Pulmonary Nodulosis and Aseptic Granulomatous Lung Disease Occurring in Patients with Rheumatoid Arthritis Receiving Tumor Necrosis Factor-α-Blocking Agent: A Case Series

Objective. To describe cases of development of pulmonary nodulosis or aseptic granulomatous lung disease in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor-α (TNF-α) therapy. Methods. A call for observation of such cases was sent to members of the French “Club Rhumatismes et Inflammation.” The cases had to occur after introduction of TNF-α-blocking therapy. Results. Eleven cases were examined: 6 patients were treated with etanercept, 2 with infliximab, and 3 with adalimumab. Pulmonary nodular lesions were observed after a mean treatment period of 23.3 ± 15.3 months. Clinical symptoms were observed in 5 cases. Radiographs or computed tomography of the chest showed single or multiple nodular lesions in 10 cases and hilar adenopathies in 1 case. Biopsy of the nodular chest lesions or mediastinal lymphadenopathies were performed in 8 patients, and revealed typical rheumatoid nodules in 4 cases and noncaseating granulomatous lesions in 4 cases. Mycobacterial or opportunistic infections were excluded for all cases. Outcome was favorable for all the patients, with either discontinuation or maintenance of anti-TNF-α treatment. Conclusion. Aseptic pulmonary nodular inflammation corresponding to rheumatoid nodules or noncaseating granulomatous inflammation can occur during anti-TNF-α therapy for RA, mainly etanercept. The mechanism explaining such a reaction is not clear but certainly includes different processes. These cases of pulmonary nodular inflammation generally have a benign course and do not systematically require withdrawal of treatment.