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IntroductionKawasaki disease (KD) is a pediatric vasculitis that can result in coronary artery aneurysm (CAA) formation, which is a dangerous complication. Treatment with intravenous immunoglobulin (IVIg) significantly decreases the risk of CAA, possibly through competitive binding to Fc-gamma receptors (FcγRs), which reduces the binding of pathological immune complexes. However, ~20% of children have recrudescence of fever and have an increased risk of CAA. Therefore, we aimed to identify genetic markers at the FCGR2/3 locus associated with susceptibility to KD, IVIg resistance, or CAA.Materials and methodsWe investigated the association of single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at the FCGR2/3 locus with KD susceptibility, IVIg resistance, and CAA risk using a family-based test (KD susceptibility) and case-control analyses (IVIg resistance and CAA risk) in different cohorts, adding up to a total of 1,167 KD cases. We performed a meta-analysis on IVIg resistance and CAA risk including all cohorts supplemented by previous studies identified through a systematic search.ResultsFCGR2A-p.166His was confirmed to be strongly associated with KD susceptibility (Z = 3.17, p = 0.0015). In case-control analyses, all of the investigated genetic variations at the FCGR2/3 locus were generally not associated with IVIg resistance or with CAA risk, apart from a possible association in a Polish cohort for the FCGR3B-NA2 haplotype (OR = 2.15, 95% CI = 1.15-4.01, p = 0.02). Meta-analyses of all available cohorts revealed no significant associations of the FCGR2/3 locus with IVIg resistance or CAA risk.DiscussionFCGR2/3 polymorphisms are associated with susceptibility to KD but not with IVIg resistance and CAA formation. Currently known genetic variations at the FCGR2/3 locus are not useful in prediction models for IVIg resistance or CAA risk.

Kawasaki disease (KD), an acute systemic vasculitis that primarily affects children under 5 years of age, is the leading cause of acquired heart disease in this age group. Recent studies propose a novel perspective on KD's etiology, emphasizing the gastrointestinal (GI) tract, particularly the role of gut permeability. This review delves into how disruptions in gut barrier function trigger systemic inflammatory responses, exacerbate vascular inflammation, and contribute to coronary artery aneurysms. Evidence suggests that children with KD often exhibit increased gut permeability, leading to an imbalance in gut immunity and subsequent gut barrier damage. These changes impact vascular endothelial cells, promoting platelet aggregation and activation, thereby advancing severe vascular complications, including aneurysms. Additionally, this review highlights the correlation between GI symptoms and increased resistance to standard treatments like intravenous immunoglobulin (IVIG), indicating that GI involvement may predict therapeutic outcomes. Advocating for a new paradigm, this review calls for integrated research across gastroenterology, immunology, and cardiology to examine KD through the lens of GI health. The goal is to develop innovative therapeutic interventions targeting the intestinal barrier, potentially revolutionizing KD management and significantly improving patient outcomes. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute systemic vasculitis that affects medium-sized vessels, particularly the coronary arteries. KD predominantly affects children under 5 years of age. Main symptoms include fever, bilateral conjunctivitis, polymorphous exanthema, oropharyngeal mucous membranes changes, palmar and/or plantar erythema and edema, and cervical lymphadenopathy. KD can present with a few clinical features, which might lead to a delayed diagnosis, particularly in infants. When the therapy is delayed, the diagnosis is missed or in refractory cases, there is a higher risk of coronary artery aneurysms to be formed. We report a clinical case of a 3-month-old male who presented initially with fever and cervical lymphadenopathy in whom a bacterial infection was suspected and treatment with antibiotics was started. In the course of the disease erythema of the palms and soles and generalized erythematous rash developed. The diagnosis of KD was made on the 11th day of onset of symptoms and despite the treatment with two doses of intravenous immunoglobulin, high-doses corticosteroids and infliximab, during follow-up the infant developed giant coronary artery aneurysms. A comprehensive review of the literature concerning KD in infants is included. Clinical suspicion is required to diagnose KD in the youngest patients, as they are more likely to present with few features of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Kawasaki disease (KD) is a medium vessel vasculitis mainly affecting children below the age of 5. KD is the leading cause of acquired heart disease in developed countries. Diagnosis of KD is clinical, and there are no pathognomonic laboratory tests to confirm the diagnosis. There is a paucity of studies that have utilized proteomic approach for biomarker discovery in KD. Identification of these biomarkers may be helpful for early and more effective diagnosis and may aid in the treatment of KD. Area covered: The present review focuses on studies that have utilized the proteomic approach in the identification of biomarkers in patients with KD. We have divided these biomarkers into three different categories: the biomarkers used for (a) assessment of risk of KD; (b) assessment of risk of coronary artery aneurysms; and (c) assessment of treatment resistance. Expert Opinion: Efforts to improve the clinical and diagnostic evaluation of KD have focused on general markers of inflammation that are not specific for KD. Identification of a proteomic-based biomarker can reliably and specifically differentiate KD from other diseases and could help in the prompt diagnosis. Comprehensive analysis of the serum proteome of patients with KD may be helpful in identifying candidate protein biomarkers. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography (US), as a routine examination for evaluating coronary artery lesions (CAL) in children with Kawasaki disease (KD), has strong subjectivity and limitations. Non‐contrast enhanced coronary magnetic resonance angiography (NCE‐CMRA) is sensitive and reliable in displaying the segments of coronary arteries (CA). Purpose: To evaluate the CA using NCE‐CMRA, to compare NCE‐CMRA with US, and to assess the correlation between KD‐related inflammatory factors and the occurrence of CAL. Study Type: Retrospective. Population: 61 children with KD who had undergone NCE‐CMRA. Ultimately, 52 cases were included (32 males and 20 females), with an average of 5.9 ± 0.3 years old. Field Strength/Sequence: 3‐T, 3D balanced turbo field echo sequence. Assessment: NCE‐CMRA and US coronary visualization rates were compared in 41 children who were imaged with both techniques. Inflammatory factors were compared between CAL and normal coronary artery (NCA) subgroups. In the CAL group, correlations of these inflammatory factors with CAL parameters were investigated. Statistical Tests: Comparison between groups was performed by the two independent samples t‐test; the comparison of enumeration data between groups was performed by chi‐square test. Receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity of inflammatory factors for detecting CAL. The correlation between CAL and inflammatory indexes was analyzed by multiple linear regression. A P value <0.05 was considered statistically significant. Results: NCE‐CMRA visualized significantly more segments than US (76% vs. 46%). There were significant differences in PLT, CRP, ESR, and D‐dimer between the CAL and NCA groups. ROC curve analysis showed that the sensitivities of these four indicators in diagnosing CAL were 39%, 44%, 72%, and 61%, respectively, at cut‐off points of 562.5 × 109/L, 48.93 mg/L, 45.5 mm/h, and 0.5 mg/L, respectively. Data Conclusion: The combination of NCE‐CMRA and inflammatory factors is helpful for the early diagnosis and disease severity of CAL in children with KD. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Kawasaki disease is a common systemic vasculitis in children, and early treatment is critical to prevent coronary artery complications. This study aimed to evaluate the impact of different aspirin dosages on the prognosis of Kawasaki disease. A total of 161 children diagnosed with Kawasaki disease were enrolled and divided into four groups based on the dosage of aspirin: 30–34 mg/kg, 35–39 mg/kg, 40–44 mg/kg, and 45–49 mg/kg. Demographic characteristics, pre-treatment laboratory indicators, post-treatment laboratory indicators, the incidence of coronary artery complications, and the rate of IVIG resistance were compared across the groups. No significant differences were found in baseline characteristics such as age, gender, weight, IVIG treatment choice, IVIG treatment duration, or the proportion of patients diagnosed before the age of 1 year. Laboratory indicators before and after treatment were also similar between groups. However, at 3-4 weeks after the onset of illness, the incidence of coronary artery complications was significantly higher in the high-dose aspirin groups compared to the low-dose aspirin group. Additionally, the high-dose aspirin group had a longer duration of fever and a higher proportion of recurrent fever compared to the low-dose group. The results suggest that although aspirin dosage did not appear to have a clear impact on the overall prognosis of Kawasaki disease, high-dose aspirin administered in the 3-4 weeks following disease onset may increase the risk of coronary artery complications and is associated with a higher incidence of recurrent fever. Caution is therefore advised in selecting aspirin dosages to minimize unnecessary risks. [ABSTRACT FROM AUTHOR]

Background: To explore the clinical characteristics, related factors, and prognosis of Kawasaki disease (KD) combined with acute febrile cholestasis and improve the understanding of the liver complications of KD to avoid misdiagnosis and missed diagnosis. Methods: We retrospectively analyzed the demographic, clinical, and laboratory data of 1803 patients with KD between January 2019 and July 2023 in our hospital. Based on the presence of cholestasis, patients were divided into the cholestatic and control groups. Logistic regression analysis was performed for the statistically significant indicators between the two groups to examine the risk factors for KD with coronary artery abnormalities (CAA) and intravenous immunoglobulin (IVIG) unresponsiveness. Additionally, patients with KD and cholestasis were compared with patients with acute febrile cholestasis due to other causes during the same period. Results: Compared to the control group (n = 1720), patients in the cholestatic group (n = 83) were older, had higher levels of white blood cell count (WBC), C-reactive protein (CRP), D-dimer, N-terminal pro-brain natriuretic peptide (NT-proBNP), a shorter fever duration, and high incidences of IVIG unresponsiveness and CAA. KD was the leading cause of acute febrile cholestasis in children (72.6%). In the multivariate logistic regression analysis, younger age, cholestasis, hypoalbuminemia, and a high NT-proBNP level were risk factors for IVIG unresponsiveness, whereas male sex, longer fever duration before treatment, and high alanine aminotransferase (ALT), and CRP levels were risk factors for CAA. Conclusion: KD with cholestasis was associated with a higher risk of IVIG unresponsiveness and coronary artery abnormalities. KD was the leading cause of acute febrile cholestasis in children. Attention to the possibility of KD is warranted in children with acute febrile cholestatic jaundice, especially if associated with elevated WBC, CRP, and D-dimer levels, or hypoalbuminemia. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether the severity of acute Kawasaki disease (KD) can be predicted based on whether a patient remains febrile or becomes afebrile immediately after the completion of initial immunoglobulin treatment (IVIG). Methods: This retrospective cohort study at a single institution involved 306 patients with KD. They were categorized into four groups according to their fever status at two specific time points (end of the initial IVIG treatment and 24–36 h later): Group F-F, patients who remained febrile at both time points; Group F-AF, patients who were febrile at the end of the initial IVIG treatment but became afebrile 24–36 h later; Group AF-F, patients who were afebrile at the end of the initial IVIG treatment but became febrile 24–36 h later; and Group AF-AF, patients who remained afebrile at both time points. The clinical characteristics of the groups were compared. Results: Group F-F (n = 38) showed a significantly higher incidence of CAAs compared to Group AF-F (n = 37), 55.3% vs. 0.0% (p < 0.0001), although both groups were classified as resistant to the initial IVIG. Conclusions: In Japanese patients with acute KD, the presence or absence of fever at the completion of initial IVIG treatment may serve as an early predictor of the occurrence of CAAs. An earlier secondary treatment may be warranted for patients who are in a febrile state immediately after the completion of the initial IVIG treatment. Future research should include a prospective cohort study with a larger number of KD cases across multiple institutions to analyze the effects of other contributing factors related to CAL formation. [ABSTRACT FROM AUTHOR]

Background: Coronary artery aneurysm (CAA) poses significant cardiovascular risks, particularly in Kawasaki disease (KD) patients. This systematic review and meta-analysis aim to evaluate and compare antithrombotic strategies in preventing CAA formation secondary to Kawasaki disease and the ensuing CAA cardiovascular complications. Methods: Following PRISMA guidelines, we systematically searched major databases, namely PubMed, Scopus, Web of Science, and Embase. Major adverse cardiovascular events (MACE), myocardial infarction (MI), stenosis, bleeding, occlusion, and coronary artery lesion (CAL) formation were primary outcomes. Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scores assessed study quality. A meta-analysis, as well as sensitivity analysis and meta-regression, was performed to compare the efficacy of pharmacological strategies on the outcomes. Results: The study included 21 studies with 1045 patients for CAA complications and 41536 patients for CAA formation prevention. In children with CAA secondary to Kawasaki disease, the addition of warfarin to aspirin was associated with a significantly lower odds of myocardial infarction (OR = 0.26, 95% CI: 0.11–0.60, I2 = 25%) and mortality (OR = 0.18, 95% CI: 0.04–0.88, I2 = 0%) compared to aspirin alone. However, there was no significant difference in MACE (OR = 0.38, 95% CI: 0.08–1.93, I2 = 60%) and occlusion (OR = 0.17, 95% CI: 0.02–1.92, I2 = 58%). Sensitivity analysis showed reduced thrombosis (OR = 0.29, 95% CI: 0.14–0.62, I2 = 0%), MACE (OR [95% CI] = 0.22[0.06–0.84], I2 = 46%), and occlusion (OR [95% CI] = 0.08[0.02–0.44], I2 = 36%). Meta-regression did not yield significant results. Conclusions: As for the acute phase of KD, no benefit was conferred from adding high-dose aspirin to the routine IVIG alone regimen. However, the complexity of outcomes and the diversity in antithrombotic interventions underscore the need for tailored approaches and further research. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous immunoglobulin (IVIG) plus methylprednisolone as initial intensive therapy or additional therapy in Kawasaki disease (KD) has been used in clinical practice. However, its molecular and cellular mechanism is unclear. Methods: We performed single-cell analysis on 14 peripheral blood mononuclear cell (PBMC) samples obtained from 7 KD patients who received either IVIG monotherapy or IVIG plus methylprednisolone therapy. This encompassed 4 samples from KD patients collected before and after IVIG treatment, as well as 3 samples from KD patients before and after IVIG plus methylprednisolone therapy. Results: Both IVIG monotherapy and IVIG plus methylprednisolone therapy can increase lymphocyte counts (e.g. CD4+T, CD8+T, and gdT cells) to address lymphopenia. They can also decrease monocyte counts and repress the expression of S100A12, NLRP3, and genes associated with immune-cell migration in monocytes. IVIG combined with methylprednisolone downregulates more monocyte-driven inflammatory pathways than IVIG alone. Additionally, this combination uniquely enhances NK cell cytotoxicity by modulating receptor homeostasis, while significantly upregulating interferon-related genes in CD4+ T cells, CD8+ T cells, and B cells, particularly type I interferons. Conclusion: The combination of IVIG with methylprednisolone attenuated monocyte-driven inflammation and improved NK cell cytotoxicity which might provide clues for pediatricians to consider treatment options for children with KD. Whether the monocyte-driven hyperinflammatory state and NK cell function can be indicators for the clinical choice of IVIG with methylprednisolone therapy in KD needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy. Methods: We performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients. Results: Overall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment. Conclusion: Our results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients. [ABSTRACT FROM AUTHOR]

Background: Background: This study aimed to describe Correlation between Kawasaki disease & MIS-C in Indira Gandhi Medical College, Shimla. Material & Methods: We conducted a cross-sectional study for MIS-C from January to July 2021, in the pediatric ward of Indira Gandhi Medical College Shimla in Himachal Pradesh, in Western Himalayas. All children admitted with a diagnosis of MIS-C were included in the study. Data regarding sociodemographic factors and Kawasaki cases were extracted and analyzed using Epi Info V7 software. Results: In the present study, a total of 31 children diagnosed & admitted as a case of MIS-C were included. Mean age of these patients was 7.12±4.78 years. Among the total 16(51.6%) were males while 15(48.4%) were females. Of, 31 cases of MIS-C, 5 children presented KD. All of them were males. 3 children were less than5 years, while 2 were 6-10 years old. Echo was normal in 4 cases and 1 had low ejection fraction. IVIG was given to all, while LMWH was given to one child. Methylprednisolone in low doses to 4 children, while in 1recieved high dose. Aspirin was given to 4 patients. Oxygen therapy in 3 patients, ventilatory support was given to one child, while inotropic support was given to 2 patients. All 5 patients were discharged after full recovery. Conclusion: Given the frequent overlap of clinical manifestations between MIS-C and those of Kawasaki disease, the majority of patients with hyperinflammatory syndrome have generally been treated with the standard therapeutic protocols used in Kawasaki disease. [ABSTRACT FROM AUTHOR]

Vasculitis in children represents a diverse group of diseases characterized by inflammation of blood vessels, which can lead to significant morbidity if not promptly recognized and managed. This review explores the epidemiology, pathophysiology, classification, and management of key pediatric vasculitides. Classification based on vessel size aids in diagnosis and treatment. Understanding these conditions” clinical features and therapeutic options is critical for improving pediatric patient outcomes and preventing long-term complications. Continued research is essential for refining treatment strategies and enhancing patient care. [ABSTRACT FROM AUTHOR]

Background: Kawasaki Disease (KD) is self-limited vasculitis, the main consequence of which may be involvement of the coronary arteries, especially in patients without treatment. It is estimated that coronary artery aneurysms occur in 15% to 25% of untreated children. Patients with coronary aneurysms may remain asymptomatic for years. The first symptom may be life-threatening sudden cardiac arrest or myocardial ischaemia. Methods: We report a case of a 17-year-old boy with an insignificant past medical history who presented with sudden cardiac arrest. Results: During diagnostics, channelopathies, structural heart defects, drug abuse, and myocardial infarction were excluded. The patient underwent coronary angiography, confirmed by CT angiogram of the coronary vessels, which revealed most likely ruptured, clotted, well-calcified aneurysm of the left anterior descending artery (LAD) with collateral circulation, probably a consequence of untreated Kawasaki disease in early childhood. Conclusions: Complications of KD should be considered in the differential diagnosis of sudden cardiac arrest, especially in a young person. [ABSTRACT FROM AUTHOR]

Objective Kawasaki disease (KD) is an acute systemic vasculitis that is one of the major causes of acquired heart disease especially in young children. The pathogenesis of KD is still unclear. The increased incidence of the disease among Japanese children and siblings of affected patients suggests a genetic component to KD susceptibility. Several reports have studied human leukocyte antigen (HLA) polymorphisms in different populations with KD and found various results. In the present study, we aimed to evaluate the association of HLA-A, -B, -C, -DRB1, and -DQB1 allele frequencies in Turkish children with KD. Methods The study was conducted between January 2016 and February 2018. HLA Class I (A, B, and C) and Class II (DRB1 and DQB1) alleles of patients and healthy controls were studied using the low-resolution DNA-based sequence-specific oligonucleotide method. Results Fifty children with KD and 500 healthy controls were included in this study. In the analysis of HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles, no statistical difference was found in the frequency of alleles between the patients with KD and the control group. However, a significantly lower frequency of the HLA-DQB1*03 allele was observed in the KD group than in the control group (p < 0.001, odds ratio [OR]: 0.29, 95% confidence interval [CI]: 0.15–0.55). When the patients with KD were divided into two subgroups with or without coronary artery lesions (CALs), the frequency of the HLA-DQB1*03 allele was also found lower in the KD group with CALs than the KD group without CALs (p = 0.008, OR: 0.19, 95% CI: 0.05–0.68). Conclusion The study may guide future studies on HLA-DQB1*03 whether it is a protective allele for KD and CALs in Turkish children. [ABSTRACT FROM AUTHOR]

Purpose: This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD). Methods: This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset. Results: Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91–2.46). Conclusions: Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients. What is Known: • Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA. What is New: • Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group. [ABSTRACT FROM AUTHOR]

Background: Predicting resistance to intravenous immunoglobulin (IVIG) in the treatment of Kawasaki disease (KD) remains a focus of research. Fibrinogen and albumin in systemic inflammation play an important role. This study aims to investigate the predictive value of fibrinogen to albumin ratio (FAR) for initial IVIG resistance in patients with KD. Methods: The study prospectively recruited 962 patients with KD between July 2015 and June 2022. The serum characteristics of the two groups were compared by comparing fibrinogen and albumin, as well as other laboratory and clinical data between the IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression was used to explore the relationship between FAR and IVIG resistance. Receiver operating characteristic (ROC) curves were used to determine the effectiveness of FAR in predicting initial IVIG resistance. Results: Our results demonstrated that IVIG-resistant patients had significantly higher fibrinogen levels (603.35 ± 99.00 mg/L), FAR (17.30 ± 3.31), and lower albumin (35.47 ± 5.24 g/L) compared to IVIG-responsive patients (fibrinogen 572.35 ± 145.75 mg/L; FAR 15.08 ± 4.32; albumin 38.52 ± 4.55 g/L). 15.20 was the best cut-off value of FAR for predicting initial IVIG resistance. The sensitivity was 72.5%, the specificity was 51.3%, the positive predictive value was 91.8%, and the negative predictive value was 20.0%. Multivariate logistic regression analysis, found that FAR was an independent predictor of initial IVIG resistance in KD children. Conclusions: The FAR was an independent risk factor for initial IVIG resistance, its predictive power for initial IVIG resistance exceeded that of albumin and fibrinogen alone. FAR may not be suitable as a single marker but might serve as a complementary laboratory marker to accurately predict initial IVIG resistance in KD. [ABSTRACT FROM AUTHOR]

Introduction: Kawasaki disease (KD), a common cause of acquired heart disease in children in developed countries, is primarily treated with intravenous immunoglobulin (IVIG), but some children demonstrate IVIG resistance with increased coronary artery injury risk. T cells have been demonstrated to be involved in the pathogenesis of KD and its treatment with IVIG. However, the role and mechanism of dual TCR T lymphocytes in the occurrence of KD and IVIG therapy remain unclear. Methods: This study, based on scRNA-seq combined with TCR-seq technology, clustered the peripheral blood mononuclear cells of 3 healthy controls and 6 KD patients before and after IVIG treatment. Comparative analysis was conducted to investigate the differences in the proportion of single/dual receptor T cells, the characteristics of CDR3 repertoires, cell types, and the expression of transcription factors among the three groups. The study aimed to explore the correlation between dual TCR T cells and KD as well as IVIG treatment. Results: In our experimental results, we observed the presence of dual TCR T cells in all three groups. However, compared to the healthy control group and the IVIG-treated group, the KD patients before IVIG treatment exhibited a lower proportion of dual TCR T cells, with variability between samples, ranging from 4% to 15%. Notably, after IVIG treatment, the proportion of dual TCR T cells significantly increased, stabilizing above 12%, and these T cells also exhibited clonal expansion and a preference for V gene usage. In addition we found differences in dual TCR T cell subsets among the three groups, for example, IVIG treatment increases the proportion of dual TCR Treg cells, but it still remains below that of healthy control groups, significantly higher proportions of both dual TCR CD8 central and effector memory T cells in IVIG-treated KD patients, and differences in the expression of transcription factors between single and dual TCR T cells. These results suggest dual TCR T cells correlate with KD and IVIG treatment. Conclusion: Dual TCR T lymphocytes, especially dual TCR CD8 T cells and Treg cells, play crucial roles in the pathogenesis of KD and during IVIG treatment, providing strong support for further elucidating KD pathogenesis and optimizing treatment strategies. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) causes vascular injury and lifelong remodeling. Excessive intimal proliferation has been observed, resulting in coronary artery lesions (CALs). However, the mechanisms underlying vascular remodeling in CAL and statin treatment have not been comprehensively elucidated. This study aimed to investigate the effects of statins on vascular remodeling using a KD mouse model. Candida albicans water‐soluble substance (CAWS) was intraperitoneally injected in 5‐week‐old male apolipoprotein‐E‐deficient mice. They were categorized as follows (n = 4): control, CAWS, CAWS+statin, and late‐statin groups. The mice were euthanized at 6 or 10 weeks after injection. Statins (atorvastatin) were initiated after CAWS injection, except for the late‐statin group, for which statins were internally administered 6 weeks after injection. Elastica van Gieson staining and immunostaining were performed for evaluation. Statins substantially suppressed the marked neointimal hyperplasia induced by CAWS. Additionally, CAWS induced TGFβ receptor II and MAC‐2 expression around the coronary arteries, which was suppressed by the statins. KD‐like vasculitis might promote the formation of aneurysm by destroying elastic laminae and inducing vascular stenosis by neointimal proliferation. The anti‐inflammatory effects of statins might inhibit neointimal proliferation. Therefore, statin therapy might be effective in adult patients with KD with CAL by inhibiting vascular remodeling. [ABSTRACT FROM AUTHOR]

Background: To explore the application value of syndecan-1 (SDC-1) in the diagnosis of coronary artery lesions (CALs) in Kawasaki disease (KD) patients and the correlation of multiple laboratory indicators in KD patients. Methods: 86 pediatric Kawasaki disease (KD) patients and 52 healthy controls admitted from January 2018 to December 2023 were retrospectively analyzed. Venous blood samples from KD patients were analyzed for white blood cells (WBC), platelets (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), syndecan-1 (SDC-1), coagulation parameters, and lipid profiles. Correlations between these laboratory indicators were assessed. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of SDC-1 for coronary artery lesions (CALs) in KD patients. SDC-1 levels were further compared across different CAL severity groups. Results: The levels of ALT, AST, WBC, PLT, CRP, IL-6, and SDC-1 in the KD group were significantly higher than those in the control group (P < 0.05). Coagulation function analysis showed that APTT, TT and FIB levels were significantly increased in the KD group compared with the control group (P < 0.05). Lipid profile analysis revealed that TC, HDL-C, and ApoA1 were significantly decreased, whereas TG, LDL-C, and ApoB100 were significantly increased in the KD group (P < 0.05). Refractory KD patients exhibited significantly higher levels of ALT, AST, SDC-1, CRP, WBC, and TG compared to responsive KD patients (P < 0.05). Correlation analysis indicated a strong positive correlation between PLT and LDL-C (r = 0.227, P = 0.035) and between IL-6 and TG (r = 0.491, P = 0.000), while CRP was negatively correlated with ApoA1 (r = -0.265, P = 0.014). Among the 86 KD patients, 41 (47.67%) developed CALs, with 19 classified as mild, 15 as moderate, and 7 as severe. For predicting CALs among KD patients, the threshold of SDC-1 was identified as 5.5 ng/ml, with a sensitivity of 70.7%, specificity of 64.4%, positive predictive value of 65.91%, negative predictive value of 69.05%, and an AUC of 0.762 (95% confidence interval 0.662–0.861, P < 0.001). SDC-1 levels significantly differed among the CAL severity groups (P = 0.008), with higher levels observed in moderate compared to mild CALs, and in severe compared to moderate CALs. Conclusion: In conclusion, SDC-1 has strong clinical value in the diagnosis of CALs in KD patients, and there is a close relationship between the levels of inflammatory factors, coagulation function and lipid levels in KD patients. [ABSTRACT FROM AUTHOR]

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts—in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis—coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis. Synopsis: mTOR signalling pathway orchestrates the formation of the SMC-derived luminal myofibroblasts that drive arterial stenosis in vasculitis. This pathway is druggable and active in patients, and thus, is an attractive therapeutic target. Smooth muscle cells (SMC) give rise to the pathogenic luminal myofibroblasts that drive arterial stenosis during vasculitis. mTOR is an intrinsic and essential regulator of luminal myofibroblast formation. Inhibiting mTOR prevents arterial stenosis developing during vasculitis. mTOR signalling pathway orchestrates the formation of the SMC-derived luminal myofibroblasts that drive arterial stenosis in vasculitis. This pathway is druggable and active in patients, and thus, is an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a significant cause of acquired heart disease in children, particularly in developed countries. Incomplete Kawasaki disease (IKD) lacks some of the classic KD symptoms, complicating diagnosis. This study explores the potential role of anterior uveitis (AU) as a diagnostic marker for IKD and its possible association with reducing the incidence of coronary artery lesions (CALs). Methods: A retrospective review of medical records was conducted on 111 pediatric patients diagnosed with IKD at two tertiary care centers between January 2018 and December 2023. The cohort consisted of 33 patients with AU and 78 without AU. The AU group had a mean age of 4.1 years, while the non-AU group had a mean age of 4.5 years. AU was present in 30% of cases. The study primarily focused on the time to diagnosis, incidence of CALs, and the independent association of AU with CALs using multivariate logistic regression analysis. Results: Patients with AU were diagnosed and treated earlier, with a mean time to diagnosis of 5.1 days compared to 7.4 days in the non-AU group. Additionally, the incidence of CALs was significantly lower in the AU group (4.4%) compared to the non-AU group (31.8%, p < 0.001). Multivariate analysis revealed that AU was independently associated with a significantly reduced risk of CALs (OR = 0.066, 95% CI = 0.009–0.494, P = 0.008). Conclusions: This study suggests that AU may be associated with earlier diagnosis and treatment of IKD, potentially lowering the risk of CALs. While AU shows promise as a diagnostic marker, further prospective studies are needed to validate these findings and determine whether AU should be integrated into clinical guidelines for earlier detection of IKD and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a medium artery vasculitis that predominantly affects children under age 5. Prompt diagnosis and treatment with IVIG and moderate dose aspirin is required to prevent the formation of coronary artery aneurysms. While scrotal edema and erythema have been seen in KD, here we present a distinctive case of incomplete Kawasaki with these features as well as penile edema. Case presentation: A 2-year-old, unvaccinated, African American male presented with 4 days of fever, bilateral limbic sparing conjunctivitis, a papular rash, unilateral shotty cervical lymphadenopathy, mild right-hand edema, and scrotal and penile edema and erythema. His labs were significant for sterile pyuria, elevated ALT, anemia for age, and hypoalbuminemia. He was diagnosed with incomplete Kawasaki disease and was treated with IVIG and moderate dose aspirin. Echocardiogram was negative for coronary aneurysms. His symptoms resolved and he was discharged home with low dose aspirin. At his 2-week follow up, he remained well-appearing with no refractory Kawasaki symptoms. Conclusion: This is a unique case of penile edema in KD which to our knowledge has not been previously reported in literature. An understanding of genitourinary symptoms in Kawasaki disease can help timely diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionThe role of inflammatory cytokines in Kawasaki disease (KD) pathogenesis is known, but causal relationships are unclear. This study investigates these connections using Mendelian randomization (MR).Genetic variations associated with KD were obtained from a GWAS including 119 cases and 6071 controls of European ancestry. Genetic data on inflammatory cytokines were sourced from a GWAS of 8,293 healthy participants.The study identified significant associations between higher levels of macrophage colony stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and increased risk of KD. The odds ratios (OR) were 1.04 (95% CI: 1.01–1.08, p = 0.010) for M-CSF, 1.03 (95% CI: 1.01–1.05, p = 0.026) for MCP-1, and 1.02 (95% CI: 1.01–1.04, p = 0.027) for TRAIL.This study suggests that M-CSF, MCP-1, and TRAIL are potentially involved in the etiology of KD. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease is a rare systemic inflammatory syndrome that mainly affects children under five years of age and is the first cause of pediatric acquired cardiovascular disease. The pathogenesis is complex and a viral trigger is suspected, as well as genetic susceptibility. Multiple studies around the world have shown a decrease in the incidence of Kawasaki disease and have hypothesized that the different sanitary measures enforced in each country during the pandemic period could be responsible to a certain extent. The aim of this study is to evaluate the effects of the COVID-19 pandemic on the disease's incidence, defining characteristics, coronary artery outcomes and management in a tertiary center in Switzerland. Methods: This study is a retrospective analysis of children who have been diagnosed with Kawasaki disease that compares clinical, laboratory, SARS-CoV-2 exposure, and echocardiographic data as well as treatments before (January 1st 2017 to February 24th 2020) and during (February 25th 2020 to December 31st 2022) the COVID-19 pandemic in Switzerland. Statistical significance of differences in the compared parameters was assessed. Results: Of the 90 patients included, 31 belonged to the first group and 59 belonged to the second group. There was a statistically significant (p < 0.05) increase in incidence during the pandemic period (5.91/100,000 children) of 88% compared to the pre-pandemic period (3.14/100,000 children). A lesser seasonal variation was observed during the pandemic. 30% of the patients in the pandemic group had an exposure to SARS-CoV-2. There was no other notable difference in demographic factors, clinical presentation, coronary outcome or administered treatment. Conclusions: To the best of our knowledge, this is the first prolonged European study comparing Kawasaki disease before and during the COVID-19 pandemic. There was a significant increase in incidence in Kawasaki disease during the COVID-19 pandemic. In contrast, studies done in Japan, South Korea and the USA have shown a decrease in incidence. Differences in methodologies, genetics, ethnicities, environments, microbiome-altering behaviors, sanitary measures and SARS-CoV-2 spread are factors that should be considered. Further studies analyzing the differences between countries with increased incidence of Kawasaki disease could help better understand the relevance of such factors and provide more insight into the etiologies of this particular disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictive value of heart rate variability (HRV) indexes combined with serum ferritin (SF) and pentraxin-3 (PTX3) on the sensitivity of intravenous immunoglobulin (IVIG) in children with Kawasaki disease (KD). Methods: 251 acute KD children were treated with IVIG combined with aspirin, HRV indexes and serum SF and PTX3 levels were detected before treatment, the children were divided into IVIG non-response group (33 cases) and IVIG sensitive group (218 cases) according to the response to IVIG treatment. The related factors affecting the sensitivity of IVIG treatment in KD children were analyzed by multivariate Logistic regression analysis and the value of HRV indexes combine with SF and PTX3 in predicting the sensitivity of IVIG treatment in KD children was analyzed by receiver operating characteristic (ROC) curve. Results: The standard deviation of normal sinus NN interval (SDNN), low frequency power (LF), high frequency power (HF), low frequency power/high frequency power (LF/HF) in IVIG sensitive group were higher than those in IVIG non-response group (P<0.05), and the serum SF and PTX3 levels were lower than those in IVIG non-response group (P<0.05). Multivariate Logistic regression analysis showed that high SF and high PTX3 were risk factors for IVIG treatment sensitivity in KD children (P<0.05), and high LF/HF was a protective factor for IVIG treatment sensitivity in KD children (P<0. 05). ROC curve analysis showed that the area under the curve of LF/HF, SF and PTX3 in predicting IVIG sensitivity in KD children was 0.844, 0.792 and 0.785 respectively, the area under the curve of the combine prediction of the three was 0.933, which was higher than that of the single prediction. Conclusion: The HRV indexes LF/HF increase and the serum SF and PTX3 levels decrease in KD children sensitive to IVIG treatment, the HRV indexes LF/HF combine with SF and PTX3 can effectively predict the sensitivity of IVIG treatment in KD children. [ABSTRACT FROM AUTHOR]

The purpose of this study is to analyze the early clinical features of coronary artery lesion (CAL) in Kawasaki disease (KD), evaluate systemic inflammation indicators, and enhance early recognition of CAL in the acute phase of KD. A total of 314 children with KD were divided into those with CAL (CAL group) and without CAL (NCAL group) using echocardiographic results, and their clinical data were retrospectively analyzed. For KD patients, male, children aged 3 to 9 years, and those with fever longer than 6 days before intravenous immunoglobulin (IVIG) use were more likely to have CAL. There were significant differences in sex, age, and fever time (P <.05). Moreover, some laboratory indicator test results revealed there was a significant difference between N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and interleukin-6 (IL-6), and the CAL (P <.05). This study has certain guiding significance for early clinical evaluation. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P <.0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P =.66). CAA occurred more frequently in patients who needed third- or later-line therapy. Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA. Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan (https://www.umin.ac.jp/ctr/index.htm) under code UMIN000024937. What is Known: • Children with Kawasaki disease (KD) who are resistant to standard intravenous immunoglobulin (IVIG) therapy have a high risk of developing coronary artery aneurysms (CAA). • Although primary adjunctive corticosteroid therapy reportedly reduced CAA development, the appropriate dosage and method are unknown. • Patients may experience treatment resistance and CAA development despite receiving timely treatment. What is New: • Primary adjunctive corticosteroid therapy with IVIG significantly improved the treatment response and suppressed inflammation. • The study found no benefit in adding methylprednisolone pulse to prednisolone therapy in KD patients with a high risk of treatment resistance. • Patients receiving primary IVIG alone achieved comparable coronary outcomes to those receiving adjunctive corticosteroid therapy although they were more likely to require additional rescue treatments. • Inflammation related to KD should be resolved no later than the third line of additional rescue treatment to prevent CAA development. [ABSTRACT FROM AUTHOR]

While Kawasaki disease (KD) induced coronary artery aneurysms (KD CAAs) in children are well studied, the features and prognosis of non-KD induced CAAs (non-KD CAAs) in the pediatric population are poorly documented. This case series study is to analyze the etiology and prognosis of non-KD CAAs in children and compare the characteristics of non-KD CAAs and KD CAAs. Non-KD CAA and KD CAA cases at our department from January 2022 to December 2023 were retrospectively collected. Etiologies and prognosis of non-KD CAAs were analyzed. Furthermore, demographic data, biochemical parameters and outcomes between children with Non-KD CAAs and children with KD CAAs were comparatively studied. Fifteen children with non-KD CAAs with a median age of 6 years and 117 children with KD CAAs with a median age of 2.0 years (p = 0.022) were included in this study. The causes of non-KD CAAs include: unknown etiologies (2 cases), coronary artery structural abnormalities (4), Takayasu arteritis (2), virus infection (2), cardiomyopathy (2), aplastic anemia with agranulocytosis (1), ANCA-associated vasculitis (1), and mucopolysaccharidosis (1). In the non-KD CAA group, there were a total of 19 CAAs with 3 being giant, 5 medium, and 11 small; 4 patients had complete CAA regression; an infant with a fistula between the right coronary artery and the coronary sinus complicated with cardiac enlargement died of heart failure. The KD group had significantly higher levels of CRP, white cells counts and ESR with zero mortality. Non-KD CAA cases had a significantly lower regression rate than KD-CAA cases (26.7% vs 66.7%, p = 0.004), and the probability of CAA regression in non-KD patients was 0.341 of that in KD patients (p = 0.006, OR = 0.341, 95% CI: 0.179–0.647). Conclusions: Various etiologies for Non-KD CAAs are identified. Patients with Non-KD CAAs were observed to have lower inflammatory indexes but poorer recovery than patients with KD CAAs. Therapeutic strategies different than those for KD may be needed for non-KD CAAs. What is Known: • Coronary artery aneurysm (CAA) in children is most commonly induced by Kawasaki disease (KD CAA), with a 50 ~ 70% regression rate in 1 to 2 years. • CAA induced by diseases other than KD (non-KD CAA) in children is rare and its prognosis remains largely unknown. What is New: • Most non-KD CAA cases are caused by coronary artery structural malformations. • Non-KD CAA in children has poorer prognosis and lower regression rate compared with KD CAA. • In addition to guideline directed anti-platelet and anti-coagulant therapies, treatments targeting the causal factor are necessary for non-KD CAA. [ABSTRACT FROM AUTHOR]

Of the primary vasculitis pediatricians are familiar with, Kawasaki disease and IgA vasculitis are the most common. The other large, medium and small vessel vasculitis are seldom seen in practice. Though rare, early diagnosis and appropriate management is critical for the best outcome. Primary vasculitis in the pediatric age group have several differential diagnoses which range from infections to monogenic causes such as deficiency of Adenosine Deaminase -2. Each child, therefore, needs a careful systematic approach. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. Methods: A narrative review of relevant studies published up to July 2024 was conducted. Results: We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Conclusions: Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous immunoglobulin is the standard of care in Kawasaki disease. However, a subset of patients exhibits resistance to intravenous immunoglobulin treatment, even when Kawasaki disease is promptly diagnosed and managed. While intravenous immunoglobulin reduces the occurrence of coronary artery abnormalities from 15–25% to 3–5%, it does not entirely eliminate the risk. Besides, management guidelines for non-coronary complications of Kawasaki disease, for instance, myocarditis, remain speculative. Areas covered: Recent literature suggests that a subset of patients with Kawasaki disease may benefit from treatment intensification with drugs, such as corticosteroids, infliximab, anakinra, and/or ciclosporin. In this manuscript, we have reviewed recent advances in the management of Kawasaki disease, especially with regard to preemptive intensification of therapy in children at high risk of cardiac complications. A comprehensive search was made using Web of Science, Scopus, and PubMed databases to gather English articles published from 1967 to 2023 on the treatment of Kawasaki disease. We incorporated the following words in the search strategy: 'Kawasaki disease,' 'intravenous immunoglobulin/IVIg,' 'intravenous immunoglobulin/IVIg-resistant Kawasaki disease,' 'treatment intensification,' or 'primary intensification of treatment/therapy.' Expert opinion: The 'high-risk' group in Kawasaki disease needs to be identified with early intensification of primary therapy for better coronary and myocardial outcomes. [ABSTRACT FROM AUTHOR]

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Jiayun Ling,1 Fang Xie,1 Qingfang Zhou,1 Qian Ouyang,1 Lin Li,1 Wei Zhao,2 Xiaohui Liu1 1Department of Rheumatology and Immunology, Jiangxi Children’s Hospital, Jiangxi Medical College, Nanchang, Jiangxi, People’s Republic of China; 2Pediatric Cardiology Treatment Center, Jiangxi Children’s Hospital, Jiangxi Medical College, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaohui Liu, Department of Rheumatology and Immunology, Jiangxi Children’s Hospital, Jiangxi Medical College, Nanchang, Jiangxi, People’s Republic of China, Email 851724846@qq.comBackground: Kawasaki disease (KD) is a leading cause of acquired heart disease in children in developed countries. While intravenous immunoglobulin (IVIG) is the standard treatment, 10– 20% of patients do not respond to IVIG. Given the significant role of interleukin-6 (IL-6) in KD pathophysiology, targeting IL-6 may offer a therapeutic option for IVIG-resistant KD.Objective: This study aims to evaluate the efficacy and safety of tocilizumab (an IL-6 receptor antagonist) in the treatment of IVIG-resistant KD through a retrospective analysis of clinical data.Methods: Clinical data from five KD patients treated with tocilizumab (TCZ) at Jiangxi Children’s Hospital from January 2023 to February 2024 were retrospectively analyzed. All patients met the 2017 American Heart Association diagnostic criteria for KD and received a single dose of TCZ. Data on clinical manifestations, laboratory indicators, and coronary artery changes before and after TCZ treatment were collected.Results: Four of the five patients had a KOBAYASHI score > 4, and initial IVIG and glucocorticoid treatments were ineffective. Following TCZ administration, body temperature normalized within 12 hours in three patients, and inflammatory markers, including C-reactive protein and interleukin-6, returned to normal levels. Coronary artery dilation was observed in 75% of patients pre-TCZ; post-TCZ, coronary arteries normalized in three patients, while one patient experienced progressive right coronary artery dilation. No adverse events were reported following TCZ administration.Conclusion: Tocilizumab effectively controls systemic inflammation and improves coronary artery outcomes in IVIG-resistant KD patients, with no observed adverse events. Larger studies are necessary to confirm these findings and further investigate long-term effects on coronary artery health.Keywords: Kawasaki disease, tocilizumab, IVIG-resistant, coronary arteries, inflammatory markers

Abstract Background To explore the clinical characteristics, related factors, and prognosis of Kawasaki disease (KD) combined with acute febrile cholestasis and improve the understanding of the liver complications of KD to avoid misdiagnosis and missed diagnosis. Methods We retrospectively analyzed the demographic, clinical, and laboratory data of 1803 patients with KD between January 2019 and July 2023 in our hospital. Based on the presence of cholestasis, patients were divided into the cholestatic and control groups. Logistic regression analysis was performed for the statistically significant indicators between the two groups to examine the risk factors for KD with coronary artery abnormalities (CAA) and intravenous immunoglobulin (IVIG) unresponsiveness. Additionally, patients with KD and cholestasis were compared with patients with acute febrile cholestasis due to other causes during the same period. Results Compared to the control group (n = 1720), patients in the cholestatic group (n = 83) were older, had higher levels of white blood cell count (WBC), C-reactive protein (CRP), D-dimer, N-terminal pro-brain natriuretic peptide (NT-proBNP), a shorter fever duration, and high incidences of IVIG unresponsiveness and CAA. KD was the leading cause of acute febrile cholestasis in children (72.6%). In the multivariate logistic regression analysis, younger age, cholestasis, hypoalbuminemia, and a high NT-proBNP level were risk factors for IVIG unresponsiveness, whereas male sex, longer fever duration before treatment, and high alanine aminotransferase (ALT), and CRP levels were risk factors for CAA. Conclusion KD with cholestasis was associated with a higher risk of IVIG unresponsiveness and coronary artery abnormalities. KD was the leading cause of acute febrile cholestasis in children. Attention to the possibility of KD is warranted in children with acute febrile cholestatic jaundice, especially if associated with elevated WBC, CRP, and D-dimer levels, or hypoalbuminemia.

Abstract Background Coronary artery aneurysm (CAA) poses significant cardiovascular risks, particularly in Kawasaki disease (KD) patients. This systematic review and meta-analysis aim to evaluate and compare antithrombotic strategies in preventing CAA formation secondary to Kawasaki disease and the ensuing CAA cardiovascular complications. Methods Following PRISMA guidelines, we systematically searched major databases, namely PubMed, Scopus, Web of Science, and Embase. Major adverse cardiovascular events (MACE), myocardial infarction (MI), stenosis, bleeding, occlusion, and coronary artery lesion (CAL) formation were primary outcomes. Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scores assessed study quality. A meta-analysis, as well as sensitivity analysis and meta-regression, was performed to compare the efficacy of pharmacological strategies on the outcomes. Results The study included 21 studies with 1045 patients for CAA complications and 41536 patients for CAA formation prevention. In children with CAA secondary to Kawasaki disease, the addition of warfarin to aspirin was associated with a significantly lower odds of myocardial infarction (OR = 0.26, 95% CI: 0.11–0.60, I2 = 25%) and mortality (OR = 0.18, 95% CI: 0.04–0.88, I2 = 0%) compared to aspirin alone. However, there was no significant difference in MACE (OR = 0.38, 95% CI: 0.08–1.93, I2 = 60%) and occlusion (OR = 0.17, 95% CI: 0.02–1.92, I2 = 58%). Sensitivity analysis showed reduced thrombosis (OR = 0.29, 95% CI: 0.14–0.62, I2 = 0%), MACE (OR [95% CI] = 0.22[0.06–0.84], I2 = 46%), and occlusion (OR [95% CI] = 0.08[0.02–0.44], I2 = 36%). Meta-regression did not yield significant results. Conclusions As for the acute phase of KD, no benefit was conferred from adding high-dose aspirin to the routine IVIG alone regimen. However, the complexity of outcomes and the diversity in antithrombotic interventions underscore the need for tailored approaches and further research.

Abstract Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future. In this case–control study, we investigated 29 consecutive KD patients [20 male, median current age, 7.9 years; median follow-up duration, 5.7 years] and a group of 29 healthy matched controls (CON) [19 male, median current age, 10.8 years]. They were assesed and compared for CAA, LVFS, GCS, GLS, coronary artery (CA) Z scores, carotid intima-media thickness (IMT) and coronary artery IMT by high-resolution transthoracic echocardiography (hrTTE). Coronary artery IMT (caIMT) was significantly higher in patients with a maximal CA Z score > 2.5 in acute KD than in CON: KD caIMT: 0.62 mm [IQR, 0.57–0.72 mm] vs. 0.53 mm [0.51–0.60 mm], p = 0.043. CAAs were found in 15 (51.7%) patients with acute KD. The maximal median LCA Z score in acute KD was 2.57z [IQR, 1.93—3.2z] and in follow-up −0.39z [IQR, −1.25 to −0.36z]. There was no significant difference in carotid IMT between KD patients and CON. Signs of CA intima-media thickening were detected by hrTTE in patients with a maximal CA Z score > 2.5 in acute KD. These data indicate that these patients may be at risk for cardiovascular sequale even in the absence of permanent CA luminal abnormalities. Therefore long-term follow-up of this group of KD patients may be required.

Abstract Background To explore the application value of syndecan-1 (SDC-1) in the diagnosis of coronary artery lesions (CALs) in Kawasaki disease (KD) patients and the correlation of multiple laboratory indicators in KD patients. Methods 86 pediatric Kawasaki disease (KD) patients and 52 healthy controls admitted from January 2018 to December 2023 were retrospectively analyzed. Venous blood samples from KD patients were analyzed for white blood cells (WBC), platelets (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), syndecan-1 (SDC-1), coagulation parameters, and lipid profiles. Correlations between these laboratory indicators were assessed. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of SDC-1 for coronary artery lesions (CALs) in KD patients. SDC-1 levels were further compared across different CAL severity groups. Results The levels of ALT, AST, WBC, PLT, CRP, IL-6, and SDC-1 in the KD group were significantly higher than those in the control group (P

Abstract Background Kawasaki disease (KD) is a medium artery vasculitis that predominantly affects children under age 5. Prompt diagnosis and treatment with IVIG and moderate dose aspirin is required to prevent the formation of coronary artery aneurysms. While scrotal edema and erythema have been seen in KD, here we present a distinctive case of incomplete Kawasaki with these features as well as penile edema. Case presentation A 2-year-old, unvaccinated, African American male presented with 4 days of fever, bilateral limbic sparing conjunctivitis, a papular rash, unilateral shotty cervical lymphadenopathy, mild right-hand edema, and scrotal and penile edema and erythema. His labs were significant for sterile pyuria, elevated ALT, anemia for age, and hypoalbuminemia. He was diagnosed with incomplete Kawasaki disease and was treated with IVIG and moderate dose aspirin. Echocardiogram was negative for coronary aneurysms. His symptoms resolved and he was discharged home with low dose aspirin. At his 2-week follow up, he remained well-appearing with no refractory Kawasaki symptoms. Conclusion This is a unique case of penile edema in KD which to our knowledge has not been previously reported in literature. An understanding of genitourinary symptoms in Kawasaki disease can help timely diagnosis and treatment of the disease.

Abstract Background Kawasaki disease is a rare systemic inflammatory syndrome that mainly affects children under five years of age and is the first cause of pediatric acquired cardiovascular disease. The pathogenesis is complex and a viral trigger is suspected, as well as genetic susceptibility. Multiple studies around the world have shown a decrease in the incidence of Kawasaki disease and have hypothesized that the different sanitary measures enforced in each country during the pandemic period could be responsible to a certain extent. The aim of this study is to evaluate the effects of the COVID-19 pandemic on the disease’s incidence, defining characteristics, coronary artery outcomes and management in a tertiary center in Switzerland. Methods This study is a retrospective analysis of children who have been diagnosed with Kawasaki disease that compares clinical, laboratory, SARS-CoV-2 exposure, and echocardiographic data as well as treatments before (January 1st 2017 to February 24th 2020) and during (February 25th 2020 to December 31st 2022) the COVID-19 pandemic in Switzerland. Statistical significance of differences in the compared parameters was assessed. Results Of the 90 patients included, 31 belonged to the first group and 59 belonged to the second group. There was a statistically significant (p

Abstract Background Kawasaki disease (KD) is a significant cause of acquired heart disease in children, particularly in developed countries. Incomplete Kawasaki disease (IKD) lacks some of the classic KD symptoms, complicating diagnosis. This study explores the potential role of anterior uveitis (AU) as a diagnostic marker for IKD and its possible association with reducing the incidence of coronary artery lesions (CALs). Methods A retrospective review of medical records was conducted on 111 pediatric patients diagnosed with IKD at two tertiary care centers between January 2018 and December 2023. The cohort consisted of 33 patients with AU and 78 without AU. The AU group had a mean age of 4.1 years, while the non-AU group had a mean age of 4.5 years. AU was present in 30% of cases. The study primarily focused on the time to diagnosis, incidence of CALs, and the independent association of AU with CALs using multivariate logistic regression analysis. Results Patients with AU were diagnosed and treated earlier, with a mean time to diagnosis of 5.1 days compared to 7.4 days in the non-AU group. Additionally, the incidence of CALs was significantly lower in the AU group (4.4%) compared to the non-AU group (31.8%, p

BACKGROUND. Kawasaki disease is a rare, self-limiting inflammatory disease primarily affecting children under 5 years old. In 25 % of cases, it can lead to coronary artery aneurysms if not treated promptly with intravenous human immunoglobulin. A significant portion of Kawasaki disease patients present with an incomplete form, complicating diagnosis, while the risk of coronary artery aneurysms remains unchanged. Particularly vulnerable are infants under 6 months old, who may exhibit even more limited clinical symptoms, making them especially susceptible to severe cardiac complications. OBJECTIVE. To analyze a clinical case of an incomplete form of Kawasaki disease in a 2-month-old girl, raise awareness of Kawasaki disease, including its incomplete form, among healthcare workers in Ukraine, emphasize the critical importance of proper diagnostic evaluation of coronary arteries, and underscore the necessity of early administration of immunoglobulin when Kawasaki disease is suspected, even in the absence of pathological changes in the heart. MATERIALS AND METHODS. The study involved collecting medical history, physical examination data, laboratory and instrumental studies, and their analysis. The diagnosis of Kawasaki disease, including its incomplete form, was based on the 2017 recommendations of the American Heart Association. CLINICAL CASE. A 2-month-old girl presented with symptoms initially resembling a urinary tract infection, with no therapeutic response to multiple courses of antibacterial therapy. During the second week of illness, she developed swelling in her hands and feet, which, along with persistent fever, significant inflammatory response, and lack of improvement with antibiotics, led to the suspicion and diagnosis of Kawasaki disease based on the algorithm for incomplete Kawasaki disease. After administration of an immunomodulatory dose of intravenous human immunoglobulin at 2 g/kg on the 11th day of illness, there was a rapid regression of symptoms, normalization of inflammation markers, and overall improvement in the child's condition. By the second week of illness, small aneurysms of the right and left coronary arteries had formed but regressed within a few weeks from the onset of the disease. CONCLUSIONS. Kawasaki disease requires prompt therapeutic intervention and should be suspected in any child, especially those under one year of age, with a high fever lasting at least 5 days, unexplained by a preliminary diagnosis, and no response to antibiotic treatment in the presence of “bacterial” blood tests. Serial echocardiograms assessing coronary arteries, absolute dimensions, and Z-scores are mandatory.

The hypercoagulable state in Kawasaki disease (KD) may lead to complex cardiovascular sequelae. We present the case of a 2-month-old infant with complete KD complicated by giant coronary artery aneurysms, coronary sinus thrombosis, and post-myocardial infarction syndrome (Dressler syndrome), resulting in 2 distinct episodes of pericardial effusion. (Level of Difficulty: Intermediate.).

Background: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan. Methods: Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions. Results: Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported. Conclusion: The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features. [ABSTRACT FROM AUTHOR]

Abstract Background Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. Methods Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. Results At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75–0.90), 0.84 (95% CI, 0.74–0.94), and 0.73 (95% CI, 0.40–0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. Conclusions Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.

Abstract Background This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect. Methods We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters. Results The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (

Abstract Background This study aimed to evaluate the effectiveness of Egami, Kobayashi and Sano scores in predicting intravenous immunoglobulin (IVIG) resistance in infant Kawasaki disease (KD), considering its unique clinical presentation. Methods We retrospectively analysed 143 infants aged

Yihua Jin,1,&ast; Zhimin Geng,1,2,&ast; Kun Lin,1 Xinyu Gu,1 Xiwei Feng,1 Songling Fu,1 Wei Wang,1 Chunhong Xie,1 Yujia Wang,1 Fangqi Gong1 1Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Pediatric Cardiovascular Diseases Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangqi Gong; Yujia Wang, Email gongfangqi@zju.edu.cn; wangyujia@zju.edu.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM.Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD.Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD.Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.Keywords: Kawasaki disease, monocyte subsets, L-Selectin, coronary artery lesions

Background: Approximately 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. Methods: This 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. Results: There 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. Conclusion: We 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.