Clinical Characteristics And Prognosis Of Infection-associated Hemophagocytic Syndrome

Objective:To investigate the clinical features and prognosis of infection-associated hemophagocytic syndrome in adults.Methods:The clinical data and baseline data of 78 newly diagnosed adult IAHLH patients admitted to the Second Hospital of Shanxi Medical University from January 1,2016 to December 31,2021 were collected and analyzed retrospectively.The comparison between groups conforms to the normal distribution,and the non-parametric test is used for the non-normal distribution.Kaplan-Meier method was used to draw the survival curve,Log-rank was used for single factor analysis,and Cox regression analysis was used for multiple factor analysis.Results:1.A total of 78 patients were included,including 40 males and 38 females,with a male to female ratio of 1.05:1,a median age of 50 years(19 years to 79 years),and a median overall survival(OS)of 4 months(0.09 months to 57 months).2.Of the 78 IAHLH patients,40(51.29%)were infected with EBV,5 with fungi,including 2 with Aspergillus fumigatus,6 with Enterococcus faecium,5 with influenza virus,3 with cytomegalovirus,2 with Leishmania donovani,2 with Klebsiella pneumoniae,3 with Mycobacterium tuberculosis,3 with Brucella melitensis,3 with methicillin-resistant coagulase-negative staphylococci,2 with herpes virus and 4 with mycoplasma/chlamydia.3.Of the 78 patients,69(88.5%)had fever,of which 61(88.4%)had fever for more than 7 days,60(76.92%)had splenomegaly,52(66.7%)had superficial lymphadenopathy,37(47.44%)had respiratory symptoms,with cough and sputum as the main manifestations and 32(41%)had digestive symptoms,and anorexia,nausea,abdominal pain,and diarrhea as the main manifestations.4.Of the 78 patients,78(100%)had a decrease in whole blood cells,44(56.41%)had a decrease in the absolute value of neutrophils and 57(73.07%)had a decrease in the absolute value of lymphocytes.Hypoalbuminemia was observed in 70 patients(89.74%).Serum ferritin(SF)≥ 500 ug/L was observed in 69 patients(88.46%).Abnormal liver function was observed in 65 patients(83.3%).C-reactive protein(CRP)increased in63 cases(80.77%)..LDH increased in 60 patients(76.92%).Procalcitonin(PCT)increased in 59 patients(75.64%).Bone marrow infiltration was observed in 59 patients(75.64%).Nineteen patients(24.35%)had hypertriglyceridemia(>3 mmol/L).The coagulation series was abnormal in 23 patients(29.49%),including prolonged prothrombin time(PT)in 20 patients(71.43%),prolonged activated partial thromboplastin time in 8patients(34.78%)and increased D-dimer in 59 patients(75.64%),and hypofibrinogenemia(<1.5 g/L)in 20 patients(25.64%).Renal function was abnormal in 10 patients(12.82%).Fifty patients underwent T-cell subsets examination,including 21 patients(42%)with elevated Th and 37 patients(47.44%)with elevated Ts.A total of 34 patients had elevated soluble CD25(s CD25)in pedestrians,including 31 patients(91.17%)with s CD25 levels ≥6400 pg/ml.Cytokine examination was performed in 22 patients,including 16patients(72.73%)with elevated tumor necrosis factor α(TNF-α),14 patients(63.64%)with elevated gamma interferon(INF-γ),4 patients(18.18%)with elevated interleukin-2(IL-2),10 patients(45.45%)with elevated IL-4,20 patients(90.91%)with elevated IL-6,21 patients(100%)with elevated IL-10,and 6 patients(27.27%)with elevated IL-17.5.Of the 78 patients,4(5.13%)were treated with HLH-1994 + anti-infection regimen,31(39.74%)with HLH-2004 + anti-infection regimen,13(16.67%)with hormone +anti-infection regimen,and 30(38.36%)with anti-infection therapy alone in the initial treatment regimen.The median OS was 11.5 months for HLH-1994 + anti-infective regimen,12 months for HLH-2004 + anti-infective regimen,3 months for hormone +antibiotic regimen,and 2 months for anti-infective therapy alone,and the difference was statistically significant(P = 0.03).6.There were statistically significant differences in platelet count(PLT),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)between EBV associated hemophagocytic lymphohistiocytosis(EBV-HLH)and non-EBV-HLH patients(P<0.05).7.The univariate analysis showed that LDH(> 276 u/L),Il-17(> 9.81 pg/m L),d-dimer(> 940 ng/m L),creatinine(> 60 μmol/L)and treatment regimen(HLH-2004)were significantly correlated with the prognosis of the patients(p < 0.05).The multivariate analysis showed that LDH(> 276 u/L)and treatment regimen were independent prognostic risk factors(p < 0.001).Conclusion:1.The clinical manifestations of HLH are various and lack of specificity.Fever is the most common clinical feature.2.The survival time of EBV-HLH patients was shorter than that of non-EBV-HLH patients(p < 0.05).3.Single factor analysis showed that LDH(> 276 u/L),Il-17(> 9.81 pg/ml),D-dimer(> 940 ng/ml),creatinine(CR)(> 60 umol/l)were correlated with prognosis(p < 0.05).4.Anti-infection therapy alone and LDH(> 276 U/L)were independent prognostic risk factors for poor OS in IAHLH patients(p < 0.01).