Predictive Value Of Neutrophil Lymphocyte Ratio On Immunoglobulin Resistance To Kawasaki Disease

Background and ObjectiveKawasaki disease(Kawasakidisease,KD),also known as cutaneous mucosal lymph node syndrome,is an immune system disease characterized by systemic inflammation of the middle and small arteries,which mainly occurs in children under 5 years old and infants.The cardiac sequela of Kawasaki disease is the main cause of death in children with KD.Intravenous injection of immunoglobulin(IntravenousImmunoglobulin)in the early stage of the disease can reduce the incidence of coronary artery aneurysms.However,about 10%to 20%of KD children still have recurrent fever after intravenous immunoglobulin,which is called intravenous immunoglobulin insensitivity(IntravenousImmunoglobulinResistance).The definition and diagnostic criteria of intravenous immunoglobulin resistance,the serious consequences of early identification,and the significance of early identification.A large number of studies have shown that the risk of coronary artery damage in children with intravenous immunoglobulin insensitive KD is significantly increased,so we need to identify children insensitive to intravenous immunoglobulin in time and give adjuvant therapy in time to improve the prognosis.Therefore,it is particularly important to actively look for meaningful predictive indicators to predict intravenous immunoglobulin sensitivity in early stage.Persistent or recurrent fever after the first intravenous injection of immunoglobulin is considered to be a sign of persistent inflammation,while neutrophils,lymphocytes and platelets participate in the whole inflammatory process in children with KD,reflecting the level of inflammation and immune status to some extent,but a single inflammatory index affects each other.Therefore,many studies have taken the combined information of inflammatory parameters such as systemic immune index(Systemic immune-inflammation index,SII),neutrophil-lymphocyte ratio(Neutrophil-to-LymphocyteRatio,NLR)and platelet-lymphocyte ratio(Platelet-to-LymphocyteRatio,PLR)as predictors of intravenous immunoglobulin sensitivity in children with KD,and related studies have shown that SII,NLR and PLR are independent risk factors for IVIG resistance.However,at present,the relevant literature is less and controversial.Therefore,in this study,115 children with KD were selected from the Department of Pediatrics of the first affiliated Hospital of Zhengzhou University to explore and compare the predictive value of SII,NLR and PLR on the sensitivity of intravenous immunoglobulin in children with KD,so as to provide a new idea for early identification of cases insensitive to intravenous immunoglobulin in clinical work,so as to take adjuvant treatment as early as possible to improve the prognosis of children with KD.Subjects and Methods1.A total of 115 children with KD were first diagnosed in Zheng Dayi affiliated Hospital from September 2019 to July 2021,including 51 males(60.7%)and 33 females(39.3%).The average age was(29.98±18.96)months.All subjects met the clinical diagnostic criteria of KD and IVIG resistance to Kawasaki disease in the American Heart Association(AHA)Diagnostic Science report of KD in 2004:the body temperature still exceeded 38℃ 36 hours after the first IVIG treatment or fever returned 2-7 days after the first IVIG treatment,accompanied by at least one main symptom of Kawasaki disease was defined as IVIG resistance.Among them,84 children with KD were sensitive to IVIG and 31 children with KD were resistant to IVIG.According to the sensitivity of IVIG,they were divided into IVIG sensitive group and IVIG resistance group.2.Record the sex and age of the children,collect the medical history(history of prodromal infection,fever,5 typical clinical symptoms,treatment history,heart disease history,family history of Kawasaki disease),and collect peripheral venous blood of KD children in the morning to detect blood routine,erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP).White blood cell count(WBC),neutrophil count(N),lymphocyte count(L),platelet count(PLT),ESR and CRP were recorded,and SII(neutrophil count × platelet count/lymphocyte count,NLR(neutrophil-lymphocyte ratio)and PLR(platelet-lymphocyte ratio)were calculated.3.Statistical analysis SPSS23.0 software analysis system is used for data analysis.The general data,SII,NLR,PLR,leukocyte count,neutrophil count,lymphocyte count,platelet count,ESR and CRP of IVIG resistance group and IVIG sensitive group were compared,and the clinical and laboratory data were analyzed to determine the predictive value of these indexes for IVIG resistance.Results1.There was no significant difference in sex and age of KD children between IVIG resistance group and IVIG sensitivity group(P>0.05).2.There was no significant difference in white blood cell count,neutrophil count,ESR,SII and PLR between the two groups(P>0.05).Compared with IVIG sensitive group,NLR and CRP in IVIG resistance group were higher,and there was significant difference between the two groups(P<0.05).Compared with IVIG sensitive group,the lymphocyte count,platelet count and fever days in IVIG resistance group were lower,and there was significant difference between the two groups(P<0.05).3.Univariate Logistic analysis of NLR,CRP,lymphocyte count,platelet count and fever days before intravenous immunoglobulin showed that NLR,CRP and PLT were independent risk factors of IVIG resistance in children with KD(OR=1.169,1.008,0.996,P=0.004,0.012,0.017,respectively).4.According to the ROC curve,when the NLR value is ≥5.075(the area under the curve is 0.679,the sensitivity is 0.516,the specificity is 0.845),the C-reactive protein value is ≥80.485mg/L(the area under the curve is 0.652,the sensitivity is 0.667,the specificity is 0.583),and the PLT value is ≤347×109xL(the area under the curve is 0.679,the sensitivity is 0.583,the specificity is 0.774).5.All patients with KD were given oral aspirin(30～50mg/kg/d)combined with intravenous immunoglobulin(1g/kg,single intravenous drip).Among them,31 cases of KD had IVIG resistance after the application of standard regimen,among them,6 cases of KD decreased to normal by themselves after continuing anti-infection,25 cases of KD returned to normal after adding IVIG,and the typical symptoms disappeared.7 cases of KD still had recurrent fever or typical symptoms persisted after adding IVIG,and the body temperature returned to normal and typical symptoms disappeared after treatment with glucocorticoid.Conclusions1.The increase of NLR and CRP and the decrease of PLT were independent risk factors of IVIG resistance.When NLR≥5.075,C-reactive protein≥80.485mg/L,PLT≤347x109/L,we should pay attention to the occurrence of IVIG resistance,and adjuvant therapy should be used in time to improve the prognosis.2.The predictive value of NLR for IVIG resistance is better than that of SII,PLR and C-reactive protein,and has high specificity.3.Additional intravenous immunoglobulin and glucocorticoid therapy are effective in children with IVIG resistance to KD,which can make the body temperature drop to normal and the typical symptoms disappear.