Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication.
Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication.
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发表时间：
2007-02
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通讯作者：
Y. Hoshida;Jing-Xian Xu;S. Fujita;Itsuko Nakamichi;J. Ikeda;Y. Tomita;S. Nakatsuka;J. Tamaru;
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作者：
Y. Hoshida;Jing-Xian Xu;S. Fujita;Itsuko Nakamichi;J. Ikeda;Y. Tomita;S. Nakatsuka;J. Tamaru;
目的：类风湿关节炎（RA）患者在使用或不使用甲氨蝶呤（MTX）治疗的情况下偶尔会发生淋巴组织增生性疾病（分别为MTX-LPD和非MTX-LPD）。RA自身的高免疫状态或MTX给药引起的免疫抑制状态可能有助于LPD的发生。我们的目的是比较类风湿关节炎患者中MTX-LPD与非MTX-LPD和散发性LPD的特征。方法对48例MTX-LPD、28例非MTX-LPD和150例散发性LPD进行比较。结果与散发性LPD患者相比，RA-LPD患者的LPD发病年龄晚，女性占优势。MTX-LPD组从RA到LPD的诊断间隔（中位数132 mo）明显短于非MTX-LPD组（中位数240 mo）。RA-LPD中弥漫性大B细胞淋巴瘤（DLBCL）和EB病毒（EBV）的阳性率分别为57.9%和27.6%，显著高于散发性LPD（42.7%和9.9%）。停药后，11例MTX-LPD病例显示肿瘤自发消退。RA-LPD的5年生存率（59.2%）明显低于散发性LPD（74.6%）。结论RA LPD患者的临床病理特征与MTX治疗无关，但MTX LPD患者停用MTX后LPD可自行消退，且MTX LPD患者从RA到LPD的诊断时间较非MTX LPD患者短。与散发性LPD相比，RA-LPD病例表现出更年轻的发病年龄、女性优势、预后不良以及更高的DLBCL和EBV阳性频率。
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.