Initial Intravenous Immunoglobulin Therapy Research Articles

Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference

ObjectiveTo clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease.DesignRetrospective cohort study.SettingMulticentre.ParticipantsThis study included 735 patients with Kawasaki...

Epidemiology and Clinical Outcomes of Refractory Kawasaki Disease in South Korea

Refractory Kawasaki disease (KD) is defined as KD resistant to initial intravenous immunoglobulin (IVIG) therapy. The proportion of refractory KD is reported to be 10%−20%, and the risk of coronary arterial aneurysm (CAA) is increased in refractory KD. We analyzed data of Korean nationwide surveys on KD to know the epidemiology, treatment modalities, and clinical outcomes of refractory KD in South Korea. We analyzed the data of three triennial Korean nationwide surveys on KD from 2009 to 2017, and selected patients with refractory KD who had persistent or recrudescent fever at least 36 hours after completion of initial IVIG therapy. Among a total of 42,705 KD patients from 2009 through 2017, 5,581 (13.1%) had refractory KD. The annual proportions of refractory KD were between 10.1% and 18.7%, which showed significant changes with the nadir in 2013 and increased proportions in 2015−2017 (P < 0.05). Treatment modalities for refractory KD were second IVIG in 86.2%, third or more IVIG in 3.8%, corticosteroids in 34.4%, infliximab in 3.7%, methotrexate in 1.0%, plasmapheresis in 0.1%, and cyclosporine in 0.02%. The use of third or more IVIG showed a decreasing trend, and the use of corticosteroids and infliximab showed an increasing trend. The incidence of CAA was significantly higher in refractory KD patients than in total KD patients (5.5% vs 1.8%; P < 0.05). The overall proportion of refractory KD was 13.1% from 2009 through 2017 in South Korea. The annual proportions of refractory KD showed significant changes with increased proportions in recent years. Treatment modalities for refractory KD showed a decreasing trend in the use of third or more IVIG and an increasing trend in the use of corticosteroids and infliximab. The incidence of CAA was significantly higher in refractory KD patients than in total KD patients.

Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease

To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.

Poor response to intravenous immunoglobulin in patients with a parental history of Kawasaki disease.

Patients whose parents had a history of Kawasaki disease (KD) often show a poor response to intravenous immunoglobulin (IVIG). There are very few reports describing the clinical characteristics and no reports on changes in C-reactive protein (CRP) level after IVIG administration in such cases. A single-center cohort study including 950 patients hospitalized for KD and treated with IVIG was conducted. The patients were divided into two groups: patients whose parents had a history of KD (PHK) (N = 16) and patients whose parents had no history of KD (NPHK) (N = 934). The clinical characteristics and responsiveness to IVIG were compared between the two groups. The PHK group had higher CRP levels before administering IVIG than the NPHK group (P = 0.0010). CRP levels after IVIG administration were higher in the PHK group than in the NPHK group (P = 0.0094). The percentage of patients who received a second administration of IVIG on day 2 after the initial IVIG therapy was higher in the PHK group than in the NPHK group (P = 0.0016). The percentage of patients who required plasma exchange therapy in the PHK group was significantly higher than that in the NPHK group (P = 0.0010). Patients in the PHK group had severe KD before IVIG administration, and these patients showed poor responsiveness to IVIG therapy.

Kawasaki disease with low C-reactive protein levels

Kawasaki disease (KD) is an acute febrile systemic vasculitis that primarily affects children, and coronary artery lesions (CALs) are severe complications. Clinical features and outcomes of patients with KD associated with low serum C-reactive protein (CRP) levels (&lt; 3.0 mg/dL) before initial treatment remain unclear. The objective of this retrospective study was to elucidate the clinical features and outcomes of patients with KD and low serum CRP levels. Data were included from 220 patients with KD who underwent acute-phase treatment from January 2009 to February 2021 in our department. Patients were divided into low group (n = 50) and high group (n = 170) according to serum CRP levels before initial treatment. The rates of incomplete KD (48.0% vs. 10.6%, P &lt; 0.001) and serum albumin levels (g/dL) before initial treatment (median 3.60 vs. 3.30, P &lt; 0.001) were significantly different between the groups. The rate of patients who required intravenous immunoglobulin (IVIG) therapy was significantly lower in the low group compared to the high group (74.0% vs. 97.1%, P &lt; 0.001). However, the rates of initial IVIG therapy resistance (10.8% vs. 25.5%, P= 0.055) and CALs (2.0% vs. 4.7%, P= 0.475) were similar between the groups. No patient in the low group experienced CALs one month after KD onset. The severity of the disease in patients with KD and low CRP levels was milder than in those with high CRP levels.

Comparison of Machine Learning Models for Prediction of Initial Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease.

We constructed an optimal machine learning (ML) method for predicting intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD) using commonly available clinical and laboratory variables. We retrospectively collected 98 clinical records of hospitalized children with KD (2–109 months of age). We found that 20 (20%) children were resistant to initial IVIG therapy. We trained three ML techniques, including logistic regression, linear support vector machine, and eXtreme gradient boosting with 10 variables against IVIG resistance. Moreover, we estimated the predictive performance based on nested 5-fold cross-validation (CV). We also selected variables using the recursive feature elimination method and performed the nested 5-fold CV with selected variables in a similar manner. We compared ML models with the existing system regardless of their predictive performance. Results of the area under the receiver operator characteristic curve were in the range of 0.58–0.60 in the all-variable model and 0.60–0.75 in the select model. The specificities were more than 0.90 and higher than those in existing scoring systems, but the sensitivities were lower. Three ML models based on demographics and routine laboratory variables did not provide reliable performance. This is possibly the first study that has attempted to establish a better predictive model. Additional biomarkers are probably needed to generate an effective prediction model.

Current Real-World Outcomes of Recurrent Kawasaki Disease

Studies have shown that recurrent Kawasaki disease (KD) is a risk factor for resistance to initial intravenous immunoglobulin (IVIG) therapy and development of coronary artery lesions (CALs). However, current real-world outcomes of recurrent KD patients remain unclear. The objective of this retrospective study was to elucidate the outcomes of recurrent KD patients in the era of 2 g/kg IVIG therapy. Data were included from 201 KD patients who underwent acute-phase treatment from January 2009 to September 2020, with 184 (91.5%) receiving 2 g/kg IVIG therapy. The patients were divided into 7 with (recurrent group) and 194 without (nonrecurrent group) recurrent KD. At the first onset, the rates of initial IVIG therapy resistance (28.6% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were similar between the recurrent and nonrecurrent groups. The rates of initial IVIG therapy resistance (14.3% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were also similar between the recurrent group at the second onset and the nonrecurrent group at the first onset. KD recurrence may no longer be a risk factor for developing CALs in the era of 2 g/kg IVIG therapy, unless CALs appear at the initial episode.

Acute Phase Treatment and Medium-Term Outcomes in Kawasaki Disease

An acute phase treatment for prevention of coronary artery stenosis caused by Kawasaki disease (KD) has not been established. The objective of this study was to clarify the medium-term outcomes of patients who received acute phase treatment in our department. This retrospective study included data from 214 patients with KD who received acute phase treatment from January 2009 to May 2020. A total of 196 (92.1%) received an initial single dose of intravenous immunoglobulin (IVIG) therapy. One patient with status epilepticus at presentation received initial IVIG plus steroid therapy. A total of 17 patients did not receive IVIG. The rate of coronary artery lesions (CALs) 1 month and 1 year after KD onset were 1.9% and 0.9%, respectively. Two patients had CAL 1 year after KD onset. However, no patients had coronary artery stenosis. One patient with a right giant CAL had a medium CAL before initial therapy. During a median follow-up period of 3 years and 4 months, no patients had cardiac events that required therapy.

Usefulness of an Initial Single Intravenous Immunoglobulin Infusion with Delayed Use of Aspirin against Kawasaki Disease Relapse: A Single-Center Retrospective Study

Background: Kawasaki Disease (KD) relapse is a risk factor for Coronary Artery Lesion (CAL) development. However, the frequency and outcomes of patients with relapse remain unclear. Objective: To determine the frequency and outcomes of patients with KD relapse and to ascertain the usefulness of treatment with initial single intravenous immunoglobulin (IVIG) therapy (2g/kg) with delayed use of aspirin (DUA). Materials and Methods: The outcomes of 207 patients who underwent initial single IVIG therapy at 2 g/ kg/ dose with DUA for KD were analyzed retrospectively. The patient data were divided according to whether the patients had relapses (relapse group, n=5) or not (non-relapse group, n=202). KD presentations were considered as relapses when a second episode appeared within 2 months of the first one. Stat Flex version 6 for Windows was used for all statistical analyses. Chi-square, Fisher’s exact, and Mann-Whitney U tests were used as appropriate, with sample size considerations. Results: The frequency of patients with disease relapse was 2.4%. The five patients who experienced relapses (two boys and three girls; median age, 10 months; range, 3 months to 3 years 11 months) received initial IVIG therapy at 5 days of illness. The median day of illness for the relapse was 16 (range, 12-29). No patients with disease relapse developed CAL. The rate of incomplete type, IVIG resistance and CAL, and timing of initial IVIG therapy with regard to the days of illness were similar between the relapse group and the non-relapse group. Three parameters, including serum C-reactive protein, albumin values, and Neutrophil-to-Lymphocyte ratio (NLR) before and after initial IVIG, were similar between the two groups. Although not statistically significant (P=0.055), the median NLR after initial IVIG therapy of the relapse group was higher than that of the non-relapse group (2.48 vs. 0.84). Conclusion: An initial single IVIG therapy (2g/ kg/ dose) with DUA for KD may lead to a low KD relapse frequency and to favorable patient outcomes.

Acute Phase Treatment for Infants Younger Than 1 Year of Age with Kawasaki Disease: A Single Center Retrospective Study

Background: Infants younger than 1 year of age with Kawasaki disease (KD) have a high risk for coronary artery lesions (CAL). However, the appropriate acute phase treatment for the infants has not been established. Objective: To ascertain the usefulness of an initial single intravenous immunoglobulin (IVIG) therapy (2g/ kg) with delayed use of aspirin (DUA) for the infants. Materials and Methods: The outcomes in 205 patients who underwent initial single IVIG therapy at 2g/ kg/ dose with DUA for KD were investigated retrospectively. These subjects were divided into those aged <1 year (infant group, n = 43) and those aged 1 year or older (non-infant group, n=162). Statistical analyses were performed using Stat Flex Version 6 for Windows. Chi-square, Fisher’s exact, and Mann-Whitney U tests were used as appropriate, with sample size considerations. Results: Numbers of major signs in infant group were significantly fewer than those in non-infant group (median 5, interquartile range [IQ]: 5-5 vs. 6, IQ: 5-6, P <0.001). The prevalence of incomplete type (20.9% vs. 11.1%, P=0.091), timing of initial IVIG therapy in regards to day of illness onset (median 5, IQ: 5-6 vs. 5, IQ: 5-6, P=0.452), the prevalence of rescue therapies (9.3% vs. 13.6%, P=0.454), and CAL (0.0% vs. 3.1%, P=0.368) were similar between the 2 groups. No infants received steroids and had the CAL 3mm. The prevalence of initial IVIG therapy resistant patients in infant group was significantly lower than that in non-infant group (9.3% vs. 26.5%, P = 0.017). The defervescence days of illness in infant group were significantly earlier than those in non-infant group (median 6, IQ: 6-7 vs. 7, IQ: 6-8, P <0.001). Conclusion: The infants who are treated appropriately may not have a chance to higher risk of large CAL. An initial single IVIG therapy (2 g/kg) with DUA was useful for prevention of CAL 3 mm in infants with KD.

Kawasaki disease in Turkish children: a single center experience with emphasis on intravenous immunoglobulin resistance and giant coronary aneurysms.

Yılmazer MM, Özdemir R, Meşe T, Küçük M, Öner T, Devrim İ, Bayram N, Güven B, Tavlı V. Kawasaki disease in Turkish children: a single center experience with emphasis on intravenous immunoglobulin resistance and giant coronary aneurysms. Turk J Pediatr 2019; 61: 648-656. Prompt diagnosis and the administration of intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery abnormalities (CAA) in Kawasaki Disease (KD). The resistance to treatment and development of the coronary sequelae remain the most important problems in KD. We aimed to determine the predicting factors of nonresponse to initial IVIG therapy and to analyze the cases who had giant coronary aneurysms. A total of 120 KD cases, including 61 children fulfilling the criteria for KD and 59 with incomplete KD were enrolled into this study. Demographic, laboratory, clinical, echocardiographic characteristics, and treatment regimens were reviewed, retrospectively. The median age of the patients was 33.5 months (range: 3-168 months). Coronary artery aneurysms were detected in 35 patients (29%) at the time of diagnosis. Twenty-eight patients had coronary aneurysms small or medium in size, one had a large, and seven had giant coronary aneurysms. CAA persisted in 8 cases in the follow-up, all of which were large or giant aneurysms. A ten month-old girl with a giant coronary aneurysm was referred to coronary bypass surgery in the subacute phase of follow-up, due to myocardial ischemia. Eighteen patients were unresponsive to the initial IVIG therapy (%15), of whom 10 were diagnosed as cKD and 8 were iKD. Patients who did not respond to initial IVIG therapy, had higher white blood cell (WBC) count, higher C-reactive protein (CRP) and lower albumin levels than those who did (P < 0.05). In univarite analysis; CRP, WBC and albumin were found to be significant predictors of nonresponse to initial IVIG therapy, while a stepwise multiple linear regression analysis showed that WBC count and albumin levels were significantly correlated with nonresponse to initial treatment with IVIG. Our study showed that WBC count and albumin levels might be used as predictors of nonresponse to the IVIG therapy in Turkish children with KD.

Acute Phase Treatment for Prevention of Coronary Artery Stenosis Caused in Kawasaki Disease: A Single Center Retrospective Study

Background: The acute phase treatment to prevent coronary artery stenosis have not been established in Kawasaki disease (KD). Objective: To ascertain the outcomes of coronary artery lesions (CAL) in patients who received an initial intravenous immunoglobulin (IVIG) therapy (2 g/kg) with delayed use of aspirin (DUA) for KD. Materials and Methods: The outcomes in 201 patients who underwent initial IVIG therapy at 2 g/kg/dose with DUA for KD were investigated retrospectively. The patients who received flurbiprofen instead of aspirin were also included. These subjects were divided into those who were associated with CAL (CAL group, n = 4) and those without CAL (non-CAL group, n = 197). Statistical analyses were performed using Stat Flex Version 6 for Windows (Artech Co., Ltd., Osaka, Japan). Chi-square, Fisher’s exact, and Mann–Whitney U tests were used as appropriate, with sample size considerations. Results: The prevalence of resistant patients and those who required rescue therapies in the CAL group were significantly higher than those in non-CAL group (75.0% vs. 21.3%, P = 0.036 and 75.0% vs. 11.1%, P = 0.006, respectively). The values of neutrophil to lymphocyte ratio (NLR) after initial IVIG therapy in CAL group were significantly higher than those in non-CAL group (median: 5.91, range: 1.01-12.65 vs. 0.87, 0.01-11.29, P = 0.013). The one patient in CAL group who required plasma exchange had the highest value of the NLR. No patient had the large CAL>6.0 mm with high-risk for stenosis, and only one patient had persistent CAL of moderate-sized solitary right coronary artery at 60th day of illness. Conclusion: An initial IVIG therapy (2 g/kg) with DUA may be useful for prevention of coronary artery stenosis caused in KD.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Treatment and follow-up of Kawasaki disease

Kawasaki disease(KD)is an acute, self-limited and systemic vasculitis.The etiology and pathogenesis of KD still remain unclear.High-dose intravenous immunoglobulin(IVIG)combined with aspirin is the standard regimen of KD in acute stage, but the treatment of KD patients who were unresponsive to initial IVIG therapy still remains controversial.The main complication of KD is coronary artery lesions.Treatments of coronary artery lesions included antiplatelet, anticoagulant, thrombolytic therapy, percutaneous coronary interventions and coronary artery bypass grafting.In addition, follow-up and management of KD were also very important. Key words: Kawasaki disease; Intravenous immunoglobulin; Coronary artery lesions; Follow-up

Novel Risk Assessment Tool for Immunoglobulin Resistance in Kawasaki Disease: Application Using a Random Forest Classifier.

Resistance to intravenous immunoglobulin (IVIG) therapy is a risk factor for coronary lesions in patients with Kawasaki disease (KD). Risk-adjusted initial therapy may improve coronary outcome in KD, but identification of high risk patients remains a challenge. This study aimed to develop a new risk assessment tool for IVIG resistance using advanced statistical techniques. Data were retrospectively collected from KD patients receiving IVIG therapy, including demographic characteristics, signs and symptoms of KD and laboratory results. A random forest (RF) classifier, a tree-based machine learning technique, was applied to these data. The correlation between each variable and risk of IVIG resistance was estimated. Data were obtained from 767 patients with KD, including 170 (22.1%) who were refractory to initial IVIG therapy. The predictive tool based on the RF algorithm had an area under the receiver operating characteristic curve of 0.916, a sensitivity of 79.7% and a specificity of 87.3%. Its misclassification rate in the general patient population was estimated to be 15.5%. RF also identified markers related to IVIG resistance such as abnormal liver markers and percentage neutrophils, displaying relationships between these markers and predicted risk. The RF classifier reliably identified KD patients at high risk for IVIG resistance, presenting clinical markers relevant to treatment failure. Evaluation in other patient populations is required to determine whether this risk assessment tool relying on RF has clinical value.

Bradycardia Associated with Prednisolone in Children with Severe Kawasaki Disease

To identify the prevalence of bradycardia associated with use of prednisolone in patients with Kawasaki disease and analyze the association between bradycardia and responsiveness to intravenous immunoglobulin (IVIG). We performed a retrospective cohort study of 176 patients with severe Kawasaki disease admitted to the Tokyo Metropolitan Children's Medical Center between March 2010 and December 2015. The group treated with IVIG plus prednisolone therapy from February 2012 was compared with the control group who received IVIG monotherapy before this date. The primary outcome was the prevalence of bradycardia, defined as heart rate less than the first percentile for normal children. Next, we determined whether bradycardia was associated with the clinical course in the patient subgroup treated with IVIG plus prednisolone therapy. The prevalence of bradycardia was significantly higher in the IVIG plus prednisolone subgroup than in the IVIG group (79.1% vs 7.1%; P?<?.001). The median time to bradycardia onset was 63.0 hours (2.6 days). Prednisolone decreased the heart rate by 15.1 beats/minute (95% CI 10.2-20.0; P?<?.001) on average from day 2 to 7 after the initial therapy. Logistic regression analysis revealed that bradycardia was associated with responsiveness to initial IVIG plus prednisolone therapy (OR 7.2; 95% CI 2.3-23.0; P?<?.001). Bradycardia frequently occurred during IVIG plus prednisolone therapy in patients with Kawasaki disease, and was associated with responsiveness to IVIG.

Difference in Risk Factors for Subtypes of Acute Cardiac Lesions Resulting from Kawasaki Disease.

Few studies discuss the risk factors for acute cardiac lesions (within 30days) resulting from Kawasaki disease (KD). We aimed to clarify the characteristics of patients with cardiac lesions within 30days and determine the risk factors for acute cardiac lesion subtypes. Using the 23rd nationwide survey of KD in Japan, we analyzed data from patients with or without acute cardiac lesions resulting from KD (n=31,380). We subdivided patients with acute cardiac lesions into three types: acute valvular lesions, coronary aneurysms, and giant coronary aneurysms (GCA), and calculated the odds ratios of potential risk factors for acute cardiac lesion subtypes. The prevalence of acute cardiac lesions was 8.6%, and these lesions were more prevalent among males than females (1.98:1). Male sex, age <1year, and atypical definite cases predicted coronary artery lesions (CAL). The risk factors for valvular lesions differed from the risk factors for CALs, but GCA risk factors were similar to CAL risk factors: age <1year, later presentation to hospital, atypical definite cases, and resistance to initial intravenous immunoglobulin (IVIG) therapy. Resistance to IVIG therapy was a significant risk factor for acute GCA. We found differences in cardiac lesion risk factors within 30days of diagnosing KD between acute CAL and valvular lesions resulting from KD. In particular, pediatricians should consider atypical definite cases and resistance to initial IVIG when assessing the risk of acute-phase GCA.

Different subgroups regarding the absence of rescue therapy in intravenous immunoglobulin-resistant Kawasaki disease

The objective of this study is the description of clinical outcomes regarding the absence of rescue therapy of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. I investigated the clinical outcomes of 33 IVIG-resistant patients who received the initial single IVIG therapy with the delayed use of anti- inflammatory drugs (DUA). These patients were divided into two groups: 11 patients who received rescue therapies (rescue group) and 22 patients who did not receive rescue therapy (non-rescue group). One patient of rescue group developed coronary artery lesions (CAL). None of the patients of non-rescue group developed CAL. The prevalence of persistent fever between rescue and non-rescue groups at 3 days and 4 days after initial IVIG therapy was 100% vs. 77% ( P = 0.144 ) and 100% vs. 18% ( P < 0.001 ), respectively. The C-reactive protein value, neutrophil counts, serum albumin levels, and sodium levels were significantly different between two groups at median 3 days after initial IVIG therapy. Two-thirds of the IVIG-resistant patients diagnosed at 24 h after completion of the initial IVIG therapy with DUA did not develop CAL after 30 days of illness without rescue therapies. The rescue therapy at this time may lead to overtreatment.

Meta-analysis of factors predicting resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease.

PurposeStudies have been conducted to identify predictive factors of resistance to intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). However, the results are conflicting. This study aimed to identify laboratory factors predictive of resistance to high-dose IVIG for KD by performing meta-analysis of available studies using statistical techniques.MethodsAll relevant scientific publications from 2006 to 2014 were identified through PubMed searches. For studies in English on KD and IVIG resistance, predictive factors were included. A meta-analysis was performed that calculated the effect size of various laboratory parameters as predictive factors for IVIG-resistant KD.ResultsTwelve studies comprising 2,745 patients were included. Meta-analysis demonstrated significant effect sizes for several laboratory parameters: polymorphonuclear leukocytes (PMNs) 0.698 (95% confidence interval [CI], 0.469–0.926), C-reactive protein (CRP) 0.375 (95% CI, 0.086–0.663), pro-brain natriuretic peptide (pro-BNP) 0.561 (95% CI, 0.261–0.861), total bilirubin 0.859 (95% CI, 0.582–1.136), alanine aminotransferase (AST) 0.503 (95% CI, 0.313–0.693), aspartate aminotransferase (ALT) 0.436 (95% CI, 0.275–0.597), albumin 0.427 (95% CI, –0.657 to –0.198), and sodium 0.604 (95% CI, –0.839 to –0.370). Particularly, total bilirubin, PMN, sodium, pro-BNP, and AST, in descending numerical order, demonstrated more than a medium effect size.ConclusionBased on the results of this study, laboratory predictive factors for IVIG-resistant KD included higher total bilirubin, PMN, pro-BNP, AST, ALT, and CRP, and lower sodium and albumin. The presence of several of these predictive factors should alert clinicians to the increased likelihood that the patient may not respond adequately to initial IVIG therapy.

Non-Responders to Intravenous Immunoglobulin and Coronary Artery Dilatation in Kawasaki Disease: Predictive Parameters in Korean Children.

Background and ObjectivesIn Kawasaki disease (KD), high dose intravenous immunoglobulin (IVIG) significantly lowers the coronary complications. However, some patients either do not respond to initial therapy or develop coronary complications. We aimed to identify the predictive factors for unresponsiveness to initial IVIG therapy and coronary artery dilatation (CAD; defined by Z-score≥2.5) in the acute phase and convalescent phase.Subjects and MethodsA retrospective review was conducted of 703 patients with KD, admitted to Gachon University Gil Medical Center between January 2005 and June 2013. The patients were divided into two groups—IVIG responders vs. non-responders—based on the IVIG treatments, and presence of fever after treatment. Further, these groups were divided into two subgroups based on their CAD.ResultsAmong the 703 patients with KD, the rate of non-responders to initial IVIG was 16.8%. Serum total bilirubin, platelet count, and neutrophil proportion were independent predictive parameters of unresponsiveness (p<0.05). CAD was found in 234 patients (33.3%) in the acute phase, and in 32 patients (4.6%) in the convalescent phase. Male gender, fever duration, serum C-reactive protein, and white blood cell count were related to CAD (p<0.05). CAD was detected more frequently in non-responders than in the responders (47.5% vs. 31.5%, p=0.001). Kobayashi, Egami, and Sano scoring systems applied to our study population reflected low sensitivities (28.0-33.9%).ConclusionSeveral independent parameters were related to unresponsiveness to the initial IVIG or CAD. These parameters might be helpful in establishing more focused and careful monitoring of high-risk KD patients in Korea.