儿童慢性活动性EB病毒感染18例病例系列报告

目的探讨慢性活动性EB病毒感染（CAEBV）患儿的临床表现、实验室检查、治疗和预后，为其诊治提供参考。方法回顾性分析2010年1月1日至2017年12月31日18例CAEBV患儿的临床资料，包括起病方式、临床表现、实验室检查（EB病毒DNA及抗体谱、细胞因子等）、治疗和随访情况。结果18例CAEBV患儿进入本文分析，男8例、女10例。发病年龄1.0~13.9岁。该病起病方式13例为EB病毒再发感染，5例为EBV相关噬血细胞综合征（EBV-HLH）。临床表现主要为反复发热，肝、脾、淋巴结肿大，肝功能损害，血细胞减少；18例EB病毒衣壳抗原（VCA）-IgM首次检测均阴性，EB VCA-IgG均强阳性，血清（18/18）、骨髓（14/14）及活检组织EBV-DNA（肝1/4，淋巴结2/3）强阳性；IL-4、IL-10及IFN-γ升高者分别占67%（12/18）、89%（16/18）、72%（13/18）。B细胞、总T细胞及CD8+T细胞、NK细胞比例降低。患儿主要接受抗病毒药物、丙种球蛋白、免疫抑制剂、联合化疗、利妥昔单抗和造血干细胞移植等治疗。1例失访，14例（78%）死亡，EBV-HLH起病者生存期明显缩短。结论CAEBV起病方式、临床表现多样，治疗方案差异较大，病死率高，预后差。EBV DNA及抗体谱、细胞因子及淋巴细胞亚群改变呈一定的特异性，可为该病的早期诊断、进行有计划造血干细胞移植等提供参考。

Clinical analysis of 18 children with chronic active Epstein-Barr virus infection

ObjectiveTo study the clinical and laboratory characteristics, treatment and follow-up results of chronic active Epstein-Barr virus infection（CAEBV）in children and to provide a basis for the diagnosis and treatment of CAEBV. MethodsThe clinical data of 18 children with CAEBV from Jan 1st, 2010 to Dec 31st, 2017 was analyzed retrospectively, including onset, clinical manifestation, EBV DNA, EBV antibodies, cytokines, treatment and follow-up results. ResultsThe onset of the disease was EBV recurrent infection at the time of first hospitalization in 13 cases, and EBV-hematophagous lymphocyte hyperplasia (HLH) in 5 cases. The common clinical manifestations were fever, hepatosplenomegaly, and lymphadenopathy. Laboratory tests showed that elevated transaminase and cytopenia were common. The anti-EB VCA-IgG antibodies were positive, while the IgM antibodies were negative in 18 cases. EBV DNA in peripheral blood(18/18), bone marrow(14/14) and biopsy sample(live: 1/4, lymphonodus: 2/3) was positive. Plasma levels of several cytokines, including IL-4,IL-10 and IFN-γ,elevated in different degrees in persons with CAEBV, while the ratio of B cells, total T cells, CD8+T cells, and NK cells in peripheral blood decreased. The patients had mainly received antiviral drugs, intravenous immune globulin, immunosuppressive agents, multi-drug chemotherapy, rituximab, and HSCT. Among 17 CAEBV patients followed up,14 cases died. The patients with EBV-associated HLH had significantly shorter survival time. ConclusionThe children with CAEBV infection had poor prognosis and high mortality due to the variety of onset, clinical manifestation and treatment. The specific changes of EBV DNA, antibody profiles, cytokines and lymphocyte subsets may be helpful in the early diagnosis and targeted therapy of CAEBV.