The Clinical Study On Adult-onset Still’s Disease Associated Macrophage Activation Syndrome

Objectives.Macrophage activation syndrome is a life-threatening complication of adult-onset Still’s disease,which is an acute systemic inflammatory complication.The estimated prevalence of MAS in AOSD patients is 10–19%and the mortality rate of AOSD associated MAS is approximately 10–20%.Due to the low incidence of AOSD,there is few research on the large-scale systematic retrospective study of AOSD associated MAS in the world,and there is no diagnostic criteria for AOSD associated MAS.Thus,we conducted a multicenter retrospective clinical study to explore the clinical characteristic of AOSD associated MAS,different treatment on prognosis,use of the etoposide in refractory AOSD associated MAS,and proposed diagnositic criteria for AOSD associated MAS.Methods.1.A total of 447 AOSD(55 AOSD associated MAS)patients who fulfilled the grouping criteria were enrolled in this study.The patients were recruited from Department of Rheumatology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Department of Rheumatology,Renji Hospital South Campus,Shanghai Jiaotong University School of Medicine,The First Affiliate Hospital of Nanjing Medical University,The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School,Xiangya Hospital of Central South University between January 1,2012 and December 31,2017.There were20 refractory AOSD associated MAS patients.Clinical manifestations,laboratory results,treatment program,and prognosis were recorded to analyze the clinical features,therapy and prognostic factors in AOSD.2.The 447 AOSD patients were collected as training set,we further collected another 99 AOSD(10 AOSD associated MAS)who were hospitalized in Department of Rheumatology,Renji Hospital as test set.Clinical manifestations and laboratory results of test set were also recorded.HScore and s JIA associated MAS criteria were validated in the training set.AOSD associated MAS criteria were recommended through ROC and logistic prediction probability in training set,and validated in test set.Results.1.In the retrospective clinical study,a total of 447 AOSD patients were included,and the mortalily of AOSD associated MAS was21.82%,which was far higher than the 2.04%in AOSD without MAS patients.In multifactorial analysis,platelets<100x10~9/L,glutamate transaminase>120U/L,triglyceride>3mmol/L,ferritin>1500 ng/m L,hemophagocytosis in bone marrow was highly correlated with the occurrence of MAS.Calcineurin inhibitors could effectively improve the prognosis of AOSD associated MAS.Etoposide could be used in refractory AOSD associated MAS patients as induction therapy,which was effective and well-tolerated.In this study,10 refractory AOSD associated MAS patients were given etoposide,and the mortality rate was 10%,which was lower than patients who had not accept etoposide(50%).Use of etoposide could improve the clinical manifestations in 7 days,and decreased the max dosage of corticosteroid and average dosage of corticosteroid.Platelets<100x 10~9/L,fibrinogen<1.5g/L,splenomegaly,and hepatitis suggested AOSD patients have poor prognosis.2.In the training set,HScore had a sensitivity of 85.45%,a specificity of 98.98%for the diagnosis of AOSD associated MAS,and Kappa value of0.872.While s JIA associated MAS criteria had a sensitivity of 100%,a specificity of 78.27%and Kappa value of 0.482.Both of those two criteria were not suitable for the diagnosis of AOSD associated MAS patients,because HScore is cumbersome and requires invasive operation,while s JIA associated MAS criteria had low specificity.To increase the specificity of s JIA with MAS criteria in AOSD,and make it apply to AOSD,we made a modification on the basis of JIA with MAS classification criteria.A febrile patient with known AOSD is classified as having MAS if the following criteria are met:ferritin>684ng/m L,and any 2 of the following:platelet count<165×10^~9,aspartate aminotransferase>151 U/L,triglycerides>1.85mmol/L,fibrinogen<2.74mg/d L.The criteria had a sensitivity of100%,a specificity of 87.50%and Kappa value of 0.609 in test set,which had higher specificity than s JIA associated MAS criteria,and were repeatable,simpler to use and noninvasive.Conclusions.Among the 447 AOSD patients(55 AOSD associated MAS)in this multi-center retrospective clinical study,AOSD associated MAS mortality was 21.82%,which was higher than AOSD without MAS patients(2.04%).Calcineurin inhibitors could effectively improve the prognosis of AOSD associated MAS.Etoposide could be used in refractory AOSD associated MAS patients as induction therapy,which could improve the survival rate,reduce the corticosteroid dosage,and be safe and reliable.Platelets<100 x 10~9/L,fibrinogen<1.5g/L,splenomegaly,and hepatitis suggested AOSD and MAS patients have poor short-term prognosis.We proposed AOSD associated MAS diagnostic criteria according to the s JIA associated MAS criteria combined with clinical features of AOSD:ferritin>684ng/m L,and any 2 of the following:platelet count≤181×10^9/liter,aspartate aminotransferase>120 units/liter,triglycerides>2.0mmol/L,fibrinogen≤2.7mg/d L.The diagnostic criteria was the first criteria for AOSD associated MAS,which is easier to use,repeatable and noninvasive.However,the application of this criteria still requires a large sample validation.