Objective: The purpose of this study is to observe epidemiologic pictures, especially yearly trend of the incidence rates of Kawasaki diseases in Japan over 30-year period since 1965.
Design and Methods: Fourteen nationwide epidemiologic surveys of Kawasaki disease have been conducted to all the pediatric departments of the hospitals with more than 100 beds throughout Japan in every two-year period since 1970.
Results: Total number of patients occurred by the end of December 1996 were 140,837 (Males: 81,783, Females: 59,054, Male/female ratio=1.38). The number of cases increased straightly year by year with three outbreaks in 1979, 1982 and 1986. The incidence rates were higher in males and in younger age groups of one year or less. The fatality rates decreased from 1% in 1974 to <0.1% in 1996. The incidence rates per 100,000 children of <5 years old were 102.6 in 1995 and 108.0 in 1996.
Conclusions: The patterns of descriptive epidemiology, such as seasonal variation and cyclic changes of the occurrence, supported the infectious agent as an etiology.
To determine recent epidemiologic trends, we surveyed all hospitals and pediatric cardiologists in Ontario to identify cases of Kawasaki disease (KD) between 1995 and 1997. Overall response rate was 87% from hospitals, with all major centers represented. From 408 cases (81% typical KD), the annual incidence (per 100,000) by age was 13.6 in <5 yrs (with relative risk for males vs. females of 1.73), 3.8 in 5 to 9 yrs and 0.8 in 10 to 14 yrs. Relative risk by race (vs. Caucasian) was Asian 5.3, Black 3.5, Hispanic 1.2 and other 1.3. There was a seasonal peak between November and February, with a smaller peak in June and July. Nearly al1 cases (96%) were admitted to hospital, with 92% treated with IVGG (94% treated within 10 days of fever onset; 10% received more than 1 dose).
Coronary artery involvement included ectasia in 35%, non-giant aneurysms in 9% and giant aneurysms (>8 mm) in 1.4%, with ventricular dysfunction noted in 2.7%. Aneurysms were noted in 6% of cases treated with IVGG within 10 days of fever onset, and 29% if treated later (p=0.001). Aneurysms were noted in 15% of cases <1 yr of age, 9% from 1 to 4 yrs., 6% from 5 to 9 yrs, and 13% from 10 to 14 yrs (p=0.33). Treatment delay (IVGG given after 10 days of fever) or no IVGG given was significantly related to age, and noted in 10% of patients <1 yr, 10% from 1 to 4 yrs, 20% from 5 to 9 yrs, and 38% from 10 to 14 yrs (p=0.004). After controlling for treatment delay or absence, age <1 year had the highest risk of aneurysms (odds ratio 3.95 relative to 10 to 14 yrs; p<0.05).
Conclusion: Epidemiologic trends are similar to previous studies in Ontario (1989·90, incidence 11.3 in <5 yrs). Diagnostic and treatment delays continue, with an associated increased risk of aneurysms.
Background: Long-term prognosis af Kawasaki disease is still unclear.
Methods: In a cohort study, 6,576 patients with Kawasaki disease were observed from the first medical encounter because of the disease through the end of 1996, or until death. Standardized mortality ratios (SMR) with 95% confidence intervals were calculated with vital statistics data of Japan for the control.
Results: Of 6,576 patients who met the eligibility criteria, 6,545 (99.5%) were followed through either the end of the study or the date of death. The average period of observation was 9.6 years. Twenty-four patients had died bv the end of 1996. An overall SMR during the study period elevated slightly. Although during the acute phase of the disease (the first 2 months after the first visit to hospitals) the SMR was higher, particularly in males, both males and females had low SMRs after the acute phase.
Conclusion: Although the mortality rate among those with a history of Kawasaki disease was elevatcd in Japan, many of the deaths that caused the elevation occurrcd during the acute phase of thc disease. Thc mortality rate did not increase after the acute phase of the disease.
Objective: Assess the pattern of occurrence of Kawasaki syndrome (KS), the frequency of KS treatment with intravenous immunoglobulin (lVIG), and the proportion of KS patients with coronary artery ectasia in the United States, 1994-1997.
Methods: Through voluntary, passive surveillance, the Centers for Disease Control and Prevention (CDC) collected and summarized information submitted by health care providers on diagnosed cases of KS.
Results: CDC received reports on 304 KS cases with onset in 1994, 324 in 1995, 313 in 1996, and 321 in 1997. The majority (60.6%) of the 4-year total of 1,262 KS cases were in boys, and 78.5% of the patients were <5 years of age. By race, 59.9% were white, 24.8% black, and 12.4% were Asian or Pacific Islanders. Overall, 98.1% of patients were reported to have recemed IVIG treatment, and 8.2% were reported to have developed coronary artery ectasia. KS was reported as recurrent for 30 of the cases. A significantly higher proportion of the patients with recurrent KS had coronary artery ectasia (20% compared with 7.9%, p<0.05).
Conclusions: During 1994 through 1997, CDC surveillance indicated no unusual nationwide increase in the occurrence of KS. Nearly all of the reported patients received IVIG treatment. The continued preventive efficacy of this treatment was indicated by the lower proportion (8.2%) of KS patients with reported coronary artery ectasia compared with that for cases reported before the use of IVIG (19.6%).
An outbreak ot Kawasaki Disease (KD) occurred in Denver, Co., Dec. 1997-June 1998. A retrospective review identified 33 cases compared to 13 cases in the same time period of the preceding year (p=.01). Males and females were equally affected, and the mean age was 2.9 years (range 3 mo.-12 yrs).
Patients presented with a mean of 10.9 days of fever (range 4-28). 10/31 patients (32%) presented > 10 days after fever onset. 17 (51%) had CAA detected by echo at presentation of which 6 (18.2%) had aneurysms. 20/33 (60.6%) had CAA at any time. These CAA included coronary artery prominence (52.4%), dilation (19%), aneurysms (28.6%), and other (23.8%). The patients who presented after day 10 had the same prevalence of CAA as those who presented earlier.
32/33 patients were treated with IVlG and aspirin. 1 patient was a treatment failure (normal echo pre-treatment). 25 patients had both a CRP and ESR done at admission. 10/25 (40%) had a discrepant CRP and ESR, arbitrarily defined as CRP>10 mg/dl and an ESR<50 mm/hr or CRP
In this outbreak: 1)CAA at presentation were higher than reported previously, 2) 1/3 of patients were diagnosed after day 10, and 3) 40% of patients had CRP and ESR discrepancies at presentation. Possible explanations for the high rate of CAA include an outbreak of unusually severe disease and/or better technology and interpretation of echocardiograms. The high rate of ESR and CRP discrepancies suggests that obtaining both tests on suspected KD patients might be prudent.
When did therapy start? (1 week/2 week/3 week) 1989-1991: 60%/30%/10%; 1996-1997: 78%/20%/2%. We found that the time at which the therapy began was of crucial importance. Since 1994 aneurysms were found in 8.7% (6% when therapy started in the first week, 25% when it started in the second week and more than 50% when it started after the second week). This clearly shows the need of early diagnosis and therapy.
Mortality has dropped considerably in Germany. Between 1978-1984 it was 2%; meanwhile it has dropped to 0.25%.
We found an incomplete KS in 11%. The high percentage of 25% with aneurysms in this group - as compared to 11% in complete KS - was noticeable. The reason for this probably is late start of therapy (in 28% of incomplete KS in the 3rd week or later as compared to 5% in complete KS) and younger age (in incomplete KS 34% of the patients were in their first year of life as compared to 20 percent in complete KS).
Incidence in the area of Heilbronn Pediatric Hospital was 9/100,000 children <5 years of age. Projecting this to tbe whole of Germany we would have to expect about 350-390 new cases of KS per year.
In Germany we plan to replace the existing form of registering cases of Kawasaki Disease by a registration method similar to that used at present in the United Kingdom. It would be a good idea if several European countries would cooperate in this survey.
Epidemiologic surveillance of KD in the United States is conducted to monitor baseline incidence of the disease and to identify epidemics. National surveillance for KD has becn conducted through the Centers for Disease Control and Prevention (CDC) since 1976, with a computerized database maintained since 1984. ln California, reporting of cases through the county and state Departments of Health Services has been mandated since mid-1989. A retrospective review of a 2-year period was performed to identify the number of patients who met CDC criteria for diagnosis of KD and who were successfully reported to the county, state, and national databases.
Number of KD Cases, 1996/97: *KD Research Center, 40/37 (100% reported); San Diego County Public Health Dept., 16/23 (50.6% reported); California Dept. of Health Services, 13/20 (42.8% reported); Centers for Disease Control, 13/20 (42.8% reported).
*Cases ascertained by chart review of patients with ICD9 code 446.1Based on 1990 U.S. census data for San Diego County, we estimate that the annual attack rate was 20.7 and 21.7 per 100,000 children <5 years of age for 1996 and 1997, respectively. Passive surveillance for KD in San Diego County resulted in thc reporting of approximately half of the eligible patients to health authorities. lmplementation of a sentinal hospital rcporting system in the U.S. should be considered as a preferred alternative to national passive surveillance in the effort to track total numbers of patients and follow disease trends over time.
The established diagnostic criteria for Kawasaki disease (KD) presently in use requires the presence of fever plus 4 out of 5 cardinal features (for typical disease); or, with fewer symptoms, the detection of coronary artery aneurysms (for atypical disease). This definition of atypical KD by its nature delays initiation of treatment until coronary arteries are clearly involved.
Aim of the study: To identify those clinical and laboratory features of atypical KD, which may assist in recognition of the disease by the 10th illness day.
Patient material: We have reviewed retrospectively the pts with typical and atypical KD with coronary abnormalities encountered at CHLA between 1984 and 1998 (the era of IVIG).
Preliminary findings: Approximately 40% of patients who ultimately developed coronary artery abnormalities had atypical presentations. The most significant feature noted was a bimodal age distribution of the atypical KD with most occurring at less than 1 yr or greater than 5 yrs of age (73% of atypical vs. 30% of typical). As expected, diagnosis of atypical KD was made later compared to typical KD cases (10.8 vs. 7.7 days from onset). Cervical adenopathy and early extremity changes are absent in more than 50% of atypical cases. Ocular and oral mucosal changes arc frequently absent. Features common to both groups included persistence of fever despite antibiotic use, anemia, hypoalbuminemia and a leftward shift in white cell differential. Sterile pyuria appeared to be present in greater pcrcentage of atypical pts.
Conclusions: The data identifies a class of pts in whom a higher index of suspicion by primary care physicians would prompt earlier referral to tertiary care centers for diagnosis and treatment, preventing significant morbidity and life-long cardiac sequela.
The clinical and demographic features of KD in older children are not well characterized. We reviewed 27 children 8 to 15 yr (mean 9.1 yr) treated for acute KD from March 1983 through April 1998. 25/27 children were White, 1 Black and 1 Hispanic. 18 boys and 8 girls met clinical criteria for the diagnosis of typical KD. One boy met only 2 criteria in addition to fever, but developed large coronary artery aneurysms (CAA) and was included. All 27 patients had conjunctival injection and extremity changes; 26/27 had mucosal involvement; 24/27 had rash; and 17/27 had cervical node enlargement. Other prominent symptoms included vomiting (13 boys, 4 girls), diarrhea (8 boys, 2 girls), arthralgias (5 boys, 5 girls), headache (4 boys, 2 girls), meningeal signs (4 boys, 2 girls), sore throat (3 boys, 1 girl), arthritis (2 boys, 1 girl), and weight loss (2 boys). CSF in 2 patients revealed pleocytosis (11 and 600 cells/mm3).
The mean time of IVGG and aspirin treatment for 21 patients was 8.9 days (range 4 to 18); 6/21 (38%) were treated after illness day 10, following a delay in diagnosis.
CAA developed in 6/27 patients (22%) including 3/15 (20%) treated with IVGG and aspirin before illness day 10, 3/6 (50%) treated with IVGG and aspirin after day 10, and 0/6 (5 boys, 1 girl) treated with aspirin alone. All 6 who developed CAA were white males.
Less common complications included transient hearing loss in 2 patients; tinnitus, salicylate hepatitis, hemolytic anemia, salicylate allergy, corneal excoriation, and coagulopathy responding to vitamin K each occurred once. Two patients had adverse reactions to IVGG, one of whom developed acute signs and symptoms of aseptic meningitis. Two patients received >1 course of IVGG.
We conclude that GI disturbances, meningeal irritation, and joint involvement occurred in our group of older KD patients and often appeared to delay diagnosis of KD despite fulfillment of criteria. White males were overrepresented in this cohort and included all 6 patients who developed CAA.
Peripheral vascular disease, most often ischemic gangrene, is a rare complication of Kawasaki disease (KD) to be due to arteritis and aneurysmal dilatation of peripheral vessels and thrombo-embolic events. However, the occurrence of vasospastic reversible peripheral arterial disease is not commonly recognized. We report 3 patients with KD who, following their initial illness, showed features suggestive of Raynaud syndrome (RS).
Typical KD clinical features were present in all patients; age at onset ranged from 4-10 months. Echocardiogram at the onset showed bilateral coronary artery aneurysms in 2 cases; one also had axillary and femoral artery dilatation, and the other a small coronary thrombus. All patients received treatment with IVIG, aspirin and dipyridamole; prednisdone was also given to the 2 cases described above.
One to 5 months later all showed episodic blanching and pain in the extremities compatible with RS. Peripheral pulses at that time were normally palpable. The frequency of episodes increased during winter and in one after viral illnesses. IV prostacyclin led to reduction of symptoms in one. Prothrombotic screen, apart frvm mild elevation of IgG anticardiolipin antibodies, was normal. Thermography in 2 cases, showed severe peripheral vasospasm with no opening of arteriovenous shunts for 10 min. following cold stress. Loss of normal nail-fold capillaries with formation of macrocapillaries was seen. Symptoms of RS ameliorated following advice to keep warm and oral nifedipine. At 30-54 months follow-up patients still manifest ischemic episodes but without digital ulceration or necrosis.
These data suggest that RS can follow KD, and persist for a number of years requiring appropriate management. It remains to be seen whether these symptoms are due to endothelial damage suffered at the time of the acute illness.
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