Rheumatoid Arthritis and the Incidence of Herpes Zoster: Risky Business

thritis are at increased risk for developing zoster. Patients with rheumatoid arthritis have a nearly 2-fold risk of developing infections compared with age- and sexmatched control subjects [2]. The increased rate of infections may be due to immunosuppressive medication used to treat rheumatoid arthritis or to the underlying disease itself. T cells from patients with rheumatoid arthritis show accelerated immunosenescence with reduced diversity, which might contribute to the increased rate of infections [3]. In the study by McDonald et al. [4] in this issue of the journal, the authors report on risk factors for zoster on the basis of a retrospective cohort study of 120,000 patients, encompassing 171,000 patientyears, with rheumatoid arthritis. The incidence of zoster in their patients with rheumatoid arthritis, 9.96 episodes per 1000 years, was similar to that of other studies of patients with rheumatoid arthritis and 2 to 5 times higher than the rate of zoster in the general population. The authors confirmed prior studies showing that older age, malignancy, chronic lung disease, and kidney disease are associated with increased rates of zoster. Because zoster is associated with impaired cellular immunity, it was not surprising that the authors found that patients receiving medications with more immunosuppressive activity (anakinra, azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, and tumor necrosis factor [TNF]‐a inhibitors) had higher rates of herpes zoster than those receiving less immunosuppressive medications (auranofin, gold, hydroxychloroquine, penicillamine, and sulfasalazine). The authors compared the risk of zoster in patients receiving different TNF-a inhibitors and found that patients receiving infliximab had a higher rate of zoster than those receiving etanercept or adalimumab. Etanercept is a fusion protein that consists of 2 TNF-a receptor molecules linked to the fragment crystallizable (Fc) domain of human immunoglobulin G1. Infliximab is a chimeric mouse-human anti‐TNF-a antibody, but adalimumab is a fully human monoclonal anti‐TNF-a antibody. Most studies [5‐7] have shown that patients with rheumatoid arthritis who receive TNF-a inhibitors have higher rates of infection compared with those who receive other immunosuppressive medications, especially during the first 6 months of