CONNECTIVE TISSUE DISEASES/INFLAMMATORY MYOPATHIES--POLYMYOSITIS/DERMATOMYOSITIS

结缔组织和疾病科开始研究炎症性 肌病(多发性肌炎、皮肌炎和相关疾病) 几年前，在试图了解自身抗体与 自身免疫性疾病。这些疾病似乎提供了最好的例子 与高度特异性疾病相关的自身免疫性疾病 自身抗体和病毒病原学的证据。他们非常罕见。 因此，与其他自身免疫性疾病相比，研究相对较少，它们 是非常虚弱的，因此需要改进治疗。为了 吸引患者到这里来，让更详细的临床，免疫学， 基因和病毒研究，我们开始进行治疗试验，并 完成了许多这样的研究。它们是为数不多的出版的作品之一。 在这个难以治疗的疾病家族中进行对照试验。 目前，有三项试验处于不同完成阶段。1)A 大剂量静脉注射甲氨蝶呤与甲氨蝶呤的随机交叉试验 口服甲氨蝶呤和硫唑嘌呤的联合治疗已于去年完成 分析已经完成，并准备在今年发表。 联合治疗的价值，即使在那些失败的患者中 仅在两种药物的试验中都有改善，这一点已经明确确立。2) 一项嘌呤类似物氟脱氧腺苷的中试纳入了14人 患者，其中最后一位最近完成了完整的观察 句号。这种优先影响淋巴细胞的药物正在被 在研究了几种自身免疫性疾病后，有广泛的经验 毛细胞性白血病。对审判的分析正在进行中。如果有 在足够数量的患者中有疗效的证据， 将进行对照、随机试验。3)试行 传统的抗甲状腺药物他咪唑正在顺利进行中。这个 这项试验的基本原理是D.Singer和L.Kohn发现 该药下调MHC I类，上调I类出现 是肌炎的重要致病事件。除了……之外 关于他巴唑的临床疗效，有广泛的研究 在实验室中与这一建议的作用机制相关(见Z01 AR 41074-08 ARB)。

The Connective Tissue and Diseases Section began studying inflammatory myopathies (polymyositis, dermatomyositis, and related diseases) some years ago in an attempt to understand the relationship of autoantibodies to autoimmune disease. These diseases seemed to offer the best example of autoimmune diseases associated with highly specific disease-related autoantibodies and evidence of a viral etiology. They are very uncommon and hence relatively less studied than other autoimmune diseases, and they are very debilitating and hence in need of improved therapy. In order to attract patients here to allow more detailed clinical, immunological, genetic, and viral studies, we began doing trials of therapy and have completed a number of such studies. They are among the very few published controlled trials in this difficult to treat family of illnesses. Currently, there are three trials in various stages of completion. 1) A randomized crossover trial of high dose intravenous methotrexate and of a combination of oral methotrexate and azathioprine was completed last year and the analysis was completed and prepared for publication this year. The value of the combination therapy, even in patients who had failed to improve in trials of either drug alone, has been clearly established. 2) A pilot trial of the purine analogue, flurodeoxyadenosine, enrolled 14 patients, the last of whom has recently completed the full observation period. This drug, which preferentially affects lymphocytes, is being studied in several autoimmune diseases after an extensive experience in hairy cell leukemia. Analysis of the trial is just underway. If there is evidence of efficacy in a sufficient number of patients, a larger controlled, randomized trial will be undertaken. 3) A pilot trial of the traditional anti-thyroid drug, methimazole, is well underway. The rationale for this trial is the discovery by D. Singer and L. Kohn that this drug down-regulates MHC Class I, and up-regulation of Class I appears to be an important pathogenetic event in myositis. In addition to studying the clinical efficacy of methimazole, there are extensive studies in the laboratory related to this proposed mechanism of action (see Z01 AR 41074-08 ARB).