阿江 竜介

BACKGROUND: Although probable sporadic Creutzfeldt-Jakob Disease (CJD) can be diagnosed without prion protein gene (PRNP) testing, some patients with genetic prion disease may meet the diagnostic criteria for sporadic CJD. We aimed to assess the potential for such misclassification in the absence of genetic information. METHODS: We analyzed data from the nationwide prospective registry of prion diseases in Japan. For patients diagnosed with probable sporadic CJD, clinical characteristics were compared according to whether PRNP testing had been performed. In addition, patients with genetic prion diseases were reclassified to evaluate potential misclassification as sporadic CJD. RESULTS: A total of 3008 patients with sporadic CJD and 1143 with genetic prion diseases were analyzed. Tested and Not-Tested groups differed in age at onset (difference, -1 year; 95% CI, -3 to -1) and CSF RT-QuIC positivity (difference, 8.2%; 95% CI, 3.4 to 13.2). The median survival time was 11.9 months for the Tested group and 9.8 months for the Not-Tested group. The proportions of misclassification after reclassification of patients with genetic prion diseases (95% CI) were 82.9% (75.5, 88.5) for E200K, 24.1% (20.9, 27.6) for V180I, 72.7% (64.6, 79.6) for M232R, 12.3% (8.1, 18.2) for P102L, 0% (0, 13.8) for P105L, and 10% (1.8, 40.4) for D178N. CONCLUSIONS: A substantial proportion of patients with genetic prion disease may meet the clinical diagnostic criteria for sporadic CJD. Opportunities for PRNP testing may be limited in patients with rapidly progressive disease.

BACKGROUND: Coronary artery (CA) lesions (CALs) are major complications of Kawasaki disease (KD). Studies have reported that coronary outcomes (CAL regression and progression) are associated with age; however, age-stratified data remain limited. METHODS: We analyzed data from 129,950 patients with KD in Japan (2011-2022). CALs were classified as CA dilatation, CA aneurysm, or giant CA aneurysm. Coronary outcomes were assessed by comparing echocardiographic findings between baseline and the subacute phase. Patients were stratified into nine 6-month age groups. Restricted cubic splines (RCS) were used to assess nonlinear associations between age and coronary outcomes. Multivariable logistic regression analyses assessed age-specific associations using the RCS-identified reference group. RESULTS: Among patients without CALs at initial echocardiography, the 0 to 6-month group had the highest proportion with subsequent CAL development (2.8%). Among patients with CA dilatation, the 0 to 6-month group showed the lowest proportion of patients with CA regression (75.5%). RCS analyses identified the 25 to 30-month group as the most likely to show CA dilatation regression and the least likely to experience CAL progression. Multivariable analysis demonstrated that patients aged 0 to 6 months were significantly less likely to show CA dilatation regression (adjusted odds ratio [95% confidence interval]: 0.44 [0.30-0.63], reference: 25-30 months) and more likely to experience CAL progression (3.84 [3.03-4.86]). CONCLUSIONS: Coronary outcomes differed substantially across age groups; patients aged 0 to 6 months had the most adverse coronary outcomes. Even without CALs at initial echocardiography, this age group had the highest risk of subsequent CAL development.

IMPORTANCE: The COVID-19 pandemic may serve as a natural experiment, with pandemic-associated changes in the epidemiology of Kawasaki disease (KD) potentially informing understanding of KD pathogenesis. OBJECTIVES: To assess long-term KD incidence across 50 years and to examine pandemic-associated changes in KD epidemiology across age groups. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a descriptive epidemiologic analysis of data from the Japanese Nationwide Survey of Kawasaki Disease conducted from 2023 to 2024, along with 50 years of historical data. Data were included from patients with KD in the current 2023-2024 survey (n = 29 841) and historical and current survey data from 1975 through 2024 (n = 467 456) for trend analysis. MAIN OUTCOMES AND MEASURES: Annual KD incidence overall and stratified by 3 age groups: infants (<1 year), 1 to 4 years, and 5 to 9 years. RESULTS: The current survey registered 15 032 and 14 809 patients with KD in 2023 and 2024, respectively (overall, 57.3% male; median [IQR] age, 2 [1-4] years). Across the 50-year study period, despite the population under 5 years of age declining in Japan by 61.6%, KD incidence rates increased 16.1-fold. Across the COVID-19 pandemic period, patient numbers reached a nadir of 10 333 in 2022, then rebounded to 15 032 cases (45.5% increase) in 2023. Notably, decline and rebound patterns differed by age. Indexed incidence rates (using 2017 as a baseline of 100) demonstrated that patients 5 to 9 years of age had the largest decline (nadir of 54.2 in 2021, 45.8% below baseline) and the largest rebound (134.8 in 2024, 34.8% above baseline). In contrast, patients younger than 1 year showed the smallest decline (nadir of 73) and incidence rates did not return to baseline levels. When comparing the magnitude of rebound in KD incidence, a distinct age-dependent dose-response pattern was observed: 26.1% for infants, 38.9% for patients aged 1 year, 42.7% for patients aged 2 years, 85.8% for patients aged 3 years, 105.3% for patients aged 4 years, and 166.7% for patients aged 5 to 9 years. CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of KD in Japan, KD incidence rebounded after the relaxation of COVID-19 pandemic-related restrictions, with age-dependent patterns. Nonpharmaceutical interventions (eg, mask-wearing) during the pandemic may explain the greater rebound pattern observed in older children; however, the minimal changes in infants suggest different exposure pathways to potential KD triggers. These findings support an age-stratified approach to KD pathogenesis research, distinguishing infants from older children.

<h4>Background</h4>A previous study reported that among patients with complete Kawasaki Disease (KD), those exhibiting all six principal clinical features were more likely to develop coronary artery (CA) sequelae than those exhibiting only five features. We aimed to determine which specific features are associated with CA sequelae.<h4>Methods</h4>This retrospective cohort study analyzed 14,732 patients diagnosed with complete KD across Japan from January 2019 to March 2020. Separate multivariable conditional logistic regression analyses were performed to evaluate relative risk for CA sequelae in patients with all six principal clinical features, compared individually to those lacking each specific feature.<h4>Results</h4>7234 (49.1%) exhibited all six principal clinical features, while 7498 (50.9%) presented with five features. CA sequelae occurred in 2.1% of those with six features versus 1.7% with five. Multivariable conditional logistic regression analysis determined that patients with conjunctival injection were significantly more likely to develop CA sequelae compared with those lacking it (adjusted odds ratio [95% confidence interval], 3.6 [1.3-10.1]).<h4>Conclusions</h4>Among patients with complete KD, the absence of conjunctival injection-a relatively rare presentation-was associated with a lower cumulative incidence of CA sequelae. This finding may help identify distinct low-risk phenotypes of KD and support risk stratification.<h4>Impact</h4>This study emphasizes the importance of feature-specific risk for coronary artery (CA) sequelae among patients with complete Kawasaki Disease (KD). We found that among patients with complete KD, those with conjunctival injection were more likely to develop CA sequelae than were those lacking it. The absence of conjunctival injection-a relatively rare presentation in KD-is associated with a markedly lower cumulative incidence of CA sequelae. This finding may help identify a distinct low-risk phenotype of KD and aid risk stratification.

Kawasaki Disease (KD) is an acute pediatric vasculitis with unclear etiology, though environmental triggers have been proposed. This scoping review synthesized epidemiological evidence on outdoor environmental exposures and KD incidence. A systematic search up to December 2024 identified 32 eligible studies. KD incidence is highest in East Asia, particularly Japan, South Korea, and Taiwan, where most research has been concentrated. Meteorological variables and air pollutants were most studied. Approximately half of the studies on meteorological variables found associations with KD, with some suggesting the role of temperatures or wind-driven transport of airborne agents. Air pollution studies showed inconsistent short-term effects, but more consistent links with long-term or prenatal particulate matter exposure. Studies on airborne biological agents, though fewer, showed consistent positive findings. These results suggest a multifactorial etiology. However, heterogeneity in methods limits comparability. Little is known about chemical substances in soil, water, or other outdoor sources, which may also affect immune pathways relevant to KD. Standardized, multinational research is needed to clarify environmental contributions and guide prevention in high-risk regions.

BACKGROUND: Kawasaki disease (KD) is a vasculitis syndrome of unknown etiology and the leading cause of acquired heart disease in children in developed countries. The Japanese Nationwide Survey of Kawasaki Disease (JNSKD) in Japan has provided valuable epidemiological data since 1970, but has inherent limitations. We aimed to evaluate the utility of the National Database of Health Insurance Claims (NDB) for describing the epidemiologic features of KD. METHODS: We conducted retrospective cohort study compared NDB data (2013-2019) against JNSKD data for the same period. We analyzed demographic characteristics, temporal and geographic distributions, treatment modalities, and cardiac complications. RESULTS: NDB identified 120,391 KD patients (2013-2019), with JNSKD estimated to cover 94.0% of cases. Demographic characteristics showed strong concordance between datasets (male-to-female ratios: 1.32 vs 1.33; similar age distributions). Initial IVIG administration rates were highly similar (93.74% vs 93.85%). Incomplete KD was significantly underestimated in NDB (8.07% vs 19.48%). NDB revealed adjunctive therapies including urinastatin and tracked increasing infliximab use. Cardiac complication detection in NDB showed limited sensitivity for mild abnormalities (overall 5.0% vs 7.33%). NDB showed higher recorded rates of giant aneurysms (0.53% vs 0.17%) and myocardial infarction (0.15% vs 0.01%). CONCLUSIONS: The NDB provides a valid, complementary data source for KD epidemiological research with near-complete population coverage. While limitations exist for identifying disease subtypes and cardiac complications, its detailed treatment data offer significant advantages for nationwide surveillance and health policy development.

BACKGROUND: Lower platelet count is associated with intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD); paradoxically, higher count is associated with coronary artery (CA) sequelae. We addressed this inconsistency. METHODS: Using a large-scale nationwide KD database in Japan, we standardized platelet counts by age and hospital visit day. We evaluated associations between standardized platelet count and IVIG resistance using multivariable modified Poisson regression models. Associations between platelet count and CA sequelae were assessed separately among IVIG-resistant and IVIG-responsive patients. RESULTS: In 41,540 patients, lower standardized platelet counts were associated with IVIG resistance in all age groups and the association increased with age: adjusted risk ratios with 95% confidence intervals per standardized platelet count decrease of 1 were 1.15 [1.06-1.25] at 0-5 months, 1.08 [1.02-1.15] at 6-11 months, 1.18 [1.14-1.22] at 1-2 years, 1.22 [1.17-1.27] at 3-4 years, and 1.26 [1.19-1.33] at ≥5 years. Lower standardized platelet count was also associated with CA sequelae in IVIG-resistant patients (1.12 [1.02-1.23]), but not in IVIG-responsive patients (0.95 [0.86-1.04]). CONCLUSION: Lower platelet counts were associated with IVIG resistance and CA sequelae in IVIG-resistant patients. Early platelet evaluation may identify high-risk patients with KD. IMPACT: Previous studies of platelet counts have shown conflicting results: lower platelet counts were associated with immunoglobulin resistance, but higher platelet counts were associated with coronary artery complications. Lower platelet counts were associated with immunoglobulin resistance across all age groups. Moreover, lower platelet counts were associated with coronary artery complications, but this association was found only in immunoglobulin-resistant patients. Our study resolves previous conflicting results by properly adjusting for age, immunoglobulin responsiveness, and platelet examination timing. Early platelet count evaluation may aid in identifying patients at high risk of immunoglobulin treatment failure and subsequent coronary involvement.

OBJECTIVES: To identify clinical characteristics of patients with non-refractory Kawasaki disease (KD), which were defined as those who successfully responded to the standard initial intravenous immunoglobulin (IVIG) treatment (2 g/kg/day, single infusion) without any secondary or later additional specific treatments, and to investigate the factors associated with the development of coronary artery (CA) complications in patients with non-refractory KD. DESIGN: Retrospective cohort study. SETTING: Hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: A total of 122 489 patients who developed KD across Japan during 2011-2018. MAIN OUTCOME MEASURES: CA abnormalities identified after acute illness of KD (defined as CA sequelae). RESULTS: A total of 69 735 patients with non-refractory KD were identified, of which 672 (0.96%) experienced CA sequelae. Among patients with non-refractory KD, the presence of CA abnormalities identified at initial echocardiographic assessment was strongly associated with CA sequelae (adjusted OR (95% CI): 37.8 (31.9 to 44.7)). CA sequelae was also associated with male patients, infants (<12 months old), older patients (≥60 months old) and patients who received delayed initial IVIG treatment (>7 days from KD onset). Subgroup analyses demonstrated that delayed initial IVIG treatment was significantly associated with the development of CA sequelae in both patients with and without CA abnormalities identified at initial echocardiographic assessment. CONCLUSIONS: Approximately 1% of patients with non-refractory KD may develop CA sequelae. Our findings highlight the importance of initial echocardiographic assessment and early initiation of IVIG treatments for patients with KD.

IMPORTANCE: Global studies have reported that the incidence of Kawasaki disease (KD) declined during the COVID-19 pandemic. These studies suggest that the global pandemic and its accompanying mitigation measures may provide an important opportunity to explore the hypothesis of a KD pathogenesis. OBJECTIVE: To compare changes in KD incidence in Japan before and after the start of the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using the data set from Japan's 26th nationwide KD survey that obtained information on patients who were diagnosed with KD in Japan from January 1, 2019, through December 31, 2020. MAIN OUTCOMES AND MEASURES: Kawasaki disease incidence rates were calculated by referring to the national population data in the vital statistics data for Japan. RESULTS: A total of 28 520 patients were identified (16 236 male individuals [56.9%]; median [IQR] age, 26 [14-44] months). A total of 17 347 patients were diagnosed with KD in 2019 and 11 173 were diagnosed in 2020, representing a 35.6% reduction in the number of patients diagnosed in 2020 compared with the previous year. Patient distributions for days of illness at the first hospital visit were almost identical in 2019 and 2020, suggesting that the decrease in KD incidence likely was not associated with pandemic-related delays in seeking treatment. The proportion of patients diagnosed with KD who were younger than 12 months was significantly larger in 2020 than in 2019 (21.6% vs 19.4%; P < .001). Compared with KD incidence among younger patients, the incidence among those 24 months and older declined rapidly after initiation of COVID-19 special mitigation measures, with a greater percentage reduction (58.3% reduction in July), but rebounded faster after the end of the special mitigation period. By contrast, the incidence among patients younger than 12 months declined moderately after the initiation of the special mitigation period, with a lower percentage reduction (40.3% reduction in October), and rebounded at a later phase. CONCLUSIONS AND RELEVANCE: In this cohort study, the number of patients diagnosed with KD decreased by approximately one-third across Japan in 2020, with no indication that parents avoided a hospital visit. Differences in KD incidence reduction patterns before and after the initiation of COVID-19 pandemic mitigation measures were found in patients with KD aged younger than 12 months compared with those 24 months or older, suggesting a potential KD pathogenesis involving transmission among children.

BACKGROUND: No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset. METHODS: We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)). RESULTS: Of 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu. CONCLUSIONS: Methionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.

Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with < 2 months residence at study onset or new admission during the study period. Three analyses were performed: (1) ESBL-E carriage statuses in Cohort 1 and Cohort 2; (2) changes in ESBL-E carriage statuses 3-12 months after the first testing and ≥ 12 months after the second testing; and (3) lengths of positive ESBL-E carriage statuses. Compared with the residents in Cohort 1, a significantly larger proportion of residents in Cohort 2 were positive for ESBL-E carriage (28.0% in Cohort 1 vs 40.0% in Cohort 2). In the subsequent testing results, 18.3% of residents who were negative in the first testing showed positive conversion to ESBL-E carriage in the second testing, while no patients who were negative in the second testing showed positive conversion in the third testing. The maximum length of ESBL-E carriage was 17 months. The findings indicated that some residents acquired ESBL-E through potential cross-transmission inside the LTCFs after short-term residence. However, no residents showed positive conversion after long-term residence, which indicates that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures could improve the ESBL-E prevalence in geriatric LTCFs.

OBJECTIVE: To assess the epidemiologic association between Kawasaki disease and common pediatric infectious diseases (PIDs) identified during the coronavirus disease 2019 (COVID-19) pandemic period to confirm whether the infection-triggered theory is a plausible hypothesis for the pathogenesis of Kawasaki disease. STUDY DESIGN: A retrospective epidemiologic study was conducted using datasets obtained from Web-based surveillance of Kawasaki disease and PIDs in Japan. We compared weekly numbers of patients who developed Kawasaki disease and specific PIDs between 2020 and 2017-2019 and evaluated the association between the percent reduction in the number of patients with these diseases. RESULTS: A total of 868 patients developed Kawasaki disease in 2020. During the social distancing period in 2020, the number of patients with Kawasaki disease was approximately 35% lower than in 2017-2019. Time from the onset of Kawasaki disease until the first hospital visit did not differ significantly among the examined years. The proportion of older children with Kawasaki disease decreased more than that of infants with Kawasaki disease (age <1 year), resulting in a significant difference in the proportion of infant patients between 2020 and 2017-2019 (24% vs 19%; P < .01). The number of patients with incomplete Kawasaki disease was unchanged from that of previous years. The weekly percent reduction in patient numbers differed between Kawasaki disease and PIDs during 2020, with no strong correlation between the 2 diseases. CONCLUSIONS: Our data indicate that parents of patients with Kawasaki disease did not avoid hospital visits during the COVID-19 pandemic period. The findings indicate the possibility that triggering Kawasaki disease might be associated with presently unidentified respiratory pathogen(s) that potentially might be acquired from both within and outside the household.

Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.

OBJECTIVE: To investigate whether redness and crusting at the bacille Calmette-Guérin inoculation site (BCGitis), identified during acute illness owing to Kawasaki disease (KD), is an independent risk factor for development of cardiac complications. DESIGN: Retrospective cohort study using data from the nationwide KD survey in Japan. SETTING: Survey respondents included hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: We included 17 181 patients with KD across Japan during 2005-2006. MAIN OUTCOME MEASURES: BCGitis and cardiac complications resulting from KD. RESULTS: BCGitis was identified in 7549 (44%) patients with KD. Compared with patients without BCGitis, those with BCGitis were younger, more likely to be male, less likely to have recurrent status and visited a hospital and underwent initial intravenous immunoglobulin (IVIG) treatment earlier after KD onset. In the unadjusted model, patients with BCGitis were significantly less likely to have cardiac complications (crude OR 0.81, 95% CI 0.71 to 0.92). However, after including treatment factors (days of illness at initial IVIG and treatment responsiveness) in the adjusted model, the association was no longer significant (adjusted OR 0.89, 95% CI 0.77 to 1.03), indicating that BCGitis was not an independent factor associated with cardiac complication and might be confounded by treatment factors. CONCLUSIONS: BCGitis was identified in comparatively early illness stages of KD. Our findings indicated that BCGitis was not an independent factor associated with developing cardiac complications but was confounded by prompt initial IVIG administration, which might result in successful treatment and prevention of cardiac complications.

OBJECTIVE: To report the epidemiologic characteristics, treatments, and cardiac complications of Kawasaki disease, using data from the nationwide survey in Japan. STUDY DESIGN: The nationwide Kawasaki disease survey in Japan has been conducted biennially since 1970. The most recent survey was completed in 2019, obtaining information for patients who developed Kawasaki disease during 2017-2018. Survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where patients with Kawasaki disease were eventually hospitalized. RESULTS: The survey identified 32 528 patients with Kawasaki disease, which consisted of 15 164 (46.6%) in 2017 and 17 364 (53.4%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100 000 children aged 0-4 years). After 1982, patients with ≤4 principal Kawasaki disease signs gradually increased, resulting in 6847 (21.1%) patients diagnosed during 2017-2018. Among the 30 784 patients receiving initial intravenous immunoglobulin administration, 6061 (19.7%) did not respond. Within 30 days of Kawasaki disease onset, 9.0% of patients were diagnosed with cardiac complications, and 2.6% of patients developed cardiac sequelae after the acute illness. CONCLUSIONS: The annual number of patients developing Kawasaki disease in Japan increased from 1970 through 2018, whereas the proportion of patients with Kawasaki disease with cardiac complications decreased in the most recent 2 decades. Early diagnosis of Kawasaki disease as well as advances in initial treatments could explain these findings.

BACKGROUND Randomized controlled trials previously provided different conclusions about the superiority of adding corticosteroids to initial intravenous immunoglobulin treatment for the prevention of coronary artery abnormalities in patients with Kawasaki disease (KD). To further assess this issue, we analyzed large-scale data from nationwide KD surveys in Japan, where combination treatment (corticosteroids added to initial standard intravenous immunoglobulin treatment) has become commonly used for patients at high risk for KD. METHODS AND RESULTS Standard intravenous immunoglobulin treatment and combination treatment were compared using data from time periods with and without combination treatment. Outcome measures were coronary artery abnormalities and initial intravenous immunoglobulin treatment failure. Hospitals where ≥20% of patients received combination treatment were identified, and treatment and control groups were selected via matching by age, sex, illness day at initial treatment, and KD recurrence. Matched group selection and subsequent analyses were conducted 1000 times to minimize sampling bias and potential confounders (bootstrapping). From 115 hospitals, 1593 patients with KD in the treatment group and 1593 controls were selected for each of the 1000 sample iterations. The median proportion of patients who developed coronary artery abnormalities among the treatment group and controls were 4.6% (95% CI, 3.8%-5.8%) and 8.8% (95% CI, 7.5%-10.0%), respectively: an estimated risk ratio of 0.53 (0.41-0.67). A median of 14.1% (95% CI, 12.4%-15.9%) of the patients in the treatment group and 21.7% (95% CI, 19.8%-23.4%) in the controls had treatment failure: an estimated risk ratio of 0.65 (0.56-0.75). CONCLUSIONS Combination treatment reduced coronary artery abnormality risk by an estimated 47% and treatment failure by 35%. Multiple-dose corticosteroids may provide benefit in selected patients at high risk for KD.

BACKGROUND: Previous studies demonstrated that coronary artery lesions (CALs) resulting from Kawasaki disease (KD) can improve over time. However, limited information is available on sub-acute outcomes of CALs detected at admission during KD illness. METHODS: The nationwide Japanese KD survey contained substantial information on KD patients with CALs detected at admission and who received standard IVIG treatment within 10 days of disease onset. Coronary outcomes were evaluated by changes in CALs from admission to the first assessment at 30 days from disease onset in three categories: improved, unchanged, and progressed. Ordinal logistic regression analysis was performed to evaluate factors associated with the outcomes. RESULTS: Of 2024 patients with CALs detected at admission, improved, unchanged, and progressed outcomes were found in 1548 (76.5%), 390 (19.3%), and 86 (4.2%), respectively. Over 80% of patients with coronary artery (CA) dilatations had improved outcome. Independent factors associated with worse outcomes were larger-size CALs (adjusted ORs [95% CIs]: CA aneurysm = 5.13 [3.65-7.22] and giant CA aneurysms = 7.49 [3.56-15.72] compared with CA dilatation, respectively), age ≥ 60 months (1.45 [1.08-1.94] compared with 12-59 months), recurrent KD (1.57 [1.07-2.29]), parental history of KD (2.23 [1.02-4.85]), and delayed admission (8-10 days from disease onset: 1.76 [1.21-2.57] compared with 1-4 days). CONCLUSIONS: KD patients with larger CALs, ≥60 months old, and with recurrent status or parental history may require more rigorous treatment. In addition, delayed admission may result in worse coronary outcome, indicating that prompt diagnosis and treatment are required.

BACKGROUND: Platelet count is considered as a biomarker for the development of coronary artery abnormalities (CAAs) among Kawasaki disease (KD) patients. However, previous studies have reported inconsistent results. We addressed the controversial association of platelet count with CAAs using a large-scale dataset. METHODS: A retrospective cohort study was conducted using KD survey data from Japan (2015-2016; n = 25,448). Classifying patients by intravenous immunoglobulin (IVIG) responsiveness, we described the trends in platelet count using the lowest and highest values along with the specific illness days. Multivariate logistic regression analysis was performed to evaluate the association between platelet count and CAAs, adjusting for relevant factors. RESULTS: Platelet counts rapidly decreased from admission, reached the lowest count at 6-7 days, and peaked after 10 days. Platelet counts in IVIG non-responders decreased with a lower minimum value than IVIG responders, but subsequently rebounded toward a higher maximum. Compared with patients with normal platelet counts (150-450 × 10/L), patients with abnormally high platelet counts (>450 × 10/L) were more likely to have CAAs at admission (adjusted odds ratio: IVIG responders, 1.50 [95% confidence interval 1.20-1.87] and non-responders, 1.46 [1.01-2.12]). By contrast, IVIG non-responding patients whose counts were below normal (<150 × 10/L) after hospitalization were at higher risk for developing CAAs (2.27 [1.44-3.58]). CONCLUSIONS: Platelet count varied widely by illness day and was confounded by IVIG responsiveness, which might have contributed to previous inconsistent findings. KD patients with abnormally high platelet counts at admission or abnormally low counts after hospitalization were at higher risk for CAAs.