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.

Frequency and association of Epstein-Barr Virus genotype in rheumatoid arthritis patients of Khyber Pakhtunkhwa, Pakistan

“…Correspondingly, a study with similar findings compared the seropositivity of EBV in patients taking immunosuppressive drugs such as steroids and DMARDs observing no significant association [ 28 ]. In accordance, other research studies [ 7 , 29 , 30 ] also didn’t show any significant positive correlation between EBV and RA medication including biologics and DMARDs.…”

Epstein–Barr virus‐associated lymphomas decoded

“…144 There is a reduced ability to generate EBV-specific CTLs in patients with RA. 147 In addition, patients with RA have higher EBV-DNA loads compared to matched controls, independent of the presence of disease-modifying agents. 148…”

“…The prevalence of EBV‐associated LPDs was significantly higher in patients with RA compared to control patients without RA and LPD 144 . There is a reduced ability to generate EBV‐specific CTLs in patients with RA 147 . In addition, patients with RA have higher EBV‐DNA loads compared to matched controls, independent of the presence of disease‐modifying agents 148 …”