PILOT INVESTIGATION OF SAFETY AND EFFICACY OF THALIDOMIDE IN SARCOIDOSIS

结节病是一种病因不明的多系统疾病，其特征是 非干酪性肉芽肿的形成。疾病的牵连可以是自身的 局限性或慢性，从无症状到终末性器官衰竭。这个 疾病可能影响肺部、胸腔淋巴结、皮肤、眼睛和其他 器官。皮质类固醇仍然是结节病的主要治疗方法。然而， 类固醇治疗有多种副作用，可能无法改变 病程。促炎细胞因子肿瘤坏死因子-α可能在 在调节结节病活动中的重要作用。肿瘤坏死因子-α 激活的巨噬细胞产生的物质是细胞中的一个重要元素。 介导的免疫反应导致肉芽肿的形成。血清中的水平 肿瘤坏死因子-α和可溶性肿瘤坏死因子-α受体在结节病中升高 并与疾病活动性相关。沙利度胺，血管紧张素转换酶抑制剂 产生的肿瘤坏死因子-α，已被证明具有抗炎和 在许多自身免疫性疾病中的免疫调节作用，包括 盘状狼疮，口腔溃疡形成，结节性麻风红斑，以及 其他。在抗生素方案中加入沙利度胺也有 改善结核分枝杆菌动物模型的发病率和死亡率 肺部和中枢神经系统的感染。这项研究将 沙利度胺每日给药治疗结节病的疗效评价 患者在4个月内，使用基于临床和实验室的 疾病活跃性衡量标准。连续记录的临床疾病活动 测量包括肺活量、皮肤照片、红细胞沉降值。 比率、健康评估问卷和联合计数。胸部X光片 并将在几个确定的时间进行几次皮肤活检 积分。基于实验室的疾病活动性测量包括血浆肿瘤坏死因子- α和可溶性肿瘤坏死因子-α受体、可溶性白介素2受体和 细胞间黏附分子-1。干扰素-γ血浆水平 也将被确定。T淋巴细胞亚群与抗原刺激 将测量淋巴细胞的增殖率。这位患者的用药安全性 将通过血液化学和细胞计数、病史和 每月进行体检和肾功能评估 探望病人。

Sarcoidosis is a multisystem disease of unknown etiology characterized by the formation of noncaseating granulomas. Disease involvement can be self limited or chronic, ranging from asymptomatic to end organ failure. The disease may affect lungs, thoracic lymph nodes, skin, eyes, and other organs. Corticosteroids remain the primary sarcoidosis therapy. However, steroid treatment has multiple side effects and may fail to alter the disease course. The proinflammatory cytokine TNF-alpha may play an important role in mediating sarcoid disease activity. TNF-alpha production by activated macrophages is an important element in the cell mediated immune response leading to granuloma formation. Serum levels of TNF-alpha and soluble TNF-alpha receptors are elevated in sarcoidosis patients and correlate with disease activity. Thalidomide, an inhibitor of TNF-alpha production, has been shown to have both anti-inflammatory and immune modulating effects in a number of autoimmune diseases, including discoid lupus, aphthous ulcer formation, erythema nodosum leprosum, and others. The addition of thalidomide to antibiotic regimens has also improved morbidity and mortality in animal models of M. tuberculosis infection of the pulmonary and central nervous systems. This study will evaluate the effect of daily thalidomide administration in sarcoidosis patients over a 4 month period, using clinical and laboratory based disease activity measures. Serially recorded clinical disease activity measures include spirometry, skin photographs, erythrocyte sedimentation rates, Health Assessment Questionnaires, and joint counts. Chest x-rays and several skin biopsies will be performed at several defined time points. Laboratory based disease activity measures include plasma TNF- alpha and soluble TNF-alpha receptor, soluble interleukin 2 receptor, and intercellular cell adhesion molecule-1. Interferon gamma plasma levels will also be determined. T-lymphocytes subsets and antigen-stimulated lymphocyte proliferation will be measured. Drug safety in this patient group will be monitored by blood chemistries and cell counts, history and physical exams, and renal function assessments performed during monthly patient visits.