Severe Pneumococcal Pneumonia Following Treatment with Infliximab for Crohn's Disease

To the Editor: We report on a young female smoker who developed severe bilateral pneumococcal pneumonia after infliximab therapy for Crohn's disease. She suffered from severe Crohn's disease involving the terminal ileum despite prolonged treatment with 6-mercaptopurine 50 mg/d over 3 weeks and intravenous steroids (prednisone 75 mg/d for 10 days. She complained of abdominal cramps and 10–15 liquid stools per day (Crohn's Disease Activity Index [CDAI] 252). C-reactive protein was elevated. After a single intravenous infusion (5 mg per kilogram body weight during 2 hours) of infliximab, an antagonist against tumor necrosis factor-alpha (TNF-α), she showed complete clinical and laboratory remission within 3 days. However, after 10 days she experienced flu-like symptoms and high fever. Severe bilateral pneumonia was documented and Streptococcus pneumoniae was isolated in blood cultures. Crohn's disease was in sustained remission (CDAI <50). Treatment with i.v. penicillin led to symptomatic and clinical improvement, and the patient was discharged from the hospital. Antitumor necrosis factor-alpha treatment with infliximab has emerged as a therapeutic option in severe cases of active Crohn's disease (1,–4). However, TNF-α plays an important role in the antiinfective host defense, and increased susceptibility to infections is a side effect following infliximab therapy. Infliximab is therefore contraindicated in patients with severe infections, e.g., sepsis, abscess, or opportunistic infections. However, in 10 studies (6 studies with 660 patients with rheumatoid arthritis and 4 trials with 233 patients with Crohn's disease), similar rates of infections that had to be treated with antimicrobial medication were seen: 32% of patients treated with infliximab compared with 22% in the placebo group. Regarding severe infections, e.g., pneumonia, there is no statistical difference between the two groups (4.8% and 4.7%, respectively). After about 100,000 treatments, active tuberculosis had been reported in 28 patients, 1 case of which was fatal. Therefore it is mandatory to rule out latent or manifest tuberculosis with the Mantoux test and a chest radiograph before starting treatment with infliximab. In pneumococcal pneumonia, TNF-α enhances the bactericidal activity of neutrophils. In mice, passive immunization against TNF-α resulted in an impaired clearance of S. pneumoniae and a decreased survival time after administration of a lethal dose of S. pneumoniae (5). This is the first report of severe pneumococcal pneumonia requiring hospitalization in a patient treated with Infliximab. Vaccination against pneumococcus especially in smokers before treatment with infliximab could lower the risk of serious adverse events and may be well considered as routine.