Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression
Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression
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DOI：
10.1111/ejh.12116
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Ohshima, Koichi
中科院分区：
文献类型：
--
作者：
Ichikawa, Ayako;Arakawa, Fumiko;Ohshima, Koichi
目的类风湿关节炎（RA）患者可发展为淋巴细胞增生性疾病（RA- lpd）。甲氨蝶呤（MTX）和eb病毒（EBV）再激活引起的免疫抑制状态被认为是原因。有时甲氨蝶呤停药后会出现自发性症状。本研究的目的是确定预测RA-LPD患者复发和生存的因素，以及MTX治疗RA-LPD患者的自发消退（MTX- lpd）。方法对102例RA-LPD的临床病理特征、临床特点及治疗结果进行分析。采用原位杂交法和聚合酶链反应法分别检测EBV感染情况和免疫球蛋白重链基因（IGH）的克隆性。结果102例患者中弥漫性大b细胞淋巴瘤（DLBCL， 53例）、霍奇金淋巴瘤（9例）、多形性b细胞LPD（20例）、反应性淋巴结炎（11例）、外周t细胞淋巴瘤（PTCL， 4例）、复合淋巴瘤（2例）、滤泡性淋巴瘤（3例）。60%（56/93）的患者检出EBV。59%（28/47）停用MTX的患者出现自发性消退。回归与EBV阳性（P=0.007）和非dlbcl （P=0.006）相关，但与MTX量和其他临床特征无关。74例患者中有31例出现单克隆条带。在DLBCL患者中，较差的无病生存期（P=0.05）与IGH的克隆性相关。在所有患者中，预测生存期缩短的因素是年龄（60 - 70岁）和DLBCL的组织学类型。结论组织学、EBV阳性和IGH单克隆性可用于预测RA-LPD患者的临床预后。
Objectives Patients with rheumatoid arthritis (RA) may develop lymphoproliferative disorders (RA-LPD). Immunosuppressive states due to methotrexate (MTX) and Epstein-Barr virus (EBV) reactivation have been regarded as causes. Sometimes spontaneous regression occurs after withdrawal of MTX. The objective of this study was to identify factors predictive of relapse and survival in patients with RA-LPD, and spontaneous regression in patients with RA-LPD treated with MTX (MTX-LPD). Methods We evaluated the clinicopathological features, clinical characteristics, and treatment outcomes in 102 cases of RA-LPD. In addition, EBV infection and clonality of immunoglobulin heavy chain gene (IGH) were analyzed by in situ hybridization and polymerase chain reaction, respectively. Results The 102 cases included patients with diffuse large B-cell lymphoma (DLBCL; n=53), Hodgkin lymphoma (n=9), polymorphic B-cell LPD (n=20), reactive lymphadenitis (n=11), peripheral T-cell lymphoma (PTCL; n=4), composite lymphoma (n=2), and follicular lymphoma (n=3). EBV was detected in 60% (56/93) of patients. Spontaneous regression occurred in 59% (28/47) of patients in whom MTX was withdrawn. Regression was associated with EBV positivity (P=0.007) and non-DLBCL (P=0.006), but not with MTX amount and other clinical features. Monoclonal bands of IGH were observed in 31 of 74 cases. In patients with DLBCL, poor disease-free survival (P=0.05) was associated with clonality of IGH. In all patients, factors predictive of shorter survival were age (>70yr) and histological type of DLBCL. Conclusions Histology, EBV positivity, and monoclonality of IGH are useful for predicting clinical outcomes in patients with RA-LPD.