Methotrexate induced lung disease

Henry Dirk Sostman, R. A. Matthay, C. E. Putman, G. J.W. Smith

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Methotrexate (MTX) has been described as producing an acute, usually self limited pneumonitis. During a 6 year period, 7 patients (ages 11-64) among 100 treated developed methotrexate induced lung disease. Total dose of MTX received prior to developing the pulmonary illness ranged from 100 to 41,000 mg. Presenting manifestations included fever (6/7), nonproductive cough (5/7) and dyspnea (4/7). Leukocytosis (5/7) and eosinophilia (5/7) were common. Cultures and serology invariably failed to reveal an infectious etiology for the lung disease. The chest radiographs of 5 patients demonstrated a pattern consistent with a combined interstitial and air space process. Despite abnormal pulmonary function tests one patient had a persistently normal radiograph. Another presented with diffuse nodularity (≤ 1 cm) that slowly cleared over a six week period. Pulmonary function studies revealed arterial hypoxemia (average PaO2 63 mmHg), a restrictive ventilatory defect (average forced vital capacity 67% predicted) and a decreased diffusing capacity for carbon monoxide, single breath method (average 50% predicted). MTX was discontinued in all patients; 3 recovered fully, 3 developed chronic interstitial lung disease and 1 died of respiratory failure. Histopathology of the lungs in 2 cases revealed organizing interstitial pneumonia and marked interstitial fibrosis. In one, the lung showed focal nodular interstitial pneumonia; electron microscopy in this case demonstrated intra alveolar cellular accumulations seen in desquamative interstitial pneumonia. Due to an apparent 7 percent incidence and potential severity of methotrexate induced lung disease, it is recommended that serial chest roentgenograms and pulmonary function tests be performed in all patients receiving this drug.

Original languageEnglish (US)
Number of pages1
JournalAmerican Review of Respiratory Disease
Issue number4 II
StatePublished - Jan 1 1976

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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