Remission of lymphoma after withdrawal of methotrexate in rheumatoid arthritis: Relationship with type of latent Epstein‐Barr virus infection

Abstract

Rheumatoid arthritis (RA) is associated with an increased risk of developing lymphoma. Although the pathogenesis is still unclear, the increased risk appears to be related to the high inflammatory activity of RA, immunosuppressive agents, or Epstein-Barr virus (EBV) infection. We investigated the relationship between EBV latent infection and methotrexate (MTX)-associated lymphoma in RA patients. Nine patients were diagnosed with non-Hodgkin's lymphoma (NHL) during MTX treatment for RA in a multicenter study. The pathologic findings were consistent with diffuse large B-cell lymphoma in 8 patients and peripheral T-cell lymphoma, unspecified in 1. EBV infection was detected in 3 patients by in situ hybridization. Among all 9 patients who were initially treated by MTX withdrawal alone, 2 obtained spontaneous complete response (CR), 1 had partial response, 2 had stable disease (SD), and 4 had progressive disease. Both patients who had a CR and 1 who had SD were positive for EBV. Further examination of the latent EBV infection patterns revealed that 2 patients who obtained a CR had latency Type III, and the other with SD had latency Type II. These results demonstrate that immunodeficiency caused by MTX treatment is associated with the development of EBV-related NHL in RA patients. In patients who were treated by MTX for RA and developed NHL, remission can be observed following MTX withdrawal especially in NHL with latency Type III EBV infection. The analysis of EBV infection, including the latency types, is useful to decide the optimum therapeutic strategy. Am. J. Hematol. 82:1106Hematol. 82: -1109Hematol. 82: , 2007

Lymphoproliferative disorder in an elderly rheumatoid arthritis patient after longterm oral methotrexate administration: A case report

“…A previous report of an RA patient receiving MTX therapy who developed MTX-LPD described a median duration of 38 months and total dose of 984 mg (7). Another previous study reported a median duration and total dose of 54 months and 940 mg, respectively (6).…”

“…The onset of MTX-LPD is shorter compared with that of lymphomas that develop in general RA patients (6). The causative role of MTX in MTX-LPD pathophysiology is supported by the observation that discontinuing treatment with MTX results in resolution of LPD (7). The onset of MTX-LPD is considered to be dose-independent, as is the case with MTX-related interstitial pneumonia (8).…”

Spontaneous regression of Epstein-Barr virusassociated lymphoproliferative disorder in a juvenile idiopathic arthritis patient after the discontinuation of methotrexate and etanercept

“…Only 6 patients with DLBCL had received disease modifying antirheumatic drugs (DMARD) therapy for a minimum of 1 year (3). In patients with RA and long-term MTX treatment, several cases have been described where the discontinuation of MTX led to the spontaneous regression or remission of LPD (4). In a Japanese analysis of 76 cases of LPD in RA patients with or without MTX therapy were compared with patients with sporadic LPD.…”

The aggressive clinical courses of Hodgkin lymphoma primarily diagnosed as methotrexate-induced non-specific lymphoproliferative disorder in patients with rheumatoid arthritis

“…On the other hand, EBV was detected in the pathological sample and serum. It has been well documented that EBV has an influence and is suggested as one of the pathogenic factors of MTX-LPD 1,5,7,9,[11][12][13][14][15] . In addition, we previously demonstrated that the viral load of serum EBV is related with the disease activity of HL 5) .…”

“…Methotrexate (MTX) is one of the most potent drugs used for treating rheumatoid arthritis (RA) and is currently regarded as the first-line medication [2][3][4] . OIIA-LPD mainly develops in patients with RA who receive MTX, and is described as MTX-LPD in RA [5][6][7][8][9][10][11] . The specific features of MTX-LPD include the occurrence of several LPD phenotypes including Hodgkin lymphoma (HL).…”