Clinical Study On Severe Infectious Mononucleosis And Hemophagocytic Lymphohistiocytosis

Objective:To analyze the clinical features and diagnostic characteristics of severe infectious mononucleosis (IM) and compare it with the common IM. To study the condition of diagnosing and treating the patients with hemophagocytic lymphohistiocytosis (HLH) in infants and children .Methods: Data from cases diagnosed with severe IM was analyzed retrospectively. The clinical features between the severe IM and the common IM were studied comparatively. The study was done prospectively on the condition of diagnosing and treating the patients with HLH in infants and children. Twenty-eight cases of pediatric HLH were comparatively studied between 8 patients less than 2 years of age and 20 patients more than 2 years of age.Statistical analysis was made by SPSS 12.0.Results:(1)All patients diagnosed with severe IM presented persisted fever, apparent hepatomegaly and splenomegaly. The percentages of sore throat and lymphadenopathy in severe IM patients were statistically less than those in the common IM patients (76.5% vs 91.2% and 41.2% vs 69.9%, p<0.05). The incidence of rash in severe IM patients were markedly higher than those in the common IM patients (35.3% vs 13.3%, p<0.01). EBV-IgM was observed in 64% of the patients with severe IM. The heterophil agglutination test of all patients with severe IM was negative.(2)The cytopenia (affected at least 2 lineages or above in the peripheral blood) presented in 92.2% of the patients with severe IM and 9.1% in the patients with common IM. The increased number of atypical lymphocytes in the peripheral blood (≥10%) accounted for 47.1% of the patients with severe IM. Increased liver transaminase,direct bilirubin and LDH were observed in all severe IM patients, and the percent of these were significantly higher than that in the common IM patients. 54% of the severe IM patients had LDH level above 1000U/L. Hypoproteinemia (58%), jaundice (54%), serous cavity fluidity (54.9%) and GI bleeding (35.3%) were associated with the diagnosis of severe IM.(3)The prognosis of these patients with severe IM showed poorer than that of the common IM patients.(4) In all diagnostic criteria for HLH, fever, cytopenia, hyperferritinemia and hemophagocytosis were observed in all patients with HLH. The incidence of splenomegaly and hypofibrinogenemia was 92.9% in HLH patients.The elevated blood levels of lactate dehydrogenase (>1000IU/L) was observed in 96.3% of HLH cases, and which was considerably higher than hypertriglyceridemia (>3.0mmol/L) (53.6%) (P=0.048). 92.9% of the patients with HLH had the evidence of infecting EBV. The sensitivity of EBV-DNA was 0.92. No differences were found in clinical signs and symptoms or other laboratory findings for the two age groups: less than 2 years and 2 years or older.(5) 26 patients with HLH (92.9%) received immunochemotherapy, but only 53.8% patients applied to HLH-2004 treatment protocol. The immunochemotherapy was successful in 42.3% of the 26 patients with HLH. The surrival overall was 39.3% in all patients. No differences were found in surrival for the two age groups: less than 2 years and 2 years or older(12.5% vs 50%, p=0.099).Conclusions:(1)The sore throat, lymphadenopathy, and heterophil agglutination test were nonspecific to the diagnosis of severe IM. At the time of the EBV antibody negative and/or the increased numbers of atypical lymphocytes in the peripheral blood (<10%), the diagnosis of severe IM may be considered.(2)The clinical and diagnostic characteristics of severe IM includes:①persisted fever, apparent hepatomegaly and splenomegaly;②cytopenia;③increased transaminase and LDH;④the presentation of hypoproteinemia,jaundice,serous cavity fluidify and GI bleeding were associated with severe IM.(3) The suspecting patients with HLH need consecutively follow-up. Serial marrow aspirates over time may also be helpful. Increased serum lactate dehydrogenase concentrations are nonspecific but might be good diagnostic parameters for HLH. The sensitivity of EBV-DNA is prior to EBV capsid antibody.(4) Refinement of the treatment is mandatory to improve the outcome of HLH in both infants and older pediatric patients.