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，这些患者中的大多数都经历了进行性疾病，具有显著的发病率和死亡率。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相似之处。此外，最近的报道表明，母胎细胞跨越胎盘膜的交换和持续的微嵌合体可能有助于硬皮病的发病。药物沙利度胺在20世纪60年代初因其致畸作用而闻名，后来被发现在许多免疫介导性疾病中具有抗炎和免疫调节作用，包括移植物抗宿主病。此外，初步研究表明，移植物抗宿主病的常规治疗方法环孢素A在治疗硬皮病方面可能有效。沙利度胺在硬皮病患者中的应用尚未见报道。这项试点研究将通过建立患者的基线临床和血清学档案，然后在超过12周的初始剂量递增过程中跟踪这些参数，并持续维持治疗长达一年，获得关于沙利度胺在硬皮病患者中的安全性和耐受性的初步数据。

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.