摘要
目的探讨我院临床诊断噬血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistio-cytosis,HLH)患儿的临床表现、预后及基因突变表型特点.方法应用回顾性调查方法对2013年4月至2018年12月我院确诊为HLH的42例患儿的临床资料及8例家族性HLH(familial HLH,FHL)患儿的基因资料进行汇总,分析HLH患儿发病年龄、临床表现、实验室检查、预后及FHL患儿基因突变表型特点,并根据是否合并EB病毒感染分组,重点分析EB病毒感染对HLH及FHL患儿临床表现及预后的影响.结果42例HLH患儿,发病年龄在1个月~13岁,<5岁者占74%,以血细胞两系降低、反复发热、肝脾淋巴结肿大、浆膜腔积液等为主要临床表现,实验室检查乳酸脱氢酶、铁蛋白、红细胞沉降率、甘油三酯等明显升高,临床预后方面,铁蛋白>4500μg/L患儿存活率及未化疗组存活率较低(P<0.05).共10例患儿化疗后存活,2例行造血干细胞移植的FHL患儿移植后已存活5~6个月.合并EB病毒感染患儿较未合并EB病毒感染发病年龄相对较年长,发热热程较长,淋巴结肿大比例更高,铁蛋白>4500μg/L患儿比例更高(P值分别为0.01、0.04、0.03、0.03),两组患儿生存时间差异无统计学意义,但合并EB病毒感染的FHL患儿与未合并EB病毒感染FHL患儿存活率差异有统计学意义(P<0.05).8例FHL患儿分别存在UNC13D(50.00%)、PRF1(25.00%)、PRKDC(12.50%)、IL2RG(12.50%)基因突变,突变类型多为复合杂合突变(62.50%),突变分别来源于父母.结论HLH以血细胞两系降低、反复发热、肝脾大等为特点,5岁以下儿童发病率高,合并EB病毒感染的HLH患儿临床表现更重、但临床预后差异无统计学意义.合并EB病毒感染的FHL患儿预后差,FHL发病比率不低,突变类型以UNC13D基因突变及复合杂合突变为多.HLH患儿应尽早进行家族性基因检测、进行标准化疗,及时造血干细胞移植是治疗FHL的良好手段.
Objective To investigate the clinical manifestations,prognosis and gene mutation phenotypes of hemophagocytic lymphohistiocytosis(HLH)in children of our hospital.Methods The clinical data of 42 patients with HLH from April 2013 to December 2018,and the genetic data of 8 patients with familial HLH(FHL)were collected retrospectively.The age,clinical manifestation,laboratory examination,prognosis and the characteristics of gene mutation phenotype of patients with HLH and FHL were analyzed emphatically.Furthermore,the clinical manifestations and prognosis of patients with HLH were analyzed according to whether EB virus was infected.Results Among these 42 patients with HLH,the onset age was ranged from 1 month to 13 years old and most of them were younger than 5 years old.The main clinical manifestations included cytopenia,prolonged fever,enlargement of liver and spleen and lymph nodes enlargement and serosal effusion.Laboratory examination showed that lactate dehydrogenas,ferritin,erythrocyte sedimentation rate and triglyceride increased significantly.The survival rate of the group in ferritin exceeding 4500μg/L and non-chemotherapy was lower than that of the group of ferritin less than 4500μg/L and chemotherapy in clinical prognosis(P<0.05).Ten patients of them survived after chemotherapy,and 2 patients survived for 5 to 6 months after hematopoietic stem cell transplantation in FHL.Patients with EB virus infection were older than those without EB virus infection.They had longer fever duration and higher proportion of lymph nodes enlargement and ferritin more than 4500μg/L(P values were 0.01,0.04,0.03,0.03 respectively).However,there was no significant difference in survival time between the two groups.Eight patients had mutations in UNC13D(50.00%),PRF1(25.00%),PRKDC(12.50%)and IL2RG(12.50%)genes respectively,and most of the mutations were complex heterozygous mutations(62.50%).All the mutations were originated from their parents.Conclusion HLH is characterized by cytopenia,prolonged fever,enlargement of liver and
作者
王静
王剑
罗丽娟
曹清
Wang Jing;Wang Jian;Luo Lijuan;Cao Qing(Department of Infectious Diseases,Shanghai Children′s Medical Center,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China;The Laboratory of Pediatric Infectious Diseases,Pediatric Translational Medicine Institute,Shanghai Children′s Medical Center,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China)
出处
《中国小儿急救医学》
CAS
2019年第12期889-894,共6页
Chinese Pediatric Emergency Medicine
基金
上海交通大学医学转化交叉基金(ZH2018QNA27)
上海交通大学医学院转化医学协同创新合作研究项目(TM201820)。
