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Objective: Kawasaki disease (KD) is a systemic vasculitis of young children that can lead to development of coronary artery aneurysms. We aimed to identify diagnostic markers to distinguish KD from other pediatric inflammatory diseases., Methods: We used the proximity extension assay to profile proinflammatory mediators in plasma samples from healthy pediatric controls (n = 30), febrile controls (n = 26), and patients with KD (n = 23), multisystem inflammatory syndrome in children (MIS-C; n = 25), macrophage activation syndrome (n = 13), systemic and nonsystemic juvenile idiopathic arthritis (n = 14 and n = 10, respectively), and juvenile dermatomyositis (n = 9). We validated the key findings using serum samples from additional patients with KD (n = 37) and febrile controls (n = 28)., Results: High-fidelity proteomic profiling revealed distinct patterns of cytokine and chemokine expression across pediatric inflammatory diseases. Although KD and MIS-C exhibited many similarities, KD differed from MIS-C and other febrile diseases in that most patients exhibited elevation in one or more members of the interleukin-17 (IL-17) cytokine family, IL-17A, IL-17C, and IL-17F. IL-17A was particularly sensitive and specific, discriminating KD from febrile controls with an area under the receiver operator characteristic curve of 0.95 (95% confidence interval 0.89-1.00) in the derivation set and 0.91 (0.85-0.98) in the validation set. Elevation of all three IL-17-family cytokines was observed in over 50% of KD patients, including 19 of 20 with coronary artery aneurysms, but was rare in all other comparator groups., Conclusion: Elevation of IL-17 family cytokines is a hallmark of KD and may help distinguish KD from its clinical mimics., (© 2023 American College of Rheumatology.)

Objectives: To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis., Study Design: Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis., Results: Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits., Conclusions: Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: This study aimed to describe the current management practices for Kawasaki disease (KD) in Australia and New Zealand., Methods: We performed a secondary analysis on the Australian and New Zealand responses to a large international survey of clinicians' perspectives on KD diagnosis and management., Results: There was general consensus among Australian and New Zealand clinicians regarding the indications for intravenous immunoglobulin and aspirin in the management of acute KD. There was less consensus on the dose of these agents, the definition and management of treatment-resistant KD and the approach to long-term thromboprophylaxis., Conclusion: Most clinicians use intravenous immunoglobulin for primary treatment of KD. There is variation regarding other aspects of KD diagnosis and important management issues. Future studies should confirm whether this reported variation occurs in real-world practice and assess potential impacts on patient outcome., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: Patients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis., Design: Single-centre, retrospective review., Patients: Patients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5., Interventions: Primary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48)., Main Outcome Measures: Treatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate., Results: Of the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002)., Conclusion: Primary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Intravenous immunoglobulin (IVIG) reduces coronary aneurysms in patients with Kawasaki disease (KD), but additional management options remain challenging, with no generalisable evidence-based recommendations. We performed a survey of 724 physicians from 73 countries to assess variation in practice. IVIG was the preferred initial treatment by 659 (91%) of respondents. Criteria for adjunctive primary treatment varied considerably and definitions of IVIG resistance varied markedly by geographical continent, Human Development Index tiers and medical specialty. A second dose of IVIG was used most often for patients with coronary aneurysm non-responsive to initial treatment (572, 79%), but corticosteroids (379, 52%) and tumour necrosis factor alpha inhibitors (208, 29%) were also frequently used. Our findings highlight the need for international collaborative efforts to optimise management of patients with KD worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs., Methods: Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up., Results: From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25)., Conclusions: LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAA Z score ≥2.5) was used. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazard models for risk factor analysis. In patients with CAA Z scores ≥10, the cumulative incidence of luminal narrowing (>50% of lumen diameter), coronary artery thrombosis, and composite major adverse cardiovascular complications at 10 years was 20±3%, 18±2%, and 14±2%, respectively. No complications were observed in patients with a CAA Z score <10. Higher CAA Z score and a greater number of coronary artery branches affected were associated with increased risk of all types of complications. At 10 years, normalization of luminal diameter was noted in 99±4% of patients with small (2.5≤ Z <5.0), 92±1% with medium (5.0≤ Z <10), and 57±3% with large CAAs ( Z ≥10). CAAs in the left anterior descending and circumflex coronary artery branches were more likely to normalize. Risk factor analysis of coronary artery branch level outcomes was performed with a total of 893 affected branches with Z score ≥10 in 440 patients. In multivariable regression models, hazards of luminal narrowing and thrombosis were higher for patients with CAAs of the right coronary artery and left anterior descending branches, those with CAAs that had complex architecture (other than isolated aneurysms), and those with CAAs with Z scores ≥20. Conclusions For patients with CAA after KD, medium-term risk of complications is confined to those with maximum CAA Z scores ≥10. Further risk stratification and close follow-up, including advanced imaging, in patients with large CAAs is warranted.

Background: Patients with coronary artery aneurysms (CAA) after Kawasaki disease (KD) are at risk of thrombosis, which can lead to myocardial infarction or sudden death. Clinical practice guidelines recommend anticoagulation for high-risk patients., Methods: Web-based worldwide survey of physicians completed between 2016 and 2017 investigating anti-thrombotic management after KD. We compared management of patients by geographic location, Human Development Index (HDI) tier, and medical specialty., Results: The survey was completed by 603 physicians from 63 countries. In patients with normal coronaries, 95 (25%) of physicians recommended low-dose aspirin during long-term follow-up (>3 months after diagnosis). In patients with non-giant CAA, dual antiplatelet (e.g. aspirin and clopidogrel) was used by 121 (32%) of physicians, and anticoagulation by 72 (19%) of physicians. In patients with giant CAA, dual antiplatelet was used by 39 (10%) of physicians and anticoagulation by 285 (74%). In multivariable analysis, cardiology (OR 6.4 [95% CI 2.7, 16.1]) and rheumatology (OR 4.3 [95% CI 1.6, 12.6]) specialty (versus general pediatrics) were the only independent predictors of anticoagulant use in patients with giant CAA., Conclusion: There is significant variation in anti-thrombosis management of patients with CAA after KD, with 26% of physicians not recommending anticoagulation of patients with giant CAA. Further studies are needed to evaluate the drivers of this practice variation to inform educational initiatives and to ascertain impact on long-term outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To evaluate the association of neighborhood socioeconomic status (SES) with time to intravenous immunoglobulin treatment, length of stay (LOS), and coronary artery aneurysms (CAAs) in patients with Kawasaki disease., Study Design: We examined the relationship of SES in 915 patients treated at a large academic center between 2000 and 2017. Neighborhood SES was measured using a US census-based score derived from 6 measures related to income, education, and occupation. Linear and logistic regression were used to examine the association of SES with number of days of fever at time of treatment, LOS, and CAA., Results: Patients in the lowest SES quartile were treated later than patients with greater SES (7 [IQR 5, 9] vs 6 [IQR 5, 8] days, P = .01). Patients in the lowest SES quartile were more likely to be treated after 10 days of illness, with an OR 1.9 (95% CI 1.3-2.8). In multivariable analysis, SES remained an independent predictor of the number of days of fever at time of treatment (P = .01). Patients in the lowest SES quartile had longer LOS than patients with greater SES (3 [IQR 2, 5] vs 3 [IQR 2, 4], P = .007). In subgroup analysis of white children, those in the lowest SES quartile vs quartiles 2-4 were more likely to develop large/giant CAA 17 (12%) vs 30 (6%), P = .03., Conclusions: Lower SES is associated with delayed treatment, prolonged LOS, and increased risk of large/giant CAA. Novel approaches to diagnosis and education are needed for children living in low-SES neighborhoods., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer-Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery ≥2.0, age <6 months, Asian race, and C-reactive protein ≥13 mg/ dL (c=0.82 in the development cohort, c=0.93 in the validation cohort). The CAA risk score assigned 2 points for baseline Z score of left anterior descending or right coronary artery ≥2.0 and 1 point for each of the other variables, with creation of low- (0-1), moderate- (2), and high- (3-5) risk groups. The odds of CAA s were 16-fold greater in the high- versus the low-risk groups in the development cohort (odds ratio, 16.4; 95% CI , 9.71-27.7 [ P<0.001]), and >40-fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8-180 [ P<0.001]). Conclusions Our risk model for CAA in Kawasaki disease consisting of baseline demographic, laboratory, and echocardiographic variables had excellent predictive utility and should undergo prospective testing.

Background: Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease. Treatment with intravenous immunoglobulin (IVIg) within 10 days of fever onset reduces the risk of CAA from 25% to <5%. Corticosteroids and infliximab are often used in high-risk patients or those with CAA at diagnosis, but there are no data on their longer-term impact on CAA., Methods: Retrospective multicenter study including children who had CAA with a z score ≥2.5 and <10 at time of diagnosis and who received primary therapy with IVIg alone or in combination with either corticosteroids or infliximab within 10 days of onset of fever., Results: Of 121 children, with a median age of 2.8 (range 0.1-15.5) years, 30 (25%) received primary therapy with corticosteroids and IVIg, 58 (48%) received primary therapy with infliximab and IVIg, and 33 (27%) received primary therapy with IVIg only. Median coronary z scores at the time of diagnosis did not differ among treatment groups ( P = .39). Primary treatment intensification with either corticosteroids or infliximab were independent protective factors against progression of coronary size on follow-up (coefficient: -1.31 [95% confidence interval: -2.33 to -0.29]; coefficient: -1.07 [95% confidence interval: -1.95 to -0.19], respectively)., Conclusions: Among a high-risk group of patients with Kawasaki disease with CAA on baseline echocardiography, those treated with corticosteroids or infliximab in addition to IVIg had less progression in CAA size compared with those treated with IVIg alone. Prospective randomized trials are needed to determine the best adjunctive treatment of patients who present with CAA., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Friedman has served as a paid expert witness in cases of missed diagnosis of Kawasaki disease (unrelated to the current study); the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Importance: American Heart Association guidelines recommend echocardiography in Kawasaki disease at baseline, 1 to 2 weeks, and 4 to 6 weeks after treatment to detect coronary artery abnormalities. However, these examinations are expensive and may require sedation in young children, which is burdensome and carries some risk., Objective: To assess the benefit of additional echocardiographic imaging at 6 weeks in patients with uncomplicated Kawasaki disease who had previously normal coronary arteries., Design, Setting, and Participants: This is a retrospective review of patients with Kawasaki disease who were cared for between 1995 and 2014 in 2 academic pediatric referral practices Eligibility criteria included receiving intravenous immunoglobulin treatment for acute Kawasaki disease at a center; the absence of significant congenital heart disease; available echocardiographic measurements of both the right and left anterior descending coronary arteries at 10 days or less after diagnosis (baseline), 2 (±1) weeks, and 6 (±3) weeks of illness; and normal coronary arteries at baseline and 2 weeks, defined as maximum coronary artery z scores less than 2.0 and no distal aneurysms. Data analysis was completed from March 2015 to November 2015., Main Outcomes and Measures: The number of patients with right coronary artery or left anterior descending coronary artery z scores of 2.0 or more at 6 weeks., Results: The median age of the 464 included patients was 3.3 years (interquartile range, 1.8-5.4 years); 264 (56.9%) were male, 351 of 414 for whom data were available (84.8%) had complete Kawasaki disease, and 66 (14.2%) received additional intravenous immunoglobulin treatment. At 6 weeks of illness, 456 patients (98.3%) who had had normal coronary artery z scores at baseline and 2 weeks continued to have normal z scores. Of the remaining 8 patients (1.7%), the maximum z score within 6 weeks was 2.0 to 2.4 in 5 patients (1.2%), 2.5 to 2.9 in 1 patient (0.2%), and 3.0 or more in 2 patients (0.4% [95% CI, 0.1%-1.5%]). Coronary artery dimensions ultimately normalized in all but 1 patient, who had minimal dilation at 6 weeks (right coronary artery z score, 2.1). Sensitivity analyses using less restrictive cut points (eg, a maximum z score <2.5) or less restrictive timing windows (eg, considering patients with incomplete echocardiographic data within 21 days) gave similar results; in these analyses, 454 to 463 of 464 patients (98% to 99.7%) had coronary artery z scores of less than 2.5 at 6 weeks., Conclusions and Relevance: New abnormalities in coronary arteries are rarely detected at 6 weeks in patients with Kawasaki disease who have normal measurements at baseline and 2 weeks of illness, suggesting that the 6-week echocardiographic imaging may be unnecessary in patients with uncomplicated Kawasaki disease and z scores less than 2.0 in the first 2 weeks of illness.

Objective: To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications., Study Design: We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5., Results: In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients., Conclusions: Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation., Methods: We conducted a systematic literature review using various reference sources to review the available evidence published in the literature., Results: We identified twenty seven publications reporting a temporal association between immunisation and Kawasaki disease. We present a systematic review of data drawn from randomised controlled trials, observational studies, case series and reports, and reviews. Overall there was a lack of standardised case definitions, making data interpretation and comparability challenging., Conclusions: Although a temporal relationship between immunisation and Kawasaki disease is suggested, evidence for an increased risk or a causal association is lacking. Implementation of a standardised Kawasaki disease case definition would increase confidence in the findings and add value to future studies of pre- or post-licensure vaccine safety studies., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Coronary artery (CA) Z scores are commonly used for clinical decisions in Kawasaki disease, including treatment, anticoagulation, and duration and frequency of follow-up. The aim of this study was to evaluate CA measurement reproducibility, Z score calculation variability, and the impact of variability on management., Methods: Twenty-one patients with Kawasaki disease with right CA (RCA) or left anterior descending CA (LAD) Z scores of 1.5 to 3 (group 1) were randomly selected, and all patients with Kawasaki disease with Z scores of 7 to 14 for either the RCA or LAD (n = 20; group 2) were included from March 2008 to May 2014. Two echocardiographers measured left main CA, LAD, and RCA dimensions. The inter- and intraobserver reliability of absolute measurements was calculated, and the CA Z scores derived from three commonly used formulas were compared., Results: Median age at echocardiography was 1.2 years (range, 0.2-11.5 years), and 68% of subjects (n = 28) were male. Interobserver reliability was high for the LAD (intraclass correlation coefficient [ICC], 96.79%) and RCA (ICC, 93.31%) and lower for the left main CA (ICC, 73.54%). Intraobserver reliability was also high for the LAD and RCA (ICC, 99.08% and 97.74%) and lower for the left main CA (ICC, 80.88%). Calculated Z scores were similar among the three formulas for group 1 but varied markedly in group 2. Calculated Z scores using the same CA measurement in each of the three formulas resulted in different clinical management in up to seven of 21 group 1 patients (22%) and in up to 10 of 20 group 2 patients (50%)., Conclusions: Although CA measurements have high inter- and intraobserver agreement, CA Z scores vary dramatically on the basis of the Z score formula at larger CA dimensions. Discrepancies in CA Z score calculators may affect clinical decision making., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of our study was to compare the indices of vascular health in Kawasaki disease (KD) patients to those of control subjects., Background: The literature on peripheral vascular health after KD is conflicting., Methods: Subjects were patients 11 to 29 years of age with the onset of KD >12 months before the study visit (n = 203) and healthy control subjects (n = 50). We measured endothelial function (using the Endothelial Pulse Amplitude Testing index), intima-media thickness (IMT) of the right common carotid artery (RCCA) and the left common carotid artery (LCCA), and fasting lipid profile and C-reactive protein (CRP). KD patients were classified according to their worst-ever coronary artery (CA) status: group I, always normal CAs (n = 136, 67%); group II, CA z-scores ≥2 but <3 (n = 20, 10%); group III, CA aneurysm z-scores ≥3 but <8 mm (n = 40, 20%); and group IV, giant CA aneurysm, defined as ≥8 mm (n = 7, 3%)., Results: At a median of 11.6 years (range, 1.2 to 26 years) after KD onset, compared with controls, KD patients had a higher peak velocity in the LCCA (p = 0.04) and higher pulsatility index of both the RCCA and LCCA (p = 0.006 and p = 0.05, respectively). However, there were no differences in the Endo-PAT index or carotid IMT or stiffness. The mean IMT of the LCCA tended to differ across the KD subgroups and control group (p = 0.05), with a higher mean in group IV. Otherwise the KD subgroups and control group had similar vascular health indexes., Conclusions: In contrast to some earlier reports, our study of North American children and young adults demonstrated that KD patients whose maximum CA dimensions were either always normal or mildly ectatic have normal vascular health indexes, providing reassurance regarding peripheral vascular health in this population., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

OBJECTIVES: To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C). METHODS: This multicenter retrospective case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes. RESULTS: Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 [95% confidence interval 1.1--4.4]), highest SVI quartile (odds ratio 2.8 [95% confidence interval 1.5--5.1]), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity. CONCLUSIONS: Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up. [ABSTRACT FROM AUTHOR]

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center. [ABSTRACT FROM AUTHOR]