Ji Whan Han

Epidemiological features of Kawasaki disease in Korea, 2006–2008

Background:u2002 The aim of this study was to estimate the incidence and describe the epidemiological characteristics of Kawasaki disease among children in Korea.

Epidemiologic features of Kawasaki disease in South Korea: data from nationwide survey, 2009-2011.

Background: To assess the recent epidemiologic features of Kawasaki disease (KD) in South Korea from the nationwide survey conducted between 2009 and 2011. Methods: We collected data regarding the incidence, symptoms, treatment and coronary complications associated with acute KD by sending questionnaires to the 100 hospitals that have pediatric residency programs from 2009 to 2011. Results: We received complete responses from 73 hospitals and partial responses from 14 hospitals. A total of 13,031 patients of KD were reported from the 87 hospitals (3941 in 2009, 4635 in 2010 and 4455 in 2011). The male to female ratio was 1.44:1, and the median age at diagnosis was 28 months. From the questionnaires with complete responses, we noted that the incidence of KD per 100,000 children <5 years of age was 115.4 in 2009, 132.9 in 2010 and 134.4 in 2011 (average rate, 127.7). KD occurred more frequently during summer (June, July and August) and during winter (December and January). The recurrence rate was 3.83%. The standard dose of intravenous immunoglobulin was administered to 93.6% of the patients, and nonresponder rate was 11.6%. Coronary aneurysm occurred in 1.9% of the patients and giant aneurysm developed in 26 patients (0.26%) over 3 years, and 2 patients had myocardial infarction. No mortality was reported. Conclusions: The average annual incidence of KD in South Korea has continuously increased to 134.4 per 100,000 children <5 years of age in 2011, which is the second highest incidence of KD worldwide, following its incidence in Japan.

Epidemiologic picture of Kawasaki disease in Korea, 2000–2002

Background :u2002The aim of this study was to investigate the incidence rate and epidemiologic patterns of Kawasaki disease in Korea for a 3u2003year period during 2000 to 2002.

Clinical manifestations of CNS infections caused by enterovirus type 71

Purpose Enterovirus 71, one of the enteroviruses that are responsible for both hand-foot-and-mouth disease and herpangina, can cause neural injury. During periods of endemic spread of hand-foot-andmouth disease caused by enterovirus 71, CNS infections are also frequently diagnosed and may lead to increased complications from neural injury, as well as death. We present the results of our epidemiologic research on the clinical manifestations of children with CNS infections caused by enterovirus 71. Methods The study group consisted of 42 patients admitted for CNS infection by enterovirus 71 between April 2009 and October 2009 at the Department of Pediatrics of 5 major hospitals affiliated with the Catholic University of Korea. We retrospectively reviewed initial symptoms and laboratory findings on admission, the specimen from which enterovirus 71 was isolated, fever duration, admission period, treatment and progress, and complications. We compared aseptic meningitis patients with encephalitis patients. Results Of the 42 patients (23 men, 19 women), hand-foot-and-mouth disease was most prevalent (n=39), followed by herpangina (n=3), upon initial clinical diagnosis. Among the 42 patients, 15 (35.7%) were classified as severe, while 27 (64.3%) were classified as mild. Factors such as age, fever duration, presence of seizure, and use of intravenous immunoglobulin (IVIG) were statistically different between the 2 groups. Conclusion Our results indicate that patients with severe infection caused by enterovirus 71 tended to be less than 3 years old, presented with at least 3 days of fever as well as seizure activity, and received IVIG treatment.

Infliximab Treatment for Refractory Kawasaki Disease in Korean Children

Background and Objectives This was a multicenter study to evaluate the usefulness of the tumor necrosis factor-alpha (TNF-α) blocker infliximab for treatment of Korean pediatric patients with refractory Kawasaki disease (KD). Subjects and Methods Data from 16 patients throughout Korea who were diagnosed with refractory KD and received infliximab were collected retrospectively. Results Complete response to therapy with cessation of fever occurred in 13 of 16 patients. C-reactive protein (CRP) concentrations decreased following infliximab infusion in all 14 patients in whom it was measured before and after treatment. There were no infusion reactions or complications associated with infliximab except in 1 case with acute hepatitis occurring during treatment followed by calculous cholecystitis 4 months later. Fifteen patients had coronary artery (CA) abnormalities before infliximab therapy. Three had transient mild dilatation and 9 had CA aneurysms, with subsequent normalization in 4 patients, persistent mild dilatation in 3, persistent aneurysm in 2, and there were 3 cases (2 with CA aneurysm, 1 with mild CA dilatation) without follow-up echocardiography. Conclusion The results of this study suggest that infliximab may be useful in the treatment of refractory KD, and it appears that there is no significant further progression of CA lesions developing after infliximab treatment. Multicenter trials with larger numbers of patients and long-term follow-up are necessary to assess the clinical efficacy and safety of infliximab in refractory KD.

Polymorphisms of Human Leukocyte Antigen Genes in Korean Children with Kawasaki Disease

BackgroundKawasaki disease is a leading cause of acquired heart disease in children. The prevalence rate varies in different ethnic groups. Recently, with the clinical application of molecular genetic technology, human leukocyte antigen (HLA) polymorphisms associated with several diseases have been identified by DNA analysis. This study aimed to assess the association of HLA alleles with susceptibility and complications of Kawasaki disease in Korean children.MethodsIn this study, DNA was extracted from 74 children with a diagnosis of Kawasaki disease. The polymorphisms of the HLA-A, -B, -C, and -DRB1 alleles of patients with Kawasaki disease were determined by polymerase chain reaction (PCR)–amplification refractory mutation system (ARMS) and PCR–sequence-specific primer (SSP) analysis. The polymorphisms identified were compared with those of 159 normal healthy control subjects.ResultsThere was a significant increase in the frequencies of the HLA-B35, -B75, and -Cw09 alleles in patients with Kawasaki disease compared with the healthy control group. There was no increase in the frequency of HLA-DRB1 alleles among the Kawasaki disease patients compared with a healthy control group. When the patients with Kawasaki disease were divided into two subgroups, with or without coronary complications, the Kawasaki disease patients with coronary complications showed a significantly increased frequency of the HLA-DRB1*11 allele compared with the healthy control group and increased frequency of HLA-DRB1*09 in a comparison of the subgroups.ConclusionsThis study suggests that polymorphisms in some alleles of B and C in HLA class I genes are associated with Kawasaki disease in Korean children.

Epidemiology and Clinical Features of Kawasaki Disease in South Korea, 2012–2014

Background: To reveal the recent epidemiologic features of Kawasaki disease (KD) in South Korea based on data from a nationwide survey. Methods: We collected data between 2012 and 2014 regarding the incidence, symptoms and signs, treatment trends and coronary complications associated with acute KD by sending questionnaires to 97 hospitals with pediatric residency programs as well as 19 community hospitals without residency training. Results: We received full and partial data from 97 and 13 hospitals, respectively (response rate: 94.8%). A total of 14,916 cases of KD were reported by these 110 hospitals (4588 in 2012, 5183 in 2013 and 5145 in 2014). The male-to-female ratio was 1.4:1, and the median age at diagnosis was 29 months. The incidence of KD per 100,000 children younger than 5 years of age were 170.9, 194.9 and 194.7 in 2012, 2013 and 2014, respectively. The recurrence rate was 4.7%. KD occurred more frequently during summer (especially June and July) and winter (December and January) seasons. Intravenous immunoglobulin was administered to 95.4% of the patients, and the nonresponder rate for the first intravenous immunoglobulin was 11.8%. Coronary aneurysm occurred in 1.7% of the patients, and giant aneurysm developed in 19 patients (0.16%) during the 3 years. One patient had myocardial infarction and 1 patient died of suspected coronary aneurysm rupture. Conclusions: The incidence of KD in South Korea increased to 194.7 per 100,000 children younger than 5 years in 2014; meanwhile, the coronary aneurysm rate decreased to 1.7%.

Establishment of Secondary Iron Overloaded Mouse Model: Evaluation of Cardiac Function and Analysis According to Iron Concentration

Periodic blood transfusion can lead to secondary iron overload in patients with hematologic and oncologic diseases. Iron overload can result in iron deposition in heart tissue, which decreases cardiac function and can ultimately lead to death due to dilated cardiomyopathy and cardiac failure. In this study, we established murine model of secondary iron overload, studied the changes in cardiac function with echocardiography, and examined the histopathologic changes. Three experimental groups of the six week-old C57/BL mice (H-2b) were injected intraperitoneally with 10xa0mg of iron dextran daily 5xa0days a week for 2, 4, and 6xa0weeks. Cumulative doses of iron for the three experimental groups were 100, 200, and 300xa0mg, while the control groups were injected with the same amounts of phosphate-buffered saline. We studied the cardiac function under anesthesia with echocardiography using a GE Vivid7 Dimension system. Plasma iron levels and liver iron contents were measured. The hearts and livers were harvested and stained with H&E and Perls Prussian blue for iron, and the levels of iron deposit were examined. We assessed the cardiac measurements after adjustment for weight. On echocardiography, thicknesses of the interventricular septum and posterior ventricular wall (PS) during diastole showed correlation with the amount of iron deposit (Pxa0<xa00.01). End-diastolic volume showed dilatation of the left ventricle in the 300xa0mg group (Pxa0<xa00.01). Changes in the fractional shortening were not statistically significant (Pxa0=xa00.07). Plasma iron levels and liver iron contents were increased proportionally according to the amount of iron loaded. The histopathologic findings of PS and liver showed higher grade of iron deposit proportional to the cumulated iron dose. In this study, we present an animal model which helps understand the cardiac function changes in patients with secondary iron overload due to repeated blood transfusions. Our results may help characterize the pathophysiologic features of cardiomyopathy in patients with secondary iron overload, and our model may be applied to in vivo iron-chelating therapy studies.

Epidemiology of Kawasaki disease in infants 3 months of age and younger

Purpose This study investigated the epidemiology of Kawasaki disease (KD) in infants ≤3-month-old. Methods To study the epidemiology of KD in Korea, data for 27,851 KD patients were collected on a 3-year basis between 2000 and 2008 in a retrospective survey. From this, data for 609 KD patients ≤3-month-old were analyzed and compared with the data for KD patients >3-month-old. Results The 609 KD patients ≤3-month-old (385 males and 224 females) constituted 2.2% of the KD patients. They included 25 infants <1-month-old, 198 infants ≤1- to 2-month-old, and 386 infants >2- and 3-months-old. The ratio of males to females was 1.72:1. The incidence of coronary artery (CA) dilatation (19.9% vs. 18.7%) and CA aneurysms (3.4% vs. 2.6%) detected by echocardiography did not differ significantly between patients with KD younger and older than 3-month-old. Conclusion Compared with the data for the KD patients >3-month-old, the data for the 609 patients ≤3-month-old did not show a significantly higher incidence of CA dilatation or CA aneurysms.

Normal Left Ventricular Torsion Mechanics in Healthy Children: Age Related Changes of Torsion Parameters Are Closely Related to Changes in Heart Rate

Background and Objectives This study was aimed at assessing left ventricular torsion (LVtor) mechanics using speckle tracking echocardiography (STE), establishing normal reference values of principal LVtor parameters, and analyzing the age-related changes in normal children. Subjects and Methods Eighty children (aged 3 months to 15 years) with normal cardiac function and rhythm were recruited. LVtor parameters including rotations, twist and untwist, torsion, and their rate indices were measured using STE. Age and heart rate related changes of the parameters were analyzed. Results Speckle tracking echocardiography analyses for LVtor parameters had excellent reliability in 64 of 80 subjects (80%) (intraclass correlation coefficients; 0.93-0.97). Early systolic twist (EST) motions (-8.4--0.1°) were observed in all subjects during an early 20±7% of systolic time intervals. The peak systolic twist and torsion were 17.0±6.5° and 2.9±1.3°/cm, respectively. The peak twist velocity was recorded at 51±13% of systolic time and the peak untwist velocity at 13.8±11.5% of diastolic time intervals. Multivariate analysis showed that heart rate change was an independent predictor of changes in torsion parameters; significantly decreasing LV length-normalized apical and basal rotation, torsion, and twist and untwist rate with increasing age. Isovolumetric recoil rate was independent of change in age and heart rate. Conclusion Left ventricle showed unique torsion mechanics in children with EST, torsion, and untwists. Heart rate was an independent predictor of the change in torsion parameters with aging.