Epstein-Barr virus-related lymphoma in rheumatoid arthritis: implications for long-term usage of immunosuppressive drugs and review of the literature

Abstract

Background: Rheumatoid arthritis (RA) is a common autoimmune disease where methotrexate (MTX) is widely used as the first-line therapy. The combination of RA and MTX is associated with lymphoproliferative disorders (LPD). RA patients with Epstein-Barr virus (EBV) have impaired T-lymphocyte function, thus allowing an overgrowth of EBV-positive lymphoblastoid cells. We examined the association of EBV with LPD in immunosuppressed RA patients, particularly those treated with MTX.

Aim: To review the relationship between RA, EBV-associated LPD and MTX use.

Methods: We reported two cases of RA patients with long-term MTX treatment who subsequently developed EBV-positive LPD, followed by a review of the relevant literature.

Results: Compared with normal population, RA patients have a higher risk of lymphoma, with diffuse large B-cell lymphoma being the most common subtype. MTX withdrawal can lead to lymphoma regression. Other biological therapies, such as abatacept and tocilizumab, are not associated with increased EBV-positive lymphoma diagnosis in RA patients.

Conclusion: The association between EBV, lymphoma and MTX highlights the need to consider reducing or stopping MTX in patients who have had stable RA for many years.

Keywords: Epstein-Barr virus; lymphoma; lymphoproliferative disorder; methotrexate; rheumatoid arthritis.