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Interstitial pneumonia in a patient undergoing treatment with leflunomide: drug-induced toxicity?

Leflunomide is an anti-rheumatic drug with immunomodulating effects. Granulomatous interstitial pneumonia has never been described in association with the use of this drug. We report the case of a 33-year-old female patient who presented with chest pain, weight loss and pulmonary infectious syndrome during the fifth month of monotherapy with leflunomide for rheumatoid arthritis, which advanced to respiratory insufficiency in the sixth month. Radiologic findings revealed pulmonary intersticial infiltrates, as well as bilateral alveolar infiltrates (mainly in the upper and medium lobes) and scattered micronodules. However, no mediastinal abnormalities were detected. Leflunomide was suspended. After resolution of the infection, interstitial reticulonodular lesions persisted, predominantly in the upper 2/3 of the right lung and in the center of the left lung, interspersed with a ground-glass pattern in the superior lobes. Surprisingly, pulmonary biopsy revealed tuberculoid granulomas without caseous necrosis. A thorough etiological investigation was carried out, but no etiologic agent was identified. After four months, the condition spontaneously and completely disappeared. This profile suggests that the pulmonary complications seen in this case were the result of leflunomide use.

Lung diseases, interstitial; Lung


Sociedade Brasileira de Pneumologia e Tisiologia Faculdade de Medicina da Universidade de São Paulo, Departamento de Patologia, Laboratório de Poluição Atmosférica, Av. Dr. Arnaldo, 455, 01246-903 São Paulo SP Brazil, Tel: +55 11 3060-9281 - São Paulo - SP - Brazil
E-mail: jpneumo@terra.com.br