Methotrexate induced lung disease

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.