Analysis Of Clinical Characteristics And Prognostic Risk Factors Of 26 Children With Macrophage Activation Syndrome

[Research background and objective]Macrophage activation syndrome(MAS)is a kind of hemophagocytic syndrome.It is one type of the connective tissue diseases related potential life-threatening complications.At present,there is more than 30 kinds of autoimmune diseases/autoinflammatory diseases associated with MAS.The most common disease is systemic juvenile idiopathic arthritis.The other connective tissue diseases are rare,for example systemic lupus erythematosus(SLE),Kawasaki disease(KD),dermatomyositis(DM),mixed connective tissue disease(MCTD),undifferentiated connective tissue disease(UCTD),etc.This disease is characterized by a variety of pathogenic factors leading to autoimmune dysfunction,excessive activation of lymphocytes and macrophages to release a large number of inflammatory cytokines.The body in hyper cytokines environment can damage the functions of various important organs.The severe progression of MAS may lead to multiple organ failure and eventual death.The mortality reported recently is 8%～23%.The early clinical manifestations and laboratory characteristics of the disease are not typical,early diagnosis is very difficult,and it is easy to delay diagnosis and treatment,resulting in poor prognosis.At present,there is a lack of relevant literature on the risk factors of MAS prognosis,so it is very important to summarize the clinical characteristics of the disease and analyze the prognostic factors for improving the diagnosis and treatment level of MAS and reducing the mortality.[The research methods]A total of 26 children with macrophage activation syndrome were selected as the research subjects who admitted to the Children’s Hospital of the First Affiliated Hospital of Zhengzhou University from January 2010 to January 2020.The clinical manifestations,laboratory examination,treatment plan and prognosis were retrospectively analyzed.The diagnosis of MAS in children with sJIA was consistent with the EULAR/ACR/Paediatric Rheumatology International Trials Organisation(PRITO)2016 classification criteria for MAS associated with sJIA.MAS associated with systemic lupus erythematosus(SLE),mixed connective tissue disease(MCTD)and undifferentiated connective tissue disease(UCTD)was diagnosed in accordance with the MAS diagnostic guidelines proposed by Raveili et al.(2005)and HLH-2004 diagnostic criteria.Children with consistent diagnosis were included in the study.The diagnosis of children with SLE accord with the 2012-SLE classification criteria of the International Tissue Cell Society(SLICC).The diagnosis of MCTD in children conforms to the standards established by the Chinese Society of Rheumatology.The diagnosis of children secondary to UCTD met the diagnostic criteria established by Marta Mosca.The basic data,clinical characteristics,laboratory data,treatment,imaging data and follow-up results of all cases were collected.SPSS21.0 software was used to conduct data statistics.Non-normal distribution measurement data was represented as median,and Mann-Whitney rank sum test was used.Counting data was represented as number of cases,and Fisher’s exact probability method was used to test.In order to P<0.05 was statistically significant.Univariate regression analysis was used to analyze related risk factors.Multivariate logistic regression analysis was used to seek possible independent predictive risk factors.[Result]1.The median age of the patients was 8.5(3～14)years old,including 10 males(38.46%)and 16 females(61.44%).The primary diseases included sJIA in 18(69.23%),SLE in 4(15.38%),UCTD in 3(11.54%)and MCTD in 1(3.85%).The main clinical manifestations were fever in 26 cases(100%),rash in 16 cases(61.54%),joint pain in 17 cases(65.38%),superficial lymph node enlargement in 11 cases(42.31%),tonsillar enlargement in 2 cases(7.7%),splenomegaly in 11 cases(42.31%),hepatomegaly in 13 cases(50%),serous cavity effusion in 5 cases(19.23%),and central nervous system symptoms in 4 cases(15.38%).The result of laboratory examination showed that there were two or three lines of blood cells decreased in 23 cases(88.46%),abnormal liver function in 26 cases(100%),ferritin increased in 24 cases(92.31%),CRP increased in 23 cases(88.46%),triglyceride increased in 19 cases(73.08%),fibrinogen decreased in 24 cases(92.31%),LDH increased in 21 cases(80.77%),ESR increased in 21 case(80.77%),and 6(23.08%)cases were positive in antinuclear antibody.There were 9 cases had NK cell killing activity data,among them,7 cases(77.8%)were decreased.There were 14 cases had data of complement C3 and C4,among them,7 cases(50%)were decreased.In bone marrow cytology,reticular cells and phagocytes were found in 8 cases(30.77%).2.Compared with the survival cases of MAS,the Hb level of death cases of MAS was significantly lower,ferritin level and LDH level were significantly higher,and the difference was statistically significant(P<0.05).There were significant differences in whether or not the central nervous system was involved and whether the liver was enlarged(P<0.05).3.Univariate regression analysis showed that the difference of ferritin>2000(μg/L)and LDH>2000(U/L)between death group and survival group was statistically significant(P<0.05).Multivariate regression analysis showed that LDH>2000(U/L)(OR=24.386,95%CI:1.383～430.009,P=0.029)was an independent risk factor affecting the prognosis of MAS.4.All children met the diagnostic criteria of sJIA-MAS in 2016,which showed its good applicability.[Conclusion]1.The clinical characteristics of MAS were not typical and varied.MAS can occur in the onset or course of the primary disease.2.MAS children with hepatomegaly,central nervous system symptoms,hemoglobin levels significantly decreased,ferritin,lactate dehydrogenase significantly increased may indicate poor prognosis.3.LDH>2000U/L is an independent risk factor for the prognosis of MAS.4.The 2016 sJIA-MAS diagnostic criteria are also applicable to MAS associated with MCTD and UCTD.