Decreased incidence of Kawasaki disease in South Korea during the SARS-CoV-2 pandemic.

Purpose: Analyzing Kawasaki disease epidemiology during the SARS-CoV-2 pandemic in South Korea using 2012-2020 National Health Insurance Service data. Methods: The incidence of Kawasaki disease for 2012-2020 was investigated to identify changes in incidence after the start of the pandemic. National Health Insurance Service data from the Republic of Korea were used. Kawasaki disease was defined based on the International Statistical Classification of Diseases and Related Health Problems, the Tenth Revision diagnostic code (M30.3), and the intravenous immunoglobulin prescription code. Prescription history was collected for the following medications: intravenous immunoglobulin, aspirin, corticosteroids, tumor necrosis factor-α antagonist, clopidogrel, and anticoagulation drugs. Results: The Kawasaki disease incidence per 100,000 individuals younger than 5 years was 238.9, 230.0, and 141.2 in 2018, 2019, and 2020, respectively. Regarding the incidence from 2012 to 2020, it was the highest in 2018 and decreased to 141.2 (p < 0.001) in 2020, after the start of the pandemic. In 2020, 28.3% of all patients with KD were infants, a percentage significantly higher than that of the previous year (p < 0.001). There was biphasic seasonality in the monthly Kawasaki disease incidence. The Kawasaki disease incidence was the highest in winter followed by that in early summer. Conclusion: After the start of the pandemic, the Kawasaki disease incidence decreased, and the percentage of patients with Kawasaki disease aged <1 year increased. These findings provide support for the hypothesis suggesting an infectious trigger in Kawasaki disease.

Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.

Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children.

BACKGROUND: Kawasaki disease shock syndrome (KDSS), though rare, has increased risk for cardiovascular complications. Early diagnosis is crucial to improve the prognosis of KDSS patients. Our study aimed to identify risk factors and construct a predictive model for KDSS. METHODS: This case-control study was conducted from June, 2015 to July, 2023 in two children's hospitals in China. Children initially diagnosed with KDSS and children with Kawasaki disease (KD) without shock were matched at a ratio of 1:4 by using the propensity score method. Laboratory results obtained prior to shock syndrome and treatment with intravenous immunoglobulin were recorded to predict the onset of KDSS. Univariable logistic regression and forward stepwise logistic regression were used to select significant and independent risk factors associated with KDSS. RESULTS: After matching by age and gender, 73 KDSS and 292 KD patients without shock formed the development dataset; 40 KDSS and 160 KD patients without shock formed the validation dataset. Interleukin-10 (IL-10) > reference value, platelet counts (PLT) < 260 × 109/L, C-reactive protein (CRP) > 80 mg/ml, procalcitonin (PCT) > 1ng/ml, and albumin (Alb) < 35 g/L were independent risk factors for KDSS. The nomogram model including the above five indicators had area under the curves (AUCs) of 0.91(95% CI: 0.87-0.94) and 0.90 (95% CI: 0.71-0.86) in the development and validation datasets, with a specificity and sensitivity of 80% and 86%, 66% and 77%, respectively. Calibration curves showed good predictive accuracy of the nomogram. Decision curve analyses revealed the predictive model has application value. CONCLUSIONS: This study identified IL-10, PLT, CRP, PCT and Alb as risk factors for KDSS. The nomogram model can effectively predict the occurrence of KDSS in Chinese children. It will facilitate pediatricians in early diagnosis, which is essential to the prevention of cardiovascular complications.

Single-Cell Transcriptome Reveals Potential Mechanisms for Coronary Artery Lesions in Kawasaki Disease.

BACKGROUND: Coronary artery lesions (CALs) are the most common and major complication of Kawasaki disease (KD) in developed countries. However, the underlying immunologic mechanisms of CAL development in KD remain unclear. METHODS: Here, we conducted single-cell transcriptome analyses of 212 210 peripheral blood mononuclear cells collected from a cross-sectional cohort of 16 children, including 4 patients with KD with CALs, 5 patients with KD without CALs, 4 healthy controls, and 3 febrile controls. RESULTS: KD altered the proportion of peripheral blood mononuclear cells, including an increasing trend in inflammatory cells (megakaryocytes and monocytes) and a decreasing trend in lymphocytes (eg, CD4+ T, CD8+ T, mucosal-associated invariant T, natural killer, and γδ T cells), highlighting the potential presence of lymphopenia phenomenon in KD. Our data indicated the presence of inflammatory cytokine storm in patients with KD with CALs, caused by systemic upregulation of TNFSF13B (tumor necrosis factor superfamily member 13b), CXCL16 (C-X-C motif chemokine ligand 16), TNFSF10 (tumor necrosis factor superfamily member 10), and IL1RN (interleukin 1 receptor antagonist), mainly produced by monocytes (especially for the Mono_CD14-CD16 cluster) and megakaryocytes. We also found that myeloid cells of patients with KD, particularly in those with CALs, might play a role in vascular injury (eg, increased MMP [matrix metalloproteinase] 9, MMP17, and MMP25) and immune cell recruitment. The immune landscape of patients with KD with CALs was featured by lower exhaustion levels in natural killer cells, a high cytotoxic state in the CD8_Pro cluster, and activation of the complement system in monocytes. Additionally, the activation of B cells was more pronounced in the early stage of KD. CONCLUSIONS: Collectively, this study provides a comprehensive understanding of the roles of various immune cells and inflammatory cytokine storms in the development of CALs in KD and offers a valuable resource for identifying novel therapeutic targets for patients with KD with CALs.

Enfermedad de Kawasaki. Presentación atípica en un paciente pediátrico

La enfermedad de Kawasaki es un síndrome mucocutáneo caracterizado por vasculitis, que afecta medianos vasos; su principal manifestación es un síndrome febril agudo de, al menos, cinco días de duración y en muchas ocasiones de etiología desconocida. Se aprecia, fundamentalmente, en niños menores de cinco años de edad. Se considera que es frecuente, pero existen subregistros. Se caracteriza por tener dos formas de presentación: típica o atípica. Se presenta el caso clínico de un niño que fue hospitalizado debido a síndrome febril agudo asociado a malestar general e irritabilidad. Al examen físico se observaron edemas discretos en manos y pies así como erupción cutánea, no hepatomegalia ni alteraciones oculares. Teniendo en cuenta la epidemiología, lo atípico del cuadro clínico y los resultados de estudios hemoquímicos, se concluyó el diagnóstico de enfermedad de Kawasaki atípica. Se impuso tratamiento específico y se logró una evolución satisfactoria y la no aparición de complicaciones inmediatas. Esta entidad nosológica requiere de una adecuada valoración clínica-epidemiológica de los pacientes, así como de un minucioso examen físico y un diagnóstico precoz para lograr la evolución favorable de los pacientes y la no presencia de secuelas cardiacas, que pondrían en peligro la vida del paciente y/o su calidad de vida futura.

Kawasaki disease (KD) is a mucocutaneous syndrome characterized by vasculitis that affects medium vessels; its main manifestation is an acute febrile syndrome lasting at least five days and often of unknown etiology. It appears mainly in children under five years of age, it is considered to be frequent, but there are underreportings. It is characterized by having two presentation forms: typical or atypical. The clinical case of a child who was hospitalized due to acute febrile syndrome associated with malaise and irritability is presented. The physical examination revealed discrete edema in the hands and feet as well as a rash, no hepatomegaly or ocular alterations. Taking into account the epidemiology, the atypical clinical picture and the results of hemochemical studies, the diagnosis of atypical Kawasaki disease was concluded. Specific treatment was imposed and a satisfactory evolution was achieved with no immediate complications. This nosological entity requires an adequate clinical-epidemiological evaluation of the patients, as well as a meticulous physical examination and an early diagnosis to achieve a favorable patients' evolution and the absence of cardiac sequelae, which would endanger the patients' life and/or their future quality of life.

The risk of pediatric cardiovascular diseases in offspring born to mothers with systemic lupus erythematosus: a nationwide study.

Background: Systemic lupus erythematosus (SLE), a common autoimmune disease predominantly affecting women, has been linked to various complications during pregnancy. The transfer of anti-Ro/SSA antibodies from SLE-affected mothers to their offspring can lead to neonatal lupus and cardiac issues. This study investigated the association between maternal SLE and the risk of pediatric cardiovascular disorders. Methods: The study utilized South Korea's National Health Insurance Service (NHIS) database, covering 3,505,737 children born between 2007 and 2017 and tracked until 2020. Maternal SLE cases were identified using the World Health Organization's International Classification of Diseases Tenth revision (ICD-10) codes and linked with delivery records. Cardiologic disorders were categorized into congenital heart disease (CHD), arrhythmic disorders, and acquired heart disease. Propensity score matching with 1:4 ratios was applied to the set control group. Results: Among 3,505,737 children, 0.7% (n = 23,330) were born to mothers with SLE. The incidence of preterm birth was significantly higher in the maternal SLE group (5.9% vs. 3.0%). Compared with the control group, children born to mothers with SLE exhibited a significantly elevated risk of overall CHDs (5.5%, adjusted odds ratio [aOR] 1.21; 95% confidence interval [CI] 1.14-1.29), including atrial septal defect (1.18; 1.09-1.28) and patent ductus arteriosus (1.15; 1.03-1.30). In addition, a notably higher risk was observed in arrhythmic disorders (complete atrioventricular block 7.20; 2.41-21.49) and acquired cardiac disorders, including cardiomyopathy (1.40; 1.17-1.68) and mucocutaneous lymph node syndrome (MCLS) (1.27; 1.15-1.43). Conclusions: Maternal SLE is associated with congenital and acquired cardiac disorders in offspring, including structural, arrhythmic, and MCLS. This study highlights the need for continuous cardiovascular monitoring from the prenatal stage to preadolescence in these children due to multifactorial influences involving maternal autoantibodies, genetic predisposition, and environmental factors.

Prediction nomogram for coronary artery aneurysms at one month in Kawasaki disease.

BACKGROUND: Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD. METHODS: Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed. RESULTS: LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911-0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001). CONCLUSION: Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.

Self-navigated coronary MR angiography for coronary aneurysm detection in Kawasaki disease at 3T: comparison with conventional diaphragm-navigated coronary MR angiography.

OBJECTIVES: To assess the scan time, image quality, and diagnostic performance of self-navigated coronary MR angiography (SN-CMRA) for coronary aneurysm (CAA) detection in Kawasaki disease (KD) patients and compare it with diaphragm-navigated CMRA (DN-CMRA). MATERIALS AND METHODS: SN-CMRA and DN-CMRA were performed on 76 pediatric patients with KD (48 males, 6.75 ± 3.59 years). Thirty-three of whom underwent coronary CT angiography (CCTA)/invasive coronary angiography (ICA). The scan time and qualitative and quantitative image quality assessment were compared between the two sequences. The diagnostic performance for CAA detection by the two approaches using CCTA/ICA as the reference standard was compared on per-patient, per-vessel, and per-segment basis. RESULTS: The scan time of SN-CMRA was significantly shorter than that of DN-CMRA (7.49 ± 2.31 min vs. 10.03 ± 4.47 min, p < 0.001). There was no difference in overall and segmental image quality to reach the clinical diagnostic criteria between the two sequences (all p > 0.05). No significant difference in vessel length of the three main coronary arteries was found between the two approaches (all p > 0.05). Moreover, SN-CMRA showed no difference from DN-CMRA in contrast ratio of blood-myocardium (1.25 (interquartile range [IQR], 1.06 to 1.51) vs. 1.18 (IQR, 0.95 to 1.64), p = 0.706). There was no difference in the diagnostic accuracy of SN-CMRA and DN-CMRA for CAA detection on per-patient, per-vessel, or per-segment basis (all p > 0.05). CONCLUSION: SN-CMRA at 3T showed reliable diagnostic performance and application value for CAA detection in children with KD. Compared with DN-CMRA, SN-CMRA can simplify the scanning procedure and shorten the scan time, achieving comparable image quality and diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: Coronary aneurysm in children with Kawasaki disease (KD) can be detected by self-navigated coronary MR angiography (CMRA) non-invasively and without radiation, achieving comparable image quality and diagnostic performance as diaphragm-navigated CMRA while shortening scanning time. It can provide reference for risk stratification and treatment management of KD. KEY POINTS: • Evaluating the size of coronary aneurysm is important for risk stratification and treatment of Kawasaki disease. • Self-navigated coronary MR angiography (SN-CMRA) shortens scan time and achieves comparable image quality and diagnostic performance compared with diaphragm-navigated coronary MR angiography. • SN-CMRA can evaluate coronary aneurysm non-invasively and without radiation, providing information for risk stratification and treatment.

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers.

BACKGROUND: Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting similar underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role in the shared pathologies of KD and MIS-C; however, the associated pathogenic mechanisms and molecular drivers remain unknown. METHODS: We performed a single-cell meta-analysis of neutrophil activation with 103 pediatric single-cell transcriptomic peripheral blood mononuclear cell data across 9 cohorts, including healthy controls, KD, MIS-C, compared with dengue virus infection, juvenile idiopathic arthritis, and pediatric celiac disease. We used a series of computational analyses to investigate the shared neutrophil transcriptional programs of KD and MIS-C that are linked to systemic damage and cardiac pathologies, and suggested Food and Drug Administration-approved drugs to consider as KD and MIS-C treatment. RESULTS: We meta-analyzed 521 950 high-quality cells. We found that blood signatures associated with risks of cardiovascular events are enriched in neutrophils of KD and MIS-C. We revealed the expansion of CD177+ neutrophils harboring hyperactivated effector functions in both KD and MIS-C, but not in healthy controls or in other viral-, inflammatory-, or immune-related pediatric diseases. KD and MIS-C CD177+ neutrophils had highly similar transcriptomes, marked by conserved signatures and pathways related to molecular damage. We found the induction of a shared neutrophil expression program, potentially regulated by SPI1 (Spi-1 proto-oncogene), which confers enhanced effector functions, especially neutrophil degranulation. CD177 and shared neutrophil expression program expressions were associated with acute stages and attenuated during KD intravenous immunoglobulin treatment and MIS-C recovery. Network analysis identified hub genes that correlated with the high activation of CD177+ neutrophils. Disease-gene association analysis revealed that the KD and MIS-C CD177+ neutrophils' shared expression program was associated with the development of coronary and myocardial disorders. Last, we identified and validated TSPO (translocator protein) and S100A12 (S100 calcium-binding protein A12) as main molecular targets, for which the Food and Drug Administration-approved drugs methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, and zolpidem, among others, are primary candidates for drug repurposing. CONCLUSIONS: Our findings indicate that CD177+ neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory drivers of CD177+ neutrophil hyperactivation and pathogenicity that may be targeted as a single therapeutic strategy for either KD or MIS-C.

Prednisolone versus cyclosporine as initial treatment for Kawasaki disease.

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

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Multisystem inflammatory syndrome in children and Kawasaki disease; comparison of their clinical findings and one-year follow-up-a cross-sectional study.

BACKGROUND: Studies on Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease (KD) have yielded inconsistent results and are lacking in Asian and African countries. This study aimed to compare the laboratory and clinical features, short-term outcomes, and one-year follow-ups of a large cohort of MIS-C and KD patients. METHODS: Data from 176 MIS-C and 56 KD patients admitted to Tehran Children's Medical Center between January 2021 and January 2022 were collected. Patients were followed up until January 2023. RESULTS: While lymphopenia and thrombocytopenia were more prevalent in MIS-C (73.2% vs. 20% in KD, p < 0.001), KD patients exhibited a higher median white blood cell count and prevalence of anemia, along with higher fibrinogen and erythrocyte sedimentation rate levels (p < 0.001, p < 0.001, p = 0.005, p < 0.001, respectively). MIS-C patients also exhibited lower ejection fraction, a greater occurrence of pericardial effusion, and a higher incidence of coronary aneurysms and ectasia, and ascites. Echocardiography after seven days of treatment showed a reduction in pathologies for both groups, but it was significant only for MIS-C. After one year, coronary artery abnormalities remained in only six cases. CONCLUSIONS: In conclusion, this study highlights differences between MIS-C and KD, including laboratory indices as well as echocardiographic and abdominal ultrasound findings. These findings contribute valuable data on Iranian patients to the existing literature on this topic and have significant implications for accurate diagnosis and improved management of pediatric patients presenting with these conditions.

Comparison of Clinical Manifestations of Kawasaki Disease According to SARS-CoV-2 Antibody Positivity.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in paediatric patients, with infectious agents being the main cause. This study aimed to determine whether there are differences in the clinical manifestations of KD between patients with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: From January 1, 2021 to August 15, 2022, 82 patients with analysable echocardiographic data were diagnosed with KD. Twelve patients with multisystem inflammatory syndrome in children were excluded. Serologic tests were performed by chemiluminescence immunoassay for both the nucleocapsid (N) and the spike (S) proteins in blood samples. Among the 70 patients diagnosed with KD at Jeonbuk University Children's Hospital, the SARS-CoV-2 antibody test was performed in 41 patients. RESULTS: The SARS-CoV-2 antibody test results for the N antigen were positive in 12 patients, while those for S protein were positive in 14 patients. N antigen SARS-CoV-2 antibody-positive KD was different from N antigen SARS-CoV-2 antibody-negative KD in terms of sex (male predominance in the positive group, 83.3% vs. female predominance in the negative group 62.1%, P = 0.008) and the incidence of refractory KD (41.7% vs. 10.3%, P = 0.034). The pro-B-type natriuretic peptide level was lower in the N-antigen SARS-CoV-2 antibody-positive KD group than that in the negative group (518.9 ± 382.6, 1,467.0 ± 2,417.6, P = 0.049). No significant differences in the echocardiographic findings between both groups were noted. In the multi-variable analysis, SARS-CoV-2 antibody (N antigen) was the only predictor of refractory KD (odds ratio, 13.70; 95% confidence interval, 1.63-115.44; P = 0.016). CONCLUSION: High incidence of intravenous immunoglobulin-refractory KD may occur in up to 40% of the patients having recent history of coronavirus disease 2019. For patients having KD with N-type SARS-CoV-2 antibody positivity, adjunctive treatment, such as corticosteroids, can be considered as the first line of treatment.

Novel Score to Predict Immunoglobulin Resistance in Kawasaki Disease.

To evaluate existing scoring systems and develop a new model to predict intravenous immunoglobulin (IVIG) resistance in patients with Kawasaki disease (KD). A retrospective cohort study performed between 2004 and 2017 identified 115 patients treated with IVIG for classic or incomplete KD. In our practice, IVIG resistance was defined as fever for > 24 h and patients were divided into responders and non-responders. A univariate analysis was performed to identify independent predictors of IVIG resistance. The predictors were combined into a new scoring system and compared with existing scoring systems. Sixty-five patients had classic KD and 50 had incomplete KD. Among the 115 patients, 80 (69.6%) responded and the remaining 35 were resistant (30.4%) to IVIG. Of the 35 resistant patients, 16 patients had incomplete KD. Hispanic children comprised 43% of our sample population. Coronary artery abnormalities developed in 14 of the 35 IVIG-resistant patients (39%). Univariate analysis showed that IVIG-resistant patients were older and present with lower platelets, potassium, and creatinine (P < 0.05). Multivariate logistic regression analysis used platelets, potassium, body surface area (BSA), and creatinine to devise the Las Vegas Scoring System (LVSS), which demonstrated a sensitivity of 76.2% and a specificity of 68.6%. Compared to published data, we observed a higher rate of IVIG resistance and coronary artery abnormalities in our patient population. The LVSS (using platelets, potassium, BSA, and creatinine) showed higher specificity and comparable sensitivity to other scoring systems devised to predict IVIG resistance.

A Ukrainian infant with giant coronary aneurysms: A case report and literature review.

Key Clinical Message: COVID may manifest multisystem inflammatory syndrome in children (MIS-C) which mimics Kawasaki disease (KD). Differentiating KD and MIS-C is difficult. Immunomodulatory treatment should be initiated promptly without accurate diagnosis. Abstract: A febrile Ukrainian infant developed giant aneurysms in coronary arteries. Differentiating between Kawasaki disease and multisystem inflammatory syndrome in children was difficult. In both illnesses, coronary aneurysm may develop unless treated promptly. Therefore, guidelines should synthesize these clinical entities so that treatment can be initiated before rigorous diagnosis.

Unexpectedly high incidence of Kawasaki Disease in a Canadian Atlantic Province- an 11-year retrospective descriptive study.

BACKGROUND: Kawasaki Disease (KD) is the leading cause of acquired heart disease in children in developed countries with a variable incidence worldwide. Previous studies reported an unexpectedly high incidence of KD in the Canadian Atlantic Provinces. The goals of our study were to validate this finding in the province of Nova Scotia and to carefully review patients' characteristics and disease outcomes. METHODS: This was a retrospective review of all children < 16 years old from Nova Scotia diagnosed with KD between 2007-2018. Cases were identified using a combination of administrative and clinical databases. Clinical information was collected retrospectively by health record review using a standardized form. RESULTS: Between 2007-2018, 220 patients were diagnosed with KD; 61.4% and 23.2% met the criteria for complete and incomplete disease, respectively. The annual incidence was 29.6 per 100,000 children < 5 years. The male to female ratio was 1.3:1 and the median age was 3.6 years. All patients diagnosed with KD in the acute phase received intravenous immunoglobulin (IVIG); 23 (12%) were refractory to the first dose. Coronary artery aneurysms were found in 13 (6%) patients and one patient died with multiple giant aneurysms. CONCLUSION: We have confirmed an incidence of KD in our population which is higher than that reported in Europe and other regions of North America despite our small Asian population. The comprehensive method to capture patients may have contributed to the detection of the higher incidence. The role of local environmental and genetic factors also deserves further study. Increased attention to regional differences in the epidemiology of KD may improve our understanding of this important childhood vasculitis.

[Diagnosis and management of Kawasaki disease]. / Maladie de Kawasaki infantile : diagnostic et prise en charge.

DIAGNOSIS AND MANAGEMENT OF KAWASAKI DISEASE. Kawasaki disease (KD) is a multi-systemic vasculitis predominantly affecting children under 5 years of age. KD's incidence is 30 times higher in Asia than in France. Elective lesional tropism for coronary arteries makes it the leading cause of acquired heart disease in children in developed countries. Diagnosis is based on the presence of fever of 5 days or more and the presence of at least for clinical criteria of cutaneous-mucosal inflammation. KD is believed to be the result of an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. Timely initiation of treatment with intravenous immunoglobulin has reduced the incidence of coronary artery aneurysms from 25% to 5%. Severe KD requires rapid treatment intensification. Coronary artery lesions are the main determinant of the prognosis. Acute coronary syndrome in adults can be a result of long-term sequelae of the disease. Different imaging techniques are required to adequately follow these patients according to the American Heart Association recommendations.

MALADIE DE KAWASAKI INFANTILE: DIAGNOSTIC ET PRISE EN CHARGE. La maladie de Kawasaki est une vascularite multisystémique qui touche principalement les enfants de moins de 5 ans. Son incidence est 30 fois plus élevée en Asie qu'en France. Son tropisme lésionnel électif pour les artères coronaires en fait la première cause de cardiopathie acquise chez l'enfant dans les pays développés. Le diagnostic est suspecté devant une fièvre de cinq jours ou plus associée à au moins quatre critères cliniques d'inflammation cutanéo-muqueuse. Elle est probablement liée à des agents infectieux entraînant une réponse inflammatoire inappropriée chez un sujet prédisposé. La précocité de la prise en charge par immunoglobulines intraveineuses diminue l'incidence des atteintes coronaires de 25 à 5 %. Les formes sévères nécessitent une intensification thérapeutique d'emblée. Son pronostic est corrélé à la survenue de lésions coronariennes et à leur évolution. Les complications coronariennes peuvent se traduire, à l'âge adulte, par un syndrome coronaire aigu secondaire à des séquelles de la maladie. Différentes techniques d'imagerie permettent de suivre les patients, selon les recommandations de l'American Heart Association.

Clinical symptoms of patients with Kawasaki disease include smoldering fever.

BACKGROUND: Persistent low-grade fever has been observed in some patients during intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD); however, smoldering fever (SF) has not previously been reported in patients with KD. This study aimed to clarify the clinical characteristics of SF in patients with KD. METHODS: A single-center retrospective cohort study, which included a total of 621 patients who received IVIG therapy, was conducted. Patients with a fever of 37.5-38°C lasting ≥3 days after 2 days of the initial-IVIG were defined as the SF group. Patients were divided into four groups according to the fever course: SF (n = 14), biphasic fever (BF, n = 78), non-fever after initial-IVIG (NF, n = 384), and persistent fever (PF, n = 145). The clinical features of SF were described and compared between the groups. RESULTS: The median duration of fever in the SF group was 16 days, which was longer than that in any other group. The neutrophil fraction after IVIG therapy in the SF group was higher than that in the BF and NF groups but similar to that in the PF group. Repeated IVIG administration in the SF group resulted in increased IgG levels but decreased serum albumin levels. In the SF group, 29% of the patients had coronary artery lesions at 4 weeks. CONCLUSIONS: The frequency of SF in KD was 2.3%. Patients with SF continued to have moderate inflammatory responses. Repeated administration of IVIG doses was not effective in treating SF, and acute coronary artery lesions were occasionally observed. Active therapeutic intervention was needed.

Z-score regression model for coronary artery diameter in healthy Chinese Han children.

BACKGROUND: Coronary artery distension and aneurysm are complications of Kawasaki disease in children. PURPOSE: To develop a Z-score regression model for coronary artery diameter in children that could be used as reference. MATERIAL AND METHODS: This retrospective analysis included children with normal heart structure between March 2013 and April 2017. Body surface area (BSA) was calculated. The diameters of the right coronary, left main coronary, left anterior descending, and circumflex arteries were measured by echocardiography. Pearson correlation analysis was used to establish linear, exponential, logarithmic, power, and square root regression models. RESULTS: The analysis included 509 children (280 boys) aged 1 day to 15.2 years. Coronary artery diameters were significantly correlated with age, height, body mass, BSA, and BSA (r = 0.663-0.826; P < 0.05), with a stronger correlation for BSA than BSA (P < 0.05). The adjusted determination coefficients (Ra2) were higher for the exponential and square root models than for the other models (P < 0.05). The random error term variance was constant for the exponential model (P > 0.05), and processing with the weighted least-square methods eliminated heteroscedasticity in the other models. The Z-scores were normally distributed for the exponential and square root models (P > 0.05). CONCLUSION: Overall, the square root model was the optimal equation for the calculation of coronary artery Z-score in Chinese Han children. This model could be used to facilitate the diagnosis of coronary artery distension in children with suspected Kawasaki disease.