Kyu Yeun Kim

Recent advances in Kawasaki disease

Kawasaki disease (KD) is characterized with acute systemic vasculitis, occurs predominantly in children between 6 months to 5 years of age. Patients with this disease recover well and the disease is self-limited in most cases. Since it can lead to devastating cardiovascular complications, KD needs special attention. Recent reports show steady increases in the prevalence of KD in both Japan and Korea. However, specific pathogens have yet to be found. Recent advances in research on KD include searches for genetic susceptibility related to KD and research on immunopathogenesis based on innate and acquired immunity. Also, search for etiopathogenesis and treatment of KD has been actively sought after using animal models. In this paper, the recent progress of research on KD was discussed.

Epidemiologic Study on Kawasaki Disease in Korea, 2007-2014: Based on Health Insurance Review & Assessment Service Claims

The aim of this study is to assess the actual epidemiologic features of Kawasaki disease (KD) in Korea using the data from Health Insurance Review & Assessment Service (HIRA) claims from 2007 to 2014. We investigated HIRA claims of patients who had KD (International Classification of Diseases-10, M30.3) as a major diagnosis and were given intravenous immunoglobulin (IVIG) from 2007 to 2014. A total of 39,082 patients were reported during the period. The male-to-female ratio was 1.42 and the median age was 28 months. The incidence rates were 168.3 per 100,000 population aged 0 to 4 years in 2007, 159.1 in 2008, 167.3 in 2009, 190.4 in 2010, 188.2 in 2011, 190.2 in 2012, 210.4 in 2013 and 217.2 in 2014. These rates were much higher than those in the previous studies in Korea. KD occurred more often in early summer (May, June and July) and winter (December and January). The annual incidence rate of KD had been increasing every year, reaching 217.2 per 100,000 population aged 0 to 4 years in 2014. It is the second highest incidence rate of KD in the world after Japan.

Burkholderia sepsis in children as a hospital-acquired infection

Purpose Hospital-acquired Burkholderia cepacia (B. cepacia) infection are not commonly recorded in patients without underlying lung disease, such as cystic fibrosis and chronic granulomatous disease. However, in 2014, B. cepacia appeared more frequently in pediatric blood samples than in any other year. In order to access this situation, we analyzed the clinical characteristics of B. cepacia infections in pediatric patients at our hospital. Materials and Methods We conducted a retrospective study of blood isolates of B. cepacia taken at our hospital between January 2004 and December 2014. Patient clinical data were obtained by retrospective review of electronic medical records. We constructed a dendrogram for B. cepacia isolates from two children and five adult patients. Results A total of 14 pediatric patients and 69 adult patients were identified as having B. cepacia bacteremia. In 2014, higher rates of B. cepacia bacteremia were observed in children. Most of them required Intensive Care Unit (ICU) care (12/14). In eleven children, sputum cultures were examined, and five of these children had the same strain of B. cepacia that grew out from their blood samples. Antibiotics were administered based on antibiotic sensitivity results. Four children expired despite treatment. Compared to children, there were no demonstrative differences in adults, except for history of ICU care. Conclusion Although there were not many pediatric cases at our hospital, awareness of colonization through hospital-acquired infection and effective therapy for infection of B. cepacia is needed, as it can cause mortality and morbidity.

DiGeorge syndrome who developed lymphoproliferative mediastinal mass.

DiGeorge syndrome is an immunodeficient disease associated with abnormal development of 3rd and 4th pharyngeal pouches. As a hemizygous deletion of chromosome 22q11.2 occurs, various clinical phenotypes are shown with a broad spectrum. Conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia are the classic triad of DiGeorge syndrome. As this syndrome is characterized by hypoplastic or aplastic thymus, there are missing thymic shadow on their plain chest x-ray. Immunodeficient patients are traditionally known to be at an increased risk for malignancy, especially lymphoma. We experienced a 7-year-old DiGeorge syndrome patient with mediastinal mass shadow on her plain chest x-ray. She visited Severance Childrens Hospital hospital with recurrent pneumonia, and throughout her repeated chest x-ray, there was a mass like shadow on anterior mediastinal area. We did full evaluation including chest computed tomography, chest ultrasonography, and chest magnetic resonance imaging. To rule out malignancy, video assisted thoracoscopic surgery was done. Final diagnosis of the mass which was thought to be malignancy, was lymphoproliferative lesion.

ITPKC and SLC11A1 Gene Polymorphisms and Gene-Gene Interactions in Korean Patients with Kawasaki Disease

Purpose Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guérin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans. Materials and Methods Associations between KD and SNPs in two genes were evaluated. Potential associations between BCG injection site erythema and SNPs in two genes were also evaluated. Gene-gene interactions between ITPKC and SLC11A1 in KD and BCG injection site erythema were also analyzed. Results Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1 were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG injection site erythema. Conclusion This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants identified in this study affected KD and erythema of BCG injection sites independently and through gene-gene interactions. Also, the effects of the polymorphisms were age-dependent.

Relationship between Pentavalent Rotavirus Vaccine and Intussusception: A Retrospective Study at a Single Center in Korea

Purpose Despite withdrawal of RotaShield® and the development of second generation live attenuated rotavirus vaccines, concerns remain regarding the relationship between rotavirus vaccine and intussusception. Nevertheless, since there is no study in Korea, we reviewed data from cases at Severance Childrens Hospital to determine the association between rotavirus vaccine and intussusception. Materials and Methods Patients coded as intussusception and following a prescription of RotaTeq® from 2007 to 2013 were reviewed. We calculated comparative incidence figures (CIFs) and 95% confidence intervals (CIs) to compare the risk of intussusception in Korea with the risk in the United States. Expected cases within the four-week post-vaccination window were calculated by applying rates of intussusception from data compiled by the Health Insurance Review and Assessment Service (for a five-year period) to numbers of vaccinations. Results In total, 10530 doses of pentavalent rotavirus vaccine were administered. A total of 65 intussusception cases were diagnosed, although only two cases occurred within four weeks after vaccination. This was compared to six cases within 999123 doses in United States from April 2008 to March 2013 (CIF, 31.63; CI, 31.33–31.93). When we adjusted incidence rate differences for both countries, the CIF decreased to 7.05 (CI, 6.72–7.40). When we compared our identified cases with the expected cases from our hospital, there was no increased intussusception occurring within four weeks of vaccination. Conclusion We found no association between pentavalent rotavirus vaccine and intussusception. Therefore, rotavirus vaccination should be considered due to its benefits of preventing rotavirus-associated diseases.

A case of Henoch-Schönlein purpura associated with posterior reversible encephalopathy and review of litereature

Henoch-Schonlein purpura (HSP) is a vasculitis that involves small vessels and seen in children predominantly. Main symptoms are purpuric rashes on body, especially on lower extremities, arthralgia, abdominal pain, and nephritis. Uncommonly, nervous system can be involved.

Variants in the gene EBF2 are associated with Kawasaki disease in a Korean population

Purpose Kawasaki disease (KD) is a mucocutaneous lymph node syndrome. It is mainly seen in young children under the age of five. KD is a multifactorial disorder that includes genetic variants. The present study investigated the association between KD and single nucleotide polymorphisms (SNPs) in the candidate gene early B cell factor 2 (EBF2), which is associated with inflammation markers. Materials and Methods An SNP analysis was performed by whole exon sequencing of the EBF2 gene. Our study comprised a total of 495 subjects (295 KD patients and 200 unrelated normal controls) from a Korean population. Tag SNPs were discovered using the Haploview program. Genotyping of the EBF2 gene was performed with the TaqMan® assay with real-time PCR methods. Results Polymorphism of rs10866845 showed a significant difference in allele frequency between KD patients and controls (p=0.040). The EBF2 gene polymorphisms were significantly associated with KD on logistic regression analysis. Conclusion EBF2 gene variants can contribute to KD in the Korean population.

Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection

Purpose During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. Materials and Methods We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children’s Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. Results During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. Conclusion Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.