{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:23:59Z","timestamp":1790029439921,"version":"4.0.1"},"reference-count":26,"publisher":"The Journal of Rheumatology","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>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)<jats:italic>in situ<\/jats:italic>hybridization and immunostaining, and HLA type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>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\u2019s method). EBV latency classification and HLA typing were not associated with the prognosis of MTX-LPD in our cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>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that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.130270","type":"journal-article","created":{"date-parts":[[2013,12,16]],"date-time":"2013-12-16T01:14:20Z","timestamp":1387156460000},"page":"293-299","source":"Crossref","is-referenced-by-count":119,"title":["A Clinical, Pathological, and Genetic Characterization of Methotrexate-associated Lymphoproliferative Disorders"],"prefix":"10.3899","volume":"41","author":[{"given":"Noriyuki","family":"Yamakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kawabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikashi","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Nishikori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Imura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoichiro","family":"Yukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Yoshifuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Ohmura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Kitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadakazu","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiko","family":"Yurugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taira","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroh","family":"Saji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Takaori-Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Haga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneyo","family":"Mimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2018112909322707000_41.2.293.1","unstructured":"Gaulard P Swerdlow SH Harris NL Jaffe ES Sundstrom C . Other iatrogenic immunodeficiency-associated lymphoproliferative disorders. In: Swerdlow SH Campo E Harris NL Jaffe ES Pileri SA Stein H , eds. Tumours of haematopoietic and lymphoid tissues. Pathology & genetics. World Health Organization classification of tumours. 4th ed. Lyon: IARC Press; 2008:350\u20131."},{"key":"2018112909322707000_41.2.293.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198503283121303"},{"issue":"Suppl 61","key":"2018112909322707000_41.2.293.3","first-page":"S52","article-title":"Drug combinations with methotrexate to treat rheumatoid arthritis","volume":"5","author":"Rath","year":"2010","journal-title":"Clin Exp Rheumatol"},{"key":"2018112909322707000_41.2.293.4","unstructured":"Harris NL Swerdlow SH . Methotrexate-associated lymphoproliferative disorders. In: Jaffe ES Harris NL Stein H Vardiman JW , eds. Tumours of haematopoietic and lymphoid tissues. Pathology & genetics. World Health Organization classification of tumours. 3rd ed. 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