Furst D E
Virginia Mason Research Center, University of Washington, Seattle 98101, USA.
Curr Opin Rheumatol. 2000 Nov;12(6):540-4. doi: 10.1097/00002281-200011000-00011.
The rational treatment of systemic sclerosis can be based on a model of its pathogenesis. This model posits a genetic background upon which external stimulae act, resulting in immune activation, vascular injury, fibroblast proliferation, and collagen deposition. The collagen, in turn, increases immune activation, thus resulting in perpetuation of the activation/injury cycle. If this pathogenetic model holds true, intervention can occur at the level of vascular damage, prevention of fibrosis or immunosuppression. Prevention of vascular damage and improvement of oxygenation has been attempted with prostacyclin derivatives, with mixed results. Prevention of fibrosis with interferon-gamma shows some hopeful results in pulmonary fibrosis. Relaxin, too, seems to hold hope for efficacy, whereas the results of therapy with D-penicillamine have been disappointing. Immunosuppression with chlorambucil has not been effective, but the study design was flawed in that trial. Methotrexate may work, but results are mixed. 5-Fluorouracil seems effective, but may be toxic. Cyclophosphamide is effective in open trials, and well-controlled trials are just starting. Finally, stem cell transplantation, a very aggressive form of immunosuppression, is showing some apparent efficacy, but its use is only in the pilot stages.
系统性硬化症的合理治疗可基于其发病机制模型。该模型假定存在一个遗传背景，外部刺激作用于其上，导致免疫激活、血管损伤、成纤维细胞增殖和胶原蛋白沉积。反过来，胶原蛋白会增加免疫激活，从而导致激活/损伤循环持续存在。如果这个发病机制模型成立，干预可以在血管损伤、预防纤维化或免疫抑制层面进行。使用前列环素衍生物尝试预防血管损伤和改善氧合，结果不一。使用γ-干扰素预防纤维化在肺纤维化方面显示出一些有希望的结果。松弛素似乎也有望产生疗效，而青霉胺治疗的结果却令人失望。使用苯丁酸氮芥进行免疫抑制无效，但该试验的研究设计存在缺陷。甲氨蝶呤可能有效，但结果不一。5-氟尿嘧啶似乎有效，但可能有毒性。环磷酰胺在开放试验中有效，而严格对照试验才刚刚开始。最后，干细胞移植作为一种非常激进的免疫抑制形式，显示出一些明显的疗效，但它的使用仅处于试验阶段。
