Abstractobjective-We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. methods-We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of ≥20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. results-Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] conclusions-Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment. KeywordsKawasaki disease (mucocutaneous lymph node syndrome); shock; echocardiography; ventricular function What's Known on This SubjectAlthough the cardiac complications of KD are well known, hemodynamic instability is unusual in the acute phase of illness, except as a complication of intravenous IVIG administration. What This Study AddsWe have observed shock and hypotension with increasing frequency in newly diagnosed KD. Compared with hemodynamically normal KD, KDSS is associated with increased inflammation, platelet consumption, IVIG resistance, coronary artery abnormalities, mitral regurgitation, and myocardial dysfunction.KAWASAKI disease (KD) is the most common cause of acquired heart disease in the pediatric age group and results in permanent damage to the coronary arteries in up to 25% of untreated children. Although no patients with KD presented with shock in the prospective database before 2003, we postulated that earlier cases might have been misdiagnosed and therefore never included in our database. To identify patients with KD who were treated for shock but were misclassified with other diagnoses, we conducted a computerized search, on the basis of International Classification of Diseases, Ninth Revision codes, for patients discharged from the critical care unit between January 1, 2001, and Augus...

Background— Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome. Methods and Results— We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total of 771 KD subjects of mainly European descent from the United States, the United Kingdom, Australia, and the Netherlands. We analyzed transcript abundance patterns using microarray and reverse transcriptase–polymerase chain reaction for these same genes, and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2 , TGFBR2 , and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in 2 independent cohorts and an intronic single nucleotide polymorphism in a separate haplotype block was also strongly associated (A/G, rs4776338) ( P =0.000022; odds ratio, 1.50; 95% confidence interval, 1.25 to 1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole-blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness. Conclusions— These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy, and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis.

OBJECTIVE-The 2004 American Heart Association (AHA) statement included a clinical case definition and an algorithm for diagnosing and treating suspected incomplete Kawasaki disease (KD).We explored the performance of these recommendations in a multicenter series of US patients with KD with coronary artery aneurysms (CAAs).METHODS-We reviewed retrospectively records of patients with KD with CAAs at 4 US centers from 1981 to 2006. CAAs were defined on the basis of z scores of >3 or Japanese Ministry of Health and Welfare criteria. Our primary outcome was the proportion of patients presenting at illness day ≤21 who would have received intravenous immunoglobulin (IVIG) treatment by following the AHA guidelines at the time of their initial presentation to the clinical center. RESULTS-Of195patients who met entry criteria, 137 (70%) met the case definition and would have received IVIG treatment at presentation. Fifty-three patients (27%) had suspected incomplete KD and were eligible for algorithm application; all would have received IVIG treatment at presentation. Of the remaining 5 patients, 3 were excluded from the algorithm because of fever for <5 days at presentation and 2 because of <2 clinical criteria at >6 months of age. Two of these 5 patients would have entered the algorithm and received IVIG treatment after follow-up monitoring. Overall, application of the AHA algorithm would have referred ≥190 patients (97%) for IVIG treatment. CONCLUSIONS-Application of the 2004AHA recommendations, compared with the classic criteria alone, improves the rate of IVIG treatment for patients with KD who develop CAAs. Future multicenter prospective studies are needed to assess the performance characteristics of the AHA algorithm in febrile children with incomplete criterion findings and to refine the algorithm further.Address correspondence to Elizabeth S. Yellen, MD, Children's Hospital Boston, Department of Cardiology, 300 Longwood Ave, Boston, MA 02115. elizabeth.yellen@cardio.chboston.org. FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2010 July 2. In 2004, the American Heart Association (AHA) published a statement on the diagnosis, treatment, and long-term management of KD, which subsequently was endorsed by the American Academy of Pediatrics. 5 The report included an algorithm to aid clinicians in the evaluation of patients with suspected KD who do not meet the complete case definition and thus may not be identified or receive timely referral for IVIG treatment. The AHA algorithm for patients with suspected incomplete KD was based on expert opinion and anecdotal reports, rather than large clinical trials or registries. In a retrospective, multicenter study, we sought to assess the performance of the AHA recommendations for IVIG treatment for children with CAAs attributable to KD. METHODS SubjectsWe performed a retrospective chart review of data for childre...