Factors related to cardiac sequelae of Kawasaki disease

Among the 35,210 patients with Kawasaki disease who were reported in nationwide surveys from 1991 to 1996, 83% were treated with gamma-globulin (GG). Those treated with a total dose of 1000 mg/kg (9098 patients) and 2000 mg/kg (7012 patients) were selected as the subjects of the study on the relationship between the development of cardiac sequelae, in particular of giant aneurysms, and related factors using logistic regression models. Among the two groups that received 1000 mg/kg and 2000 mg/kg, respectively, the odds ratios for cardiac sequelae were significantly high for males, those <6 months and ≧ 7 years of age, and typical or recurrent cases. Except for those <6 months of age, the odds ratios of all the factors mentioned above were higher for the incidence of giant coronary aneurysms than those for cardiac sequelae. The preventive effects of GG therapy for cardiac sequelae and in particular giant aneurysms, were significantly low when GG administration was initiated on day 8 or later after onset. In the group treated with 1000 mg/kg, the preventive effect was low when GG administration was spread over 3 days or longer. Conclusion To prevent the development of cardiac sequelae, in particular giant coronary aneurysms, gamma-globulin therapy should be started as soon as possible and be completed within 2 days. Received: 8 July 1998 / Accepted: 18 December 1998     

Factors relating to the cardiac sequelae of Kawasaki disease one month after initial onset

This study aimed to determine the risk factors related to the presence of cardiac sequelae 1 mo after initial onset and to examine the preventive effect of the early administration of high-dose gamma-globulin (GG) on cardiac sequelae in patients with Kawasaki disease. Patients treated with high-dose GG of 2000 +/- 100 mg kg(-1) were selected as subjects from the 15th nation-wide survey in Japan. Univariate and logistic multiple variable analyses were used to test the effects of background variables such as age and gender, variables relating to laboratory findings such as the percentage of neutrophil leucocytes, and variables relating to the GG treatment on the presence of cardiac sequelae. The odds ratios were significantly higher for males (1.48), those younger than 1 y of age (1.71), recurrent cases (2.42), and those with a low haematocrit (<32.5%) (1.45) and high percentage of neutrophil leucocytes (>68%) (1.63). The odds ratio was low for those who started GG administration in less than 6 d from onset between the patients with and without cardiac sequelae. The odds ratio for the duration of GG treatment was not significantly different between those with and without cardiac sequelae. Conclusion: Patients who received early administration of GG, less than 6 d from onset of the disease, had a lower risk than those received GG more than 6 d from the onset. The percentage of neutrophil leucocytes and the haematocrit level are useful indicators in predicting the development of cardiac sequelae.     

Use of Intravenous γ-Globulin for Kawasaki Disease: Effects on Cardiac Sequelae

The administration of intravenous γ-globulin (IVGG) for Kawasaki disease was investigated throughout Japan in 1993 by obtaining information from pediatric departments in 2652 hospitals that had more than 100 beds. Of 11,221 reported patients, 8958 patients (79.8%) received IVGG treatment. Of all the patients to whom IVGG was administered, the most common total dose was 1000 mg/kg (36.3%) followed by 2000 mg/kg (16.9%) and 1200 mg/kg (16.8%). The treatment was started in 53.8% by day 5 of the illness and in 83.7% by day 7. The proportion of those with cardiac sequelae was higher among patients administered >2000 mg/kg or in those started on IVGG on day 9 of their illness or later. The possible reasons are (1) those who were more severely affected were treated with high-dose IVGG earlier; or (2) IVGG does not effectively prevent cardiac sequelae. We concluded that there is a risk of unfavorable effects with IVGG regarding cardiac sequelae when the IVGG dose is >2000 mg/kg or if IVGG is started on day 9 or later. We believe that only a randomized controlled trial, undertaken prospectively, can adequately address the question of the optimal use of IVGG.     

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.     

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.     

Pathological Study of Postcoronary Arteritis in Adolescents and Young Adults: With Reference to the Relationship Between Sequelae of Kawasaki Disease and Atherosclerosis

To clarify whether the cardiac sequelae of Kawasaki disease (KD), postcoronary arteritis lesions can become a risk factor for atherosclerosis of the coronary arteries, six autopsy cases of patients older than 15 years of age with coronary arterial lesions caused by arteritis in childhood were examined histologically. Twenty-four arteries were inspected: 10 had no evidence of aneurysm formation, 7 arteries manifested simple dilatation of the lumen, and in 7 arteries there were aneurysms with recanalization. In the group in which there were no aneurysms, ``new intimal thickening' was observed in addition to the preexisting intimal thickening which had been caused by arteritis in the acute phase of KD. In the second group with aneurysmal arteries whose lumen remained dilated, thrombotic occlusion occurred in 4 of 6 aneurysms. In addition, advanced atherosclerotic changes (i.e., complicated lesions) were found in a 39-year-old patient. Finally, in the third group of arteries which manifested recanalized lumens after thrombotic occlusion of the aneurysms, new intimal thickening was seen on the internal side and some of them were occluded. The findings in this study suggest that aneurysms present in coronary arteries in individuals with a history of KD constitute a risk factor for atherosclerosis later in life.     

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.     

Elevation of Cardiac Troponin I in the Acute Stage of Kawasaki Disease

The study was performed to investigate the level of serum cardiac troponin I (cTnI), a marker specific for myocardial damage, using a chemiluminescent immunoassay in the acute febrile stage of Kawasaki disease (KD). The study population consisted of 45 KD patients before intravenous gamma-globulin (IVGG) therapy and a control group of 20 patients without KD. Among KD patients the results from measurements of the level of cTnI were positive in 18 cases (40%) and the creatine kinase (CK)-MB was positive in 11 cases (24%), but in the control group both the cTnI and CK-MB results were negative. Seven KD patients (15.6%) showed increases in both cTnI and CK-MB that were significantly correlated with each other (p < 0.05); however, CK-MB is not heart-specific. A significant increase in the level of cTnI in the acute stage of KD suggests that acute myocarditis or myocardial cell injury begins in the early phase of the disease (p < 0.05). The serologic test for cTnI can thus be a useful method for the early diagnosis of acute myocarditis and may enable early treatment with IVGG to reduce the cardiovascular abnormalities in KD patients.     

Noninvasive evaluation of systolic pressures of pulmonary artery and right ventricle using contrast-enhanced doppler echocardiography: Comparative study using sonicated albumin or glucose solution

Evaluation of pulmonary arterial pressure is essential for the diagnosis and management of patients with congenital heart disease; it is usually done by cardiac catheterization. An alternative, noninvasive method may be clinically more useful. The purpose of this study was to assess the usefulness of the noninvasive determination of systolic pressure of the pulmonary artery and right ventricle by contrast-enhanced Doppler echocardiography. We selected 30 pediatric patients (28 with trivial or nonsignificant tricuspid regurgitant Doppler signals and 2 with significant tricuspid regurgitant Doppler signals) aged 2 months to 21 years. The flow velocity of tricuspid regurgitation was measured with continuous-wave Doppler of the right ventricular inflow view or left parasternal or apical four-chamber view before and after injection of two types of contrast medium (hand-agitated 5% glucose or sonicated albumin). The systolic pressure of the pulmonary artery was assessed as the estimated right ventricular systolic pressure (albumin method) minus the peak pressure gradient across the pulmonary valve (nonenhanced Doppler method). After injection of hand-agitated 5% glucose and sonicated albumin, trivial tricuspid regurgitation signals were enhanced in 25 of 28 patients (89%). In two patients, spectral envelopes were well defined enough to obtain the peak systolic velocity of the tricuspid regurgitation jet without contrast medium injection. Peak velocity was not altered by injection of contrast medium in these patients. There was significant correlation between the estimation by contrast-enhanced Doppler using hand-agitated 5% glucose and the cardiac catheterization measurement of the transtricuspid pressure gradient (r= 0.88). The transtricuspid pressure gradients obtained by continuous-wave Doppler during sonicated albumin enhancement corresponded closely to those measured by cardiac catheterization (r = 0.95). Pulmonary arterial and right ventricular systolic pressures measured by Doppler using sonicated albumin and those obtained by cardiac catheterization were highly correlated (right ventricle, r = 0.96; pulmonary artery, r = 0.95). In conclusion, this technique may be a valuable noninvasive method for determining accurate right ventricular and pulmonary arterial systolic pressures.     

Circulating Cardiac Troponin I Levels in Kawasaki Disease

In addition to the vascular findings of Kawasaki disease (KD), clinical, electrocardiographic, and/or echocardiographic signs of myocarditis are recognizable in the acute phase of KD in many patients. The mechanism of myocarditis and an association with the development of subsequent coronary artery abnormalities in KD is unknown. Previous studies of serum cardiac troponin I (cTnI) measurements in pediatric populations have suggested a possible utility of measurements in diagnosis and follow-up of KD. We designed a retrospective study to evaluate cTnI measurements during acute KD and to assess the predictive value of cTnI measurements in acute KD for the subsequent development of coronary artery abnormalities. Twenty-nine children were studied. Group 1 consisted of 15 KD patients who developed coronary artery abnormalities as detected by transthoracic echocardiographic evaluation. Group 2 consisted of 14 KD patients with persistently normal coronary artery findings on echocardiograms. A control group consisted of 11 children, none of whom were known to have had clinical findings of KD or myocarditis. The mean cTnI values for all three groups were lower than the values suggestive of cardiac damage: group 1 = 0.11 ± 0.16 ng/ml, group 2 = 0.15 ± 0.34 ng/ml, and control = 0.04 ± 0.08 ng/ml. The current study demonstrates that there is no significant elevation of cTnI in KD patients. Additionally, there is no correlation between cTnI measurements and the finding of myocarditis, as reflected by decreased cardiac function, or the subsequent development of coronary artery abnormalities.     

Macro Creatine Kinase in Kawasaki Disease

This report describes a case of Kawasaki disease with macro creatine kinase (CK). A 13-month-old boy developed typical symptoms of Kawasaki disease and was treated with flurbiprofen, dipyridamole, and intravenous γ-globulin. The serum level of CK increased during treatment from 371 U/L, at 4 days after the onset of Kawasaki disease, to 13,222 U/L 3 days later. Immunofixation electrophoresis identified macro CK as containing immunoglobulin A (κ, λ). The presence of macro CK may result from muscle tissue involvement in Kawasaki disease.     

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.     

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.     

Age Dependency of Stiffness of the Abdominal Aorta and the Mechanical Properties of the Aorta in Kawasaki Disease in Children

Measuring aortic distensibility has been shown to be useful in adults as a noninvasive method in the early detection of atherosclerosis. This study had two purposes: to assess the stiffness of the abdominal aorta by using two-dimensional echocardiography (2DE) in healthy neonates, children, and adults and to assess aortic distensibility in children with Kawasaki disease in acute and subacute phases. The study comprised 168 healthy subjects and 40 patients with Kawasaki disease. We recorded systolic (P _s) and diastolic (P _d) blood pressure and measured aortic diameter (D _d) at both minimum diastolic pressure and maximum systolic expansion (D _s) by 2DE. These measurements were used to determine (1) aortic strain (S) = (D _s−D _d)/D _d, (2) pressure strain elastic modulus (E _p) = (P _s−P _d)/S, and (3) normalized E _p (E _p*) =E _p/P _d. Significant correlations were found between S and age, E _p and age, and E _p* and age. In Kawasaki disease, E _p and E _p* showed negative correlations to day after onset. The aorta was less distensible in infants, became soft in 12- to 16-year-olds, and then stiffened with increasing age among normal subjects. In Kawasaki disease, aortic stiffness was high at the acute phase and normal at the subacute phase. These tendencies may be related to the biological characteristics of smooth muscle cells.     

Acute Renal Insufficiency and Renal Replacement Therapy After Pediatric Cardiopulmonary Bypass Surgery

The aim of the study was to investigate renal function and renal replacement therapy after cardiopulmonary bypass surgery in children. Patient characteristics (sex, age, diagnosis), operation type, and death were listed. The study was performed retrospectively using serum creatinine level before, and peak values after, cardiopulmonary bypass surgery for assessment of renal function. Of the children on renal replacement therapy, indication, efficacy, and complications were recorded. In a 5-year period, 1075 children had cardiopulmonary bypass surgery at the Department of Cardiothoracic Surgery at Leiden University Medical Center and Academic Medical Center of Amsterdam. One-hundred eighty (17%) patients developed acute renal insufficiency. Twenty-five (2.3%) patients required renal replacement therapy. Peritoneal dialysis is a safe and effective treatment for children after cardiopulmonary bypass surgery. However, 15 (60%) of 25 children on renal replacement therapy died of nonrenal causes. In 9 out of 10 surviving children, renal function was normal at time of discharge from hospital. Acute renal insufficiency is a frequent complication after open-heart surgery, although renal replacement therapy was infrequently necessary. Peritoneal dialysis is a safe and effective therapeutic measure for children after cardiac bypass surgery.     

Kawasaki Disease Complicated by Peripheral Gangrene

An 8.5-month-old male infant with Kawasaki disease (KD) received high-dose intravenous immunoglobulin (IVIG) therapy on the fifth day after fever onset. However, multiple peripheral limb ischemias occurred 2 days later. Accordingly, heparin followed by dipyridamole was administered. Aside from a small amputation at the tip of the right middle finger, all other digital ischemias resolved. This presentation demonstrates that early recognition and management of peripheral gangrene in KD may keep its sequela to a minimum.     

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.     

Aerobic exercise function of patients with persistent coronary artery aneurysms secondary to Kawasaki disease

Nine patients with persistent coronary artery aneurysms 1.7–14.0 years after an episode of Kawasaki disease underwent progressive bicycle ergometry with expiratory gas analysis. Two of the patients had aneurysms complicated by angiographically documented coronary artery stenosis. Results of the exercise tests were compared to those obtained from a group of age- and gender-matched normal control subjects. The Kawasaki disease patients did not differ significantly from the control subjects with regard to peak oxygen consumption (81 ± 7% versus 79 ± 12% predicted), peak workload (75 ± 13% versus 77 ± 9% predicted), anaerobic threshold (21.9 ± 6.5 versus 18.9 ± 4.0 ml/kg per minute) or oxygen pulse (96 ± 7% versus 90 ± 14% predicted). None of the patients developed significant ST segment changes or rhythm disturbances during exercise. The exercise function of the patients with coronary artery stenosis did not differ from that of patients without stenosis. It was concluded that the aerobic exercise function of patients with persistent coronary artery aneurysms after an episode of Kawasaki disease appears to be well preserved. Kawasaki disease patients with significant coronary artery pathology are not accurately identified by a single assessment of aerobic exercise function.     

Radiofrequency Catheter Ablation of Tachycardia in Patients with Congenital Heart Disease

Patients with anomalies of the heart frequently suffer from arrhythmias that either are associated with a congenital heart defect or result from the course of the disease. For most of the bradyarrhythmias, appropriate timing of the initiation of treatment is more challenging than its eventual execution. In the case of tachycardias, technical aspects of treatment require more attention because the often imperative impact such tachycardias have on quality of life, morbidity, and mortality determine intervention timing. Increasingly, interventional electrophysiology is turned to as a potentially definitive and substrate-related treatment because of antiarrhythmic drug therapy's failure to prevent arrhythmia recurrences and the potential detrimental side effects from drug therapy seen in this particular patient population. Using the experience gained during the past 10 years in the treatment of patients with arrhythmias but without associated structural heart disease, several groups reported their results and difficulties with the application of such therapy to patients with congenital heart defects. In this report, we summarize our hospital's experience with transcatheter radiofrequency current application for treatment of various types of tachyarrhythmias in 139 children and adults with congenital heart defects, emphasizing the current limitations of such therapy and addressing the potential benefits expected from future technology. Patient ages ranged from 5 months to 76 years (mean 25.3 ± 17.7 years), including 56 children and adolescents less than 16 years of age. At least one attempt at surgical palliation or correction was made in 93 patients; the remaining 46 patients had no surgical intervention attempts. A total of 225 different tachycardias were found, 93 of which were based on a congenital arrhythmogenic substrate (e.g., an accessory pathway). Acquired substrates (e.g., scars or myocardial fibrosis) gave rise to the remaining 132 tachycardias. Radiofrequency current ablation (183 sessions) successfully treated 121 of 139 patients. Within a follow-up period of 21 months a recurrence of the intrinsically treated tachycardia was seen in 24 patients (10.7%); 13 of the 24 underwent a successful repeat session. There were no significant procedure-related complications. Young and adult patients with congenital heart disease can be safely and successfully treated for tachycardias with the use of radiofrequency current ablation. Because such treatment meets the specific needs of this patient group, early consideration for this therapy is recommended.     

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.