Marder Wendy, McCune W Joseph
Department of Internal Medicine, Division of Rheumatology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Semin Respir Crit Care Med. 2004 Oct;25(5):581-94. doi: 10.1055/s-2004-836149.
Several recent advances in the use of immunosuppressive drugs in autoimmune disease are relevant to management of autoimmune pulmonary disease. Sequential immunosuppression combining remission induction with cyclophosphamide with less toxic maintenance therapy such as azathioprine, methotrexate, or mycophenolate mofetil is described in Wegener's granulomatosis, systemic vasculitis, and lupus. Less aggressive forms of diseases that have been routinely treated with cyclophosphamide have been treated with alternate regimens (e.g., methotrexate treatment of limited Wegener's granulomatosis, and mycophenolate mofetil for lupus). Finally, strategies to minimize severe side effects of immunosuppression include genetic testing for predisposition to drug toxicity and proposed techniques for fertility preservation during cyclophosphamide treatment. We review established principles of immunosuppressive drug use and focus on clinical trials in autoimmune diseases that illustrate therapeutic approaches which are likely to be applied more widely in the future. More detailed reviews of treatment of individual diseases will be found in elsewhere in this issue.
免疫抑制药物在自身免疫性疾病中的应用取得了多项最新进展,这些进展与自身免疫性肺病的治疗相关。在韦格纳肉芽肿、系统性血管炎和狼疮中,描述了序贯免疫抑制疗法,即先用环磷酰胺诱导缓解,再用毒性较小的维持疗法,如硫唑嘌呤、甲氨蝶呤或霉酚酸酯。一些原本常规用环磷酰胺治疗的病情较轻的疾病,已采用替代方案治疗(例如,用甲氨蝶呤治疗局限性韦格纳肉芽肿,用霉酚酸酯治疗狼疮)。最后,将免疫抑制严重副作用降至最低的策略包括进行药物毒性易感性基因检测,以及在环磷酰胺治疗期间采用提议的生育力保存技术。我们回顾了免疫抑制药物使用的既定原则,并重点关注自身免疫性疾病的临床试验,这些试验阐明了未来可能会更广泛应用的治疗方法。本期其他地方会有对个别疾病治疗的更详细综述。