Rheumatoid nodules have always been one of the most recognizable and important clinical findings in rheumatoid arthritis. In the past, they have been found in a particular 20% subset of rheumatoid arthritis (RA) patients in whom the disease is the most aggressive, systemic, and damaging.
Over the past 25 years, the early, aggressive use of weekly methotrexate at doses of 15-25 mg/week, administered either orally or intramuscularly, has had a profoundly positive impact upon RA, with patients living longer and fewer patients needing hospitalization and joint replacements. This occurred, by the way, before anti-TNF medications were available. However, some methotrexate-treated patients develop multiple, small and painful nodules of the elbows and the fingers, clearly related to the therapy. This has also been seen with leflunomide. Why this paradoxical occurrence exists is unknown, but it may reflect the differential impact of adenosine (increased in tissues by methotrexate therapy) on the development of granulomas and the calming of synovitis. Many therapeutic regimens have been used to try to limit this methotrexate-related nodule formation, such as colchicine, hydroxychloroquine, and sulfasalazine. None have been successful.
Overall, net, fewer RA patients present today with nodules, probably due to the early treatment of RA with disease-modifying drugs like methotrexate. Tumor necrosis factor alpha blockers, such as etanercept, infliximab and adalimumab, all lead to a decrease in nodule size and formation.