)₂ D₃ in the treatment of patients with generalized morphea. Three patients with generalized morphea, entered an open prospective study. They were treated with oral calcitriol (1,25 dyhidroxyvitamin D₃) in an oral daily dose of 0.50-0.75 μg. After the treatment period of 4–6 months, a significant clinical improvement was observed. The mobility of the joints improved, the skin extensibility increased and a substantial improvement of the skin induration. No serious side effects were observed. The improvement persisted after discontinuation of therapy during a follow-up period of one year. The evolution of the patients’ condition during the 6 months therapy with calcitriol, suggests that it can be used as a beneficial agent in the treatment of generalized morphea. Double- blind, placebo-controlled trials are needed to assess its therapeutic value and a larger number of patients is desirable.

Scleroderma is a chronic connective tissue disease in which, after an inflammatory phase, sclerosis of circumscribed or generalized areas of skin develops with or without the involvement of internal organs. Morphea is a form of scleroderma that is limited to the skin.

The etiology and pathogenesis of scleroderma remains unknown, hereditary tendency is sometimes present and an autoimmune basis is widely suspected, but actual mechanisms have not been precisely identified. Various therapeutic modalities have been used or proposed for the treatment of scleroderma, but their efficacy has not been proven in most cases.

Recently, Hulshof et al. [4] and Humbert et al. [3] reported a beneficial effect of oral 1 ,25-dihydroxyvitamin D3 (calcitriol) in patients with morphea. Calcitriol is the biologically active metabolite of Vitamin D3 and acts on target tissues (fibroblasts and lymphocytes), passing cellular membra:o.es easily and bind with high affinity to a nuclear receptor [6].

1,25 (OH)2 D3 causes dose-dependent inhibition of fibroblast growth and collagen synthesis, and has numerous immunoregulatory activities [3]. Therefore, encouraged by the promising results in the literature, we decided to begin treatment with calcitriol in three patients with generalized morphea (disseminated localized scleroderma).