Retrospective Analysis Of Clinical Features And Prognostic Factors Of 185 Cases Of Hemophagocytic Lymphohistiocytosis

Objective:Hemophagocytic syndrome is an excessive inflammatory response syndrome,which is caused by abnormally activated macrophages and cytotoxic T cells.HLH often has acute onset,rapid progression,poor prognosis and easy misdiagnosis.In order to improve the clinical understanding and diagnosis and treatment level of HLH,the epidemiological characteristics,clinical manifestations,laboratory examination,clinical diagnosis and treatment status and prognosis of HLH were summarized by retrospective data analysis,and the risk factors of prognosis and death were discussed,which verified the feasibility of the current expert consensus on diagnosis and treatment of HLH,and provided some clinical research data for revising the diagnosis and treatment scheme of HLH.Methods:The related electronic medical records of 145 children and 40 adult patients with HLH who were diagnosed for the first time in the First Affiliated Hospital of Kunming Medical University and Kunming Children’s Hospital from January 2018 to June 2020 and met the diagnostic criteria of "HLH-2004" were reviewed retrospectively.SPSS 19.0 software was used for statistical analysis of the related data.When P<0.05,statistical significance was indicated for the difference.Results:1.145 cases,the ratio of male to female was 1:1.27,the median age of onset was 3.4 years old,and the peak age of onset was 1-3 years old.The male to female ratio of 40 adult patients was 1:0.82,with a median age of 37 years and a peak of 15 to 45 years.The infection-related HLH was the most common(mainly due to EB virus infection),and the rest were immune disease-related HLH and tumor-related HLH,etc.The most common clinical symptoms were fever,hepatosplenomegaly,etc.Laboratory tests showed that blood phagocytosis was found in bone marrow,and elevated SF was more common.The survival curve showed that the mortality of HLH patients showed a downward trend over time within six months.The mortality declined rapidly in the early stage,but tended to be stable in the middle stage.There were no deaths in the late stage.2.ROC analysis showed that the optimal cutoff values of FIB,ANC,PLT,Hb,TG and SF in 145 children with HLH were 1.91,1.425,87.5,101.5,2.18 and 796.5,respectively.The optimal cutoff values for HLHFIB,ANC,PLT,Hb,TG,and SF in 40 adults were 1.755,1.55,100,101,2.515,and 1297,respectively.3.Compared with the positive control group,CD3+CD8+cells in children with HLH increased,and CD 16+CD56+NK cells decreased(both P<0.05).The values of IL-4,IL-6,IL-17,IFN-γ and IL-10 were increased,and the differences were statistically significant(P<0.05).Compared with the negative control group,the CD3+CD4+cells and the CD4+/CD8+ratio in HLH adults were decreased,and the difference was statistically significant(P<0.05).The values of IL-2,IL-4,IL-6,IL-8,IL-10,IL-12P70,IFN-γ and TNF-α increased and the differences were statistically significant(P<0.05).4.After treatment,the values of Hb,ANC,spleen smaller cases and body temperature returning to normal in the standard protocol group were higher than those of the non-standard protocol group,and the SF value was lower than that of the non-standard protocol group in children with 4.HLH.The differences were statistically significant(P<0.05).After adult treatment with HLH,the Hb and ANC values in the standard protocol group were higher than those in the non-standard protocol group,and the differences were statistically significant(P<0.05),while the PLT value was higher than that in the non-standard protocol group,and the differences were statistically significant(P<0.01).5.COX analysis shows that children with HLH are accompanied by hepatomegaly,low T3,FT3,decreased CD4+/CD8+ratio,decreased PLT and increased ALT when they develop the disease.In adults with HLH,prolongation of APTT and elevation of ALT had statistically significant effects on the prognosis(P<0.05),both of which were independent risk factors for poor prognosis.Spearman analysis showed that the levels of T3 and FT3 in children were positively correlated with their prognosis.Conclusions:1.Etiology and clinical manifestations of HLH are diverse,with enzymological changes in liver function,respiratory tract involvement and other manifestations.In particular,we found that some patients with HLH had low T3 and FT3 levels.This result has not been reported in the related literature before,and the specific mechanism is still unclear.It is considered to be related to the massive secretion of cytokines which inhibit thyroid function at different levels.We speculated that low T3 and FT3 might be an important reference index for the diagnosis of HLH.Standard treatment has its theoretical basis and positive clinical value for the treatment of HLH.2.ROC analysis was used to explore the optimal cutoff value of each diagnostic indicator.In the previous literature,only the cutoff value of ferritin was predicted,but we tried to get the cutoff values with high sensitivity and specificity of multiple indicators.Compared with the current diagnostic criteria,this cutoff value has certain reference significance for timely and early diagnosis,and efforts should be made to correct better cutoff value in the future.3.When the proportion of CD3+CD8+cells was increased,the proportion of CD16+CD56+NK cells was decreased,and the levels of IL-4,IL-6,IL-17,IFN-γ and IL-10 were increased in children;In adults,the proportion of CD3+CD4+cells is decreased,as well as the CD4+/CD8+ratio and the levels of IL-2,IL-12P70,IL-4,IL-6,IL-8,IL-10,IFN-y and TNF-α,which may be of great clinical significance for the early and timely diagnosis of HLH.4.The standardized use of the "HLH-94,HLH-2004" regimen is superior to the non-standard regimen(hormone shock,gamma globulin shock,etc.),and the exploration of layered treatment plan according to the etiological classification and severity of the disease are the new directions of HLH treatment in the future.5.Children with hepatomegaly,low T3,FT3,decreased CD4+/CD8+ratio,decreased PLT,and increased ALT at the onset of disease;In adult onset,prolonged APTT and elevated ALT are both risk factors affecting the prognosis,which provide a basis for treatment and evaluation of clinical prognosis.