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， 非干酪化性肉芽肿的形成。 疾病可以是自我 局限性或慢性，从无症状到终末器官衰竭。 的 疾病可能会影响肺，胸部淋巴结，皮肤，眼睛和其他 机关 皮质类固醇仍然是结节病的主要治疗方法。 然而，在这方面， 类固醇治疗有多种副作用， 病程。 促炎细胞因子TNF-α可能在炎症反应中起作用。 在介导结节病活动中的重要作用。 TNF-alpha 由活化的巨噬细胞产生的产物是细胞中的重要元素 介导的免疫反应导致肉芽肿形成。 的血清水平 结节病中TNF-α和可溶性TNF-α受体升高 患者，并与疾病活动相关。沙利度胺，一种 TNF-α的产生，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、阿弗他溃疡形成、麻风结节性红斑，以及 他人 在抗生素治疗方案中加入沙利度胺也 改善M.结核 肺部和中枢神经系统感染。本研究将 评价沙利度胺每日给药治疗结节病的效果 患者在4个月内，使用基于临床和实验室的 疾病活动的测量。 连续记录的临床疾病活动 测量包括肺量测定、皮肤照片、红细胞沉降 比率、健康评估表和关节计数。 胸部x光 并在几个规定的时间进行几次皮肤活检 点 基于实验室的疾病活动性测量包括血浆TNF-α。 α和可溶性TNF-α受体，可溶性白细胞介素2受体，和 细胞间粘附分子-1。 γ干扰素血浆水平 也将被确定。T淋巴细胞亚群和抗原刺激 将测量淋巴细胞增殖。 该患者的药物安全性 将通过血液化学和细胞计数、病史和 每月进行一次体格检查和肾功能评估 病人访问。

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.