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

OBJECTIVES: To explore the predictive factors for non-response to intravenous immunoglobulin (IVIG) in children with Kawasaki disease (KD) and to establish an IVIG non-response prediction scoring model for the Sichuan region. METHODS: A retrospective study was conducted by collecting clinical data from children with KD admitted to four tertiary hospitals in Sichuan Province between 2019 and 2023. Among them, 940 children responded to IVIG, while 74 children did not respond. Multivariate logistic regression analysis was used to identify the predictive factors for non-response to IVIG and to establish a predictive scoring model. The model's effectiveness was assessed using the receiver operating characteristic curve (ROC) and validated with an independent dataset. RESULTS: Multivariate logistic regression analysis showed that the platelet-to-lymphocyte ratio (PLR), hemoglobin (Hb), serum creatinine, aspartate aminotransferase (AST), and platelet count (PLT) were closely related to non-response to IVIG in children with KD (P<0.05). Based on these indicators, a predictive scoring model was established: PLR > 199, 0.4 points; Hb ≤ 116 g/L, 4 points; AST > 58 U/L, 0.2 points; serum creatinine > 38 µmol/L, 3.9 points; PLT count ≤ 275 × 10⁹/L, 0.3 points. Using this model, children with KD were scored, and a total score greater than 4.3 was considered high risk of non-response to IVIG. The sensitivity of the model in predicting non-response to IVIG was 77.0%, specificity was 65.7%, and the area under the ROC curve was 0.746 (95%CI: 0.688-0.805). CONCLUSIONS The predictive scoring model based on PLR, Hb, serum creatinine, AST, and PLT demonstrates good predictive performance for non-response to IVIG in children with KD in the Sichuan region and can serve as a reference for clinical decision-making.
Humans ; Mucocutaneous Lymph Node Syndrome/blood* ; Immunoglobulins, Intravenous/therapeutic use* ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Infant ; Logistic Models ; Child ; Platelet Count ; ROC Curve

OBJECTIVES: To explore the role of berberine (BBR) in ameliorating coronary endothelial cell injury in Kawasaki disease (KD) by regulating the complement and coagulation cascade. METHODS: Human coronary artery endothelial cells (HCAEC) were divided into a healthy control group, a KD group, and a BBR treatment group (n=3 for each group). The healthy control group and KD group were supplemented with 15% serum from healthy children and KD patients, respectively, while the BBR treatment group received 15% serum from KD patients followed by the addition of 20 mmol/L BBR. Differential protein expression was analyzed and identified using isobaric tags for relative and absolute quantitation technology and liquid chromatography-tandem mass spectrometry, followed by GO functional enrichment analysis and KEGG signaling pathway enrichment analysis of the differential proteins. Western blot was used to detect differential protein expression. RESULTS: A total of 518 differential proteins were identified between the KD group and the healthy control group (300 upregulated proteins and 218 downregulated proteins). A total of 422 differential proteins were identified between the BBR treatment group and the KD group (221 upregulated proteins and 201 downregulated proteins). Bioinformatics analysis showed that compared to the healthy control group, the differential proteins in the KD group were enriched in the complement and coagulation cascade and ribosome biogenesis in eukaryotes. Compared to the KD group, the differential proteins in the BBR treatment group were also enriched in the complement and coagulation cascade and ribosome biogenesis in eukaryotes. Western blot results indicated that compared to the healthy control group, the expression of complement C1q subcomponent subunit C (C1QC), kininogen-1 (KNG1), complement C1s subcomponent (C1S), and C4b-binding protein alpha chain (C4BPA) was increased in the KD group (P<0.05). Compared to the KD group, the expression of KNG1, C1S, C1QC, and C4BPA was decreased in the BBR treatment group (P<0.05). CONCLUSIONS The complement and coagulation cascade may be involved in the regulation of BBR treatment for coronary injury in KD, and C1QC, KNG1, C1S, and C4BPA may serve as biomarkers for this treatment.
Mucocutaneous Lymph Node Syndrome/blood* ; Humans ; Endothelial Cells/pathology* ; Complement System Proteins/physiology* ; Coronary Vessels/drug effects* ; Male ; Blood Coagulation/drug effects* ; Berberine/therapeutic use* ; Female ; Child, Preschool ; Infant

This paper comprehensively compares the Kawasaki disease (KD) guidelines from seven countries/regions, including China, Argentina, Europe, Italy, Japan, Spain, and the United States, as retrieved from the PubMed database. It analyzes the similarities and differences in KD diagnosis and treatment among these guidelines. The results show that all guidelines consistently recommend a single infusion of immunoglobulin at a dosage of 2 g/kg as the first-line treatment for KD, and none advocate for the routine use of methylprednisolone or prednisone as standalone first-line treatment options for KD. However, there are some differences among the guidelines regarding classification, diagnostic criteria, and specific treatment methods for KD. Therefore, it is essential to further strengthen international collaboration in guideline development and conduct multicenter clinical research in the future, aiming to achieve a higher level of expert consensus, thereby promoting the enhancement of KD diagnosis and treatment.
Mucocutaneous Lymph Node Syndrome/drug therapy* ; Humans ; Practice Guidelines as Topic

OBJECTIVES: To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula. METHODS: A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated. RESULTS: The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas. CONCLUSIONS The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans ; Male ; Female ; Child, Preschool ; Child ; Coronary Artery Disease/diagnostic imaging* ; Infant ; Mucocutaneous Lymph Node Syndrome ; Regression Analysis ; Coronary Vessels/diagnostic imaging* ; Echocardiography ; Adolescent

Clinical management of Kawasaki disease faces several challenges, including difficulties in early diagnosis, insufficient personalized treatment, delayed access to information, and inefficient multidisciplinary collaboration. This paper explores the application of the DeepSeek AI model in the management of Kawasaki disease: (1) Enhancing early diagnosis accuracy through the integration and analysis of multimodal data (imaging, laboratory, and clinical data); (2) Dynamically adjusting treatment plans to achieve personalized medicine; (3) Integrating the latest global guidelines and research findings in real-time to optimize clinical processes; (4) Providing personalized health education content to enhance parental involvement; (5) Establishing a platform for sharing clinical data to support intelligent decision-making and multidisciplinary collaboration.
Humans ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Child ; Artificial Intelligence ; Precision Medicine ; East Asian People

OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

INTRODUCTION

Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are two related conditions that primarily affect pediatric patients. The overlap in clinical symptoms, physical findings, and laboratory results between MIS-C and KD complicates diagnosis and treatment, as children with MIS-C may fulfill the criteria for KD. Early recognition of distinguishing clinical, laboratory, and echocardiographic findings is crucial for timely diagnosis and appropriate treatment, which can mitigate the risk of severe cardiovascular, gastrointestinal, and neurological complications.

This study aims to compare the clinical profile, laboratory profile, 2-D echocardiographic findings, treatment, and outcome ofchildren with KD vs MIS-C at a tertiary hospital in the Philippines.

A retrospective, analytic cohort study was done to differentiate the clinical profiles, laboratory profile, treatments, and outcomesof pediatric patients aged less than 19 years old, admitted with a diagnosis of KD, from January 2016 to December 2019 (pre-COVID-19 pandemic), and MIS-C cases admitted from January 2020 to December 2023, in a private, urban, tertiary hospital. Descriptive statistics (frequency and proportion, mean and standard deviation, median and inter-quartile range) were used to summarize the general and clinical characteristics of the participants. Independent T-test, Mann-Whitney U test and Fisher’s Exact/Chi-square test were used to determine the difference of mean, median and frequency of laboratory parameters among groups.

The study included 87 patients, with 60 categorized in the KD group (13 diagnosed with complete KD and 47 with incomplete KD) and 27 in the MIS-C group. MIS-C patients were more likely to be older (p = 0.023), present with GI symptoms such as vomiting (48.2% in MIS-C vs. 12.8% in KD) and abdominal pain (40.7% vs. 6.4%), respiratory symptoms such as shortness of breath (29.6% vs 0%) and wheezing (14.8% vs 0%), have lower WBC (6.30 in MIS-C vs. 13.07 in complete KD and 10.18 in incomplete KD, p < 0.001), ANC (5,940 in MIS-C vs. 13,660 in complete KD and 10,432 in incomplete KD, p = 0.002), and platelet count (280 in MIS-C vs. 368 incomplete KD and 364 in incomplete KD, p = 0.13), and experience more complications such as myocarditis (14.81% vs. 0%), hypotension (18.52% vs. 0%), shock (14.81% vs. 0%), and pneumonia (40.74% vs. 17.02% for incomplete KD and 7.69% for complete KD). In contrast, key features of KD, including conjunctival injection (100% in KD vs. 25.9% in MIS-C), rash (100% vs 59.3%), oral changes (92.3% vs. 22.2%), and cervical lymphadenopathy (92.3% vs. 29.6%), elevated laboratory results of CRP (12.89 in MIS-C vs. 46.53 incomplete KD and 111.15 in incomplete KD, p < 0.001), ESR (41.91 in MIS-C vs. 61.73 in complete KD and 82.49 in incomplete KD, p= 0.003), and AST/ALT ratios (0.42 in MIS-C vs. 1.88 in complete KD and 0.62 in incomplete KD, p = 0.034) were more frequently observed in KD patients. Combination therapy involving intravenous immunoglobulin (IVIG), methylprednisolone, and acetylsalicylic acid (ASA) was more common in MIS-C patients than in KD patients (48.15% in MIS-C vs. 7.69% for complete KD and 2.13% forincomplete KD), who mainly received IVIG and ASA alone (84.62% in complete KD and 93.62% in incomplete KD vs 3.7% in MIS-C).

This study highlights key clinical and laboratory differences between MIS-C and KD in a private tertiary hospital setting. MIS-C patients were generally older, exhibited more GI and respiratory symptoms, and had a higher risk of serious complications. In contrast, KD cases more often presented with classic mucocutaneous signs and elevated inflammatory markers. These findings underscore the importance of early differentiation, as MIS-C often requires more intensive management. The study also identifies practical diagnostic indicators including CBC parameters such as WBC, ANC, and platelet count that may aid clinicians, particularly in resource-limited settings. Further multicenter research involving both public and private hospitals is needed to validate and enhance the diagnostic criteria.

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.
Child ; Humans ; Infant ; Mucocutaneous Lymph Node Syndrome/therapy* ; Coronary Vessels ; China

OBJECTIVES: To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS: A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS: Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.
Humans ; Child ; Infant ; Aged, 80 and over ; Immunoglobulins, Intravenous/therapeutic use* ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Interleukin-17 ; Clinical Relevance ; Prospective Studies ; C-Reactive Protein/analysis* ; Retrospective Studies