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Over the last 20 years, Kawasaki disease is being increasingly recognized in India and it may soon replace acute rheumatic fever to become the commonest cause of acquired heart disease amongst children. However, the vast majority of children with Kawasaki disease in India are still not being diagnosed. Diagnosis of Kawasaki disease is based on a constellation of clinical findings which have a typical temporal sequence. All pediatricians must we familiar with the nuances involved in arriving at a diagnosis of Kawasaki disease. With early diagnosis and prompt treatment, the risk of coronary artery abnormalities can be significantly reduced.

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.

We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material.

Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease.We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940.We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group.Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted.Japanese Ministry of Health, Labour and Welfare.

Background: Kawasaki disease (KD) has been reported in many countries. However, the incidence of KD in Mongolia is not known. This is the first report of incident cases of KD in Mongolia, which were identified using data from 2 nationwide surveys.Methods: Two nationwide retrospective surveys were conducted: medical histories were collected from patients aged 0 to 16 years who were hospitalized countrywide between 1996 and 2008. Hospital records for these patients were also reviewed. Nationwide training seminars on KD were conducted before each survey.Results: For the nationwide surveys, the participation rates among all hospitals with pediatric wards were 97% and 94%. Inpatient medical histories from 1996 through 2008 were reviewed, and, among children younger than 16 years, 9 patients with KD were investigated. The age of KD patients ranged from 1.4 to 14 years; 7 of 9 patients were male. Six (67%) patients fulfilled all 6 clinical diagnostic criteria; the other 3 (33%) were defined as having KD based on the presence of 5 such criteria. Fever persisting 5 or more days, bilateral conjunctival congestion, and changes of the lips and oral cavity were the most common symptoms, and cervical lymphadenopathy was the least common symptom. Cardiac sequelae developed in 5 of the patients, 4 of whom were older than 10 years.Conclusions: The results of these nationwide surveys reveal that KD cases do exist in Mongolia. However, knowledge of KD among Mongolian pediatricians is likely to be poor. Thus, there is a need to augment their understanding to improve management of KD patients. Further studies are crucial to clarify the epidemiologic characteristics of KD in Mongolia.

Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5' untranslated region of CASP3 (rs72689236; P = 4.2 x 10(-8) in the Japanese and P = 3.7 x 10(-3) in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.

Aim: To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age-matched healthy individuals. Methods: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results: Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77–1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71–4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed. Conclusion: Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca(2+)/NFAT pathway in the pathogenesis of this disorder.

Kawasaki disease (KD; MIM611775) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD have suggested up-regulation of Ca2+/NFAT pathway as one of the main pathophysiological processes in KD. In this study, we focused on ORAI1, a gene for a channel involved in store operated Ca2+ entry located on 12q24 where positive linkage signal was seen in our previous sib pair study of KD, and conducted a genetic association study. By re-sequencing 17.4kb of ORAI1 region for 94 subjects, we identified 37 variants with minor allele frequencies larger than 0.05. After selecting 9 tagging SNPs which represent 37 variants we performed an association study using 730 KD cases and 1315 controls. As a result, one tagging SNP located within exon2 showed nominal association (rs3741596; OR = 1.19, 95%CI 1.02~1.40, P = 0.028). The same trend of association was observed in an independent case control panel (1813 KD cases and 1097 controls, OR=1.22, 95% CI 1.06-1.40, P = 0.0056) and a significant P value was observed in a meta-analysis (OR = 1.21, 95%CI 1.09~1.34, P = 0.00041). Furthermore, we also found a rare 6 base-pair insertion polymorphism which cause elongation of proline repeat within N-terminal cytoplasmic domain of the ORAI1 protein was overrepresented in KD cases (rs78448924; OR = 3.91, 95%CI 1.30~11.80, P=0.010). These data indicate altered ORAI1 function confers susceptibility of KD and further highlight importance of the Ca2+/NFAT pathway in the disease pathogenesis.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. The cause of KD is largely unknown, but its higher incidence in the Asian population and increased risk in patients’ families suggests the existence of underlying genetic factors. To determine the loci of a susceptibility gene for KD, a genomewide linkage analysis with affected sib pairs was performed on 78 family samples collected from all over Japan. Multipoint linkage analysis using MAPMAKER/SIBS 2.0 identified evidence of linkage on 12q24 [maximum lod score (MLS) = 2.69]. Possible linkage (MLS > 1.0) was also found on 4q35, 5q34, 6q27, 7p15, 8q24, 18q23, 19q13, Xp22, and Xq27. This is the first large-scale study of the genetic susceptibility to KD, and our results, combined with the accumulated knowledge of the human genome, could greatly promote research on identification of the molecular pathogenesis of KD.

Kawasaki syndrome is an acute, self-limited vasculitis of infants and children with unknown etiology. Seasonality of this condition was first reported by Tomisaku Kawasaki in 1967.1 He described an increase in cases in the spring and summer and a decrease in the fall and winter during a 5-year period (1961–1966). An increased incidence of Kawasaki syndrome in the winter-spring months has been reported from many different geographic regions.2-6 This syndrome is recognized by a constellation of clinical signs (including fever, rash, and conjunctival injection) lasting 1 to 2 weeks. An infectious etiology is suspected on the basis of the clinical similarities to other infectious diseases. Peak incidence occurs in the infant/toddler age group, with only rare cases in infants younger than 3 months of age and in adults. This suggests that transplacental antibodies may confer protection and also that most infections are asymptomatic and result in the development of protective antibodies. The major complication of Kawasaki syndrome is damage to the coronary arteries, which can be prevented in most cases with a high dose of intravenous gamma globulin administered within the first 10 days of fever. Kawasaki syndrome is now the leading cause of acquired heart disease in children in the United States and Japan. The rising incidence in Japan and perhaps the United Kingdom lends a sense of urgency to finding the cause.7,8 At current rates, 1 of every 150 children in Japan will suffer from Kawasaki syndrome. Clear documentation of seasonality and clustering of Kawasaki syndrome cases would lend further weight to the hypothesis that Kawasaki syndrome has an environmental trigger.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4+121 A>G) is marginally over-represented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR=2.0, 95% CI=1.07-3.66; P=0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.

Kawasaki disease is an acute vasculitis of unknown etiology that predominantly affects children

Objective. The objective of this article is to describe the epidemiologic pictures of Kawasaki disease(KD) in Japan during the 2-year period of 1993 and 1994 based on the data obtained by the thirteenth nationwide epidemiologic survey of KD which was conducted by the Japan Kawasaki Disease Research Committee. Methods. A survey form and diagnostic criteria of KD were sent to all hospital pediatric departments (2, 640) throughout Japan with 100 or more beds. The patients to be reported in this surveys were all the incident KD cases who satisfied the diagnostic criteria. Results.(1) A total of 1, 730 (65.5%) hospitals responded, reporting 11, 458(5, 389 in 1993 and 6, 069 in 1994; 6, 729 males and 4, 729 females; male/female ratio=1.42) with an incidence rate of 95.1 per 100, 000 children of age

OBJECTIVE: To determine whether the mortality rate of patients with a history of Kawasaki disease is higher than that of the general population. DESIGN: In a cohort study, 6585 patients with Kawasaki disease were observed from the first medical encounter because of the disease through the end of 1992, or until death. Standardized mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated with vital statistics data of Japan for the control. RESULTS: Of 6585 patients who met the eligibility criteria, 6550 (99.5%) were followed through either the end of the study or the date of death. Nineteen patients (14 male subjects) died during the study period; an overall SMR of 1.56 (95% CI, 0.94 to 2.43) was calculated for the entire study period. The SMR was 1.78 (95% CI, 0.97 to 2.99) for male subjects and 1.16 (95% CI, 0.38 to 2.71) for female subjects. During the acute phase of the disease (the first 2 months after onset), the SMR was higher, particularly in male subjects (SMR, 10.12; 95% CI, 3.72 to 22.07). After the acute phase, however, both boys and girls had low SMRs. Nine of the 19 deaths were caused by Kawasaki disease; there were 2 deaths as a result of congenital anomalies of the circulatory system and 2 subjects died of malignant neoplasms of lymphatic or hematopoietic tissues. CONCLUSIONS: Although the mortality rate among those with a history of Kawasaki disease was elevated in Japan, many of the deaths that caused the elevation occurred during the acute phase of the disease. The mortality rate was not increased after the acute phase of the disease. (J PEDIATR 1996;128:75-81)

Objective. Since 1970, twelve nationwide epidemiologic surveys of Kawasaki disease (KD) have been conducted throughout Japan every two years to describe KD in Japan. By the end of 1992, a total of 116 848 cases were reported. This paper summarizes the statistical analysis of the latest survey for the 2-year period from January 1991 through December 1992. Method. A questionnaire form and diagnostic guidelines for KD were sent to all pediatric departments of hospitals with 100 or more beds throughout Japan and information was obtained on patients with KD diagnosed during the 2-year period from January 1991 through December 1992. Results. The summary of the results is: 1) the number of patients reported was 11 221 (6604 males and 4617 females; male/female ratio = 1.43) with a yearly incidence rate of 90 per 100 000 children Conclusion. The incidence rates of KD in Japan are ten times higher than those reported in western countries and almost constant over 6 years. The descriptive epidemiology of the disease, which supports the infection theory, does not change for years.

This paper discusses the brief history of Kawasaki disease, its main clinical features, diagnosis, main laboratory findings, cardiovascular complications in brief, treatment, epidemiology mainly in Japan, a summary of the pathology and concludes with five major problems which must be solved.

Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown etiology that primarily affects the coronary artery (CA) and presents during childhood. The characteristic coronary arterial lesion of KD is an aneurysm. Ischemic heart disease derived from a CA aneurysm is experienced approximately two decades after the onset of acute KD. In recent years, the primary issue of concern has been asymptomatic adults with a CA aneurysm caused by undiagnosed KD. We present a case of sudden death as a late KD sequel in a young adult. A postmortem CT scan revealed a coarse calcification of a left anterior descending CA aneurysm, which was confirmed at the time of autopsy. A postmortem CT scan is useful in cases of sudden death where the detection of a calcified CA aneurysm would suggest to the forensic pathologist that the deceased suffered from a late sequel of KD. The use of screening postmortem CT scans for young people may detect cases of unsuspected CA aneurysms, raising the possibility of untreated KD.

The long-term outcome of myocardial revascularization by coronary artery bypass grafting in patients with severe coronary obstruction caused by Kawasaki disease is largely unknown. A multicenter follow-up study was performed in 1991. A total of 168 patients with Kawasaki disease (127 male [75.6%] and 41 female patients [24.4%]) who had undergone coronary bypass grafting were enrolled. Obstructive coronary artery disease affected the left main trunk in 11.8%, the right coronary artery in 77.6%, the left anterior descending in 87.6%, and the left circumflex in 25.9%. Old myocardial infarction was noted in 46.0% of the patients. Fifty-four patients (32%, 12.4 ± 9.8 years) underwent bypass grafting with saphenous vein grafts alone. The remaining 114 patients (68%, 9.8 ± 7.1 years) received at least one internal thoracic artery graft to the left anterior descending coronary artery. Gastroepiploic artery grafts were used in 12 patients. There were no significant differences between the saphenous vein and internal thoracic artery groups in the mean age at operation (12.4 versus 9.8 years), female ratio (22% versus 25%), the number of patients over 20 years of age (9.3% versus 9.6%), previous history of infarction (51.9% versus 41.2%), impaired left ventricular function (ejection fraction p p p p n = 151) than for vein grafts (46.2% ± 6.3%, n = 126) 85 months after the operation ( p p n = 39) than for vein grafts (37.5% ± 8.0%, n = 81) to the left circumflex and right coronary arteries. The difference in patency was even greater in children younger than 7 years old at operation ( p

To get information about secular trend of age-specific incidence rate, cumulative incidence up to 5 years of age, and whether there is a cohort effect of incidence rate of Kawasaki disease, we analyzed the data of nationwide incidence surveys of the disease in Japan from 1970 through 1990. The age-specific incidence rate increased gradually except for three nationwide epidemic years. Cumulative incidence from birth through 4 years of age also increased, and was about 0.5% for males and 0.4% for females who were born in early and middle 1980's. Although some birth cohort showed a high relative risk of incidence rate with statistical significance, there was no meaningful cohort effect on Kawasaki disease. J Epidemiol, 1994; 4 : 13-16.

The objective of this paper is to describe the epidemiological and clinical characteristics of Kawasaki disease (KD) in Shaanxi Province, China during the 5-year period from January 1993 to December 1997. A province-wide epidemiological survey on KD was made by the China-Japan Kawasaki Disease Study Group. The questionnaire form and the diagnostic criteria of KD, which were prepared by the Japan Kawasaki Disease Research Committee and translated into Chinese, were sent to the departments of pediatrics of all the hospitals with 100 beds or more in Shaanxi province. All the KD patients who were diagnosed during the observation period from 1993 to 1997 were asked to take part in this survey. The databases of reported KD in this survey were analysed at the Department of Pediatrics of the Shaanxi Provincial People's Hospital, Xi'an, China. All the patients that satisfied the diagnostic criteria were included in the report. A total of 105 (70 per cent) hospitals responded and 376 cases of KD were confirmed. More cases were reported in 1993 and 1994. Of the total patients reported, 69 per cent were children under 3 years old with a male to female ratio of 1.6:1. The proportion of patients with cardiac sequelae was 19 per cent with a male to female ratio of 3:1. There were four fatal cases with a fatality rate of 1 per cent. It is concluded that KD is common in China. Continuous surveillance is necessary to maintain high awareness of KD so as to find possible risk factors and their association with the disease.

Ten years after starting my pediatric career at the Japanese Red Cross Central Hospital (now Japanese Red Cross Medical Center) in Tokyo, I examined on January 5, 1961, a 4 year-3 month old boy, with curious clinical symptom-complex I had never experienced. This patient was a typical Kawasaki disease patient. But at that time I was unable to make a diagnosis. In February 1962, a case of suspected sepsis was referred to me from a neighboring doctor. After admitting the child into the hospital, the patient had a similar clinical course as the previous patient. I realized that there were 2 patients with similar unique clinical symptom complexes that did not exist in any medical reference book. From March to September 1962, I was able to see 5 patients who fell into the same category. In 1967, I published my original article entitled, "Infantile Acute febrile Muco-cutaneous lymph node syndrome: clinical observations of 50 cases".

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.

BACKGROUND: Epidemiologic features of Kawasaki disease in China is still not clear. METHODS: A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to hospitals in Shanghai, which provided with pediatric medical care. All patients with Kawasaki disease diagnosed during January 1998 through December 2002 were recruited in this study.RESULTS: A total of 768 patients with Kawasaki disease were reported. The incidence rates of Kawasaki disease for each year were 16.79 (1998), 25.65 (1999), 28.16 (2000), 28.05 (2001), and 36.76 (2002) per 100,000 children under 5 years of age. The male/female ratio was 1.83:1. The age at onset ranged from 1 month to 18.8 years (median: 1.8 years). The disease occurred more frequently in spring and summer. Fever was the most common clinical symptom, followed by oral changes, extremities desquamate, rash, conjunctive congestion, lymphadenopathy, extremities swelling, and crissum desquamate. Cardiac abnormalities were found in 24.3% of patients. The most common cardiac abnormality was coronary artery lesions including dilatation (68%) and aneurysm (10%). The case-fatality rate at acute stage of the disease was 0.26%. A second onset of the disease occurred in 1.82% of patients.CONCLUSIONS: The incidence rate of Kawasaki disease in Shanghai is lower than that reported in Japan, but higher than those in western countries. The increasing trend in incidence, sex distribution and cardiac abnormalities are similar to those in previous reports. The seasonal distribution is similar to the report from Beijing and different from other reports.J Epidemiol 2006; 16: 9-14.

SummaryIn this review, I have outlined the clinical picture, epidemiology, pathology, etiology, and current treatment and management of Kawasaki disease. The disease in question has unique features which cannot be classified into any of the categories of conventional pediatric diseases, and thus the elucidation of the etiology and mode of onset may well raise many new medical problems. It is hoped that young practitioners of clinical and fundamental medicine will be able to resolve the problems relating to the disease which remain as quickly as possible.

To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age-matched healthy individuals.Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number.Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77-1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71-4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed.Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.

Background. Kawasaki disease (KD) is the most common acquired cardiac disease in children in developed nations. The etiology is unknown, but a ubiquitous infectious agent appears to be likely. Immunoglobulin A plasma cells infiltrate inflamed tissues in acute KD, producing oligoclonal, antigen-driven antibodies. Methods. To identify antigens important in the pathogenesis of KD, oligoclonal KD antibodies were prepared in vitro and tested by immunohistochemistry experiments on tissues from patients with acute Kl) and from control subjects and were also tested for reactivity with human inflammatory proteins. Results. By use of synthetic antibody A, specific binding to a cytoplasmic antigen in proximal bronchial epithelium was observed in 10 of 13 patients with acute KD but in 0 of 9 control subjects (P = .001). A subset of macrophages was positive in at least 1 inflamed tissue from all 17 patients with acute KD. Antigen was detected in 9 of 12 acute KD coronary artery aneurysms but in 0 of 10 control coronary arteries (P

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

Objective. To clarify whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population after the disease occurrence. Study design. Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new definite diagnosis of Kawasaki disease. Patients were followed until December 31, 1997, or death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results. Of 6576 patients enrolled, 25 (19 males and 6 females) died. The standardized mortality ratio (SMR) was 1.35. In spite of the high SMRs during acute phase, the mortality rate was not high after the acute phase for all patients. Although the SMR after the acute phase was 0.76 for those without cardiac sequelae, 6 males (no females) with cardiac sequelae died during this period and the SMR for the male group with cardiac sequelae was 2.77. Conclusion. The mortality rate among males with cardiac sequelae due to Kawasaki disease was 2.8 times as high as in general population, whereas mortality rates for females with the sequelae and both males and females without sequelae were not elevated. J Epidemiol, 2000 ; 10 : 372-375

Kawasaki disease has been researched for 32 years but its aetiology is still unknown. Conventional therapy for the disease includes corticosteroids and aspirin (acetylsalicylic acid) as anti-inflammatory and/or antithrombotic agents but they have not been proven to prevent coronary artery aneurysms. Although a high incidence of liver dysfunction in Japanese patients with Kawasaki disease receiving high dose aspirin (or =80 mg/kg/day) suggests racial differences in salicylate sensitivity, the duration of fever in patients receiving high dose aspirin is shorter than that in patients receiving moderate dosages (30 to 50 mg/kg/day). Furthermore, most corticosteroid-resistant patients were found to develop coronary artery aneurysms, many of which were large. With the clarification of the pathogenesis and clinical features of Kawasaki disease, advances in its treatment have been achieved. The introduction of high-dose intravenous gamma-globulin (IVGG) was an epoch in this field and IVGG is now a standard therapy with the incidence of persistent coronary aneurysms 1.9% in children with the disease receiving IVGG. Today, research is mainly directed toward the treatment of IVGG-resistant patients. One to 3 days of pulsed doses of methylprednisolone (30 mg/kg/day) or readministration of IVGG 1 g/kg (once to several times) has been recommended for patients with IVGG-resistant Kawasaki disease.

OBJECTIVE—This study was undertaken to clarify whether cardiac sequelae due to Kawasaki disease are more frequent among recurrent cases than initial onset cases. STUDY DESIGN—A cross sectional study using data from nationwide surveys of Kawasaki disease in Japan was conducted. A total of 33 976 patients reported were divided into two groups: initial onset cases (32 923 patients) and recurrent cases (1053 patients). Proportions of cardiac sequelae such as coronary aneurysms/dilatation, coronary stenosis/narrowing, myocardial infarction, and valvular lesions were compared between the two groups. RESULTS—The proportions of patients with the sequelae were significantly more common among recurrent cases. In men 25.5% of the recurrent cases had the sequelae in comparison with 14.9% for initial onset cases, and in women 16.1% of recurrent cases had the sequelae compared with 9.8% of initial onset cases. Giant coronary aneurysms were twice as likely in men in whom the disease was recurring than in initial onset cases, and 1.5 times more likely in women in whom the disease was recurring than in initial onset cases. CONCLUSION—Cardiac sequelae of Kawasaki disease are more likely to appear on recurrent case patients.

The administration of i.v. gamma globulin (IVGG) for Kawasaki disease was investigated throughout Japan in 1993 by obtaining information from the pediatric departments of 2652 hospitals with more than 100 beds. A total of 1826 hospitals (68.9%) responded, reporting on 11,221 patients who were diagnosed during the survey period from January 1991 to December 1992. There were 8958 patients (79.8%) who received IVGG treatment. The most common treatment modality was 200 mg/kg (29.6%), followed by 400 mg/kg (18.7%) and 300 mg/kg (12.9%), all for 5 days. The distributions of total dose were: 1000 mg/kg or less, 45.7%; 1001-1500 mg/kg, 27.3%; and over 1500 mg/kg, 23.8%. For all patients to whom IVGG was administered, treatment was started in 53.8% by day 5 of illness and in 86.1% by day 7. The proportion of those with cardiac sequelae was higher in patients who were treated with IVGG, possibly due to the fact that those who were more severely affected were more likely to be treated with IVGG.

Background The acute phase of KD is characterized by a deficiency of suppressor T cells, marked activation of the immune system and increased secretion of cytokines by immune effector cells. Moreover, it has been shown that myeloid-related protein (MRP-8 and MRP-14) and S100proteins, the major calcium-binding proteins secreted by activated neutrophils and monocytes, contribute to cause inflammation in acute lesions of KD, and indeed one of the more common hematological alteration in KD is the increase of peripheral blood monocytes. Calprotectin, one of the major calcium-binding proteins, can lead to direct and indirect effects that result not only in inflammation but also in modification of microvascular wall in acute vasculitis syndromes.

It is not certain whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population. We therefore undertook a study to investigate this question. Between July 1982 and December 1988, 53 collaborating treatment centers collected data on all patients who had an unequivocal new diagnosis of Kawasaki disease; patients who had recurrent disease or whose first visit to the treatment center occurred more than 14 days after the onset of symptoms were excluded. Patients were followed from the time of the first visit to the treatment center until December 31, 1989, or until death, whichever occurred first. The expected number of deaths was calculated from Japanese vital-statistics data and compared with the number observed.Of 4676 patients who met the eligibility criteria, 4608 (98.5 percent) were followed through either the end of the study or the date of death. Thirteen patients (10 boys and 3 girls) died during the study period. The number of deaths expected was 7.61 (ratio of observed to expected deaths, 1.71; 95 percent confidence interval, 0.91 to 2.92). The ratio was 2.04 (95 percent confidence interval, 0.98 to 3.76) for boys and 1.11 (95 percent confidence interval, 0.23 to 3.23) for girls. During the acute phase of the disease (the first two months after onset), the ratios of observed to expected deaths were higher: 9.86 overall (95 percent confidence interval, 3.95 to 20.31), 13.33 for boys (95 percent confidence interval, 4.89 to 29.07), and 3.85 for girls (95 percent confidence interval, 0.10 to 21.42). After the acute phase, however, both sexes had ratios of observed to expected deaths that were lower than 1, and the difference from the control population was not statistically significant.The mortality rate among boys with Kawasaki disease in Japan is twice that among healthy boys of the same age, and most deaths occur within two months of diagnosis. The mortality rate among girls with the disease appears similar to that among healthy girls, although the numbers are very small.

The proportions of Kawasaki disease patients with cardiac sequelae in Japan were analyzed using nationwide survey data from the 6½-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 on 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.

The winter/spring seasonality of KD has been recognized for over two decades and a recent study found that KD incidence in San Diego (SD) County was positively associated with average monthly precipitation (r=0.52, p

Objective To determine whether patients with Kawasaki disease have a higher death rate than an age-matched healthy population after disease occurrence. Study Design From July 1, 1982, to December 31, 1992, 52 collaborating hospitals collected data on all patients with a new definite diagnosis of Kawasaki disease. Patients were followed up until December 31, 1999, or death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results Of 6576 patients enrolled, 27 (19 male, 8 female) died. The standardized mortality ratio (the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.25 (95% confidence interval, 0.84-1.85). Despite the high standardized mortality ratios during the acute disease phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the standardized mortality ratio after the acute phase was 0.76 for those without cardiac sequelae, 6 male patients (no female patients) with cardiac sequelae died during this period, and the standardized mortality ratio for the male group with cardiac sequelae was 2.35 (95% confidence interval, 0.96-5.19). Conclusions Although it was not statistically significant, the mortality rate among male patients with cardiac sequelae due to Kawasaki disease seemed higher than that in the general population. On the other hand, mortality rates for female patients with sequelae and both male and female patients without sequelae were not elevated.

Objective To acquire the situation of pathogeresis, diagnosisand treatment of Kawasaki disease in Shannxi Province. Methods we had a retrospective clinical study on children with KD in six hospital in Xi'an between 1998 and 1999. This is a consecutive study based on the epidemic study on KD of Sino-Japanese between 1993 and 1997. The evaluation include age, sex, season, clinical symptoms and signs, the counting of thrombocyte, ESR, cardiac enzyme series. With the dose of IVGG, all the patients were designed into four groups: A 300~400mg/kg/d; B 400~800mg/kg/d; C 1000mg/kg/d; D 2000mg/kg/d, together with aspirin and anticoagulant. Results Sex: male 73; female 31. Age: 1 year 24.03%; 1~3 years 50.4%; 3~7 years 22.11%; 7~14 years 2.88%. 80.76% patients had fever persisting for fine days or more; 82.69%, changes in the extremities; 74.03%, polymorphous exanthema; 78.84%, changes in the lips and oral cavity; 74.63%, nonpurulent cervical lymphalenopathy. There were 21 patients to be diagnosed as acute upper respiratory infection (AURI) by impression; 14, herpangina; 5, cervical lymphadenopathy; 2, lymphomas; 1, thrombocythemia. Conclusion According to recent study, the cardiovascular damage of KD was gradually increased, especially in coronal artery and became the main cause of acquired heart disease in Chinese children with KD. IVGG has been an effective therapy for KD in recent years, using in 400mg/kg/d for 4~5days was superior to 100~200mg/kg/d in China.

Objective. Kawasaki disease (KD) is supposed to be more susceptible in Asian race. This study sought to evaluate the epidemiologic pictures of KD in Beijing and suburb area. Method. A questionnaire form and diagnostic guidelines for KD were sent to all hospitals with pediatric in-patient beds in Beijing and suburb areas. Pediatricians were asked to review medical records and report all patients with KD diagnosed during the 5-year period from January 1995 to December 1999.Results. A total of 710 patients with KD were reported from 37 (95%) of 39 hospitals with pediatric in-patient beds, with a mean annual incidence of 24.4 per 100000 children under 5 years of age. The incidence was 18.2, 21.1, 21.2, 30.6 and 35.5 per 100000 children under 5 years old in 1995, 1996, 1997, 1998 and 1999, respectively. The male to female ratio was 1.7:1. The age at onset ranged from 1 month to 13.4 years, with 85.2% under 5 years and peak age at 1 year old. The disease occurred more frequently in spring and summer. Lymph node enlargement was the least common sign, and its incidence decreased from 1995 to 1999. Cardiac sequelae was found in 21.5% patients, and was more prevalent in patients diagnosed 10 days after onset. No patients died in the acute stage. Conclusion. The incidence of KD in Beijing is lower than Japan, but higher than other western countries. The age and gender distribution, and increasing trend in incidence are similar to previous reports, but seasonal distribution is unique.