Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.
Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.
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DOI：
10.1097/00007890-200109150-00008
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发表时间：
2001-09-15
期刊：
影响因子：
6.2
通讯作者：
Kreis, H
中科院分区：
文献类型：
--
作者：
Morelon, E;Stern, M;Kreis, H
背景。西罗莫司是一种很有前景的用于器官移植的新型免疫抑制药物，目前存在血小板减少和高脂血症等副作用。8例在西罗莫司治疗期间发生不明原因间质性肺炎的肾移植受者，对所有病因的肺炎进行了广泛的重新筛查。间质性肺炎在胸部x线和肺部计算机断层扫描上以双侧间质浸润为特征，除1例患者外，所有患者均有明显的一般症状。支气管肺泡灌洗（BAL）显示淋巴细胞性肺泡炎（以CD4型为主）7例，肺泡出血1例。两例患者经支气管肺活检显示闭塞性细支气管炎合并组织性肺炎合并淋巴细胞间质性肺炎。通过BAL、支气管吸出物和血液培养的特异性染色和培养排除肺部感染。在排除了所有可能的原因后，西罗莫司引起的肺炎被认为是可能的。停用西罗莫司7例，其余病例减少剂量，在几周内显著改善了临床和放射学状况，并在3个月内完全缓解。西罗莫司很可能导致间质性肺炎，原因如下：(a)在西罗莫司治疗期间发生肺炎；(b)无其他原因；(c)西罗莫司停药或减量后3个月内的缓解。西罗莫司现在应该被添加到肾移植后肺部并发症的可能原因列表中。停药或减少西罗莫司的剂量导致症状的完全和持久的解决。
Background. Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia.Methods. Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis.Results. Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months.Conclusions. Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.