甲氨蝶呤相关性淋巴增生性疾病的临床、病理和遗传学特征。

A clinical, pathological, and genetic characterization of methotrexate-associated lymphoproliferative disorders.

机构信息

From the Department of Rheumatology and Clinical Immunology, the Department of Diagnostic Pathology, the Center for Genomic Medicine, and the Department of Hematology and Oncology, Kyoto University Graduate School of Medicine; the Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital; the HLA Foundation Laboratory, Kyoto, Japan.

出版信息

J Rheumatol. 2014 Feb;41(2):293-9. doi: 10.3899/jrheum.130270. Epub 2013 Dec 15.

DOI:10.3899/jrheum.130270

PMID:24334644

Abstract

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that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD.

摘要

目的

甲氨蝶呤相关性淋巴组织增生性疾病（MTX-LPD）在甲氨蝶呤停药后常自发消退，但预后因素仍不清楚。本研究旨在阐明预测 MTX-LPD 患者结局的临床、组织学和遗传因素。

方法

回顾性分析 2000 年至 2012 年间诊断的 MTX-LPD 患者的临床病程、活检部位、组织学类型、EB 病毒（EBV）原位杂交和免疫组化以及 HLA 类型。

结果

共分析了 21 例患者，其中 20 例为类风湿关节炎（RA），1 例为多发性肌炎。MTX 的平均剂量为 6.1mg/周，平均治疗时间为 71.1 个月。临床方面，5 例诊断为 EBV 阳性黏膜溃疡（EBVMCU），具有多形性组织学表现。单纯停用 MTX 治疗成功的患者比例明显高于无 EBVMCU 的患者（75% vs 7.7%，p=0.015）。与健康日本对照相比，携带 HLA-B15:11 单倍型的 EBV+RA 患者 MTX-LPD 发生率更高（p=0.0079，Bonferroni 法）。EBV 潜伏期分类和 HLA 分型与本队列 MTX-LPD 的预后无关。