Fatal acute pulmonary injury associated with everolimus.
Fatal acute pulmonary injury associated with everolimus.
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DOI：
10.1345/aph.1q623
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发表时间：
2012-03-01
期刊：
影响因子：
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通讯作者：
Caes, Frank
中科院分区：
文献类型：
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作者：
Depuydt, Pieter;Nollet, Joke;Caes, Frank
目的：报告一例致命的肺泡出血与使用依维莫司的患者谁经历了一个实体organ transplant.CASE概要：在一个71岁的心脏移植患者，环孢霉素被替换为依维莫司，因为肾功能恶化。在接下来的几周内，患者出现干咳和呼吸困难加重。他的病情恶化为急性呼吸衰竭伴咯血，需要住院治疗。胸部X线和计算机断层扫描显示双侧斑片状肺泡浸润明显。排除心力衰竭，开始经验性抗菌治疗。额外的广泛检查无法记录机会性感染。停用依维莫司，开始高剂量皮质类固醇治疗。尽管如此，患者仍需要有创机械通气，并因顽固性大咯血死亡。尸检显示弥漫性肺泡出血。讨论：依维莫司是一种哺乳动物雷帕霉素抑制剂的靶点，被批准用作免疫抑制剂和免疫抑制剂。其相对于钙调磷酸酶抑制剂（他克莫司和环孢霉素）的主要优势是独特的安全性。虽然依维莫司诱导肺毒性的频率比最初认为的更高，但迄今为止，大多数已发表的病例均为轻度和可逆性疾病，无致死性病例。在这里，我们报告了一个病例的肺毒性发展超过几个星期后，引入依维莫司，其中一个致命的结果不能阻止药物停药和皮质类固醇治疗。依维莫司和这种综合征的关联是可能的根据Naranjo概率scale.CONCLUSIONS：这种情况下表明，随着越来越多地使用依维莫司，临床医生应该知道的罕见的，但危及生命的表现肺毒性。
OBJECTIVE: To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant.CASE SUMMARY: In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage.DISCUSSION: Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale.CONCLUSIONS: This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.