Mayumi Yashiro

Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey.

Background Although the number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan, the most recent epidemiologic features of KD are not known. Methods The 21st nationwide survey of KD was conducted in 2011 and included patients treated for the disease in 2009 and 2010. Hospitals specializing in pediatrics, and hospitals with a total of 100 or more beds and a pediatric department, were asked to report all patients with KD during the 2 survey years. Results A total of 1445 departments and hospitals reported 23 730 KD patients (10 975 in 2009 and 12 755 in 2010): 13 515 boys and 10 215 girls. The annual incidence rates were 206.2 and 239.6 per 100 000 children aged 0 to 4 years in 2009 and 2010, respectively; the 2010 rate was the highest ever reported in Japan. Monthly number of patients peaked during winter to spring months; lower peaks were noted during summer months. However, the seasonal patterns in 2009 and 2010 differed from those of previous years. The age-specific incidence rate had a monomodal distribution, with a peak during the latter half of the year of birth. The prevalences of cardiac lesions during acute KD and cardiac sequelae were higher among infants and older age groups. Despite a decrease in prevalence, the proportion of patients with giant coronary aneurysms—the most severe sequela of KD—did not substantially decrease. Conclusions The incidence rate and number of patients with KD continue to increase in Japan.

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.

Epidemiologic Features of Kawasaki Disease in Japan: Results from the Nationwide Survey in 2005-2006

Background The most recent epidemiologic features of Kawasaki disease are unknown. Methods The 19th nationwide survey of the disease was conducted in 2007, targeting patients who were affected by this disease in 2005 and 2006. All pediatric departments in hospitals with 100 or more beds and pediatric hospitals were asked to report all Kawasaki disease patients during the 2 survey years. Results From 1543 departments and hospitals, a total of 20475 patients (10041 in 2005 and 10434 in 2006) were reported. There were 11892 male patients and 8583 female patients. The average annual incidence rate was 184.6 per 100000 children aged 0-4 years. The number of patients and the incidence rate have increased significantly during the past 12 years. The age-specific incidence rate was distributed monomodally with a peak at 6-8 months of age. The prevalence of cardiac lesions in the acute phase of the disease and of cardiac sequelae were higher among infants and old patients. Conclusion The number of patients with Kawasaki disease and its incidence rate in Japan are continuously increasing.

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.

Kawasaki disease in parents and children

Aim: To estimate the probability that the parents of patients with Kawasaki disease also had a history of the same disease. Methods: Self‐reported parents’histories of Kawasaki disease were collected from data of the 16th nationwide survey of the disease conducted in Japan from January 1999 to December 2000. The incidence of Kawasaki disease was calculated by using data reported in all 16 nationwide surveys and live births in the Japanese vital statistics. The expected number of parents with a history of Kawasaki disease in the general population, which was calculated by using the assumed number of parents in the vital statistics and the incidence of this disease, was compared with the observed number. Results: Among 14163 parent pairs of patients with Kawasaki disease, 33 parents (25 mothers and 8 fathers) had a history of the disease. The number of parents expected to have a history of Kawasaki disease was 16.1 (8.4 mothers and 7.7 fathers). From a Poisson distribution, the probability of the observed number was less than 0.001 among parents or mothers. The prevalence of a recurrence of Kawasaki disease and incidences involving siblings of patients whose parents had a history of the disease were five or six times higher than those of all patients who were reported in the 16th survey.

Prevalence of coronary artery abnormality in incomplete Kawasaki disease

Background: The aim of the present study was to determine the prevalence of coronary artery abnormality (CAA) and other clinical features in patients with incomplete Kawasaki disease (iKD) using the data from the 17th Japanese nationwide survey of KD.

Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999-2002.

Objective: The purpose of the present study was to describe the results of nationwide epidemiologic surveys of Kawasaki disease for the 4 year period 1999–2002.

Seasonality and Temporal Clustering of Kawasaki Syndrome

Background: 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. Methods: Seasonality and clustering of Kawasaki syndrome cases were studied in Japanese children with Kawasaki syndrome reported in nationwide surveys in Japan. Excluding the years that contained the 3 major nationwide epidemics, 84,829 cases during a 14-year period (1987–2000) were analyzed. To assess seasonality, we calculated mean monthly incidence during the study period for eastern and western Japan and for each of the 47 prefectures. To assess clustering, we compared the number of cases per day (daily incidence) with a simulated distribution (Monte Carlo analysis). Results: Marked spatial and temporal patterns were noted in both the seasonality and deviations from the average number of Kawasaki syndrome cases in Japan. Seasonality was bimodal with peaks in January and June/July and a nadir in October. This pattern was consistent throughout Japan and during the entire 14-year period. Some years produced very high or low numbers of cases, but the overall variability was consistent throughout the entire country. Temporal clustering of Kawasaki syndrome cases was detected with nationwide outbreaks. Conclusions: Kawasaki syndrome has a pronounced seasonality in Japan that is consistent throughout the length of the Japanese archipelago. Temporal clustering of cases combined with marked seasonality suggests an environmental trigger for this clinical syndrome.

Increasing incidence of Kawasaki disease in Japan: Nationwide survey

Background: The last nationwide survey of Kawasaki disease in Japan was conducted in 2003; the epidemiologic features of the disease in Japan since then are unknown.

Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan.

Background: Some Kawasaki disease (KD) patients do not respond to initial treatment with intravenous immunoglobulin (IVIG). The purpose of this study was to determine potential risk factors associated with IVIG nonresponse among KD patients in Japan. Methods: Data were obtained from questionnaires used for the 18th nationwide KD survey of patients who visited hospitals in Japan from 2003 through 2004. Data for patients who met the case definition for KD and received 2 g/kg single infusion IVIG as the initial treatment within 10 days of illness were analyzed. IVIG nonresponders were defined as patients who needed secondary treatment after initial IVIG administration. Results: Among 15,940 KD patients in Japan during 2003–2004, 6330 patients received 2 g/kg single infusion IVIG within 10 days of illness onset. IVIG nonresponders accounted for 20.3% of them (n = 1286). Male sex [odds ratio (OR), 1.21, 95% confidence interval (CI), 1.06–1.37], receipt of the initial IVIG before the fifth day of illness (OR: 1.89, 95% CI: 1.66–2.15), and having recurrent KD (OR: 1.38, 95% CI: 1.00–1.90) were significantly associated with IVIG nonresponse. In addition, IVIG nonresponders had significantly higher risks for coronary artery aneurysms (OR: 10.38, 95% CI: 6.98–15.45) or giant coronary artery aneurysms (OR: 54.06, 95% CI: 12.84–227.65). Conclusions: Physicians should consider potential IVIG nonresponse among recurrent KD patients or KD patients diagnosed and treated before the fifth day of illness, particularly if they are boys and have laboratory values associated with nonresponse such as low platelet count, and elevated alanine aminotransferase and C-reactive protein. Some of these patients may benefit from administration of the alternative secondary treatment early during the illness along with the initial IVIG treatment.