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      Risk Factors of Coronary Artery Abnormality in Children With Kawasaki Disease: A Systematic Review and Meta-Analysis

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          Abstract

          While coronary artery abnormality (CAA) has been established as the most serious complication of Kawasaki disease (KD), there have been no detailed systematic reviews of the risk factors associated with this condition. We searched six databases and performed a systematic review and meta-analysis. Study-specific odds ratios (ORs) for each factor were pooled using a random effects model. We identified four risk factors for CAA children with KD: gender (OR, 1.75; 95% confidence interval [CI], 1.59–1.92), intravenous immunoglobulin (IVIG) resistance (OR, 3.43; 95% CI, 2.07–5.67), IVIG treatment beyond 10 days of onset of symptoms (OR, 3.65; 95% CI, 2.23–5.97), and increased C-reactive protein levels (OR, 1.02; 95% CI, 1.01–1.02). More number of the five typical symptoms of KD was identified as a protective factor against CAA (OR, 0.47; 95% CI, 0.33–0.66). Pediatric patients with IVIG resistant were more likely to develop CAA within 1 month of the onset of KD than the general population, even in patients with other risk factors for CAA. Thus, there is a potential risk of CAA misdiagnosis if echocardiography is not carried out frequently. In summary, we report four risk factors for CAA and a protective factor against CAA in children with KD. We recommend that pediatricians consider these factors much more closely. With accurate prediction and early preventive treatment in high-risk patients, we can expect a reduction in CAA rates. Further research is now required to investigate the associations between CAA and other factors including the interval between KD onset and IVIG administration, platelet count, and the duration of fever. We also need to confirm whether the frequency of echocardiography within a month of KD onset should be increased in IVIG-resistant patients.

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          Most cited references48

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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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            Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease.

            In the present study, we developed models to predict unresponsiveness to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD). We reviewed clinical records of 546 consecutive KD patients (development dataset) and 204 subsequent KD patients (validation dataset). All received IVIG for treatment of KD. IVIG nonresponders were defined by fever persisting beyond 24 hours or recrudescent fever associated with KD symptoms after an afebrile period. A 7-variable logistic model was constructed, including day of illness at initial treatment, age in months, percentage of white blood cells representing neutrophils, platelet count, and serum aspartate aminotransferase, sodium, and C-reactive protein, which generated an area under the receiver-operating-characteristics curve of 0.84 and 0.90 for the development and validation datasets, respectively. Using both datasets, the 7 variables were used to generate a simple scoring model that gave an area under the receiver-operating-characteristics curve of 0.85. For a cutoff of 0.15 or more in the logistic regression model and 4 points or more in the simple scoring model, sensitivity and specificity were 86% and 67% in the logistic model and 86% and 68% in the simple scoring model. The kappa statistic is 0.67, indicating good agreement between the logistic and simple scoring models. Our predictive models showed high sensitivity and specificity in identifying IVIG nonresponders among KD patients.
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              Kawasaki syndrome.

              Kawasaki syndrome is an acute, self-limited vasculitis that occurs in children of all ages and presents a challenge for the clinician: the disorder can be difficult to recognise; there is no diagnostic laboratory test; there is an extremely effective therapy; and there is a 25% chance of serious cardiovascular damage if the treatment is not given early in the course of the disease. This review includes discussion of the history of the syndrome, the diagnostic challenges, epidemiology, aetiology, pathology, immunopathogenesis, therapy, genetic influences, and the long-term cardiovascular sequelae.
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                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                26 September 2019
                2019
                : 7
                : 374
                Affiliations
                [1] 1Department of Cardiology, Children's Hospital of Chongqing Medical University , Chongqing, China
                [2] 2Ministry of Education Key Laboratory of Child Development and Disorders , Chongqing, China
                [3] 3National Clinical Research Center for Child Health and Disorders (Chongqing) , Chongqing, China
                [4] 4Chongqing Key Laboratory of Pediatrics , Chongqing, China
                [5] 5China International Science and Technology Cooperation Base of Child Development and Critical Disorders , Chongqing, China
                Author notes

                Edited by: Xupei Huang, Florida Atlantic University, United States

                Reviewed by: Fangqi Gong, ZheJiang University, China; Deepti Suri, Post Graduate Institute of Medical Education and Research (PGIMER), India; Howard Prentice, Florida Atlantic University, United States; Wen Shen, Florida Atlantic University, United States

                *Correspondence: Mi Li lm_dhm@ 123456163.com

                This article was submitted to Pediatric Cardiology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2019.00374
                6776089
                31612117
                a7d8cf75-5f11-41e4-a72f-ef1cbd9e4bc5
                Copyright © 2019 Yan, Pan, Sun, Tian and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 January 2019
                : 30 August 2019
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 56, Pages: 13, Words: 6946
                Categories
                Pediatrics
                Systematic Review

                risk factors,coronary artery abnormality,kawasaki disease,systematic review and meta-analysis,children

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