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.     

A case-control study of recurrent Kawasaki disease using the database of the nationwide surveys in Japan

Abstract In spite of many reports of recurrent Kawasaki disease, little information about the risk factors associated with recurrence is available. We conducted a case-control study on 150 cases of recurrent Kawasaki disease and 1173 pair-matched controls selected from the database of nationwide surveys of the same disease in Japan. Items observed were: sex, age, use of intravenous gamma globulin, and cardiac sequelae at the first episode. Sex and cardiac sequenlae did not affect the risk of recurrence. One- to 2-year-old chilren were more likely to be affected again than infants (odds ratio [OR]=1.42; 95% confidence interval [CI], 0.94–2.13), and children who were 3 years of age or older were less likely to experience a recurrence than infants (OR=0.59; 95% CI, 0.34–1.02). Intravenous gamma globulin therapy at the first episode increased the risk for recurrence of Kawasaki disease within 12 months (OR=2.66, 95% CI, 1.06–6.66). However, it did not affect recurrences 12 months after the first episode (OR=1.02; 95% CI, 0.53–1.97).Conclusion Patients with Kawasaki disease treated with intravenous gamma globulin are 2.66 times as likely to be affected by the disease again within 12 months as those treated without intravenous gamma globulin.     

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

BACKGROUND: 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. METHODS: The design is a retrospective incidence survey. The patients reported in these two surveys are all new patients who were reported during the two study periods (1999-2000 and 2001-2002), although the data were collected retrospectively. A questionnaire was sent to all pediatric departments of hospitals with 100 beds or more throughout Japan, requesting data on patients with Kawasaki disease, such as sex, age, date of first hospital visit, recurrence, and cardiac lesions. RESULTS: The total number of patients reported in the 4 year period 1999-2002 was 32 266 (18 604 male, 13 662 female), with an average annual incidence of 137.7 per 100 000 children younger than 5 years old. The male/female ratio was 1.30. The incidence peaked at 9-11 months of age, and the proportion of patients under 1 year of age was 26%. The monthly distribution had a high peak in January and a gradual increase in summer. Geographically, the high-incidence areas were limited to certain prefectures and moved from year to year. The cardiac lesions at acute stage and cardiac sequelae occurred more in children under 1 year and older than 4 years. Among the principal symptoms, fever persisting >or=5 days occurred most commonly, followed by conjunctival congestion, changes in lips and oral cavity, polymorphous exanthema, and changes of extremities. Cervical lymphadenopathy occurred less. CONCLUSION: More than 32 000 patients with Kawasaki disease during the 4 year period 1999-2002 were reported to the nationwide incidence surveys. The number of patients is steadily increasing despite the decrease of children. The seasonal variation, geographical distribution, and age-specific distribution support the infection theory for the etiology of Kawasaki disease.     

A multicenter collaborative study on the risk factors of cardiac sequelae due to Kawasaki disease: a one-year follow-up study

Objective: To measure the prevalence of cardiac sequelae 1 y after the onset of Kawasaki disease and determine the risk factors associated with these cardiac sequelae. Material and methods: 1594 patients who initially visited one of the 87 target hospitals in 1996 for Kawasaki disease participated. Selection of the target hospitals was based on a nationwide survey. The patients were followed‐up and information concerning cardiac sequelae occurring within 1 y of onset was obtained by mail survey. Results: The prevalence of cardiac sequelae 1 mo after onset was 10.2% and decreased to 4.2% in 1 y. The prevalence was higher among males than females and higher in patients less than 1 y and 5 ys or older than in 1–4 year‐olds. Of the patients with cardiac sequelae at 1 mo, the sequelae disappeared in 60.7% after 1 y. Analysis revealed low serum albumin as a risk factor related to the occurrence of cardiac sequelae 1 y after onset. Of the 1594 patients, 10 had giant anuerysms and 3 had a fatal outcome. Conclusions: Approximately 60% of cardiac sequelae due to Kawasaki disease that developed within 1 mo after onset disappeared in 1 y. The odds ratio was significantly higher among patients with a low serum albumin level 1 y after onset.     

Cardiac involvement in Kawasaki disease. Our experience

BACKGROUND: Kawasaki disease is an acute vasculitis of unknown cause that affects children under 5 years of age and in 20-25% of cases can cause coronary artery anomalies. Early therapy with intravenous gamma globulin and aspirin greatly decreases the risk of developing coronary anomalies, but sometimes coronary disease develops even in timely diagnosed and treated cases. METHODS: Personal experience in 41 children with Kawasaki disease is reported. Age was within three months and 5 years. All patients had electrocardiography and echocardiography at diagnosis, after 1 week, at the third, sixth, and eighth week, after six months and after 1 year from diagnosis. Echocardiographic cardiac anomalies were found only in 5 cases (12.19%). Average age in these cases was lower. RESULTS: In these cases coronary involvement developed in spite of early diagnosis and therapy (intravenous gamma globulin 400 mg/kg die and aspirin) electrocardiographic findings were not relevant or specific to coronary arteries anomaly. In three cases coronary anomalies regressed during the first year from diagnosis, the other two are still in the first year of follow-up. Nine children had a long term follow-up (6 to 9 years) and they were all normal except one with renal arteritis and another with slight mitral incompetence. CONCLUSIONS: The authors underline the role of clinical and instrumental follow-up that should be extended to all patients affected by Kawasaki disease with coronary anomalies even if early regressed.     

Iv gamma globulin treatment of Kawasaki disease in Japan: results of a nationwide survey

The administration of iv 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 200mg/kg (29.6%), followed by 400mg/kg (18.7%) and 300mg/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. Epidemiology, gamma globulin treatment, Japan, Kawasaki disease     

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.     

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 disease in Sweden: incidence and clinical features

The incidence and clinical pattern of patients with Kawasaki disease in Sweden and the outcome of treatment with iv immunoglobulin (Sandoglobulin) and aspirin were examined in a national prospective study over a 2-year period. Cases not referred to the study were identified by inquiry. Ninety-nine children were diagnosed as having Kawasaki disease. The annual incidence rate was calculated to be 2.9per 100 000 in children younger than 16 years of age and 6.2 per 100000 in children younger than 5 years of age. The median age of our patients was 2.2 years and the male-to-female ratio was 2.3:1. Cardiac ultrasonography revealed abnormalities in 33% of all patients, and 14% of cases in the prospective study had pronounced abnormalities. In most cases (91%) treatment had a prompt effect on fever and morbidity in general, and side effects were mild. Two infants, identified from the inquiry, died from rupture of an aneurysm in the coronary artery in the acute phase of the disease. The risk of cardiac involvement is obvious and emphasizes the importance of early diagnosis and treatment. Incidence, Kawasaki disease, vasculitis     

Prevention of giant coronary artery aneurysms in Kawasaki disease by intravenous gamma globulin therapy

Previous studies have demonstrated the efficacy of intravenous gamma globulin in the prevention of coronary artery abnormalities in Kawasaki disease. We retrospectively reviewed our single-hospital experience with patients in whom Kawasaki disease was diagnosed from January 1979 to July 1987. Only 3 of 68 (4%) patients treated with intravenous gamma globulin in the first 10 days of illness developed coronary artery abnormalities (one of the three had abnormalities before gamma globulin therapy), in comparison with 39 of 119 (33%) patients not treated with gamma globulin (p less than 0.001). Giant coronary artery aneurysms, which are associated with the greatest morbidity and mortality rates in Kawasaki disease, developed in none of the 68 patients treated with gamma globulin but in 7 of 119 patients (6%) not treated with gamma globulin (p = 0.04). Intravenous gamma globulin appears to be effective not only in reducing the overall prevalence of coronary artery abnormalities in Kawasaki disease but, more important, in preventing the formation of giant aneurysms, the most serious form of coronary abnormality after this illness.     

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.     

川崎病患者易早发动脉粥样硬化

川崎病是一种急性自限性全身性血管炎,其心血管并发症,尤其是冠状动脉损害(冠状动脉扩张、冠状动脉瘤形成、冠状动脉狭窄甚至闭塞等)使其受到了临床医师,尤其是儿科临床医师的广泛关注.川崎病首次被认识至今已经40余年,随着那些最早的川崎病患者逐渐迈入中年,关于川崎病长期预后的研究引起了临床工作者的极大兴趣.虽然动脉粥样硬化性心血管疾病临床表现多出现在中老年期,但近年来其被认为是一种病变始于儿童时期,并在各种危险因素的作用下逐渐进展的疾病.越来越多的研究发现,川崎病尤其是伴有冠状动脉损害的川崎病可能是早发动脉粥样硬化的危险因素.     

High persistence rate of established coronary artery lesions secondary to Kawasaki disease among a panethnic Canadian population

The incidence of resolution of proximal coronary artery lesions subsequent to Kawasaki disease over an 11-year period was studied retrospectively. In 28 patients proximal coronary artery lesions were identified by two-dimensional echocardiography or angiography at 1 to 3 months after disease onset. Follow-up data were adequate in 27 patients, 17 of whom were boys; 18 were white, two black, four Oriental (non-Japanese), and three of East Indian origin. Age at onset of Kawasaki disease ranged from 11 weeks to 9 years (mean 2.5 years). Coronary artery lesions were categorized as ectatic (internal diameter greater than 3 mm in those less than 5 years of age) or aneurysmal (internal lumen of a segment one and one-half times larger than an adjacent segment). Resolution was assessed by two-dimensional echocardiography or angiography during a follow-up period of 3 months to 11 years (mean 2.7 years). Apparent resolution (vessel diameter less than 3 mm) of coronary artery lesions occurred in four (15%) patients--one with aneurysmal lesions, three with ectatic lesions--all within 1 year of disease onset. Eight patients developed myocardial infarction; one of these patients died. The resolution rate was less than previously reported. This high rate would warrant closer attention to the state and sequelae of coronary artery lesions, including obstructive coronary artery disease, in follow-up assessments.     

Leukocyte counts in patients with Kawasaki disease: from the results of nationwide surveys of Kawasaki disease in Japan

In the latest survey of Kawasaki disease in Japan, questionnaires on maximal leukocyte counts of the patients were included to clarify whether leukocyte counts could be of value for the diagnosis and prediction of outcome. A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to all pediatric departments of hospitals with ≥100 beds throughout Japan, and information including maximal leukocyte counts was obtained on patients with Kawasaki disease diagnosed during the 2-y period from January 1993 to December 1994. Of the 11 458 patients diagnosed during the 2-y period, maximal leukocyte counts were reported in 11 062 patients (96.5%). The mean value and the distribution of maximal leukocyte counts were lower in the age group under 1 y. The mean values and the distribution of leukocyte counts were lowest in suspected cases among three diagnostic categories: typical cases of Kawasaki disease, atypical cases, and suspected cases. The mean values of maximal leukocyte counts of the patients with cardiac sequelae were significantly higher than those without cardiac sequelae in each age group. The proportion of patients with cardiac sequelae increased with leukocyte counts in each age group. The Receiver/Response Operating Characteristic (ROC) curve for maximal leukocyte counts in Kawasaki disease revealed that the accuracy of maximal leukocyte counts for prediction of cardiac sequelae was highest in the age group <6 months, and the most accurate cut-off point was 16 × 10⁹/l. The strongest association between higher leukocyte counts (≥16 × 10⁹/l) and cardiac sequelae was observed in the age group <6M. A large-scale analysis of leukocyte counts in patients with Kawasaki disease revealed age-dependent relationship between maximal leukocyte counts, diagnostic categories and outcome. Maximal leukocyte counts may be helpful for the prediction of outcome with the consideration of age.     

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.     

Epidemiologic and clinical characteristics of Kawasaki disease in Shaanxi Province, China, 1993-1997

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.     

Failure to diagnose Kawasaki disease at the extremes of the pediatric age range

To learn about physician practices in diagnosing Kawasaki disease, we surveyed general pediatricians and pediatric infectious disease physicians by questionnaire. A high proportion of general pediatricians (>50%) and infectious disease subspecialists (25%) did not consider the diagnosis of Kawasaki disease in children younger than 6 months and older than 8 years. Failure to consider the diagnosis at the extremes of the pediatric age range puts children at risk because coronary artery abnormalities occur more often in young infants and adolescents with Kawasaki disease.     

Kawasaki disease

PURPOSE OF REVIEW: Kawasaki disease is an acute, self-limited vasculitis of childhood characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately 15 to 25% of untreated children with the disease and may lead to myocardial infarction, sudden death, or ischemic heart disease. RECENT FINDINGS: In the United States, Kawasaki disease has now surpassed acute rheumatic fever as the leading cause of acquired heart disease in children. The cause of Kawasaki disease remains unknown, but fortunately intravenous immune globulin therapy has proved to be effective at reducing the prevalence of coronary aneurysms in most children treated in the acute phase. Therapy for Kawasaki disease resistant to intravenous immune globulin therapy is an area of research and controversy. The long-term treatment of children with Kawasaki disease is dependent on coronary artery status. SUMMARY: This review covers key data on the etiology, pathogenesis, treatment, and long-term outcomes of Kawasaki disease, highlighting recent publications.     

Mortality among persons with a history of Kawasaki disease in Japan: the fifth look

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.     

Kawasaki disease: four case reports of cardiopathy with an institutional and literature review.

Kawasaki disease (KD) is a systemic vasculitis condition with a relatively unknown etiology. First described in 1967 by Tomisaku Kawasaki in Japan, KD has come to be widely diagnosed in every region of the world. The disease has a high prevalence in children ages 6 months to 5 years, particularly in those of Japanese descent. Patients often present with a high fever, rash, lymphadenopathy, and conjunctival injections, but there is no diagnostic test for KD. This paper presents data from our Kawasaki registry including 99 patients with emphasis on Kawasaki cardiopathy. Three patients died from complications of KD, and 1 patient underwent heart transplant for massive aneurysmal dilatation. The 4 explanted hearts showed a spectrum of pathological findings (acute thrombosis, vasculitis, and myocarditis), and 1 patient showed the long-term sequelae of vasculitis in the form of massive aneurysmal dilatation. Among the survivors, 30% showed aneurysmal dilatation. This paper reviews the most recent information regarding Kawasaki cardiopathy and underlying molecular mechanisms.