Shimada Hiromi, Dobashi Hiroaki, Morimoto Hisanori, Kameda Tomohiro, Susaki Kentaro, Izumikawa Miharu, Takeuchi Yohei, Nakashima Shusaku, Imataki Osamu, Bandoh Shuji
Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Department of Internal Medicine, Mitoyo general hospital, 708 Himehama, Toyohama-cho, Kanonji-si, Kagawa, 769-1695, Japan.
BMC Res Notes. 2015 Mar 19;8:88. doi: 10.1186/s13104-015-1040-0.
Rheumatoid arthritis is a systemic inflammatory disease characterized by synovitis and the destruction of articular structures in multiple joints. Methotrexate is recommended as an anchor drug for rheumatoid arthritis treatment to achieve the therapeutic goal of reducing damage to joints and improving clinical score. However, several studies have shown that methotrexate has been associated with the development of lymphoproliferative disorders, namely methotrexate-associated lymphoproliferative disorders. On the other hand, primary central nervous system lymphoma is an aggressive disease with poor prognosis. Both methotrexate-associated lymphoproliferative disorders and primary central nervous system lymphoma are reported to be associated with Epstein-Barr virus.
A Japanese female patient of between 60 and 70 years of age with rheumatoid arthritis was admitted to our hospital because of sudden convulsion and impaired consciousness. Just before admission, she was treated with adalimumab and methotrexate. Contrast-enhanced computed tomography scan showed a densely stained mass with surrounding edema in both frontal lobes and the left nucleus basalis, and enlarged lymph nodes in the right supraclavicular fossa. We performed a biopsy of the right cervical lymph node, but could not establish a histopathological diagnosis. In situ hybridization showed the presence of Epstein Barr virus, therefore we diagnosed this case as methotrexate-associated lymphoproliferative disorders mediated by Epstein Barr virus after considering the drug history of the patient. After we discontinued methotrexate, patient symptoms gradually improved. The masses at both frontal lobes and the left nucleus basalis were gradually regressed.
Since the frequency of methotrexate use and the maximum dosage has been increasing, particular attention should be paid to the development of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients who are treated with methotrexate.
类风湿关节炎是一种全身性炎症性疾病,其特征为滑膜炎以及多个关节的关节结构破坏。甲氨蝶呤被推荐作为类风湿关节炎治疗的基础药物,以实现减少关节损伤和改善临床评分的治疗目标。然而,多项研究表明,甲氨蝶呤与淋巴增殖性疾病的发生有关,即甲氨蝶呤相关淋巴增殖性疾病。另一方面,原发性中枢神经系统淋巴瘤是一种侵袭性疾病,预后较差。据报道,甲氨蝶呤相关淋巴增殖性疾病和原发性中枢神经系统淋巴瘤均与爱泼斯坦-巴尔病毒有关。
一名60至70岁的日本类风湿关节炎女性患者因突然抽搐和意识障碍入院。入院前,她正在接受阿达木单抗和甲氨蝶呤治疗。增强计算机断层扫描显示双侧额叶和左侧基底核有高密度染色肿块并伴有周围水肿,右侧锁骨上窝淋巴结肿大。我们对右侧颈部淋巴结进行了活检,但未能建立组织病理学诊断。原位杂交显示有爱泼斯坦-巴尔病毒存在,因此在考虑患者用药史后,我们将该病例诊断为由爱泼斯坦-巴尔病毒介导的甲氨蝶呤相关淋巴增殖性疾病。停用甲氨蝶呤后,患者症状逐渐改善。双侧额叶和左侧基底核的肿块逐渐消退。
由于甲氨蝶呤的使用频率和最大剂量一直在增加,对于接受甲氨蝶呤治疗的类风湿关节炎患者,应特别注意甲氨蝶呤相关淋巴增殖性疾病的发生。