儿童传染性单核细胞增多症并发EB病毒相关性噬血细胞综合征临床危险因素分析

Clinical risk factors for Epstein-Barr virus-associated hemophagocytic syndrome in children with infectious mononucleosis

目的比较传染性单核细胞增多症（infectious mononucleosis，IM）和EB病毒相关性噬血细胞综合征（EBV-associated hemophagocytic syndrome，EBV—AHS）的临床特点，分析IM患儿发生EBV-AHS的临床危险因素。方法回顾性比较我院2000年1月至2006年4月430例IM和EBV-AHS患儿临床症状、体征和实验室检查特点，采用Logistic回归分析IM患儿发生EBV-AHS的临床危险因素。结果（1）本组IM病例中EBV-AHS发生率为3．72％（16／430），EBV-AHS组患儿热程明显长于IM组患儿，体温峰值、肝脏和脾脏肿大程度均较IM组患儿明显，但咽峡炎发生率（37．5％）显著低于IM组（91．1％），差异均有统计学意义。（2）EBV-AHS组外周血三系均低于IM组，且变异淋巴细胞升高不明显，其比例（中位数10％）显著低于IM组（中位数18％），差异亦有统计学意义。（3）EBV—ASH组肝功能损害显著重于IM组，尤其乳酸脱氢酶（LDH）（中位数为2128．5U／L）和天冬氨酸氨基转移酶（AST）（中位数为489U／L）水平升高显著高于IM组，且常伴有高胆红素血症及低白蛋白血症。（4）多因素Logistic回归分析发现：热程〉10d（OR=8．097）、LDH进行性升高〉1000U／L（OR=7．998）、低白蛋白血症（OR=7．838）、中性粒细胞〈1．5×10^9／L（OR=7．587）和血小板〈100×10^9／L（OR=7．190）是本组IM患儿发生EBV—AHS的临床危险因素，本组EBV-AHS病死率高达50％。结论绝大多数IM患儿呈良性自限性过程，约3．7％患儿进展为EBV—ASH。热程〉10d、LDH〉1000U／L、低白蛋白血症、中性粒细胞〈1．5×10^9／L、血小板〈100×10^9／L是IM患儿发生EBV-AHS的临床危险因素，该病预后凶险，病死率高，多次骨髓检查有助于及时诊断。

Objective To compare the clinical features of infectious mononucleosis （IM） and Epstin-Barr virus （EBV）-associated hemophagocytic lymphohistiocytosis （EBV-AHS） and identify the clinical risk factors in IM patients complicated with EBV-AHS. Method A retrospective study was carried out to analyze the clinical and laboratory data of 414 IM and 16 EBV-AHS children from January, 2000 to April, 2006. Then Logistic regression was used to identify the risk factors for progression to EBV-ASH. Results （ 1 ） The incidence of EBV-AHS among the IM children was 3.72% （ 16/430 ）. There were significant differences between EBV-ASH and IM children in duration of fever （20 days vs. 7 days, P 〈 0. 001 ） , the peaks of fever （40. 0℃ vs. 39. 0℃ , P 〈0. 001 ） , the degree of hepatomegaly （3.5 cm vs 2.0 cm below costal arch, P 〈 0. 05 ） and splenomegaly （ 2.75 cm vs. 1.0 cm below costal arch, P 〈 0. 05 ） , while the incidence of isthmitis in EBV-AHS patients was markedly lower than that of IM patients（37.5% vs. 91.1%, P 〈 0.01 ）. （2） Pancytopenia was often observed in EBV-AHS patients and significant differences between two groups were found in median of leukocytes （3.1 × 10^9/L vs. 12. 8 × 10^9/L, P 〈 0. 001 ） ,median of neutrophils （0. 53 × 10^9/L vs. 3. 17 × 10^9/L, P 〈 0. 001 ） , mean of hemoglobin （80g/L vs. 120 g/L, P 〈0.001） and median of platelet （27.5 × 10^9/L vs. 183 × 10^9/L, P 〈0.001）. （3） Hepatic derangement evidenced by elevated serum enzymes, hyperbilirubinemia and hypoalbuminemia in EBV-ASH children was much more severe than that in IM children, especially LDH level （2128.5 U/L vs. 445 U/L, P 〈0. 001 ） and AST level（489 U/L vs. 59 U/L, P 〈0. 001 ）. （4） The clinical risk factors for IM patients progressing to EBV-ASH were lasting fever ≥ 10 days（ OR = 8. 097, P = 0. 008 ）, LDH 〉 1000 U/L （ OR = 7. 998, P = 0. 033 ）, hypo-albuminemia （ albumine 〈 35g/L, OR = 7. 838, P = 0. 038 ）, neutrophils 〈 1.5 × 10^9/L （ OR = 7. 587, P = 0.022） and Pit 〈 100 × 10^9/L（ OR = 7. 190, P = 0.027 ）. The mortality of EBV-AHS in the patients was 50. 0% （8/16）. Conclusion Most of IM children clinically manifest self-limited process, but about 3.72% of whom may progress to fatal EBV-ASH. The clinical risk factors for EBV-AHS are lasting fever 〉 10 days, LDH 〉 1000 U/L, hypoalbuminemia, neutropenia and Plt 〈 100 × 10^9/L. EBV-ASH is an extremely dangerous state with high mortality. Repeated bone marrow examinations are helpful for diagnosis in time.