Kawasaki Disease Newburger, Jane W., MD, MPH; Takahashi, Masato, MD; Burns, Jane C., MD
Journal of the American College of Cardiology,
04/2016, Letnik:
67, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Abstract Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that occurs predominantly in infants and children. If not treated early with high-dose intravenous immunoglobulin, 1 ...in 5 children develop coronary artery aneurysms; this risk is reduced 5-fold if intravenous immunoglobulin is administered within 10 days of fever onset. Coronary artery aneurysms evolve dynamically over time, usually reaching a peak dimension by 6 weeks after illness onset. Almost all the morbidity and mortality occur in patients with giant aneurysms. Risk of myocardial infarction from coronary artery thrombosis is greatest in the first 2 years after illness onset. However, stenosis and occlusion progress over years. Indeed, Kawasaki disease is no longer a rare cause of acute coronary syndrome presenting in young adults. Both coronary artery bypass surgery and percutaneous intervention have been used to treat Kawasaki disease patients who develop myocardial ischemia as a consequence of coronary artery aneurysms and stenosis.
Objectives To characterize the clinical presentation and outcome in infants <6 months of age with Kawasaki disease (KD) and to describe the use of newer anti-inflammatory therapies in this young ...population. Study design We evaluated 88 infants <6 months old and 632 ≥6 months old treated for KD. We compared differences in laboratory data, response to treatment, and coronary artery outcomes between the 2 cohorts. Fisher exact test was used to analyze categorical variables, whereas the Wilcoxon rank sum test was used for continuous variables. Results The majority of children in both cohorts were diagnosed and treated within the first 10 days of illness (median illness day 6 in both cohorts). For patients treated within the first 10 days after fever onset, a larger proportion of infants <6 months old had a dilated or aneurysmal coronary artery on the initial echocardiogram compared with those ≥6 months old (43.4% vs 19.5%). Furthermore, 18.6% of infants <6 months old who had a normal echocardiogram at diagnosis, developed a dilated or aneurysmal coronary artery on a subsequent echocardiogram within 8 weeks of diagnosis. Twenty-eight infants <6 months old received a single dose of infliximab without any untoward effects. Conclusions Despite treatment in the first 10 days, infants <6 months old with acute KD are more likely to develop coronary artery abnormalities. Thus, the development of adjunctive therapies to reduce coronary artery damage should target this population.
Objective To test the hypothesis that first re-treatment with infliximab, compared with intravenous immunoglobulin (IVIG), might improve outcomes in IVIG-resistant Kawasaki disease. Study design In a ...two-center retrospective review from January 2000 to March 2008, we compared duration of fever and coronary artery dimensions in patients with IVIG-resistance whose first re-treatment was with IVIG compared with infliximab given for fever ≥38.0°C beyond 36 hours after first IVIG completion. Results Patients in the IVIG group (n = 86, 2 g/kg) and infliximab group (n = 20, 5 mg/kg) were similar in demographics, days of fever at diagnosis, and baseline coronary artery dimensions. Patients had similar coronary dimensions 6 weeks after diagnosis, both in univariate and multivariate analysis. The infliximab group had fewer days of fever (median 8 days versus10 days, P = .028), and in a multivariate analysis, the infliximab group had 1.2 fewer days of fever ( P = .033). Patients who received infliximab had shorter lengths of hospitalization (median 5.5 days versus 6 days, P = .040). Treatment groups did not differ significantly in adverse events (0% versus 2.3%, P = 1.0). Conclusions In our retrospective study, patients with IVIG-resistant Kawasaki disease whose first re-treatment was with infliximab, compared with IVIG, had faster resolution of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar; the power of the study was limited.
Abstract Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to ...adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.
Objective To analyze associations of short-term exposure to fine particulate matter (diameter ≤ 2.5 µm PM2.5 ), a measurable component of urban pollution, with the event date of fever onset for ...patients with Kawasaki disease (KD) residing in 7 metropolitan regions. Study design A case-crossover study design was used. Time trends, seasonality, month, and weekday were controlled for by matching. We assembled PM2.5 exposure measurements from urban monitors and imputed PM2.5 to provide day-to-day temporal variability and resolution for time series indexes of exposures. Selected exposure windows (to 14 days) of PM2.5 were examined. Results A total of 3009 KD events were included for which the subject resided within a study metropolitan area and the event date occurred during years with available PM2.5 . The estimated ORs (with 95% CIs) of an event of KD associated with a 10 µg/m3 PM2.5 lagged moving average concentration of lagged exposure period (ie, concurrent, preceding days) revealed no evidence of a consistent, statistically significant, positive association between elevated PM2.5 exposure and increased risk of KD. Extended analysis with stratification by city, sex, age, ethnic origin, incomplete or complete clinical manifestations, the presence of coronary aneurysm, and intravenous immunoglobulin resistance did not provide evidence of a consistent, statistically significant, positive association between elevated exposure to PM2.5 and increased risk of KD for any of the strata studied. Conclusions This multicity study failed to establish a risk of the event of KD with short-term fine particulate exposure. Our negative findings add to the growing field of environmental epidemiology research of KD.
Objective To investigate the safety, tolerability, and pharmacokinetics of the anti–tumor necrosis factor-α monoclonal antibody infliximab in subjects with intravenous immunoglobulin (IVIG)-resistant ...Kawasaki disease (KD). Study design We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever after initial treatment with IVIG. Primary outcome measures were the safety, tolerability, and pharmacokinetics of infliximab. Secondary outcome measures were duration of fever and changes in markers of inflammation. Results Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and in 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. Conclusions Both infliximab and a second IVIG infusion were safe and well tolerated in the subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined.
Objectives To explore the increased incidence of intravenous immunoglobulin- (IVIG) resistance among San Diego County patients with Kawasaki disease (KD) in 2006 and to evaluate a scoring system to ...predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. With multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3% of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher percent bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase. They also had lower platelet counts and age-adjusted hemoglobin concentrations and were more likely to have aneurysms ( P = .0008). A scoring system developed to predict IVIG-resistant patients using illness day, percent bands, γ-glutamyl transferase, and age-adjusted hemoglobin had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population.
Objective To describe the clinical course and outcome of 10 patients with Kawasaki disease (KD) treated with a calcineurin inhibitor after failing to respond to multiple therapies. Study design ...Demographic and clinical data were prospectively collected using standardized case report forms. T-cell phenotypes were determined by flow cytometry, and KD risk alleles in ITPKC (rs28493229), CASP3 (rs72689236), and FCGR2A (rs1801274) were genotyped. Results Intravenous followed by oral therapy with cyclosporine (CSA) or oral tacrolimus was well tolerated and resulted in defervescence and resolution of inflammation in all 10 patients. There were no serious adverse events, and a standardized treatment protocol was developed based on our experiences with this patient population. Analysis of T-cell phenotype by flow cytometry in 2 subjects showed a decrease in circulating activated CD8+ and CD4+ T effector memory cells after treatment with CSA. However, suppression of regulatory T-cells was not seen, suggesting targeting of specific, proinflammatory T-cell compartments by CSA. Conclusion Treatment of refractory KD with a calcineurin inhibitor appears to be a safe and effective approach that achieves rapid control of inflammation associated with clinical improvement.
Abstract Objectives The aim of this study was to characterize the range of management issues raised by adults with cardiovascular sequelae from Kawasaki disease (KD) in childhood. Background ...Aneurysms resulting from vascular inflammation associated with KD in childhood may remain clinically silent until adulthood. Adults with large aneurysms, unstable angina, or myocardial infarction following KD in childhood present unique challenges to interventional cardiologists and cardiothoracic surgeons. Methods In an observational study of adults with histories of KD in childhood, data were collected regarding the medical histories and outcomes of 154 adult KD patients, of whom 21 underwent either percutaneous interventions or surgery. Results Of the 21 subjects with interventions, 11 had been diagnosed with KD in childhood, and 10 had histories of KD-compatible illnesses. Seventeen subjects were asymptomatic until experiencing acute cardiovascular symptoms: acute myocardial infarction (n = 12), angina (n = 2), end-stage congestive heart failure requiring cardiac transplantation (n = 1), and claudication (n = 2). Conclusions Cardiovascular complications in these subjects illustrate the following points: 1) even small to moderate-sized aneurysms that “normalize” on echocardiography in childhood can lead to stenosis and thrombosis decades after the acute illness; 2) coronary interventions without intravascular ultrasound may result in clinically significant underestimation of vessel luminal diameter; 3) failure to assess the extent of calcification may lead to suboptimal procedural outcomes; and 4) patients with symptomatic peripheral aneurysms may benefit from endarterectomy or resection. Interventional cardiologists should be aware of the potential challenges in treating this growing population of adults.
Objective To identify characteristics differentiating the node-first presentation of Kawasaki disease (NFKD) from bacterial cervical lymphadenitis (BCL) and typical Kawasaki disease (KD). Study ...design From our prospectively collected database, we compared clinical, laboratory, and imaging characteristics of NFKD and BCL cohorts and performed multivariable logistic regression to identify variables that distinguish NFKD from BCL. We then compared outcomes of patients with NFKD and patients with typical KD treated during the same period. Results Over 7 years, 57 patients were hospitalized for NFKD, 78 for BCL, and 287 for typical KD. Patients with NFKD were older and had more medical encounters and longer duration of illness before the correct diagnosis was made than did patients with BCL. Of patients with NFKD, 33% had an admission diagnosis of bacterial adenitis or abscess. Compared with patients with BCL, patients with NFKD had lower leukocyte (white blood cell), hemoglobin, and platelet counts and higher absolute band counts (ABCs), C-reactive protein (CRP), alanine transaminase and γ-glutamyl transpeptidase levels, and erythrocyte sedimentation rates. In the multivariable analysis, smaller nodes, lower white blood cell count, and higher ABC and CRP were independently associated with NFKD. Patients with NFKD had multiple enlarged solid nodes and comparable rates of retropharyngeal edema. Compared with patients with typical KD, patients with NFKD were older, had more severe inflammation, and had similar rates of coronary artery abnormalities and resistance to intravenous immune globulin. Conclusions High ABC and CRP values and multiple enlarged solid nodes in febrile patients with cervical adenopathy should prompt consideration of NFKD to prevent delayed diagnosis of KD. Retropharyngeal edema on radiography should not dissuade from the diagnosis of NFKD.
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