Ultrasonography of the shoulder in patients with rheumatoid arthritis: comment on the article by Hermann et al

To the Editor: We read with interest the review by Ellerin et al on infections and anti–tumor necrosis factor (anti-TNF) therapy (1), as well as the article by Netea et al reporting 2 cases of Salmonella enterica septicemia secondary to treatment with adalimumab and infliximab (2). Netea and colleagues also demonstrated decreased interferonproduction and inhibition of Toll-like receptor 4 expression on dendritic cells in anti-TNF–treated rheumatoid arthritis patients, providing a potential explanation for the increased susceptibility to intracellular organism infection associated with anti-TNF therapy. We have recently seen a patient with disseminated Salmonella typhimurium infection secondary to anti-TNF therapy. This is, to our knowledge, the first published report of such a finding. The patient was a Fijian Indian man who developed psoriasis and psoriatic arthritis in 1992. He migrated to Australia in 1993. His skin and joint disease remained very active despite a variety of treatments administered over a period of years, including psoralen ultraviolet A, acitretin, sulfasalazine, methotrexate, and cyclosporine. At the time of presentation to us in January 2003, at the age of 39 years, he was taking prednisone (10 mg/day) and sulfasalazine. His erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were both elevated (ESR 80 mm/hour [normal 10], CRP 82 mg/liter [normal 3]). Cyclosporine treatment was reinstituted in late January 2003 and was mildly efficacious, but was discontinued in early April due to intolerable side effects including hypertension, headaches, and impairment of short-term memory. In mid-April 2003, treatment with infliximab combined with methotrexate (7.5 mg/week) was started. Infliximab infusions (5 mg/kg) were given at weeks 0, 2, 6, 14 and 22, with dramatic clinical response. At week 2, the swollen and tender joint counts were 0 and the ESR and CRP were 7 mm/hour and 1 mg/liter, respectively. The patient’s psoriasis also improved rapidly, and the Psoriasis Area and Severity Index score was 0 at the time of the third infusion. Prednisone and sulfasalazine were discontinued after the third infusion. During the twenty-eighth week of infliximab therapy, the patient presented with a 2-day history of fever, chills, rigor, headache, and myalgia. His temperature was 41°C. No other specific abnormalities were detected on physical examination. He was admitted to the hospital. Laboratory investigations revealed a CRP level of 226 mg/liter and an ESR of 53 mm/hour. S typhimurium was isolated from 5 of 6 blood cultures. The patient was treated initially with intravenous (IV) ceftriaxone, and then with IV ciprofloxacin after identification of the organism. The fever resolved after 4 days of IV antibiotic treatment, and he was discharged from the hospital after 10 days, with no complications. S typhimurium is the second most frequently isolated Salmonella serotype from human sources, after Salmonella enteritidis (3). Infection often results in self-limited gastroenteritis, and the diarrhea typically lasts 3–7 days. Only 1–4% of immunocompotent individuals have positive blood cultures (4). The risk of disseminated salmonellosis is increased in immunocompromised patients. This case demonstrates that patients receiving antiTNF therapy may present with manifestations secondary to disseminated infection rather than with localized symptoms as might be expected in immunocompotent patients, and parallels the unusual patterns of presentation of Mycobacterium tuberculosis infection in the setting of anti-TNF therapy (5). Hess et al (6) demonstrated decreased adherence of S typhimurium to cultured intestinal epithelial cell lines after the lines were pretreated with TNF . This could be one possible explanation for the increased risk of disseminated salmonellosis in patients treated with TNF -blocking agents.