A population based, case control study of non-Hodgkin's lymphoma in patients with rheumatoid arthritis.

Objective: Epstein-Barr virus (EBV) associated lymphoproliferative disorders (LPD) similar to those that occur in immunosuppressed solid organ recipients have been reported in patients with rheumatoid arthritis (RA). These LPD cause significant morbidity and/or mortality in a state of sustained immunosuppression, but may spontaneously regress if immunocompetence is restored. We determined the population based frequency of EBV associated LPD relative to all non-Hodgkin's lymphomas (NHL) that occur in the general population of patients with RA.

Methods: Forty-two case patients with NHL and RA and 49 control patients with NHL and no RA were identified in a population based, case control study of NHL that occurred in a 6 county Northern California area during the years 1988-94. The lymphoma tissue specimens were reviewed and the diagnosis of NHL was confirmed. In addition, the specimens were analyzed for NHL grade, histologic subtype, histopathologic features associated with immunosuppression, immunophenotype, and the presence of EBV genome in the tumor cells.

Results: No significant differences were identified between NHL in the RA case group and the control group (no RA) with respect to any variables investigated. One patient (2%) in the case group and one (2%) in the control group developed LPD containing EBV.

Conclusion: Our findings reveal that EBV associated lymphomas represent only a small fraction of all NHL in the general RA patient population. EBV associated LPD should be recognized when they occur because they require a special approach to patient management. However, these data indicate that the majority of NHL that occurs in patients with RA is probably coincidental with RA and not the result of significant immunosuppression.