严重慢性活动性EB病毒感染12例临床回顾与随访

Clinical characteristics and follow-up of 12 cases with severe chronic active Epstein-Barr virus infection

目的报告12例符合诊断标准的严重慢性活动性EB病毒感染（SCAEBV）。方法回顾性分析12例SCAEBV患儿的临床资料、实验室、血清学、影像学和病理学检查以及初步随访的结果。结果SCAEBV临床主要表现为发热、脾肿大、肝肿大、淋巴结肿大，其他表现有皮疹、黄疸、肺动脉高压、口腔溃疡和胆囊炎等。辅助检查的异常包括乳酸脱氢酶升高、肝功能异常、贫血、白细胞降低、中性粒细胞降低、血小板减少以及胸部X线的异常等。所有患者均有抗EB病毒衣壳抗原KgG抗体的升高，而其IgM和IgA的阳性率分别为33．3％和66．7％；检测5例EB病毒早期抗原IgG均为阳性，而其IgA的阳性率为40．0％。实时定量聚合酶链反应检测外周血EB病毒DNA载量（中位数）为8．12×10^6copies／ml。12例患者中4例死亡，其中2例死于噬血细胞综合征，1例死于多重感染，1例死于多脏器功能衰竭；其余病例随访中1例发生了T细胞性非霍奇金淋巴瘤，1例脾切除术后发生了肝肺综合征。结论SCAEBV临床表现多样，常伴有各系统严重并发症，预后差，死亡率高，应引起儿科临床医师的关注。

Objective There are two different types of chronic active Epstein-Barr virus （CAEBV） infection： chronic EBV （CEBV） having persistent infectious mononucleosis （IM）-like illness with relatively good prognosis, and severe CAEBV （SCAEBV）infection that has rather severe manifestations and generally poor prognosis with many life-threatening complications, such as EBV-associated malignant lymphoma and hemophagocytic syndrome （ HPS ） . The purpose of this study was to clarify the clinical and prognostic characteristics in 12 cases with SCAEBV infection. Method Data of 12 cases with SCAEBV infection were analyzed retrospectively, which included clinical and auxiliary examination, pathological data, especially EB virus （EBV）-antibodies and DNA in peripheral blood mononuclear cells （PBMC） and infected tissue, and follow-up information. Result Of the 12 cases, 7 were male and 5 were female. The age at the onset of diseases ranged from 35 months to 14 years （median, 11 years）. The major manifestations were fever （100%）, splenomegaly （91.7%）, hepatomegaly （83.3%）, lymphadenopathy （75.0%）, and others, including skin rash, development retardation, jaundice, ascites, pulmonary hypertension, oral ulcer, choleeystitis and pleural effusion. The abnormalities of auxiliary examination were as follows： elevated LDH level （ 91.7% ）, liver dysfunction （ 83.3% ）, anemia （ 75.0% ）, leukopenia （ 58.3% ） , neutropenia （50. 0% ）, thrombocytopenia （25. 0% ） and abnormal chest X-ray findings. At the time of onset, 58.3% of the patients had an IM-like illness. In all of the 12 cases, EBV serologic tests revealed high IgG antibody levels against EB viral capsid antigen （VCA）. The patients often had positive IgM and lgA antibodies against VCA （33.3% and 66. 7% ） as well. Elevated IgG antibody level to early antigen （EA） （100. 0% ）, occasionally positive IgA antibody （40. 0% ） were also seen. The mean load of EBV-DNA detected by real-time polymerase chain reaction （PCR） in the PBMC was（8. 12 ×10^6, median）eopies/ml. Four of 12 cases presented a poor clinical course, two of whom died from EBV-assoeiated HPS, 1 from severe multiple pathogens infection, and 1 from multiple organ failure. In addition, 1 case developed Hodgkin＇s T cell lymphoma and another case showed hepatopulmonary syndrome in 2 years after splenectomy. Conclusions The clinical feature of SCAEBV infection varied exceedingly. EBV-DNA load in PBMC of SCAEBV infected patients was significantly increased. More attention should be paid to the disease because of its severe complications, poor prognosis and high mortality.