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Angom RS, Singh M, Muhammad H, Varanasi SM, Mukhopadhyay D. Zebrafish as a Versatile Model for Cardiovascular Research: Peering into the Heart of the Matter. Cells 2025; 14:531. [PMID: 40214485 PMCID: PMC11988917 DOI: 10.3390/cells14070531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/25/2025] [Accepted: 03/30/2025] [Indexed: 04/14/2025] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death in the world. A total of 17.5 million people died of CVDs in the year 2012, accounting for 31% of all deaths globally. Vertebrate animal models have been used to understand cardiac disease biology, as the cellular, molecular, and physiological aspects of human CVDs can be replicated closely in these organisms. Zebrafish is a popular model organism offering an arsenal of genetic tools that allow the rapid in vivo analysis of vertebrate gene function and disease conditions. It has a short breeding cycle, high fecundity, optically transparent embryos, rapid internal organ development, and easy maintenance. This review aims to give readers an overview of zebrafish cardiac biology and a detailed account of heart development in zebrafish and its comparison with humans and the conserved genetic circuitry. We also discuss the contributions made in CVD research using the zebrafish model. The first part of this review focuses on detailed information on the morphogenetic and differentiation processes in early cardiac development. The overlap and divergence of the human heart's genetic circuitry, structure, and physiology are emphasized wherever applicable. In the second part of the review, we overview the molecular tools and techniques available to dissect gene function and expression in zebrafish, with special mention of the use of these tools in cardiac biology.
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Affiliation(s)
- Ramcharan Singh Angom
- Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine and Science, Jacksonville, FL 32224, USA; (R.S.A.); (H.M.); (S.M.V.)
| | - Meghna Singh
- Department of Pathology and Lab Medicine, University of California, Los Angeles, CA 92093, USA;
| | - Huzaifa Muhammad
- Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine and Science, Jacksonville, FL 32224, USA; (R.S.A.); (H.M.); (S.M.V.)
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Sai Manasa Varanasi
- Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine and Science, Jacksonville, FL 32224, USA; (R.S.A.); (H.M.); (S.M.V.)
| | - Debabrata Mukhopadhyay
- Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine and Science, Jacksonville, FL 32224, USA; (R.S.A.); (H.M.); (S.M.V.)
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Lee ZM, Chang HC, Liu SF, Huang YH, Kuo HC. Argonaute2 and Argonaute4 Involved in the Pathogenesis of Kawasaki Disease via mRNA Expression Profiles. CHILDREN (BASEL, SWITZERLAND) 2025; 12:73. [PMID: 39857904 PMCID: PMC11763442 DOI: 10.3390/children12010073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/27/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Argonautes (AGOs) are a type of protein that degrade specific messenger RNAs, consequently reducing the expression of a specific gene. These proteins consist of small, single-stranded RNA or DNA and may provide a route for detecting and silencing complementary mobile genetic elements. In this research, we investigated which AGO(s) were involved in Kawasaki disease (KD). METHODS AND MATERIALS We obtained mRNA-level gene expression profiles from leukocyte samples that had previously been gathered in another study and uploaded to the NCBI GEO database. The Human Transcriptome Array (HTA 2.0) analysis included 50 children with KD prior to IVIG (KD1), 18 children with KD three weeks post-IVIG (KD3), 18 non-febrile controls (HC), and 18 febrile controls (FC), which were arranged in the quoted publications for all materials and methods in order to collect data. We used the default value of the commercialized microarray tool Partek to perform an analysis of variance and determine any significant fold changes (KD1, KD3, HC, and FC individually). RESULTS The data revealed that the AGO2 and AGO4 genes displayed significant within-group differences with p = 0.034 and 0.007, respectively. In AGO2, significant differences were observed between KD1 vs. HC + FC with p = 0.034. KD1 appears higher than the other specimens in AGO4, with significant differences between KD1 and HC (p = 0.033), KD1 and FC (p = 0.033), KD1 and KD3 (p = 0.013), and KD1 and HC + FC (p = 0.007). We observed no substantial differences in AGO1 or AGO3 (p > 0.05). There were no significant differences between AGO(s) and coronary artery lesions or intravenous immunoglobulin resistance. (p > 0.05) Conclusion: Endothelial cell inflammation and injury, two basic pathological mechanisms, are thought to be involved in coronary endothelial dysfunction in KD. AGO2 and AGO4 are likely to participate in the endothelial dysfunction of children with KD, with AGO4 potentially playing a key role, while AGO1 and AGO3 appear not to participate.
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Affiliation(s)
- Zon-Min Lee
- Department of Pharmacy and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
- Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan
| | - Hui-Chuan Chang
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (H.-C.C.); (S.-F.L.)
- Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Shih-Feng Liu
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (H.-C.C.); (S.-F.L.)
- Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Ying-Hsien Huang
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Ho-Chang Kuo
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
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Migowa A, Njeru CM, Were E, Ngwiri T, Colmegna I, Hitchon C, Scuccimarri R. Kawasaki disease in Kenya and review of the African literature. Pediatr Rheumatol Online J 2024; 22:43. [PMID: 38616268 PMCID: PMC11016229 DOI: 10.1186/s12969-024-00977-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 03/24/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report. METHODS A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature. RESULTS Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3-10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2-20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa. CONCLUSIONS This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa.
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Affiliation(s)
- A Migowa
- Department of Pediatrics and Child Health, Aga Khan University Medical College (East Africa), Nairobi, Kenya
| | - C M Njeru
- Department of Pediatrics and Child Health, Aga Khan University Medical College (East Africa), Nairobi, Kenya
| | - E Were
- Department of Pediatrics, Gertrude's Children's Hospital, Nairobi, Kenya
| | - T Ngwiri
- Department of Pediatrics, Gertrude's Children's Hospital, Nairobi, Kenya
| | - I Colmegna
- Division of Rheumatology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - C Hitchon
- Section of Rheumatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - R Scuccimarri
- Division of Pediatric Rheumatology, Department of Pediatrics, McGill University Health Centre, 1001 boul. Décarie, A04.6306, H4A 3J1, Montreal, QC, Canada.
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Hayashi K, Miyakoshi C, Hoshino S, Kobayashi N, Nakajima R, Sagawa H, Hayashiya T, Suzuki A, Aota C, Nishijima S, Shimizu Y, Yamakawa M, Tsuda E. Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference. BMJ Paediatr Open 2024; 8:e002312. [PMID: 38233084 PMCID: PMC10806463 DOI: 10.1136/bmjpo-2023-002312] [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: 09/28/2023] [Accepted: 12/26/2023] [Indexed: 01/19/2024] Open
Abstract
OBJECTIVE To clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease. DESIGN Retrospective cohort study. SETTING Multicentre. PARTICIPANTS This study included 735 patients with Kawasaki disease aged ≤10 years and hospitalised between 4 and 10 days of illness in eight Japanese hospitals from January 2016 to December 2020. EXPOSURES High-dose (HD) ASA was administered with initial IVIG to 333 patients in 6 hospitals (HD group). ASA was not administered routinely to 402 patients in the other two hospitals, and low-dose ASA was only administered when patients developed coronary artery lesions or pericardial effusion (non-HD group). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was the presence of coronary artery lesions, defined as a coronary artery diameter >+2.5 SD of body surface area within 1 month of onset. The secondary outcome was responsiveness to the initial IVIG therapy. Adjusted risk ratios for the outcomes were calculated using modified Poisson regression models. Bayesian analysis was conducted to estimate the posterior probability of the treatment effect of HD ASA under several prior distributions. RESULTS The incidence of coronary artery lesions was not significantly higher in the HD group than in the non-HD group (12/333 (3.6%) vs 15/402 (4.0%)). The proportion of non-responders to initial IVIG was similar between the two groups (HD group: 78/333 (23%); non-HD group: 83/402 (22%)). In the Bayesian analysis, considering a difference of ≤2% to be of no clinical importance, there was only a 9.3% chance of reduced risk of coronary artery lesions in the HD group compared with the non-HD group even with a strongly enthusiastic prior for HD treatment. CONCLUSIONS Compared with HD ASA treatment, treatment without ASA in the acute phase of Kawasaki disease was not associated with increased complications from Kawasaki disease.
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Affiliation(s)
- Ken Hayashi
- Department of Pediatrics, Osaka University Hospital, Suita, Japan
| | - Chisato Miyakoshi
- Department of Pediatrics and Neonatology, Kobe City Medical Center General Hospital, Kobe, Japan
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Research Support, Center for Clinical Research and Innovation, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Shinsuke Hoshino
- Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan
| | - Naho Kobayashi
- Department of Pediatrics, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Ryo Nakajima
- Department of Pediatrics, Saiseikai Shiga Hospital, Ritto, Japan
| | - Hironori Sagawa
- Department of Pediatrics, Omihachiman Community Medical Center, Oumihachiman, Japan
| | - Toshikazu Hayashiya
- Department of Pediatrics, Omihachiman Community Medical Center, Oumihachiman, Japan
| | - Atsushi Suzuki
- Department of Pediatrics, Oumikusatsu Tokushukai Hospital, Kusatsu, Japan
| | - Chie Aota
- Department of Pediatrics and Neonatology, Kobe City Medical Center General Hospital, Kobe, Japan
| | | | - Yasuyo Shimizu
- Department of Pediatrics, Nagahama Red Cross Hospital, Nagahama, Japan
| | - Masaru Yamakawa
- Department of Pediatrics and Neonatology, Kobe City Medical Center General Hospital, Kobe, Japan
- Sonoda Women's University, Amagasaki, Japan
| | - Etsuko Tsuda
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center Hospital, Suita, Japan
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Singh S, Inban P, Mishra A, Yadav AS, Singh T, Singh R, Savaliya BP, Mankad SP, Gowthavaram CA, Khan A. Atypical Kawasaki Disease in a 16-Month-Old Baby: A Case Report and Literature Review. Cureus 2023; 15:e39336. [PMID: 37378132 PMCID: PMC10292155 DOI: 10.7759/cureus.39336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Kawasaki illness is an inflammatory condition of small- to medium-sized vessels that primarily affects children. It affects the lymph nodes, skin, mucous membranes, and heart, especially the coronary arteries. Patients who lack the comprehensive clinical manifestations of classic Kawasaki disease (KD) are typically evaluated for incomplete KD. Such patients have persistent fever and lack one or more characteristic clinical signs. Here, we present a case of a 16-month-old baby presented with fever for nine days, excessive crying and irritability for four days, and refusal to feed for one day with pallor and developed lip cracking, mucositis, bilateral edema, and redness in the palms and soles followed by periungual desquamation. Lab evaluations revealed anemia, elevated white cell count, and c-reactive protein along sterile pyuria. Since the child became afebrile after ten days of illness, inflammatory marker levels decreased, and no coronary artery abnormalities were detected on 2D echocardiography, and the child was diagnosed with incomplete KD based on the clinical, laboratory, and radiological evaluations after ruling out all other possible causes. He was managed conservatively with low-dose aspirin, and the child was doing well on a two-month follow-up.
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Affiliation(s)
- Sonali Singh
- Pediatrics, King George's Medical University, Lucknow, IND
| | - Pugazhendi Inban
- General Medicine, Government Medical College Omandurar, Chennai, IND
| | - Anshika Mishra
- Pediatrics, King George's Medical University, Lucknow, IND
| | - Anupam S Yadav
- Psychiatry, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, IND
| | - Tanveer Singh
- College of Medicine, Sri Guru Ram Das University of Health Sciences, Punjab, IND
| | - Ramandeep Singh
- College of Medicine, Punjab Institute of Medical Sciences, Punjab, IND
| | | | | | | | - Aadil Khan
- Internal Medicine, Lala Lajpat Rai Hospital, Kanpur, IND
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[Pediatric expert consensus on the application of aspirin in Kawasaki disease]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2022; 24:597-603. [PMID: 35652428 PMCID: PMC9250407 DOI: 10.7499/j.issn.1008-8830.2203190] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/03/2022] [Indexed: 01/24/2023]
Abstract
Kawasaki disease (KD) is one of the common acquired heart diseases in children aged <5 years and is an acute systemic vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for the prevention of coronary artery lesion in acute KD; however, there are still controversies over the role and optimal dose of aspirin. The consensus was formulated based on the latest research findings of KD treatment in China and overseas and comprehensive discussion of pediatric experts in China and put forward recommendations on the dose, usage, and course of aspirin treatment in the first-line treatment of KD.
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Alghamdi KT, Waggass RA, Aga SS, Alrohaili AA, Alaidroos AH, Alghamdi MD, Algamdi MK, Alghamdi AT. The Most Common Clinical Features of Kawasaki Disease Patients in King Abdulaziz Medical City. Cureus 2021; 13:e15127. [PMID: 34159029 PMCID: PMC8212913 DOI: 10.7759/cureus.15127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background Kawasaki disease (KD) is an acute idiopathic vasculitis affecting the small and medium-sized arteries especially coronary artery (CA). it occurs in childhood mostly below five years of age. Objective This study aims to identify the most common clinical features among KD patients in King Abdulaziz Medical City in Jeddah, Saudi Arabia from 1/1/1982 to 31/12/2018. Methods A case series study was conducted in all KD patients that were admitted to the King Abdulaziz Medical City from 1/1/1982 to 31/12/2018 except those who were diagnosed in other hospitals or whose diagnosis has later changed. The identification of patient was done by using the International Classification of Diseases (ICD) coding for KD (ICD9 446.1). Our data consisted of the patient’s file number, age at presentation, gender, whether the patients received IVIG treatment or not, number of days of fever before starting IVIG treatment, response to IVIG treatment, season in which the symptoms started and clinical features based on body’s system. Result The study included 18 patients, 11 males showed that (55.6%) of patients met the criteria of typical KD and most of them were less than five years old. In addition, most patients were reported to have polymorphous rash, cough, irritability, vomiting, and a murmur. All patients who received intravenous immunoglobulin (IVIG) treatment which demonstrated an improvement even though those who started the treatment after 10 days of fever. Conclusion In typical KD patients, the distribution of the clinical features was almost identical. However, there were some variations in them among atypical KD patients. Moreover, Evan though KD in our region is not common as in Japan, the incidence of giant aneurism was higher. In addition to that, this study and other study conducted in Saudi Arabia found that screened patients reported tachycardia more than patients in Japan. Recommendation As KD is still idiopathic, we recommend more details to be collected from the patients, especially consanguinity as it is common in Saudi Arabia
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Affiliation(s)
- Khalid Talal Alghamdi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
| | | | - Syed Sameer Aga
- Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
| | - Abdulaziz Ahmed Alrohaili
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
| | - Ali Hassan Alaidroos
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
| | - Mohammed Dakhilallah Alghamdi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
| | - Mohannd Khalid Algamdi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
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Leung AKC, Sergi CM, Leong KF, Kantor PF, Md. Visual Diagnosis: High Fever, Maculopapular Rash, Perianal Desquamation, and Conjunctivitis in a 3-year-old Boy. Pediatr Rev 2021; 42:e17-e22. [PMID: 33931516 DOI: 10.1542/pir.2018-0330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
| | - Consolato Maria Sergi
- Departments of Pediatrics, Laboratory Medicine, and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Kin Fon Leong
- Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia
| | | | - Md
- Division of Cardiology, Department of Pediatrics, University of Southern California, Los Angeles, CA
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Porritt RA, Chase Huizar C, Dick EJ, Kumar S, Escalona R, Gomez AC, Marek-Iannucci S, Noval Rivas M, Patterson J, Forsthuber TG, Arditi M, Gorelik M. Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis. Front Immunol 2021; 12:630196. [PMID: 33897686 PMCID: PMC8064710 DOI: 10.3389/fimmu.2021.630196] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 03/12/2021] [Indexed: 02/01/2023] Open
Abstract
Objective Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in the developed world. 10% of KD patients are resistant to front-line therapy, and no interventions exist to address secondary complications such as myocardial fibrosis. We sought to identify proteins and pathways associated with disease and anti-IL-1 treatment in a mouse model of KD. Methods Vasculitis was induced via Lactobacillus casei cell wall extract (LCWE) injection in 5-week-old male mice. Groups of mice were injected with LCWE alone, LCWE and IL-1 receptor antagonist anakinra, or saline for controls. Upper heart tissue was assessed by quantitative mass spectrometry analysis. Expression and activation of STAT3 was assessed by immunohistochemistry, immunofluorescence and Western blot, and IL-6 expression by RNA-seq and ELISA. A STAT3 small molecular inhibitor and anti-IL-6R antibody were used to evaluate the role of STAT3 and IL-6 in disease development. Results STAT3 was highly expressed and phosphorylated in cardiac tissue of LCWE-injected mice, and reduced following anakinra treatment. Il6 and Stat3 gene expression was enhanced in abdominal aorta of LCWE-injected mice and reduced with Anakinra treatment. IL-6 serum levels were enhanced in LCWE-injected mice and normalized by anakinra. However, neither inhibition of STAT3 nor blockade of IL-6 altered disease development. Conclusion Proteomic analysis of cardiac tissues demonstrates differential protein expression between KD-like, control and anakinra treated cardiac tissue. STAT3 and IL-6 were highly upregulated with LCWE and normalized by anakinra treatment. However, both STAT3 and IL-6 were dispensable for disease development indicating they may be bystanders of inflammation.
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Affiliation(s)
- Rebecca A. Porritt
- Departments of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Carol Chase Huizar
- Department of Biology, University of Texas San Antonio, San Antonio, TX, United States
| | - Edward J. Dick
- Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States
| | - Shyamesh Kumar
- Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States
| | - Renee Escalona
- Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States
| | - Angela C. Gomez
- Departments of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Stefani Marek-Iannucci
- Departments of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Magali Noval Rivas
- Departments of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Jean Patterson
- Texas Biomedical Research Institute, San Antonio, TX, United States
| | - Thomas G. Forsthuber
- Department of Biology, University of Texas San Antonio, San Antonio, TX, United States
| | - Moshe Arditi
- Departments of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Mark Gorelik
- Department of Pediatric Allergy, Immunology and Rheumatology, Columbia University Medical Center, New York, NY, United States
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Martelli Júnior H, Machado RA, Martelli DRB, Barbosa MC, Bonan PRF, Coletta RD. Potential link between SARS-CoV-2 and Kawasaki disease: importance of dentists for the diagnosis. Braz Oral Res 2021; 35:e047. [PMID: 33729297 DOI: 10.1590/1807-3107bor-2021.vol35.0047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/26/2020] [Indexed: 01/04/2023] Open
Abstract
Kawasaki disease (KD) is a vasculitis with predilection for coronary arteries. Due to a lack of reliable confirmatory laboratory tests, the diagnosis of KD is based on a characteristic pattern of clinical findings that appear in a typical temporal sequence. The diagnostic criteria have been periodically modified and the American Heart Association has proposed the most recent guidelines for its diagnosis. However, patients may have incomplete or atypical forms of KD and diagnosis can often be difficult. Because oropharyngeal manifestations are a common and important feature for diagnosing KD and recent studies have hypothesized a possible association between KD and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this review we highlight the importance of dentists in the diagnosis of KD and its potential association with SARS-CoV-2.
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Affiliation(s)
- Hercílio Martelli Júnior
- Universidade de Montes Claros - Unimontes, Dental School Health Sciences Postgraduate Program, Montes Claros, MG, Brazil
| | - Renato Assis Machado
- Universidade de São Paulo - USP, School of Dentistry, Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, SP, Brazil
| | | | - Mauro Costa Barbosa
- Universidade de Montes Claros - Unimontes, Dental School, Department of Oral Diagnosis, Montes Claros, MG, Brazil
| | | | - Ricardo Della Coletta
- Universidade Estadual de Campnas - Unicamp, School of Dentistry, Department of Oral Diagnosis, Piracicaba, SP, Brazil
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Kim JJ, Kim HJ, Yu JJ, Yun SW, Lee KY, Yoon KL, Kil HR, Kim GB, Han MK, Song MS, Lee HD, Jun HO, Ha KS, Hong YM, Jang GY, Lee JK. IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease. Korean Circ J 2021; 51:267-278. [PMID: 33655727 PMCID: PMC7925970 DOI: 10.4070/kcj.2020.0345] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/06/2020] [Accepted: 11/11/2020] [Indexed: 11/11/2022] Open
Abstract
Background and Objectives Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs). Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). Conclusions High IgA levels in patients with KD are prognostic for the risk of CALs.
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Affiliation(s)
- Jae Jung Kim
- Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
| | - Hea Ji Kim
- Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Jin Yu
- Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sin Weon Yun
- Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea
| | - Kyung Yil Lee
- Department of Pediatrics, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon, Korea
| | - Kyung Lim Yoon
- Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Hong Ryang Kil
- Department of Pediatrics, Chungnam National University Hospital, Daejeon, Korea
| | - Gi Beom Kim
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Myung Ki Han
- Department of Pediatrics, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea
| | - Min Seob Song
- Department of Pediatrics, Inje University Paik Hospital, Busan, Korea
| | - Hyoung Doo Lee
- Department of Pediatrics, Pusan National University Hospital, Busan, Korea
| | - Hyun Ok Jun
- Department of Pediatrics and Adolescent Medicine, Myongji Hospital, Goyang, Korea
| | - Kee Soo Ha
- Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea
| | - Young Mi Hong
- Department of Pediatrics, Ewha Womans University Hospital, Seoul, Korea
| | - Gi Young Jang
- Department of Pediatrics, Korea University Ansan Hospital, Ansan, Korea
| | - Jong Keuk Lee
- Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
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12
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Rehman S, Majeed T, Ansari MA, Al-Suhaimi EA. Syndrome resembling Kawasaki disease in COVID-19 asymptomatic children. J Infect Public Health 2020; 13:1830-1832. [PMID: 32919931 PMCID: PMC7439985 DOI: 10.1016/j.jiph.2020.08.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/07/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022] Open
Abstract
The current knowledge about the COVID-19 (Coronavirus Disease-2019) pandemic is still limited and is unravelling with the passing days, especially clinical data, and research in pediatric age group. Recently, there is a new and crucial development reported recently among the COVID-19 asymptomatic children, a novel syndrome affecting asymptomatic COVID-19 children, presenting as a hyperinflammatory syndrome which is like Kawasaki disease shock syndrome. The purpose of this correspondence is to discuss some important findings of the syndrome for the better understanding of the disease.
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Affiliation(s)
- Suriya Rehman
- Department of Epidemic Diseases Research, Institute of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, 31441 Dammam, Saudi Arabia.
| | - Tariq Majeed
- Department of General Pediatric, Maternity and Children Hospital, Dammam, Saudi Arabia
| | - Mohammad Azam Ansari
- Department of Epidemic Diseases Research, Institute of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, 31441 Dammam, Saudi Arabia
| | - Ebtesam A Al-Suhaimi
- Department of Biology, College of Science and Institute of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, 31441 Dammam, Saudi Arabia.
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13
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Hicar MD. Antibodies and Immunity During Kawasaki Disease. Front Cardiovasc Med 2020; 7:94. [PMID: 32671098 PMCID: PMC7326051 DOI: 10.3389/fcvm.2020.00094] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 04/30/2020] [Indexed: 12/14/2022] Open
Abstract
The cause of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology studies support that an infectious disease is involved in at least starting the inflammatory cascade set off during KD. Clues from epidemiology support that humoral immunity can have a protective effect. However, the role of the immune system, particularly of B cells and antibodies, in pathogenesis of KD is still unclear. Intravenous immunoglobulin (IVIG) and other therapies targeted at modulating inflammation can prevent development of coronary aneurysms. A number of autoantibody responses have been reported in children with KD and antibodies have been generated from aneurysmal plasma cell infiltrates. Recent reports show that children with KD have similar plasmablast responses as other children with infectious diseases, further supporting an infectious starting point. As ongoing studies are attempting to identify the etiology of KD through study of antibody responses, we sought to review the role of humoral immunity in KD pathogenesis, treatment, and recovery.
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Affiliation(s)
- Mark Daniel Hicar
- University at Buffalo, Buffalo, NY, United States.,John R. Oishei Children's Hospital, Buffalo, NY, United States.,Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
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14
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Complete Regression of Giant Aneurysms in an Infant with Delayed Diagnosis and Refractory Kawasaki Disease via Combination Anticytokine Therapy: Case Report and Review of Similar Cases. Case Rep Rheumatol 2020; 2020:6249013. [PMID: 32280552 PMCID: PMC7142349 DOI: 10.1155/2020/6249013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 02/13/2020] [Accepted: 02/20/2020] [Indexed: 11/25/2022] Open
Abstract
Background Kawasaki disease (KD) is an inflammatory vasculitis and is the most common cause of acquired childhood heart disease in developed countries. Current treatment with intravenous immunoglobulin (IVIG) is often ineffective in patients with delayed or refractory disease. We present a case of combination anticytokine therapy in an infant with delayed and refractory KD. Case Presentation. A 3-month-old infant presented with refractory KD with giant aneurysms after a delayed diagnosis of one month. Use of combination anticytokine therapy led to resolution of giant aneurysms over approximately 6 months. Conclusions Our case is unique in effective use of anticytokine therapy in very delayed disease with giant aneurysms. Additionally, we review other cases for a broader perspective. Prospective study of anticytokine therapy for patients with giant aneurysms may be warranted.
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15
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Platt B, Belarski E, Manaloor J, Ofner S, Carroll AE, John CC, Wood JB. Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin. JAMA Netw Open 2020; 3:e1918565. [PMID: 31899532 PMCID: PMC6991313 DOI: 10.1001/jamanetworkopen.2019.18565] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
IMPORTANCE Timely initiation of intravenous immunoglobulin plus aspirin is necessary for decreasing the risk of recrudescent fever and coronary artery abnormalities in children with Kawasaki disease (KD). The optimal dose of aspirin, however, remains unclear. OBJECTIVE To evaluate whether initial treatment with low-dose compared with high-dose aspirin in children with KD is associated with an increase in fever recrudescence. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 260 children with KD at Riley Hospital for Children, Indianapolis, Indiana, between January 1, 2007, and December 31, 2018, was conducted. Children aged 0 to 18 years with a first episode of KD, identified by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes treated within 10 days of symptom onset with high-dose intravenous immunoglobulin plus aspirin were eligible. Patients who received an alternative diagnosis, experienced a second episode of KD, did not receive intravenous immunoglobulin plus aspirin for initial treatment, were not treated within 10 days of symptoms, or had incomplete records were excluded. EXPOSURES High-dose (≥10 mg/kg/d) or low-dose (<10 mg/kg/d) aspirin therapy. MAIN OUTCOMES AND MEASURES The primary outcome was recrudescent fever necessitating retreatment of KD. The secondary outcomes were coronary artery abnormalities and hospital length of stay. RESULTS Among the 260 patients included, the median (interquartile range) age was 2.5 (1.6-4.3) years, 103 (39.6%) were girls, 166 (63.8%) were non-Hispanic white, 57 (21.9%) were African American, 22 (8.5%) were Asian, 11 (4.2%) were Hispanic, and 4 (1.5%) were of unknown race/ethnicity. One hundred-forty-two patients (54.6%) were treated with low-dose aspirin. There was no association between recrudescent fever and aspirin dose, with 39 children (27.5%) having recrudescent fever in the low-dose group compared with 26 children (22.0%) in the high-dose group (odds ratio [OR], 1.34; 95% CI, 0.76-2.37; P = .31), with similar results after adjusting for potential confounding variables (OR, 1.63; 95% CI, 0.89-2.97; P = .11). In a subset analysis of 167 children with complete KD, however, there was nearly a 2-fold difference in the odds of recrudescent fever with low-dose aspirin (OR, 1.87; 95% CI, 0.82-4.23; P = .14), although this difference did not reach statistical significance. In addition, no association was identified between treatment group and coronary artery abnormalities (low-dose, 7.4% vs high-dose, 9.4%; OR, 0.86; 95% CI, 0.48-1.55; P = .62) or median (interquartile range) length of stay (3 [3-5] days for both groups; P = .27). CONCLUSIONS AND RELEVANCE In this study, low-dose aspirin for the initial treatment of children with KD was not associated with fever recrudescence or coronary artery abnormalities. Given the potential benefits, further study of low-dose aspirin to detect potentially clinically relevant outcome differences is warranted to inform treatment decisions and guideline development.
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Affiliation(s)
- Brooks Platt
- Indiana University School of Medicine, Indianapolis
| | | | - John Manaloor
- Indiana University School of Medicine, Indianapolis
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis
| | - Susan Ofner
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis
| | - Aaron E. Carroll
- Indiana University School of Medicine, Indianapolis
- Center for Pediatric and Adolescent Comparative Effectiveness Research, Indiana University School of Medicine, Indianapolis
| | - Chandy C. John
- Indiana University School of Medicine, Indianapolis
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis
| | - James B. Wood
- Indiana University School of Medicine, Indianapolis
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis
- Center for Pediatric and Adolescent Comparative Effectiveness Research, Indiana University School of Medicine, Indianapolis
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16
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Arnold KA, Gao J, Stein SL. A review of cutaneous hypersensitivity reactions in infants: From common to concerning. Pediatr Dermatol 2019; 36:274-282. [PMID: 31025427 PMCID: PMC7167752 DOI: 10.1111/pde.13827] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cutaneous hypersensitivity reactions in infants present in a variety of patterns. These skin eruptions can be dramatic, causing alarm in parents and medical personnel. Many of these syndromes have overlapping features, which adds to the confusion and uncertainty regarding diagnosis and management. This review discusses the spectrum of hypersensitivity responses with a focus on their presentation in infants. The clinical findings, pathophysiology, histopathology, management, and complications of these conditions will be reviewed.
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Affiliation(s)
- Kathryn A Arnold
- University of Chicago Pritzker School of Medicine, Chicago, Illinois
| | - Jingyun Gao
- Section of Dermatology, Department of Medicine and Pediatrics, University of Chicago, Chicago, Illinois
| | - Sarah L Stein
- Section of Dermatology, Department of Medicine and Pediatrics, University of Chicago, Chicago, Illinois
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17
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Lindquist ME, Hicar MD. B Cells and Antibodies in Kawasaki Disease. Int J Mol Sci 2019; 20:ijms20081834. [PMID: 31013925 PMCID: PMC6514959 DOI: 10.3390/ijms20081834] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/09/2019] [Accepted: 04/11/2019] [Indexed: 12/22/2022] Open
Abstract
The etiology of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology supports a relationship of KD to an infectious disease. Several pathological mechanisms are being considered, including a superantigen response, direct invasion by an infectious etiology or an autoimmune phenomenon. Treating affected patients with intravenous immunoglobulin is effective at reducing the rates of coronary aneurysms. However, the role of B cells and antibodies in KD pathogenesis remains unclear. Murine models are not clear on the role for B cells and antibodies in pathogenesis. Studies on rare aneurysm specimens reveal plasma cell infiltrates. Antibodies generated from these aneurysmal plasma cell infiltrates showed cross-reaction to intracellular inclusions in the bronchial epithelium of a number of pathologic specimens from children with KD. These antibodies have not defined an etiology. Notably, a number of autoantibody responses have been reported in children with KD. Recent studies show acute B cell responses are similar in children with KD compared to children with infections, lending further support of an infectious disease cause of KD. Here, we will review and discuss the inconsistencies in the literature in relation to B cell responses, specific antibodies, and a potential role for humoral immunity in KD pathogenesis or diagnosis.
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Affiliation(s)
- Michael E Lindquist
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
| | - Mark D Hicar
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14222, USA.
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18
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Chen Y, Hua Y, Zhang C, Chen S, Zhang Q, Liao Y, Yan H, Wang Y, Liu P, Qi J, Liu X, Chen Y, Tang C, Jin H, Du J. Neutrophil-to-Lymphocyte Ratio Predicts Intravenous Immunoglobulin-Resistance in Infants Under 12-Months Old With Kawasaki Disease. Front Pediatr 2019; 7:81. [PMID: 30941338 PMCID: PMC6433842 DOI: 10.3389/fped.2019.00081] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/26/2019] [Indexed: 12/15/2022] Open
Abstract
Objective: We evaluated the ability of peripheral blood neutrophil-to-lymphocyte ratio (NLR) to predict the intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) patients under 1-year of age. Methods: A total of 92 KD patients under the age of 1-year and who were hospitalized in Peking University First Hospital from June 2007 to August 2016 were recruited in this study. The clinical and laboratory data were analyzed to see if peripheral blood NLR was useful for predicting the IVIG-resistance in KD. Results: Totally 81 out of 92 patients were IVIG responders while 11 resistant to IVIG, with no significant difference in age, gender, ratio of the number of the incomplete to the number of complete KD, and the number of patients with coronary artery lesion between two groups (p > 0.05). Peripheral blood NLR was increased significantly in IVIG-resistant children compared to the IVIG responders [2.6 (interquartile range: 1.4, 3.8) vs. 1.7 (interquartile range: 0.9, 2.3), p = 0.039]. A cut-off value of NLR of 2.51 in KD patients younger than 1-year old yielded a sensitivity of 0.545 and specificity of 0.840, respectively, in the prediction of IVIG resistance. An area under the curve of 0.692 (95% confidence interval 0.526-0.859, p = 0.039) was determined. Conclusions: The peripheral blood NLR ≥ 2.51 is useful to predict the IVIG resistance in KD patients younger than 1-year old.
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Affiliation(s)
- Yongbing Chen
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Ying Hua
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Chunyu Zhang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Selena Chen
- Division of Biological Sciences, University of California, San Diego, San Diego, CA, United States
| | - Qingyou Zhang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Ying Liao
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Hui Yan
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Yuli Wang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Ping Liu
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Jianguang Qi
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Xueqin Liu
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Yonghong Chen
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Chaoshu Tang
- Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China
| | - Hongfang Jin
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Junbao Du
- Department of Pediatrics, Peking University First Hospital, Beijing, China.,Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China
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19
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Pilania RK, Bhattarai D, Singh S. Controversies in diagnosis and management of Kawasaki disease. World J Clin Pediatr 2018; 7:27-35. [PMID: 29456929 PMCID: PMC5803562 DOI: 10.5409/wjcp.v7.i1.27] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/13/2017] [Accepted: 12/28/2017] [Indexed: 02/06/2023] Open
Abstract
Kawasaki disease (KD) is a common medium vessel systemic vasculitis that usually occurs in small children. It has a predilection for the coronary arteries, but other medium sized arteries can also be involved. The etiology of this disorder remains a mystery. Though typical presentation of KD is quite characteristic, it may also present as incomplete or atypical disease in which case the diagnosis can be very challenging. As both incomplete and atypical forms of KD can be associated with serious coronary artery complications, the pediatrician can ill afford to miss these diagnoses. The American Heart Association has enunciated consensus guidelines to facilitate the clinical diagnosis and treatment of this condition. However, there are still several issues that remain controversial. Intravenous immunoglobulin remains the cornerstone of management but several other treatment modalities, especially glucocorticoids, are increasingly finding favour. We review here some of the contemporary issues, and the controversies thereon, pertaining to management of KD.
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Affiliation(s)
- Rakesh Kumar Pilania
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Dharmagat Bhattarai
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Surjit Singh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
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20
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Mărginean CO, Meliț LE, Gozar L, Mărginean CD, Mărginean MO. Incomplete Refractory Kawasaki Disease in an Infant-A Case Report and a Review of the Literature. Front Pediatr 2018; 6:210. [PMID: 30101141 PMCID: PMC6074057 DOI: 10.3389/fped.2018.00210] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 07/09/2018] [Indexed: 12/23/2022] Open
Abstract
Kawasaki disease (KD) is a febrile vasculitis, which is commonly defined by fever and at least four specific clinical symptoms. Incomplete KD is defined by suggestive echocardiographic findings with an incomplete clinical picture. Refractory KD is diagnosed in patients resistant to intravenous immunoglobulin (IVIG). We report the case of a 6-month-old male infant admitted to our clinic for persistent fever and onset of a generalized polymorphous rash, accompanied by high fever, rhinorrhea, and cough for the past 7 days. The laboratory tests, on the day of admission, revealed leukocytosis with neutrophilia, anemia, thrombocytosis, hypernatremia, hypoalbuminemia, elevated C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Echocardiography showed dilation of the left anterior descending coronary artery (LAD). Based on all these findings, we established the diagnosis of KD, and we initiated IVIG and intravenous pulsed methylprednisolone, with an initial favorable outcome. However, the symptoms reappeared, and we administered a second higher single dose of IVIG, but without any clinical improvement. Moreover, the laboratory parameters and echocardiographic findings worsened. We reinitiated a longer course of intravenous methylprednisolone in a smaller dose, which had a favorable impact on the clinical, laboratory, and echocardiographic parameters. Multiple uncertainties exist related to the management of refractory KD despite the wide spectrum of therapeutic options that have been proposed. Our case demonstrates that in patients refractory to aggressive initial therapy, low or moderate doses of steroid given daily may be helpful.
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Affiliation(s)
- Cristina O Mărginean
- Department of Pediatrics, University of Medicine and Pharmacy TîrguMures, Târgu Mures, Romania
| | - Lorena E Meliț
- Department of Pediatrics, University of Medicine and Pharmacy TîrguMures, Târgu Mures, Romania
| | - Liliana Gozar
- Department of Pediatric Cardiology, University of Medicine and Pharmacy TîrguMures, Târgu Mures, Romania
| | - Cristian Dan Mărginean
- Department of Pediatrics, University of Medicine and Pharmacy TîrguMures, Târgu Mures, Romania
| | - Maria O Mărginean
- Department of Pediatrics, University of Medicine and Pharmacy TîrguMures, Târgu Mures, Romania
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21
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A Case of Kawasaki Disease With Severe Lip and Oral Mucosa Involvement Complicated With Microstomia and Corrected With Surgery. Arch Rheumatol 2017; 33:238-240. [PMID: 30207579 DOI: 10.5606/archrheumatol.2018.6434] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 08/31/2017] [Indexed: 11/21/2022] Open
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22
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Okuzaki D, Ota K, Takatsuki SI, Akiyoshi Y, Naoi K, Yabuta N, Saji T, Nojima H. FCN1 (M-ficolin), which directly associates with immunoglobulin G1, is a molecular target of intravenous immunoglobulin therapy for Kawasaki disease. Sci Rep 2017; 7:11334. [PMID: 28900133 PMCID: PMC5595863 DOI: 10.1038/s41598-017-11108-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 08/18/2017] [Indexed: 12/26/2022] Open
Abstract
Kawasaki disease (KD), an acute systemic vasculitis of early childhood, is of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is an effective treatment, but its molecular target remains elusive. DNA microarray analysis of peripheral blood mononuclear cells (PBMCs) revealed that at least 21 genes are drastically down-regulated after IVIG treatment in most KD patients. qRT-PCR analysis confirmed that the mRNA levels of five of these genes were considerably reduced in almost all KD patients after IVIG treatment. Western blot (Wb) of PBMC extracts revealed that levels of FCN1 (M-ficolin), a protein of the complement system that defends against infectious agents, were reduced after IVIG treatment in many KD patients. In another set of KD patients, Wb confirmed that levels of both FCN1 were greatly reduced after IVIG therapy. Wb revealed that the collagen-like domain of FCN1 directly bound to IgG1 in vitro through a portion of the CH1 and CH3 domains, and synthetic peptides corresponding to these domains of IgG1 efficiently inhibited these associations. These results suggest that FCN1 is a molecular target of intravenous IVIG in KD patients. We propose that these peptides and a humanized monoclonal antibody against FCN1 could be useful in combination therapy with IVIG.
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Affiliation(s)
- Daisuke Okuzaki
- DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kaori Ota
- Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shin-Ichi Takatsuki
- Department of Pediatrics, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ohta, Tokyo, 143-8541, Japan
| | - Yukari Akiyoshi
- Fukae Kasei Co., Ltd., 2-2-7 Murotani, Nishi-ku, Kobe, Hyogo, 651-2241, Japan
| | - Kazuyuki Naoi
- Department of Pediatrics, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ohta, Tokyo, 143-8541, Japan
| | - Norikazu Yabuta
- Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Tsutomu Saji
- Department of Pediatrics, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ohta, Tokyo, 143-8541, Japan.
| | - Hiroshi Nojima
- DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
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23
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Telcharova-Mihaylovska A, Nikolova I, Marinov R, Stefanov S, Gaidarova M, Ganeva M, Temelkova K. Kawasaki disease – experience of Pediatric University Hospital, Sofia, Bulgaria, 1993–2014. Part II: cardiovascular manifestations and treatment. BIOTECHNOL BIOTEC EQ 2017. [DOI: 10.1080/13102818.2017.1347522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Albena Telcharova-Mihaylovska
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Irina Nikolova
- Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
| | - Rumen Marinov
- Department of Pediatric Cardiology, National Cardiology Hospital, Sofia, Bulgaria
| | - Stefan Stefanov
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Maria Gaidarova
- Clinic of Nephrology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Margarita Ganeva
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Katya Temelkova
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
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Abstract
Cutaneous vasculitis, inflammatory destruction of blood vessels, can present with a wide range of clinical and pathologic findings across a number of heterogeneous conditions. Although some vasculitides are present in both children and adults, some important differences exist in clinical presentation, etiology, management, and prognosis in childhood vasculitis versus adult vasculitis. Cutaneous vasculitis is rare in children, and most childhood vasculitides, of which Henoch-Schönlein purpura is the most common, histologically are small vessel leukocytoclastic vasculitis. In children, infectious etiologies are more common than in adults. Childhood cutaneous vasculitis is most often self-limited with a good prognosis, and treatment is mainly supportive. © 2017 Elsevier Inc. All rights reserved.
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Affiliation(s)
- Nikita Lakdawala
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI.
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An atypical case of a 2-year-old boy with acute kidney injury: a race against time. Answers. Pediatr Nephrol 2017; 32:1177-1179. [PMID: 27704255 DOI: 10.1007/s00467-016-3516-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 08/31/2016] [Accepted: 09/01/2016] [Indexed: 02/07/2023]
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Saviour MJ, Hassan S. Kawasaki Disease Presenting with Bloody Diarrhea and Acute Renal Failure: First Case. Pediatr Rep 2017; 9:7163. [PMID: 28706619 PMCID: PMC5494447 DOI: 10.4081/pr.2017.7163] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 06/06/2017] [Accepted: 06/08/2017] [Indexed: 01/12/2023] Open
Abstract
Kawasaki disease (KD) is an acute febrile vasculitis of an unknown cause. It affects children <5 year of age, even if cases over 5 years old have been also reported. It is the commonest cause of acquired heart diseases in children which may lead to serious morbidity and mortality. The complications and mortality increase when the diagnosis is delayed. One of the main reasons leading to delayed diagnosis and consequent delayed treatment is the unusual presentation of KD. Its unusual manifestations have been increasingly reported to jeopardize the timely diagnosis and proper treatment. As there is not yet available blood test to diagnose it, low threshold should be taken into account for considering KD, when the clinical criteria are not typical. KD with renal manifestations is infrequently described. We present and discuss a case of an unusual presentation of KD presenting as bloody diarrhea and acute renal failure.
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Affiliation(s)
| | - Sam Hassan
- Mediclinic City Hospital, Dubai Health Care City, Dubai, United Arab Emirates
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27
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Dallaire F, Fortier-Morissette Z, Blais S, Dhanrajani A, Basodan D, Renaud C, Mathew M, De Souza AM, Dionne A, Blanchard J, Saulnier H, Kaspy K, Rached-d'Astous S, Dahdah N, McCrindle BW, Human DG, Scuccimarri R. Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease. Pediatrics 2017; 139:peds.2017-0098. [PMID: 28562282 DOI: 10.1542/peds.2017-0098] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/20/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3-5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: -4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was -1.9% (95% CI: -5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.
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Affiliation(s)
- Frederic Dallaire
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre de recherche du centre hospitalier universitaire de Sherbrooke, University of Sherbrooke, Sherbrooke, Canada;
| | - Zoe Fortier-Morissette
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre de recherche du centre hospitalier universitaire de Sherbrooke, University of Sherbrooke, Sherbrooke, Canada
| | - Samuel Blais
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre de recherche du centre hospitalier universitaire de Sherbrooke, University of Sherbrooke, Sherbrooke, Canada
| | | | - Dania Basodan
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | - Claudia Renaud
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | - Mathew Mathew
- Labatt Family Heart Center, The Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, Canada; and
| | - Astrid M De Souza
- Cardiology, Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, Canada
| | - Audrey Dionne
- Division of Pediatric Cardiology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
| | - Joel Blanchard
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre de recherche du centre hospitalier universitaire de Sherbrooke, University of Sherbrooke, Sherbrooke, Canada
| | - Harrison Saulnier
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | - Kimberley Kaspy
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
| | - Soha Rached-d'Astous
- Division of Pediatric Cardiology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
| | - Nagib Dahdah
- Division of Pediatric Cardiology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
| | - Brian W McCrindle
- Labatt Family Heart Center, The Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, Canada; and
| | - Derek G Human
- Cardiology, Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, Canada
| | - Rosie Scuccimarri
- Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Canada
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Matiz Mejía S, Ariza Correa C, Salinas Suárez C, Huertas Quiñones M, Sanguino Lobo R. Enfermedad de Kawasaki. REVISTA COLOMBIANA DE CARDIOLOGÍA 2017. [DOI: 10.1016/j.rccar.2016.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Engelberg R, Martin M, Wrotniak BH, Hicar MD. Observational study of Interleukin-21 (IL-21) does not distinguish Kawasaki disease from other causes of fever in children. Pediatr Rheumatol Online J 2017; 15:32. [PMID: 28427414 PMCID: PMC5397673 DOI: 10.1186/s12969-017-0163-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Accepted: 04/11/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Kawasaki disease (KD) is a febrile childhood vasculitis of unknown etiology. The diagnosis is highly concerning as over a quarter of children who fail to receive timely treatment with intravenous immunoglobulin (IVIG) will develop coronary aneurysms. Diagnosis relies on proper symptomatology and is supported by non-specific markers of inflammation. Previous studies have identified elevated plasma levels of interleukin-21 (IL-21) as a sensitive and specific biomarker in KD. The aim of this study is to assess the validity of IL-21 as a diagnostic biomarker for KD in febrile children in North America. METHODS Plasma samples were collected from children who presented to an urban Emergency Department in North America. IL-21 levels were measured using commercial ELISA kits in 12 KD versus 60 controls subjects. RESULTS Our study shows that IL-21 levels were non-specifically elevated across all febrile children, irrespective of KD diagnosis. Length of fever prior to sample collection does not correlate with IL-21 levels. Other inflammatory markers and laboratory values were also compared to IL-21 and show no significant correlation. CONCLUSIONS Since IL-21 is elevated non-specifically in this cohort, our data supports that IL-21 is not an appropriate biomarker for diagnosis of KD in North American pediatric populations.
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Affiliation(s)
- Rachel Engelberg
- 0000 0004 1936 9887grid.273335.3Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY USA
| | - Meghan Martin
- 0000 0004 1936 9887grid.273335.3Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY USA ,0000 0004 1936 9887grid.273335.3Department of Pediatrics, University at Buffalo, Buffalo, NY USA
| | - Brian H. Wrotniak
- 0000 0004 1936 9887grid.273335.3Department of Pediatrics, University at Buffalo, Buffalo, NY USA
| | - Mark Daniel Hicar
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA. .,Department of Pediatrics, University at Buffalo, Buffalo, NY, USA.
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30
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Telcharova-Mihaylovska A, Nikolova I, Marinov R, Stefanov S, Gaidarova M, Ganeva M, Temelkova K. Kawasaki disease – experience of Pediatric University Hospital, Sofia, Bulgaria, 1993–2014. Part I: clinical manifestations. BIOTECHNOL BIOTEC EQ 2017. [DOI: 10.1080/13102818.2017.1316683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Kawasaki Disease and Exposure to Fine Particulate Air Pollution. J Pediatr 2016; 177:179-183.e1. [PMID: 27496266 DOI: 10.1016/j.jpeds.2016.06.061] [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: 02/24/2016] [Revised: 05/25/2016] [Accepted: 06/17/2016] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To analyze associations of short-term exposure to fine particulate matter (diameter ≤ 2.5 µm [PM2.5]), a measurable component of urban pollution, with the event date of fever onset for patients with Kawasaki disease (KD) residing in 7 metropolitan regions. STUDY DESIGN A case-crossover study design was used. Time trends, seasonality, month, and weekday were controlled for by matching. We assembled PM2.5 exposure measurements from urban monitors and imputed PM2.5 to provide day-to-day temporal variability and resolution for time series indexes of exposures. Selected exposure windows (to 14 days) of PM2.5 were examined. RESULTS A total of 3009 KD events were included for which the subject resided within a study metropolitan area and the event date occurred during years with available PM2.5. The estimated ORs (with 95% CIs) of an event of KD associated with a 10 µg/m(3) PM2.5 lagged moving average concentration of lagged exposure period (ie, concurrent, preceding day[s]) revealed no evidence of a consistent, statistically significant, positive association between elevated PM2.5 exposure and increased risk of KD. Extended analysis with stratification by city, sex, age, ethnic origin, incomplete or complete clinical manifestations, the presence of coronary aneurysm, and intravenous immunoglobulin resistance did not provide evidence of a consistent, statistically significant, positive association between elevated exposure to PM2.5 and increased risk of KD for any of the strata studied. CONCLUSIONS This multicity study failed to establish a risk of the event of KD with short-term fine particulate exposure. Our negative findings add to the growing field of environmental epidemiology research of KD.
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Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies. Expert Rev Clin Immunol 2016; 13:247-258. [PMID: 27590181 DOI: 10.1080/1744666x.2017.1232165] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Kawasaki disease is an acute febrile systemic vasculitis that predominantly occurs in children below five years of age. Its etiopathogenesis is still not clear, but it is thought to be a complex interplay of genetic factors, infections and immunity. Areas covered: This review article discusses in detail Kawasaki disease, with particular emphasis on the recent updates on its pathogenesis and upcoming alternate treatment options. Though self-limiting in many cases, it can lead to severe complications like coronary artery aneurysms and thrombo-embolic occlusions, and hence requires early diagnosis and urgent attention to avoid them. Intravenous immunoglobulin (IVIG) with or without aspirin has remained the sole treatment option for these cases, but 10-15% cases develop resistance to this treatment. Expert commentary: There is a need to develop additional treatment strategies for children with Kawasaki disease. Targeting different steps of pathogenesis could provide us with alternate therapeutic options.
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Affiliation(s)
- Shreya Agarwal
- a Department of Clinical & Translational Science , Creighton University School of Medicine , Omaha , NE , USA
| | - Devendra K Agrawal
- a Department of Clinical & Translational Science , Creighton University School of Medicine , Omaha , NE , USA
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Johnston N, Snow A, McMahon CJ. Unexpected coronary arterial calcification and thrombosis late after Kawasaki disease. BMJ Case Rep 2016; 2016:bcr-2016-216451. [PMID: 27402589 DOI: 10.1136/bcr-2016-216451] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Affiliation(s)
- Niall Johnston
- Department of Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
| | - Aisling Snow
- Department of Radiology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
| | - Colin J McMahon
- Department of Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland University College Dublin, Dublin, Ireland
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Abstract
Aspirin has been one of the oldest drugs in the field of medicine, with a wide range of applications. In dermatology, aspirin has shown benefit in a variety of disorders. Recently, reduction of melanoma risk with aspirin has been demonstrated. Although an analgesic to begin with, aspirin has come a long way; after cardiology, it is now found to be useful even in dermatology.
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Affiliation(s)
- Aditya Kumar Bubna
- Department of Dermatology, Sri Ramachandra University, Chennai, Tamil Nadu, India
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35
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Ding Y, Li G, Xiong LJ, Yin W, Liu J, Liu F, Wang RG, Xia K, Zhang SL, Zhao L. Profiles of responses of immunological factors to different subtypes of Kawasaki disease. BMC Musculoskelet Disord 2015; 16:315. [PMID: 26497060 PMCID: PMC4619387 DOI: 10.1186/s12891-015-0744-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 10/01/2015] [Indexed: 12/31/2022] Open
Abstract
Background The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood. Methods We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry. Results The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections. Conclusions Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD.
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Affiliation(s)
- Yan Ding
- Department of Rheumatology and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, P.R. China.
| | - Gang Li
- Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, P.R. China.
| | - Li-Juan Xiong
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China.
| | - Wei Yin
- Department of Rheumatology and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, P.R. China.
| | - Jie Liu
- Department of Critical-Care Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, P.R. China.
| | - Fan Liu
- Department of Rheumatology and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, P.R. China.
| | - Rui-Geng Wang
- Department of Rheumatology and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, P.R. China.
| | - Kun Xia
- Department of Rheumatology and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, P.R. China.
| | - Shu-Ling Zhang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China.
| | - Lei Zhao
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, P.R. China.
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Watanabe T. Pyuria in patients with Kawasaki disease. World J Clin Pediatr 2015; 4:25-29. [PMID: 26015877 PMCID: PMC4438438 DOI: 10.5409/wjcp.v4.i2.25] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 01/08/2015] [Accepted: 02/04/2015] [Indexed: 02/06/2023] Open
Abstract
Kawasaki disease (KD) is an acute, febrile vasculitis that predominantly develops in children ≤ 5 years of age and can lead to multiple organ injuries including the kidneys. Of these injuries, pyuria is a common feature of patients with KD, occurring in 30%-80% of patients. Sterile pyuria is most common in KD patients ≤ 1 year of age. KD patients with sterile pyuria exhibit more severe inflammatory reactions and may have sub-clinical renal injuries. Sterile pyuria in KD is associated with mononuclear cells (not neutrophils) in the urine. Although sterile pyuria in KD was at one time thought to be due to urethritis caused by a non-specific vasculitis of the urethra, recent studies suggest that sterile pyuria in KD originates from the urethra, the kidney as a result of mild and sub-clinical renal injuries, and/or the bladder due to cystitis. Pyuria is not always sterile in KD, but can result from a urinary tract infection (UTI). As causative pathogens, Escherichia coli and Klebsiella oxytoca have been reported. The clinical phenotypes do not differ between those with or without UTI. Because some KD patients with UTIs have urinary tract abnormalities such as vesicoureteral reflux, a complete UTI workup including renal ultrasound, voiding cystourethrogram and/or dimercaptosuccinic acid renal scan recommended in KD patients with UTIs.
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Sotelo-Cruz N. [A review of Kawasaki disease, a perspective from the articles published in Mexico since January 1977 to May 2012]. ARCHIVOS DE CARDIOLOGIA DE MEXICO 2015; 83:214-22. [PMID: 23663892 DOI: 10.1016/j.acmx.2013.02.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Revised: 01/23/2013] [Accepted: 02/01/2013] [Indexed: 11/24/2022] Open
Abstract
Kawasaki disease was described in 1967 by Tomisu Kawasaki. It affects children aged between one and 5 years, and it evolves with fever and small vessel vasculitis, which leads to cardiovascular complications, including coronary aneurisms, myocarditis, valve injuries, pericardial effusion and myocardial infarction; eventually involving many others organs. The etiology actually is not well known, as the exactly pathogenic mechanisms; however, now there are important advances. If the clinical signs and symptoms are identify early and the children received treatment with aspirin and intravenous immunoglobulin, the patients evolves without sequels. The Kawasaki disease is an infrequent disease in Mexico.
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Affiliation(s)
- Norberto Sotelo-Cruz
- Departamento de Medicina y Ciencias de la Salud, Universidad de Sonora, Hermosillo, Sonora, México.
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Abstract
Kawasaki Disease, a systemic vasculitis of unknown origin with specific predilection for the coronary arteries, is the most common cause of childhood-acquired heart disease in western countries. Despite its world-wide incidence, the pathophysiology of this enigmatic disease is still under investigation. Diagnosis is made on a clinical basis, with supportive laboratory evidence and imaging. Once identified, timely initiation of treatment is imperative in order to quell the inflammatory response and decrease the incidence of long-term sequelae, specifically coronary artery aneurysms. Finally, longitudinal follow-up should be implemented based on risk stratification and individualized to each patient.
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Chen Y, Li X, Boini KM, Pitzer AL, Gulbins E, Zhang Y, Li PL. Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2014; 1853:396-408. [PMID: 25450976 DOI: 10.1016/j.bbamcr.2014.11.012] [Citation(s) in RCA: 83] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/05/2014] [Accepted: 11/10/2014] [Indexed: 12/20/2022]
Abstract
Inflammasomes play a critical role in the development of vascular diseases. However, the molecular mechanisms activating the inflammasome in endothelial cells and the relevance of this inflammasome activation is far from clear. Here, we investigated the mechanisms by which an Nlrp3 inflammasome is activated to result in endothelial dysfunction during coronary arteritis by Lactobacillus casei (L. casei) cell wall fragments (LCWE) in a mouse model for Kawasaki disease. Endothelial dysfunction associated with increased vascular cell adhesion protein 1 (VCAM-1) expression and endothelial-leukocyte adhesion was observed during coronary arteritis in mice treated with LCWE. Accompanied with these changes, the inflammasome activation was also shown in coronary arterial endothelium, which was characterized by a marked increase in caspase-1 activity and IL-1β production. In cultured endothelial cells, LCWE induced Nlrp3 inflammasome formation, caspase-1 activation and IL-1β production, which were blocked by Nlrp3 gene silencing or lysosome membrane stabilizing agents such as colchicine, dexamethasone, and ceramide. However, a potassium channel blocker glibenclamide or an oxygen free radical scavenger N-acetyl-l-cysteine had no effects on LCWE-induced inflammasome activation. LCWE also increased endothelial cell lysosomal membrane permeability and triggered lysosomal cathepsin B release into cytosol. Silencing cathepsin B blocked LCWE-induced Nlrp3 inflammasome formation and activation in endothelial cells. In vivo, treatment of mice with cathepsin B inhibitor also abolished LCWE-induced inflammasome activation in coronary arterial endothelium. It is concluded that LCWE enhanced lysosomal membrane permeabilization and consequent release of lysosomal cathepsin B, resulting in activation of the endothelial Nlrp3 inflammasome, which may contribute to the development of coronary arteritis.
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Affiliation(s)
- Yang Chen
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Xiang Li
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Krishna M Boini
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Ashley L Pitzer
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
| | - Erich Gulbins
- Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany
| | - Yang Zhang
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
| | - Pin-Lan Li
- Department of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
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Watanabe T. Kawasaki Disease with Retropharyngeal Edema following a Blackfly Bite. Case Rep Pediatr 2014; 2014:296456. [PMID: 25349761 PMCID: PMC4202199 DOI: 10.1155/2014/296456] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 09/24/2014] [Accepted: 09/24/2014] [Indexed: 11/18/2022] Open
Abstract
We describe a patient with Kawasaki disease (KD) and retropharyngeal edema following a blackfly bite. An 8-year-old boy was referred to our hospital because of a 3-day-history of fever and left neck swelling and redness after a blackfly bite. Computed tomography of the neck revealed left cervical lymph nodes swelling with edema, increased density of the adjacent subcutaneous tissue layer, and low density of the retropharyngeum. The patient was initially presumed to have cervical cellulitis, lymphadenitis, and retropharyngeal abscess. He was administered antibiotics intravenously, which did not improve his condition. The patient subsequently exhibited other signs of KD and was diagnosed with KD and retropharyngeal edema. Intravenous immunoglobulin therapy and oral flurbiprofen completely resolved the symptoms and signs. A blackfly bite sometimes incites a systemic reaction in humans due to a hypersensitive reaction to salivary secretions, which may have contributed to the development of KD in our patient.
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Affiliation(s)
- Toru Watanabe
- Department of Pediatrics, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata 950-1197, Japan
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41
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Kawasaki disease is associated with sensorineural hearing loss: a systematic review. Int J Pediatr Otorhinolaryngol 2014; 78:1216-20. [PMID: 24951399 DOI: 10.1016/j.ijporl.2014.05.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Revised: 05/19/2014] [Accepted: 05/20/2014] [Indexed: 11/21/2022]
Abstract
CONTEXT Kawasaki Disease (KD), a systemic vasculitis of unknown etiology, has been associated with the development of sensorineural hearing loss (SNHL). KD is primarily a disease of young children, who are the most susceptible to complications from even minimal hearing loss. If there is a connection between KD and the development of SNHL, a better understanding of this relationship may improve our management of this disease and its complications. OBJECTIVE To perform a systematic review according to a standardized guideline to evaluate the possible association between KD and SNHL. DATA SOURCES Medline and PubMed online databases were reviewed for appropriate articles. STUDY SELECTION All studies available in English discussing KD and SNHL were included. DATA EXTRACTION Studies were assessed primarily for the incidence of SNHL. Where possible, they were assessed for the degree and laterality of the loss, length of follow up and change in hearing over time. RESULTS 8 studies meeting the criteria were assessed. 3 were case reports, 1 was a case series and the remaining 4 were prospective control trials. 8 patients have been reported as cases, and 240 assessed in PCT. 36% of patients assessed had some degree of SNHL, and overall 14% had evidence of persistent SNHL at follow up. CONCLUSIONS This systematic review would suggest there is an association between KD and SNHL. It is important for physicians caring for patients with KD to be aware of this complication and consider screening these patients given possible complications of hearing loss in this age group.
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Bayers S, Shulman ST, Paller AS. Kawasaki disease: part I. Diagnosis, clinical features, and pathogenesis. J Am Acad Dermatol 2013; 69:501.e1-11; quiz 511-2. [PMID: 24034379 DOI: 10.1016/j.jaad.2013.07.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Revised: 06/30/2013] [Accepted: 07/09/2013] [Indexed: 02/07/2023]
Abstract
Kawasaki disease, or mucocutaneous lymph node syndrome, most commonly affects children between 6 months and 5 years of age. Approximately 90% of patients have mucocutaneous manifestations. This article will focus on the epidemiology of Kawasaki disease in the United States as it relates to other countries, the diagnosis of Kawasaki disease, its clinical course, and the currently accepted theories of pathogenesis. A particular focus is given to the various dermatologic manifestations that may occur.
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Affiliation(s)
- Stephanie Bayers
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Magnetic resonance angiography of the pediatric abdomen and pelvis: techniques and imaging findings. Magn Reson Imaging Clin N Am 2013; 21:843-60. [PMID: 24183529 DOI: 10.1016/j.mric.2013.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Although traditional catheter-based angiography has been the gold standard for pediatric abdominal and pelvic vascular imaging for the past several decades, advances in magnetic resonance angiography (MRA) have made it a viable alternative. MRA offers several advantages in that it is noninvasive, can be performed without ionizing radiation, and does not necessarily rely on contrast administration. The ability of modern MRA techniques to define variant vascular anatomy and detect vascular disease may obviate traditional angiography in some patients.
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Watanabe T. Kidney and urinary tract involvement in kawasaki disease. Int J Pediatr 2013; 2013:831834. [PMID: 24288547 PMCID: PMC3833317 DOI: 10.1155/2013/831834] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Revised: 09/12/2013] [Accepted: 09/17/2013] [Indexed: 02/08/2023] Open
Abstract
Kawasaki disease (KD) is a systemic vasculitis and can develop multiple organ injuries including kidney and urinary tract involvement. These disorders include pyuria, prerenal acute kidney injury (AKI), renal AKI caused by tubulointerstitial nephritis (TIN), hemolytic uremic syndrome (HUS), and immune-complex mediated nephropathy, renal AKI associated with either Kawasaki disease shock syndrome or unknown causes, acute nephritic syndrome (ANS), nephrotic syndrome (NS), renal tubular abnormalities, renal abnormalities in imaging studies, and renal artery lesions (aneurysms and stenosis). Pyuria is common in KD and originates from the urethra and/or the kidney. TIN with AKI and renal tubular abnormalities probably result from renal parenchymal inflammation caused by T-cell activation. HUS and renal artery lesions are caused by vascular endothelial injuries resulting from vasculitis. Some patients with ANS have immunological abnormalities associated with immune-complex formation. Nephromegaly and renal parenchymal inflammatory foci are detected frequently in patients with KD by renal ultrasonography and renal scintigraphy, respectively. Although the precise pathogenesis of KD is not completely understood, renal vasculitis, immune-complex mediated kidney injuries, or T-cell immune-regulatory abnormalities have been proposed as possible mechanisms for the development of kidney and urinary tract injuries.
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Affiliation(s)
- Toru Watanabe
- Department of Pediatrics, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata City 950-1197, Japan
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Abstract
Aims. Kawasaki disease is an acute systemic vasculitis and is the most common cause of acquired heart disease in children in the developed world. This review aims to synthesise recent insights into the disease and provide an update for clinicians on diagnostic and treatment practices. Methods. We conducted a review of the literature exploring epidemiology, aetiology, diagnosis, and management of Kawasaki disease. We searched MEDLINE, Medline In-Process, Embase, Google Scholar, and reference lists of relevant articles. Conclusions. Kawasaki disease is a febrile vasculitis which progresses to coronary artery abnormalities in 25% of untreated patients. The disease is believed to result from a genetically susceptible individual's exposure to an environmental trigger. Incidence is rising worldwide, and varies widely across countries and within different ethnic groups. Diagnosis is based on the presence of fever in addition to four out of five other clinical criteria, but it is complicated by the quarter of the Kawasaki disease patients with "incomplete" presentation. Treatment with intravenous immunoglobulin within ten days of fever onset improves clinical outcomes and reduces the incidence of coronary artery dilation to less than 5%. Given its severe morbidity and potential mortality, Kawasaki disease should be considered as a potential diagnosis in cases of prolonged paediatric fever.
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Bayers S, Shulman ST, Paller AS. Kawasaki disease. J Am Acad Dermatol 2013; 69:513.e1-8; quiz 521-2. [DOI: 10.1016/j.jaad.2013.06.040] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 06/18/2013] [Indexed: 02/03/2023]
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Laurito M, Stazi A, Delogu AB, Milo M, Battipaglia I, Scalone G, Infusino F, Villano A, Russo G, Iannotta R, Saracino A, Parrinello R, Figliozzi S, Sestito A, Romagnoli C, Lanza GA, Crea F. Endothelial and platelet function in children with previous Kawasaki disease. Angiology 2013; 65:716-22. [PMID: 24019084 DOI: 10.1177/0003319713502392] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We investigated whether children with a previous Kawasaki disease (KD) have evidence of abnormal vascular and/or platelet function. We included 14 patients with previous KD and 14 matched controls. We assessed endothelial function by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary microvascular function by coronary blood flow response (CBFR) to cold pressor test, and platelet reactivity by measuring monocyte-platelet aggregates (MPAs) and CD41-platelet expression by flow cytometry. No differences were found between the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in patients with KD and controls. CD41-platelet expression, however, was significantly increased in patients with KD compared with controls, both at rest (14.3 ± 1.9 vs 12.4 ± 1.9 mean fluorescence intensity [mfi], P = .01) and after adenosine diphosphate stimulation (19.3 ± 1.3 vs 17 ± 1.7 mfi, P < .001). In conclusion, children with a previous episode of KD showed increased platelet activation, compared with healthy participants despite no apparent vascular abnormality at follow-up.
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Affiliation(s)
- Marianna Laurito
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alessandra Stazi
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Angelica B Delogu
- Institute of Pediatrics, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Milo
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Irma Battipaglia
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giancarla Scalone
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Fabio Infusino
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Angelo Villano
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giulio Russo
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Rossella Iannotta
- Institute of Pediatrics, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Annalisa Saracino
- Institute of Pediatrics, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Stefano Figliozzi
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alfonso Sestito
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Gaetano A Lanza
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Filippo Crea
- Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy
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[The role of immunosuppressive agents in Kawasaki disease: a discussion of two cases]. Arch Pediatr 2013; 20:748-53. [PMID: 23693156 DOI: 10.1016/j.arcped.2013.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Revised: 12/29/2012] [Accepted: 04/09/2013] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Kawasaki disease (KD) is the most common cause of acquired heart disease in developed countries. Ten percent of patients with KD develop coronary aneurism. Ten percent of patients treated with intravenous immunoglobulin (IgIV) have persistent coronary dilatations, which sustains the search for new therapies. We describe 2 cases of refractory KD and discuss the therapeutic options. CLINICAL REPORT A 3-year-old child and a 3-month-old infant had refractory KD. Both were treated with IgIV and corticosteroids. They both had persistent fever and major coronary artery dilatation. The first patient received a treatment with acetyl-salicylic-acid (ACA) only. The second received an immuno-therapy with an anti-TNF-α agent. Fever and inflammatory symptoms disappeared within 12h in the second case. Coronary artery aneurisms worsened during the first month and then stabilized. The first child had fever and inflammatory symptoms for a longer duration, but coronary artery dilatations stabilized and disappeared with no additional treatment than ACA. DISCUSSION AND CONCLUSION TNF-α is known to be one of the inflammatory factors involved in KD disease. Anti-TNF-α agents have been tested in treatment of refractory KD. In one of the cases reported herein, this therapy was not effective on coronary artery aneurism. More studies are needed to define the optimal treatment of refractory KD.
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Vierucci F, Tuoni C, Moscuzza F, Saggese G, Consolini R. Erythema multiforme as first sign of incomplete Kawasaki disease. Ital J Pediatr 2013; 39:11. [PMID: 23406772 PMCID: PMC3632492 DOI: 10.1186/1824-7288-39-11] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Accepted: 01/09/2013] [Indexed: 12/18/2022] Open
Abstract
Incomplete Kawasaki disease represents a diagnostic challenge for pediatricians. In the absence of classical presentation, the laboratoristic evaluation of systemic inflammation can help in placing the correct diagnosis to promptly start adequate therapy. Erythema multiforme is an acute, self-limiting condition considered to be a hypersensitivity reaction commonly associated with various infections or medications. This aspecific skin condition has been rarely described as a sign of Kawasaki disease. We report on the case of a 4 years old boy presenting high-grade fever associated with erythema multiforme and evidence of systemic inflammation who showed a good response to prompt treatment with intravenous immunoglobulins.
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Affiliation(s)
- Francesco Vierucci
- Pediatric Unit, Maternal & Infant Department, S. Chiara University-Hospital, Via Roma 67, Pisa 56126, Italy.
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