Initial Intravenous Immunoglobulin Treatment Research Articles

Predictive indicators and risk model construction for coronary artery lesions in Kawasaki disease children over 5 years old

To study predictive indicators for coronary artery lesions (CAL) and construct a risk prediction model for CAL in Kawasaki disease (KD) children over 5 years old. A retrospective analysis of KD children over 5 years old at Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2018 to January 2023 was conducted. Among them, 47 cases were complicated with CAL, and 178 cases were not. Multivariate logistic regression analysis was used to explore predictive indicators for CAL in KD children over 5 years old and construct a risk prediction model. The receiver operating characteristic curve was used to evaluate the effectiveness of the prediction model. Finally, the Framingham risk scoring method was used to quantify the predictive indicators, calculate the contribution of each indicator to the prediction of CAL in KD children over 5 years old, and construct a risk prediction scoring model. The multivariate logistic regression analysis showed that the duration of fever before the initial intravenous immunoglobulin (IVIG) treatment (OR=1.374, 95%CI: 1.117-1.689), levels of hypersensitive C-reactive protein (hs-CRP; OR=1.008, 95%CI: 1.001-1.015), and serum ferritin levels (OR=1.002, 95%CI: 1.001-1.003) were predictive indicators for CAL in KD children over 5 years old. The optimal cutoff values for predicting CAL were: duration of fever before initial IVIG treatment of 6.5 days (AUC=0.654, 95%CI: 0.565-0.744), hs-CRP of 110.50 mg/L (AUC=0.686, 95%CI: 0.597-0.774), and ferritin of 313.62 mg/L (AUC=0.724, 95%CI: 0.642-0.805). According to the Framingham risk scoring method, the low, medium, and high-risk states of CAL occurrence were defined as probabilities of <10%, 10%-20%, and >20%, respectively, with corresponding scores of 0-4 points, 5-6 points, and ≥7 points. In KD children over 5 years old, those with a longer duration of fever before initial IVIG treatment, higher levels of hs-CRP, or elevated serum ferritin levels are more likely to develop CAL.

The efficacy and safety of intravenous immunoglobulin infusion in 12 h for the initial treatment of Kawasaki disease

BackgroundApproximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. MethodsThis retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. ResultsThere were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. ConclusionWe concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients.

Thyroid hormone may predict treatment failure in Kawasaki disease.

In systemic inflammatory conditions, inflammatory cytokines can cause low thyroid hormone levels. There are no reports discussing the relation between thyroid hormone levels and response to treatment for Kawasaki disease. We investigated 67 patients who underwent treatment in the acute phase of Kawasaki disease. We divided patients into two groups based on their response to initial intravenous immunoglobulin (IVIG) treatment: the responder group (n = 40), and the non-responder group (n = 27). The serum levels of the thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were compared before and after treatment in all patients, and between responder and non-responder groups. The FT3, FT4, and TSH levels were low before the initial treatment and increased significantly after treatment (p < 0.05). The FT3, FT4, and TSH levels before treatment were significantly lower in the non-responder group than in the responder group (p < 0.05). Logistic regression analysis suggested that the addition of pre-treatment FT4 values to Gunma score was useful in predicting treatment failure. Thyroid hormone and TSH levels were lower in the non-responder group than in the responder group in the initial IVIG treatment for Kawasaki disease. This study suggests that Kawasaki disease in the acute phase is associated with low thyroid hormone levels and TSH. It is possible that these hormone levels predict response to the initial IVIG.

Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment.

To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.

Serum amyloid A as a biomarker for immunoglobulin resistance in Kawasaki disease

Background Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. Methods SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. Results During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40–547.25] vs 230.85 [105.40–490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p < .05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p < .05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p = .008), neutrophils (p < .001), total bilirubin (p = .001), platelet count (p = .004), and serum sodium level (p = .019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. Conclusions SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management.

A simple scoring model based on machine learning predicts intravenous immunoglobulin resistance in Kawasaki disease

IntroductionIn Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions.ObjectiveTo establish a simple scoring model predicting IVIG resistance in KD patients based on the machine learning model.MethodsA retrospective cohort study of 1002 KD patients diagnosed at 12 facilities for 10 years, in which 22.7% were resistant to initial IVIG treatment. We performed machine learning with diverse models using 30 clinical variables at diagnosis in 801 and 201 cases for training and test datasets, respectively. SHAP was applied to identify the variables that influenced the prediction model. A scoring model was designed using the influential clinical variables based on the Shapley additive explanation results.ResultsLight gradient boosting machine model accurately predicted IVIG resistance (area under the receiver operating characteristic curve (AUC), 0.78; sensitivity, 0.50; specificity, 0.88). Next, using top three influential features (days of illness at initial therapy, serum levels of C-reactive protein, and total cholesterol), we designed a simple scoring system. In spite of its simplicity, it predicted IVIG resistance (AUC, 0.72; sensitivity, 0.49; specificity, 0.82) as accurately as machine learning models. Moreover, accuracy of our scoring system with three clinical features was almost identical to that of Gunma score with seven clinical features (AUC, 0.73; sensitivity, 0.53; specificity, 0.83), a well-known logistic regression scoring model.ConclusionA simple scoring system based on the findings in machine learning seems to be a useful tool to accurately predict IVIG resistance in KD patients.Key Points• In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions.• Machine learning model predicted IVIG resistance in KD patients, and Shapley additive explanation (SHAP) was a useful approach for explaining the outcome of the machine learning model.• A simple scoring system using three clinical features (days of illness at initial therapy, serum levels of CRP, and total cholesterol at diagnosis) based on SHAP efficiently predicted IVIG resistance.

Prednisolone versus cyclosporine as initial treatment for Kawasaki disease.

Several studies have demonstrated the efficacy of prednisolone and cyclosporine as initial combination treatments for the prevention of coronary artery abnormalities (CAA) in patients with Kawasaki disease. However, whether prednisolone or cyclosporine results in superior clinical outcomes is unknown. Thus, this study aimed to compare the outcomes of these two treatments. Using the Japanese Diagnosis Procedure Combination database, we identified patients with Kawasaki disease who had received prednisolone or cyclosporine in addition to initial intravenous immunoglobulin treatment between April 2014 and March 2021. The primary outcome was the proportion of CAA; secondary outcomes included intravenous immunoglobulin resistance, medical costs, and length of hospital stay. Propensity score matching was conducted to compare outcomes between the two groups. We identified 6288 patients with Kawasaki disease who had received prednisolone (n = 6147) or cyclosporine (n = 141) as an initial treatment in combination with intravenous immunoglobulin. Four-to-one propensity score-matched analysis demonstrated no significant difference in the proportion of CAA (0.7% vs. 2.8%; p = 0.098), intravenous immunoglobulin resistance, or medical costs between the treatment groups. The length of hospital stay was significantly longer in the prednisolone group (14 vs. 11 days, p < 0.001). Prednisolone and cyclosporine used in the initial combination treatment for Kawasaki disease showed similar clinical outcomes regarding the risk of CAA, intravenous immunoglobulin resistance, and medical costs, whereas the length of hospital stay was longer in the prednisolone group than in the cyclosporine group.

Predictors for Intravenous Immunoglobulin Resistance in Patients with Kawasaki Disease.

Background Between 10 and 20% of Kawasaki disease (KD) patients are resistant to treatment with initial intravenous immunoglobulin (IVIG) and have a high risk of developing coronary artery lesions. Some studies have been conducted to identify predictive factors. However, the results are controversial. This study aims to identify the risk factors for IVIG-resistant KD patients in a Chinese population. Methods We performed a retrospective analysis of medical records of consecutive KD patients from two medical centers in South China from January 2015 to December 2017. A total of 1281 KD patients were eligible for inclusion in this study and maintained follow-up for over 12 months. The KD patients were divided into two groups based on IVIG response. Clinical characteristics and laboratory variables were compared between the two groups. Multivariate logistic regression analysis was performed to identify the risk factors of IVIG resistance in KD patients. Results Of the 1281 KD patients, 141 (11.0%) cases who were IVIG resistant to adjunctive therapies for primary treatment were classified as group 1. The remaining patients were in group 2 (n = 1140), classified as the control group. There was a significant difference in male to female ratio and the length of hospital stay between the two groups (P < 0.05). Group 1 had a higher white blood cell count (P=0.01) and C-reactive protein level (P < 0.01) before IVIG treatment than in group 2. Group 1 had a significantly higher white blood cell count and percentage of neutrophils after the IVIG infusion than in group 2 (P < 0.001). In addition, the mean values of C-reactive protein level and neutrophil percentage before and after treatment difference comparison were significantly different. Multivariate analysis showed that patients presenting with coronary artery lesions in the acute phase and a C-reactive protein level >100 mg/L at diagnosis were associated with IVIG resistance in KD. During the 12-month follow-up period, group 1 had an obviously higher incidence of coronary artery lesions than group 2, and the difference between the groups was statistically significant (P < 0.001). Conclusions Patients presenting with coronary artery lesions in the acute phase and elevated C-reactive protein levels before IVIG treatment might be a useful and important value for predicting IVIG resistance in KD. Risk assessment based on coronary artery lesions and C-reactive protein levels prior to the treatment may improve the outcome of IVIG resistance.

Infliximab Superior to IVIG for Rescue in IVIG-Refractory Kawasaki Disease

Infliximab Superior to IVIG for Rescue in IVIG-Refractory Kawasaki Disease

Correlation between the Level of Inflammatory Cytokines and Prognosis in Children with IVIG-sensitive Kawasaki Disease and IVIG-resistant Kawasaki Disease.

Objectives:To investigate whether the levels of interleukin 1β (IL-1β), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) in children with Kawasaki disease (KD) are correlated with coronary artery lesion (CAL) and resistance to intravenous immunoglobulin (IVIG) treatment.Methods:A total of 216 children in line with KD diagnostic criteria were continuously included as subjects, and 50 healthy children at the same period were selected as the control group, and their levels of IL-1β, IFN-γ, and TNF-α were detected.Results:Subjects were subdivided according to the presence or absence of CAL: 42 cases (19.4%) of 216 children with KD developed CAL and were subdivided into the CAL group, while 174 (80.6%) of those who did not develop CAL were subdivided into the NCAL group. The levels of IL-1β, IFN-γ, and TNF-α in the CAL group and the NCAL group were higher than those in the control group (P<0.05), and the levels of those in the CAL group were higher than those in the NCAL group (P<0.05). Subjects were subdivided according to the effect of IVIG treatment: 194 cases (89.8%) of 216 children with KD had a good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-sensitive KD and divided into the IVIG-sensitive group; 22 cases (10.2%) could not get good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-resistant KD and divided into the IVIG-resistant group. The levels of IL-1β, IFN-γ, and TNF-α in the IVIG-sensitive group and the IVIG-resistant group were higher than those in the control group; The levels of IL-1β, IFN-γ, and TNF-α in the IVIG-resistant group were higher than those in the IVIG-sensitive group (P<0.05), while the fever time of the IVIG-sensitive group was lower than that of the IVIG-resistant group (P<0.05).Conclusion:Children with KD may experience changes in IL-1β, IFN-γ, and TNF-α levels in the acute phase. Such a significant increase in levels may be a risk factor for CAL and resistance to IVIG treatment in children with KD, while the prolonged fever time is a risk factor for resistance to IVIG treatment in children with KD.

Predictive value of serum ferritin and a new predictive model for intravenous immunoglobulin resistance in Kawasaki disease

Objective: To evaluate the predictive value of serum ferritin (SF) and construct a novel predictive model for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) (IVIGRKD). Methods: The clinical data of 422 children with KD from January 2017 to December 2019 in Quanzhou Women's and Children's Hospital were retrospectively analyzed. According to the response to IVIG, they were divided into IVIG-resistant group and IVIG-sensitive group. Forty-one clinical indicators including general characteristics and laboratory results were compared between the two groups. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of SF for IVIGRKD. Binary Logistic regression analysis was used to test whether SF was an independent risk factor for IVIGRKD. Meanwhile, a novel predictive scoring system was established. The comparisons between the new predictive scoring system with four commonly used prediction scoring systems were conducted. Results: A total of 422 KD cases (285 males and 137 females, 17.0 (9.0,29.0) years of age) were enrolled and divided into IVIG-resistant group (n=57) and IVIG-sensitive group (n=365). Seventeen clinical indicators differed significantly between the two groups. SF level of the IVIG-resistant group was significantly higher than that of the sensitive group (245.0 (131.0, 519.0) vs. 145.0 (92.5, 232.5) μg/L, Z=-5.109, P<0.05). ROC curve showed that the Youden index of SF for predicting IVIGRKD was 0.326 (cutoff value 403.5 μg/L). Binary logistic regression analysis showed that SF, days of illness at initial IVIG treatment, cervical lymphadenopathy, pleomorphic rash, white blood cell, C-reactive protein (CRP), activated partial thromboplastin time (APTT), alanine transaminase (ALT) and creatinine were independent risk factors for IVIGRKD. A novel prediction model was constructed, and the cutoff points and score points were as follows: pleomorphic rash, 2 points; cervical lymphadenopathy, 1 point; SF≥ 403.5 μg/L, 1 point; white blood cell ≥ 18.3×109/L, 1 point; CRP≥83.1 mg/L, 1 point; APTT≥25.3 s, 1 point; ALT≥37.5 U/L, 1 point. And patients with scores of 4 or more were at high-risk for IVIGRKD. The Youden index of the four commonly used scoring systems ranged from 0.315 to 0.512. However, the Youden index of the new scoring system was 0.695 (sensitivity 0.772, specificity 0.923) and was the highest among the five scoring systems. Conclusions: SF shows well predictive efficiency for IVIGRKD and is an independent risk factor for IVIGRKD. SF can be used as a new predictor of IVIGRKD.

Prediction of repeated intravenous immunoglobulin resistance in children with Kawasaki disease

BackgroundRepeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD.MethodsA total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.ResultsThe Pre-IVIG laboratory data showed the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium and albumin (ALB) were significantly lower (P < 0.05). The post-IVIG laboratory values of N% and C-reactive protein (CRP) were significantly higher in the repeated IVIG-resistant group compared with repeated IVIG-responsive group, while hemoglobin and ALB were lower (P < 0.05). Pre-IVIG PCT and post-IVIG CRP exhibited AUC of 0.751 and 0.778 respectively in predicting repeated IVIG resistance in KD. Pre-IVIG PCT > 1.81ng/ml (OR 4.1, 95 % CI 1.4 ~ 12.0, P < 0.05) and post-IVIG CRP > 45 mg/L (OR 4.6, 95 % CI 1.3 ~ 16.2, P < 0.05) were independent predictors of repeated IVIG resistance in KD.ConclusionsOur study illustrates the serum PCT level before initial IVIG treatment and CRP after initial IVIG could be used to predict repeated IVIG resistance in KD.

Clinical Characteristics of Patients With Kawasaki Disease Whose Siblings Had the Same Disease.

Some patients with Kawasaki disease (KD) have siblings who developed the same disease. Using a large-scale epidemiologic dataset, the present study aimed to determine the clinical characteristics of this population. We analyzed 89,725 patients diagnosed with KD during 2011-2018 who were registered in the nationwide Japanese KD survey database. Multivariable logistic regression analyses were performed to determine factors associated with sibling history of KD. Of the 89,725 patients, 1777 (2%) had sibling history of KD. Annual prevalence ranged from 1.5% to 2.3% during the study period and showed a tendency toward an increasing trend. Patients with recurrent KD and parental history of KD were significantly associated with sibling history of KD (adjusted odds ratio [95% confidence interval] = 2.15 [1.82-2.54] and 2.64 [2.02-3.47], respectively). Although patients with a sibling history of KD were significantly associated with initial intravenous immunoglobulin treatment resistance (1.14 [1.02-1.28]), no significant association was found between sibling history and coronary artery abnormality development. Among patients with a sibling history of KD, male patients were less likely to have recurrent KD than female patients (0.68 [0.49-0.96]). The significant association between sibling history and parental history may indicate genetic susceptibility to KD onset. Among those with a sibling history, recurrent KD was more likely to occur in female patients. Further studies focusing on this population may contribute toward identification of the cause of KD onset.

Corticosteroids Added to Initial Intravenous Immunoglobulin Treatment for the Prevention of Coronary Artery Abnormalities in High-Risk Patients With Kawasaki Disease.

BACKGROUNDRandomized controlled trials previously provided different conclusions about the superiority of adding corticosteroids to initial intravenous immunoglobulin treatment for the prevention of coronary artery abnormalities in patients with Kawasaki disease (KD). To further assess this issue, we analyzed large‐scale data from nationwide KD surveys in Japan, where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk for KD.METHODS AND RESULTSStandard intravenous immunoglobulin treatment and combination treatment were compared using data from time periods with and without combination treatment. Outcome measures were coronary artery abnormalities and initial intravenous immunoglobulin treatment failure. Hospitals where ≥20% of patients received combination treatment were identified, and treatment and control groups were selected via matching by age, sex, illness day at initial treatment, and KD recurrence. Matched group selection and subsequent analyses were conducted 1000 times to minimize sampling bias and potential confounders (bootstrapping). From 115 hospitals, 1593 patients with KD in the treatment group and 1593 controls were selected for each of the 1000 sample iterations. The median proportion of patients who developed coronary artery abnormalities among the treatment group and controls were 4.6% (95% CI, 3.8%–5.8%) and 8.8% (95% CI, 7.5%–10.0%), respectively: an estimated risk ratio of 0.53 (0.41–0.67). A median of 14.1% (95% CI, 12.4%–15.9%) of the patients in the treatment group and 21.7% (95% CI, 19.8%–23.4%) in the controls had treatment failure: an estimated risk ratio of 0.65 (0.56―0.75).CONCLUSIONSCombination treatment reduced coronary artery abnormality risk by an estimated 47% and treatment failure by 35%. Multiple‐dose corticosteroids may provide benefit in selected patients at high risk for KD.

Utility of Soluble CD163 in the Clinical Management of Patients With Kawasaki Disease.

Objective: Intravenous immunoglobulin (IVIG) therapy is a useful first-line treatment for Kawasaki disease (KD); however, 10–20% of patients fail to respond and require additional IVIG. Soluble CD163 (sCD163) is considered a biomarker for macrophage activation. There are no reports measuring serum sCD163 in KD patients. This study aimed to explore its possible utility in the clinical management of patients with KD.Methods: Eighty-seven patients with well-defined KD were retrospectively enrolled together with 19 healthy individuals with comparable ages. KD patients were classified into three groups, Group A (initial IVIG responders), Group B (additional IVIG responders), and Group C (additional IVIG non-responders). Serum sCD163 together with complete blood counts, C-reactive protein, d-dimer, albumin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured before the initial IVIG treatment in all cases, and afterward in a fraction of cases.Results: Serum sCD163 in KD patients before initial IVIG was generally much higher than the control group. The median (interquartile range) of sCD163 was as follows: Control 446 (385–521) ng/mL; Group A, 699 (478–1,072); Group B, 1,349 (1,116–1,390); and Group C, 665 (544–1,094). In general, sCD163 showed close positive correlation with ALT and AST, but none with other markers. Among the KD groups, Group B showed the highest sCD163: Group B vs. A: p = 0.0003; B vs. C: p = 0.035). Serum sCD163 was significantly increased after IVIG in Group A, while no change occurred in others.Conclusion: The serum sCD163 levels could be a useful biomarker in the clinical management of KD, especially for predicting responsiveness to IVIG.

Do cytokines correlate with refractory Kawasaki disease in children?

BackgroundKawasaki disease (KD) is a type of pediatric vasculitis. Ten to twenty percent of children with KD do not respond to initial intravenous immunoglobulin (IVIG) treatment which called refractory Kawasaki disease. If untreated, approximately 15–25% of KD patients have complications. Therefore, it is important to predict whether KD is resistant to IVIG at an early stage. The aim of this study was to determine whether cytokines are predictors of refractory KD in children. MethodsWe retrospectively reviewed the medical records of 265 children diagnosed with KD who received IVIG within 10 days of fever onset at Beijing Children’s Hospital. Refractory Kawasaki disease was defined as persistent or recrudescent fever beyond 36 h after IVIG. Before IVIG and 3 days after temperature normalization following IVIG treatment, the concentrations of cytokines in the serum including interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), interleukin-2 (IL-2) and other conventional inflammatory mediators including white blood cells counts (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and albumin were detected. The patients were divided into 2 groups: IVIG-sensitive group and refractory group. ResultsOf the 265 patients, 47 (17.7%) were refractory. After treatment with IVIG, the serum levels of IFN-γ, TNF-α, IL-10 and IL-6 in both groups were significantly lower than those before treatment (P < 0.05). Before treatment, the serum levels of IFN-γ, TNF-α, IL-10 and IL-6 in refractory group were significantly higher than those in IVIG-sensitive group (P < 0.05). There were no significant differences in IL-4 or IL-2 levels between the 2 groups. The results of logistic regression analysis showed that IFN-γ, IL-6, fever duration and serum albumin were independent risk factors for refractory KD. The area under the receiver operating characteristic curve (ROC curve) for IFN-γ was 0.781, and the cut-off value for refractory was 7.37 pg/ml, while the area under the ROC curve for IL-6 was 0.837, and the cut-off value for refractory was 70.13 pg/ml. ConclusionsIFN-γ and IL-6 were independent risk factors for refractory Kawasaki disease in children. KD patients with serum levels of IFN-γ above 7.37 pg/ml and IL-6 above 70.13 pg/ml before treatment were prone to refractory.

Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease

About 10–20% of patients with Kawasaki disease (KD) are unresponsive to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations. We investigated the accuracy of 3 Japanese scoring systems and studied factors associated with IVIg unresponsiveness in a large multiethnic French population of children with KD to build a new scoring system. Children admitted for KD between 2011–2014 in 65 centers were enrolled. Factors associated with second line-treatment; i.e. unresponsiveness to initial IVIg treatment, were analyzed by multivariate regression analysis. The performance of our score and the Kobayashi, Egami and Sano scores were compared in our population and in ethnic subgroups. Overall, 465 children were reported by 84 physicians; 425 were classified with KD (55% European Caucasian, 12% North African/Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 14–61%). On multivariate regression analysis, predictors of secondary treatment after initial IVIG were hepatomegaly, ALT level ≥30 IU/L, lymphocyte count <2400/mm3 and time to treatment <5 days. The best sensitivity (77%) and specificity (60%) of this model was with 1 point per variable and cut-off ≥2 points. The sensitivity remained good in our 3 main ethnic subgroups (74–88%). We identified predictors of IVIg resistance and built a new score with good sensitivity and acceptable specificity in a non-Asian population.

Treatment Options for Refractory Kawasaki Disease

Kawasaki Disease (KD) is a self-limiting systemic vasculitis common among children under five years of age. Diagnosis of the disease is made primarily from the clinical features presented during the illness. Coronary artery aneurysm (CAA) is the main complication of this disease which can be prevented largely by the early diagnosis and administration of IVIG (Intravenous Immunoglobulin). Even with first dose of IVIG up to 10% - 20% of patients develop refractory Kawasaki Disease, i.e., remain unresponsive to initial IVIG treatment. Second dose of IVIG is recommended treatment for refractory Kawasaki Disease but other alternative treatments are also being considered to lower the risk of complications. Different drugs are still in trial phase and some others have limited studies on larger population. Most of the study reports that involved newer drugs have limited patients or are from single centers which are very hard to apply to larger population. We will review general treatment approach in refractory Kawasaki disease.

Acute Kawasaki Disease Therapy

We review the acute management of patients with Kawasaki disease (KD), including adjunctive primary therapies and the treatment of patients with resistance to intravenous immunoglobulin (IVIG). IVIG administered within 10 days of fever in patients with (KD decreases the risk of coronary artery complication from ~ 25% to < 5%. However, patients at high risk of IVIG resistance or those with coronary changes at diagnosis may benefit from additional primary anti-inflammatory therapies. All patients with suspected KD should be treated with aspirin and IVIG (2 g/kg). Patients at high risk of treatment resistance and/or coronary complications may benefit from adjunctive treatments, including corticosteroids or infliximab. Patients with persistent fever after initial IVIG treatment are at high risk of coronary complications and usually are retreated with IVIG. Corticosteroids, infliximab, cyclosporine, anakinra, and cyclophosphamide have also been described in patients refractory to initial therapy, though optimal therapy in this high-risk group remains unknown.

PB2246 CLINICAL FEATURES AND TREATMENT OUTCOMES OF IMMUNE THROMBOCYTOPENIC PURPURA IN INFANTS; A SINGLE CENTER RETROSPECTIVE STUDY

Background:Immune thrombocytopenic purpura (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school‐age children.Aims:Since children of different ages may have differing clinical courses, better delination of the natural history of ITP in infants is needed.Methods:We retrospectively reviewed the admission records of 248 consecutive pediatric patients between 1 month and 15 year of age admitted and treated for acute ITP at Pusan National University Children's Hospital from 2009 through 2017. All of these patients less than 1 year of age were identified and enrolled. We investigated their demographics, clinical features, laboratory examinations, respond to treatment and long‐term outcomes and compared to those of children 1 to 10 years of age.Results:Ninety nine infants were identified. Male to female ratio was highest in infants and decreased with age. Seventy nine (79.8%) of the 99 infant were found to be under 6 months old. The median platelet counts at diagnosis was 6 x 109/L (0∼76). Minor bleeding (bleeding score 0‐2) was significantly dominant in infant compared to older ages. Eighty two out of 85 patients (96.5%) achieved complete remission after initial intravenous immunoglobulin(IVIG) treatment. The relapse rate after initial CR was significantly lower than older ages (p = 0.003). The platelet count after IVIG treatment in infant showed more rapid rising compared to older ages (p = 0.02), and the mean time to platelet counts above 100x109/L was 6.4+4.5 days. Follow up information at 6 months was available for 85 infants. Chronic ITP at 6 month was seen less frequently in infants (4.7%) than in children 1 to 10 years of age. (23.2%. P &lt; 0.01).Summary/Conclusion:Infants with acute ITP respond more favorably to IVIG treatment and are less likely to develop chronic ITP compared to children 1 to 10 years of age.