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BackgroundInfection with SARS-CoV-2 virus has been associated with cardiovascular sequelae including multisystem inflammatory syndrome (MIS-C) in children. Patients with a prior history of Kawasaki disease, may be more susceptible to changes in echocardiographic or laboratory findings after COVID-19. The objective of this study was to investigate the echocardiographic and laboratory findings in children with a prior history of Kawasaki disease after SARS-CoV-2 infection.Materials and methodsIn this study, we performed a retrospective chart review of 41 children younger than 18 years old who were diagnosed with COVID-19 from April to August of 2022 and had a prior history KD. We included echocardiography and blood draw data obtained at the last outpatient follow-up at our hospital for KD, and within 4 months of SARS-CoV-2 infection. Echocardiographic data obtained from 82 age-matched and gender matched controls were also included for comparison.ResultsWe found that COVID-19 resulted in slightly higher RCA Z-scores within the first month after infection (mean ± SE, 1.20 ± 0.18 vs. 0.83 ± 0.18, p = 0.030), although this increase did not result in coronary artery dilatation, defined as a Z-score of at least 2.5. In addition, we found that degree of RCA dilatation after COVID-19 infection was negatively correlated with the change in monocyte percentage (Pearson's correlation coefficient—0.363, p = 0.020). Moreover, RCA Z-score changes were lower in patients who received at least one dose of mRNA COVID-19 vaccine when compared those who did not receive any (mean ± SE, −0.23 ± 0.16 vs. 0.39 ± 0.17, p = 0.031).ConclusionIn this pilot study we found that COVID-19 infection resulted in slightly higher RCA Z-scores in children with a prior history of KD, although not large enough to be classified as coronary aneurysms. While these changes could be the result of measurement imprecision or interobserver variation, further study of the cardiac outcomes of COVID-19 infection in children with a prior history of KD are needed in the future.

Abstract Background Kawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD. Methods We retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL. Results During the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696. Conclusions Identifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.

Abstract Background Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet. Method This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients. Result Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%. Conclusion PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness.

Systemic lupus erythematosus (SLE) is an autoimmune disease that may cause vital organ damage. Although not rare for child-onset SLE to have cardiovascular or pulmonary involvement, myocarditis, and pulmonary hypertension are infrequent features and can be life-threatening. In this case report, we describe an 11-year-old girl with SLE who initially presented with fulminant myocarditis pulmonary hypertension, and massive pericardial effusion. Initial immunosuppressive therapy with methylprednisolone pulse therapy, and IVIG were administered, followed by cyclophosphamide, which was ultimately successful, with no residual pulmonary hypertension and no recurrence of myocarditis for over 3 years after the initial episode. Our case highlights the need for clinicians to be aware of systemic lupus erythematosus as a possible diagnostic entity in pediatric patients with severe myocarditis or pulmonary hypertension. Aggressive immunosuppressive therapy should be strongly considered in such cases, as it may lead to good short-term and long-term outcomes.

Kawasaki disease (KD) is an autoimmune-like vasculitis of childhood involving the coronary arteries. Macrophages require scavenger receptors such as CD36 to effectively clear cellular debris and induce self-tolerance. In this study, we hypothesized that CD36 plays an important role in the immunopathogenesis of KD, by aiding in the clearance of plasma mitochondrial DNA, and by amplifying the immune response by activating the inflammasome pathway via AIM2. Fifty-two healthy controls, 52 febrile controls, and 102 KD patients were recruited for RT-PCR of target mRNA expression and plasma mitochondrial DNA. Blood samples were obtained 24 hours prior and 21 days after the administration of intravenous immunoglobulin (IVIG) therapy. Patients with acute KD had higher plasma levels of cell-free mitochondrial DNA (ND1, ND4, and COX1), and higher mRNA expressions of CD36 and AIM2 when compared to both healthy and febrile controls. A greater decrease in both CD36 and AIM2 mRNA expression after IVIG therapy was associated with the development of coronary artery lesions. Coronary artery lesions were associated with a larger decrease of CD36 expression following IVIG therapy, which may indicate that prolonged expression of the scavenger receptor may have a protective effect against the development of coronary artery lesions in KD.

Background: Allergic diseases are frequently observed in children with Kawasaki disease (KD). However, the evidence supporting the association between KD and allergies has been conflicting. The objective of the current study is to examine the association between KD and allergic diseases.Methods: We conducted an electronic search using PubMed, Embase, and the Cochrane through 24 July 2021. The inclusion criteria consisted of studies that examined the prevalence of allergic diseases in children with a previous diagnosis of KD and in a comparison group. We pooled studies by using a random effects model. The effects of KD on the subsequent risk of allergic diseases were expressed as odds ratio (OR) with 95% confidence intervals (CI).Results: We included a total of four studies that assessed the effect of KD on asthma, allergic rhinitis, and atopic dermatitis vs. non-KD children (KD individuals for asthma, four studies, n = 8,474; allergic rhinitis, four studies, n = 8,474; atopic dermatitis, three studies, n = 8,330). The overall prevalence of asthma, allergic rhinitis, and atopic dermatitis was 9.12, 27.63, and 6.55% among patients with previous KD. The meta-analysis showed a significantly increased risk of asthma (OR:1.437, CI: 1.067–1.937) and allergic rhinitis (OR: 1.726, CI: 1.291–2.307) in patients with KD, compared with the control groups. However, patients with KD did not have a significantly different level of risk of atopic dermatitis (OR: 1.243, 95% CI: 0.857–1.802).Conclusion: This meta-analysis supports that individuals with KD are more likely to have asthma and allergic rhinitis compared to controls.

Aspirin was once believed to reduce the mortality of Kawasaki disease (KD) due to its effect on the thrombotic occlusion of coronary arteries. However, conflicting evidence has been found regarding aspirin treatment and its benefit in patients with acute KD. We compared the efficacy of different aspirin doses in acute KD. A literature search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies comparing different doses of aspirin for acute KD. The primary outcome of interest was coronary artery lesions (CAL). We used random-effects network meta-analysis. Six retrospective studies, including 1944 patients receiving aspirin in doses of 0, 3–5, 30–50, or 80–100 mg/kg/day, were selected. The risks of CAL were not significantly different for the various doses of aspirin compared to the placebo: odds ratio (OR) was 1.10 [95% confidence interval (CI): 0.70–1.71] for patients with aspirin 3–5 mg/kg/day; OR = 1.23 (95% CI: 0.67–2.26) for aspirin 30–50 mg/kg/day, and OR = 1.59 (95% CI: 0.74, 3.421) for 80–100 mg/kg/day. The P-score ranged from 0.76 for placebo to 0.19 for aspirin 80–100 mg/kg/day. The different doses of aspirin exhibited no significant difference with regard to the efficacy of CAL or with the secondary outcomes of intravenous immunoglobulin resistance or hospital stays for acute KD. Therefore, we found that treatment without any aspirin is not inferior to other doses of aspirin and can also slightly reduce the risk of CAL.

Abstract Background Although the sternoclavicular joint (SCJ) may be involved in ankylosing spondylitis, rheumatic arthritis, and Behçet’s disease and participates in the systemic inflammatory process of arthritis, it is often neglected during routine rheumatologic clinical examinations. To the best of our knowledge, this is the first study to report etanercept treatment in juvenile idiopathic arthritis (JIA) with SCJ involvement. Case presentation In this study, we describe an unusual case of a child with juvenile idiopathic arthritis with an initial presentation of sternoclavicular mass. The patient (age, 14 years 10 months) presented with an insidious onset atraumatic swelling of the left SCJ and complained of right hip and bilateral ankle tenderness without an apparent cause. Initial ultrasonography indicated a heterogeneous mass in the left SCJ, while computed tomography identified mild swelling of the left SCJ with a thickened synovial lining, mild bone erosion, and some turbid fluid. The patient ultimately underwent left SCJ arthrotomy, during which tapping of the SCJ revealed 2 cc of yellowish fluid, inflammation and necrosis of tissues within the SCJ. A clear yellow joint fluid was aspirated, and testing revealed a negative culture result. The patient was diagnosed with JIA. The joint tenderness improved and erythrocyte sedimentation rate decreased after administering anti-tumor necrosis factor etanercept. An additional ultrasonography demonstrated that the initial imaging findings have been resolved. At the end of a 2-year follow-up period, the patient was completely symptom-free. Conclusions JIA with SCJ involvement is an uncommon presentation in adolescents. Etanercept may be a beneficial treatment for SCJ involvement in patients with JIA. The upper limbs showed no signs of limited range of motion during the follow-up period. Further studies are warranted to elucidate the efficacy of etanercept in JIA with sternoclavicular joint involvement.

Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937–0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD.

Background: Kawasaki disease (KD) is an inflammatory disorder with an unknown etiology. It is the leading cause of acquired heart disease, which leads to coronary vasculitis among children. Studies of frequent manifestation of allergic diseases in children with KD have been the subject of mounting clinical interest. However, evidence supporting the association between KD and allergies has yet to be systematically reviewed.Methods: In this article, we reviewed current literature regarding the association between KD and allergic diseases. References for this review were identified through searches of PubMed, Cochrane, and Embase through the end of August 2020.Results: The results of the analyses of immune repertoire, clinical, and epidemiological studies have indicated some of the characteristics of infectious disease for KD. Although some allergic disorders, such as asthma, may be exacerbated by viral infections, allergies are typically caused by an allergen that triggers an immune response, with the potential involvement of type 2 inflammation and immune disturbances leading to tissue remodeling in genetically susceptible hosts. The effect of intravenous immunoglobulin is multi-faceted and results in a decrease in activating Fc gamma receptor IIA and an increase in anti-inflammatory eosinophils. The findings from this review demonstrate that children who have suffered from KD are more likely to have allergic rhinitis than the general population and their siblings, a condition that lasts until the age of 17. When followed up as teenagers and adults, children with KD are more likely to develop urticaria.Conclusions: This review supports that allergic diseases, such as allergic rhinitis, have been demonstrated to increase following KD. Therefore, the importance of allergic diseases in patients with KD should be emphasized in long-term care. Interventions that include strategies for managing allergies in children with KD would be beneficial.

BackgroundKawasaki disease (KD) is a systematic vasculitis that occurs predominantly in young children, and is the leading cause of acquired heart disease in children younger than five-years-old in developed countries. Although the etiology of KD is unknown, it is believed to be an inflammatory disease resulting from abnormal immune responses to possible environmental or infectious stimuli in genetically predisposed individuals. Breast milk contains numerous anti-inflammatory factors which may protect against allergic and autoimmune diseases. In this study we tried to examine the effect of breastfeeding for 6 months or more on disease outcomes in patients with Kawasaki disease.MethodsA retrospective cohort study of 249 KD patients admitted from 1999- 2013 who were older than 6 months at time of diagnosis and had data regarding breastfeeding in the first 6 months of life. Demographic, clinical and laboratory data was collected by chart review. Continuous data was compared using Student's t-test and categorical variables were compared using Chi-square. Stepwise multivariate regression of all demographic factors was performed.ResultsBreastfeeding for 6 months or more was associated with a shorter total duration of fever (5.980± 1.405 Vs. 6.910 ± 2.573 days, p = 0.001) and a lower risk of developing persistent coronary artery lesions (CALs) (7.8% Vs. 20.2%, p-value = 0.039) on univariate analysis. Multivariate regression of all factors associated with CALs including breastfeeding for 6 months found that only the presence of CALs at baseline (β-coefficient = 0.065, p < 0.001) and white blood count (β-coefficient = 0.065, p = 0.018) remained significant after regression analysis.ConclusionsBreastfeeding for 6 months or more was associated with a shorter duration of fever and a lower risk of persistent CAL formation in patients with KD on univariate analysis, although this effect may be modest when other factors such as the presence of CALs at baseline and white blood cell count are also taken into consideration.

(1) Background: Kawasaki disease (KD) mainly affects children under the age of 5 years and eosinophilia in KD patients might be associated with the development of allergic diseases. We compared the age-adjusted Z-score (Z) of eosinophils and aimed to evaluate the impact of onset age on eosinophils in KD patients. (2) Methods: We divided 398 KD patients into seven age subgroups. Laboratory data and the age-adjusted Z-score of eosinophils during the phases of Kawasaki disease were analyzed. (3) Results: The absolute eosinophil count among all age groups showed significant differences in the post-intravenous immunoglobulin (IVIG) phase and throughout the course of KD with Z-score adjusted for age. Further analysis showed persistent elevation of the age-adjusted Z-score of eosinophils (Z-eosinophil) especially in the under six-month-old age subgroup. In addition, we divided the Z-eosinophil into two groups to find the relationship with coronary artery lesions (CALs). Patients with a higher eosinophil count than average age values had a higher risk of developing CALs, while those with a lower eosinophil count than average age values had a lower risk of having CALs. (4) Conclusions: These findings may provide information to clinicians to pay attention to allergic diseases during the follow-up of KD, especially for children who are younger than 6 months old at the onset of KD, and eosinophil count could be a crucial focus in KD.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0–18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed or diagnosis delayed when initial clinical symptoms do not fulfill the traditional criteria or a normal echocardiography was found. In this study, we aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD.Method: We retrospectively enrolled in this study a total of 50 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data (initial data in the first visit).Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A higher neutrophil-to-lymphocyte ratio (NLR, p = 0.037) and higher C-reactive protein levels (CRP, p = 0.02) were found in group 1 when compared to group 2. A patient with a NLR >1.33 combined with a CRP more than 33 mg/L was more likely to have KD (Sensitivity 90%, specificity 69.2%, p = 0.001; Odds ratio 20.25, 95% confident interval 2.3–178.25).Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Kawasaki disease (KD) is a common systemic vasculitides in children younger than 5 years of age. Activated macrophages are key drivers of vascular inflammation in KD. The aim of this study was to examine differences in M1 and M2 macrophage marker expression in patients with KD. Blood samples were obtained from 18 healthy controls and 18 patients with KD at 24 h prior and 21 days after to intravenous immunoglobulin therapy. GeneChip Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip were used to examined the mRNA expression and corresponding CpG site methylation ratios of 10 M1 surface markers and 15 M2 surface markers. Of the markers examined 2 M1 markers (TLR2, IL2RA) and 8 M2 markers (ARG1, CCR2, TLR1, TLR8, TLR5, MS4A6A, CD36, and MS4A4A) showed increased mRNA expression in the acute phase of KD which decreased after IVIG therapy (P < 0.05). Corresponding CpG sites in the promoter regions these markers were hypomethylated in the acute phase of KD and significantly increased after IVIG therapy. In conclusion, both M1 and M2 markers showed increased mRNA expression in the acute phase of KD. CpG site methylation may be one of the mechanisms governing macrophage polarization in KD.

Background: Non-pharmaceutical interventions (NPIs) introduced in response to the COVID-19 pandemic, including mask-wearing and social distancing, have changed the prevalence of circulating viruses in the community. Since viral infections represent a potential triggering factor for the development of Kawasaki disease (KD), we examined the relationship between KD admission rates and the number of COVID-19, severe influenza, and severe enterovirus infections both before and after the COVID-19 pandemic. Methods: We conducted a retrospective study using data obtained from the Chang Gung Research Database (including seven Taiwanese hospitals and more than 10,000 beds) and the Centers for Disease Control in Taiwan from January 2018 to December 2020. We recorded the number of KD admissions, as well as COVID-19, severe influenza, and severe enterovirus infections. Results: The numbers of KD admissions, severe enterovirus infections, and severe influenza infections were significantly lower from April to September 2020. The number of KD hospitalizations was positively correlated with the number of domestic COVID-19 cases (p = 0.001). A decrease in KD admission numbers was positively correlated with a decrease in severe enterovirus case numbers (p = 0.007). Conclusion: Our findings provide further evidence that viral infections may be an important trigger factor in the development of KD. Therefore, NPIs may not only prevent transmissible viral infections in children, but also decrease the risk of KD.

Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.

Abstract Background Kawasaki disease (KD) is an acute febrile systemic vasculitis most commonly seen in children under 5 years old. High-dose aspirin is often administered, but the duration of such treatment varies. Many centers reduce the aspirin dose once the patient is afebrile, even before treating said patient with intravenous immunoglobulin (IVIG). However, a randomized controlled trial regarding high-dose aspirin in the acute stage of KD has not previously been carried out. Methods/design This trial has been designed as a multi-center, prospective, randomized controlled, evaluator-blinded trial with two parallel groups to determine whether IVIG alone as the primary therapy in acute-stage KD is as effective as IVIG combined with high-dose aspirin therapy. The primary endpoint is defined as coronary artery lesion (CAL) formation at 6–8 weeks. Patients meeting the eligibility criteria are randomly assigned (1:1) to a test group (that receives only IVIG) or a standard group (that receives IVIG plus high-dose aspirin). This clinical trial is conducted at three medical centers in Taiwan. Discussion Since high-dose aspirin has significant anti-inflammatory and anti-platelet functions, it does not appear to affect disease outcomes. Furthermore, it can decrease hemoglobin levels. Therefore, we have initiated this randomized controlled trial to evaluate the necessity of high-dose aspirin in the acute stage of KD. Trial Registration Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan. ClinicalTrials.gov Identifier: NCT02951234. Release Date: November 3, 2016.

Background: Kawasaki disease (KD) is a form of febrile vasculitis that primarily occurs in children. It can cause inflammation of the coronary arteries, which leads to aneurysms. The pathogenesis of coronary arteries may be associated with apoptosis or pyroptosis mediated by caspases activity, but this idea has not been discussed much in KD. Materials and Methods: We enrolled 236 participants in this study. In the Affymetrix GeneChip® Human Transcriptome Array 2.0 study, there were 18 KD patients analyzed prior to receiving intravenous immunoglobulin (IVIG) treatment, at least 3 weeks after IVIG treatment, and 36 non-KD control subjects. We also recruited 24 KD patients prior to receiving IVIG treatment, at least 3 weeks after IVIG treatment, and 24 non-KD control subjects for Illumina HumanMethylation450 BeadChip study. A separate cohort of 134 subjects was analyzed to validate real-time quantitative PCR. Results: The mRNA levels of caspase-1, -3, -4, and -5 were significantly increased in KD patients compared with control subjects (p < 0.05). After administration of IVIG, the expression of these genes decreased considerably. Of particular note, the methylation status of the CpG sites of the caspase-4 and -5 genes demonstrated significant opposite tendencies between the KD patients and controls. Furthermore, compared with patients who responded to IVIG, refractory KD patients had a lower expression of the caspase-3 gene prior to IVIG treatment. Conclusion: Our study is the first to report the upregulation of pyroptotic caspase-1, -4, and -5 in peripheral leukocytes of KD patients. Moreover, the expression of caspase-3 may be associated with IVIG resistance in KD.

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.

Kawasaki disease (KD) or Kawasaki syndrome is known as a vasculitis of small to medium-sized vessels, and coronary arteries are predominantly involved in childhood. Generally, 20-25% of untreated with IVIG and 3-5% of treated KD patients have been developed coronary artery lesions (CALs), such as dilatation and aneurysm. Understanding how coronary artery aneurysms (CAAs) are established and maintained in KD patients is therefore of great importance. Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10(-9); OR = 32.22) and rs7922552 (P = 8.43 × 10(-9); OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10(-9); OR = 21.03)). Their known functions have been reported to associate with cardiac muscle and tubulin, respectively. As a result, this might imply their putative roles of establishing CAAs during KD progression. Additionally, various model analyses have been utilized to determine dominant and recessive inheritance patterns of identified susceptibility mutations. Finally, all susceptibility genes hit by significant genetic variants were further investigated and the top three representative gene-ontology (GO) clusters were regulation of cell projection organization, neuron recognition, and peptidyl-threonine phosphorylation. Our results help to depict the potential routes of the pathogenesis of CAAs in KD patients and will facilitate researchers to improve the diagnosis and prognosis of KD in personalized medicine.

Kawasaki disease (KD) is also known as multiple mucocutaneous lymph node syndrome of systemic vasculitis and is a leading cause of coronary artery lesions (CAL) in childhood. Intravenous immunoglobulin (IVIG) has been proven to effectively reduce the incidence of CAL, but the role and effect dose of aspirin in KD is still unclear. Moreover, overt bleeding and anemia are associated with the use of aspirin, and anemia is common in patients with KD. Thus, the aim of this study was conducted to compare the treatment efficacy, degree of anemia and inflammation, and changes in serum hepcidin in children who received a combination of high-dose aspirin and IVIG in the acute stage of KD, and those who received IVIG alone.KD patients from two medical centers were retrospectively analyzed from 1999-2009. All patients were initially treated with a single dose of IVIG (2 g/kg) as the standard care of treatment. In group 1, high-dose aspirin was prescribed (> 30 mg/kg/day) until the fever subsided, and then low-dose aspirin (3-5 mg/kg/day) was prescribed until all the inflammation signs had resolved. In group 2, low-dose aspirin was prescribed without high-dose aspirin. Laboratory data were collected for analysis in both groups.A total of 851 KD patients (group 1, N = 305, group 2, N = 546) were enrolled in this study. There were no significant differences between group 1 and group 2 in terms of gender (p = 0.51), IVIG resistance rate (31/305 vs. 38/546, p = 0.07), CAL formation (52/305 vs. 84/546, p = 0.67), and duration of hospitalization (6.3 ± 0.2 vs. 6.7 ± 0.2 days, p = 0.13). There were also initially no significant differences in total white blood cell count, hemoglobin level, platelet count, and CRP before IVIG treatment between groups (all p>0.1). After IVIG treatment, group 1 had significantly lower levels of hemoglobin (p = 0.006) and higher CRP (p

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children < 5 years old. Genes significantly associated with KD mostly involve cardiovascular, immune, and inflammatory responses. Recent studies have observed stronger associations for KD risk with multiple genes compared to individual genes. Therefore, we investigated whether gene combinations influenced KD susceptibility or coronary artery lesion (CAL) formation. We examined 384 single-nucleotide polymorphisms (SNPs) for 159 immune-related candidate genes in DNA samples from KD patients with CAL (n = 73), KD patients without CAL (n = 153), and cohort controls (n = 575). Individual SNPs were first assessed by univariate analysis (UVA) and multivariate analysis (MVA). We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models. UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05). Significant associations in MDR analysis were only observed for the two-locus models after permutation testing (p ≤ 0.05). In logistic regression, combined possession of PDE2A (rs341058) and CYFIP2 (rs767007) significantly increased KD susceptibility (OR = 3.54; p = 4.14 x 10(-7)), while combinations of LOC100133214 (rs2517892) and IL2RA (rs3118470) significantly increased the risk of CAL in KD patients (OR = 5.35; p = 7.46 x 10(-5)). Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.

BackgroundPrenatal dexamethasone exposure has been reported to increase allergy potential in childhood possibly by interference with normal immunological development in utero. This study investigated the effects of prenatal dexamethasone on T helper cell immune responses in a rat model.MethodsPregnant rats received either dexamethasone 0.1 mg/kg/day or normal saline from gestational day 14-21. Off-springs were cared for by their biological mother, or cross-fostered by the opposing group. Spleen and blood samples were collected at post-natal day 7 and 120 and tested for mRNA expression and plasma cytokine levels of Th1/Th2/Th17 immune response.ResultsBoth Th1 (T-bet) and Th2 (GATA-3) mRNA expression were shown to have a significant increase in the prenatal dexamethasone exposure group at day 120 (p0.05). The mRNA expression of Th17 (RORγt) showed a significant decrease at post-natal day 120 as well as the plasma level of IL-17A at day 7 (11.21±1.67 vs. 6.23±1.06 pg/ml, p = 0.02). Cross-fostering by a dexamethasone exposed mother resulted in a significant increase in Th1/Th2 mRNA expression (pConclusionsPrenatal dexamethasone exposure increased Th1, Th2 and decreased Th17 expression. Cross-fostering by a dexamethasone exposed mother results in more prominent increase of Th1 and Th2 expression.

Kawasaki disease (KD) is known to be associated with T help (Th) 2 reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been reported to be involved in Th2 mediated diseases such as allergic diseases. However, the role of IL-31 in KD has not been previously reported. The aim of this study is to investigate whether IL-31 is associated with KD and its clinical outcome.A total of 78 KD patients who met the criteria of KD were enrolled in this study as well as 20 age-matched controls. Plasma samples were conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment (KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA).Our findings showed that IL-31 expression was higher in KD patients after IVIG treatment significantly (KD2>KD1: 1265.0±199.3 vs. 840.2±152.5 pg/ml, p