INTRODUCTION: Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD). METHOD: A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers. RESULTS: Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60). CONCLUSION Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans ; Takayasu Arteritis/complications* ; Singapore/epidemiology* ; Male ; Female ; Child ; Adolescent ; Age of Onset ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Cohort Studies ; Child, Preschool ; Fever/etiology* ; Stroke/epidemiology* ; Retrospective Studies

Kawasaki disease (KD) is an acute self-limiting vasculitis, and it is the most common cause of acquired heart disease in children under 5 years old. One of the improvement goals in pediatric quality control work for the year 2023, as announced by the National Health Commission, is to reduce the incidence of cardiac events and KD-related mortality in children with KD. In order to standardize the diagnosis, treatment, and long-term management practices of KD in China, and effectively prevent and reduce the incidence of coronary artery lesions and long-term adverse effects, the guideline working group followed the principles and methods outlined by the World Health Organization and referenced existing evidence and experiences to develop the "Evidence-based guidelines for the diagnosis and treatment of Kawasaki disease in children in China (2023)". The guidelines address the clinical questions regarding the classification and definition of KD, diagnosis of different types of KD, treatment during the acute phase of KD, application of echocardiography in identifying complications of KD, and management of KD combined with macrophage activation syndrome. Based on the best evidence and expert consensus, 20 recommendations were formulated, aiming to provide guidance and decision-making basis for healthcare professionals in the diagnosis and treatment of KD in children.
Child ; Humans ; Child, Preschool ; Mucocutaneous Lymph Node Syndrome/complications* ; Vasculitis/drug therapy* ; Heart ; Heart Diseases ; China ; Immunoglobulins, Intravenous/therapeutic use*

Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.
Child ; Humans ; Mucocutaneous Lymph Node Syndrome/complications* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Polymorphism, Genetic ; Coronary Vessels/pathology* ; Polymorphism, Single Nucleotide

OBJECTIVES: To investigate the clinical features and treatment strategies of multisystemic inflammatory syndrome in children (MIS-C) after severe acute respiratory syndrome coronavirus 2 infection. METHODS: A retrospective analysis was performed on the medical data of four children with MIS-C who were admitted to the Department of Cardiology, Xuzhou Children's Hospital, Xuzhou Medical Universityfrom January to February 2023. RESULTS: All four children had multiple organ involvements and elevated inflammatory markers, with a poor response to standard therapy for Kawasaki disease after admission. Two children were treated with intravenous immunoglobulin therapy pulse therapy twice, and all four children were treated with glucocorticoids. The children had a good prognosis after the treatment. CONCLUSIONS MIS-C often appears within 4-6 weeks or a longer time after severe acute respiratory syndrome coronavirus 2 infection, and anti-inflammatory therapy in addition to the standard treatment regimen for Kawasaki disease can help to achieve a favorable treatment outcome.
Child ; Humans ; COVID-19/complications* ; SARS-CoV-2 ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies ; Systemic Inflammatory Response Syndrome/therapy*

We reported a pediatric case of Kawasaki disease complicated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from Beijing Tsinghua Changgung Hospital. The clinical data were retrospectively analyzed and the related literature was reviewed. The clinical features, treatment and prognosis of the disease were summarized to improve recognition of Kawasaki disease complicated with MERS. A 7-year-old boy was diagnosed with Kawasaki disease due to continuous high fever for 6 d, accompanied by strawberry tongue, conjunctival congestion, erythema-like hyperemia rash, and cervical enlarged lymph nodes. And treatment was started with intravenous immunoglobulin (IVIG: 2 g/kg) and oral aspirin [40 mg/(kg·d)]. Twenty-four hours after the treatment of IVIG, the patient' s fever persisted and in addition he developed headache and drowsiness. His cranial magnetic resonance imaging (MRI) demonstrated a localized lesion in the splenium of the corpus callosum with high intensity signal on diffusion-weighted images (DWI) and T2-weighted, and low intensity signal on apparent diffusion coefficient (ADC) and T1-weighted. Based on these findings, he was diagnosed with MERS-complicated Kawasaki disease. Methylprednisolone [2 mg/(kg·d)] treatment was started intravenously, and within several hours he was afebrile and the neurological symptoms disappeared. A follow-up MRI was conducted after 1 week was normal. He was discharged without any neurological sequelae and coronary artery lesions. A total of 12 qualified foreign literature were retrieved, with no Chinese literature searched. Seventeen children were reported, the median age was 6.5 years (range: 1-14 years), among them 11 cases were children over 5 years old, and 4 cases were complicated with coronary artery lesions. All children had neurological symptoms, such as consciousness disorder, visual hallucination or convulsion. MRI conformed to MERS imaging changes. After active treatment, the neurological manifestations and radiological abnormalities completely disappeared, leaving no neurological sequelae. Kawasaki disease complicated with MERS had not been reported in China by now. Literature that identified Kawasaki disease complicated with MERS mostly occurred in children over 5 years old. Cranial MRI examination is helpful for early diagnosis. Timely treatment can reverse MERS in a short time, without neurological sequelae left.
Brain Diseases/diagnosis* ; Child ; Child, Preschool ; Encephalitis/pathology* ; Fever ; Humans ; Hyperplasia/complications* ; Immunoglobulins, Intravenous/therapeutic use* ; Magnetic Resonance Imaging ; Male ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Retrospective Studies

Humans ; Coronary Aneurysm/etiology* ; Mucocutaneous Lymph Node Syndrome/complications* ; Hemodynamics ; Coronary Angiography ; Thrombosis ; Risk Assessment

Child ; Coronary Artery Disease/etiology* ; Humans ; Immune System Diseases ; Mucocutaneous Lymph Node Syndrome/complications*

OBJECTIVE: To study the clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA). METHODS: A total of 77 KD children who were diagnosed with multiple small/medium-sized CAAs by echocardiography between January 2013 and June 2018 were enrolled. They were randomly divided into observation group with 38 children (treated with clopidogrel and aspirin) and control group with 39 children (treated with low-molecular-weight heparin and aspirin). All children were followed up regularly, and the first 3 months of the course of the disease was the observation period. The children were observed in terms of the change of the coronary artery and the incidence of complications. RESULTS: At month 3 of follow-up, among the children in the observation group, 6 had normal coronary artery, 11 had coronary artery retraction, 19 had stable coronary artery, and 2 progressed to giant coronary aneurysm; among the children in the control group, 7 had normal coronary artery, 12 had coronary artery retraction, 19 had stable coronary artery, and 1 progressed to giant coronary aneurysm; there was no significant difference in the change of the coronary artery between the two groups (P>0.05). There were 2 cases of epistaxis and 6 cases of skin ecchymosis in the observation group, and 1 case of epistaxis and 7 cases of petechiae and ecchymosis at the injection site in the control group, and no other serious bleeding events were observed in either group. CONCLUSIONS Clopidogrel combined with low-dose aspirin is safe and effective in antithrombotic therapy for children with KD complicated by CAA.
Aspirin ; therapeutic use ; Child ; Clopidogrel ; Coronary Aneurysm ; drug therapy ; etiology ; Coronary Vessels ; Fibrinolytic Agents ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications

INTRODUCTION: Kawasaki disease (KD) is a challenging diagnosis. Erythema and induration of the Bacillus Calmette-Guérin (BCG) site is increasingly recognised as a significant clinical clue. However, there is little data to support its specificity for KD as compared to other febrile illnesses. We aimed to evaluate BCG reaction or induration as a diagnostic tool for KD. METHODS: A retrospective case-controlled study of patients discharged with a diagnosis of KD from 2007 to 2010 was conducted. Another group of patients admitted over the same period for possible KD, but later found not to have KD, served as control. RESULTS: Significantly more infants with KD (69.7%) had BCG site changes than older children (27.8%; p < 0.001). It also presented earlier in the course of KD; < 5 days (53.3%) compared to ≥ 5 days of fever (30.0%; p < 0.001). Positive predictive value of BCG site reaction or induration for KD was 90.8% (95% confidence interval [CI] 0.819-0.962) for infants and 96.2% (95% CI 0.868-0.995) for older children. The prevalence rate of changes at the BCG site was 9.9% among patients with non-KD febrile illnesses and 42.6% among patients with KD. CONCLUSION BCG site reaction or induration is a useful clinical clue for the diagnosis of KD in both infants and older children, with a higher prevalence in infants. Physicians should consider KD in children with febrile illness and redness or crust formation at the BCG site, especially in view of low rates of BCG reaction or induration in non-KD febrile illnesses.
BCG Vaccine ; administration & dosage ; adverse effects ; Case-Control Studies ; Child, Preschool ; Erythema ; complications ; epidemiology ; Female ; Fever ; complications ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; diagnosis ; epidemiology ; Risk Factors ; Singapore ; epidemiology

OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood