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

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2128.5 U/L)和天冬氨酸氨基转移酶(AST)(中位数为489 U/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＞10 d(OR=8.097)、LDH进行性升高＞1000 U/L(OR=7.998)、低白蛋白血症(OR=7.838)、中性粒细胞＜1.5×109/L(OR=7.587)和血小板＜100×109/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＞10 d、LDH＞1000U/L、低白蛋白血症、中性粒细胞＜1.5×109/L、血小板＜100 x 109/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.

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

OBJECTIVE: To compare the clinical features of infectious mononucleosis (IM) and Epstein-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 degrees C vs. 39.0 degrees C, 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 x 10(9)/L vs. 12.8 x 10(9)/L, P < 0.001), median of neutrophils (0.53 x 10(9)/L vs. 3.17 x 10(9)/L, P < 0.001), mean of hemoglobin (80 g/L vs. 120 g/L, P < 0.001) and median of platelet (27.5 x 10(9)/L vs. 183 x 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 < 35 g/L, OR = 7.838, P = 0.038), neutrophils < 1.5 x 10(9)/L (OR = 7.587, P = 0.022) and Plt < 100 x 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 x 10(9)/L. EBV-ASH is an extremely dangerous state with high mortality. Repeated bone marrow examinations are helpful for diagnosis in time.