n contrast, the same PubMed search switching the IBD terms for rheumatoid arthritis yielded 166 results, a large portion of which were directly related to lymphoproliferative disorders associated with the use of methotrexate in rheumatologic diseases. Patients with rheumatoid arthritis are believed to be at a higher baseline risk of lymphoma than the general population, making it difficult to determine how much treatment contributes to the higher rate.17 EBV may also play a role in these lymphomas. Baecklund and coworkers found that in their large series of 348 lymphomas in patients with rheumatoid arthritis, 37 were EBV-positive.17 Of these patients, 29 had prior exposure to immunomodulators (primarily methotrexate) whereas the other 8 did not. As seen in the IBD literature with AZA and 6-MP, studies examining the relationship between methotrexate and lymphoma show discordant results. In 2008, Buchbinder and colleagues reported on a cohort followed in community practices in Australia that included over 4,000 patient-years of follow-up time.34 They noted that 458 patients had received methotrexate and 8 developed NHL compared to 1.6 expected NHLs, resulting in a SIR of 5.1 (2.2–10). Dr. Frederick Wolfe, who maintains a large prospective registry of rheumatoid arthritis patients in the United States,35 found that, among nearly 20,000 patients (and almost 90,000 patient-years of follow-up), 68% received methotrexate at some point in their disease course. The use of methotrexate alone had an elevated odds ratio of 1.4 for developing lymphoma, but this was not statistically significant (95% CI 0.7–2.9). Interestingly, another recent report found that the use of corticosteroids in rheumatoid arthritis is associated with a decreased risk of lymphoma.36 Perhaps maintaining disease control is a critically important factor
