来氟米特诱导的间质性肺炎文献分析

目的研究来氟米特诱导的间质性肺炎(Lef-IP)的临床特征,为其临床诊治、预防提供参考。方法收集2004年1月-2021年6月国内公开发表的Lef-IP病例报告,提取患者相关信息(基本特征、临床表现、影像学表现、实验室检查结果、组织病理学检查结果、治疗与转归等),进行回顾性分析。结果共纳入24篇文献,包含54例Lef-IP患者,中位年龄61岁(9~83岁),肺部症状出现在用药后3.3~132.9周(中位时间14.5周),给予来氟米特负荷剂量的患者出现肺部症状中位时间更短(7.5周)。患者主要的临床表现为呼吸困难(占85.2%)、咳嗽(占57.4%)、发热(占53.7%);影像学检查中CT表现为双肺磨玻璃影的有19例,胸片表现为双肺间质性浸润的有29例;血气分析可表现为低氧血症和低碳酸血症;C反应蛋白和涎液化糖链抗原水平增高;组织病理学检查主要表现为间质性肺炎(8例),其中弥漫性肺泡损伤3例、支气管肺泡灌洗液出现淋巴细胞4例、非干酪性肉芽肿1例。停用来氟米特并给予相应处理(抗菌药物、激素、考来烯胺、血浆置换)后,35例(占64.8%)患者肺部症状恢复正常或好转。12例(占22.2%)患者死亡,而与未发热患者(8.0%)相比,发热患者可能有更高的病死率(34.5%,P=0.02)。结论Lef-IP的主要临床表现为呼吸困难、咳嗽、发热。应该避免一开始就给予负荷剂量来氟米特治疗;当出现Lef-IP时,停用来氟米特并给予相应治疗,大部分患者肺部症状可恢复正常或好转。

Literature analysis of leflunomide-induced interstitial pneumonia

OBJECTIVE To study the clinical characteristics of leflunomide-induced interstitial pneumonia(Lef-IP),and to provide reference for its clinical diagnosis,treatment and prevention.METHODS Lef-IP cases published in domestic and foreign journals from January 2004 to June 2021 were collected.Relevant information of patients were extracted and analyzed retrospectively,including basic characteristics,clinical manifestations,imaging manifestations,laboratory examinations,histopathological examinations,treatment and outcome.RESULTS A total of 54 Lef-IP patients from case reports of 24 publications were included,with a median age of 61 years(9-83 years).Pulmonary symptoms appeared from 3.3 weeks to 132.9 weeks(median time of 14.5 weeks).Patients with a loading dose of leflunomide have a shorter median time to pulmonary symptoms appearing(7.5 weeks).The main clinical manifestations were dyspnea(85.2%),cough(57.4%),fever(53.7%).CT imaging examination showed 19 cases with ground-glass shadow in both lungs,and 29 cases showed interstitial infiltration in both lungs on chest radiograph;blood gas analysis showed hypoxemia and hypocapnia;the levels of C-reactive protein and Krebs von Den lungen-6(KL-6)increased;histopathological examination mainly showed interstitial pneumonia(8 cases),including 3 cases of diffuse alveolar injury,4 cases of lymphocytes in bronchoalveolar lavage fluid,and 1 case of noncaseating granuloma.After discontinued leflunomide and symptomatic treatment(antibiotics,hormones,colecenamine,plasma exchange),35 patients(64.8%)recovered or improved their lung symptoms.Twelve patients(22.2%)died,and patients with fever may had a higher mortality rate(34.5%,P=0.02).CONCLUSIONS The main clinical manifestations of Lef-IP are dyspnea,cough and fever.Loading doses of leflunomide should be avoided at the beginning of treatment.When lef-IP occurs,leflunomide is discontinued and corresponding treatment is given,and most of the patients’pulmonary symptoms can return to normal or be improved.