Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis

Interstitial pneumonitis is an uncommon complication of low-dose methotrexate therapy in patients with psoriasis but occurs in 3%-5% of patients with rheumatoid arthritis. We found a higher incidence of interstitial pneumonitis in patients with primary biliary cirrhosis (14%) and describe its clinical manifestations, treatment, and possible etiology. Blood tests, arterial blood gas determinations, chest radiographs, bronchoscopy, tear production, autoantibody tests, and serum immunoglobulin levels were obtained in six women who developed interstitial pneumonitis while receiving methotrexate in a double-blind prospective trial of methotrexate vs. colchicine in 87 patients with primary biliary cirrhosis. Six of 43 patients (14%) who received methotrexate compared with no patients receiving colchicine developed interstitial pneumonitis 19-61 weeks after starting treatment. The pneumonitis was characterized by dyspnea, hypoxemia, and bilateral lung infiltrates, all of which responded within 24 hours to the administration of intravenous glucocorticoids. There was no correlation between the pneumonitis and pre-existing lung disease, the severity of the primary biliary cirrhosis, the titer of antimitochondrial antibody, or other diseases associated with primary biliary cirrhosis. Patients with primary biliary cirrhosis receiving low-dose methotrexate (15 mg/wk) are more susceptible to interstitial pneumonitis than patients with psoriasis or rheumatoid arthritis. The pneumonitis appears to be a hypersensitivity reaction and responds rapidly to intravenous glucocorticoid therapy.