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Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10 ), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10 ). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10 ) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10 to 5.24 × 10 ). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10 ). These results provide new insights into the pathogenesis and pathophysiology of KD.

Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, ~15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89–3.46, P = 0.0109–0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 × 10−4). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 × 10−4). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children, and can result in coronary artery lesions (CAL). A patient with KD who is resistant to treatment with intravenous immunoglobulin (IVIG) has a higher risk of developing CAL. Incomplete KD has increased in prevalence in recent years, and is another risk factor for the development of CAL. Although the pathogenesis of KD remains unclear, there has been increasing evidence for the role of genetic susceptibility to the disease since it was discovered in 1967. We retrospectively reviewed previous genetic research for known susceptibility genes in the pathogenesis of KD, IVIG resistance, and the development of CAL. This review revealed numerous potential susceptibility genes including genetic polymorphisms of ITPKC, CASP3, the transforming growth factor-β signaling pathway, B lymphoid tyrosine kinase, FCGR2A, KCNN2, and other genes, an imbalance of Th17/Treg, and a range of suggested future treatment options. The results of genetic research may improve our understanding of the pathogenesis of KD, and aid in the discovery of new treatment modalities for high-risk patients with KD.

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Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10-5], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10-4), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10-5). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10-4 in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10-7), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility.

Kawasaki disease (KD) is a systemic vasculitis affecting infants and children; it manifests as fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) treatment effectively attenuates the fever and systemic inflammation. However, 10–20% patients are unresponsive to IVIG. To identify genetic variants influencing IVIG non-response in KD, a genome-wide association study (GWAS) and a replication study were performed using a total of 148 IVIG non-responders and 845 IVIG-responders in a Korean population. rs28662 in the sterile alpha motif domain-containing protein 9-like (SAMD9L) locus showed the most significant result in the joint analysis of GWAS and replication samples (odds ratio (OR) = 3.47, P = 1.39 × 10−5). The same SNP in the SAMD9L locus was tested in the Japanese population, and it revealed a more significant association in a meta-analysis with Japanese data (OR = 4.30, P = 5.30 × 10−6). These results provide new insights into the mechanism of IVIG response in KD.

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Purpose In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Recently, we observed a higher incidence of coronary lesions in KD patients with high anti-streptolysin O (ASO) titer. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions. Methods A retrospective review was performed in 723 patients with KD who were admitted to 2 major hospitals between June 2010 and September 2017. Results Among 723 patients with KD, 11 initially showed an elevated ASO titer (>320 IU/mL) or elevated follow-up ASO titer after treatment. Of these patients, 5 showed no response to the first intravenous immunoglobulin treatment, 3 had abnormalities of the coronary arteries. This is a significantly higher proportion of patients with a high ASO titer (n=3, 27.3%) than those with a normal ASO titer (n=53 [7.4%], P=0.047). A severe clinical course was seen in 81.8% of patients in the high ASO group versus 14.5% of patients in the normal ASO group. Conclusion It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. It may be helpful to analyze concurrent streptococcal infection in patients with a severe clinical course.

Purpose Chest pain is common in children and adolescents and is a reason for referral to pediatric cardiologists. Although most cases of chest pain in these age groups are benign and do not require treatment, timely diagnosis is important not to miss life-threatening diseases requiring prompt treatment. We investigated certain clinical characteristics that may be useful in the diagnosis of such critical diseases. Methods Patient medical records between July 2006 and September 2013 were retrospectively examined. We included 517 patients who presented with chest pain to the Department of Pediatrics at Kyung Hee University Hospital in Gangdong. Results Most cases of chest pain were idiopathic in origin (73.6%), followed by cases with respiratory (9.3%), musculoskeletal (8.8%), cardiac (3.8%), gastrointestinal (2.9%), and psychiatric (1.4%) causes. In 6 patients (1.2%) with air-leak syndrome including pneumothorax or pneumomediastinum, the pain was abrupt, continuous, and lasted for a short period of 1-2 days after onset in the older adolescents. Of the patients with cardiac pain, 13 had cardiac arrhythmias (65.0%), 6 had congenital heart diseases (30%), and 1 had coronary aneurysms caused by Kawasaki disease (5.0%). One patient with atrial flutter had only symptoms of syncope and chest pain. Conclusion The abrupt, continuous chest pain of a short duration in the older children was characteristic of air-leak syndrome. In patients with pneumomediastinum, radiological diagnosis was difficult without careful examination. Combined syncope should not be neglected and further cardiac workup is essential in such patients.

The processus vaginalis within the inguinal canal forms the canal of Nuck, which is a homolog of the processus vaginalis in women. Incomplete obliteration of the processus vaginalis causes indirect inguinal hernia or hydrocele of the canal of Nuck, a very rare condition in women. Here, we report 2 cases of hydrocele of the canal of Nuck that were diagnosed with ultrasonography in both cases and magnetic resonance imaging in 1 case to confirm the sonographic diagnosis. High ligation and hydrocelectomy were conducted in both patients. In 1 patient, 14 months later, the occurrence of contralateral inguinal hernia was suspected, but did not require surgery. The other patient had a history of surgery for left inguinal hernia 11 months before the occurrence of right hydrocele of the canal of Nuck. In both cases, the occurrence of an inguinal hernia on the contralateral side was noted.