儿童病毒相关性噬血细胞综合征32例临床研究

目的探讨儿童病毒相关性噬血细胞综合征(VAHS)的临床特点、诊断、治疗及预后。方法回顾性分析2005年5月至2009年5月我院儿科诊治的32例儿童VAHS患儿临床资料,应用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)检测VAHS患儿血清病毒抗体。结果①年龄分布:<2岁～14岁。②性别分布:男18例,女14例。③病因特点:32例病例中爱泼斯坦病毒(Epstein-Bart Virus,EBV)单一感染者18例(56.3%)、巨细胞病毒(CMV)单一感染者8例(25%),腺病毒(ADV)单一感染者2例(6.3%),EBV与CMV复合感染者3例(9.4%),EBV、CMV、柯萨奇病毒(CVB)、ADV及呼吸道合胞病毒(RSV)复合感染者1例(3.1%)。④临床特点:持续高热(100%)、肝肿大(81.2%)、脾肿大(90.6%)、外周血细胞白细胞计数减少(84.4%)、血红蛋白<90 g/L(62.5%)、血小板减少(71.9%)、高甘油三酯(TG)血症(53.1%)、低纤维蛋白原血症(65.6%)、血清铁蛋白(SF)≥500μg/L(100%)、谷丙转氨酶(ALT)升高(71.9%)、谷草转氨酶(AST)升高(78.1%)、乳酸脱氢酶(LDH)升高(90.6%)、高密度脂蛋白(HDL)降低(100%),32例骨髓均找到噬血组织细胞;其中EBV感染及复合感染较其他病毒单一感染临床表现更重;随着患儿病情好转,体温下降,脾脏缩小,症状消失,复查SF、LDH逐渐恢复正常水平。⑤治疗及转归:治疗全部采用抗病毒、对症支持治疗及HLH-2004方案,32例中治疗痊愈15例(46.9%),完全缓解后继续治疗中3例(9.4%),完全缓解后失访3例(9.4%),复发治疗中2例(6.3%),放弃治疗4例(12.5%),死亡5例(15.6%)。结论①儿童VAHS以EBV感染多见,其临床主要表现持续高热,肝、脾肿大,实验室检查主要特点:白细胞计数降低、血小板低、肝功能异常、甘油三酯及LDH及SF升高、纤维蛋白原低、骨髓找到噬血细胞。②EBV感染及复合感染较其他病毒单一感染临床表现更重。③SF、LDH检测对于其早期诊断及治疗效果的评价意义较大;LDH发病时水平较高的提示预后不好。④早期应用HLH-2004方案治疗有较好疗效并可改善预后。

Clinical research of 32 children with virus-associated hemophagocytic syndrom

Objective To investigate the clinical characteristics,diagnosis,treatment and prognosis of children with virus associated hemophagocytic syndrome(VAHS).Methods The clinical and laboratory data of 32 cases with VAHS diagnosed in the first affiliated hospital of Zhengzhou University from May 2005 to May 2009 were retrospectively analyzed.Viral Antibodies in serum weredetected by enzyme linked immunosorbent assay(ELISA) in 32 children with VAHS.Results ①Age distribution: 9 cases <2 yrs,12 cases 2~5 yrs,2 cases 5~8 yrs,3 cases 8~11 yrs and 6 cases 11~14 yrs.②Gender distribution: 18 males and 14 females.③Pathogenical characteristics: In all the 32 cases of VAHS,18 cases were infected with Epstein Bart virus(EBV)(56.3%),8 cases with cytomegalo virus(CMV)(25.0%),2 cases with adenovirus(ADV)(6.3%),3 cases were double infected with EBV and CMV(9.4%) and 1 case were multiple infected with EBV,CMV,Coxsackievirus(CVB),ADV and Respiratory Syncytial Virus(RSV)(3.1%).④Clinical characteristics: sustaining fever(100%),hepatomegaly(81.2%),splenomegaly(90.6%),leucocytopenia(84.4%),Hb<90g/L(62.5%),thrombocytopenia(71.9%),hypertriglyceridemia(53.1%),hypofibrinogenemia(65.6%),High SF(≥500μg/L)(100%),high ALT(71.9%),high AST(78.1%),high LDH(90.6%),low HDL and hemophagocytic histiocytes in marrow slides(100%).The clinical manifestations of VAHS with EBV or multiply infection are more serious than others.As disease improving,temperature decreasing,spleen size reducing and symptoms disappearing,the SF and LDH would gradually recover to normal ranges.⑤Treatments and prognosis: All patients accepted symptomatic supportive treatment and scheme of HLH 2004.In all the 32 cases,15 cases(46.9%) got recovery;3 cases(9.4%) kept maintenance treatment after complete remission(CR);3 case(9.4%) were lost after CR;2 cases(6.3%) continued treatment after relatpse;4 cases(12.5%) quit from hospital and 5 cases(15.6%) died during hospitalization.Conclusion ① EBV is the leading pathogen in VAHS with infection,and VAHS has fulminant courses and high mortality.The main clinical features of VAHS includes persistent hyperpyrexia,and hepatosplenomegaly.The laboratory data may probably suggest leucocytopenia,,thrombocytopenia,hepatic dysfunction,hypertriglyceridemia,high LDH,high serum ferritin,hypofibrinogenemia and hemophagocytic histiocytes in marrow slides observed.② The clinical manifestations of VAHS with EBV and multiple infection are more serious than others resulting in higher mortality.③ The detection of SF and LDH may play an important role in earlier diagnosis and evaluation of therapeutic effect.High level of LDH at the onset of VAHS may suggest a poor prognosis.④ It is beneficial to apply scheme of HLH 2004 early for improving the prognosis of VAHS.