title: 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.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan. miyazaki_takuya@ybb.ne.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Katsumichi
authors.initials: K
authors.lastname: Fujimaki
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shirasugi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yoshiba
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohsaka
authors.forename: Koji
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Etsuko
authors.initials: E
authors.lastname: Yamazaki
authors.forename: Rika
authors.initials: R
authors.lastname: Sakai
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tamaru
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishi
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy*; D020031:Epstein-Barr Virus Infections / Q000145:classification / Q000150:complications*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate