儿童EB病毒相关性噬血细胞综合征52例临床特点及预后危险因素分析

目的：分析EB病毒相关性噬血细胞性淋巴组织细胞增生症（Epstein?Barr virus?associated hemophagocytic lymphohistiocytosis，EBV?HLH）患儿的临床特点、转归及预后危险因素。方法：选取南京医科大学附属南京儿童医院2012年8月—2018年9月诊治的EBV?HLH患儿52例，对患儿临床资料进行回顾性分析探讨影响预后的危险因素。结果：52例临床表现主要为持续性不规则发热（100.0%）、肝脏肿大（96.2%）及脾脏肿大（80.8%）。实验室检查中，所有患儿血浆EBV?DNA均为阳性（100.0%），其他主要表现有肝功能异常（100.0%）、铁蛋白升高（94.3%）及甘油三酯升高（91.4%）。52例中11例死亡（包括4例复发），好转或痊愈33例，出院后失访8例。生存组与死亡组在发热天数（P=0.036）、血红蛋白（P < 0.001）、谷氨酰转肽酶（P=0.040）、白蛋白（P=0.012）、凝血酶原时间（P=0.006）及国际标准化比值（P=0.028）之间差异有统计学意义。发热天数>14 d（P=0.003）、血红蛋白减少（P=0.003）、谷氨酰转肽酶增高（P=0.047）、低白蛋白血症（P=0.043）和凝血酶原时间延长（P=0.013）是影响预后的不良因素，EB病毒再次活跃是复发的重要原因（P < 0.001）。使用HLH?1994（或HLH?2004）方案患儿存活率更高，但因病例数太少无统计学意义（P=0.565）。结论：发热天数>14 d、血红蛋白下降、谷氨酰转肽酶增高、白蛋白下降、凝血酶原时间延长是影响EBV?HLH患儿预后的不良因素，EB病毒再活跃患儿更易复发，预后极差。

Retrospective and prognositic analysis of 52 Epstein-Barr Virus-associated Hemophagocytic lymphohistiocytosis

Objective: To investigate the clinical features, outcomes and prognostic factors of children with EBV-HLH. Methods: A retrospective study was carried out to analyze the clinical data of 52 EBV-HLH cases, from August 2012 to September 2018, to reveal the prognosis of children with risk factors. They were divided into two groups according to their specificity. One was death and survival group, and the other was relapsed and conventional group. Results:The main clinical manifestations of 52 cases included persistent irregular fever(100%), hepatic enlargement(96.2%), splenomegaly(80.8%) and respiratory symptoms(69.2%).All children had positive plasma EB-DNA copy number (100%), and other major manifestations included abnormal liver function(100%), elevated ferritin(94.3%) and higher triglyceride(91.4%). Among the 52 cases, 11 cases died (including 4 cases of recurrence), 33 cases were improved or recovered, and 8 cases were lost to follow-up after discharge. There was statistical difference between the survival and death group in terms of the febrile days(P=0.036), hemoglobin(P=0.000), procalcitonin(P=0.032), gamama-glutamyl transferase(P=0.001), albumin(P=0.012), prothrombin time(P=0.001) and international normalized ration(P=0.007). Febrile days>14(P=0.003), hemoglobin reduction(P=0.003), gamama-glutamyl transferase increase(P=0.016), hypoalbuminemia(P=0.049) and prothrombin time prolongation(P=0.026) were risk factors for adverse. EBV reactivation was an important cause of recurrence(P<0.005). The survival rate of children with HLH-2004 was higher, but the cases was too little(P=0.565). Conclusion:Febrile days>14, hemoglobin reduction, gamama-glutamyl transferase increase, hypoalbuminemia and prothrombin time prolongation were adverse factors affecting prognosis. Children with reactive Epstein-Barr virus are more likely to relapse and have poor prognosis.