title: Primary central nervous system lymphoma in a rheumatoid arthritis patient treated with methotrexate: a case report.
abstract: BACKGROUND
  Rheumatoid arthritis is a systemic inflammatory disease characterized by synovitis and the destruction of articular structures in multiple joints. Methotrexate is recommended as an anchor drug for rheumatoid arthritis treatment to achieve the therapeutic goal of reducing damage to joints and improving clinical score. However, several studies have shown that methotrexate has been associated with the development of lymphoproliferative disorders, namely methotrexate-associated lymphoproliferative disorders. On the other hand, primary central nervous system lymphoma is an aggressive disease with poor prognosis. Both methotrexate-associated lymphoproliferative disorders and primary central nervous system lymphoma are reported to be associated with Epstein-Barr virus.
  
  
  METHODS
  A Japanese female patient of between 60 and 70 years of age with rheumatoid arthritis was admitted to our hospital because of sudden convulsion and impaired consciousness. Just before admission, she was treated with adalimumab and methotrexate. Contrast-enhanced computed tomography scan showed a densely stained mass with surrounding edema in both frontal lobes and the left nucleus basalis, and enlarged lymph nodes in the right supraclavicular fossa. We performed a biopsy of the right cervical lymph node, but could not establish a histopathological diagnosis. In situ hybridization showed the presence of Epstein Barr virus, therefore we diagnosed this case as methotrexate-associated lymphoproliferative disorders mediated by Epstein Barr virus after considering the drug history of the patient. After we discontinued methotrexate, patient symptoms gradually improved. The masses at both frontal lobes and the left nucleus basalis were gradually regressed.
  
  
  CONCLUSIONS
  Since the frequency of methotrexate use and the maximum dosage has been increasing, particular attention should be paid to the development of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients who are treated with methotrexate.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. h_kizu@med.kagawa-u.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. hdobashi@med.kagawa-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Dobashi
authors.affiliation: Department of Internal Medicine, Mitoyo general hospital, 708 Himehama, Toyohama-cho, Kanonji-si, Kagawa, 769-1695, Japan. mrmthsnr@mitoyo-hosp.jp.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Morimoto
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. t-kameda@med.kagawa-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kameda
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. susakike@kms.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Susaki
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. miharu-i@med.kagawa-u.ac.jp.
authors.forename: Miharu
authors.initials: M
authors.lastname: Izumikawa
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. y-take@med.kagawa-u.ac.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. s-naka@med.kagawa-u.ac.jp.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. oima@med.kagawa-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Imataki
authors.affiliation: Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. sbandoh@med.kagawa-u.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Bandoh
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016543:Central Nervous System Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D014057:Tomography, X-Ray Computed
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate