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Chiang WN, Huang PY, Kuo HC, Huang YH, Chang LS. Evaluation of Formosa score and diagnostic sensitivity and specificity of four Asian risk scores for predicting intravenous immunoglobulin resistance in Kawasaki disease: a bivariate meta-analysis. Front Cardiovasc Med 2023; 10:1164530. [PMID: 37378410 PMCID: PMC10291052 DOI: 10.3389/fcvm.2023.1164530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Background In 2016, Lin et al. developed a prediction score of non-responsiveness to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD) (Lin et al., 2016). Various studies have attempted to validate the Formosa score, but inconsistent results have given us new opportunities and challenges. The aim of this meta-analysis is to explore the role of the Formosa score as a risk score in detecting IVIG-resistant KD patients and then compare the pooled sensitivity and specificity of four Asian risk scores, Egami, Formosa, Kobayashi, and Sano risk scores. Methods A comprehensive search of Cochrane, Embase, and PubMed was conducted through 20 December 2021, using key terms relevant to the research question "What are the sensitivities and specificities of the four Asian predicting scores, Egami, Formosa, Kobayashi, and Sano, in Kawasaki disease patients with IVIG resistance?" The reference lists of the included studies were manually reviewed to identify pertinent references. A random-effects bivariate model was used to estimate the summary of sensitivity and specificity of the tools. Results We found 41 relevant studies of the four Asian risk scores that were eligible to analyze for pooled accuracy. Eleven studies involving 5,169 KD patients reported the diagnostic performance of the Formosa score for the risk of IVIG resistance. The overall performance of the Formosa score was as follows: pooled sensitivity, 0.60 [95% confidence interval (CI), 0.48-0.70]; pooled specificity, 0.59 (95% CI, 0.50-0.68); and area under the hierarchical summary receiver operating characteristic curve, 0.62. The Formosa score exhibited the highest sensitivity 0.76 (95% CI, 0.70-0.82) for detecting IVIG-resistant KD patients among the 21,389 children included in the 41 studies. In terms of specificity estimates, Formosa had the lowest specificity of 0.46 (95% CI, 0.41-0.51). Conclusion Patients at high risk for IVIG resistance may receive adjunctive treatment to reduce coronary lesions and thus also cardiovascular morbidity. Among all of the included studies, we found Formosa score to have the best sensitivity (0.76) but unsatisfactory specificity (0.46) for predicting IVIG resistance in Kawasaki disease. In the future, network meta-analysis should also incorporate the accuracy of the new scores after they have undergone a certain degree of validation around the world. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, PROSPERO CRD42022341410.
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Affiliation(s)
- Wan-Ni Chiang
- Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Po-Yu Huang
- Department of Traditional Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ho-Chang Kuo
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ying-Hsien Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ling-Sai Chang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Sapountzi E, Fidani L, Giannopoulos A, Galli-Tsinopoulou A. Association of Genetic Polymorphisms in Kawasaki Disease with the Response to Intravenous Immunoglobulin Therapy. Pediatr Cardiol 2023; 44:1-12. [PMID: 35908117 PMCID: PMC9978270 DOI: 10.1007/s00246-022-02973-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 07/11/2022] [Indexed: 01/26/2023]
Abstract
Kawasaki disease (KD) is an acute febrile and systemic vasculitis disease mainly affecting children < 5 years old. Although the first case of KD was reported in 1967 and despite extensive research on KD since then, the cause of the disease remains largely unknown. The most common complications of KD are coronary artery lesions (CAL), which significantly increase the risk of coronary heart disease. The standard treatment for KD is high-dose intravenous immunoglobulin (IVIG) plus aspirin within 10 days from symptoms' appearance, which has been shown to decrease the incidence of CAL to 5-7%. Despite the benefits of IVIG, about 25% of the patients treated with IVIG develop resistance or are unresponsive to the therapy, which represents an important risk factor for CAL development. The cause of IVIG unresponsiveness has not been fully elucidated. However, the role of gene polymorphisms in IVIG response has been suggested. Herein, we comprehensively review genetic polymorphisms in KD that have been associated with IVIG resistance/unresponsiveness and further discuss available models to predict IVIG unresponsiveness.Kindly check and confirm inserted city in affiliation [1] is correctly identified.confirm.
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Affiliation(s)
- E Sapountzi
- Second Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloníki, Greece.
| | - L Fidani
- Second Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloníki, Greece
| | - A Giannopoulos
- Second Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloníki, Greece
| | - A Galli-Tsinopoulou
- Second Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloníki, Greece
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Roh DE, Lim YT, Kwon JE, Kim YH. Kawasaki disease following SARS-CoV-2 infection: Stronger inflammation with no increase in cardiac complications. Front Pediatr 2022; 10:1036306. [PMID: 36467487 PMCID: PMC9714663 DOI: 10.3389/fped.2022.1036306] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 10/24/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Herein we investigate the difference between Kawasaki disease (KD) with and without a recent history of SARS-CoV-2 infection. METHODS We compared the clinical characteristics of patients with KD during the SARS-CoV-2 pandemic in a single children's hospital in Korea. Fifty-two patients were enrolled and divided into group 1 (with a history of COVID-19, n = 26) and group 2 (without a history of COVID-19, n = 26) according to whether or not they contracted COVID-19 within the 8 weeks before hospitalization. Data, including clinical features and laboratory results, were analyzed and compared between groups. RESULTS The median age of patients was significantly higher in group 1 than in group 2 (53 months [IQR, 24-81] vs. 15 months [IQR, 6-33], p = 0.001). The incidence of cervical lymphadenopathy was significantly higher (p = 0.017), while that of BCGitis was significantly lower in group 1 (p = 0.023), and patients had a significantly longer hospital stay (5 days [IQR, 3-8] vs. 3 days [IQR, 3-4], p = 0.008). In group 1, platelet count was significantly lower (p = 0.006), and hemoglobin and ferritin levels were significantly higher (p = 0.013 and p = 0.001, respectively) on the first admission day. Following treatment with intravenous immunoglobulin (IVIG), the platelet count was significantly lower (p = 0.015), and the percentage of neutrophils and neutrophil-to-lymphocyte ratio were significantly higher in group 1 (p = 0.037 and p = 0.012). Although there was no statistical difference, patients requiring infliximab treatment due to prolonged fever was only in group 1. The incidence of cardiovascular complications did not differ between the groups. CONCLUSIONS Post-COVID KD showed a stronger inflammatory response than KD-alone, with no differences in cardiac complications.
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Affiliation(s)
- Da Eun Roh
- Department of Pediatrics, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - Young Tae Lim
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Jung Eun Kwon
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea.,Division of Pediatric Cardiology, Kyungpook National University Children's Hospital, Daegu, South Korea
| | - Yeo Hyang Kim
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea.,Division of Pediatric Cardiology, Kyungpook National University Children's Hospital, Daegu, South Korea
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Verification of "Japanese Scoring Systems" to Predict IVIG Resistance and Identification of Predictors for IVIG Resistance in Thai Children with Kawasaki Disease. Pediatr Cardiol 2021; 42:1799-1804. [PMID: 34173835 DOI: 10.1007/s00246-021-02668-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/20/2021] [Indexed: 10/21/2022]
Abstract
The objective of this study was to assess the validity of using the Kobayashi, Sano and Egami scoring systems to predict the intravenous immunoglobulin (IVIG) resistance of Kawasaki disease (KD) and to identify the predictors of IVIG resistance in our Thai population. A retrospective study involving 130 KD patients who were admitted between January 2005 and April 2018 was performed. We found that 17 (13%) KD patients did not respond to the first IVIG dose. The three scoring systems have good specificity (80.8%, 74% and 92.1%, respectively) but low sensitivity (0%, 33.3% and 22.2%, respectively). Multivariate analysis suggested that a body temperature greater than 40.2 °C (odds ratio of 3.80, P value = 0.03), a neutrophil percentage greater than 74% (odds ratio of 3.82, P value = 0.03) and serum albumin less than 3 g/L (odds ratio of 5.09, P value = 0.01) were predictors of IVIG resistance. Our study cannot conclude that the three Japanese scoring systems are not suitable for predicting IVIG resistance in the Thai population due to study limitations. However, a high-grade fever (≥ 40.2 °C), neutrophil predominance ≥ 74% and hypoalbuminemia (serum albumin level < 3 g/L) were predictors of IVIG resistance in Thai KD patients.
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Huang CN, Wu FF, Chang YM, Huang HC, Lin MT, Wang JK, Wu MH. Comparison of risk scores for predicting intravenous immunoglobulin resistance in Taiwanese patients with Kawasaki disease. J Formos Med Assoc 2020; 120:1884-1889. [PMID: 33358267 DOI: 10.1016/j.jfma.2020.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 11/30/2020] [Accepted: 12/03/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND/PURPOSE Kawasaki disease (KD) is the most common type of acquired heart disease in children, and intravenous immunoglobulin (IVIG) therapy is the preferred treatment. Several risk scoring systems have been developed to predict IVIG resistance, which is important in KD management, including the Kobayashi, Egami, and Formosa scores. We evaluated the performance of these scoring systems with a KD patient cohort from Taiwan. METHODS We retrospectively analyzed the medical records of all KD patients admitted to our institution from 2012 to 2017. We compared the characteristics of IVIG-resistant and non-resistant patients and evaluated the predictive ability of the scoring systems for IVIG resistance. RESULTS We included 84 patients, with 73 receiving IVIG therapy. Eight patients were unresponsive to the first IVIG course. Compared to those with good response to therapy or spontaneous improvement, IVIG-resistant patients had a higher C-reactive protein level (16.1 mg/dL vs. 8.6 mg/dL, p < 0.001), higher percentage of segmented leukocytes (75.7% vs. 61.7%, p = 0.008), and lower albumin level (2.98 mg/dL vs. 3.78 mg/dL, p = 0.001). In determining IVIG resistance, the sensitivity and specificity varied among scoring systems (Kobayashi, 37.5% and 86.8%; Egami, 37.5% and 84.2%; and Formosa, 87.5% and 73.7%, respectively). The positive and negative predictive values of the Formosa score were 25.9% and 98.2%, respectively. CONCLUSION The Formosa score had the highest sensitivity in determining IVIG resistance. Although the positive predictive value was low, the negative predictive value could reach 98.2%. The Formosa score was superior to other scoring systems in predicting IVIG resistance in Taiwanese KD patients.
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Affiliation(s)
- Chi-Nan Huang
- Department of Pediatrics, Heping-Fuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Fen-Fen Wu
- Department of Pediatrics, Heping-Fuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Ya-Mei Chang
- Department of Pediatrics, Heping-Fuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Hsin-Chung Huang
- Department of Pediatrics, Heping-Fuyou Branch, Taipei City Hospital, Taipei, Taiwan
| | - Ming-Tai Lin
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
| | - Jou-Kou Wang
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
| | - Mei-Hwan Wu
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
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Qiu H, Jia C, Wang Z, He Y, Rong X, Wu R, Chu M, Shi H. Prognosis and Risk Factors of Coronary Artery Lesions before Immunoglobulin Therapy in Children with Kawasaki Disease. Balkan Med J 2020; 37:324-329. [PMID: 32720495 PMCID: PMC7590540 DOI: 10.4274/balkanmedj.galenos.2020.2020.1.56] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Many children with Kawasaki disease develop coronary artery lesions before intravenous immunoglobulin treatment. However, little data are available on the prognosis of children with Kawasaki disease who developed coronary artery lesions before intravenous immunoglobulin treatment. Aims: To explore the outcomes of coronary artery lesions before intravenous immunoglobulin treatment in children with Kawasaki disease and analyze the factors that influence the duration of coronary artery lesions. Study Design: Retrospective cohort study. Methods: All patients with Kawasaki disease who developed coronary artery lesions before intravenous immunoglobulin treatment in our hospital from January 2009 to December 2014 were reviewed. A Cox proportional hazards model was used to determine the factors influencing the prognosis of coronary artery lesions. Results: Among 182 patients included, 28.6% were male, 83.50% were younger than 36 months, and 181 exhibited resolution of coronary artery lesions 2 years after disease onset. The median duration of coronary artery lesions was 31 days, and the proportion of coronary artery lesions was 52% at 1 month, 35% at 2 months, 33% at 3 months, 25% at 6 months, 14% at 1 year, and 0.5% at 2 years. The univariate analysis showed that overweight status, higher platelet count, lower albumin level, and starting treatment more than 10 days after disease onset were factors that possibly affect the duration of coronary artery lesions in children. The multivariate Cox regression analysis showed that female sex (adjusted hazard ratio, 1.661; 95% confidence interval, 1.117-2.470) was an independent protective factor, and overweight status (adjusted hazard ratio, 0.469; 95% confidence interval, 0.298-0.737), higher platelet count (adjusted hazard ratio, 0.649; 95% confidence interval, 0.443-0.950), and starting treatment more than 10 days after disease onset (adjusted hazard ratio, 0.392; 95% confidence interval, 0.215-0.716) were independent risk factors for a longer duration of coronary artery lesions. Conclusion: The average duration of coronary artery lesions before intravenous immunoglobulin therapy in children with Kawasaki disease is approximately 1 month. Male gender, overweight status, higher platelet count, and initiation of treatment more than 10 days after the onset of the disease are independent risk factors for longer-lasting coronary artery lesions.
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Affiliation(s)
- Huixian Qiu
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China,These authors contributed equally to this work
| | - Chang Jia
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China,These authors contributed equally to this work
| | - Zhenquan Wang
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China
| | - Yuee He
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China
| | - Xing Rong
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China
| | - Rongzhou Wu
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China
| | - Maoping Chu
- Children’s Heart Center, The Second Affiliated Hospital & Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China
| | - Hongying Shi
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Zhejiang, China
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Piram M, Darce Bello M, Tellier S, Di Filippo S, Boralevi F, Madhi F, Meinzer U, Cimaz R, Piedvache C, Koné-Paut I. Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease. Sci Rep 2020; 10:3125. [PMID: 32080307 PMCID: PMC7033244 DOI: 10.1038/s41598-020-59972-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 01/27/2020] [Indexed: 11/22/2022] Open
Abstract
About 10–20% of patients with Kawasaki disease (KD) are unresponsive to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations. We investigated the accuracy of 3 Japanese scoring systems and studied factors associated with IVIg unresponsiveness in a large multiethnic French population of children with KD to build a new scoring system. Children admitted for KD between 2011–2014 in 65 centers were enrolled. Factors associated with second line-treatment; i.e. unresponsiveness to initial IVIg treatment, were analyzed by multivariate regression analysis. The performance of our score and the Kobayashi, Egami and Sano scores were compared in our population and in ethnic subgroups. Overall, 465 children were reported by 84 physicians; 425 were classified with KD (55% European Caucasian, 12% North African/Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 14–61%). On multivariate regression analysis, predictors of secondary treatment after initial IVIG were hepatomegaly, ALT level ≥30 IU/L, lymphocyte count <2400/mm3 and time to treatment <5 days. The best sensitivity (77%) and specificity (60%) of this model was with 1 point per variable and cut-off ≥2 points. The sensitivity remained good in our 3 main ethnic subgroups (74–88%). We identified predictors of IVIg resistance and built a new score with good sensitivity and acceptable specificity in a non-Asian population.
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Affiliation(s)
- Maryam Piram
- Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, Inserm, 1018, Le Kremlin Bicêtre, France. .,AP-HP, CHU de Bicêtre, Pediatric Rheumatology, CEREMAIA, Le Kremlin Bicêtre, France.
| | - Martha Darce Bello
- AP-HP, CHU de Bicêtre, Pediatric Rheumatology, CEREMAIA, Le Kremlin Bicêtre, France
| | - Stéphanie Tellier
- CHU de de Toulouse, Paediatric Rheumatology, Nephrology and Internal medicine, Toulouse, France
| | | | | | | | - Ulrich Meinzer
- APHP, CHU Robert Debré, Paediatrics,Paediatric Internal Medicine,Rheumatology and Infectious Diseases, RAISE, Paris, France
| | - Rolando Cimaz
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Celine Piedvache
- APHP, CHU de Bicêtre, Clinical Research Unit, Le Kremlin Bicêtre, France
| | - Isabelle Koné-Paut
- Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, Inserm, 1018, Le Kremlin Bicêtre, France.,AP-HP, CHU de Bicêtre, Pediatric Rheumatology, CEREMAIA, Le Kremlin Bicêtre, France
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Money NM, Darby JB. Balancing Value and Risk in Early Discharge of Patients With Kawasaki Disease. Hosp Pediatr 2019; 9:824-826. [PMID: 31548263 DOI: 10.1542/hpeds.2019-0204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Affiliation(s)
- Nathan M Money
- Section of Pediatric Hospital Medicine, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas; and
| | - John B Darby
- Section of Pediatric Hospital Medicine, Department of Pediatrics, Brenner Children's Hospital and School of Medicine, Wake Forest University, Winston-Salem, North Carolina
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Hester GZ, Watson D, Nickel AJ, Ryan N, Jepson B, Gray J, Bergmann KR. Identifying Patients With Kawasaki Disease Safe for Early Discharge: Development of a Risk Prediction Model at a US Children's Hospital. Hosp Pediatr 2019; 9:749-756. [PMID: 31501220 DOI: 10.1542/hpeds.2019-0049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To develop a model to predict risk of intravenous immunoglobulin (IVIg) nonresponse in patients with Kawasaki disease (KD) to assist in early discharge decision-making. METHODS Retrospective cohort study of 430 patients 0 to 18 years old discharged from a US children's hospital January 1, 2010, through July 31, 2017 with a diagnosis of KD. IVIg nonresponse was defined as at least 1 of the following: temperature ≥38.0°C between 36 hours and 7 days after initial IVIg dose, receipt of a second IVIg dose after a temperature ≥38.0°C at least 20 hours after initial IVIg dose, or readmission within 7 days with administration of a second IVIg dose. Backward stepwise logistic regression was used to select a predictive model. RESULTS IVIg nonresponse occurred in 19% (81 of 430) of patients. We identified a multivariate model (which included white blood cell count, hemoglobin level, platelet count, aspartate aminotransferase level, sodium level, albumin level, temperature within 6 hours of first IVIg dose, and incomplete KD) with good predictive ability (optimism-adjusted concordance index: 0.700) for IVIg nonresponse. Stratifying into 2 groups by a predictive probability cutoff of 0.10, we identified 26% of patients at low risk for IVIg nonresponse, with a sensitivity and specificity of 90% and 30%, respectively, and a negative predictive value of 93%. CONCLUSIONS We developed a model with good predictive value for identifying risk of IVIg nonresponse in patients with KD at a US children's hospital. Patients at lower risk may be considered for early discharge by using shared decision-making. Our model may be used to inform implementation of electronic health record tools and future risk prediction research.
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Affiliation(s)
| | - David Watson
- Children's Research Institute, Children's Minnesota, Minneapolis, Minnesota
| | - Amanda J Nickel
- Children's Research Institute, Children's Minnesota, Minneapolis, Minnesota
| | | | - Bryan Jepson
- Pediatric Residency Program, University of Minnesota, Minneapolis, Minnesota; and
| | - James Gray
- Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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Grignani R, Rajgor DD, Leow YG, Heng CK, Quek SC. A novel model for predicting non-responsiveness to intravenous immunoglobulins in Kawasaki disease: The Singapore experience. J Paediatr Child Health 2019; 55:962-967. [PMID: 30520192 DOI: 10.1111/jpc.14329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 11/01/2018] [Accepted: 11/09/2018] [Indexed: 11/28/2022]
Abstract
AIM We aimed to assess the utility of four published risk-scoring methods in predicting intravenous immunoglobulins (IVIG) non-responsiveness in Kawasaki disease (KD) patients from Singapore and develop a new predictive model. METHODS We reviewed the medical records of 215 KD children. The performance of existing scoring methods in identifying non-responsive cases based on sensitivities (SN) and specificities (SP) was evaluated in 122 Singaporean Chinese. From our dataset, a model involving six predictors was built. RESULTS The following respective SN (%) and SP (%) were obtained: Egami: 26%, 68%; Kobayashi: 21%, 62%; Sano: 13%, 86% and Fukunishi: 46%, 71%. These results indicated that the existing scoring methods performed poorly compared to those reported in their respective original publications, which ranged between 68 and 87%. The new predictive model was derived with an improved SN (80%) and SP (80%). CONCLUSIONS Currently available risk-scoring methods have less applicability in the Singaporean Chinese population. The proposed new risk-scoring predictive model derived based on data from Chinese cohort demonstrated much better SN and SP.
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Affiliation(s)
- Robert Grignani
- Division of Paediatric Cardiology, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Cardiovascular Research Institute, National University Health System, Singapore.,Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
| | - Dimple D Rajgor
- Division of Paediatric Cardiology, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yao-Guang Leow
- Division of Paediatric Cardiology, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chew-Kiat Heng
- Division of Paediatric Cardiology, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Swee-Chye Quek
- Division of Paediatric Cardiology, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Platelet-Derived Microparticles: A New Index of Monitoring Platelet Activation and Inflammation in Kawasaki Disease. Indian J Pediatr 2019; 86:250-255. [PMID: 30159809 DOI: 10.1007/s12098-018-2765-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 08/01/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To investigate the dynamic changes of platelet-derived microparticles (PDMP) in Kawasaki disease (KD) and its clinical significance and to study its relationship with intravenous immunoglobulin (IVIG) resistance, inflammatory indicators and aspirin treatment in children with KD. METHODS Twenty children with KD were enrolled as the experimental group, while 20 age- and gender-matched children with common febrile disease were included in the control group. Blood samples were drawn before and 7-10 d after IVIG infusion and thereafter at 1, 2, and 3 mo after the onset of KD to estimate the PDMP concentrations by enzyme linked immunosorbent assay (ELISA). C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and cytokines [Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and Soluble interleukin-2 (sIL-2R)] were also measured. RESULTS The level of PDMP in KD children before IVIG was significantly higher than that in controls (P < 0.0001). The PDMP level in KD children decreased significantly at 7 to 10 d after IVIG (P < 0.0001) and then decreased to the lowest level in the course of 1 to 2 mo. Some children's PDMP level rebounded in the course of 3 mo (P = 0.047). In addition, the mean level of PDMP in IVIG-resistant children was higher than that in IVIG-effective children; however, there was no significant difference between the two groups (P = 0.1945). Furthermore, PDMP was positively correlated with hs-CRP, IL-6, and sIL-2R levels, but no correlation was observed with ESR, PCT, and TNF-α levels. CONCLUSIONS PDMP can be used as an index to monitor inflammation in children at the acute stage of KD. And the duration of platelet activation in KD is individualized.
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Yan F, Pan B, Sun H, Tian J, Li M. Risk Factors of Coronary Artery Abnormality in Children With Kawasaki Disease: A Systematic Review and Meta-Analysis. Front Pediatr 2019; 7:374. [PMID: 31612117 PMCID: PMC6776089 DOI: 10.3389/fped.2019.00374] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 08/30/2019] [Indexed: 12/12/2022] Open
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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Affiliation(s)
- Fan Yan
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Bo Pan
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Huichao Sun
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Jie Tian
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.,National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, China.,China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China
| | - Mi Li
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China
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Failure to Predict High-risk Kawasaki Disease Patients in a Population-based Study Cohort in Germany. Pediatr Infect Dis J 2018; 37:850-855. [PMID: 29406464 DOI: 10.1097/inf.0000000000001923] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Diverse scores on high-risk Kawasaki disease (KD) patients have proven a good prognostic validity in the Japanese population. However, data on non-Japanese have been inconclusive. Do the Kobayashi, Egami and Sano scores or application of up-to-date statistical methods (Random Forest) predict response to standard intravenous immunoglobulin (IVIG) therapy and the risk of persistent coronary artery aneurysm (CAA) in patients with KD in a mainly Caucasian population in Germany? METHODS Data on 442 children (German population-based survey, 2013 and 2014) were used to assess the prognostic validity of the Kobayashi, Egami and Sano scores for being refractory to IVIG treatment and for predicting the risk of persistent CAA. Additionally, an up-to-date statistical approach (Random Forest) was applied to identify a potentially more valid score. RESULTS A total of 301 children were eligible for assessment of their response to IVIG treatment. Among those, 177 children were followed-up for 1 year to identify persistent CAA. Although all scores were significantly associated with being refractory to IVIG (relative risk range between 2.32 and 3.73), the prognostic properties were low (likelihood ratio positive: 1.83-4.57; sensitivity in the range of 0.28-0.53). None of the scores was a significant predictor of CAA 1 year after acute illness. Application of statistical analysis such as Random Forest did not yield a more valid score. CONCLUSIONS None of the available scores appears to be appropriate for identifying high-risk Caucasian children with KD who might need intensified therapy.
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Marchesi A, Tarissi de Jacobis I, Rigante D, Rimini A, Malorni W, Corsello G, Bossi G, Buonuomo S, Cardinale F, Cortis E, De Benedetti F, De Zorzi A, Duse M, Del Principe D, Dellepiane RM, D’Isanto L, El Hachem M, Esposito S, Falcini F, Giordano U, Maggio MC, Mannarino S, Marseglia G, Martino S, Marucci G, Massaro R, Pescosolido C, Pietraforte D, Pietrogrande MC, Salice P, Secinaro A, Straface E, Villani A. Kawasaki disease: guidelines of Italian Society of Pediatrics, part II - treatment of resistant forms and cardiovascular complications, follow-up, lifestyle and prevention of cardiovascular risks. Ital J Pediatr 2018; 44:103. [PMID: 30157893 PMCID: PMC6116479 DOI: 10.1186/s13052-018-0529-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 07/29/2018] [Indexed: 02/08/2023] Open
Abstract
This second part of practical Guidelines related to Kawasaki disease (KD) has the goal of contributing to prompt diagnosis and most appropriate treatment of KD resistant forms and cardiovascular complications, including non-pharmacologic treatments, follow-up, lifestyle and prevention of cardiovascular risks in the long-term through a set of 17 recommendations.Guidelines, however, should not be considered a norm that limits the treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient's condition, and disease severity or individual complications.
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Affiliation(s)
| | | | - Donato Rigante
- Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy
| | | | | | | | | | - Sabrina Buonuomo
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | | | | | | | - Andrea De Zorzi
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | - Marzia Duse
- Università degli Studi Sapienza, Rome, Italy
| | | | | | | | - Maya El Hachem
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | | | | | - Ugo Giordano
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | | | | | | | | | - Giulia Marucci
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | | | | | | | | | | | - Aurelio Secinaro
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
| | | | - Alberto Villani
- Bambino Gesù Children’s Hospital, Piazza S. Onofrio n. 4, 00165 Rome, Italy
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Kawai R, Nomura O, Tomobe Y, Morikawa Y, Miyata K, Sakakibara H, Miura M. Retrospective observational study indicates that the paediatric assessment triangle may suggest the severity of Kawasaki disease. Acta Paediatr 2018; 107:1049-1054. [PMID: 29385646 DOI: 10.1111/apa.14249] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/23/2017] [Accepted: 01/25/2018] [Indexed: 02/06/2023]
Abstract
AIM We examined whether the paediatric assessment triangle (PAT) could predict the severity of Kawasaki disease. METHODS We enroled patients diagnosed with Kawasaki disease between July 2012 and June 2016 at the emergency department of Tokyo Metropolitan Children's Medical Center in Tokyo, Japan. Triage nurses assigned participants to unstable or stable PAT groups. We compared the incidence of coronary artery aneurysms (CAA), the Kobayashi score, which measures resistance to intravenous immunoglobulin treatment, and the incidence of initial treatment resistance. RESULTS Of the 420 participants, who were aged 0-145 months with a mean age of 31.2 ± 23.9 months, 66 (16%) were assigned to the unstable PAT group. The incidence of CAA was similar between the two groups. The percentage of unstable PAT group participants with a Kobayashi score of at least five points (39 versus 18%, p < 0.001) and initial treatment resistance (25 versus 15%, p = 0.047) were significantly higher than in the stable PAT group. Unstable PAT was an independent risk factor for initial treatment resistance (odds ratio 2.02, 95% confidence interval 1.05-3.90, p = 0.035). CONCLUSION An unstable PAT was able to predict the severity of Kawasaki disease when measured by a higher rate of initial treatment resistance.
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Affiliation(s)
- Reiko Kawai
- Department of General Pediatrics; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Osamu Nomura
- Department of Pediatric Emergency Medicine; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Yutaro Tomobe
- Department of Neonatology; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Yoshihiko Morikawa
- Clinical Research Support Center; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Koichi Miyata
- Department of Cardiology; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Hiroshi Sakakibara
- Department of General Pediatrics; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
| | - Masaru Miura
- Clinical Research Support Center; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
- Department of Cardiology; Tokyo Metropolitan Children's Medical Center; Tokyo Japan
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Abstract
Kawasaki disease is an acute systemic vasculitis that was first reported in 1961. Over the last 5 decades multiple papers have been published to further understand this disease. The diagnosis of Kawasaki disease is made based on the clinical findings. Atypical Kawasaki disease includes patients who do not meet all the criteria for diagnosis. The main complication of Kawasaki disease is coronary aneurysm, and the treatment is intravenous immunoglobulin and aspirin. A second dose of immunoglobulin is given if the patient does not improve, and several other treatment options have been proposed over the last few years as second and third line options.
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Takatsuki S, Ogata S, Ishii M, Yokozawa M, Ono M, Fujiwara M, Ida H, Motomura H, Moriuchi H, Taketazu M, Kawamura Y, Kawano T, Izumi T, Shiono J, Tsuchiya S, Tsuchiya K, Goushi T, Ichida F, Saji T. Low risk of treatment resistance in Down syndrome with Kawasaki disease. Pediatr Int 2017; 59:1236-1239. [PMID: 28960680 DOI: 10.1111/ped.13429] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 07/24/2017] [Accepted: 09/22/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND A Japanese nationwide survey has reported that Down syndrome (DS) is a less-frequently occurring comorbidity in Kawasaki disease (KD). Although altered immune responses are frequently observed in DS, no studies have focused on the treatment response and risk for coronary artery abnormalities (CAA) in DS patients with KD. The aim of this study was therefore to evaluate the clinical manifestations, treatment response and prevalence of CAA in DS with KD. METHODS We retrospectively reviewed the medical records of DS patients with KD from 2005 through 2012. The survey questionnaires were sent to facilities nationwide, and clinical data regarding KD in DS were collected. A control group consisted of non-DS patients with KD who were managed at Toho University. RESULTS Of the 94 233 children diagnosed with acute KD from 2005 to 2012, 16 children with acute KD also had DS (0.017%). The DS-KD patients were significantly older than the non-DS patients (median, 8 years vs 1 year, P < 0.05, respectively). Half of the DS patients had incomplete KD. Although 50% of the DS children were at high risk of immunoglobulin resistance, all children responded to initial treatment and none had CAA. CONCLUSIONS All DS-KD patients responded to initial i.v. immunoglobulin (IVIG) or aspirin despite having a high risk of IVIG resistance, and none of the DS patients had CAA. This suggests that the risk of treatment resistance and development of CAA may be not higher in DS patients with acute KD.
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Affiliation(s)
- Shinichi Takatsuki
- Department of Pediatrics, Toho University Omori Medical Center, ota, Tokyo, Japan
| | - Shohei Ogata
- Department of Pediatrics, Tokyo Teishin University Hospital, Chiyoda, Tokyo, Japan
| | - Masahiro Ishii
- Department of Pediatrics, Tokyo Teishin University Hospital, Chiyoda, Tokyo, Japan
| | - Masato Yokozawa
- Department of Pediatrics, Jikei University Hospital, Minato, Tokyo, Japan
| | - Masae Ono
- Department of Pediatrics, Japan Red Cross Medical Center, Shibuya, Tokyo, Japan
| | - Masako Fujiwara
- Department of Pediatrics, Kitasato University Hospital, Sagamihara, Kanagawa, Japan
| | - Hiroyuki Ida
- Department of Pediatrics, Kitasato University Hospital, Sagamihara, Kanagawa, Japan
| | - Hideki Motomura
- Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan
| | - Hiroyuki Moriuchi
- Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan
| | - Mio Taketazu
- Department of Pediatrics, Asahikawa-Koisei General Hospital, Asahikawa, Hokkaido, Japan
| | - Yoichi Kawamura
- Department of Pediatrics, Nagasaki Medical Center, Omura, Nagasaki, Japan
| | - Tatsuya Kawano
- Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan
| | - Tatsuro Izumi
- Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan
| | - Junko Shiono
- Department of Pediatrics, Soka Municipal Hospital, Soka, Saitama, Japan
| | - Shiro Tsuchiya
- Department of Pediatrics, Oita University Hospital, Yuhu, Japan
| | - Keiji Tsuchiya
- Department of Pediatrics, Nakatsu Municipal Hospital, Nakatsu, Oita
| | - Terufumi Goushi
- Department of Pediatric Cardiology, Ibaraki Children's Hospital, Mito, Ibaraki, Japan
| | - Fukiko Ichida
- Department of Pediatrics, Toyama University Hospital, Toyama, Toyama, Japan
| | - Tsutomu Saji
- Department of Pediatrics, Toho University Omori Medical Center, ota, Tokyo, Japan
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Giant coronary aneurysms in infants with Kawasaki disease. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2017. [DOI: 10.1016/j.anpede.2016.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation 2017; 135:e927-e999. [PMID: 28356445 DOI: 10.1161/cir.0000000000000484] [Citation(s) in RCA: 2393] [Impact Index Per Article: 299.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
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Sánchez Andrés A, Salvador Mercader I, Seller Moya J, Carrasco Moreno JI. [Giant coronary aneurysms in infants with Kawasaki disease]. An Pediatr (Barc) 2016; 87:65-72. [PMID: 27649630 DOI: 10.1016/j.anpedi.2016.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 07/12/2016] [Accepted: 07/15/2016] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Kawasaki disease (KD) is an acute vasculitis of unknown origin and predominant in males. The long-term effects of the disease depend on whether there are coronary lesions, particularly aneurysms. The prognosis of patients with giant aneurysms is very poor due to their natural progression to coronary thrombosis or severe obstructive lesions. OBJECTIVES A series of 8 cases is presented where the epidemiology and diagnostic methods are described. The treatment of the acute and long-term cardiovascular sequelae is also reviewed. METHODS A descriptive analysis was conducted on patients admitted to the Paediatric Cardiology Unit of La Fe University Hospital (Valencia) with KD and a coronary lesion. RESULTS More than one artery was involved in all patients. Although early diagnosis was established in only two cases, none of the patients had severe impairment of ventricular function during the acute phase. Treatment included intravenous gammaglobulin and acetylsalicylic acid at anti-inflammatory doses during the acute phase. A combination of dual antiplatelet therapy and corticosteroids was given in cases of coronary thrombosis. The silent aneurysms continue to persist. CONCLUSIONS KD is the most common cause of acquired heart disease in children. The delay in diagnosis is associated with a greater likelihood of coronary lesions that could increase the risk of cardiovascular events in adulthood. Thus, this subgroup requires close clinical monitoring for a better control of cardiovascular risk factors over time.
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Affiliation(s)
- Antonio Sánchez Andrés
- Servicio de Cardiología Pediátrica, Hospital Universitario y Politécnico La Fe, Valencia, España.
| | | | - Julia Seller Moya
- Servicio de Cardiología Pediátrica, Hospital Universitario y Politécnico La Fe, Valencia, España
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He L, Sheng Y, Huang C, Huang G. Identification of Differentially Expressed Genes in Kawasaki Disease Patients as Potential Biomarkers for IVIG Sensitivity by Bioinformatics Analysis. Pediatr Cardiol 2016; 37:1003-12. [PMID: 27160104 DOI: 10.1007/s00246-016-1381-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 03/21/2016] [Indexed: 12/19/2022]
Abstract
Kawasaki disease (KD) is a leading cause of acquired heart disease predominantly affecting infants and young children. Intravenous immunoglobulin (IVIG) is applied as the most favorable treatment against KD, but IVIG resistant remains exist. Although several clinical scoring systems have been developed to identify children at highest risk of IVIG resistance, there is a need to identify sufficiently sensitive biomarkers for IVIG treatment. Some differentially expressed genes (DEGs) could be the promising potential biomarkers for IVIG-related sensitivity diagnosis. We employed a systematic and integrative bioinformatics framework to identify such kind of genes. The performance of the candidate genes was evaluated by hierarchical clustering, ROC analysis and literature mining. By analyzing three datasets of KD patients, 34 DEGs of the three groups have been found to be associated with IVIG-related sensitivity. A module of 12 genes could predict resistant group patients with high accuracy, and a module of ten genes could predict responsive group patients effectively with accuracy of 96 %. And three of them are most likely to serve as drug targets or diagnostic biomarkers in the future. Compared with unsupervised hierarchical clustering analysis, our modules could distinct IVIG-resistant patients efficiently. Two groups of DEGs could predict IVIG-related sensitivity with high accuracy, which are potential biomarkers for the clinical diagnosis and prediction of IVIG treatment response in KD patients, improving the prognosis of patients.
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Affiliation(s)
- Lan He
- Pediatric Heart Center, Children's Hospital, Fudan University, Shanghai, China
| | - Youyu Sheng
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Chunyun Huang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Guoying Huang
- Pediatric Heart Center, Children's Hospital, Fudan University, Shanghai, China.
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The Validity of a Scoring System in Predicting Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2015. [DOI: 10.5812/pedinfect.27527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Yu JJ. Use of corticosteroids during acute phase of Kawasaki disease. World J Clin Pediatr 2015; 4:135-142. [PMID: 26566486 PMCID: PMC4637804 DOI: 10.5409/wjcp.v4.i4.135] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 08/28/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.
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Ramos-Casals M, Brito-Zerón P, Kostov B, Sisó-Almirall A, Bosch X, Buss D, Trilla A, Stone JH, Khamashta MA, Shoenfeld Y. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases. Autoimmun Rev 2015; 14:670-9. [PMID: 25842074 DOI: 10.1016/j.autrev.2015.03.008] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 03/30/2015] [Indexed: 01/08/2023]
Abstract
Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge.
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Affiliation(s)
- Manuel Ramos-Casals
- Josep Font Laboratory of Autoimmune Diseases, CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
| | - Pilar Brito-Zerón
- Josep Font Laboratory of Autoimmune Diseases, CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain
| | - Belchin Kostov
- Primary Care Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Primary Care Centre Les Corts, CAPSE, Barcelona, Spain
| | - Antoni Sisó-Almirall
- Primary Care Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Primary Care Centre Les Corts, CAPSE, Barcelona, Spain
| | - Xavier Bosch
- Department of Internal Medicine, ICMiD, Hospital Clínic, Barcelona, Spain
| | - David Buss
- Josep Font Laboratory of Autoimmune Diseases, CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain
| | - Antoni Trilla
- Preventive Medicine and Epidemiology Unit, Hospital Clínic-Universitat de Barcelona, Barcelona Centre for International Health Research, Barcelona, Catalonia, Spain
| | - John H Stone
- Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Munther A Khamashta
- Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, King's College University, London, UK
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Epidemiology of immunoglobulin resistant Kawasaki disease: results from a large, national database. Pediatr Cardiol 2015; 36:374-8. [PMID: 25179461 DOI: 10.1007/s00246-014-1016-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 08/22/2014] [Indexed: 12/12/2022]
Abstract
Few data exist evaluating the epidemiology of Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) in the United States on a national level, and characterization of the epidemiology of IVIG resistance may improve patient care. We aim to characterize the incidence of KD resistant to IVIG therapy and risk factors for resistance in children's hospitals in the United States. A large, administrative database was used to identify pediatric patients admitted with an ICD-9 code for mucocutaneous lymph node syndrome (446.1) and a charge for at least one dose of IVIG. Patients were identified as resistant to IVIG therapy if there were ≥2 calendar days between an initial IVIG dose and a subsequent dose of IVIG, methylprednisolone, rituximab, or infliximab. Patient demographic and hospital information were collected, as well as the charges for imaging, laboratory, and medications. Resistance occurred in 16.3% (hospital range 8.0-26.8%) of the population and was not associated with time or number of patients admitted with KD. Patients admitted to hospitals in the highest quartile of resistance were more likely to be African-American (26.5 vs 20.1%, p < 0.01), less likely to have an echocardiogram performed (93.6 vs 97.1%, p < 0.01), were more likely to have a C-reactive protein drawn (93 vs 79.9%, p < 0.01), and were less likely to have an erythrocyte sedimentation rate drawn (87.9 vs 91.6%, p < 0.01). The incidence of KD resistant to IVIG is highly variable among pediatric hospitals and treatment patterns vary between hospitals with high- and low-resistance patterns. Further evaluation of diagnostic and treatment patterns at pediatric hospitals is warranted.
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Kuo HC, Hsu YW, Wu MS, Chien SC, Liu SF, Chang WC. Intravenous immunoglobulin, pharmacogenomics, and Kawasaki disease. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2014; 49:1-7. [PMID: 25556045 DOI: 10.1016/j.jmii.2014.11.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 07/14/2014] [Accepted: 11/04/2014] [Indexed: 11/20/2022]
Abstract
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and it is therefore worth examining the multifactorial interaction of genes and environmental factors. Targeted genetic association and genome-wide association studies have helped to provide a better understanding of KD from infection to the immune-related response. Findings in the past decade have contributed to a major breakthrough in the genetics of KD, with the identification of several genomic regions linked to the pathogenesis of KD, including ITPKC, CD40, BLK, and FCGR2A. This review focuses on the factors associated with the genetic polymorphisms of KD and the pharmacogenomics of the response to treatment in patients with intravenous immunoglobulin resistance.
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Affiliation(s)
- Ho-Chang Kuo
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Wen Hsu
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Mei-Shin Wu
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Shu-Chen Chien
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shih-Feng Liu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Respiratory Therapy and Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Wei-Chiao Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
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Tewelde H, Yoon J, Van Ittersum W, Worley S, Preminger T, Goldfarb J. The Harada score in the US population of children with Kawasaki disease. Hosp Pediatr 2014; 4:233-8. [PMID: 24986993 DOI: 10.1542/hpeds.2014-0008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To describe and quantify the presentations of Kawasaki disease (KD) in a children's hospital over 10 years to assess the Harada score in a US population. METHODS A retrospective chart review from 2001 to 2011 of children discharged from Cleveland Clinic with the diagnosis of KD. Demographic and clinical data were collected and Harada scores were derived to evaluate efficacy in predicting risk for coronary artery aneurysms (CAAs). RESULTS A total of 105 children met diagnostic criteria for KD, and 97 of 105 had long-term follow-up. Full criteria for KD were found in 67 of 105 (64%); 38 had incomplete presentations. CAA developed in 10 children, 5 during follow-up despite treatment with intravenous immunoglobulin (IVIG.) Children with incomplete presentations had a higher risk of developing CAA (20% vs 5%, P = .03) and a delayed diagnosis (median days from fever to diagnosis 8.0 vs 5.0 days, P < .001). Of children who developed CAA, 9 of 10 had a positive Harada score (sensitivity of 90%). All children who developed CAA after IVIG were in the high-risk group, but 1 child with an incomplete presentation who had a CAA at presentation was missed by the score. Overall, the negative predictive value was 98%. CONCLUSIONS As in Japanese studies, a positive Harada score in a US population could be used to identify a high-risk population for CAA development. All children who developed CAA after treatment with IVIG would have been assigned to a high-risk category. Though not specific enough to select initial therapy, the score might be useful in identifying high-risk children for evaluation of new therapies and more frequent follow-up.
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Affiliation(s)
| | | | | | | | | | - Johanna Goldfarb
- Pediatric Infectious Diseases, Cleveland Clinic Children's Hospital, Cleveland, Ohio
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Abstract
Childhood vasculitis is a complex and fascinating area in pediatric rheumatology that has experienced an unprecedented surge in research, leading to new knowledge over the past several years. Vasculitis is defined as the presence of inflammatory cell infiltration in blood vessel walls, usually with multisystemic involvement. The most frequent forms of vasculitis in childhood are the small-size vasculitides, of which Henoch-Schoenlein Purpura and other leucocytoclastic vasculitis are the best examples, followed by Kawasaki disease, a midsize vasculitis, and Takayasu arteritis, a large-size vasculitis, both of which are topics in this article.
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Sánchez-Manubens J, Bou R, Anton J. Diagnosis and classification of Kawasaki disease. J Autoimmun 2014; 48-49:113-7. [PMID: 24485156 DOI: 10.1016/j.jaut.2014.01.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 11/13/2013] [Indexed: 02/04/2023]
Abstract
Kawasaki disease is an acute systemic vasculitis of unknown etiology. Diagnosis is based on clinical criteria that include fever, exanthema, conjunctivitis, changes in the extremities, erythema of oral mucosa and lips and cervical lymphadenopathy. However, these criteria have low sensitivity and specificity and therefore, other clinical and laboratory features may be helpful in establishing the diagnosis, especially for cases of atypical or incomplete Kawasaki disease. Prognosis depends on the extent of cardiac involvement; coronary aneurysms develop in 20-25% of untreated patients and these may lead to myocardial infarction and sudden death. Treatment with high-dose intravenous immunoglobulin is effective in reducing the risk of coronary aneurysms in most cases and is the treatment of choice for initial Kawasaki disease.
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Affiliation(s)
| | - Rosa Bou
- Pediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Spain.
| | - Jordi Anton
- Pediatric Rheumatology Unit, Hospital Sant Joan de Déu, Universitat de Barcelona, Spain.
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Comparative effectiveness of intravenous immunoglobulin for children with Kawasaki disease: a nationwide cohort study. PLoS One 2013; 8:e63399. [PMID: 23650564 PMCID: PMC3641142 DOI: 10.1371/journal.pone.0063399] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Accepted: 04/01/2013] [Indexed: 02/07/2023] Open
Abstract
Introduction Different immunoglobulin manufacturing processes may influence its effectiveness for Kawasaki disease. However, nationwide studies with longitudinal follow-up are still lacking. The aim of this study was to evaluate the comparative effectiveness of immunoglobulin preparations from a nationwide perspective. Materials and Methods This is a nationwide retrospective cohort study with a new user design. Data came from the National Health Insurance Research Database of Taiwan. From 1997 to 2008, children under 2 years old who received immunoglobulin therapy for the first time under the main diagnosis of Kawasaki disease were enrolled. The manufacturing processes were divided into β-propiolactonation, acidification and those containing IgA. The endpoints were immunoglobulin non-responsiveness, acute aneurysm, prolonged use of anti-platelets or anti-coagulants, and recurrence. Results In total, 3830 children were enrolled. β-propiolactonation had a relative risk of 1.45 (95% CI 1.08∼1.94) of immunoglobulin non-responsiveness, however, the relative risks for acidification and containing IgA were non-significant. For acute aneurysms, acidification had a relative risk of 1.49 (95% CI 1.17∼1.90), however the relative risks for β-propiolactonation and containing IgA were non-significant. For prolonged use of anti-platelets or anti-coagulants, β-propiolactonation had a relative risk of 1.44 (95% CI 1.18∼1.76), and acidification protected against them both with a relative risk of 0.82 (95% CI 0.69∼0.97), whereas the relative risk for containing IgA was non-significant. For recurrence, all three factors were non-significant. Conclusions The effectiveness of immunoglobulin may differ among different manufacturing processes. β-propiolactonation had a higher risk of treatment failure and prolonged use of anti-platelets or anti-coagulants. Acidification may increase the risk of acute coronary aneurysms.
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Piram M, Koné-Paut I. [Kawasaki disease: what's new in 2012?]. Arch Pediatr 2012; 19:1012-4. [PMID: 22939648 DOI: 10.1016/j.arcped.2012.07.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 07/07/2012] [Indexed: 01/27/2023]
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Reindel R, Shulman ST. Corticosteroids as primary therapy in Kawasaki disease. Nat Rev Rheumatol 2012; 8:373-4. [DOI: 10.1038/nrrheum.2012.65] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Kobayashi T, Saji T, Otani T, Takeuchi K, Nakamura T, Arakawa H, Kato T, Hara T, Hamaoka K, Ogawa S, Miura M, Nomura Y, Fuse S, Ichida F, Seki M, Fukazawa R, Ogawa C, Furuno K, Tokunaga H, Takatsuki S, Hara S, Morikawa A. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet 2012; 379:1613-20. [PMID: 22405251 DOI: 10.1016/s0140-6736(11)61930-2] [Citation(s) in RCA: 446] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
BACKGROUND Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. METHODS We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. FINDINGS We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group. INTERPRETATION Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted. FUNDING Japanese Ministry of Health, Labour and Welfare.
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Affiliation(s)
- Tohru Kobayashi
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan.
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