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Wang N, Gao Y, Wang Y, Dai Y, Tang Y, Huang J, Sun L, Qian G, Ma J, Li X, Liu Y, Yang D, Huang X, Wang W, Li W, Zhuo W, Lv H, Liu Z. Plasma proteomic profiling reveals that SERPINE1 is a potential biomarker associated with coronary artery lesions in Kawasaki disease. Int Immunopharmacol 2024; 139:112698. [PMID: 39029232 DOI: 10.1016/j.intimp.2024.112698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 06/28/2024] [Accepted: 07/13/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment. METHODS Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort. RESULTS According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs). CONCLUSIONS Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.
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Affiliation(s)
- Nana Wang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Yang Gao
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China; Department of Pediatrics, The First People's Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang (Lianyungang Clinical College of Nanjing Medical University), Lianyungang, JiangSu province, China
| | - Yan Wang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China; Department of Cardiology, Children's Hospital Affiliated to Xuzhou Medical University, Xuzhou, JiangSu province, China
| | - Yuan Dai
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Yunjia Tang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Jie Huang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Ling Sun
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Guanghui Qian
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Jin Ma
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Xuan Li
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Ying Liu
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Daoping Yang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Xin Huang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Wang Wang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Wenjie Li
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Wenyu Zhuo
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China
| | - Haitao Lv
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China.
| | - Zhiheng Liu
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, JiangSu province, China.
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Wang L, He M, Wang W, Li S, Zhao G. Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis. Eur J Pediatr 2024; 183:1765-1776. [PMID: 38240765 DOI: 10.1007/s00431-024-05437-2] [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: 11/08/2023] [Revised: 12/31/2023] [Accepted: 01/13/2024] [Indexed: 04/09/2024]
Abstract
Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67-7.52) and defervescence rate (OR = 5.01, 95% CI 2.99-8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61-1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65-2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02-5.01) and a larger reduction of right coronary artery Z score (MD = -0.24, 95% CI -0.27 to -0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups. Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD. What is Known: • Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders. • The efficacy of infliximab in treating children with Kawasaki disease is controversial. What is New: • Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.
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Affiliation(s)
- Lihe Wang
- Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China.
| | - Milan He
- Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China
| | - Wei Wang
- Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China
| | - Shiya Li
- Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China
| | - Guoxiao Zhao
- Department of Pediatrics, Yuncheng Central Hospital, Shanxi Medical University, No. 3690, Hedong East Street, Yanhu District, Yuncheng City, Shanxi Province, 044000, China
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Kuo NC, Lin CH, Lin MC. Comparative effectiveness of two intravenous immunoglobulin products in children with Kawasaki disease, a nationwide cohort study. Sci Rep 2023; 13:18629. [PMID: 37903825 PMCID: PMC10616269 DOI: 10.1038/s41598-023-45092-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 10/16/2023] [Indexed: 11/01/2023] Open
Abstract
Kawasaki Disease (KD) is the most common acquired pediatric heart disease in the developed world. Rapid infusion of high-dose intravenous immunoglobulin is the standard therapy. Different manufacturing processes of IVIG may influence their efficacy. This study aims to conduct a head to head comparison of two IVIGs, TBSF and Privigen, from a nationwide perspective. The main data source was the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 3368 KD cases involving children under 2 years of age were enrolled from January 2015 to November 2020. The primary endpoint was IVIG resistance, which we defined as the total amount exceeding 26 g in one admission. The secondary endpoints encompassed two distinct criteria: coronary involvement, which was defined as the prolonged use of aspirin or anti-coagulation agents between 180 and 360 days after the index date, and recurrence, which was defined as readmission for IVIG therapy occurring more than 30 days after previous KD index day and continuing until the end of the follow-up period. Privigen demonstrated a lower IVIG resistance rate at 9.4% in comparison to TBSF, which exhibited a rate of 9.7% (odds ratio 0.72, 95% CI 0.52-0.99). Privigen had a lower odds of coronary involvement (odds ratio 0.38, 95% CI 0.18-0.82). There is no difference in recurrence rate (odds ratio 0.60, 95% CI 0.22-1.68). Privigen might have a lower rate of IVIG resistance and reduced coronary artery involvement. The discrepancy may be due to the concentration, the stabilizers, or the source of plasma. Further investigation is needed to compare the effectiveness of different IVIGs in the large randomized controlled clinical trial.
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Affiliation(s)
- Ni-Chun Kuo
- Children's Medical Center, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sec. 4, Taichung, 40705, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ming-Chih Lin
- Children's Medical Center, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sec. 4, Taichung, 40705, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- Department of Food and Nutrition, Providence University, Taichung, Taiwan.
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
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Cai JH, Tang M, Zhang HX, Dan Luo E, Zhang R, Shuai SP, Liang H, Tao WJ, Wu MJ, Wen Y, Yang YF. Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study. J Pediatr (Rio J) 2023; 99:161-167. [PMID: 35995125 PMCID: PMC10031361 DOI: 10.1016/j.jped.2022.07.003] [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: 05/26/2022] [Revised: 07/25/2022] [Accepted: 07/26/2022] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.
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Affiliation(s)
- Jiang Hui Cai
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Mi Tang
- School of Medicine, University of Electronic Science and Technology of China; Office of Good Clinical Practice, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hong Xi Zhang
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Er Dan Luo
- Office of Good Clinical Practice, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Rui Zhang
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Shu Ping Shuai
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hua Liang
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wan Jun Tao
- Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Meng Jun Wu
- Department of Anesthesiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yang Wen
- Department of Ultrasound, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yan Feng Yang
- Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Singh J, Chang A, Fusco NM, Hicar M. Predicting Intravenous Immunoglobulin Resistance Among North American Children Hospitalized With Kawasaki Disease. J Pediatr Pharmacol Ther 2022; 27:669-676. [PMID: 36186240 PMCID: PMC9514769 DOI: 10.5863/1551-6776-27.7.669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/10/2021] [Indexed: 07/20/2023]
Abstract
OBJECTIVE The Kobayashi score (KS) is the most widely used tool for predicting intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). The KS has shown good sensitivity (86%) and specificity (68%) in Japanese children; however, its use is limited outside of Japan. No models accurately predict IVIG resistance of children with KD in the United States. We sought to develop and test a novel scoring system to predict IVIG resistance in hospitalized children with KD. METHODS A retrospective chart review was conducted of all children diagnosed with KD from January 2000 to December 2015. Subjects were divided into 2 groups: IVIG susceptible or resistant. Variables that differed between the groups were identified and used to create a "new score" to predict resistance to IVIG. The new score was then compared with the KS and performance characteristics were determined. RESULTS A total of 208 subjects were reviewed. White blood cell count, neutrophil percentage, age, and serum albumin were used in the new score with equal weighting. Overall, the new score achieved improved sensitivity (54% vs 26%) and similar specificity (69% vs 74%) compared with the KS in predicting IVIG resistance in hospitalized children diagnosed with KD. CONCLUSIONS Predicting IVIG resistance in children diagnosed with KD remains challenging. The KS has low sensitivity in predicting IVIG resistance in children with KD in the United States. The new score resulted in improved sensitivity, but many children with true IVIG resistance may be missed. Further research is needed to improve IVIG resistance prediction.
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Affiliation(s)
- Jasdip Singh
- Department of Pharmacy Practice (JS, NF), University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY
| | - Arthur Chang
- Department of Pediatrics (AC, MH), University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY
| | - Nicholas M. Fusco
- Department of Pharmacy Practice (JS, NF), University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY
| | - Mark Hicar
- Department of Pediatrics (AC, MH), University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY
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Vasudeva R, Poku FA, Thommana M, Parmar G, Umscheid J, Parmar N, Koranteng CA, Singh A, Patel K, Yagnik P, Donda K, Bhatt P, Dapaah-Siakwan F. Trends and Resource Utilization in Kawasaki Disease Hospitalizations in the United States, 2008-2017. Hosp Pediatr 2022; 12:257-266. [PMID: 35106586 DOI: 10.1542/hpeds.2021-006142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To explore trends in hospitalization rate, resource use, and outcomes of Kawasaki Disease (KD) in children in the United States from 2008 to 2017. METHODS This was a retrospective, serial cross-sectional analysis of pediatric hospitalizations with International Classification of Disease diagnostic codes for KD in the National Inpatient Sample. Hospitalization rates per 100 000 populations were calculated and stratified by age group, gender, race, and US census region. Prevalence of coronary artery aneurysms (CAA) were expressed as proportions of KD hospitalizations. Resource use was defined in terms of length of stay and hospital cost. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for categorical and continuous variables, respectively. P <.05 was considered significant. RESULTS A total of 43 028 pediatric hospitalizations identified with KD, yielding an overall hospitalization rate of 5.5 per 100 000 children. The overall KD hospitalization rate remained stable over the study period (P = .18). Although KD hospitalization rates differed by age group, gender, race, and census region, a significant increase was observed among Native Americans (P = .048). Rates of CAA among KD hospitalization increased from 2.4% to 6.8% (P = .04). Length of stay remained stable at 2 to 3 days, but inflation-adjusted hospital cost increased from $6819 in 2008 to $10 061 in 2017 (Ptrend < 0.001). CONCLUSIONS Hospitalization-associated costs and rates of CAA diagnostic codes among KD hospitalizations increased, despite a stable KD hospitalization rate between 2008 and 2017. These findings warrant further investigation and confirmation with databases with granular clinical information.
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Affiliation(s)
- Rhythm Vasudeva
- Department of Pediatrics, University of Kansas School of Medicine, Wichita, Kansas
| | | | - Mary Thommana
- K. J. Somaiya Medical College & Research Centre, Mumbai, India
| | - Garima Parmar
- Department of Pediatrics, Kasturba Medical College, Mangalore, India
| | - Jacob Umscheid
- Department of Pediatrics, University of Kansas School of Medicine, Wichita, Kansas
| | - Narendrasinh Parmar
- Department of Pediatrics, Brookdale University Hospital Medical Center, Brooklyn, New York
| | | | | | - Kripa Patel
- Smt. NHL Municipal Medical College, Ahmedabad, India
| | - Priyank Yagnik
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Keyur Donda
- Department of Pediatrics, University South Florida, Tampa, Florida
| | - Parth Bhatt
- Department of Pediatrics, United Hospital Center, Bridgeport, West Virginia
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Comparison of IVIG resistance predictive models in Kawasaki disease. Pediatr Res 2022; 91:621-626. [PMID: 33753891 DOI: 10.1038/s41390-021-01459-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 01/25/2021] [Accepted: 02/22/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. METHODS Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. RESULTS A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count <300 × 109/L and GGT serum levels were independent risk factors for IVIG resistance (OR: 3.896; 95% CI: 1.054-14.404; p = 0.042 and OR: 1.008; 95% CI: 1.001-1.015; p = 0.050). CONCLUSIONS The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. IMPACT Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.
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Phamduy TT, Smith S, Herbst KW, Phamduy PT, Brimacombe M, Hogan AH, Salazar JC, Sturm J. Kawasaki Disease Hospitalizations in the United States 2016-2020: A Comparison of Before and During the Coronavirus Disease 2019 Era. Pediatr Infect Dis J 2021; 40:e407-e412. [PMID: 34382611 PMCID: PMC8505141 DOI: 10.1097/inf.0000000000003289] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/14/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Kawasaki disease (KD) is an acute vasculitis of young children. A comparison of US hospitalization rates and epidemiologic features of KD in 2020 to those of precoronavirus disease years has yet to be reported. METHODS Using a large, inpatient database, we conducted a retrospective cohort study and analyzed data for patients with (1) diagnosis coding for KD, (2) IV immunoglobulin treatment administered during hospitalization and (3) discharge date between January 1, 2016, and December 30, 2020. Severe cases were defined as those requiring adjunctive therapy or IV immunoglobulin-resistant therapy. RESULTS The annual number of KD hospitalizations were stable from 2016 to 2019 (n = 1652, 1796, 1748, 1692, respectively) but decreased in 2020 (n = 1383). KD hospitalizations demonstrated seasonal variation with an annual peak between December and April. A second peak of KD admissions was observed in May 2020. The proportion of KD cases classified as severe increased to 40% in 2020 from 33% during the years 2016-2019 (P < 0.01). Median age in years increased from 2.9 in subjects hospitalized from 2016 to 2019 to 3.2 in 2020 (P = 0.002). CONCLUSIONS Compared with the previous 4 years, the annual number of pediatric KD admissions decreased, and children discharged with diagnostic codes for KD in 2020 were generally older and more likely to have severe morbidity possibly reflective of misdiagnosed multisystem inflammatory syndrome in children. Clinicians should be wary of a possible rise in KD rates in the postcoronavirus disease 2019 era as social distancing policies are lifted and other viruses associated with KD return.
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Affiliation(s)
- Timothy T. Phamduy
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
| | - Sharon Smith
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
- Division of Emergency Medicine, Connecticut Children’s Medical Center
| | | | - Paul T. Phamduy
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
- Division of Emergency Medicine, Connecticut Children’s Medical Center
- Division of Research, Connecticut Children’s Medical Center
- Division of Pediatric Hospital Medicine, Connecticut Children’s Medical Center
- Division of Pediatric Infectious Diseases and Immunology, Connecticut Children’s Medical Center, Hartford, Connecticut
| | | | - Alexander H. Hogan
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
- Division of Pediatric Hospital Medicine, Connecticut Children’s Medical Center
| | - Juan C. Salazar
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
- Division of Pediatric Infectious Diseases and Immunology, Connecticut Children’s Medical Center, Hartford, Connecticut
| | - Jesse Sturm
- From the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut
- Division of Emergency Medicine, Connecticut Children’s Medical Center
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Porritt RA, Zemmour D, Abe M, Lee Y, Narayanan M, Carvalho TT, Gomez AC, Martinon D, Santiskulvong C, Fishbein MC, Chen S, Crother TR, Shimada K, Arditi M, Noval Rivas M. NLRP3 Inflammasome Mediates Immune-Stromal Interactions in Vasculitis. Circ Res 2021; 129:e183-e200. [PMID: 34517723 DOI: 10.1161/circresaha.121.319153] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Rebecca A Porritt
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - David Zemmour
- Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA (D.Z.)
| | - Masanori Abe
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Youngho Lee
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Meena Narayanan
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Thacyana T Carvalho
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Angela C Gomez
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Daisy Martinon
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Chintda Santiskulvong
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.,CS Cancer (C.S.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michael C Fishbein
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.C.F.)
| | | | - Timothy R Crother
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Kenichi Shimada
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Moshe Arditi
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA.,Smidt Heart Institute (M.A.), Cedars-Sinai Medical Center, Los Angeles, CA
| | - Magali Noval Rivas
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Department of Biomedical Sciences, Infectious and Immunologic Diseases Research Center (IIDRC) (R.A.P., M.A., Y.L., M.N., T.T.d.C., A.C.G., D.M., S.C., T.R.C., K.S., M.A., M.N.R.), Cedars-Sinai Medical Center, Los Angeles, CA
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Li D, Li X, Dou W, Zheng Y. The effectiveness of infliximab for Kawasaki disease in children: systematic review and meta-analysis. Transl Pediatr 2021; 10:1294-1306. [PMID: 34189087 PMCID: PMC8193009 DOI: 10.21037/tp-20-482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms (CAAs) and threatens children's health and lives. The therapeutic effects of single intravenous immunoglobulin gamma (IVIG) vs. infliximab (IFX) (with or without IVIG) in young children with KD remain unclear. Thus, we made a meta-analysis and systematic review, including all of the studies which have evaluated the effectiveness and safety of IFX and IVIG KD patients. METHODS The databases of the Cochrane Library, PubMed and Embase websites were searched for articles appearing from inception until December 31, 2020. Clinical studies that compared IFX either as initial therapy plus IVIG or rescue therapy after IVIG (IFX group) failure compared with IVIG treatment alone (IVIG group) in treating KD patients were included. RESULTS The meta-analysis included nine studies characterizing 712 patients. The treatment response was significantly higher in the adjunctive IFX therapy group than in the IVIG therapy group [odds ratio (OR) 2.64; 95% CI: 1.52-4.59; P=0.0005]. Subgroup analysis, the effect of IFX therapy on treatment response is more effectiveness in the group of the high-risk KD patients than IVIG therapy (OR 6.07; 95% CI: 2.30-16.04; P=0.0003; random-effects model). Further analysis showed no difference in the improvement of CAAs in short-term follow-up between the two groups. However, adding IFX either as initial therapy or as additional therapy all showed an advantageous effect regarding the ∆Z score of the left anterior descending (LAD) (MD =0.29; 95% CI: 0.27-0.31; P<0.00001) and right coronary artery (RCA) (MD =0.24; 95% CI: 0.22-0.26; P<0.00001). Further, IFX exhibited significant effect on the treatment response compared with IVIG therapy in the Asian group (OR, 2.84; 95% CI: 1.51-5.36; P=0.001; random-effects model), and the beneficial effects of IFX were given without increasing the risk of AEs. CONCLUSIONS This meta-analysis emphasizes the importance of IFX on the treatment response in the high-risk KD patients. IFX may play a role in the Asian KD patients and prevention of progressive CAA, and does not increase the risk of AEs in KD patients.
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Affiliation(s)
- Dan Li
- Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.,Graduate School of Peking Union Medical College, Capital Institute of Pediatrics, Beijing, China
| | - Xiaohui Li
- Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China.,Graduate School of Peking Union Medical College, Capital Institute of Pediatrics, Beijing, China
| | - Wenting Dou
- Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China
| | - Yang Zheng
- Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, Beijing, China
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11
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Lo J, Gauvreau K, Baker AL, de Ferranti SD, Friedman KG, Lo MS, Dedeoglu F, Sundel RP, Newburger JW, Son MBF. Multiple Emergency Department Visits for a Diagnosis of Kawasaki Disease: An Examination of Risk Factors and Outcomes. J Pediatr 2021; 232:127-132.e3. [PMID: 33453202 DOI: 10.1016/j.jpeds.2021.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/31/2020] [Accepted: 01/07/2021] [Indexed: 11/17/2022]
Abstract
OBJECTIVES To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis. STUDY DESIGN Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis. RESULTS Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits. CONCLUSIONS Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis.
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Affiliation(s)
- Jeffrey Lo
- Division of Immunology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Kimberlee Gauvreau
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Annette L Baker
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Sarah D de Ferranti
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Kevin G Friedman
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Mindy S Lo
- Division of Immunology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Fatma Dedeoglu
- Division of Immunology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Robert P Sundel
- Division of Immunology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Jane W Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Mary Beth F Son
- Division of Immunology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA.
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12
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Lu Z, Wang F, Lv H. Efficacy of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis. Exp Ther Med 2020; 21:15. [PMID: 33235624 PMCID: PMC7678622 DOI: 10.3892/etm.2020.9447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 02/20/2020] [Indexed: 01/11/2023] Open
Abstract
The present study aimed to review the relevant studies in order to determine the efficacy of infliximab (IFX) in the treatment of Kawasaki disease (KD). The relevant studies were retrieved using the PubMed, Cochrane and Embase databases. Key sources in the literature were reviewed; all articles published by July 2019 were considered for inclusion. For each study, odds ratios, mean difference and 95% confidence interval (95% CI) were assessed to evaluate study outcomes. A total of 16 studies involving 429 patients were relevant to the questions of interest of the current meta-analysis. Compared with intravenous immunoglobulin (IVIG), IFX or IFX plus IVIG significantly reduced the incidence of adverse events, including the number of patients with fever, changes in lip and oral cavity and/or cervical lymphadenopathy. The white blood cell (WBC), neutrophil and C-reactive protein (CRP) levels were also reduced in the IFX or IFX plus IVIG group compared with those in the IVIG or polyethylene glycol-treated human immunoglobulin (VGIH) groups. The platelet counts, alanine aminotransferase (ALT) levels and Z-scores were increased in the IFX or IFX plus IVIG groups compared with those in the IVIG or VGIH groups. In the single-arm studies, the incidence of coronary artery aneurysm was 0.150 (95% CI: 0.024, 0.277), the non-response rate was 0.097 (95% CI: 0.056, 0.138), and the incidence of adverse events was 0.156 (95% CI: 0.122, 0.190). IFX not only effectively reduced the incidence of fever, conjunctival injection, changes in lip and oral cavity and cervical lymphadenopathy polymorphous exanthema, but also the WBC, neutrophil, ALT and CRP levels. The platelet levels were increased in patients after the IFX therapy compared with patients in the IVIG or VGIH groups. IFX or IFX plus IVIG exhibited improved clinical efficacy in the treatment of KD compared with that of IVIG or VGIH. However, as a limited number of studies was included in the current study, the findings should be verified further.
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Affiliation(s)
- Zhongxing Lu
- Department of Pediatrics, Changzhou Maternal and Child Health Care Hospital, Changzhou, Jiangsu 213023, P.R. China
| | - Fen Wang
- Department of Pediatrics, Taicang First People's Hospital, Suzhou, Jiangsu 215000, P.R. China
| | - Haitao Lv
- Department of Pediatrics, Soochow Children's Hospital, Suzhou, Jiangsu 215000, P.R. China
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13
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Abstract
OBJECTIVE Kawasaki disease (KD) is the most common cause of coronary artery aneurysm (CAA) in children. The available risk scores to predict intravenous immunoglobulin (IVIG) resistance and CAA were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. This study aimed to evaluate the ability of 5 risk scoring systems to predict IVIG resistance and CAA in Turkey patients with KD. METHODS Patients with KD were retrospectively evaluated with clinical, laboratory, and echocardiographic findings. Data analyses were performed in 5 scoring systems (Harada, Kobayashi, Egami, Formosa, and Sano). RESULTS A total of 259 patients (Male: Female, 1.7) were treated for KD in our hospital. The mean age of diagnosis in patients with KD, CAA, and IVIG resistance were 3.31, 2.19, and 2.06, respectively. CAA development and IVIG resistance were seen in 11.6% and 12.3% of cases, respectively. IVIG resistance was detected in 35.6% of patients with CAA. In our study, 5 risk scoring systems were applied to our patients. ROC analysis results were found highest in Kobayashi scoring system for IVIG resistance (AUC, 0.864) and in Harada scoring system for CAA development (AUC, 0.727). CONCLUSION Harada score was significant in predicting CAA risk, and Kobayashi score was significant in predicting the risk of developing IVIG resistance. It is necessary to determine more specific and sensitive risk scores that increase the risk of IVIG resistance and the development of CAA in Turkey.
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Abstract
Kawasaki disease is an acute febrile illness and systemic vasculitis of unknown aetiology that predominantly afflicts young children, causes coronary artery aneurysms and can result in long-term cardiovascular sequelae. Kawasaki disease is the leading cause of acquired heart disease among children in the USA. Coronary artery aneurysms develop in some untreated children with Kawasaki disease, leading to ischaemic heart disease and myocardial infarction. Although intravenous immunoglobulin (IVIG) treatment reduces the risk of development of coronary artery aneurysms, some children have IVIG-resistant Kawasaki disease and are at increased risk of developing coronary artery damage. In addition, the lack of specific diagnostic tests and biomarkers for Kawasaki disease make early diagnosis and treatment challenging. The use of experimental mouse models of Kawasaki disease vasculitis has considerably improved our understanding of the pathology of the disease and helped characterize the cellular and molecular immune mechanisms contributing to cardiovascular complications, in turn leading to the development of innovative therapeutic approaches. Here, we outline the pathophysiology of Kawasaki disease and summarize and discuss the progress gained from experimental mouse models and their potential therapeutic translation to human disease. This Review outlines the pathophysiology of Kawasaki disease and discusses the progress gained from experimental mouse models and their potential therapeutic translation to human disease.
Kawasaki disease is a childhood systemic vasculitis leading to the development of coronary artery aneurysms; it is the leading cause of acquired heart disease in children in developed countries. The cause of Kawasaki disease is unknown, although it is suspected to be triggered by an unidentified infectious pathogen in genetically predisposed children. Kawasaki disease might not be a normal immune response to an unusual environmental stimulus, but rather a genetically determined unusual and uncontrolled immune response to a common stimulus. Although the aetiological agent in humans is unknown, mouse models of Kawasaki disease vasculitis demonstrate similar pathological features and have substantially accelerated discoveries in the field. Genetic and transcriptomic analysis of blood samples from patients with Kawasaki disease and experimental evidence generated using mouse models have demonstrated the critical role of IL-1β in the pathogenesis of this disease and the therapeutic potential of targeting this pathway (currently under investigation in clinical trials).
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Kim HS, Shin SW, Choi BG, Choi HJ. Differences over 10 years in epidemiologic and clinical features of Kawasaki disease at a single tertiary center. Clin Exp Pediatr 2020; 63:157-158. [PMID: 32023400 PMCID: PMC7170786 DOI: 10.3345/cep.2019.01109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 01/20/2020] [Indexed: 11/27/2022] Open
Affiliation(s)
- Hyun Su Kim
- Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Suk Won Shin
- Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Bo Geum Choi
- Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Hee Joung Choi
- Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
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16
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Abstract
PURPOSE OF THE REVIEW Kawasaki disease (KD) is a childhood systemic vasculitis of unknown etiology that causes coronary artery aneurysms (CAA), and if left undiagnosed can result in long-term cardiovascular complications and adult cardiac disease. Up to 20% of KD children fail to respond to IVIG, the mainstay of therapy, highlighting the need for novel therapeutic strategies. Here we review the latest findings in the field regarding specific etiology, genetic associations, and advancements in treatment strategies to prevent coronary aneurysms. RECENT FINDINGS Recent discoveries using the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model have accelerated the study of KD pathophysiology and have advanced treatment strategies including clinical trials for IL-1R antagonist, Anakinra. KD remains an elusive pediatric vasculitis syndrome and is the leading cause of acquired heart disease among children in the USA and developed countries. Advancements in combination treatment for refractory KD with further understanding of novel genetic risk factors serve as a solid foundation for future research endeavors in the field.
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Deep Neck Space Involvement of Kawasaki Disease in the US: A Population-Based Study. J Pediatr 2019; 215:118-122. [PMID: 31477383 DOI: 10.1016/j.jpeds.2019.07.054] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 07/05/2019] [Accepted: 07/23/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To describe the rate and risk factors of deep neck space involvement of Kawasaki disease. STUDY DESIGN We performed a retrospective analysis using the Kids' Inpatient Database from 2006, 2009, 2012, and 2016. Kawasaki disease and deep neck space involvement cases were identified using International Classification of Diseases codes among children aged <12 years. Demographic and outcome data of Kawasaki disease cases with and without deep neck space involvement were compared. RESULTS Of 20 787 patients with Kawasaki disease, 0.6% (130 cases) had deep neck space involvement. On multivariable analysis, children aged ≥4 years (OR 8.41; 95% CI 3.79-18.7 in those aged 6-11 years), Asian or Pacific Islanders (OR 3.72; 95% CI 1.90-7.27), non-Hispanic black children (OR 2.39; 95% CI 1.34-4.28), and Northeast hospital region (OR 2.32; 95% CI 1.21-4.46) were associated with deep neck space involvement. Surgical drainage was performed in 21.7% of patients with deep neck space involvement. Deep neck space involvement was associated with longer hospital stay and greater costs. CONCLUSIONS Approximately 0.6% of patients with Kawasaki disease present with deep neck space involvement in the US. Deep neck space involvement of Kawasaki disease occurs primarily in older (≥4 years old), non-white, non-Hispanic children. Deep neck space involvement is associated with operative procedures for presumed abscess, longer hospital stay, and greater costs. In caring for children with suspected deep neck space abscess, particularly when they are not responding to antibiotics, clinicians should evaluate them for the possibility of Kawasaki disease.
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18
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Xie LP, Yan WL, Huang M, Huang MR, Chen S, Huang GY, Liu F. Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017. J Epidemiol 2019; 30:429-435. [PMID: 31548437 PMCID: PMC7492704 DOI: 10.2188/jea.je20190065] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Background We sought to investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL). Methods As in our previous three surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL. Results A total of 4,452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged <5 years from 2013 to 2017. Age at onset ranged from 15 days to 14.0 years (median: 1.8 years). KD occurred more frequently in spring and summer. Of 4,325 patients (97.0%) receiving intravenous immunoglobulin (IVIG), 362 (8.4%) were resistant to initial IVIG. CAL occurred in 406 (9.1%) patients, including 118 (2.7%) with medium aneurysms and 31 (0.7%) with giant aneurysms. Recurrent cases were 60 (1.3%). No death was found in this survey. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were independently associated with CAL. Conclusions The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.
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Affiliation(s)
- Li-Ping Xie
- Heart Center, Children's Hospital of Fudan University
| | - Wei-Li Yan
- Department of Clinical Epidemiology, Children's Hospital of Fudan University
| | - Min Huang
- Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University
| | - Mei-Rong Huang
- Pediatric Heart Center, Shanghai Children's Medical Center
| | - Sun Chen
- Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine
| | | | - Fang Liu
- Heart Center, Children's Hospital of Fudan University
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Balch A, Wilkes J, Thorell E, Pavia A, Sherwin CMT, Enioutina EY. Changing trends in IVIG use in pediatric patients: A retrospective review of practices in a network of major USA pediatric hospitals. Int Immunopharmacol 2019; 76:105868. [PMID: 31487613 DOI: 10.1016/j.intimp.2019.105868] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 08/06/2019] [Accepted: 08/27/2019] [Indexed: 01/19/2023]
Abstract
The use of immunoglobulins is gradually increasing. Intravenous immunoglobulins (IVIG) are used as replacement therapy for primary and secondary immune deficiencies, and as an anti-inflammatory and immunomodulatory medication for the treatment of neurologic, dermatologic, and rheumatologic diseases. The objective of this study was to analyze trends in the IVIG use in pediatric patients hospitalized to 47 US-based children's hospitals from 2007 to 2014. IVIG was used for the treatment of >2300 primary diagnoses in 53,648 unique patients. The number of IVIG admissions increased by 30.2% during the study period, while the mean rate of IVIG admissions/100,000 admissions increased only 5.8%. Most patients receiving IVIG were children and adolescents. IVIG was frequently used off-label or for the treatment of FDA-approved indications in children under two years of age and BMT patients <20 years of age. Primary immune deficiencies represented only 1.2% of all IVIG admissions. Pediatric patients with mucocutaneous lymph node syndrome (Kawasaki disease, KD) and idiopathic thrombocytopenic purpura (ITP) were two primary consumers of the IVIG. Another top-ranked indications were acute infectious polyneuritis (Guillain-Barré syndrome, GBS) and prophylaxis of infections in patients receiving antineoplastic chemotherapy. IVIG usage is a dynamic process guided by emerging evidence and FDA approval for new indications. IVIG was mostly prescribed for treatment of diseases with pathologic immune responses to foreign of self-antigens. These indications usually, require higher amounts of IVIG per admission. More studies are needed to understand whether IVIG treatments of off-label indications are effective and cost-efficient.
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Affiliation(s)
- Alfred Balch
- Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Jacob Wilkes
- Intermountain Healthcare, Salt Lake City, UT, USA
| | - Emily Thorell
- Division of Infectious Diseases, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Andrew Pavia
- Division of Infectious Diseases, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Catherine M T Sherwin
- Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children's Hospital, Dayton, OH, USA
| | - Elena Y Enioutina
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
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Wang H, Shang J, Tong M, Song Y, Ruan L. Evaluation of left ventricular function in immunoglobulin-resistant children with Kawasaki disease: a two-dimensional speckle tracking echocardiography study. Clin Cardiol 2019; 42:753-759. [PMID: 31173382 PMCID: PMC6671829 DOI: 10.1002/clc.23213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 04/08/2019] [Accepted: 05/28/2019] [Indexed: 11/09/2022] Open
Abstract
Background Kawasaki disease (KD) patients who are unresponsive to intravenous immune globulin (IVIG) have a high occurrence of coronary artery lesions (CALs). The characteristics of left ventricular (LV) function alternation in IVIG‐resistant patients are not well‐described. Hypothesis Two‐dimensional speckle tracking echocardiography (STE) is a useful technique that can accurately detect myocardium subclinical dysfunction in resistant patients and may assist in differentiating patients with KD at a higher risk of IVIG resistance. Methods A consecutive sample of 50 IVIG‐resistant patients (25 males, 2.2 ± 0.9 years), 50 IVIG‐responsive patients (27 males, 2.2 ± 0.7 years) and 50 normal subjects (27 males, 2.1 ± 0.9 years) were analyzed using STE, and receiver operating characteristic curve (ROC) analysis was utilized to determine the threshold values of STE parameters associated with IVIG resistance. Results Compared with normal children, IVIG‐resistant patients had lower global longitudinal strain (GLS) (15.82 ± 3.32 vs 20.01 ± 2.98, P = 0.000) and lower global circumferential strain (GCS) (16.65 ± 3.12 vs 20.11 ± 2.86, P = 0.042). Both GLS and GCS in IVIG‐resistant patients were significantly lower than in IVIG‐responsive patients (15.82 ± 3.32 vs 19.95 ± 3.01, 16.65 ± 3.12 vs 19.01 ± 3.00, P = .000, .030, respectively). ROC analysis demonstrated that the absolute values of GLS < 16.8% and GCS < 15.9% were optimal predictors of IVIG unresponsiveness (area under the curve = 0.78, 0.75; sensitivity = 0.83, 0.79; specificity = 0.69, 0.65, respectively). Conclusion IVIG‐resistant patients presented with more severe LV systolic dysfunction compared with IVIG‐responsive patients, which may be the result of myocarditis rather than CALs. STE may be a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance.
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Affiliation(s)
- Haiyong Wang
- Department of Ultrasound Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Jing Shang
- Department of Ultrasound Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Minghui Tong
- Department of Ultrasound Medicine, The Second Affiliated Hospital, Lanzhou University, Lanzhou, China
| | - Yan Song
- Department of Ultrasound Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Litao Ruan
- Department of Ultrasound Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
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21
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Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in Kawasaki Disease. Pediatr Infect Dis J 2018; 37:1227-1234. [PMID: 29570178 DOI: 10.1097/inf.0000000000002019] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Kawasaki disease (KD) is the most common cause of acquired heart disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a known risk factor for cardiac sequelae. Previously reported risk factors for nonresponse include age, male sex and laboratory abnormalities. We set out to identify additional risk factors for IVIG nonresponse in a racially diverse KD population. METHODS We conducted a retrospective chart review at a referral center in the Southeastern United States of children meeting ICD-9 (International Statistical Classification of Disease and Related Health Problems) criteria for KD and being treated with IVIG. RESULTS Four-hundred and fifty-nine children met inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis, unknown race, or failure to meet the American Heart Association guideline criteria. Our final cohort consisted of 392 subjects, with median age of 2.7 years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4% developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more likely to be Black, have higher white blood cell, erythrocyte sedimentation rate and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require critical care and hospital readmission. Responders achieved echocardiographic normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002) and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year. Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02). CONCLUSIONS Nonresponders have higher rates and greater severity of coronary involvement than responders. Our study uniquely demonstrates Black race as a risk factor for nonresponse and for delayed normalization of cardiac involvement at 1-year follow-up.
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Infliximab Plus Intravenous Immunoglobulin (IVIG) Versus IVIG Alone as Initial Therapy in Children With Kawasaki Disease Presenting With Coronary Artery Lesions: Is Dual Therapy More Effective? Pediatr Infect Dis J 2018; 37:976-980. [PMID: 29461447 PMCID: PMC6093799 DOI: 10.1097/inf.0000000000001951] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND We previously demonstrated that 80% of Kawasaki disease (KD) patients who develop coronary artery lesions (CALs) have them at diagnosis. We postulated that KD patients presenting with CALs represent a group that may benefit from more aggressive initial therapy. Infliximab has been shown to decrease inflammation in KD patients when added to standard therapy. We compared outcomes of KD patients with CALs initially treated with intravenous immunoglobulin (IVIG) alone versus IVIG plus infliximab. METHODS Medical records of KD patients from January 2009 to July 2016 were retrospectively reviewed. CALs were defined as a left anterior descending or right coronary artery Z score ≥2.5. KD patients with CALs on initial echocardiogram treated with IVIG alone were compared with those treated with IVIG plus infliximab. Clinical characteristics were compared between groups using Wilcoxon rank-sum test, χ test and Fischer's exact tests; length of stay was analyzed using log-normal regression and need for additional therapy using logistic regression. Effect of treatment on CALs between groups was assessed using linear mixed models. RESULTS Sixty-nine KD patients with CALs at presentation were included. Fifteen of 34 (44%) patients treated with IVIG alone required additional therapy compared with 4 of 35 (11%) patients treated with IVIG plus infliximab (P = 0.003). There were no significant differences between treatment groups for length of stay, CALs or C-reactive protein fall. CONCLUSIONS IVIG plus infliximab as initial therapy reduces the need for additional therapy in KD patients presenting with CALs. Intensified initial therapy, consisting of infliximab plus IVIG, could be considered for this group of KD patients.
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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 the Italian Society of Pediatrics, part I - definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase. Ital J Pediatr 2018; 44:102. [PMID: 30157897 PMCID: PMC6116535 DOI: 10.1186/s13052-018-0536-3] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 05/03/2018] [Indexed: 12/18/2022] Open
Abstract
The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists' contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations.Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits 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 complications.
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Affiliation(s)
- Alessandra Marchesi
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy.
| | | | - Donato Rigante
- Fondazione Policlinico Universitario A. Gemelli, Università Cattolica Sacro Cuore, Rome, Italy
| | | | | | | | | | - Sabrina Buonuomo
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | | | | | - Fabrizio De Benedetti
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | - Andrea De Zorzi
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | - Marzia Duse
- , Università degli Studi Sapienza, Rome, Italy
| | | | | | | | - Maya El Hachem
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | | | | | - Ugo Giordano
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | | | | | | | | | - Giulia Marucci
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | | | | | | | | | | | - Aurelio Secinaro
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
| | | | - Alberto Villani
- Bambino Gesù Children's Hospital, Rome, Italy, Piazza S. Onofrio n. 4, 00165, Rome, Italy
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Chantasiriwan N, Silvilairat S, Makonkawkeyoon K, Pongprot Y, Sittiwangkul R. Predictors of intravenous immunoglobulin resistance and coronary artery aneurysm in patients with Kawasaki disease. Paediatr Int Child Health 2018; 38:209-212. [PMID: 29768976 DOI: 10.1080/20469047.2018.1471381] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
BACKGROUND Patients with Kawasaki disease (KD) who have intravenous immunoglobulin (IVIG) resistance are at increased risk for development of coronary artery abnormalities. Although in Japan several risk scoring systems are able to predict patients with IVIG-resistant (KD), they do not accurately predict non-responders in other regions. AIM The objectives of this study were to determine the predictors of IVIG resistance and coronary artery aneurysm (CAA) and to develop risk scoring systems for predicting IVIG-resistant KD in the Thai population. METHODS A total of 217 patients with KD between 2004 and 2014 were retrospectively reviewed. All patients including 116 with complete KD and 101 with incomplete KD were diagnosed and treated with 2 g/kg IVIG. RESULTS Twenty-six patients (85% male) with IVIG-resistant KD had a reduced platelet count and increased neutrophil-to-lymphocyte ratio compared with those with an IVIG response. Fifty-five patients with CAA eight weeks after diagnosis had a longer duration of fever (≥8 days) and increased platelet count (≥550 × 109/L) than those with non-CAA. Based on analysis by multivariate logistic regression, haematocrit ≤30%, platelet count ≤300 × 109/L, aspartate aminotransferase ≥40 U/L and neutrophil-to-lymphocyte ratio ≥3.2 were predictors of IVIG resistance. The new scoring system using these significant factors had a sensitivity of 80.8% and a specificity of 66.8% in identifying patients with IVIG resistance. Japanese scoring systems had low sensitivity and specificity. CONCLUSIONS KD patients with reduced mean haemoglobin, increased AST level, increased neutrophil-to-lymphocyte ratio and reduced platelet count should be considered for conjunctive therapy such as a corticosteroid in combination with standard treatment. Duration of fever ≥8 days and platelet count ≥550 × 109/L were predictors of CAA. To prevent cardiovascular complications, patients should be treated promptly after KD has been diagnosed.
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Affiliation(s)
- Nattika Chantasiriwan
- a Faculty of Medicine, Department of Pediatrics , Chiang Mai University , Chiang Mai , Thailand
| | - Suchaya Silvilairat
- a Faculty of Medicine, Department of Pediatrics , Chiang Mai University , Chiang Mai , Thailand
| | - Krit Makonkawkeyoon
- a Faculty of Medicine, Department of Pediatrics , Chiang Mai University , Chiang Mai , Thailand
| | - Yupada Pongprot
- a Faculty of Medicine, Department of Pediatrics , Chiang Mai University , Chiang Mai , Thailand
| | - Rekwan Sittiwangkul
- a Faculty of Medicine, Department of Pediatrics , Chiang Mai University , Chiang Mai , Thailand
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25
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Buonsenso D, Cristaldi S, Reale A, de Jacobis IT, Granata L, Marchesi A. Very Early Development and Recognition of Coronary Involvement in a Febrile Infant with Typical Signs of Kawasaki Disease. Mediterr J Hematol Infect Dis 2018; 10:e2018037. [PMID: 30002793 PMCID: PMC6039088 DOI: 10.4084/mjhid.2018.037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 05/14/2018] [Indexed: 12/19/2022] Open
Abstract
Kawasaki disease (KD) is an acute, self-limited, inflammatory disease affecting medium-sized arteries and particularly the coronary arteries in about 25% of untreated cases. KD is a clinical diagnosis based on the presence of ≥5 days of fever and the presence of ≥4 of the 5 principal clinical criteria. We described, for the first time to our knowledge, a case of a very early development (on day 1) of typical KD with transient coronary involvement, diagnosed on day 2 of disease and treated with aspirin and steroids on day 3, with complete resolution of clinical signs and coronary involvement.
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Affiliation(s)
- D Buonsenso
- Pediatric Emergency Department, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
| | - S Cristaldi
- Pediatric Emergency Department, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
| | - A Reale
- Pediatric Emergency Department, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
| | - I Tarissi de Jacobis
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
| | - L Granata
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
| | - A Marchesi
- Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy
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26
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Yang TJ, Lin MT, Lu CY, Chen JM, Lee PI, Huang LM, Wu MH, Chang LY. The prevention of coronary arterial abnormalities in Kawasaki disease: A meta-analysis of the corticosteroid effectiveness. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2018; 51:321-331. [PMID: 28927685 DOI: 10.1016/j.jmii.2017.08.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 08/31/2017] [Accepted: 08/31/2017] [Indexed: 01/28/2023]
Abstract
OBJECTIVE The use of corticosteroid in Kawasaki disease (KD) remains controversial among current guidelines. The objective of this study is to summarize the effectiveness and safety of corticosteroid to prevent coronary arterial lesions in Kawasaki disease, both as initial and rescue therapy. METHODS The Medline, EMBASE, Google scholar, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, and Japanese Institutional Repositories Online were searched for studies up to 31 March 2017. Studies that compared incidence of coronary artery lesions between regimens with corticosteroid and regimen without it in a well-defined controlled group were included. The incidence of coronary artery lesion was analyzed by meta-analysis. RESULTS Nineteen studies published between 1999 and 2016 fulfilled eligibility criteria. There were 3591 patients included for analysis. There was a significant reduction in incidence of coronary artery lesions with usage of corticosteroid with a pooled odds ratio of 0.72 (95% CI 0.57-0.92; p = 0.01) than that without usage of corticosteroid. In general, a greater effect was seen in the patient received corticosteroid as initial and adjuvant therapy with intravenous immune globulin (pooled odds ratio 0.39, 95% CI 0.21-0.73, p = 0.007) than those who received corticosteroid as rescue therapy. The risk reduction was statistically significant in Japanese groups (OR 0.56, 95% CI 0.42-0.75 in fixed effects model) but not significant in non-Japanese groups (OR 1.45, 95% CI 0.91-2.30 in fixed effects model). CONCLUSIONS We demonstrated an overall reduction in incidence of coronary artery lesions with the use of corticosteroid as initial and adjuvant treatment for Kawasaki disease.
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Affiliation(s)
- Tsung-Ju Yang
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Ming-Tai Lin
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Chun-Yi Lu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan.
| | - Jong-Min Chen
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Ping-Ing Lee
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Li-Min Huang
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Mei-Hwan Wu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan
| | - Luan-Yin Chang
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taiwan.
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27
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Mori M, Hara T, Kikuchi M, Shimizu H, Miyamoto T, Iwashima S, Oonishi T, Hashimoto K, Kobayashi N, Waki K, Suzuki Y, Otsubo Y, Yamada H, Ishikawa C, Kato T, Fuse S. Infliximab versus intravenous immunoglobulin for refractory Kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial. Sci Rep 2018; 8:1994. [PMID: 29386515 PMCID: PMC5792468 DOI: 10.1038/s41598-017-18387-7] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 12/05/2017] [Indexed: 12/31/2022] Open
Abstract
We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1–10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.
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Affiliation(s)
- Masaaki Mori
- Yokohama City University Medical Center, Yokohama, Japan. .,Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University, Tokyo, Japan.
| | - Takuma Hara
- Yokohama City University Medical Center, Yokohama, Japan.,Department of Pediatrics, Hara Children's Clinic, Tokorozawa, Japan
| | - Masako Kikuchi
- Department of Pediatrics, Yokohama City University Hospital, Yokohama, Japan
| | - Hiroyuki Shimizu
- Children's Medical Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Tomoyuki Miyamoto
- Department of Pediatrics, Yokosuka General Hospital Uwamachi, Yokosuka, Japan
| | - Satoru Iwashima
- Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Pediatrics, Chutoen General Medical Center, Kakegawa, Japan
| | - Tatsuya Oonishi
- Department of Pediatrics, National Hospital Organization Shikoku Medical Center for Children and Adults, Zentsuji, Japan
| | - Kunio Hashimoto
- Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Norimoto Kobayashi
- Department of Pediatrics, Shinsyu University School of Medicine, Matsumoto, Japan
| | - Kenji Waki
- Department of Pediatrics, Kurashiki Central Hospital, Kurashiki, Japan
| | - Yasuo Suzuki
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yoshikazu Otsubo
- Department of Pediatrics, Sasebo City General Hospital, Sasebo, Japan
| | | | | | - Taichi Kato
- Department of Pediatrics, Nagoya University Hospital, Nagoya, Japan
| | - Shigeto Fuse
- Department of Pediatrics, NTT Sapporo Medical Center, Sapporo, Japan
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28
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Lin MT, Wu MH. The global epidemiology of Kawasaki disease: Review and future perspectives. Glob Cardiol Sci Pract 2017; 2017:e201720. [PMID: 29564341 PMCID: PMC5856963 DOI: 10.21542/gcsp.2017.20] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Kawasaki disease (KD) is one of the most common childhood vasculitides and may lead to coronary arterial complications. KD has been reported in more than 60 countries over five continents. Previous publications have provided a comprehensive description of the epidemiologic features of KD including incidence, age of onset, seasonal trends, and rates of cardiac lesions. However, the interactions among the KD patients, time (seasons) and place have been less well studied. We review the current global epidemiology of KD and focus on the longitudinal changes in incidence, seasonality and response to intravenous immunoglobulin (IVIG) therapy.
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Affiliation(s)
- Ming-Tai Lin
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hwan Wu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
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29
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Abstract
BACKGROUND To reveal the recent epidemiologic features of Kawasaki disease (KD) in South Korea based on data from a nationwide survey. METHODS We collected data between 2012 and 2014 regarding the incidence, symptoms and signs, treatment trends and coronary complications associated with acute KD by sending questionnaires to 97 hospitals with pediatric residency programs as well as 19 community hospitals without residency training. RESULTS We received full and partial data from 97 and 13 hospitals, respectively (response rate: 94.8%). A total of 14,916 cases of KD were reported by these 110 hospitals (4588 in 2012, 5183 in 2013 and 5145 in 2014). The male-to-female ratio was 1.4:1, and the median age at diagnosis was 29 months. The incidence of KD per 100,000 children younger than 5 years of age were 170.9, 194.9 and 194.7 in 2012, 2013 and 2014, respectively. The recurrence rate was 4.7%. KD occurred more frequently during summer (especially June and July) and winter (December and January) seasons. Intravenous immunoglobulin was administered to 95.4% of the patients, and the nonresponder rate for the first intravenous immunoglobulin was 11.8%. Coronary aneurysm occurred in 1.7% of the patients, and giant aneurysm developed in 19 patients (0.16%) during the 3 years. One patient had myocardial infarction and 1 patient died of suspected coronary aneurysm rupture. CONCLUSIONS The incidence of KD in South Korea increased to 194.7 per 100,000 children younger than 5 years in 2014; meanwhile, the coronary aneurysm rate decreased to 1.7%.
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30
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Lo JY, Minich LL, Tani LY, Wilkes J, Ding Q, Menon SC. Factors Associated With Resource Utilization and Coronary Artery Dilation in Refractory Kawasaki Disease (from the Pediatric Health Information System Database). Am J Cardiol 2016; 118:1636-1640. [PMID: 27665207 DOI: 10.1016/j.amjcard.2016.08.039] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 08/19/2016] [Accepted: 08/19/2016] [Indexed: 11/28/2022]
Abstract
Management guidelines for refractory Kawasaki disease (KD) are vague. We sought to assess practice variation and identify factors associated with large/complex coronary artery aneurysms (LCAA) and resource utilization in refractory KD. This retrospective cohort study identified patients aged ≤18 years with KD (2004 to 2014) using the Pediatric Health Information System. Refractory KD was defined as receiving >1 dose of intravenous immunoglobulin. Demographics, medications, concomitant infections, length of stay (LOS), and charges were collected. Antithrombotic therapy was a surrogate for LCAA. LOS and hospital charges assessed resource utilization. Multivariate regression identified factors associated with LOS, charges, and LCAA. Of 14,194 patients with KD, 2,974 (21%) had refractory KD and 203 of those 2,974 (7%) had LCAA. Additional intravenous immunoglobulin was the sole medication in 77%. Other medications added were steroids (18%), infliximab (2%), and both (3%). Warfarin, low-molecular-weight heparin, tissue plasminogen activator, and clopidogrel were prescribed with equal frequency (2%). Male gender (adjusted relative risk 1.52, 95% confidence interval [CI] 1.08 to 2.16, p <0.01), admission to an intensive care unit (4.79, 95% CI 3.40 to 6.74, p <0.001), arrhythmia (3.00, 95% CI 1.94 to 4.65, p <0.001), and concomitant viral infection (2.29, 95% CI 1.49 to 3.52, p <0.001) were associated with LCAA. Severe illness, race, region, and payer were independently associated with increased charges (p <0.05 for all). In conclusion, treatment for refractory KD varies widely. Concomitant viral infection was associated with a greater risk of LCAA in refractory KD. Better understanding of optimal management may improve outcomes and decrease both variability in management and resource utilization for refractory KD.
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Affiliation(s)
- Jennifer Y Lo
- Department of Pediatric Cardiology, University of Utah at Primary Children's Hospital, Salt Lake City, Utah.
| | - L LuAnn Minich
- Department of Pediatric Cardiology, University of Utah at Primary Children's Hospital, Salt Lake City, Utah
| | - Lloyd Y Tani
- Department of Pediatric Cardiology, University of Utah at Primary Children's Hospital, Salt Lake City, Utah
| | - Jacob Wilkes
- Department of Pediatrics, University of Utah, Salt Lake City, Utah
| | - Qian Ding
- Study Design and Biostatistics Center, University of Utah School of Medicine, Salt Lake City, Utah
| | - Shaji C Menon
- Department of Pediatric Cardiology, University of Utah at Primary Children's Hospital, Salt Lake City, Utah
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31
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Kibata T, Suzuki Y, Hasegawa S, Matsushige T, Kusuda T, Hoshide M, Takahashi K, Okada S, Wakiguchi H, Moriwake T, Uchida M, Ohbuchi N, Iwai T, Hasegawa M, Ichihara K, Yashiro M, Makino N, Nakamura Y, Ohga S. Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin. Int J Cardiol 2016; 214:209-15. [PMID: 27070994 DOI: 10.1016/j.ijcard.2016.03.017] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 03/12/2016] [Indexed: 12/25/2022]
Abstract
BACKGROUNDS Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. METHODS Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). RESULTS The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. CONCLUSIONS IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae.
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Affiliation(s)
- Tetsuhiro Kibata
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yasuo Suzuki
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shunji Hasegawa
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
| | - Takeshi Matsushige
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Takeshi Kusuda
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Madoka Hoshide
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Kazumasa Takahashi
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Seigo Okada
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hiroyuki Wakiguchi
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Tadashi Moriwake
- Division of Pediatrics, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan
| | - Masashi Uchida
- Division of Pediatrics, JCHO Tokuyama Central Hospital, Shunan, Japan
| | - Noriko Ohbuchi
- Division of Pediatrics, Yamaguchi Red Cross Hospital, Yamaguchi, Japan
| | - Takashi Iwai
- Division of Pediatrics, Yamaguchi-ken Saiseikai Shimonoseki General Hospital, Shimonoseki, Japan
| | | | - Kiyoshi Ichihara
- Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Mayumi Yashiro
- Department of Public Health, Jichi Medical University, Shimotsuke, Japan
| | - Nobuko Makino
- Department of Public Health, Jichi Medical University, Shimotsuke, Japan
| | - Yosikazu Nakamura
- Department of Public Health, Jichi Medical University, Shimotsuke, Japan
| | - Shouichi Ohga
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan
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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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Aoyagi R, Hamada H, Sato Y, Suzuki H, Onouchi Y, Ebata R, Nagashima K, Terauchi M, Terai M, Hanaoka H, Hata A. Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial). BMJ Open 2015; 5:e009562. [PMID: 26628527 PMCID: PMC4679944 DOI: 10.1136/bmjopen-2015-009562] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca(2+)/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. METHODS AND ANALYSIS This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. ETHICS AND DISSEMINATION The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER JMA-IIA00174; Pre-results.
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Affiliation(s)
- Reiko Aoyagi
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Hiromichi Hamada
- Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Yasunori Sato
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Hiroyuki Suzuki
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
| | - Yoshihiro Onouchi
- Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Ryota Ebata
- Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Kengo Nagashima
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Moe Terauchi
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Masaru Terai
- Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Hideki Hanaoka
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Akira Hata
- Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan
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Phadke D, Patel SS, Dominguez SR, Heizer H, Anderson MS, Glode MP, Jone PN. Tissue Doppler Imaging as a Predictor of Immunoglobulin Resistance in Kawasaki Disease. Pediatr Cardiol 2015; 36:1618-23. [PMID: 25991572 DOI: 10.1007/s00246-015-1206-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 05/14/2015] [Indexed: 12/19/2022]
Abstract
Kawasaki disease (KD) is characterized by myocarditis and left ventricular dysfunction during the acute phase of the illness. Despite treatment with intravenous immunoglobulin (IVIG), a significant number of patients are IVIG resistant. We evaluated KD patients in the acute phase of illness using tissue Doppler imaging (TDI) to assess whether myocardial dysfunction may predict IVIG resistance. All patients with acute KD presenting to Children's Hospital Colorado from February 2007 through March 2014 were included in this study and underwent echocardiograms with TDI evaluation at diagnosis. Patients were divided into two groups: IVIG resistant and IVIG responder. Group differences were assessed using Wilcoxon-Mann-Whitney and Chi-square testing. Receiver operating characteristic (ROC) curve analysis was utilized to determine threshold values of TDI measurements associated with IVIG resistance. Fifty-one age-matched IVIG resistant patients were compared to 51 IVIG responder patients [median age, IQR 44.57 (20.13-77.07) vs. 33.49 (17.30-62.89) months, p < 0.44]. There were significant differences in the septal and mitral early diastolic velocities (E') (p < 0.001 and p < 0.01), respectively. ROC analysis demonstrated that tricuspid E' <0.15 cm/s, septal E' <0.12 cm/s, and mitral E' <0.16 cm/s were good predictors of IVIG unresponsiveness (AUC = 0.66, 0.66, and 0.70, respectively). There were no differences between the systolic velocities and late diastolic velocities (A'). IVIG resistant KD patients present with significantly greater diastolic dysfunction compared to responders in patients with KD. TDI may be a useful tool to differentiate KD patients at higher risk of IVIG resistance.
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Affiliation(s)
- Daniel Phadke
- Department of Biology, University of Alabama, Tuscaloosa, AL, USA
| | - Sonali S Patel
- Pediatric Cardiology, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Avenue, B100, Aurora, CO, 80045, USA
| | - Samuel R Dominguez
- Pediatric Infectious Disease, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA
| | - Heather Heizer
- Pediatric Infectious Disease, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA
| | - Marsha S Anderson
- Pediatric Infectious Disease, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA
| | - Mary P Glode
- Pediatric Infectious Disease, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA
| | - Pei-Ni Jone
- Pediatric Cardiology, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Avenue, B100, Aurora, CO, 80045, USA.
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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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