Emergence of Legionella pneumophila Pneumonia in Patients Receiving Tumor Necrosis Factor–α Antagonists

Background. Patients treated with tumor necrosis factor–α (TNF-α) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy.Methods. A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axee sur la Tolerance des Biotherapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-α antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-α antagonists was compared with the rate in France overall.Results. We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40–69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-α antagonist treatment at onset of infection was 38.5 weeks (range, 3–73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-α antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy.Conclusions. L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti–TNF-α therapy. In patients receiving anti–TNF-α who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.