TY - JOUR
T1 - A clinical, pathological, and genetic characterization of methotrexate-associated lymphoproliferative disorders
AU - Yamakawa, Noriyuki
AU - Fujimoto, Masakazu
AU - Kawabata, Daisuke
AU - Terao, Chikashi
AU - Nishikori, Momoko
AU - Nakashima, Ran
AU - Imura, Yoshitaka
AU - Yukawa, Naoichiro
AU - Yoshifuji, Hajime
AU - Ohmura, Koichiro
AU - Fujii, Takao
AU - Kitano, Toshiyuki
AU - Kondo, Tadakazu
AU - Yurugi, Kimiko
AU - Miura, Yasuo
AU - Maekawa, Taira
AU - Saji, Hiroh
AU - Takaori-Kondo, Akifumi
AU - Matsuda, Fumihiko
AU - Haga, Hironori
AU - Mimori, Tsuneyo
PY - 2014/2
Y1 - 2014/2
N2 - 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that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD. (First Release Dec 15 2013; J Rheumatol 2014;41:293-9; doi:10.3899/jrheum.130270).
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. (First Release Dec 15 2013; J Rheumatol 2014;41:293-9; doi:10.3899/jrheum.130270).
KW - HLA antigens
KW - Hematopoietic system
KW - Rheumatic diseases
KW - Rheumatoid arthritis
KW - Skin manifestations
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U2 - 10.3899/jrheum.130270
DO - 10.3899/jrheum.130270
M3 - Article
C2 - 24334644
AN - SCOPUS:84893612458
SN - 0315-162X
VL - 41
SP - 293
EP - 299
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 2
ER -