Background Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.
The clinical features of Kawasaki disease (KD) overlap with those of other paediatric febrile illnesses. A missed or delayed diagnosis increases the risk of coronary artery damage. Our computer algorithm for KD and febrile illness differentiation had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 94.8%, 70.8%, 93.7% and 98.3%, respectively, in a single-centre validation study. We sought to determine the performance of this algorithm with febrile children from multiple institutions across the USA.We used our previously published 18-variable panel that includes illness day, the five KD clinical criteria and readily available laboratory values. We applied this two-step algorithm using a linear discriminant analysis-based clinical model followed by a random forest-based algorithm to a cohort of 1059 acute KD and 282 febrile control patients from five children's hospitals across the USA.The algorithm correctly classified 970 of 1059 patients with KD and 163 of 282 febrile controls resulting in a sensitivity of 91.6%, specificity of 57.8% and PPV and NPV of 95.4% and 93.1%, respectively. The algorithm also correctly identified 218 of the 232 KD patients (94.0%) with abnormal echocardiograms.The expectation is that the predictive accuracy of the algorithm will be reduced in a real-world setting in which patients with KD are rare and febrile controls are common. However, the results of the current analysis suggest that this algorithm warrants a prospective, multicentre study to evaluate its potential utility as a physician support tool.
Objective Children with Kawasaki disease (KD) and an initial echocardiogram that demonstrates coronary artery aneurysms (CAAs, Z score ≥2.5) are at high risk for severe cardiovascular complications. We sought to determine if primary adjunctive infliximab treatment at a dose of either 5 or 10 mg/kg, compared with intravenous immunoglobulin (IVIG) alone, is associated with a greater likelihood of CAA regression in patients with KD with CAA at the time of diagnosis. Design and setting Single-centre observational study. Patients Children with acute KD and Z score ≥2.5 at baseline. Interventions Primary adjunctive infliximab (5 or 10 mg/kg) within 48 hours of initiating IVIG 2 g/kg. Main outcome measures Incidence of CAA regression to Zmax <2 within 2 months of disease onset. Results Of the 168 patients with KD, 111 received IVIG alone and 57 received primary adjunctive infliximab therapy: 39 received 5 mg/kg and 18 received 10 mg/kg. Incidence of CAA regression to Zmax <2 within 2 months was statistically significant at 52%, 62% and 83% in the IVIG alone, IVIG+infliximab 5 mg/kg and IVIG+infliximab 10 mg/kg, respectively. The multivariable logistic regression model adjusting for age, sex, baseline Zmax and bilateral CAA at baseline showed that IVIG plus 10 mg/kg infliximab was significantly associated with a greater likelihood of CAA regression (adjusted OR: 4.45, 95% CI 1.17 to 16.89, p=0.028) compared with IVIG alone. The difference between IVIG+infliximab 5 mg/kg and IVIG alone was not significant. Conclusions Primary adjunctive high-dose 10 mg/kg infliximab treatment was associated with a greater likelihood of CAA regression in patients with CAA at the time of diagnosis.
Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups.We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex.Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup.Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation.US National Institutes of Health and the Irving and Francine Suknow Foundation.
The distribution of a syndrome in space and time may suggest clues to its etiology. The cause of Kawasaki syndrome, a systemic vasculitis of infants and children, is unknown, but an infectious etiology is suspected.
Background: Kawasaki disease (KD) disproportionately affects children of Asian descent. San Diego is home to a large Vietnamese population but no previous study has addressed the outcome of KD in this group. Methods: We performed a retrospective review of Vietnamese patients seen at Rady Children’s Hospital San Diego from 2001 to 2019. Non-Vietnamese Asian and non-Asian KD patients were matched (2:1) based on date of onset and age with Vietnamese patients. Demographic, clinical, and echocardiographic data were compared. Interviews with cardiologists at the Children’s Hospital 1 in Ho Chi Minh City, Vietnam, explored local practices in the diagnosis and management of KD patients. KD publications in Vietnamese were translated and summarized. Results: Of 978 KD patients for whom both parents had the same ethnicity, 20 were Vietnamese (2.1%), 168 (17%) were non-Vietnamese Asian, and 789 (81%) were non-Asian. Vietnamese and non-Vietnamese Asians had an earlier median day of diagnosis at day 6 (interquartile range [IQR] 5–6) and 5.5 (IQR 4–6.75), respectively, compared with non-Asians (day 7, IQR 5–8.75, P = 0.02). Prominent cervical lymphadenopathy at diagnosis was more common in both Vietnamese and non-Vietnamese Asians (20% and 40%, respectively) compared with non-Asians (12.5%, P = 0.01). Importantly, Vietnamese KD patients had a higher rate of coronary artery aneurysms (60% vs. 27.5%) compared to non-Asians ( P = 0.024). Vietnamese literature review and structured interviews suggested a high incidence and severity of KD in Vietnamese children. Conclusions: Physicians should be aware that Vietnamese children may be disproportionately affected by KD and have worse coronary artery outcomes.
