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Kawasaki disease (KD) is a systemic vasculitis that affects young children and can result in coronary artery aneurysms. The etiology is currently unknown, but new clues from the epidemiology of KD in Japan, the country of highest incidence, are beginning to shed light on what may trigger this acute inflammatory condition. Additional clues from the global changes in KD incidence during the COVID-19 pandemic, coupled with a new birth cohort study from Japan, point to the potential role of person-to-person transmission of an infectious agent. However, the rising incidence of KD in Japan, with coherent waves across the entire country, points to an increasing intensity of exposure that cannot be explained by person-to-person spread. This Review discusses new and historical observations that guide us toward a better understanding of KD etiology and explores hypotheses and interpretations that can provide direction for future investigations. Once the etiology of KD is determined, accurate diagnostic tests will become available, and new, less expensive, and more effective targeted therapies will likely be possible. Clearly, solving the mystery of the etiologies of KD remains a priority for pediatric research.

BackgroundAbout 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features.MethodsData were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation.ResultsFive machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort.ConclusionsUsing commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility.ImpactWe demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.

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]

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]

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]

Objective: Rare disease. Background: Coronary artery aneurysms in patients with Kawasaki disease may develop acute myocardial infarction. It is challenging to achieve complete revascularization solely through percutaneous coronary intervention in these patients. Therefore, coronary artery bypass grafting is often necessary. Case Report: We present a case of a 68-year-old woman who developed multiple acute myocardial infarctions due to giant aneurysms formed in the right coronary artery (RCA) and the left circumflex artery (LCx). We diagnosed the cause of the aneurysms as Kawasaki disease based on the coronary angiogram, laboratory results, and family history. After the primary balloon angioplasty, we conducted coronary artery bypass grafting, which involved grafting 2 vessels to the LCx and 1 vessel to the RCA. The internal thoracic arteries, which are the standard graft vessels, were occluded, most likely due to Kawasaki disease vasculitis. Instead, we used saphenous vein grafts harvested using the "no-touch" technique, which preserves the perivascular adipose tissue, to improve the long-term patency. In addition, we ligated the LCx aneurysm to prevent occlusion of the grafts and rupture of the aneurysm. Four years after the uneventful discharge, the patient is in good health and coronary computed tomography angiography revealed good patency of all grafts. Conclusions: This report highlights a successful combination of "no-touch" saphenous vein grafting and coronary aneurysm ligation in an adult patient with Kawasaki disease. These techniques may be especially useful for this vasculitic illness which is often associated with occlusion of internal thoracic arteries. [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]

A 25-year-old man presented with a rash, headache, confusion, and speech problems following an upper respiratory tract infection. He exhibited various neurological symptoms and cutaneous manifestations resembling erythema nodosum. After extensive testing, he was diagnosed with Neuro-Sweet syndrome, a rare condition characterized by febrile neutrophilic dermatosis and neurological manifestations. Treatment with systemic corticosteroids led to significant improvement in his symptoms, highlighting the importance of early diagnosis and appropriate management in such cases. [Extracted from the article]

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms' pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical features of pediatric Kawasaki disease (KD) complicated with pleural effusion (PE) and construct a clinical prediction model. Methods A retrospective review was conducted on clinical data of 462 children with KD from June 2017 to June 2023. Eleven KD children with PE were selected as the KD-PE group, and 118 patients without PE were selected as the KD control group. Using propensity score matching, the clinical data including clinical manifestation, auxiliary examination, treatment process and complications were collected and analyzed. Univariate and Lasso-Logistic regression were used to analyze influence factors of PE in children with KD. A line chart model for predicting KD-PE was constructed, and the prediction efficiency of the model was evaluated. Results The respiratory symptoms were generally mild in the KD-PE group, with 10 cases exhibiting mild PE. Two variables of C-reactive protein (CRP, OR=1.045, 95%CI: 1.009-1.082) and albumin (ALB, OR=0.755, 95%CI: 0.591-0.964) were screened out by Lasso regression and multi-factor Logistic regression to construct the prediction model. The regression equation was Logit (P) = 2.221+0.044×CRP-0.281×ALB. The area under the ROC curve of the prediction model was 0.957 (95%CI: 0.911-1.000), and the Hosmer-Lemeshow test showed that the curve of the calibration model was well coincident with the curve of the actual model (χ2=4.320, P=0.827). The evaluation model using clinical decision curve and clinical impact curve had good clinical applicability. Conclusion KD complicated with PE in children is rare, elevated CRP is a risk factor for KD-complicated PE, and elevated ALB is a protective factor. The model has higher accuracy, discriminatory power and net benefit. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin (IVIg) has been used for almost 40 years in the treatment of autoimmune and systemic inflammatory diseases. Numerous cells are involved in the innate immune response, including monocytes/macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, natural killer cells, and innate lymphoid cells. Many studies have investigated the mechanisms by which IVIg down-modulates inflammatory and autoimmune processes of innate immune cells. However, questions remain regarding the precise mechanism of action in autoimmune or inflammatory conditions. The aim of this work was to review the immunomodulatory effect of IVIg on only human innate immune cells. A narrative review approach was chosen to summarize key evidence on the immunomodulatory effects of commercially available and unmodified IVIg on human innate immune cells. Summary: Numerous different immunomodulatory effects of IVIg have been reported, with some very different effects depending on the immune cell type and disease. Several limitations of the different studies were identified. Of the 77 studies identified and reviewed, 29 (37.7%) dealt with autoimmune or inflammatory diseases. Otherwise, the immunomodulatory effects of IVIg were studied only in healthy donors using an in vitro experimental approach. Some of the documented effects showed disease-specific effects, such as in Kawasaki disease. Various methodological limitations have also been identified that may reduce the validity of some studies. Key Message: As further insights have been gained into the various inflammatory cascades activated in immunological diseases, interesting insights have also been gained into the mechanism of action of IVIg. We are still far from discovering all the immunomodulatory mechanisms of IVIg. [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]

Introduction: Kawasaki 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 (FcgRs), 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 methods: We 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. Results: FCGR2A-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. Discussion: FCGR2/3 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. [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]

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 (< 10 µg/mL). Serum SA levels during the recovery period were significantly lower in patients who received steroids. There were no significant differences in IVIG responsiveness based on serum SA levels. Conclusions: Serum SA trough levels in KD patients treated with moderate-dose ASA were highly variable and did not reach sufficient levels. Serum SA levels were not associated with IVIG responsiveness. [ABSTRACT FROM AUTHOR]

Coronary artery aneurysms (CAAs) are uncommon but significant cardiovascular abnormalities characterized by an abnormal increase in vascular diameter. CAAs are classified based on their shape as either saccular or fusiform, and their causes can range from atherosclerosis, Kawasaki disease, to congenital and iatrogenic factors. CAAs often present asymptomatically, but when symptoms occur, they can include angina, myocardial infarction, or even sudden cardiac death due to intravascular thrombosis involving the CAA. Diagnosis is typically confirmed through coronary angiography, though CT and other imaging techniques can provide additional details. The management of CAAs is variable depending on their size, location, and the presence of symptoms or complications. Treatment options include medical therapy, percutaneous coronary intervention (PCI), or surgical approaches. In this paper, we describe the case report of a 79-year-old male who presented with palpitations and was diagnosed with a right coronary artery aneurysm, and a review of the literature is delineated, underscoring the importance of individualized treatment strategies for CAAs. [ABSTRACT FROM AUTHOR]

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C--two conditions presenting with overlapping symptoms--with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including antiinflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored. Methods: In this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism. Results: Our in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition. Conclusion: In conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future. [ABSTRACT FROM AUTHOR]

Background: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. Case presentation: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. Conclusions: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course. [ABSTRACT FROM AUTHOR]

Complex coronary atherosclerosis may exhibit different phenotypes of coronary plaques, from non-calcified highly vulnerable atheroma to heavily calcified ones. Computed coronary tomography angiography (CCTA) may identify these different phenotypes and the recently introduced CCTA-based techniques for mapping coronary inflammation along the coronary arteries may provide useful additional information on cardiovascular risk. Here we present the case of a 68-year-old male patient with acute coronary syndrome in whom invasive coronary angiography and CCTA revealed a severe three-vessel disease with a heavily calcified lesion. Mapping of the CT fat attenuation index along the coronary arteries identified a high level of coronary inflammation, especially associated with the non-calcified lesions. All lesions were successfully revascularized by implantation of drug-eluting stents. A cutting balloon was used for the lesion identified by CCTA as heavily calcified, followed by stent implantation, with good results. In conclusion, CCTA, in association with novel techniques for mapping coronary inflammation, may represent an extremely useful tool for preparing complex interventions in multivessel diseases, helping preprocedural planning in high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: Several studies have reported outbreaks of Kawasaki disease among children amid the coronavirus disease 2019 (COVID-19) pandemic. Vitamin D possesses high utility in modulating the immune system to repair and prevent severe inflammation in COVID-19. This study aims to explore the association between Kawasaki disease and vitamin D levels in pediatric patients and describe the potential role of vitamin D in promoting recovery and preventing complications associated with Kawasaki disease in pediatric patients with COVID-19. Materials and Methods: The association between Kawasaki disease and vitamin D was explored adhering to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) 2020 guidelines, utilizing databases such as PubMed, Google Scholar, and ScienceDirect. The association between COVID-19 and Kawasaki disease was also assessed by reviewing relevant literature. Results: Most studies indicated that patients with Kawasaki disease had lower vitamin D levels. Vitamin D supplementation was also found to be deficient in the pediatric population with Kawasaki disease. Inflammation of the endothelium, cytokine storms, and endothelial dysfunction in patients suffering from COVID-19 may contribute to the development of Kawasaki disease. Vitamin D is believed to have protective potential for Kawasaki disease outcomes by modulating the inflammatory response. Conclusion: Administering vitamin D to pediatric patients with viral infections like COVID-19 is expected to accelerate clinical improvement and prevent complications from Kawasaki disease. [ABSTRACT FROM AUTHOR]

A recent study published in the journal Pediatric Allergy & Immunology examined the incidence of allergic diseases in children who had previously been diagnosed with Kawasaki disease (KD). The study found that there was a delayed increase in allergic diseases in KD patients, suggesting a possible common underlying mechanism between KD and allergic diseases. The study utilized a large cohort and considered patient characteristics, making it unique from previous studies. The findings highlight the complex and multifactorial nature of allergic disease development and the importance of considering the dynamic nature of these patterns in epidemiological research. However, the study design using a nationwide insurance claim database has potential limitations, such as selection bias and data quality issues. [Extracted from the article]

Key Clinical Message: Kawasaki disease (KD), a self‐limiting vasculitis, can present with a broader spectrum of vascular involvements, necessitating early recognition and prompt management. This case exemplifies the importance of involving multiple teams on board in managing complex presentations of KD. It also highlights the importance of close monitoring for the progression of the disease spectrum as well as family education to ensure favorable outcomes. The case also emphasizes the importance of long‐term follow‐up and further research to understand the prognosis, early screening tools, and possible complications due to multi‐organ involvement in KD along with their management strategies. Kawasaki disease (KD) is a multisystem vascular inflammatory syndrome, which predominantly affects the small and medium vessels in children within the age group of less than 5 years. The most threatened complication is the development of coronary artery aneurysms (CAAs). We present an extremely rare case of KD in a 2‐month, 21‐day‐old male infant with extensive vascular involvement, expanding the disease spectrum beyond the involvement of coronary arteries. These included aneurysmal dilatations of both internal carotid arteries, the descending aorta, bilateral multilevel intercostal arteries, coeliac artery, superior mesenteric artery, and both renal arteries. Implementing a multidisciplinary approach with early treatment via intravenous immunoglobulin (IVIG) and dexamethasone proved to be most effective in the patient's management. Despite unique challenges such as severe coronary dilation and pseudomonas sepsis during the special care, the patient was stabilized and discharged after 11 days of hospital stay, highlighting the importance of early prompt management and a centered approach to evaluate in a broader spectrum. This case emphasizes the importance of long‐term follow‐up and further research to understand the prognosis, early screening tools, and possible complications due to multi‐organ involvement in KD along with their management strategies. [ABSTRACT FROM AUTHOR]

Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43−0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46− 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74− 0.90, p < 0.01). However, no significant difference was observed in the risk of developing KD when comparing partial breastfeeding to formula feeding exclusively. Regarding secondary outcomes, no statistically significant difference was found in the risk of CAL or IVIG resistance across any comparison formats. Our study suggests that breastfeeding correlated with a reduced risk of KD but not with a reduced risk of CAL or IVIG resistance. These findings advocate for the implementation of breastfeeding policies in clinical practice. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Purpose: 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. [ABSTRACT FROM AUTHOR]

Background Spontaneous coronary artery dissection (SCAD) is the most important cause of acute coronary syndromes during pregnancy and in the post-partum period and involves a spontaneous intimal tear or intramural haematoma of a coronary artery. Pregnancy-associated SCAD accounts for a minority of SCAD cases but is associated with a high rate of adverse events. Case summary We present a series of three cases with pregnancy-associated SCAD. All patients presented with acute coronary syndromes in the post-partum period, between 12 days and 5 months after delivery. They all had additional conditions that are associated with SCAD, such as fibromuscular dysplasia and migraine. The management of one patient was uncomplicated, however, the courses of the other two were characterized by adverse events. One presented after an out-of-hospital cardiac arrest, the other presented with multivessel SCAD and developed progression and recurrence of SCAD during follow-up. In conclusion, the patients could be successfully treated conservatively and were in good condition at their latest follow-ups. Discussion This case series highlights the wide range of clinical courses that could exist in pregnancy-associated SCAD, from a benign manifestation to a life-threatening condition. Importantly, those patients are at an increased risk for acute and late adverse events. [ABSTRACT FROM AUTHOR]

Background A sinus of Valsalva aneurysm involving a single cusp is a rare condition, and coronary computed tomography angiography with fractional flow reserve-computed tomography helps evaluate not only the anatomical aspects of the aneurysm and coronary artery but also the physiological details of coronary artery disease. Case summary A 71-year-old woman presented with exertional chest pain and dyspnoea. Enhanced computed tomography revealed an aneurysmal change in the right sinus of Valsalva, and coronary computed tomography angiography revealed diffuse narrowing of the proximal segment of right coronary artery due to mechanical stretching by the large Valsalva aneurysm. Fractional flow reserve-computed tomography revealed a significantly low fractional flow reserve (0.50 in the distal right coronary artery). A modified Bentall procedure was performed with a 21 mm bioprosthetic valve and a 24 mm Valsalva graft conduit for the aortic root aneurysm; mitral valve annuloplasty was performed for mitral valve regurgitation. Post-operative coronary computed tomography angiography revealed no significant stenosis in the proximal segment of the right coronary artery. Furthermore, fractional flow reserve-computed tomography revealed a normalized fractional flow reserve in the distal right coronary artery. The patient experienced relief from chest pain and was discharged 19 days after the surgery. Discussion A right coronary sinus of Valsalva aneurysm, which caused right coronary artery ischaemia, was successfully treated using a modified Bentall procedure. Coronary computed tomography angiography and fractional flow reserve-computed tomography revealed anatomical and functional improvements in the right coronary artery ischaemia post-operatively. [ABSTRACT FROM AUTHOR]

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a pediatric vasculitis, leading to coronary artery aneurysms (CAAs) in ~4–14%. Attention to the etiology and course of KD was generated by the close mimic of a SARS-CoV-2-induced phenotype, called multisystem inflammatory syndrome in children (MIS-C). Methods: A total of 1179 cases were collected from 2012 with ~50% of cases retrospectively included. Clinical characteristics were described and risk factors for CAA (persistence) were investigated. Phenotypic patterns of the prospectively included KD patients were evaluated. These patterns were also compared to the seronegative KD and seropositive MIS-C cases identified during the SARS-CoV-2 pandemic. Results: KD mostly affected boys and children < 5 years. IVIG resistance, CAAs, and giant CAAs occurred in 24.5%, 21.4%, and 6.6%, respectively. Giant CAAs were significantly more likely to normalize to a normal Z score in patients that were younger than 2.5 years old at the time of initial giant CAA (χ2 test p = 0.02). In our prospective (SARS-CoV-2-seronegative) KD series, there was a diminishing male predominance over time, whereas the proportions of incomplete presentations (p < 0.001) and patients with circulatory shock (p = 0.04) increased since the COVID-19 pandemic. Pre- and post-pandemic KD cases presented with different levels of C-reactive protein, thrombocyte counts, and hemoglobin levels over the years. Compared to pandemic KD, SARS-CoV-2-seropositive MIS-C patients were older (p < 0.001), and more often required intensive care admission (p < 0.001), with a gradual decrease over time between 2020 and 2022 (p = 0.04). KD carried a substantial risk of CAA development in contrast to MIS-C. Conclusion: the phenotypic changes seen over the last twelve years of our prospective follow-up study suggest a spectrum of hyperinflammatory states with potentially different triggering events within this clinical entity. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort. [ABSTRACT FROM AUTHOR]

Coronary artery aneurysm or ectasia (CAAE) is a term that includes both coronary artery ectasia (CAE) and coronary artery aneurysm (CAA), despite distinct phenotypes and definitions. This anomaly can be found in 0.15–5.3% of coronary angiography. CAE is a diffuse dilatation of the coronary artery at least 1.5 times wider than the diameter of the normal coronary artery in a patient with a length of over 20 mm or greater than one-third of the vessel. CAE can be further subdivided into diffuse and focal dilations by the number and the length of the dilated vessels. Histologically, it presents with extensive destruction of musculoelastic elements, marked degradation of collagen and elastic fibers, and disruption of the elastic lamina. Conversely, CAA is a focal lesion manifesting as focal dilatation, which can be fusiform (if the longitudinal diameter is greater than the transverse) or saccular (if the longitudinal diameter is smaller than the transverse). Giant CAA is defined as a 4-fold enlargement of the vessel diameter and is observed in only 0.02% of patients after coronary. An aneurysmal lesion can be either single or multiple. It can be either a congenital or acquired phenomenon. The pathophysiological mechanisms responsible for the formation of CAAE are not well understood. Atherosclerosis is the most common etiology of CAAE in adults, while Kawasaki disease is the most common in children. Other etiological factors include systemic connective tissue diseases, infectious diseases, vasculitis, congenital anomalies, genetic factors, and idiopathic CAA. Invasive assessment of CAAE is based on coronary angiography. Coronary computed tomography (CT) is a noninvasive method that enables accurate evaluation of aneurysm size and location. The most common complications are coronary spasm, local thrombosis, distal embolization, coronary artery rupture, and compression of adjacent structures by giant coronary aneurysms. The approach to each patient with CAAE should depend on the severity of symptoms, anatomical structure, size, and location of the aneurysm. Treatment methods should be carefully considered to avoid possible complications of CAAE. Simultaneously, we should not unnecessarily expose the patient to the risk of intervention or surgical treatment. Patients can be offered conservative or invasive treatment. However, there are still numerous controversies and ambiguities regarding the etiology, prognosis, and treatment of patients with coronary artery aneurysms. This study summarizes the current knowledge about this disease's etiology, pathogenesis, and management. [ABSTRACT FROM AUTHOR]

We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD). This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR. A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively. LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD), which is also known as cutaneous mucosal lymph node syndrome, is an acute, self-limiting, necrotizing vasculitis with unclear cause that primarily affects small- and medium-sized blood vessels and most commonly affects children aged 6 months to 5 years. Currently, diagnosis is based primarily on typical clinical symptoms. Approximately 15%–20% of patients are highly suspected of having KD; however, they do not match the diagnostic criteria for typical KD, which is referred to as incomplete Kawasaki disease (IKD), and this has become a major challenge in the diagnosis and treatment of KD. We describe a case of a 7-year-old boy who had a fever and jaundice as his initial symptoms. After a series of clinical laboratory and imaging examinations and marked improvement of symptoms after treatment with intravenous immunoglobulin (IVIG), IKD was considered as the diagnosis. When children present with jaundice and fever, physicians should consider KD as a possible diagnosis to ensure early detection and treatment of the disease. [ABSTRACT FROM AUTHOR]

Objective: The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD. Methods: One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed. Results: A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the-log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values. Conclusion: The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD. [ABSTRACT FROM AUTHOR]

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions. [ABSTRACT FROM AUTHOR]

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = −0.72, FDP: r = −0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin. [ABSTRACT FROM AUTHOR]

Background: Kawasaki Disease (KD) involves arterial inflammation, primarily affecting the coronary arteries and leading to coronary artery lesions. Recent advancements in understanding the immunomodulatory roles of vitamin D have prompted investigations into the potential correlation between serum vitamin D levels and the risk of coronary artery lesions (CAL) in KD. This review aims to explore this association. Methods: A systematic search utilizing relevant keywords related to Kawasaki disease and coronary artery lesions was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). The quality of the incorporated studies was assessed utilizing the Newcastle-Ottawa Scale. The study protocol is registered in PROSPERO under the registry code CRD42024493204. Results: In a review of five studies involving 442 KD patients and 594 healthy controls, KD patients generally had lower serum vitamin D levels compared to controls, with mixed findings on the association with coronary artery lesions and IVIG resistance. While three studies supported lower vitamin D in KD, one showed no significant difference. Regarding CAL, one study found lower vitamin D, another found higher levels associated with CAL, and two found no significant difference. Conclusions: Overall, the evidence is inconclusive, but there's a trend suggesting potential benefits of sufficient vitamin D levels in Kawasaki disease rather than evidence refuting any association with clinical outcomes. [ABSTRACT FROM AUTHOR]