PILOT INVESTIGATION OF THE SAFETY AND EFFICACY OF THALIDOMIDE IN SCLERODERMA

硬皮病是一种病因不明的结缔组织疾病，其特征是皮肤和内脏器官过度纤维化。硬皮病患者对传统的免疫抑制和抗炎方案没有反应，并且这些患者中的大多数经历具有显著发病率和死亡率的进行性疾病。发生在骨髓移植患者中的慢性移植物抗宿主病与硬皮病有许多共同特征。 此外，最近的报告表明，跨胎盘膜的母胎细胞交换和持续的微嵌合体可能有助于硬皮病的发病机制。 在20世纪60年代早期以其致畸作用而闻名的药物沙利度胺，此后被发现在许多免疫介导的疾病（包括移植物抗宿主病）中具有抗炎和免疫调节作用。 此外，初步研究表明，移植物抗宿主病的常规治疗，环孢素A，可能是有效的治疗硬皮病。 沙利度胺在硬皮病患者中的使用尚未报道。 这项初步研究将通过建立患者的基线临床和血清学特征，获得沙利度胺在硬皮病患者中的安全性和耐受性的初步数据，然后在12周的初始剂量递增过程中每日暴露于沙利度胺期间跟踪这些参数，并继续维持治疗长达一年。

Scleroderma is a connective tissue disease of unknown etiology characterized by excessive fibrosis of the skin and visceral organs. Scleroderma patients have not responded to traditional immunosuppressive and anti-inflammatory regimens, and the majority of these patients experience progressive disease with marked morbidity and mortality. Chronic graft versus host disease that occurs in bone marrow transplant patients shares many characteristics with scleroderma. In addition, recent reports have suggested that maternal-fetal exchange of cells across placental membranes and persistent microchimerism may contribute to scleroderma pathogenesis. The drug thalidomide, previously known for its teratogenic effects in the early 1960's, has since been found to have anti-inflammatory and immune-modulating effects in a number of immune mediated diseases, including graft-versus-host disease. Furthermore, preliminary studies suggest that the conventional treatment of graft-versus-host disease, cyclosporin A, may be effective in treating scleroderma. Thalidomide use has not been reported in scleroderma patients. This pilot study will obtain preliminary data on the safety and tolerability of thalidomide in scleroderma patients by establishing baseline clinical and serological profiles of patients and then follow those parameters during daily exposure to thalidomide over an initial dose escalation course over 12 weeks, with continued maintenance therapy for up to one year.