Lymphoproliferative disorders in rheumatoid arthritis: Clinicopathological analysis of 76 cases in relation to methotrexate medication

Yoshihiko Hoshida, Jing Xian Xu, Shigeki Fujita, Itsuko Nakamichi, Jun Ichiro Ikeda, Yasuhiko Tomita, Shin Ichi Nakatsuka, Jun Ichi Tamaru, Atsushi Iizuka, Tsutomu Takeuchi, Katsuyuki Aozasa

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218 Citations (Scopus)

Abstract

Objective. Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. Methods. We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. Results. Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). Conclusion. The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD. and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.

Original languageEnglish
Pages (from-to)322-331
Number of pages10
JournalJournal of Rheumatology
Volume34
Issue number2
Publication statusPublished - 2007 Feb

Keywords

  • Epstein-Barr virus
  • Hyperimmune state
  • Immunosuppressive state
  • Lymphoproliferative disorders
  • Methotrexate
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Hoshida, Y., Xu, J. X., Fujita, S., Nakamichi, I., Ikeda, J. I., Tomita, Y., Nakatsuka, S. I., Tamaru, J. I., Iizuka, A., Takeuchi, T., & Aozasa, K. (2007). Lymphoproliferative disorders in rheumatoid arthritis: Clinicopathological analysis of 76 cases in relation to methotrexate medication. Journal of Rheumatology, 34(2), 322-331.