FCGR2/3 polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms.

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 (FcγRs), 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.

MIS-C Like Features in a Patient of Atypical Kawasaki Disease: A Case Report.

ABSTRACT: Kawasaki Disease is multisystem vasculitis affecting young children and infants. While the diagnosis of a typical form of Kawasaki Disease is obvious, there are some patients who do not fulfill the classic diagnostic criteria for the disease which is termed as 'incomplete Kawasaki Disease' or 'Atypical Kawasaki Disease'. We present a case of a 6 months old child with fever who after failing to respond to IV antibiotics showed considerable improvement after administering aspirin and Intravenous Immunoglobulin thus diagnosed as Atypical Kawasaki Disease. Moreover, due to sharing of similar features by both Kawasaki Disease and Multiple Inflammatory Syndrome in Children, the case posed a diagnostic dilemma.

Kawasaki disease before and during the COVID-19 pandemic: a single-center comparative study in Switzerland.

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.

"No-Touch" Saphenous Vein Grafting and Coronary Aneurysm Ligation in an Adult Patient with Suspected Prior Kawasaki 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.

Scrotal and penile edema in a patient with incomplete kawasaki disease: a case report and brief literature review.

BACKGROUND: Kawasaki disease (KD) is a medium artery vasculitis that predominantly affects children under age 5. Prompt diagnosis and treatment with IVIG and moderate dose aspirin is required to prevent the formation of coronary artery aneurysms. While scrotal edema and erythema have been seen in KD, here we present a distinctive case of incomplete Kawasaki with these features as well as penile edema. CASE PRESENTATION: A 2-year-old, unvaccinated, African American male presented with 4 days of fever, bilateral limbic sparing conjunctivitis, a papular rash, unilateral shotty cervical lymphadenopathy, mild right-hand edema, and scrotal and penile edema and erythema. His labs were significant for sterile pyuria, elevated ALT, anemia for age, and hypoalbuminemia. He was diagnosed with incomplete Kawasaki disease and was treated with IVIG and moderate dose aspirin. Echocardiogram was negative for coronary aneurysms. His symptoms resolved and he was discharged home with low dose aspirin. At his 2-week follow up, he remained well-appearing with no refractory Kawasaki symptoms. CONCLUSION: This is a unique case of penile edema in KD which to our knowledge has not been previously reported in literature. An understanding of genitourinary symptoms in Kawasaki disease can help timely diagnosis and treatment of the disease.

Diagnostic value of syndecan-1 for coronary artery lesions and correlation analysis of laboratory indicators in Kawasaki disease patients.

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.

Anterior uveitis as an early diagnostic marker in incomplete Kawasaki disease.

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.

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children.

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Progression prediction of coronary artery lesions by echocardiography-based ultrasomics analysis in Kawasaki disease.

BACKGROUND: Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. METHODS: Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. RESULTS: At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75-0.90), 0.84 (95% CI, 0.74-0.94), and 0.73 (95% CI, 0.40-0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. CONCLUSIONS: Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.

Evaluating the performance of egami, kobayashi and sano scores in predicting IVIG resistance in infant kawasaki disease.

BACKGROUND: This study aimed to evaluate the effectiveness of Egami, Kobayashi and Sano scores in predicting intravenous immunoglobulin (IVIG) resistance in infant Kawasaki disease (KD), considering its unique clinical presentation. METHODS: We retrospectively analysed 143 infants aged < 12 months and diagnosed with KD at a single centre from 2019 to 2023. Patients were divided into IVIG-resistant and IVIG-responsive groups. Demographic, clinical and laboratory data were compared between the groups. The diagnostic performance of Egami, Kobayashi and Sano scores in predicting IVIG resistance was evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC). Additionally, we developed a new scoring system based on significant predictors identified in our cohort. RESULTS: Among 143 infants, 45 (31.5%) showed IVIG resistance. The IVIG-resistant group had a significantly higher rate of coronary artery lesions (15.6% vs. 5.1%, p = 0.036). Incomplete KD was observed in 61.5% of cases. Egami, Kobayashi and Sano scores exhibited low sensitivity (35.6%, 55.6% and 20%, respectively) and moderate specificity (77.6%, 63.3% and 95.9%, respectively) in predicting IVIG resistance. The AUC ranged from 0.583 to 0.674, indicating poor to fair discriminative ability. Our newly developed scoring system, based on total bilirubin and albumin levels, showed similar performance (AUC 0.633) to existing scores. CONCLUSIONS: Existing Japanese risk scoring systems and our newly developed score showed limited effectiveness in predicting IVIG resistance in infant KD. The high proportion of incomplete presentation and IVIG resistance in infants highlights the need for age-specific risk assessment and management. Further research is necessary to develop more sophisticated, dedicated prediction model for IVIG resistance in infants with KD.

Serum salicylic acid levels in children with Kawasaki disease.

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.

Kawasaki Disease Presenting with Fever and Jaundice: Case Report.

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.

A large thrombus within a giant coronary artery aneurysm in a child with Kawasaki disease: A case report.

Kawasaki disease (KD) is an acute systemic vasculitis that preferentially involves coronary arteries in young children, and predominantly affects young children. Cardiovascular lesions are the most severe complications of this disease. Even though giant aneurysms are rare, they can complicate thrombus formation, leading to myocardial ischemia, myocardial infarction, and even cardiac death. Later in life, it can lead to steno-occlusive lesions. Follow-up led to coronary artery stenosis. In this article, we report a case of a pediatric patient with KD who presented with a large thrombus within a giant coronary aneurysm as a consequence of delayed treatment with intravenous immunoglobulin (IVIG) and IVIG resistance, which contributed to the formation of coronary artery lesions. Transthoracic echocardiography is a valuable tool for detecting coronary artery abnormalities; however, computed tomography coronary angiography is valuable for precisely delineating coronary anatomy and complications. It is important to maintain a slightly higher international normalized ratio to decrease the risk of thrombosis in coronary artery aneurysms.

mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis.

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts-in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis-coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.

Regression effect of renin-angiotensin-aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study.

PURPOSE: This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD). METHODS: This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset. RESULTS: Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91-2.46). CONCLUSIONS: Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients. WHAT IS KNOWN: • Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA. WHAT IS NEW: • Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report.

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.

[Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions].

Objective: To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy. Methods: A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children's Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results: Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR (OR=4.69, 10.00, 95%CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR (OR=0.08, 0.13, 95%CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion: KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.