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      Ethnic Kawasaki Disease Risk Associated with Blood Mercury and Cadmium in U.S. Children

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          Abstract

          Kawasaki disease (KD) primarily affects children <5 years of age (75%–80%) and is currently the leading cause of acquired heart disease in developed nations. Even when residing in the West, East Asian children are 10 to 20 times more likely to develop KD. We hypothesized cultural variations influencing pediatric mercury (Hg) exposure from seafood consumption may mediate ethnic KD risk among children in the United States. Hospitalization rates of KD in US children aged 0–4 years ( n = 10,880) and blood Hg levels in US children aged 1–5 years ( n = 713) were determined using separate US federal datasets. Our cohort primarily presented with blood Hg levels <0.1 micrograms (µg) per kg bodyweight (96.5%) that are considered normal and subtoxic. Increased ethnic KD risk was significantly associated with both increasing levels and detection rates of blood Hg or cadmium (Cd) in a linear dose-responsive manner between ethnic African, Asian, Caucasian, and Hispanic children in the US ( p ≤ 0.05). Increasing low-dose exposure to Hg or Cd may induce KD or contribute to its later development in susceptible children. However, our preliminary results require further replication in other ethnic populations, in addition to more in-depth examination of metal exposure and toxicokinetics.

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          Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association

          Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for > or =5 days and < or =4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-alpha antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.
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            Epidemiology of Kawasaki Disease in Asia, Europe, and the United States

            Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. Although Dr. Tomisaku Kawasaki first reported KD over 40 years ago, the cause of the disease remains unknown. Currently, KD has been diagnosed in more than 60 countries, including those in Asia, the Middle East, Latin America, and Africa, as well as in North America and Europe. The purpose of this review is to describe the epidemiologic features of KD—particularly its incidence, seasonality, and the occurrence of coronary artery abnormalities—primarily in Japan and the United States, but also in Europe and other Asian countries.
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              Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

              Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                05 January 2016
                January 2016
                : 13
                : 1
                : 101
                Affiliations
                [1 ]Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Niaosong, Kaohsiung 83301, Taiwan; wenching.chan@ 123456gmail.com (W.-C.C.); kshsieh@ 123456hotmail.com (K.-S.H.)
                [2 ]Division of Cardiology, Department of Pediatrics, Seattle Children’s Research Institute, University of Washington, Seattle, WA 98101, USA; michael.portman@ 123456seattlechildrens.org
                [3 ]Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA; michael.aschner@ 123456einstein.yu.edu
                [4 ]Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina 88040, Brazil; marcelo.farina@ 123456ufsc.br
                [5 ]Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Niaosong, Kaohsiung 83301, Taiwan
                [6 ]Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Niaosong, Kaohsiung 83301, Taiwan
                [7 ]College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
                Author notes
                [* ]Correspondence: deniz.aydin.yeter@ 123456gmail.com (D.Y.); erickuo48@ 123456yahoo.com.tw (H.-C.K.); Tel.: +886-7-731-7123 (ext. 8795) (H.-C.K.); Fax: +886-7-733-8009 (H.-C.K.)
                Article
                ijerph-13-00101
                10.3390/ijerph13010101
                4730492
                26742052
                3a7b1998-d076-406a-bbd9-5e1132aa72fb
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 November 2015
                : 30 December 2015
                Categories
                Article

                Public health
                allergy,autoimmunity,infantile acrodynia,kawasaki disease,mercury,methylmercury,pediatrics,pollution,seafood,toxicology

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