PT  - JOURNAL ARTICLE
AU  - Noriyuki Yamakawa
AU  - Masakazu Fujimoto
AU  - Daisuke Kawabata
AU  - Chikashi Terao
AU  - Momoko Nishikori
AU  - Ran Nakashima
AU  - Yoshitaka Imura
AU  - Naoichiro Yukawa
AU  - Hajime Yoshifuji
AU  - Koichiro Ohmura
AU  - Takao Fujii
AU  - Toshiyuki Kitano
AU  - Tadakazu Kondo
AU  - Kimiko Yurugi
AU  - Yasuo Miura
AU  - Taira Maekawa
AU  - Hiroh Saji
AU  - Akifumi Takaori-Kondo
AU  - Fumihiko Matsuda
AU  - Hironori Haga
AU  - Tsuneyo Mimori
TI  - A Clinical, Pathological, and Genetic Characterization of Methotrexate-associated Lymphoproliferative Disorders
AID  - 10.3899/jrheum.130270
DP  - 2013 Dec 15
TA  - The Journal of Rheumatology
PG  - jrheum.130270
4099  - http://www.jrheum.org/content/early/2013/12/12/jrheum.130270.short
4100  - http://www.jrheum.org/content/early/2013/12/12/jrheum.130270.full
AB  - Objective Methotrexate-associated lymphoproliferative disorders (MTX-LPD) often regress spontaneously during MTX withdrawal, but the prognostic factors remain unclear. The aim of our study was to clarify the clinical, histological, and genetic factors that predict outcomes in patients with MTX-LPD. Methods Patients with MTX-LPD diagnosed between 2000 and 2012 were analyzed retrospectively regarding their clinical course, site of biopsy, histological typing, Epstein-Barr virus (EBV) in situ hybridization and immunostaining, and HLA type. Results Twenty-one patients, including 20 with rheumatoid arthritis (RA) and 1 with polymyositis, were analyzed. The mean dose of MTX was 6.1 mg/week and the mean duration of treatment was 71.1 months. Clinically, 5 patients were diagnosed with EBV-positive mucocutaneous ulcer (EBVMCU) and had polymorphic histological findings. The proportion of those patients successfully treated solely by withdrawal of MTX was significantly greater than that of those without EBVMCU (75% vs 7.7%, p = 0.015). The HLA-B15:11 haplotype was more frequent in patients with EBV+ RA with MTX-LPD than in healthy Japanese controls (p = 0.0079, Bonferroni’s method). EBV latency classification and HLA typing were not associated with the prognosis of MTX-LPD in our cohort. Conclusion Our data demonstrate that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD.