Kim Ju Hye, Chung Ji Yeon, Bong Jeong Bin
Department of Neurology, Chosun University College of Medicine, Gwangju, Republic of Korea.
Front Neurol. 2024 Mar 11;15:1363072. doi: 10.3389/fneur.2024.1363072. eCollection 2024.
Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory disease commonly characterized by histiocyte infiltration in multiple organs, such as the liver, spleen, lymph nodes, bone marrow, and central nervous system. The clinical features of HLH include fever, splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated blood ferritin levels. HLH is categorized as either primary or secondary. Coronavirus disease 2019 (COVID-19) vaccines may occasionally trigger secondary HLH, which is related to hyperinflammatory syndrome.
A 58-year-old woman, previously diagnosed with Graves' disease, presented with cognitive decline 2 weeks after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Brain MRI revealed a hyperintense lesion on T2-weighted and fluid-attenuated inversion recovery images in the bilateral subcortical white matter and right periventricular area. Vaccination-associated acute disseminated encephalomyelitis was suspected and methylprednisolone and intravenous immunoglobulin (IVIg) were administered. From the 5th day of IVIg administration, the patient developed fever and pancytopenia. In the findings of bone marrow biopsy, hemophagocytosis was not observed; however, six of the eight diagnostic criteria for HLH-2004 were met, raising the possibility of HLH. Although there was no definitive method to confirm causality, considering the temporal sequence, suspicion arose regarding vaccine-induced HLH. Splenectomy was considered for therapeutic and diagnostic purposes; however, the patient died on the 28th day of hospitalization owing to multiple organ failure.
To date, 23 cases of COVID-19 vaccine-related HLH have been reported. Additionally, HLH in COVID-19 patients has been reported in various case reports. To the best of our knowledge, this is the first reported case of central nervous system involvement in HLH related to any type of COVID-19 vaccine. This case suggests that even when there are no systemic symptoms after COVID-19 vaccination, HLH should be considered as a differential diagnosis if brain lesions are suggestive of CNS demyelinating disease.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的全身性炎症性疾病，其常见特征是组织细胞浸润多个器官，如肝脏、脾脏、淋巴结、骨髓和中枢神经系统。HLH的临床特征包括发热、脾肿大、血细胞减少、高甘油三酯血症、低纤维蛋白原血症和血铁蛋白水平升高。HLH分为原发性或继发性。2019冠状病毒病（COVID-19）疫苗偶尔可能引发继发性HLH，这与过度炎症综合征有关。
一名58岁女性，既往诊断为格雷夫斯病，在接种第一剂ChAdOx1 nCoV-19疫苗后2周出现认知功能下降。脑部磁共振成像显示双侧皮质下白质和右侧脑室周围区域在T2加权和液体衰减反转恢复图像上有高信号病变。怀疑为疫苗相关急性播散性脑脊髓炎，给予甲泼尼龙和静脉注射免疫球蛋白（IVIg）。从静脉注射免疫球蛋白第5天起，患者出现发热和全血细胞减少。骨髓活检结果未观察到噬血细胞现象；然而，符合HLH-2004八项诊断标准中的六项，增加了HLH的可能性。尽管没有确定因果关系的明确方法，但考虑到时间顺序，怀疑是疫苗诱导的HLH。考虑进行脾切除术以用于治疗和诊断目的；然而，患者在住院第28天因多器官衰竭死亡。
迄今为止，已报告23例与COVID-19疫苗相关的HLH病例。此外，各种病例报告中也报道了COVID-19患者中的HLH。据我们所知，这是首例报告的与任何类型COVID-19疫苗相关的HLH累及中枢神经系统的病例。该病例表明，即使COVID-19疫苗接种后没有全身症状，如果脑部病变提示中枢神经系统脱髓鞘疾病，也应将HLH视为鉴别诊断。
