Kawasaki disease (KD) is an acute, self-limited systemic vasculitis of unknown etiology that occurs predominantly in infants and young children and was first described in 1967 by Tomisaku Kawasaki(1-3). Though its incidence varies among countries, higher rates of KD have been reported in Asian countries such as Japan and Korea(5-7). According to a recent nationwide epidemiologic study, the number of Korean children with KD has steadily increased each year with an annual incidence of 105/100,000 children, which is second only to Japan(8).

KD is the leading cause of acquired heart disease in childhood, causing overt damage in up to 15-25% of untreated children and 2-4% of those who receive appropriate treatment, and may lead to myocardial infarction, sudden death, or ischemic heart disease(2,4,9-12). Prompt diagnosis using intra-venous immunoglobulin (IVIG) can reduce the incidence of coronary artery abnormalities from 20-25% to 5%(13,14). Reported risk factors for coronary artery lesions include delayed diagno-sis(15,16) and an age of onset outside the typical age distribution(17,18). Some studies have shown that risk factors for delayed diagnosis include an age of < 6 mo and incomplete KD(16). In addition, more patients are being diagnosed who do not meet the classic diagnostic criteria(19). It has been reported that in incomplete KD and younger children, the clinical features are fewer and more subtle and consequently, diagnosis may be more difficult and delayed(16).

Although conventional diagnostic criteria are useful in preventing overdiagnosis, some studies suggest that these should be revised to include guidelines that recognize incomplete forms of KD(2,20), and a revision of new diagnostic guidelines has been attempted(21,22). General pediatricians may hesitate to make an early diagnosis and treat those outside the typical age range (£6 mo and ³5 y of age) and those who do not fully meet the classic criteria. This may delay diagnosis and prompt treatment, and worsen outcome, as discussed above(23). In this study the clinical features, laboratory findings and outcome were compared in patients with KD within and outside the typical age range.

A total of 198 patients with KD were treated at Severance Children’s Hospital of Yonsei University College of Medicine, Seoul, Korea, between 2006 and 2007. Thirteen cases of recurrent KD were excluded. To investigate age-related differences in clinical characteristics, a retrospective analysis of 185 KD children with a discharge diagnosis of KD was performed after seeking approval from the Institute’s Ethics Committee. Diagnosis of KD was made as per AHA Guidelines(2). Subjects were also evaluated to determine whether they satisfied the classic diagnostic criteria. Incomplete KD was defined as meeting less than 4 clinical criteria, irrespective of echocardiography findings(2,24,25). Overall, there were 63 (34%) cases with classic KD and 122 cases with incomplete KD (66%). Subjects were categorized by age in Group A (22 cases, £5 mo of age), Group B (131 cases, 6 mo-4 y of age) and group C (32 cases, ³5 y of age).

Echocardiography was performed within 2 wk of the onset of illness, during the 4th wk, and subsequently repeated depending on the initial findings. Coronary artery lesion (CAL) was defined as an internal lumen diameter >3 mm in children <5 y of age or >4 mm in children ³5 y of age, if the internal diameter of a segment measured ³1.5 times that of an adjacent segment, or if the lumen was clearly irregular (the Japanese Ministry of Health criteria)(26). When a coronary artery was larger than normal (dilated) and without a segmental aneurysm, the vessel was considered ecstatic(2). All patients underwent laboratory investigations for leukocyte (WBC) count, hemoglobin, thrombocyte, C-reactive protein, erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase (CK), CK-MB, N-terminal fragment of B-type natriuretic peptide (NT-proBNP), and urine WBC, which were performed at admission and 1 day after the initial IVIG infusion, in keeping with normal clinical practice at our hospital.

Statistical analysis was performed using SPSS 13.0 for Windows. The three age groups were compared for clinical characteristics including presence of coronary artery lesions, hematological and bio-chemical parameters, and for presence of classical or incomplete KD. The means of the continuous variables in the 3 age groups were compared using 1-way ANOVA. If there were significant differences among the 3 groups, identification of the 2 groups that showed significant differences were made by post hoc tests (Scheffe, LSD and Tukey’s). Chi-square test was used for comparing categorical variables. A probability of £0.05 was considered statistically significant.

TABLE I



Clinical Characteristics of Kawasaki Disease According to Age at Diagnosis

With no specific diagnostic test for KD, phy-sicians are likely to diagnose it on the basis of clinical findings. Rigorous application of the classical clinical diagnostic criteria is inappropriate and may result in missed diagnoses(2). Since some clinical and laboratory findings are characteristic, they can help prevent misdiagnosis(20). BCG site change and NT-proBNP may be highly suggestive markers for acute KD to differentiate from other acute febrile illnesses and also be useful as additional diagnostic tools(30). Recently published less stringent diagnostic algorithms may prove particularly useful, especially in younger age groups(2,22). Further research is needed to continue the revision of diagnostic criteria of the Kawasaki disease.