Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis
Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis
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DOI：
10.1007/s10875-020-00814-6
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发表时间：
2020-07-07
影响因子：
9.1
通讯作者：
Haddad, Elie
中科院分区：
文献类型：
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作者：
Blincoe, Annaliesse;Heeg, Maximilian;Haddad, Elie
家族性噬血细胞性淋巴组织细胞增生症（FHL）的病例报告中描述了孤立的神经炎症性疾病，但疾病表现的临床谱、对治疗的反应和预后仍然不清楚。我们将国际调查与文献检索相结合，以确定FHL患者（i）最初表现为孤立的神经系统症状;（ii）表现时无血细胞减少和脾肿大;（iii）神经系统表现后不早于3个月的全身HLH特征。确定了38例（20例未报告）患者的初始诊断包括急性脱髓鞘性脑病、白质脑病、CNS血管炎、多发性硬化和脑炎。就诊时的中位年龄为6.5岁，最常见的是共济失调/步态障碍（75%）和癫痫发作（53%）。弥漫性多灶性白色改变（79%）和小脑受累（61%）是常见的MRI表现。CSF细胞计数和蛋白质分别在22/29和15/29例患者中增加。14例患者在首次神经系统表现后平均36.9个月进展为符合HLH-2004标准的全身性炎症性疾病。23例患者（61%）检测到PRF 1突变，10例患者（26%）检测到RAB 27 A突变，3例患者（8%）检测到UNC 13 D突变，1例患者（3%）检测到LYST突变，1例患者（3%）检测到STXBP 2突变，平均诊断间隔为28.3个月。19例接受HSCT的患者中，11例神经功能改善，4例稳定，1例复发，3例死亡。在14例非移植患者中，只有3例病情好转或稳定，1例复发，10例死亡。孤立的CNS-HLH是一种罕见的，经常被忽视的炎性脑病的原因。HLH导向治疗后HSCT似乎可以改善生存率和结局。
Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected inPRF1in 23 patients (61%),RAB27Ain 10 (26%),UNC13Din 3 (8%),LYSTin 1 (3%), andSTXBP2in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.