Kaneko Masahiko, Shikata Hisaharu, Matsukage Shoichi, Maruta Masaki, Shinomiya Hiroto, Suzuki Tadaki, Hasegawa Hideki, Shimojima Masayuki, Saijo Masayuki
Department of Internal Medicine, Uwajima City Hospital, 1-1 Goten-machi, Uwajima City, Ehime 798-8510, Japan.
Department of Pathology, Uwajima City Hospital, 1-1 Goten-machi, Uwajima City, Ehime 798-8510, Japan.
J Infect Chemother. 2018 Apr;24(4):292-297. doi: 10.1016/j.jiac.2017.10.016. Epub 2017 Nov 11.
Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS.
严重发热伴血小板减少综合征（SFTS）是一种由新型布尼亚病毒——SFTS病毒（SFTSV）引起的严重传染病，在中国、韩国和日本呈地方性流行。大多数SFTS患者存在意识异常。目前尚无关于SFTS患者中枢神经系统（CNS）病理结果的报道。一名53岁的日本男性因发热和腹泻8天入住宇和岛市立医院。实验室检查显示白细胞减少、血小板减少和肝酶升高。在其血液中检测到SFTSV基因组后，他被诊断为患有严重发热伴血小板减少综合征（SFTS）。骨髓穿刺显示噬血细胞性淋巴组织细胞增生症。他出现进行性中枢神经系统功能障碍，并在首次出现症状后的第13天死亡。在疾病过程中，血液中的SFTSV基因组载量和某些细胞因子水平升高。免疫组织化学（IHC）分析显示，系统性淋巴组织出现坏死性淋巴结炎，SFTSV核衣壳蛋白（NP）呈阳性。在包括中枢神经系统在内的所有检查器官以及每个器官的血管腔内均检测到SFTSV-NP阳性免疫母细胞。免疫组织化学分析显示，所有检查器官的实质细胞SFTSV-NP均为阴性。脑桥的显微镜检查显示局灶性神经元细胞变性，扩张微血管周围有含铁血黄素的巨噬细胞，伴有血管周围炎性细胞浸润和血管内纤维蛋白沉积。尸检证实该SFTS患者全身性噬血细胞性淋巴组织细胞增生症呈阳性，包括中枢神经系统。该患者的神经异常可能是由功能性和器质性异常共同引起的。这些新发现为SFTS的病理生理学提供了重要见解。
