Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome

Patients with rheumatoid arthritis (RA) have a greater risk of developing both Hodgkin lymphoma (HL) and non-HL than the general population. Non-Hodgkin lymphoma is more common than HL in these patients, and diffuse large B cell lymphoma is the most frequent subtype observed. Although the clinical course of lymphoma in RA is often aggressive, the prognosis in these cases is similar to that of lymphoma in the general population. In this review, we summarize data derived from both retrospective and prospective studies, regarding incidence, pathogenesis, and outcome of lymphomas in RA patients and outline the possible mechanisms and hypotheses linking these 2 disorders. Over the years, 3 main theories have been suggested to explain this association. These hypotheses relate to genetic predisposition, persistence of long standing disease activity with continued immune stimulation, and the role of anti-RA therapy given. A common genetic predisposition linking RA and lymphoma has not been established. As for treatment of RA, this includes immunosuppressive antitumor necrosis factor drugs or conventional disease modifying antirheumatic drugs like methotrexate. Neither of these drug categories appears to be associated with a higher risk of lymphoma in RA. The impact of continuing disease activity and immune stimulation appears to be the most significant in lymphomagenesis in these patients.