Age-Dependent Variations in Kawasaki Disease Incidence in Japan.

Importance: The etiology of Kawasaki disease (KD) remains elusive, with immunologic and epidemiologic data suggesting different triggers in individuals who are genetically susceptible. KD remains the most common cause of acquired heart disease in pediatric patients, and Japan is the country of highest incidence, with an increasing number of cases. Objective: To investigate whether an analysis of the epidemiologic KD record in Japan stratified by age and prefecture (subregion) may yield new clues regarding mechanisms of exposure to etiologic agents associated with KD. Design, Setting, and Participants: This cross-sectional study was conducted using a dataset of patients with KD with detailed information on location and age at onset created through nationwide surveys of hospitals caring for pediatric patients with KD throughout Japan. Pediatric patients hospitalized in Japan for KD from 1970 to 2020 were included. Data were analyzed from January 2022 to January 2024. Exposure: Pediatric patients with KD. Main Outcomes and Measures: The KD dataset was analyzed by patient age (infants [aged <6 months], toddlers [aged 6 to <24 months], children aged 2 years [aged 24 to <36 months], and children and adolescents aged 3 years or older [aged ≥36 months]), with investigations of seasonal cycles, interannual variations, and correlations across regions. Results: Among 422 528 pediatric patients (243 803 males [57.7%] and 178 732 females [42.3%]; median [IQR] age, 23.69 [11.96-42.65] months), infants, toddlers, and patients aged 3 years or older exhibited different rates of increase in KD incidence, seasonality, and degrees of coherence of seasonality across prefectures. Although the mean (SD) incidence of KD among infants remained relatively stable over the past 30 years compared with older patients (1.00 [0.07] in 1987-1992 to 2.05 [0.11] in 2011-2016), the mean (SD) incidence rate for children and adolescents aged 3 years or older increased 5.2-fold, from 1.00 (0.08) in 1987 to 1992 to 5.17 (0.46) in 2014 to 2019. Patients aged 3 years or older saw a reduction in mean (SD) incidence, from peaks of 5.71 (0.01) in October 2014 through June 2015 and July 2018 through March 2019 to 4.69 (0.11) in 2016 to 2017 (17.8% reduction) not seen in younger children. The seasonal cycle varied by age group; for example, mean (SD) incidence peaked in July and August (5.63 [0.07] cases/100 000 individuals) for infants and in December and January (4.67 [0.13] cases/100 000 individuals) for toddlers. Mean (SD) incidence changed dramatically for toddlers beginning in the early 2010s; for example, the normalized mean (SD) incidence among toddlers for October was 0.74 (0.03) in 1992 to 1995 and 1.10 (0.01) in 2016 to 2019. Across Japan, the seasonal cycle of KD incidence of older children and adolescents exhibited mean (SD) correlation coefficients between prefectures as high as 0.78 (0.14) for prefecture 14 among patients aged 3 years or older, while that of infants was much less (highest mean [SD] correlation coefficient, 0.43 [0.23]). Conclusions and Relevance: This study found distinct temporal signatures and changing spatial consistency of KD incidence across age groups, suggesting different age-related mechanisms of exposure. Some results suggested that social factors may modulate exposure to etiologic agents of KD; however, the increase in KD incidence in older children coupled with the correlation across prefectures of KD incidence suggest that the intensity of an environmental exposure that triggers KD in this age group may have increased over time.

Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan.

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment. Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts. Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P < 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics (n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels. Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.

Assessment of Pediatric Admissions for Kawasaki Disease or Infectious Disease During the COVID-19 State of Emergency in Japan.

Importance: The development of Kawasaki disease (KD) has been suggested to be associated with droplet- or contact-transmitted infection; however, its triggers and transmission modes remain to be determined. Under an epidemic of SARS-CoV-2, the COVID-19 state of emergency in Japan served as a nationwide social experiment to investigate the impact of quarantine or isolation on the incidence of KD. Objective: To assess the role of droplet or contact transmission in the etiopathogenesis of KD. Design, Setting, and Participants: This multicenter, longitudinal, cross-sectional study was conducted from 2015 to 2020 at Fukuoka Children's Hospital and 5 adjacent general hospitals. The number of admissions for KD and infectious diseases were analyzed. Participants were pediatric patients admitted to the participating hospitals for KD or infectious diseases. Exposures: Quarantine and isolation owing to the COVID-19 state of emergency. Main Outcomes and Measures: The primary end points were the ratios of patients with KD to patients with respiratory tract or gastrointestinal infections admitted from April to May in 2015 to 2019 and 2020. A Poisson regression model was used to analyze them. Results: The study participants included 1649 patients with KD (median [interquartile range] age, 25 [13-43] months; 901 boys [54.6%]) and 15 586 patients with infectious disease (data on age and sex were not available for these patients). The number of admissions for KD showed no significant change between April and May in 2015 to 2019 vs the same months in 2020 (mean [SD], 24.8 [5.6] vs 18.0 [4.0] admissions per month; 27.4% decrease; adjusted incidence rate ratio [aIRR], 0.73; 95% CI, 0.48-1.10; P = .12). However, the number of admissions for droplet-transmitted or contact-transmitted respiratory tract infections (mean [SD], 157.6 [14.4] vs 39.0 [15.0] admissions per month; 75.3% decrease; aIRR, 0.25; 95% CI, 0.17-0.35; P < .001) and gastrointestinal infections (mean [SD], 43.8 [12.9] vs 6.0 [2.0] admissions per month; 86.3% decrease; aIRR, 0.14; 95% CI, 0.04-0.43; P < .001) showed significant decreases between April and May in 2015 to 2019 vs the same months in 2020 (total, 12 254 infections). Thus, the ratio of KD to droplet- or contact-transmitted respiratory tract and gastrointestinal infections incidence in April and May 2020 was significantly increased (ratio, 0.40 vs 0.12; χ21 = 22.76; P < .001). Conclusions and Relevance: In this study, the significantly increased incidence of KD compared with respiratory tract and gastrointestinal infections during the COVID-19 state of emergency suggests that contact or droplet transmission is not a major route for KD development and that KD may be associated with airborne infections in most cases.

Treatment change and coronary artery abnormality in incomplete Kawasaki disease.

BACKGROUND: Incomplete Kawasaki disease (iKD) showed a higher incidence of coronary artery abnormalities (CAAs) than complete KD. However, the incidence of CAAs among iKD patients may have changed recently. METHODS: We examined KD patients from recent nationwide surveys conducted between 2013 and 2016 and compared them with the results of a previous survey (2001-2002). RESULTS: Of 63 270 KD patients, 13 770 patients (22%) had iKD. They showed a higher incidence of convalescent-phase CAAs (cCAAs, 2.8%) than complete KD (2.1%). The incidence of cCAAs in patients with one or two symptoms (6.7%) was significantly higher than those with three or four symptoms (2.6%) (P < 0.0001). Intravenous immunoglobulin (IVIG) treatment was administered to 80% of iKD patients; 30% of them received IVIG before the fifth illness day (early treatment) and 12% of patients received IVIG after the seventh illness day (late treatment). In the previous survey, the incidence of cCAAs was higher in both iKD (5.9%) and cKD (4.4%). Intravenous immunoglobulin was administered to 62% of iKD patients; 26% of them received early treatment, and 16% received late treatment. CONCLUSIONS: The incidence of cCAAs remained higher among iKD patients than cKD patients but this difference was reduced by the increased proportion of iKD patients treated with IVIG and those at an earlier time point. It is important to recognize the possibility that patients may have iKD and perform echocardiography even if they present with a few principal symptoms.

Cardiac Valvular Lesions due to Kawasaki Disease: A Japanese Nationwide Survey.

OBJECTIVES: To clarify the characteristics of valvular lesions after Kawasaki disease with a Japanese nationwide survey. STUDY DESIGN: Among 137 026 patients in the nationwide Japanese surveys between 2007 and 2016, 290 (0.2%) with valvular sequelae were investigated by questionnaires. RESULTS: Among the 290 patients with valvular sequelae, mitral regurgitation (MR), tricuspid regurgitation, aortic regurgitation, and pulmonary regurgitation were present 1 month after the development of Kawasaki disease in 183 (63%), 112 (39%), 39 (13%), and 49 (17%) patients, respectively. The numbers of patients with MR during the acute phase and 1 year after developing Kawasaki disease were 208 (72%) and 95 (33%), respectively. MR improved significantly during the late period (P < .0001). Although aortic regurgitation and tricuspid regurgitation also improved significantly (P < .001), pulmonary regurgitation did not change. Ruptured mitral valves chordae tendineae occurred in 6 infants by 6 months of age, within 4 months after the onset of Kawasaki disease. Three patients needed mitral valve plasty, and 1 patient died of acute heart failure. Another 4-month-old girl died of an acute myocardial infarction with MR. In the acute phase, there was a significant difference in the MR severity between the intravenous immunoglobulin-responder group and the intravenous immunoglobulin-resistant group (P < .05). CONCLUSIONS: The inflammation caused by acute Kawasaki disease affects the function of the mitral valves. Most cases of MR improve with the alleviation of inflammation. Severe MR may have decreased with the development of treatment for acute vasculitis. However, ruptured mitral valves chordae tendineae rarely occurs in infants younger than 6 months old, within 4 months after Kawasaki disease.

Cumulative incidence of Kawasaki disease with cardiac sequelae in Japan.

BACKGROUND: Some patients with Kawasaki disease (KD) develop cardiac sequelae, which increase the risk of subsequent ischemic heart events. Knowing the cumulative incidence (CI) of KD with cardiac sequelae may contribute to developing health policies to prevent subsequent ischemic events in these patients. METHODS: Study participants consisted of 254 984 patients aged 0-9 years with KD who were registered in nationwide surveys in Japan from 1991-2016. We calculated the incidence probabilities by dividing the number of patients with KD aged 0-9 years by the population used in vital statistics of each calendar year. We calculated the cumulative proportion of those not affected by KD, by multiplying each probability in patients aged from age 0-9 years. The CI of KD was obtained by subtracting this value from 1. We also calculated the number of patients in each birth cohort (BC). The same was done to calculate the CI of KD-related cardiac sequelae. RESULTS: The CIBC steadily increased from 0.005067 in males and 0.003668 in females in 1991 to 0.011431 in males and 0.0088253 in females in 2007. The CIBC of KD with cardiac sequelae decreased from 0.000478 in males and 0.000213 in females in 1997 to 0.000339 in males and 0.000169 in females in 2007. CONCLUSION: The increasing CIBC of KD indicates an increased susceptibility to KD in accordance with birth year. The decreasing CIBC of cardiac sequelae suggests the efficacy of KD treatment.

Seasonality of i.v. immunoglobulin responsiveness in Kawasaki disease.

BACKGROUND: Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016. METHODS: In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared. RESULTS: From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex. CONCLUSIONS: The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015-2016.

BACKGROUND: Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD. METHODS: The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians. RESULTS: The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0-4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age-specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age. CONCLUSIONS: We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture.

Epidemiologic features of Kawasaki disease distinguished by seasonal variation: an age-specific analysis.

PURPOSE: The purpose of this study was to review the seasonal variation of Kawasaki disease (KD) by an age-specific analysis to clarify the distribution of infectious agents. METHODS: Data obtained from nationwide surveys of KD in Japan, which targeted patients for 12 years (2003-2014), were analyzed. The monthly numbers of patients were classified into the following age groups: 0-11 months, 1 year, 2-3 years 5 months, and 3 years 6 months-4 years. Factors associated with disease onset were analyzed using a 12-month moving average method. RESULTS: In winter, a sharp peak was observed in all age groups, but this was notably sharper in the 1-year age group. Plateaus in disease occurrence were observed in two periods: from March to May in the 2- to 4-year age group and from June to August in the 0- to 11-month age group. Seasonal index was analyzed into two factors that differed depending on the age group. CONCLUSIONS: The age-specific analysis of KD clearly identified age-related differences in the seasonal occurrence of this disease.

The effects of early intravenous immunoglobulin therapy for Kawasaki disease: The 22nd nationwide survey in Japan.

BACKGROUND: Although intravenous immunoglobulin (IVIG) therapy is the standard therapy for Kawasaki disease (KD) to prevent coronary aneurysms including dilatations, it is unclear whether early IVIG therapy is more efficient in the acute stage of KD. METHODS: We conducted a cohort study using data from the 22nd nationwide survey of KD in Japan from January 2011 to December 2012. We excluded patients with recurrent KD and whose first admission day was later than seven days from the onset of symptoms. Finally, 20,933 patients with echocardiography assessment and IVIG therapy were divided into three groups according to the start of the IVIG therapy: 1) early: ≤4 days, 2) conventional: 5-7 days, and 3) late: 8-10 days. Then we investigated whether the early IVIG therapy prevented coronary dilatation or aneurysm after multiple adjustments for age, sex, total amount of IVIG, use of steroids, infliximab, other immunosuppressive agents, and plasma exchange. RESULTS: After multiple adjustments, conventional therapy had similar risks for coronary dilatation or aneurysm compared with early therapy (odds ratio [OR]:0.95; 95% confidence interval [CI], 0.78-1.16), whereas late therapy had a higher risk (OR:1.66; 95% CI, 1.03-2.68). Other risk factors for coronary dilatation or aneurysm were young male, older age, use of steroids, infliximab, other immunosuppressive agents, and a larger amount of total IVIG. CONCLUSIONS: Early IVIG therapy for KD did not reduce the risk for coronary dilatation or aneurysm compared with conventional therapy. It is recommended to start IVIG therapy within 7 days from the onset of symptoms.

Epidemiological observations of Kawasaki disease in Japan, 2013-2014.

BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. In Japan, the number of patients and incidence rate of KD has increased continuously since its discovery. The aim of this report was to analyze the latest nationwide epidemiological survey of KD in Japan. METHODS: The 23rd nationwide survey of KD was conducted in 2015. To report on all patients diagnosed with KD in 2013 and 2014, a questionnaire was sent to hospitals with ≥100 beds containing pediatric departments, as well as specialized pediatric hospitals. RESULTS: The number of KD patients reported was 15 696 in 2013 and 15 979 in 2014, resulting in an annual incidence rate of 302.5 and 308.0 per 100 000 population aged 0-4 years, respectively. The number of patients and incidence rate of KD in 2014 were the highest ever recorded in Japan. The number of patients diagnosed per month peaked in January, and a gradual increase in summer was also observed. Eight patients died of KD in 2013 and 2014. CONCLUSIONS: The number of patients and incidence rate of KD in Japan continue to increase. Continued surveillance of epidemiological trends of KD is therefore required.

Cumulative incidence of Kawasaki disease in Japan.

BACKGROUND: Although the incidence rates of Kawasaki disease (KD) in Japan have been determined in nationwide surveys, the cumulative incidence, that is, the proportion of those with a history of KD in the general population of 10-year-olds, is currently unknown. The aim of this study was therefore to assess the cumulative incidence of KD in Japan. METHODS: Using the age- and sex-specific incidence rate of KD in Japan from the results of the nationwide surveys, incidence probabilities, that is, the age-specific number of KD patients divided by the population used in the vital statistics, and cumulative proportions of those not affected by KD up to the end of 9 years of age, were calculated. The cumulative incidence was then defined as 1 minus the cumulative proportion. The observed age classes were 0, 1, 2, 3, 4, and 5-9 years. All data were calculated by sex. RESULTS: The cumulative incidence was 0.004833 for boys and 0.003474 for girls in 1991, but was 0.015284 and 0.012145 in 2014, respectively. According to these figures, 15.284 per 1,000 boys and 12.145 per 1,000 girls have been affected by KD by the age of 10 years. The birth-cohort cumulative incidences had similar trends. CONCLUSIONS: More than 10 persons in 1,000 have a history of KD at age 10 years in Japan.

Nationwide Survey of Patients With Giant Coronary Aneurysm Secondary to Kawasaki Disease 1999-2010 in Japan.

BACKGROUND: Giant coronary aneurysm is the most severe sequela in Kawasaki disease, occurring in approximately 0.2% of patients in Japan. Regression is rare, while myocardial infarction (MI) and sudden death are relatively common. Herein, we reviewed patients with giant coronary aneurysm in a 10-year period.Methods and Results:A nationwide questionnaire survey was conducted based on a national epidemiological database from 1999 to 2010. We identified 355 giant coronary aneurysm patients, of whom 209 were analyzed. The 5- and 10-year total cardiac event-free rates were 0.72 and 0.68, respectively. Twelve patients died, and MI was observed in 32 patients (18.1%). Five and 6 deaths were due to coronary rupture and MI, respectively. All ruptures occurred within 1 month of onset, while most MI occurred within 18 months. There was no death beyond 2 years. Aneurysm size was significantly related to the occurrence of MI in both the right and left coronary arteries. At the time of writing, 55% of patients had no exercise limitations. And including patients who cannot perform strenuous exercises, 81% of patients were leading ordinary lives. CONCLUSIONS: Severe cardiac events are likely to occur within 2 years from onset of Kawasaki disease, while no deaths occurred beyond this time. Hence, careful monitoring is needed especially for the first 2 years. Most patients with giant coronary aneurysms can lead ordinary lives with appropriate management.

Epidemiologic features of Kawasaki disease: Winter versus summer.

BACKGROUND: The epidemiology of Kawasaki disease (KD) shows seasonal variations, although the etiology of KD is unknown. In this study, we compared the clinical epidemiology of KD onset in winter versus that in summer to identify its etiology, that is, infectious agents. METHODS: Epidemiologic features of KD were compared between two seasons with high incidence (January [winter] and July [summer]) using a dataset of the 22nd nationwide survey in Japan. Data on patients who visited hospital during 2011-2012 in Japan were analyzed after adjusting for age differences. Subgroup analysis was carried out for day of illness at the day of first hospital visit. RESULTS: The total number of KD patients reported in the survey was 26 691. The number of patients who visited hospital with KD for the first time in January and July was 2,812 and 2,302, respectively. The proportion of patients in the age group 15 months-3 years was 38.8% in January and 33.5% in July. Mean serum albumin was significantly lower in January than in July (at days 2-5 of illness, P < 0.05). There were no between-group differences with respect to treatment, incidence of cardiac lesions, recurrence, or history of KD among the patients' siblings and parents. CONCLUSION: No significant differences were observed between KD with onset in January and July, although minor differences with respect to age distribution and serum albumin were observed.

Difference in Risk Factors for Subtypes of Acute Cardiac Lesions Resulting from Kawasaki Disease.

Few studies discuss the risk factors for acute cardiac lesions (within 30 days) resulting from Kawasaki disease (KD). We aimed to clarify the characteristics of patients with cardiac lesions within 30 days and determine the risk factors for acute cardiac lesion subtypes. Using the 23rd nationwide survey of KD in Japan, we analyzed data from patients with or without acute cardiac lesions resulting from KD (n = 31,380). We subdivided patients with acute cardiac lesions into three types: acute valvular lesions, coronary aneurysms, and giant coronary aneurysms (GCA), and calculated the odds ratios of potential risk factors for acute cardiac lesion subtypes. The prevalence of acute cardiac lesions was 8.6%, and these lesions were more prevalent among males than females (1.98:1). Male sex, age <1 year, and atypical definite cases predicted coronary artery lesions (CAL). The risk factors for valvular lesions differed from the risk factors for CALs, but GCA risk factors were similar to CAL risk factors: age <1 year, later presentation to hospital, atypical definite cases, and resistance to initial intravenous immunoglobulin (IVIG) therapy. Resistance to IVIG therapy was a significant risk factor for acute GCA. We found differences in cardiac lesion risk factors within 30 days of diagnosing KD between acute CAL and valvular lesions resulting from KD. In particular, pediatricians should consider atypical definite cases and resistance to initial IVIG when assessing the risk of acute-phase GCA.

Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.

BACKGROUNDS: Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. METHODS: Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). RESULTS: The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. CONCLUSIONS: IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae.

Recurrent Kawasaki disease: USA and Japan.

BACKGROUND: Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. METHODS: Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984-2008) and the 17th Japanese nationwide survey (2001-2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non-recurrent KD patients. RESULTS: Of the 5557 US KD patients <18 years of age during 1984-2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non-recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment. CONCLUSIONS: Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD.

Cardiac lesions and initial laboratory data in Kawasaki disease: a nationwide survey in Japan.

BACKGROUND: Cardiac lesions, such as coronary dilatation, aneurysms, narrowing, myocardial infarction, and valvular lesions, sometimes occur in Kawasaki disease, but most studies have only evaluated cardiac lesions in the later phase of the disease. This study was undertaken to clarify the related factors between cardiac lesions and laboratory data in the initial phase of Kawasaki disease. METHODS: We conducted a cross-sectional study using data for 26 691 patients from the 22nd nationwide survey of Kawasaki disease in Japan, the observation period of which was from January 2011 through December 2012. We excluded patients with recurrent Kawasaki disease and who were more than seven days from the start of symptoms at admission. We analyzed 23 155 cases (13 353 boys; mean age: 923 ± 734 days) with available laboratory data for white blood cell count, platelet count, serum albumin, and C-reactive protein (CRP). RESULTS: Cardiac lesions were detected in 984 cases (656 boys and 328 girls); lesions were classified as coronary dilatation (764 cases), coronary aneurysm (40), giant coronary aneurysm (6), coronary narrowing (3), and valvular lesions (204). The significant related factors of initial coronary dilatation were male sex (odds ratio [OR] 1.73), older age (OR per 100 days increase 1.03), higher platelet count (OR per 10 000 cells/µL increase 1.006), lower albumin (OR per 1 g/dL increase 0.66), and higher CRP (OR per 1 mg/dL increase 1.02). The factors related to coronary aneurysm were higher platelet count (OR 1.01) and lower albumin (OR 0.34). No factors were significantly related to giant coronary aneurysm. The related factors of valvular lesions were age (OR 0.98), and higher CRP (OR 1.05). CONCLUSIONS: Clinicians should consider male sex, older age, higher platelet count, lower albumin levels, and higher CRP levels when assessing risk of cardiac lesions in the initial phase of Kawasaki disease.

Descriptive epidemiology of Kawasaki disease in Japan, 2011-2012: from the results of the 22nd nationwide survey.

BACKGROUND: The number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan. We have therefore characterized the latest epidemiological information on KD. METHODS: The 22nd nationwide survey of KD, which targeted patients diagnosed with KD in 2011 and 2012, was conducted in 2013 and included a total of 1983 departments and hospitals. In order to report on all patients with KD during the 2 survey years, we targeted hospitals of 100 beds or more with pediatric departments, or specialized pediatric hospitals. RESULTS: From a total of 1420 hospitals and departments (71.6% response rate), 26,691 KD patients were reported (12,774 in 2011 and 13,917 in 2012; 15,442 males and 11,249 females). The annual incidence rates were 243.1 per 100,000 population aged 0 to 4 years in 2011 and 264.8 in 2012. The number of cases of KD recorded in 2012 was the highest ever reported in Japan. The incidence rate of complete cases was also the highest ever reported in Japan and contributed to the increase in the rate of total cases in recent years. The number of patients diagnosed per month peaked in January, and additional peaks were noted during summer months, although these peaks were lower than those seen in winter. Age-specific incidence rate showed a monomodal distribution with a peak in the latter half of the year in which patients were born. CONCLUSIONS: The number of patients and the incidence rate of KD in Japan continue to increase. A similar trend has also been seen for patients with complete KD.