Kawasaki Disease Complicated With Macrophage Activation Syndrome:Report Of 9 Cases And Literature Review

Objective: To explore the clinical features of Kawasaki disease(KD)complicated with macrophage activation syndrome(MAS)and the biological significance of related gene and protein expression.Methods: Clinical data and laboratory results of patients with MAS in KD admitted to Children’s Hospital of Chongqing Medical University from August 2008 to June 2017 were retrospectively studied and compared with the patients from published literature.The patients were divided into two groups according to the prognosis: improvement group and poor prognosis group(dead or abandoned therapy).Results: 27 patients with MAS in KD were enrolled in this study.The incidence of clinical manifestations was as follows: hepatosplenomegaly and intravenous immunoglobulin(IVIG)unresponsiveness 100%(9/9),rashes 88.9%(8/9),changes in the extremities 88.9%(8/9),changes in the lips and oral cavity 77.8%(7/9),lymphadenopathy 66.7%(6/9),bilateral conjunctival injection 44.4%(4/9),coronary lesions 88.9%(8/9),incomplete Kawasaki disease(iKD)44.4%(4/9).C-reactive protein(CRP)increase,fibrinogen < 1.5g/L and ferritin level >1500 ng/ml were found in 8 patients separately.The rate of alanine aminotransferase(ALT),aspartate aminotransferase(AST)increase,hemophagocytic phenomenon in bone marrow and triglyceride(TG)>3.0 mmol/L were 77.8%(7/9),66.7%(6/9),66.7%(6/9)and 44.4%(4/9),respectively.HLH-related gene and protein expression were measured in 2 children with MAS in KD.Reduced expression of perforin in NK cells was detected in 2 cases,but reduced granzyme B in NK cell and reduced perforin in CTL cells were found in only one case.No mutation of 24 genes related to HLH was found in 2 cases.According to the prognosis,27 cases were divided into improvement group(18 cases)and poor prognosis group(9 cases).The incidence of iKD in poor prognosis group was higher than those in the improvement group(55.56% vs 5.88%,P=0.004).Conclusion: MAS complicating KD should be considered when KD with IVIG unresponsiveness,hepatosplenomegaly,elevated AST and ALT,hyperferritinemia occur.KD complicated with MAS showed no genetic susceptibility.Reduced perforin expression may be closely related to KD-MAS.Incomplete Kawasaki disease may be one of the risk factors affecting the prognosis of children with KD-MAS.