The Clinical Analysis Of 624 Children With Non-neoplastic Diseases Associated With Epstein-barr Virus Infection

Objective:To understand the clinical manifestations,laboratory tests,treatment and prognosis of children with non-neoplastic diseases associated with Epstein-Barr virus（EBV）infection and to provide a clinical data for the standard diagnosis and treatment of non-neoplastic diseases associated with EBV infection.Methods:Choose 624 children,who have accepted treatment in the first affiliated hospital of Zhengzhou University,with Epstein-Barr virus related-infection mononucleosis（EBV-IM）,chronic active Epstein-Barr virus infection（CAEBV）and Epstein-Barr virus-related hemophagocytic lymphohistiocytosis（EBV-HLH）,as the research object.Clinical data of the children were retrospectively analyzed,including age,gender,clinical symptoms,signs,blood routine,alanine aminotransferase,lactic dehydrogenase,blood coagulation function,ferritin,cell immunity,humoral immunity,EBV-DNA,treatment and outcome.The clinical data of the three groups were compared and analyzed,and the clinical characteristics and internal relations of each disease were summarized.Results:1.A total of 624 children are admitted to the group.The onset age is from 2months to 13-year-old and 10 months,mean age is 4.28±3.21 years,the median age is 3.42 years.EBV infection is more common in early childhood and pre-school age,with relatively fewer in infants and school-age children,including 373 males and 251females,with a ratio of 1.49 to 1.There was no significant difference in age of onset between the two groups（P>0.05）.There were 544 cases of EBV-IM,14 cases of CAEBV and 66 cases of EBV-HLH.The age of onset of different disease groups were significantly different（P<0.05）,IM children in the 1-3-year-old group and3-7-year-old group more common,CAEBV occurred in children over the age of 7.The age distribution characteristics of EBV-HLH were not as obvious as IM and CAEBV groups,with incidence in all age groups,which were more common in1-3-year-old group and 3-7-year-old group.2.Fever,angina and hepatosplenomegaly are common in children after EBV infection.The extent of hepatosplenomegaly was different in the three groups of diseases,and the degree of hepatosplenomegaly in CAEBV group and EBV-HLH group was heavier than that in IM group,the difference was statistically significant（P<0.05）.Eyelid edema in children with IM is common,and didn’t combined with abnormal urinalysis.Two patients with EBV-HLH at the beginning of the disease with capillary leak syndrome both died within 1 week.3.The levels of NE and PLT in EBV-HLH group were lower than those in the other two groups,but WBC and LY in IM group were significantly higher than those in the other two groups（P<0.05）.Among the EBV-HLH group,FIB was lower than that in the other two groups,while D-dimer was higher（P<0.05）.D-dimer have increased to varying degrees in all three groups of children.The level of ALT and LDH in the EBV-HLH group were higher than those in the other two groups.The level of ferritin was gradually increased in the IM,CAEBV,and EBV-HLH groups（P<0.05）.4.In terms of cellular immunity,the levels of CD₃⁺and CD₄⁺in IM group were significantly higher than those in CAEBV and EBV-HLH groups（P<0.05）.The proportion of CD₈⁺T lymphocytes in IM group was higher than those in other two groups,while the CAEBV group was lower than the other two groups,and the differences were statistically significant（P<0.05）.The ratio of CD₄⁺/CD₈⁺in EBV-HLH group was lower than that in IM group（P<0.05）.The proportion of CD⁺₅₆cells in EBV-HLH was lower than the other two groups,the differences were statistically significant（P<0.05）.5.In humoral immunity,the levels of IgA,IgG and IgM in EBV-HLH group were significantly different from those in the other two groups（P<0.05）,and the level of IgE in CAEBV group was higher than the other two groups（P<0.05）.The level of complement C4 in CAEBV group and EBV-HLH group was lower than that in IM group（P<0.05）,the difference in complement C3 among the three groups was not statistically significant（P>0.05）.6.The EBV-DNA load of EBV-HLH group was higher than that of IM group and CAEBV group（P<0.05）.There was no significant difference in EBV-DNA level between the IM group and the CAEBV group at initial diagnosis（P>0.05）.The EBV-DNA load of IM patients turned negative within 4 weeks,while the CAEBV group showed a slight decrease of viral nucleic acid load but no negative conversion within 4 weeks.EBV-DNA levels in children with CAEBV who were diagnosed as IM initially were（8.73-44.6）×10⁵ copies/μg,significantly higher than those of children with IM.7.Among them,624 cases were enrolled.There were 544 cases of EBV-IM,5cases supervened with CAEBV,and 2 cases died.14 cases were CAEBV,6 cases supervened with HLH,and 4 cases died.And there were 66 cases of EBV-HLH,21cases of death,7 cases of losing to follow-up,and now known to survive 38 cases.Conclusions:1.Among the children with non-neoplastic diseases associated with EBV infection,the prevalence of different diseases is different.IM patients are mainly in preschool and early childhood,while CAEBV is predominantly in school-age children.EBV-HLH incidence in all age groups,early childhood and pre-school age slightly more.2.The disease often involves multiple systems and organs.Eyelid edema is a characteristic clinical manifestations,if you can rule out kidney disease,be highly vigilant the possibility of IM.3.There is cellular immune dysfunction in EBV-IM and CAEBV patients,while in EBV-HLH children,cellular immune dysfunction and humoral immune dysfunction are both present.4.The EBV-DNA load is related to the type of the disease.For children who are initially diagnosed with IM,a dynamic surveillance of serum EBV-DNA levels for at least 4 weeks is necessary,which is of great value in the early detection and diagnosis of CAEBV with onset of IM symptoms.