Emergence of Legionella pneumophila pneumonia in patients receiving tumor necrosis factor-alpha antagonists.
BACKGROUND
Patients treated with tumor necrosis factor-alpha (TNF-alpha) 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 Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha 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-alpha 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-alpha 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-alpha 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-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.
Tubach
F
F
Université Paris 7, Faculté de Medecine, Paris, France. florence.tubach@bch.aphp.fr
Ravaud
P
P
Salmon-Céron
D
D
Petitpain
N
N
Brocq
O
O
Grados
F
F
Guillaume
J C
JC
Leport
J
J
Roudaut
A
A
Solau-Gervais
E
E
Lemann
M
M
Mariette
X
X
Lortholary
O
O
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D021821:Communicable Diseases, Emerging / Q000188:drug therapy; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D016952:Legionella pneumophila; D007877:Legionnaires' Disease / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept