Drug-induced pneumonitis: The role of methotrexate

Methotrexate (MTX) is a folate antagonist used in several chronic inflammat ory and neoplastic conditions. Pulmonary toxicity occurs in 0.5% to 14% of patients receiving low-dose MTX. Manifestations of pulmonary toxicity are p rotean and include parenchymal inflammation, pneumonia, airway hyperreactiv ity, air trapping and possibly neoplasm. We performed an exhaustive review of the English literature and identified 189 cases of methotrexate-induced pneumonitis (MIP). Rheumatoid arthritis (RA) was the most frequent underlyi ng disease. In most patients, symptoms present subacutely with progression over several weeks. Most patients present with dyspnea, dry cough, fever, a nd bibasilar crackles. Peripheral eosinophilia has been cited in one third of cases. The chest radiograph may be normal, but more commonly reveals bil ateral interstitial or mixed, interstitial and alveolar infiltrates with a predilection for the bases. Chest computed tomography (CT) scans demonstrat e ground-glass opacities, interstitial infiltrates, septal lines or widespr ead consolidation. Pulmonary function studies reveal a restrictive ventilat ory defect and/or impaired gas exchange. Bronchoalveolar lavage (BAL) may b e helpful in ruling out an infectious etiology and in supporting the diagno sis of MIR Cellular interstitial infiltrates, granulomas, fibrosis, atypica l epithelial cells, and diffuse alveolar damage (DAD) are the main histolog ic features. Once MIP is suspected, the MTX should be withdrawn. Corticoste roids may accelerate resolution and are recommended in severe or fulminant cases. The prognosis of MIP is usually favorable, but occasionally the outc ome may be fatal.