Cardiac sequelae of Kawasaki disease in Japan: statistical analysis.

The proportions of Kawasaki disease patients with cardiac sequelae in Japan were analyzed using nationwide survey data from the 6 1/2-year period July 1982 through December 1988. Of 46,864 cases of Kawasaki disease reported in the surveys, 7637 or 16.3% had cardiac sequelae such as dilation or stenosis of coronary arteries, myocardial infarction, and valvar lesions 1 month or more after onset. The prevalence of cardiac sequelae was particularly high in males, infants younger than 1 year, and children older than 5 years of age. In sequential observation, there was no correlation between the prevalence of cardiac sequelae and periods of high or low incidence of the disease. The prevalence of cardiac sequelae overall declined steadily over the observation period, perhaps as a consequence of increasing use of intravenous gamma globulin. However, children older than the age of 5 years manifested increasing prevalence of cardiac sequelae over the observation period, probably as a result of lower rates of intravenous gamma globulin administration.     

Cardiac sequelae of Kawasaki disease in Japan over 10 years

To observe the secular trend of a proportion of Kawasaki disease patients with cardiac sequelae in Japan, we analyzed patients with Kawasaki disease reported to nationwide surveys of the disease during 10.5 years from July 1982 to December 1992. Of 69 382 patients reported to the surveys, 10 596 (15.3%) were reported to have cardiac sequelae such as dilatation or stenosis of coronary arteries, myocardial infarction or valvar lesions, 1 month or more after onset. The percentage of cardiac sequelae was particularly high in males, infants younger than 1 year and children older than 5 years of age. The overall prevalence declined steadily over the observed period. However, the percentage for children older than 5 years of age did not decrease, whether treated with intravenous gamma globulin or untreated. As a consequence of the increased number of patients treated with intravenous gamma globulin, the proportion of Kawasaki disease patients with cardiac sequelae decreased annually. However, the proportion of children older than 5 years of age did not decrease.     

上海地区1998－2002年川崎病流行病学特征

目的 对上海地区川崎病发病情况进行调查，了解中国发达地区川崎病的流行病学特征。方法 参照日本流行病学调查方案，制作统一调查表和诊断指南，调查对象为1998年1月1日－2002年12月31日上海地区50家有儿科临床服务的二级及二级以上医院收治的所有川崎病病例。结果 调查表回收率100％，将18例不符合表格填写要求者剔除后，对768例进行分析。上海地区5岁以下儿童川崎病发病率呈逐年增高趋势， 1998年为16.79/10万，1999年为25.65/10万，2000年为28.16/10万，2001年为28.05/10万，2002年为36.76/10万。男女性别比为1.83:1；发病年龄为1个月～18.8岁（中位数1.8岁），发病年龄高峰为9.6个月；全年均可发病，但以春夏之交较多见。主要症状表现为发热持续5 d以上者最为常见（99.3％），其后依次为口唇、口腔黏膜损害（83.5％）、指（趾）端脱皮（82.9％）、皮疹（81.0％）、结膜充血（78.4％）、颈部淋巴结肿大（69.3％）、肢端充血硬肿（48.1％），45.2％的病例有肛周脱皮。心血管损害发生率24.3％，以冠状动脉扩张最为常见，占68％，其次为冠状动脉瘤，占10%。急性期病死率为0.26%，死因为冠状动脉瘤破裂和急性心力衰竭。再发率为1.82%。 结论 上海地区川崎病发病率明显低于日本，但高于西方国家。发病率呈增高趋势，性别分布和心血管损害与其他报道相似。发病季节分布与北京地区的报道相似，但与其他报道不同。     

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.
Methods: All the hospitals with a pediatric department and a bed capacity of ≥100, or hospitals having a bed capacity of <100 but specializing in pediatrics in Japan were asked to report (by mail) all patients with Kawasaki disease who visited the hospital due to the disease in 2003 and 2004.
Results: Of the 2335 hospitals asked to participate, 1058 reported 19 138 patients with Kawasaki disease during the 2 year period 2003–2004. The annual incidence in 2004 reached 174.0 per 100 000 children under 5 years of age. The yearly number of patients and annual incidence increased significantly after the last nationwide epidemic of the disease in 1986. The number of patients was largest in January and lowest in October. The age-specific incidence was highest for those aged 9–11 months, and 88.9% of the patients were under 5 years of age. Of the reported patients, 2595 (13.6%) had cardiac lesions in the acute phase of the disease and 844 (4.4%) had cardiac sequelae 1 month after the onset of the disease.
Conclusion: The number of patients and the incidence of Kawasaki disease in Japan has increased year by year in the last two decades.     

Clinical features of patients with Kawasaki disease whose parents had the same disease

OBJECTIVE: To observe the clinical characteristics of patients with Kawasaki disease whose parent also had the same disorder. DESIGN: Cross-sectional study using the data from nationwide surveys of Kawasaki disease in Japan. SETTING: All hospitals with a bed capacity of 100 or more and pediatric departments in Japan. PATIENTS: All patients described on the 16th and 17th surveys covering the 4-year period from January 1, 1999, through December 31, 2002. MAIN OUTCOME MEASURES: We compared clinical details, including sibling case, recurrence, diagnosis, administration of intravenous immunoglobulin, and coronary abnormalities, between patients whose parents had Kawasaki disease and patients with no parental history of Kawasaki disease. We also observed age at onset and sex of affected parent-offspring pairs with Kawasaki disease confirmed by using the data of previous nationwide surveys. RESULTS: The odds for having sibling cases were significantly increased among patients whose parents also had Kawasaki disease (odds ratio, 6.94; 95% confidence interval, 2.77-17.38). Patients with parental Kawasaki disease were more likely to experience recurrent Kawasaki disease, receive additional administration of intravenous immunoglobulin, and experience coronary abnormalities at 1 month after onset. Among confirmed parent-offspring pairs with Kawasaki disease, the mean age at onset of offspring was younger than that of their parents (25.6 vs 41.8 months), despite the lack of statistical significance. CONCLUSIONS: Some cases of Kawasaki disease show familial susceptibility to the disorder. Family history, especially parental history of Kawasaki disease, may be an indicator of disease severity.     

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 14 163 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.

Conclusion: When compared with parents in the general population, the probability of a history of Kawasaki disease was significantly higher in those parents whose children suffered from the same disease. This suggests that, epidemiologically, a genetic predisposition to Kawasaki disease may be implicated in its occurrence.     

Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan

To investigate the incidence of recurrent Kawasaki disease, and to discuss some of the potential risk factors, data of the 13th and 14th nationwide surveys of Kawasaki disease in Japan were analyzed. To calculate the rate of recurrence, 10 679 patients with 31 501.9 person-years were observed. The mean observation period was 2.95 y. The rate of recurrence was 6.89 per 1000 person-years, with a high incidence within the 12 mo following the first episode. Conclusion: The incidence was high among those under 3 y of age and those with cardiac sequelae during the first episode. None of the other factors affected the incidence.     

Incidence of Kawasaki disease in northern European countries

Background: The aim of the present study was to compare the epidemiologic features of Kawasaki disease (KD) in three northern European countries and Japan. Methods: Data were obtained from discharge databases for hospitals in Finland, Norway, and Sweden for 1999–2009 and from nationwide epidemiologic surveys in Japan for 1998–2008. Annual incidence for each country was calculated using regional census data. Results: During the 11 year period, 1390 KD patients were recorded in the registries of the three northern European countries. Average annual incidence rates per 100 000 children aged <5 years were: Finland, 11.4; Norway, 5.4; and Sweden, 7.4. Overall, 86.4% of Japanese KD patients were aged <5 years compared to only 67.8% in the four northern European countries (P < 0.001). Conclusions: The incidence of KD in northern Europe was constant over the study period and much lower than in Japan. There was a significant age difference between northern European and Japanese KD patients that remains unexplained.     

1997～2001年四川省川崎病流行病学调查

目的了解四川省川崎病(KD)的发病率和流行病学特点。方法按日本川崎病研究中心提供的川崎病诊断标准、问卷表格和调查方法,对四川省内设有儿科病床的医院进行问卷调查。收集1997年1月1日～2001 年12月31日的川崎病患儿住院资料。结果调查全省212所医院,调查表回收率达到91．5％,全省共报告了KD 患儿1811例,符合川崎病诊断标准1511例。1997～2001年<5岁儿童患病率分别为4．26／10万、5．21／10万、8．57／ 10万、7．70／10万、9．81／10万,5年平均发病率为7．06％。男女之比为1．66:1,发病高峰为1～2岁,17．0％的川崎病患儿有心脏冠脉损伤。典型病例占94．6％,使用静脉丙种球蛋白(IVIG)治疗者占70．9％。结论 1997～2001年四川省5年川崎病的发病率低于日本,与国内其他地区KD流行病学资料相比,发病率高于江苏、陕西和广东,低于北京,有逐年增高趋势。     

Epidemiologic picture of Kawasaki disease in Korea, 2000–2002

BACKGROUND: The aim of this study was to investigate the incidence rate and epidemiologic patterns of Kawasaki disease in Korea for a 3 year period during 2000 to 2002. METHODS: An epidemiologic survey on Kawasaki disease was retrospectively performed. The questionnaire was sent to all 112 hospitals having pediatric residency programs, and obtained data were analyzed. RESULTS: The 9150 cases of Kawasaki disease from 92 hospitals which responded (response rate, 82.1%) included 5515 males and 3635 females (male : female ratio, 1.52:1). The incidence rate per 100,000 children <5 years old was 73.7 in 2000, and increased to 90.8 in 2001, and 95.5 in 2002 (average rate, 86.4). The monthly number of patients was slightly higher in May, June and July. Their mean age of onset, the proportion of sibling cases, and a rate of recurrent cases were 30.5 months, 0.17%, and 2.9%, respectively. Coronary arterial abnormalities occurred in 18.6% of cases including dilatations of 17.3% and aneurysms of 3.1%. CONCLUSION: The average annual incidence, 86.4/100 000 in children <5 years old is the second highest rate in the world.     

Epidemiologic picture of Kawasaki disease in Beijing from 1995 through 1999

OBJECTIVE: Kawasaki disease (KD) is supposed to be more common in the Asian race. The incidence in Japan is 10-fold higher than rates reported from western countries. This study sought to evaluate the epidemiologic picture of KD in Beijing and its suburbs. METHOD: A questionnaire form and diagnostic guidelines for KD were sent to all hospitals with pediatric inpatient beds throughout Beijing and its suburbs. Pediatricians were asked to review the medical records and report all patients with KD diagnosed during the 5-year period from January, 1995, through December, 1999. RESULTS: A total of 710 patients with KD were reported from 37 (95%) of 39 hospitals with pediatric inpatient beds. The incidences of KD for each year of the study were 18.2 (1995), 21.1 (1996), 18.6 (1997), 30.6 (1998) and 27.8 (1999) per 100,000 children <5 years of age. The male:female ratio was 1.7:1. The age at onset ranged from 1 month to 13.4 years (median, 2.3 years), with 85.2% <5 years old. The disease occurred more frequently in spring and summer and less frequently in autumn and early winter. Lymph node enlargement was the least common clinical sign, and its incidence decreased from 1995 to 1999. Cardiac abnormalities were found in 21.5% of patients and were more prevalent in patients diagnosed 10 days or longer after the onset. No patients died in the acute stage. CONCLUSION: The incidence of KD in Beijing is lower than that reported in Japan, similar to the incidence in the United States and higher than in other western countries. The age and gender distribution and increasing trend in incidence are similar to those in previous reports, but seasonal distribution is unique.     

Nationwide survey on Kawasaki disease in Japan

Results of the statistical analysis of a nationwide survey of patients with Kawasaki disease diagnosed within a 2-year 6-month period, from July 1982 to December 1984, are as follows. (1) The cumulative number of patients reported by the end of 1984 was 63,399 (36,891 boys and 26,508 girls; male to female ratio 1.4). (2) There were two epidemic years, 1979 and 1982, in which the numbers of patients were more than twofold that of the previous years. (3) A curve plotted for age-specific incidence rate showed a unimodal peak at age 1 year. (4) Steroid therapy was used for 6.3% of the patients, aspirin for 89.8%, antibiotics for 57.6%, and gamma-globulin for 11.4%. (5) The proportion of sibling cases was 1.4% and that of recurrent cases was 3.9% of all cases reported. (6) The incidence of cardiac sequelae in 1 month after disease onset was 17.2%.     

Parents with a history of Kawasaki disease whose child also had the same disease

Background: The aim of this study was to describe time trends of prevalence and detailed characteristics of parents with a history of Kawasaki disease (KD) who had a child with the same disease using data from Japanese nationwide surveys on KD. Methods: Parents with a history of KD were identified using nationwide surveys of KD patients who visited hospitals between 1999 and 2008. To confirm KD histories, a parental questionnaire was sent to pediatricians who reported parental cases to the surveys for KD patients who visited hospitals from 2001 through 2004. Parental history was ascertained by merging data from the parental questionnaire with data from previous nationwide surveys, and detailed information about childhood KD was obtained from survey reports. Results: During the 10‐year study period, 407 parents with a child with KD were reported as having a KD history (0.43%). The prevalence of such parents significantly increased during this study period (regression coefficient: 0.13, 95% confidence interval: 0.05–0.20). Thirty‐one confirmed parents with the history were diagnosed between 1966 and 1984. All parents met the case definition of KD, and 33% had been treated with steroids. No parent with a KD history received intravenous immunoglobulin (IVIG). Conclusions: The prevalence of parents with KD history with a child with the same disease increased during the study period. Some of these parents had not been treated with IVIG because they were diagnosed before its use was widespread in Japan. An increase in the number of parents with the history is expected, thus continuous monitoring of familial cases with KD is required.     

Effects of Gamma-Globulin on the Cardiac Sequelae of Kawasaki Disease

Our aim was to delineate the effect of various factors, such as sex, age, serum albumin levels, and the timing of gamma-globulin (GG) therapy, on cardiac sequelae of Kawasaki disease. The patients with Kawasaki disease who were reported at the 1995–1996 nationwide survey and received 2000 mg/kg at specified hospitals were selected as the subjects of the study. A total of 2221 patients actually received the basic dose. The relationships of the GG therapy with the cardiac sequelae, sex, age, timing of GG administration (the date of initiation and duration of the regimen following disease onset), and serum albumin levels were examined by using logistic regression analysis. The odds ratios for the cardiac sequelae in patients with Kawasaki disease were high in males (1.63), in those under the age of 1 year (1.54), and in those with a serum albumin level <3.2 g/dl (2.64). The odds ratio was low in those who received GG before day 8 of the illness (0.69) or in those for whom the administration period was for 2 days or less (0.67). To prevent cardiac sequelae of Kawasaki disease it is desirable that GG therapy be started as soon as possible and completed within 2 days.     

Kawasaki syndrome in Chinese children

A retrospective analysis of the clinical features and outcome of 39 Chinese children with Kawasaki syndrome was made. The mean age of onset was 2.7 years (range: 0.2-13 years). The male:female ratio was 2.9:1. One child presented with nephrotic syndrome. This renal manifestation has not been described in Kawasaki disease. Ten (32%) out of 31 patients were found to have coronary aneurysms by cross-sectional echocardiography. The only significant risk factor detected in this group of patients was anaemia (P less than 0.007). There was one (2.5%) death from acute myocardial infarction and the rest of the patients were clinically well with a mean follow-up period of 1 year (mean: 5-40 days). This study indicates that there is a high incidence of coronary aneurysm complicating Kawasaki syndrome in Chinese comparable with that reported in Japanese children.     

Epidemiological features of Kawasaki disease in Korea, 2006–2008

Background: The aim of this study was to estimate the incidence and describe the epidemiological characteristics of Kawasaki disease among children in Korea. Methods: Questionnaires for surveying the epidemiology of Kawasaki disease were distributed to a total of 101 hospitals that conduct pediatric residency programs. Then, we retrospectively obtained the data, which covered a three‐year period (2006–2008) and analyzed them. Results: During the three‐year study period, a total of 9039 cases of Kawasaki disease were reported from 84 hospitals (response rate, 83.2%), comprising 5375 boys and 3664 girls (male : female ratio, 1.47:1). The outbreak rate per 100 000 children <5 years old was 108.7 in 2006, 118.3 in 2007 and 112.5 in 2008 (average rate, 113.1). The seasonal distribution showed a slightly higher incidence rate in winter and summer. The patients’ mean age of onset was 32.6 months, while the proportions of sibling cases and recurrent cases were 0.17% and 2.2%, respectively. Coronary arterial abnormalities were detected during follow up by echocardiogram in 17.5% of all cases including dilatations (16.4%) and aneurysms (2.1%). Conclusions: The average annual incidence rate of Kawasaki disease in Korea has been continuously increasing, and reached 113.1/100 000 children <5 years old, which is the second highest rate in the world.     

Kawasaki syndrome hospitalizations among children in Hawaii and Connecticut

OBJECTIVES: To estimate the incidence and describe recent trends of Kawasaki syndrome (KS) in 2 different areas of the United States. METHODS: Retrospective analysis of Hawaii and Connecticut State KS hospital discharge records for children younger than 5 years. RESULTS: In Hawaii, 175 KS hospitalizations for children younger than 5 years were reported during 1994 through 1997; the annual hospitalization rate per 100,000 children was 47.7. The rate for Hawaiian children younger than 1 year (83.2) was greater than that for 1- to 4-year-old children (39.0), and most hospitalizations occurred prior to age 2 years (median age, 17 months). In Connecticut, 171 KS hospitalizations for children younger than 5 years were reported during 1993 through 1996; the annual hospitalization rate per 100,000 children was 18.8, and the median age at hospitalization was 28 months. For both states, most hospitalizations were for boys. Although no clear seasonality was apparent, monthly peaks occurred in some of the years from December through March. CONCLUSIONS: Kawasaki syndrome seems to remain an endemic disease in the United States. A high KS annual hospitalization rate was seen in Hawaii, especially in children younger than 1 year, whereas in Connecticut, the KS rate was more consistent with those previously reported in the continental United States. Arch Pediatr Adolesc Med. 2000;154:804-808     

Serum C-reactive protein levels in patients with Kawasaki disease: from the results of nation-wide surveys of Kawasaki disease in Japan

Thirteen nation-wide epidemiological surveys of Kawasaki disease have been carried out successively since 1970 in Japan. In the latest survey, questionnaires on serum C-reactive protein (CRP) levels of the patients were included to clarify whether serum CRP levels could be available for the diagnosis and prediction of prognosis. A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to all paediatric departments of hospitals with 100 or more beds throughout Japan, and information including maximal serum CRP levels was obtained on patients with Kawasaki disease diagnosed during the 2-year period from January 1993 to December 1994. Of the 11 458 patients diagnosed during the 2-year period, maximal serum CRP levels were reported in 11040 patients (96.4%). The values of maximal serum CRP were higher in the age groups < 6 months and >2 years. The mean value and the distribution of serum CRP levels in suspected cases were lowest among the three diagnostic categories and this difference among diagnostic categories was highly significant in the age groups 6M-1Y and 1-2Y. The proportion of patients with cardiac sequelae increased with serum CRP levels in each age group. The mean value and the distribution of serum CRP levels of the patients with cardiac sequelae was higher than those without it and this difference between cardiac prognoses was outstanding in the age groups 6M-1Y and <6M. The Receiver/Response Operating Characteristic (ROC) curve for maximal serum CRP levels in Kawasaki disease revealed that accuracy of maximal serum CRP levels for prediction of cardiac sequelae was highest in the age group 6M-1Y. A large-scale observation and analysis of serum CRP levels of the patients with Kawasaki disease revealed age-dependent relationships among maximal serum CRP levels, diagnostic categories and prognosis. Serum CRP levels may be helpful for the prediction of prognosis with the consideration of age.     

Kawasaki syndrome in Denmark

OBJECTIVE: To describe the epidemiologic characteristics of Kawasaki syndrome (KS) and to estimate national KS incidence rates among children in Denmark. METHODS: A retrospective population-based study using hospital discharge records with a KS diagnosis for children younger than 15 years selected from the Danish National Hospital Register for 1981-2004. Incidence rates were calculated using the number of KS patients and corresponding census data. RESULTS: During 1981-2004, 360 children younger than 15 years were hospitalized with KS in Denmark, with 73% younger than 5 years. In this age group, the average annual incidence of KS gradually increased from 1981 to 1999 and thereafter stabilized at 4.5 to 5.0 per 100,000 person-years. The incidence was greater for boys than for girls (RR = 1.6, 95% CI = 1.2-2.0) and was highest among infants younger than 1 year (4.5), declining with increasing age (P = 0.03). However, the age-specific decline in incidence was only observed for boys, whereas the incidence for girls remained unchanged by age. The median length of hospital stay was 12 days, and the incidence peaked in the winter months. CONCLUSIONS: Major epidemiologic characteristics identified among Danish childhood KS are consistent with those described in previous studies, such as highest incidence among young children and winter-seasonality. The KS incidence rate among children younger than 5 years in Denmark increased steadily during the early study period (coinciding with global recognition of KS) and seems to have stabilized from 1998-1999 onwards. Although the incidence among Danish children was lower than that reported for several other European countries, differences in methodology challenge definite comparisons.     

Epidemiologic Survey of Kawasaki Disease in Jilin from 1999 Through 2008

The epidemiologic pictures of Kawasaki disease (KD) in Jilin Province of China is still not clear. We sent a questionnaire form and diagnostic guidelines for KD to the province's 32 hospitals above the county and city level with pediatric in-patients. All patients with KD diagnosed during January 1999 through December 2008 were recruited in this survey. The incidence of KD was 1.39 to 11.07 (5.26 ± 3.97) per 100,000 children under the age of 5 years between 1999 and 2008. The ratio of male to female was 1.96 to 1. Ages at onset ranged from 58 days to 14 years. Patients under 5 years of age accounted of 88.73%. The disease occurred throughout the year, but it occurred more frequently in May to July and November. The most common cardiac abnormality was coronary artery dilatation (49.5%). Age at onset and hypoalbuminemia (<30 g/l) were selected for multivariate logistic regression equation. In conclusion, incidences of KD increased in Jilin Province. Age and gender distribution shared similarities with previous reports, and the seasonal distribution was different. Age and lower serum albumin were the most important risk factors of coronary arterial lesions (CAL) in KD. In addition, patients treated with steroids also had a possible heightened risk of contracting CAL.