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Kawasaki disease (KD) is the most common form of pediatric vasculitis. Though its etiology is unknown, researchers have suggested that it is related to genetics. The inositol 1,4,5-triphosphate receptor type 3 (ITPR3) gene has a strong association with the development of type 1 diabetes and, plays a critical role in the development of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease. The aim of study is to examine the association of ITPR3 polymorphisms with KD risk in Taiwanese children. This study evaluates the single nucleotide polymorphisms (SNP) rs2229634 in the ITPR3 gene with KD in a case-control study involving 93 KD patients and 680 healthy, gender- and age-matched controls. The frequency of the rs2229634 T/T genotype was significantly higher in KD patients with coronary artery aneurysm (CAA) than in patients without CAA [odds ratio (OR) = 2.56, 95% confidence interval (95% CI) = 1.35-4.88, P = 0.004]. In addition, KD patients with the T/T genotype elevated mean serum levels of C-reactive protein compared with patients with the C/C or C/T genotype (12.2 mg dL(-1) vs. 8.5 mg dL(-1) , P = 0.036). In conclusion, the results of this study suggest that the rs2229634 SNP in the ITPR3 gene is associated with the risk of CAA formation in Taiwanese KD patients., (© 2010 Blackwell Publishing Ltd.)

Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown etiology wherein genetic influence is suspected. Gene clusters within the HLA region at chromosome 6p21.3 have been linked to KD and other autoimmune disorders. As collagen is a strong autoantigen inducing chronic inflammation in patients with vasculitis, this study tests a hypothesis that single-nucleotide polymorphism (SNP) of a collagen gene, COL11A2, located in this HLA region may affect susceptibility to Kawasaki disease and its arterial sequels. SNP sites rs2294478 (at promoter) and rs2076311 (at intron 19) were genome-typed on 93 KD patients and 680 healthy subjects. Genotypic and allelic frequencies analyses found A allele at rs2076311 as a risk allele for KD. Clinical association study showed protective potential of C/C genotype at rs2294478 and A/A at rs2076311 for developing coronary artery lesions (CALs) in patients. In addition, C-A haplotype of COL11A2 gene associates with KD development and can serve as a genetic marker to differentiate KD patients lacking CALs from those with such lesions. Our findings suggest the involvement of genetic variations of COL11A2 in Kawasaki disease and CAL formation., (© 2010 Blackwell Publishing Ltd.)

Objective: Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population., Methods: The 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients., Results: Eleven single-nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3'-untranslated region of HLA-E (rs2844724) was highly associated (P < 1 x 10(-7)). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA-E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA-E in KD patients with the CT and TT genotypes of the HLA-E gene polymorphism., Conclusion: Our results suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of KD.

High expression of circulating vascular endothelial growth factor (VEGF) has been reported in patients with Kawasaki disease (KD). In the pathophysiology of KD, VEGF is considered to be involved, especially in the development of coronary artery lesions. This study aimed to examine whether the VEGF-634 promoter polymorphism is a marker of KD susceptibility or severity in Chinese patients in Taiwan. The study included 93 KD patients and 96 normal control subjects. Genotype and allelic frequencies for the VEGF gene polymorphism in the two groups were compared. The number of individuals with the VEGF-634 G/G genotype was significantly greater among the patients with KD than among the healthy control subjects (p = 0.011). The odds ratio for the development of KD in individuals with the VEGF-634 G/G genotype was found to be 2.03 (95% confidence interval [CI], 1.14-3.63) compared with the VEGF-634 G/C and VEGF-634 C/C genotypes. No significant difference was observed in the genotype or allelic frequencies of VEGF C-634 G polymorphism between the patients with and those without coronary artery lesions. In conclusion, the results suggest that VEGF-634 G/G genotype may be involved in the development of KD in Taiwanese children.

Background: Many infectious agents have been implicated as an etiology to develop Kawasaki disease (KD). In Taiwan, studies on the relationship between Yersinia and KD have not been reported., Methods: We measured sera for anti-Yersinia antibodies by using enzyme immunoassay (EIA) in 31 patients with KD and 60 healthy children (HC). Yersinia strains included Y. pseudotuberculosis I, II, III, IV, V, VI and Y. enterocolitica O3, O8 and O9., Results: Data of 31 patients with KD showed that for the IgG antibody, serum anti-Y. pseudotuberculosis II, III, Y. O8 and O9 antibody were significantly higher when compared to the HC. Except for Y. pseudotuberculosis IV, all other Yersinia strains of either IgA or IgM antibodies increased significantly in patients with KD vs. the HC. If we compared the number of patients who had significant elevation of OD and those of HC, we found IgA anti-Yersinia antibodies (PST I, PST II, O3, O8, O9), IgM (PST VI, O8) and IgG (PST II, O8, O9) were significantly elevated in KD patients than in HC. A significant relationship was present between KD with myocarditis and increased anti-Yersinia antibody titer., Conclusions: The findings in this study suggest that preceding Yersinia infection may play a role in the pathogenesis of KD. Further study of the relationship between KD with myocarditis and increased anti-Yersinia antibody is needed.

Kawasaki disease is an acute febrile illness typically elicited by vasculitis and occurring in young children. We investigated the polymorphism of the angiotensin-1 converting enzyme (ACE) gene in children with Kawasaki disease and also in age-matched controls. A total of 107 children, with a mean age at diagnosis of 1.71 +/- 1.48 years, who suffered from Kawasaki disease and who were treated with aspirin as well as intravenous immunoglobulin were enrolled in this study. Control subjects consisted of 107 children, with a mean age of 1.84 +/- 1.20 years. The polymorphisms of the ACE gene, including I/D, A-240T, and G2350A, were examined using a polymerase chain reaction method for Kawasaki disease patients and also for control subjects. We noted a significant difference in the distribution of the ACE gene I/D genotype between Kawasaki disease and control groups. The ACE gene G2350A polymorphism and associated allelic frequencies demonstrated an association with Kawasaki disease. Our results revealed no evidence of any association between the ACE gene polymorphism and the frequency of coronary artery aneurysm associated with Kawasaki disease, although our results do support a role for the I/D and G2350A polymorphism of the ACE gene in determining the risk of Kawasaki disease in the population of Taiwan.

An 8.5-month-old male infant with Kawasaki disease (KD) received high-dose intravenous immunoglobulin (IVIG) therapy on the fifth day after fever onset. However, multiple peripheral limb ischemias occurred 2 days later. Accordingly, heparin followed by dipyridamole was administered. Aside from a small amputation at the tip of the right middle finger, all other digital ischemias resolved. This presentation demonstrates that early recognition and management of peripheral gangrene in KD may keep its sequela to a minimum.

Intensive echocardiographic studies were undertaken in 37 patients with Kawasaki disease (KD) and 12 febrile controls during the acute stages. Video-tape recordings were read doubly-blinded by 3 pediatric cardiologists at 2 hospitals. Three characteristics of subtle coronary arterial lesions, including contour of lumen, smoothness of endothelium and sono-homogeneity of the surrounding tissue were particularly described. Seven of the 37 KD patients (19%) were found to have coronary arterial aneurysms (CAA) at the end of the convalescent stage. The 3 cardiologists agreed in the diagnosis of the subtle lesions by 72%. More patients with Kawasaki disease were found to have an irregular endothelium than the controls (P < 0.001). KD patients later complicated with CAA were more likely to have had the three characteristics of subtle coronary lesions during the acute stage than the KD patients without aneurysms (P < 0.001). Also, the coronary arterial size measured during the acute stage were found to be positively correlated with their largest dilatation at the convalescent stage (P = 0.0001, r = 0.61). We conclude that early subtle coronary arterial lesions can herald the development of coronary arterial aneurysms.

Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown aetiology that affects infants and children, with most patients having myocardial involvement. To evaluate the incidence and nature of myocardial involvement, 30 patients with Kawasaki disease underwent both dipyridamole 201Tl-chloride myocardial single photon emission tomography (SPET) and two-dimensional echocardiography (2D-Echo), which were performed within 7 days of each other. The SPET image of 15 of 30 (50%) patients showed 27 segments with myocardial perfusion abnormalities: 6 patients had one or more segments showing redistribution; 6 patients had both one or more segments of reverse redistribution and redistribution; 2 patients had reverse redistribution; and one patient had one redistribution and one fixed defect. Eight of 15 (53.3%) SPET abnormalities included reverse redistribution. Of 15 patients with positive SPET, 13 were male (age 0.3-12 years, mean = 3.55) and 2 were female (age 3-4 years, mean = 3.5). The interval between the onset of disease and SPET ranged from 1 to 594 weeks. Of the 15 patients with a negative SPET, 10 were male (age 0.4-6 years, mean = 2.08) and 5 were female (age 0.2-5 years, mean = 1.8). The interval between the onset of the disease and SPET ranged from 2 to 54 weeks. There were no significant differences in age (P = 0.10), sex (P = 0.41) or interval between the onset of disease and SPET in the patients with positive SPET and those with negative SPET (P = 0.60). With 2D-Echo, 16 (11/15 patients with positive SPET and 5/15 patients with negative SPET) of 30 (53.3%) patients had demonstrable coronary aneurysms. There was no statistical difference (P = 0.4) in the ability to detect myocardial abnormalities between SPET and 2D-Echo. Combining SPET and 2D-Echo, detectability of myocardial involvement was 66.6% (20/30). We conclude (1) that more than 50% of the patients' myocardial involvement was expressed by the myocardial perfusion status on SPET or by coronary aneurysm on 2D-Echo. Combined SPET and 2D-Echo may be of additive benefit for the detection of myocardial involvement. All 15 patients with SPET abnormalities had one or more segments of redistribution and/or reverse redistribution, indicating myocardial ischaemia and/or damaged but viable myocardium.