The Clinical Research On Epstein-Barr Virus Associated Severe IM And HLH

Objective: To provide clinical data for controlling Epstein-Barr virus associated hemophagocytic lymphohistiocytosis(EBV-HLH) by investigat- -ing the clinical features, diagnosis, treatment and outcome of EBV associated severe infectious mononucleosis(severe IM) and EBV-HLH, and analyzing the risk factors for the presence of EBV-HLH.Methods: Clinical manifestations, laboratory features, diagnosis, therapy and outcome were evaluated retrospectively in 41 patients of severe IM and EBV-HLH. The risk factors for the presence of EBV-HLH were analyzed.Results: (1) The ratio of boys versus girls was 2.4:1. 70.7% of the patients were youger than 6 years old. Seasonal peak was in summer and autumn (from July to October). The ratio of city versus village was 1:4.1. All of them had no family history. (2) The main symptoms and signs of the patients included fever (100%), hepatomegaly (90.2%), splenomegaly (90.2%), tonsillopharyngitis(87.8%) and cervical lymphadenopathy(53.7%). Longer febrile duration and higher peak temperature were found in EBV-HLH. The differences were statistically significant between the two groups. Tonsillopharyngitis, hepatomegaly, splenomegaly and cervical lymphadenopathy appeared to be similar in the two groups. (3) WBC, ANC, Hb, PLT and ALB were lower in EBV-HLH than severe IM. TB, AST and LDH were higher in EBV-HLH group than severe IM. The differences were statistically significant between the two groups. The percentage of lymphocytes and AL, and the concentration of DB, ALT, ALP elevated in the two groups (The differences were not statistically significant between EBV-HLH and severe IM groups). The number of injured organs was significantly more in EBV-HLH group (P=0.006). (4) Elevated SF and TG were noted in 100% (12/12) and 88.2% (15/17) of patients in EBV-HLH group. Fg decreased in 94.1% (16/17) of patients in EBV-HLH group. (5) The positive rates were 88.0%, 85.4%, 54.5% and 4.5% in the tests of EBV-DNA PCR, serum EBV antibody, quick diagnosis experiment and Paul-Bunnell test, respectively. EBV-DNA PCR was positive in all patients of EBV-HLH group, while serum EBV antibody was negative in 3 patients of them. (6) The accrementition of karyocytes was inhibitive in 70.6% (12/17) patients of EBV-HLH group in the cytological examination of bone marrow; but the accrementition of karyocytes was active in 85.7% (12/14) patients of the other group. The percentage of histiocytes elevated in both two groups, with a highest ratio of 35.5%. Hemophagocytosis was found in 15 patients of EBV-HLH group. (7) 9 patients of EBV-HLH group were treated with ED immunochemotherapy. 6 of them got improvement (The time of therapy was longer than 1 week), and 3 of them didn't get any improvement (The course of treatment was shorter than 1 week in 2 patients). 8 patients of EBV-HLH group were treated with antivirus drugs and steroids. 2 of them got improvement (The time of therapy was longer than 1 week). All patients of severe IM without EBV-HLH were treated with antivirus drugs or steroids. 13 of them got improvement (The time of therapy was longer than 1 week), and 7 of them didn't get any improvement (The course of treatment was shorter than 1 week in 5 patients).Conclusions: (1) Most patients of severe IM and EBV-HLH were male and younger than 6 years old. Seasonal peak was in summer and autumn (from July to October). The common clinical features were fever, hepatomegaly, splenomegaly, tonsillopharyngitis and lymphadenopathy. The total febrile duration and peak temperature may be helpful for the decision of EBV-HLH. (2) Injuries of hemotopoietic system and liver could be found in all patients of our study. The injuries of hematopoietic system and liver were much more serious in EBV-HLH. The number of injured organs was more in EBV-HLH, too. SF, TG and Fg were noticeable abnormal in EBV-HLH. Therefore, SF, TG and Fg should be examined when someone was suspected a diagnosis of EBV-HLH. (3) The tests of EBV-DNA PCR and serum EBV antibody were much more sensitive than quick diagnosis experiment and Paul-Bunnell test. Especially in EBV-HLH, the test of EBV-DNA PCR was more sensitive than serum EBV antibody. So, EBV infection could't be excluded and EBV-DNA PCR should be determined when serum EBV antibody was negative. (4) Many patients of EBV-HLH had characteristic changes in cytological examination of bone marrow. The accrementition of karyocytes was inhibitive. The percentage of histiocytes elevated. And hemophagocytosis was discovered. The inhibition of the accrementition of karyocytes was a significant risk factor for the presence of EBV-HLH. So, early intervention should be carried out once the risk factor was discovered. (5) EBV-HLH could get notable improvement in a short term by the administration of ED immuno- -chemotherapy. The temperature and PLT should be regarded as the index of the therapeutic effect. Most patients of severe IM could get improvement by the administration of antivirus drugs. If the therapy didn't get any effect, the possibility of EBV-HLH should be kept in mind. Immunochemotherapy should be performed while diagnosing EBV-HLH. The time of therapy was very important in EBV associated severe IM and EBV-HLH.