病患使用Methotrexate所引發之肺炎的臨床表徵兒－－南台灣一醫學中心之經驗

Clinical characteristics of patients with methotrexate-related pneumonitis in a medical center in southern Taiwan

Methotrexate（MTX）是類風濕關節炎最廣為使用的疾病修飾抗風濕藥物。雖並非常見之副作用，自一九八零年代起已有報告指出每週給予低劑量的MTX可造成肺毒性或肺炎。在此我們報告於使用MTX過程中發生此副作用的四位類風濕關節炎及一位多發性肌炎合併關節炎病患，並根據三套MTX肺炎的診斷準則加以區分這些病患為確定是、很可能是或可能是MTX肺炎的病例。病患之臨床表現包括急性至亞急性的呼吸及體質性症狀，其發生頻率與過去文獻所報導的相當。胸部影像學檢查顯示間質性浸潤或肺泡性陰影。在我們這些病例中，高齡及低蛋白血症可能是發生MTX肺炎的危險因子。住院後所有病患皆立即停用MTX並於住院初期給予抗生素，大部分病患使用類固醇以加速病情的改善。大邪分病患的臨床症狀及影像學異常皆迅速恢復。當病患僅有乾咳時，支氣管肺泡灌洗液的培養可確認肺部發炎並非源自於感染。若能適當使用MTX的肺炎診斷準則，肺部切片對MTX肺炎的診斷並非絕對需要。所有病人於開始投予MTX前應接受胸部影像學檢查，並教育病患隨時告知醫師任何呼吸道或肺部不過的症狀以盡早診斷此藥物副作用。

Methotrexate (MTX) is the most widely used disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). Occurrence of pulmonary toxicity/pneumonitis while on low dose weekly MTX treatment, though uncommon, has been recognized since 1980s. We report four cases of RA plus one case of polymyositis with arthritis that developed pneumonitis during MTX therapy. Three sets of criteria for diagnosing MTX pneumonitis were used to classify our patients as definite, probable or possible cases. Clinical manifestations included acute to subacute respiratory and constitutional symptoms with frequencies consistent with literature cases. Chest radiography revealed interstitial infiltration in the majority, with or without alveolar shadowing. Older age and hypoalbuminemia are the most probable risk factors for the development of MTX pneumonitis in our series. MTX was discontinued in all patients and antibiotics administered in early hospitalization stages. Corticosteroids were used in most patients to hasten recovery. Both clinical and radiological resolutions were seen in most cases. Cultures of bronchoalveolar lavage fluid may assist in confirming negative sputum cultures if patients only had nonproductive cough. Lung biopsy is not absolutely necessary for diagnosis of MTX pneumonitis if proposed criteria are applied appropriately. Patients should have a chest radiograph before institution of MTX treatment and be instructed to report any pulmonary symptoms during MTX therapy without delay.