Mycophenolate mofetil for localized scleroderma

Commentary Systemic sclerosis is one of the rheumatic diseases that is associated with the worst prognosis. Systemic sclerosis is divided into localized and systemic forms. Localized scleroderma comprises four subtypes, namely morphea, generalized morphea, linear scleroderma and en coup de saber, and is more commonly encountered in children. Although conversion into systemic sclerosis is very uncommon [1], localized scleroderma can be extremely disabling owing to formation of mutilating contractures and deformities, and cosmetic dis figurement, as well as the increased susceptibility of the sclerodermatous tissue to ulceration and malignant transformation. There are many treatment options of localized scleroderma, but their efficacy have not been confirmed by controlled trials. These include ultraviolet-A phototherapy, highly potent topical glucocorticoids, calcipotriol, d-penicillamine, hydroxychloroquine, methotrexate (MTX) and cyclosporin A [2–4]. A recent, open-label, prospective study has reported efficacy and safety of monthly intravenous pulse methylprednisolone and oral MTX (15 mg/week) in the treatment of severe localized scleroderma [5]. Combined high-dose methylprednisolone, cyclosporin A and antithymocyte globulin has also been reported to be effective in a patient with refractory pansclerotic morphea [6]. However, these treatment regimens are not universally effective and may be associated with potentially serious side effects. Thus, there is a need to explore safer and more effective treatment for localized scleroderma. Mycophenolate mofetil (MMF) is an immunosuppressive agent commonly used in transplant medicine and autoimmune diseases owing to its inhibitory effects on lymphocyte functions. Recent in vitro studies have also revealed that MMF suppresses the functions of smooth muscle cells and fibroblasts [7]. Martini et al. recently reported good response of ten juvenile patients with severe or refractory localized scleroderma to MMF treatment [8]. Although the findings of this retrospective study are anecdotal and have to be confirmed by larger scale, placebo-controlled trials, they suggest that MMF exerts both antiinflammatory and antifibrotic actions on skin lesions of scleroderma.