Kano Kohei, Katayama Takayuki, Takeguchi Shiori, Asanome Asuka, Takahashi Kae, Saito Tsukasa, Sawada Jun, Saito Masato, Anei Ryogo, Kamada Kyousuke, Miyokawa Naoyuki, Nishihara Hiroshi, Hasebe Naoyuki
Division of Neurology, First Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Japan.
Neuropathology. 2017 Jun;37(3):259-264. doi: 10.1111/neup.12356. Epub 2016 Dec 22.
A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.
一名75岁女性因意识障碍迅速恶化入住我院。她有7年类风湿关节炎（RA）病史，一直使用甲氨蝶呤（MTX）和泼尼松龙治疗。脑部T2加权磁共振成像（MRI）显示大脑皮质下和深部白质、双侧基底神经节和丘脑有弥漫性高强度病变。脑脊液检查显示蛋白水平升高，爱泼斯坦-巴尔病毒（EBV）DNA呈阳性。人类免疫缺陷病毒检测为阴性。脑活检显示实质和脑膜血管周围淋巴细胞浸润，伴有EBV编码的小RNA（EBER）。由于该病例不符合慢性活动性EBV感染（CAEBV）的标准，则诊断为中枢神经系统爱泼斯坦-巴尔病毒（EBV）相关血管炎。大剂量甲泼尼龙、阿昔洛韦、更昔洛韦和膦甲酸均无效。虽然EBV是传染性单核细胞增多症（IM）、淋巴瘤和鼻咽癌的病原体，但老年人中EBV重新激活导致中枢神经系统血管炎病理改变的情况罕见。类固醇和MTX等免疫抑制药物广泛用于治疗自身免疫性疾病，但可能会加剧EBV的重新激活。这是首例在使用MTX和类固醇治疗RA期间经活检证实的EBV阳性/ HIV阴性血管炎病例。该病例表明，EBV相关血管炎需要作为中枢神经系统血管炎的鉴别诊断加以考虑。
