Kawasaki Disease Research Articles

Seasons of Kawasaki Disease during the COVID-19 pandemic.

The incidence of Kawasaki Disease has a peak in the winter months with a trough in late summer/early fall. Environmental/exposure factors have been associated with a time-varying incidence. These factors were altered during the COVID-19 pandemic. The study was performed through the International Kawasaki Disease Registry. Data from patients diagnosed with acute Kawasaki Disease and Multiple Inflammatory Syndrome-Children were obtained. Guideline case definitions were used to confirm site diagnosis. Enrollment was from 1/2020 to 7/2023. The number of patients was plotted over time. The patients/month were tabulated for the anticipated peak Kawasaki Disease season (December-April) and non-peak season (May-November). Data were available for 1975 patients from 11 large North American sites with verified complete data and uninterrupted site reporting. The diagnosis criteria were met for 531 Kawasaki Disease and 907 Multiple Inflammatory Syndrome-Children patients. For Multiple Inflammatory Syndrome-Children there were peaks in January of 2021 and 2022. For Kawasaki Disease, 2020 began (January-March) with a seasonal peak (peak 26, mean 21) with a subsequent fall in the number of cases/month (mean 11). After the onset of the pandemic (April 2020), there was no clear seasonal Kawasaki Disease variation (December-April mean 12 cases/month and May-November mean 10 cases/month). During the pandemic, the prevalence of Kawasaki Disease decreased and the usual seasonality was abolished. This may represent the impact of pandemic public health measures in altering environmental/exposure aetiologic factors contributing to the incidence of Kawasaki Disease.

An Update on Kawasaki Disease.

To summarize advances in research on the epidemiology, pathogenesis, diagnosis, and treatment of Kawasaki Disease (KD), a systemic inflammatory illness of unknown etiology that affects children globally. The epidemiology of KD was affected by the COVID-19 pandemic and advances in molecular immunology and machine learning have enabled research into its pathogenesis. There is ongoing research into agents that can be used to intensify initial treatment and accumulating evidence supporting the use of certain rescue regimens for refractory disease over others. There is promise surrounding a new coronary artery aneurysm prediction model. Research into the post-acute morbidity of KD continues. The COVID-19 pandemic temporarily reduced the incidence of KD. The NLRP3 inflammasome plays a key role in KD pathogenesis. Intensified initial treatment benefits high-risk patients, yet no intensification regimen shows superiority over another. Corticosteroids, infliximab, or combination therapy with IVIg plus another agent may be superior rescue regimens compared to IVIg alone for refractory KD. The Son score, developed in North America, predicted coronary artery lesions in Japanese and Italian cohorts. Patients with a history of KD may carry long-term physical and emotional burdens that persist into adulthood yet appear to have typical neurocognitive development. Successful transition to adult healthcare presents a challenge.

Differences in glucocorticoid use in childhood vasculitis

This review aimed to explore the differences in glucocorticoid use across various subtypes of childhood vasculitis, focusing on their effectiveness, potential side effects, and tapering strategies to minimize toxicity. A comprehensive review was conducted to evaluate the clinical applications of glucocorticoids in pediatric vasculitis subtypes. Recommendations from recent studies and guidelines were assessed, focusing on glucocorticoid protocols for conditions such as IgA vasculitis, Kawasaki disease, polyarteritisnodosa, ANCA-associated vasculitis, and Takayasu arteritis. Glucocorticoid tapering strategies and toxicity indices, such as the Pediatric Glucocorticoid Toxicity Index (pGTI), were also analyzed. Glucocorticoid use varied across vasculitis subtypes. For IgA vasculitis, mild cases were managed with oral prednisolone, while severe nephritis required intravenous methylprednisolone and immunosuppressants. In Kawasaki disease, corticosteroids were used for refractory cases alongside IVIG and aspirin. Severe polyarteritis nodosa cases showed better outcomes with cyclophosphamide and high-dose glucocorticoids, whereas non-severe cases benefitted from low-dose glucocorticoids and NSAIDs. ANCA-associated vasculitis studies reported no significant correlation between glucocorticoid dose and outcomes, although side effects were dose-dependent. In Takayasu arteritis, children generally received lower doses than adults, based on adult treatment guidelines. The pGTI was highlighted as a valuable tool to monitor and assess glucocorticoid toxicity in pediatric patients. Glucocorticoids remain a cornerstone of treatment in pediatric vasculitis, but their use must be carefully tailored to balance efficacy and toxicity. Early tapering and transitioning to alternative therapies, when feasible, are critical to minimizing adverse effects.

Increasing incidence of Kawasaki disease and associated coronary aneurysm in Aotearoa New Zealand: a retrospective cohort study

BackgroundKawasaki disease (KD) is a childhood vasculitis which causes coronary artery aneurysms (CAA). There is a paucity of data regarding KD in Aotearoa New Zealand. We aimed to provide up-to-date...

Illuminating the enigmatic pathogenesis of Kawasaki disease: Unveiling novel therapeutic avenues by targeting FCGR3B-S100A12 pathway

Kawasaki disease (KD) primarily affects the pediatric population and exhibits a notable incidence of drug resistance, resulting in coronary artery damage and thrombosis. This study aimed to identify innovative therapeutic targets for KD treatment. By harnessing single-cell data derived from peripheral blood mononuclear cells, we identified differentially expressed genes. Through the integration of eQTL data and Mendelian randomization analysis, we identified FCGR3B and S100A12 were causally linked to KD. The DrugBank database showed their potential as drug target candidates. GSEA further elucidated their roles on coronary artery damage and thrombosis. Furthermore, we have confirmed that the ligand-FCGR3B complex enhances the intracellular calcium concentration (Ca2+) within the cytoplasm, which in turn accelerates the secretion of S100A12, a pro-inflammatory cytokine that targets endothelial cells, from neutrophils. By integrating existing research, we proposed a synergistic effect that FCGR3B-S100A12 pathway positively modulates the development of coronary artery damage and thrombus formation, suggesting their perspectives in clinical treatment.

Nationwide Survey of Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019 in Japan.

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. 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. Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7years). 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. The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features.

Features of hyperinflammation link the biology of EBV infection and cytokine storm syndromes

BackgroundOvert immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). ObjectiveWe aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. MethodsWe recruited children who presented to the emergency room with fever for ≥ 3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C). ResultsWe enrolled 352 febrile patients and studied 110 cases with confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, tumor necrosis factor, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH / MAS, but less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH / MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection. ConclusionThis work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH / MAS.

Urinary exosomal microRNA-200 family: diagnostic biomarkers for Kawasaki disease and their link to inflammatory markers.

The microRNA-200 family plays a key role in inflammatory and vascular processes, making it a relevant target for Kawasaki disease, a vasculitis with coronary complications. This study aimed to evaluate the diagnostic potential of urinary exosomal microRNA-200 family members in Kawasaki disease patients. Urine samples from 15 Kawasaki disease patients and 15 healthy controls underwent total exosome isolation and high-throughput sequencing. Differential expression of microRNA-200 family members was validated using quantitative real-time polymerase chain reaction. Diagnostic potential was assessed via receiver operating characteristic analysis, and correlations with clinical parameters were evaluated using Spearman correlation. High-throughput sequencing identified upregulation of microRNA-429, microRNA-200b-3p/5p, microRNA-141-3p, microRNA-200a-3p/5p, and microRNA-200c-3p in Kawasaki disease patients. We confirmed significant upregulation of microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, with receiver operating characteristic analysis showing high diagnostic potential for these microRNAs (area under the curves of 0.844, 0.791, 0.942, 0.842, and 0.898, respectively) and a combined analysis yielding a perfect area under the curve of 1.000. MicroRNA-141 and microRNA-200c-3p/5p, however, showed no significant diagnostic value. MicroRNA-200a-3p and microRNA-200a-5p were positively correlated with white blood cells, platelet counts, and C-reactive protein, while microRNA-200b-3p and microRNA-429 were positively correlated with white blood cells, platelet counts, erythrocyte sedimentation rate, and C-reactive protein. microRNA-200b-5p showed moderate correlations with platelet counts and erythrocyte sedimentation rate. Urinary exosomal microRNA-200 family members, especially microRNA-200a-3p/5p, microRNA-200b-3p/5p, and microRNA-429, demonstrate strong diagnostic potential for Kawasaki disease, correlating with key inflammatory markers. MicroRNA-141 and microRNA-200c did not demonstrate significant diagnostic utility.

Analysis of the clinical characteristics of patients with Kawasaki disease complicated with cholestasis

BackgroundTo 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.MethodsWe 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.ResultsCompared 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.ConclusionKD 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.

Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis

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.

Successful biventricular assist device Berlin heart implantation leading to heart transplant in a complicated pediatric case: an experience from a single center

The use of the Berlin heart EXCOR ventricular assist device (VAD) as a bridge to heart transplantation in pediatric patients has become increasingly widespread. This case report presents a detailed account of the successful implantation of a biventricular assist device (BIVAD) Berlin heart device in a complex pediatric case at the esteemed King Faisal Specialist Hospital and Research Center. The patient, diagnosed with dilated cardiomyopathy (DCM) and Kawasaki disease, underwent a series of interventions and treatments before requiring extracorporeal membrane oxygenation (ECMO) support and subsequently receiving the Berlin heart device. The post-implantation period was marked by significant challenges, including instances of bleeding and clot formation, necessitating multiple interventions and careful management. Ultimately, a heart transplant was performed; however, the patient encountered humoral rejection, leading to additional targeted treatment. Despite these intricate complications, the patient exhibited substantial improvement in left ventricular ejection fraction (LVEF) following the transplant, indicating a positive outcome. This case underscores the successful use of a BIVAD Berlin heart device as a viable bridge to heart transplantation in a complicated pediatric case, highlighting the crucial role of a multidisciplinary approach and meticulous management of complications throughout the entire treatment process.

The Predictive Value of Fibrinogen-to-Albumin Ratio for Predicting Intravenous Immunoglobulin Resistance in Kawasaki Disease: A Prospective Cohort Study.

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. 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. 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. 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.

Severity of Acute Kawasaki Disease Can Be Predicted by Evaluating the Body Temperature at the Completion of an Initial Immunoglobulin Treatment.

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.

Identification of key ferroptosis‑related biomarkers in Kawasaki disease by clinical and experimental validation.

Kawasaki disease (KD) is an acute febrile rash that is primarily characterized by systemic vasculitis and is the leading cause of childhood-acquired heart disease. At present, a KD diagnosis is solely dependent on clinical symptoms and effective diagnostic markers are unavailable. Ferroptosis, a novel form of programmed cell death, contributes to the pathophysiology of infectious diseases. The present study aimed to identify key ferroptosis-related genes (FRGs) involved in the pathological process of KD and thus potential diagnostic biomarkers for this disease. For this purpose, differentially expressed-FRGs (DE-FRGs) between patients with KD and healthy controls were screened. The least absolute shrinkage and selection operator (LASSO) algorithm and a logistic regression model combined with receiver operating characteristic analysis were then used to identify and assess ferroptosis-related markers. Additionally, immune cell infiltration landscapes in the KD and control groups were evaluated using CIBERSORT. Moreover, the predictive value of the identified markers was validated in the clinical samples as well as vascular endothelial cells. A total of 10 DE-FRGs were screened from the KD and control samples. These 10 DE-FRGs were then applied to the LASSO model and 6 key ferroptosis-related markers were obtained. The subsequent Gene Set Variation Analysis results suggested that high expression levels of these markers were closely associated with innate immune activation and metabolism, while low expression was mainly linked to adaptive immune-related pathways. In addition to validating each gene in the training and validation sets, the diagnostic potential of these markers was assessed utilizing KD samples obtained from Shenzhen Baoan Women's and Children's Hospital. As a result, MAPK14, SLC2A3 and PGD were selected as potential diagnostic markers for KD. Additionally, changes in the expression of marker genes during inflammatory activation of vascular endothelial cells were measured by reverse transcription-quantitative PCR. The results of the present study will help to understand the role of FRGs in the pathogenesis of KD. Moreover, the identified FRGs may serve as diagnostic biomarkers, providing new strategies for KD prediction and treatment.

Accuracy of Machine Learning in Discriminating Kawasaki Disease and Other Febrile Illnesses: Systematic Review and Meta-Analysis.

Kawasaki disease (KD) is an acute pediatric vasculitis that can lead to coronary artery aneurysms and severe cardiovascular complications, often presenting with obvious fever in the early stages. In current clinical practice, distinguishing KD from other febrile illnesses remains a significant challenge. In recent years, some researchers have explored the potential of machine learning (ML) methods for the differential diagnosis of KD versus other febrile illnesses, as well as for predicting coronary artery lesions (CALs) in people with KD. However, there is still a lack of systematic evidence to validate their effectiveness. Therefore, we have conducted the first systematic review and meta-analysis to evaluate the accuracy of ML in differentiating KD from other febrile illnesses and in predicting CALs in people with KD, so as to provide evidence-based support for the application of ML in the diagnosis and treatment of KD. This study aimed to summarize the accuracy of ML in differentiating KD from other febrile illnesses and predicting CALs in people with KD. PubMed, Cochrane Library, Embase, and Web of Science were systematically searched until September 26, 2023. The risk of bias in the included original studies was appraised using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Stata (version 15.0; StataCorp) was used for the statistical analysis. A total of 29 studies were incorporated. Of them, 20 used ML to differentiate KD from other febrile illnesses. These studies involved a total of 103,882 participants, including 12,541 people with KD. In the validation set, the pooled concordance index, sensitivity, and specificity were 0.898 (95% CI 0.874-0.922), 0.91 (95% CI 0.83-0.95), and 0.86 (95% CI 0.80-0.90), respectively. Meanwhile, 9 studies used ML for early prediction of the risk of CALs in children with KD. These studies involved a total of 6503 people with KD, of whom 986 had CALs. The pooled concordance index in the validation set was 0.787 (95% CI 0.738-0.835). The diagnostic and predictive factors used in the studies we included were primarily derived from common clinical data. The ML models constructed based on these clinical data demonstrated promising effectiveness in differentiating KD from other febrile illnesses and in predicting coronary artery lesions. Therefore, in future research, we can explore the use of ML methods to identify more efficient predictors and develop tools that can be applied on a broader scale for the differentiation of KD and the prediction of CALs.

A Case of Refractory Kawasaki Disease With Yersinia pseudotuberculosis Infection Successfully Treated With Cefotaxime Following Immunosuppressive Therapy

A Case of Refractory Kawasaki Disease With Yersinia pseudotuberculosis Infection Successfully Treated With Cefotaxime Following Immunosuppressive Therapy

Clinical analysis of systemic juvenile idiopathic arthritis with Kawasaki disease-like symptoms

Objective: To analyze the clinical characteristic of systemic juvenile idiopathic arthritis (sJIA) patients with Kawasaki disease like onset symptom. Methods: A retrospective case-control study was performed. A total of 24 patients with sJIA with Kawasaki disease-like symptoms in the Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University from January 2018 to August 2024 were selected as the Kawasaki disease combined with sJIA group. A total of 96 patients with Kawasaki disease as the Kawasaki disease group and 83 patients with sJIA were selected as the sJIA group. The general information, clinical manifestations, laboratory examinations and complications of the patients were compared between the three groups. Differences between groups were assessed by Mann-Whitney U test, Kruskal-Wallis H test and Chi-square test was used for counting data. Results: There were significant differences in age and fever course between Kawasaki disease combined with sJIA groups, Kawasaki disease groups, and sJIA groups (3.4 (2.5, 7.3) vs. 3.4 (1.9, 4.8) vs. 8.8 (5.1, 11.7) years, 24.5 (18.0, 37.3) vs. 23.0 (18.0, 31.0) vs. 7.0 (6.0, 8.0) d, Z=67.09, 138.24, both P<0.05). Among the 24 cases of Kawasaki disease combined with sJIA, 20 cases (83%) had joint symptoms and 9 cases (38%) had conjunctival congestion. There were significant differences in the incidence of coronary artery injury between Kawasaki disease combined with sJIA group, Kawasaki disease group and sJIA group (58% (14/24) vs. 44% (42/96) vs. 6% (5/83), χ2=40.50, P<0.05). There were significant differences in the risk of macrophage activation syndrome between Kawasaki disease combined with sJIA group, sJIA group and Kawasaki disease group (17% (4/24) vs. 10% (8/83) vs. 0 , χ2=16.91, P<0.05). In the Kawasaki disease combined with sJIA group, 11 cases (46%) did not respond after 2 courses of intravenous immunoglobulin (IVIG) treatment, and 21 cases (88%) used glucocorticoids. The use rate of high-dose hormones in the Kawasaki disease combined with sJIA group was higher than that in the sJIA group (29% (7/24) vs. 5% (4/83), χ2=12.95, P<0.05). In the Kawasaki disease combined with sJIA group, 17 cases (71%) used biological agents, 1 case used adalimumab, and 16 cases received tocilizumab treatment, of which 4 cases (25%) were allergic to tocilizumab. In the group of Kawasaki disease combined with sJIA, 11 patients (46%) treated with tocilizumab were followed up regularly for 1 month, and 10 patients were effective. Conclusions: Children with sJIA who present with Kawasaki disease-like clinical symptoms have clinical features of Kawasaki disease and sJIA. Children with Kawasaki disease who present at a young age, have a long fever course, are accompanied by joint symptoms, and are IVIG-resistant need to be alert to the possibility of sJIA and receive timely treatment with hormones and biological agents.

Concurrent Coxsackievirus A6 Infection and Kawasaki Disease: A Case Report

Background and Clinical Significance: Kawasaki disease (KD) is an acute febrile vasculitis that primarily affects children and is associated with systemic inflammation, particularly in the coronary arteries. Coxsackievirus A6 (CVA6) has emerged as a significant agent in atypical presentations of hand, foot, and mouth disease (HFMD), raising the possibility of its involvement in KD. Case Presentation: This report presents the case of an 18-month-old Thai boy admitted with symptoms of high fever, sore throat, and ulcerative lesions, initially diagnosed with herpangina. As his condition progressed, additional KD symptoms developed, including conjunctival injection, rash, and elevated inflammatory markers, fulfilling the diagnostic criteria for KD. Notably, throat swab analysis confirmed CVA6 as the causative agent. Phylogenetic analysis revealed that the CVA6 strain closely aligned with Chinese strains from 2023, showing a high nucleotide sequence homology of 98.4%. Conclusions: In conclusion, this case highlights a possible association between CVA6-associated herpangina and KD, suggesting that CVA6 infection may act as a trigger for KD in genetically susceptible children. These findings highlight the need for increased awareness among healthcare providers to promptly identify and manage Kawasaki Disease during peak enterovirus seasons, reducing its impact on children.

Different antithrombotic strategies to prevent cardiovascular complications in Kawasaki patients: a systematic review and meta-analysis

BackgroundCoronary 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.MethodsFollowing 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.ResultsThe 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.ConclusionsAs 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.

Macrophage Activation Syndrome in MIS-C.

Multisystem inflammatory syndrome (MIS-C) represents a diagnostic challenge because of its overlap with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome. Macrophage activation syndrome (MAS) is a frequently fatal complication of various pediatric inflammatory disorders and has been reported in MIS-C. Early diagnosis and prompt initiation by immune modulating therapies are essential for effectively managing MAS. We conducted a retrospective study to determine the frequency, natural history, diagnostic metrics, treatment, and outcome of MAS in MIS-C within a large cohort of patients across 84 Latin American centers in 16 countries. We compared the clinical and laboratory characteristics between patients with and without MAS. Among 1238 patients with MIS-C, 212 (17.1%) fulfilled MAS criteria. Gastrointestinal and neurologic manifestations were more frequent in cases where MIS-C was complicated by MAS. Patients presenting with MIS-C complicated by MAS had a mortality rate of 12%, which was higher than those without it. Mortality was associated with MAS, seizures, arthritis, and shock. A ferritin or erythrocyte sedimentation rate ratio of >18.7 exhibited a sensitivity of 88.2% and a specificity of 75% in diagnosing MAS in MIS-C. MAS in MIS-C patients is associated with increased morbidity and mortality rates in the largest MIS-C Latin American cohort. Early recognition and appropriate management are crucial in improving patient outcomes and reducing mortality rates.