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Jafari N, Zolfi Gol A, Shahabi Rabori V, Saberiyan M. Exploring the role of exosomal and non-exosomal non-coding RNAs in Kawasaki disease: Implications for diagnosis and therapeutic strategies against coronary artery aneurysms. Biochem Biophys Rep 2025; 42:101970. [PMID: 40124995 PMCID: PMC11930191 DOI: 10.1016/j.bbrep.2025.101970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/19/2025] [Accepted: 03/03/2025] [Indexed: 03/25/2025] Open
Abstract
Kawasaki disease (KD) is an acute vasculitis primarily affecting children, with a potential risk of developing coronary artery aneurysms (CAAs) and cardiovascular complications. The emergence of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has provided insights into Kawasaki disease pathogenesis and opened new avenues for diagnosis and therapeutic intervention. Furthermore, polymorphism analysis of ncRNA genes offers significant insights into genetic predisposition to Kawasaki disease, facilitating tailored treatment approaches and risk assessment to improve patient outcomes. Exosomal ncRNAs, which are ncRNAs encapsulated within extracellular vesicles, have garnered significant attention as potential biomarkers for Kawasaki disease and CAA due to their stability and accessibility in biological fluids. This review comprehensively discusses the biogenesis, components, and potential of exosomal and non-exosomal ncRNAs in Kawasaki disease diagnosis and prognosis prediction. It also highlights the roles of non-exosomal ncRNAs, such as miRNAs, lncRNAs, and circRNAs, in Kawasaki disease pathogenesis and their implications as therapeutic targets. Additionally, the review explores the current diagnostic and therapeutic approaches for Kawasaki disease and emphasizes the need for further research to validate these ncRNA-based biomarkers in diverse populations and clinical settings.
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Affiliation(s)
- Negar Jafari
- Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Zolfi Gol
- Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Venus Shahabi Rabori
- Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammadreza Saberiyan
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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2
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Liu W, Zu J, Li S. General dermatology and dermatology in primary care. Clin Exp Dermatol 2025; 50:1055-1056. [PMID: 39657976 DOI: 10.1093/ced/llae529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/05/2024] [Accepted: 12/03/2024] [Indexed: 12/12/2024]
Abstract
A 13-year-old boy presented with a 14-day history of painful necrotic papules and plaques on his trunk and extremities, accompanied by persistent fever for 6 days.
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Affiliation(s)
- Wei Liu
- Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, China
| | - Jianjiao Zu
- Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, China
| | - Shanshan Li
- Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, China
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Lam JY, Shimizu C, Gardiner MA, Giorgio T, Wright V, Baker A, Anderson MS, Heizer H, Mohandas S, Kazarians A, Kaneta K, Jone PN, Dominguez SR, Szmuszkovicz JR, Newburger JW, Tremoulet AH, Burns JC. External Validation of a Machine Learning Model to Diagnose Kawasaki Disease. J Pediatr 2025; 282:114543. [PMID: 40122277 DOI: 10.1016/j.jpeds.2025.114543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/24/2025] [Accepted: 03/12/2025] [Indexed: 03/25/2025]
Abstract
We investigated the generalizability of a machine learning model trained to predict Kawasaki disease using laboratory and clinical data. The algorithm performed with >89% accuracy at 3 children's hospitals across the United States, demonstrating its potential as a physician support tool for diagnosing Kawasaki disease.
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Affiliation(s)
- Jonathan Y Lam
- Department of Biomedical Informatics, University of California San Diego, La Jolla, CA
| | - Chisato Shimizu
- Department of Pediatrics, Rady Children's Hospital and University of California San Diego, San Diego, CA
| | - Michael A Gardiner
- Department of Pediatrics, Rady Children's Hospital and University of California San Diego, San Diego, CA
| | - Thomas Giorgio
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Veronique Wright
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Annette Baker
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Marsha S Anderson
- Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
| | - Heather Heizer
- Department of Pediatric Infectious Diseases, Oklahoma Children's Hospital and University of Oklahoma Health Science Center, Oklahoma City, OK
| | - Sindhu Mohandas
- Division of Infectious Disease, Children's Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, CA
| | - Alicia Kazarians
- Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA
| | - Kelli Kaneta
- Division of Nephrology, Children's Hospital Los Angeles, Los Angeles, CA
| | - Pei-Ni Jone
- Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Samuel R Dominguez
- Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
| | - Jacqueline R Szmuszkovicz
- Division of Cardiology, Children's Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, CA
| | - Jane W Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Adriana H Tremoulet
- Department of Pediatrics, Rady Children's Hospital and University of California San Diego, San Diego, CA
| | - Jane C Burns
- Department of Pediatrics, Rady Children's Hospital and University of California San Diego, San Diego, CA.
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Tharwat S, Nassar MK. Assessment of sleep problems in patients with Kawasaki disease: a survey-based study. BMC Pediatr 2025; 25:96. [PMID: 39905354 PMCID: PMC11796227 DOI: 10.1186/s12887-025-05418-w] [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: 08/03/2024] [Accepted: 01/09/2025] [Indexed: 02/06/2025] Open
Abstract
INTRODUCTION Kawasaki disease (KD) is a rare systemic inflammatory disease that primarily affects children under the age of five. It is now recognized as the most prevalent cause of acquired heart diseases in children in developed countries. OBJECTIVES The aim of this study was to evaluate sleep disturbances in patients with KD and identify their prevalence and associations. METHODS This cross-sectional analytic survey-based study was carried out on 262 participants (130 KD patients and 132 age- and sex-matched healthy controls). Participants were invited via social media groups. Sociodemographic data, clinical characteristics and therapeutic data of KD patients were collected. To identify the presence of sleep disturbances, all participants completed Children's Sleep Habits Questionnaire (CSHQ). RESULTS The median age for KD patients was 6 years, and 51.5% of them were female, the median age at disease onset was 2.5 years, and the median disease duration was 3 years. The sleep scores of patients with KD were significantly higher than those of the control group (55.72 ± 11.97 vs. 49.45 ± 8.54, p < 0.001). The total duration of sleep did not exhibit any statistically significant difference between patients with KD and healthy controls (p = 0.399). KD patients exhibited significantly elevated scores in sleep onset delay, sleep duration, night wakings, parasomnias, and sleep-disordered breathing (p < 0.001). Additionally, they showed marginally higher scores in daytime sleepiness (p = 0.059). Younger age of KD patients was associated with higher rates of bedtime resistance (p < 0.001) and sleep anxiety (p = 0.005). Younger age at KD onset was associated significantly with higher rates of bedtime resistance (p = 0.009), sleep anxiety (p = 0.038), night wakings (p = 0.017), and worse sleep quality (p = 0.033). KD Patients who exhibited lethargy, and received corticosteroid medication had significantly higher sleep scores than those who did not. CONCLUSION Patients with KD experience higher sleep disturbance than their healthy counterparts. Young age, early disease onset, lethargy and corticosteroid administration are linked to poor sleep quality.
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Affiliation(s)
- Samar Tharwat
- Rheumatology & Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
- Department of Internal Medicine, Faculty of Medicine, Horus University, New Damietta, Egypt.
- Mansoura University Hospital, El Gomhouria St, Mansoura, Dakahlia Governorate, 35511, Egypt.
| | - Mohammed Kamal Nassar
- Mansoura Nephrology and Dialysis Unit, Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Yan R, Chen S, Lang X, Liu J, Zhou T. Identification of key ferroptosis‑related biomarkers in Kawasaki disease by clinical and experimental validation. Biomed Rep 2025; 22:16. [PMID: 39624783 PMCID: PMC11609609 DOI: 10.3892/br.2024.1894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/11/2024] [Indexed: 01/06/2025] Open
Abstract
Kawasaki disease (KD) is an acute febrile rash that is primarily characterized by systemic vasculitis and is the leading cause of childhood-acquired heart disease. At present, a KD diagnosis is solely dependent on clinical symptoms and effective diagnostic markers are unavailable. Ferroptosis, a novel form of programmed cell death, contributes to the pathophysiology of infectious diseases. The present study aimed to identify key ferroptosis-related genes (FRGs) involved in the pathological process of KD and thus potential diagnostic biomarkers for this disease. For this purpose, differentially expressed-FRGs (DE-FRGs) between patients with KD and healthy controls were screened. The least absolute shrinkage and selection operator (LASSO) algorithm and a logistic regression model combined with receiver operating characteristic analysis were then used to identify and assess ferroptosis-related markers. Additionally, immune cell infiltration landscapes in the KD and control groups were evaluated using CIBERSORT. Moreover, the predictive value of the identified markers was validated in the clinical samples as well as vascular endothelial cells. A total of 10 DE-FRGs were screened from the KD and control samples. These 10 DE-FRGs were then applied to the LASSO model and 6 key ferroptosis-related markers were obtained. The subsequent Gene Set Variation Analysis results suggested that high expression levels of these markers were closely associated with innate immune activation and metabolism, while low expression was mainly linked to adaptive immune-related pathways. In addition to validating each gene in the training and validation sets, the diagnostic potential of these markers was assessed utilizing KD samples obtained from Shenzhen Baoan Women's and Children's Hospital. As a result, MAPK14, SLC2A3 and PGD were selected as potential diagnostic markers for KD. Additionally, changes in the expression of marker genes during inflammatory activation of vascular endothelial cells were measured by reverse transcription-quantitative PCR. The results of the present study will help to understand the role of FRGs in the pathogenesis of KD. Moreover, the identified FRGs may serve as diagnostic biomarkers, providing new strategies for KD prediction and treatment.
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Affiliation(s)
- Rui Yan
- Department of Pediatrics, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, Guangdong 518100, P.R. China
| | - Shuiwen Chen
- Department of Pediatrics, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, Guangdong 518100, P.R. China
| | - Xinling Lang
- Department of Pediatrics, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, Guangdong 518100, P.R. China
| | - Jimin Liu
- Department of Pediatrics, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, Guangdong 518100, P.R. China
| | - Tao Zhou
- Department of Pediatrics, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, Guangdong 518100, P.R. China
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Shumnalieva R, Mileva N, Padjen I, Siliogkas P, Chervenkov L, Bakopoulou K, Kaouri IE, Vasilska A, Miteva D, Vassilev D, Velikova T. Management of Coronary Artery Diseases in Systemic Vasculitides: Complications and Strategies. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1574. [PMID: 39459361 PMCID: PMC11509434 DOI: 10.3390/medicina60101574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/13/2024] [Accepted: 09/20/2024] [Indexed: 10/28/2024]
Abstract
Coronary artery disease (CAD) presents a significant risk for patients with systemic vasculitides, a group of disorders characterized by the inflammation of blood vessels. In this review, we focus on the pathophysiological mechanisms, complications, and management strategies for CAD in systemic vasculitides. We highlight how the inflammatory processes inherent in vasculitis contribute to accelerated atherosclerosis and myocardial ischemia. Key strategies in managing CAD in this patient population include using medicine treatments to mitigate vascular inflammation while balancing the risk of promoting cardiovascular events and lifestyle modifications. Understanding the nuanced relationship between systemic vasculitides and CAD is crucial for improving patient outcomes and guiding therapeutic approaches.
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Affiliation(s)
- Russka Shumnalieva
- Department of Rheumatology, Clinic of Rheumatology, University Hospital St. Ivan Rilski, Urvich Str. 13, 1612 Sofia, Bulgaria;
- Faculty of Medicine, Medical University of Sofia, Urvich Str. 13, 1612 Sofia, Bulgaria
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
| | - Niya Mileva
- Cardiology Department, SHATC Medica Cor, Riga Str. 35, 7013 Ruse, Bulgaria;
| | - Ivan Padjen
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, University of Zagreb, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia;
| | - Periklis Siliogkas
- General Hospital of Athens Korgialeneio—Benakeio Hellenic Red Cross, Athanasaki 11, 11526 Athens, Greece;
| | - Lyubomir Chervenkov
- Department of Diagnostic Imaging, Medical University Plovdiv, Bul. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria; (L.C.); (A.V.)
- Research Complex for Translational Neuroscience, Medical University of Plovdiv, Bul. Vasil Aprilov 15A, 4002 Plovdiv, Bulgaria
| | - Konstantina Bakopoulou
- Faculty of Medicine, Medical University Sofia, Boulevard ‘Akademik Ivan Evstratiev Geshov’ 15, 1431 Sofia, Bulgaria; (K.B.); (I.E.K.)
| | - Issa El Kaouri
- Faculty of Medicine, Medical University Sofia, Boulevard ‘Akademik Ivan Evstratiev Geshov’ 15, 1431 Sofia, Bulgaria; (K.B.); (I.E.K.)
| | - Anna Vasilska
- Department of Diagnostic Imaging, Medical University Plovdiv, Bul. Vasil Aprilov 15A, 4000 Plovdiv, Bulgaria; (L.C.); (A.V.)
| | - Dimitrina Miteva
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
- Department of Genetics, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tzankov Str., 1164 Sofia, Bulgaria
| | - Dobrin Vassilev
- Ruse University Angel Kanchev, ul. “Studentska” 8, 7017 Ruse, Bulgaria;
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria;
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Kostara M, Otal-Buesa M, Leung ASY, Eigenmann P. Editorial comment on "Six-year trend of subsequent allergic diseases following Kawasaki disease and its clinical implications: A population-based matched cohort study of 34,712 patients". Pediatr Allergy Immunol 2024; 35:e14248. [PMID: 39319932 DOI: 10.1111/pai.14248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 09/12/2024] [Indexed: 09/26/2024]
Affiliation(s)
- Maria Kostara
- Child Health Department, University of Ioannina School of Medicine, Ioannina, Greece
| | - Maria Otal-Buesa
- Allergy Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Agnes S Y Leung
- Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Hong Kong Hub of Paediatric Excellence (HOPE), The Chinese University of Hong Kong, Hong Kong, China
| | - Philippe Eigenmann
- Pediatric Allergy Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, Switzerland
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8
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Wang C, Zhang H, Zhang J, Hong Z, Miao C, Wang T, Lin H, Li Y, Liu G. Mycoplasma pneumoniae-induced Kawasaki disease via PINK1/Parkin-mediated mitophagy. Exp Cell Res 2024; 441:114182. [PMID: 39094903 DOI: 10.1016/j.yexcr.2024.114182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/22/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024]
Abstract
Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that primarily affects children. The objective of this study was to explore the function and underlying mechanism of mitophagy in Mycoplasma pneumoniae (MP)-induced KD. To create MP-induced KD models, Human coronary endothelial cells (HCAECs) and DBA/2 mice were employed and treated with Mp-Lipid-associated membrane proteins （LAMPs）. Lactate dehydrogenase (LDH) levels were tested to determine cellular damage or death. The inflammatory cytokines tumor necrosis factor (TNF)--α and interleukin (IL)-6 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. RT-qPCR and Western blotting were used to determine the expression of Intercellular Adhesion Molecule(ICAM)-1, vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase(iNOS), LC3, p62, PINK1(a mitochondrial serine/threonine-protein kinase), and PARKIN(a cytosolic E3-ubiquitin ligase). The adenosine triphosphate （ATP）, reactive oxygen species （ROS）, and mitochondrial membrane potential（MMP） levels were measured to determine mitochondrial function. Mitophagy was investigated using immunofluorescence and a mitophagy detection test. Autophagosome and mitochondrial morphology were examined using transmission electron microscopy. To identify inflammatory cell infiltration, hematoxylin and eosin staining was utilized. Mp-LAMPs increased the levels of TNF-α, IL-6, ICAM-1, VCAM-1, and iNOS in an HCAEC cell model, along with LDH release. After Mp-LAMPs exposure, there was a rise in LC3 and a reduction in p62. Meanwhile, the expression of PINK1 and Parkin was increased. Cyclosporin A dramatically increased ATP synthesis and MMP in HCAEC cells treated with Mp-LAMPs, while suppressing ROS generation, demonstrating excessive mitophagy-related mitochondrial dysfunction. Additionally, neither body weight nor artery tissue were affected due to PINK1 and Parkin suppression Cyclosporin A in Mp-LAMPs-treated mice. These findings indicated that PINK1/Parkin-mediated mitophagy inhibition may be a therapeutic target for MP-induced KD.
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Affiliation(s)
- Chengyi Wang
- College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China
| | - Huijie Zhang
- Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China
| | - Jinyan Zhang
- College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China
| | - Zesheng Hong
- College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China
| | - Chong Miao
- College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China
| | - Tengyang Wang
- Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China
| | - Han Lin
- Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China
| | - Yinglin Li
- Pediatric Intensive Care Unit, The Affiliated Hospital(Group) of Putian University, Putian 351100, PR China.
| | - Guanghua Liu
- Department of Pediatrics, Fujian Children's Hospital(Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, PR China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Maternity and Child Health Hospital, Fuzhou 350001, PR China.
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Chen S, Nie R, Wang C, Luan H, Ma X, Gui Y, Zeng X, Yuan H. A two sample mendelian randomization analysis investigates causal effects between gut microbiome and immune related Vasculitis. Sci Rep 2024; 14:18810. [PMID: 39138194 PMCID: PMC11322650 DOI: 10.1038/s41598-024-68205-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 07/22/2024] [Indexed: 08/15/2024] Open
Abstract
Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.
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Affiliation(s)
- Si Chen
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Rui Nie
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Chao Wang
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Haixia Luan
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Xu Ma
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Yuan Gui
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China
| | - Xiaoli Zeng
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China.
| | - Hui Yuan
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road No. 2, Chaoyang District, Beijing, 100029, China.
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Markandran K, Clemente KNM, Tan E, Attal K, Chee QZ, Cheung C, Chen CK. The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key. Int J Mol Sci 2024; 25:8062. [PMID: 39125631 PMCID: PMC11311979 DOI: 10.3390/ijms25158062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/13/2024] [Accepted: 07/19/2024] [Indexed: 08/12/2024] Open
Abstract
Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a "liquid biopsy" approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future.
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Affiliation(s)
- Kasturi Markandran
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; (K.M.)
| | - Kristine Nicole Mendoza Clemente
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; (K.M.)
| | - Elena Tan
- School of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
| | - Karan Attal
- School of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
| | - Qiao Zhi Chee
- Division of Cardiology, Department of Paediatrics, Khoo Teck Puat–National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
| | - Christine Cheung
- Lee Kong Chian School of Medicine, Experimental Medicine Building, 59 Nanyang Drive, Nanyang Technological University, Singapore 636921, Singapore
- Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
| | - Ching Kit Chen
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; (K.M.)
- Division of Cardiology, Department of Paediatrics, Khoo Teck Puat–National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
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11
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Mohamed M, Harahsheh A, Choueiter N, Agha HM, Alrabte H, Abu Al-Saoud SY, Al-Saloos H, Al Senaidi K, Alzyoud R, Al Awadhi Z, Belbouab R, Bouayed K, Bouaziz A, El Ganzoury M, Fitouri Z, Kotby A, Ladj MS, Bekkar MM, Rugige N, Salih AF, Sulaiman M, Dahdah N. Advancing Kawasaki Disease Research in the Arab World: Scoping Literature Review Analysis with Emphasis on Giant Coronary Aneurysms. Pediatr Cardiol 2024:10.1007/s00246-024-03589-4. [PMID: 39037592 DOI: 10.1007/s00246-024-03589-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 07/11/2024] [Indexed: 07/23/2024]
Abstract
To evaluate giant aneurysms (GiAn) prevalence in Arab countries and examine contributing factors; and to review Kawasaki disease (KD) publication trends and collaborations among Arab nations. A scoping literature review was conducted to analyze the publications across the Arab world, spanning 16 countries from 1978 to 2023. The collected articles were a combination of database search with a call on Kawasaki Disease Arab Initiative (Kawarabi) members to share non-PubMed publications. Over 45 years, 50 articles originated from the Arab Countries with a 30% average annual growth rate in KD research output. Publications were evenly split between case reports (42%) and institutional series (52%). Research productivity lagged in developing nations with UAE, KSA and Egypt, contributed to 64% of total publications. Among 26 institutional series, 256 coronary artery aneurysms (CAA) from a total of 1264 KD cases were reported. Of those, 25 CAA were GiAn (prevalence 1.43% [range 0-12.5%]). The initial KD misdiagnosis rate was 4%, and incomplete KD (iKD) averaged 10.6%. Series (38.5%) that did not report iKD correlated with a higher prevalence of CAA, but not of GiAn. Longer fever duration emerged as a pivotal factor for GiAn (OR 5.06, 95%CI 1.51-17). This review unveils the research landscape of KD in the Arab world over 45 years. Initial misdiagnosis, untreated cases, delayed diagnosis and underreporting of iKD are contributing factors for an underestimated epidemiology, explaining the higher GiAn prevalence. This calls for strategic interventions to enhance KD research in these countries, aligning with Kawarabi's mission.
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Affiliation(s)
- Mariam Mohamed
- Faculty of Medicine, University of Montreal, Montreal, QC, Canada
| | - Ashraf Harahsheh
- Division of Cardiology Department of PediatricsSchool of Medicine & Health Sciences, Children's National Hospital, The George Washington University, Washington, USA
| | | | - Hala M Agha
- Pediatric Cardiology Division, Cairo University, Giza, Egypt
| | - Hanifa Alrabte
- Pediatric Cardiology Department, Tripoli Children Hospital, Tripoli, Libya
| | - Sima Y Abu Al-Saoud
- Department of Pediatrics, Faculty of Medicine, Makassed Hospital, Al-Quds University, Jerusalem, Palestine
| | - Hesham Al-Saloos
- Division of Cardiology, Sidra Medicine, Clinical Pediatrics, Weill Cornell Medicine, Ar-Rayyan, Qatar
| | - Khalfan Al Senaidi
- Division of Pediatric Cardiology, Sultan Qaboos University Hospital, Muscat, Oman
| | - Raed Alzyoud
- Pediatric Immunology, Allergy, and Rheumatology Division, Queen Rania Children's Hospital, Amman, Jordan
| | - Zainab Al Awadhi
- Al Jalila Children's Speciality Hospital, Dubai, United Arab Emirates
| | - Reda Belbouab
- Faculty of Medicine, Pediatric Department University Hospital, Mustapha Bacha Algiers, Algiers University, Algiers, Algeria
| | - Kenza Bouayed
- Abderrahim Harouchi Mother-Child Hospital, CHU Ibn Rochd, Casablanca, Morocco
| | - Asma Bouaziz
- Headmaster of Children and Neonatal Department, Hôpital Régional Ben Arous, Ben Arous, Tunisia
| | - Mona El Ganzoury
- Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Zohra Fitouri
- Division of Rheumatology, Emergency Department of Béchir Hamza Pediatric Hospital of Tunis, Tunis, Tunisia
| | - Alyaa Kotby
- Pediatric Cardiology Division, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed S Ladj
- Department of Pediatrics, Faculty of Medicine, Djillali Belkhenchir University Hospital, Algiers University, Algiers, Algeria
| | - Mohammed Mokhtar Bekkar
- Pediatric Cardiology Unit, Department of Pediatrics, Faculty of Medicine, CHU Oran, Oran University, Oran, Algeria
| | - Najat Rugige
- Pediatric Cardiology Department, Benghazi Children Hospital, Benghazi University, Benghazi, Libya
| | - Aso Faeq Salih
- Pediatric Cardiology Department/Children's Heart Hospital, Sulaimani College of Medicine-Sulaimani University, Al-Sulaimaniyah, Iraq
| | | | - Nagib Dahdah
- Division of Pediatric Cardiology, CHU Sainte-Justine, Montreal, Canada.
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12
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Reddy Konda VV, Jindal AK, Nadig PL, Banday AZ, Vinay K, Singh S. Microvascular changes on nailfold capillaroscopy in acute stage of Kawasaki disease: a new diagnostic paradigm for an enigmatic condition. Rheumatology (Oxford) 2024; 63:392-398. [PMID: 37202349 DOI: 10.1093/rheumatology/kead213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/01/2023] [Accepted: 04/30/2023] [Indexed: 05/20/2023] Open
Abstract
OBJECTIVES Kawasaki disease (KD) is a medium vessel vasculitis with a predilection to involve coronary arteries. However, there is a paucity of literature on microvascular changes in patients with KD. METHODS Children diagnosed with KD based on American Heart Association guidelines 2017 were enrolled prospectively. Demographic details and echocardiographic changes in coronaries were recorded. Nailfold capillaries were assessed using Optilia Video capillaroscopy and data were analysed using Optilia Optiflix Capillaroscopy software at acute (prior to IVIG administration) and subacute/convalescent phase. RESULTS We enrolled 32 children with KD (17 boys) with a median age of 3 years. Nailfold capillaroscopy (NFC) was performed in 32 patients in the acute phase (compared with 32 controls) and in 17 during the subacute/convalescent phase at a median follow-up of 15 (15-90) days after IVIG treatment. The following findings were seen in NFC in the acute phase of KD: reduced capillary density (n = 12, 38.6%), dilated capillaries (n = 3, 9.3%), ramifications (n = 3, 9.3%) and capillary haemorrhages (n = 2, 6.2%). Capillary density was reduced significantly in the acute phase of KD (38.6%) as compared with the subacute/convalescent phase (25.4%) (P-value <0.001) and controls (0%) (P-value = 0.03). We observed no correlation between coronary artery involvement and mean capillary density (P = 0.870). CONCLUSION Results show that patients with KD have significant nailfold capillary changes in the acute phase. These findings may provide a new diagnostic paradigm for KD and a window to predict coronary artery abnormalities.
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Affiliation(s)
- Vishnu Vardhan Reddy Konda
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ankur Kumar Jindal
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pallavi L Nadig
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aaqib Zaffar Banday
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Keshavamurthy Vinay
- Department of Dermatology, Venerology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Surjit Singh
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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13
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Zhang Y, Liu J. Clinical value of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of Kawasaki disease complicated with coronary artery lesions. Heart Vessels 2024; 39:18-24. [PMID: 37758852 DOI: 10.1007/s00380-023-02315-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023]
Abstract
To analyze the clinical value of echocardiography combined with serum lacuna protein-1 (Cav-1), activated T cell nuclear factor C1 (NFATc1), and plasminogen activator inhibitor-1 (PAI-1) in the diagnosis of Kawasaki disease (KD) complicated with coronary artery lesions (CAL). A total of 200 children with KD treated in our hospital from January 2019 to October 2021 were grouped as the KD alone group (n = 56) and the KD complicated with CAL group (n = 144) according to the results of coronary angiography. The levels of Cav-1, NFATc1, and PAI-1 were detected by enzyme-linked immunosorbent assay. Echocardiography was performed and the internal diameters of left and right coronary arteries were compared between the two groups. The area under the curve (AUC), sensitivity, and specificity of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of KD complicated with CAL were analyzed with receiver operating characteristic (ROC) curve. Coronary angiography, as the gold standard, showed that the sensitivity of echocardiography in diagnosing KD with CAL was 88.19% (127/144), the specificity was 66.07% (37/56), and the accuracy was 82.00% (164/200). ROC curve analysis revealed that the AUC of KD complicated with CAL diagnosed by echocardiography, Cav-1, NFATc1, and PAI-1 was 0.819, 0.715, 0.688, and 0.663, respectively, and the AUC of combined diagnosis of the four was 0.896. The combination of echocardiography, Cav-1, NFATc1, and PAI-1 has high value in diagnosing KD complicated with CAL, which can be widely used in clinical practice.
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Affiliation(s)
- Yanxia Zhang
- Department of Ultrasonography, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, Shanxi, China
| | - Jieqiong Liu
- Department of Ultrasonography, Children's Hospital of Shanxi Province (Shanxi Maternal and Child Health Care Hospital), Taiyuan, 030013, Shanxi, China.
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14
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Aggarwal R, Pilania RK, Sharma S, Kumar A, Dhaliwal M, Rawat A, Singh S. Kawasaki disease and the environment: an enigmatic interplay. Front Immunol 2023; 14:1259094. [PMID: 38164136 PMCID: PMC10757963 DOI: 10.3389/fimmu.2023.1259094] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 12/05/2023] [Indexed: 01/03/2024] Open
Abstract
Kawasaki disease (KD) is a common systemic vasculitis of childhood. Although it has been almost 6 decades since Dr. Tomisaku Kawasaki reported the first case series of KD, the underlying cause remains a mystery. KD is a self-limiting disease. However, a dreaded complication is development of coronary artery abnormalities (CAAs). KD is the most common cause of acquired heart disease in children in the developed world and is being increasingly reported from developing countries too. Over the years, significant observations have been made about epidemiology of KD. It usually affects children below 5, has male preponderance and has significantly higher incidence in North East Asian countries. While several hypotheses have been proffered for etiology of KD, none have been conclusive. These include associations of KD epidemics in Japan and the United Stated with changes in tropospheric wind patterns suggesting wind-borne agents, global studies showing peaks of incidence related to season, and increased rates in populations with a higher socioeconomic profile related to hygiene hypothesis and vaccination. Furthermore, the self-limiting, febrile nature of KD suggests an infectious etiology, more so with sudden decline noted in cases in Japan with onset of COVID-19 mitigation measures. Finally, single nucleotide polymorphisms have been identified as possible risk alleles in patients with KD and their significance in the pathogenesis of this disease are also being defined. The purpose of this review is to elucidate the puzzling associations of KD with different environmental factors. Looking at patterns associated with KD may help us better predict and understand this disease.
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Affiliation(s)
| | - Rakesh Kumar Pilania
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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15
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Kostara M, Serbis A, Pavlou M, Kotanidou E, Tsabouri S, Vlahos A, Makis A, Siomou E. Unusual Manifestations of Kawasaki Disease in the COVID Era: A Case Series and Review of the Literature. Cureus 2023; 15:e51104. [PMID: 38274908 PMCID: PMC10809307 DOI: 10.7759/cureus.51104] [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: 12/25/2023] [Indexed: 01/27/2024] Open
Abstract
Kawasaki disease (KD) is an acute medium-vessel vasculitis, mainly affecting infants older than six months and children under five years. It predisposes to the development of coronary artery aneurysms and constitutes the leading cause of acquired heart disease in children. Its diagnosis is based on clinical criteria, namely, fever lasting for ≥ five days together with at least four of the five principal clinical features of the disease. Occasionally, children with KD present with fever, but they fulfill only some of the five principal criteria, and this is described as incomplete KD. Furthermore, "atypical" KD is a term that is usually used for cases that appear with rather unusual clinical manifestations, which complicate clinical judgment and may delay diagnosis and treatment. In this case series, we present four cases of KD with rather unusual clinical features: a five-year-old boy with lobar pneumonia, a six-year-old girl with orange-brown chromonychia appearing on the 10th day of the disease, a 2.5-month-old infant with prolonged fever and urinary tract infection, and an 18-month-old infant with refractory KD and high suspicion of multisystem inflammatory syndrome in children (MIS-C). A literature review on the unusual manifestations of atypical KD was performed to identify clinical findings that must alert the clinician to consider this clinical entity.
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Affiliation(s)
- Maria Kostara
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Anastasios Serbis
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Maria Pavlou
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Eleni Kotanidou
- Second Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, GRC
| | - Sofia Tsabouri
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Antonios Vlahos
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Alexandros Makis
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
| | - Ekaterini Siomou
- Department of Pediatrics, University Hospital of Ioannina, Ioannina, GRC
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16
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An X, Ma X, Liu H, Song J, Wei T, Zhang R, Zhan X, Li H, Zhou J. Inhibition of PDGFRβ alleviates endothelial cell apoptotic injury caused by DRP-1 overexpression and mitochondria fusion failure after mitophagy. Cell Death Dis 2023; 14:756. [PMID: 37980402 PMCID: PMC10657461 DOI: 10.1038/s41419-023-06272-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 10/23/2023] [Accepted: 11/03/2023] [Indexed: 11/20/2023]
Abstract
Kawasaki disease (KD), described as "mucocutaneous lymph node syndrome", affects infants and toddlers. Patients with KD suffer from an inflammatory cascade leading to vasculitis with a predilection for coronary arteries. While the symptoms and pathogenesis of KD have received more and more attention, the precise mechanisms are still debated. Researches show that endothelial dysfunction process in KD leads to arterial damage and affect clinical outcome. In this study, we constructed a Candida albicans water soluble fraction (CAWS)-induced KD murine model and penetrated investigating the mechanisms behind endothelial dysfunction. CAWS-induced mice presented remarkably elevated vascular endothelial cell growth factor (VEGF) levels. Abundant expression of VEGF was documented in all vessels that showed edema from acute KD. It has been reported that Platelet-derived growth factor (PDGF) co-expression normalizes VEGF-induced aberrant angiogenesis. Hyperexpression of PDGFRβ was induced in the thickened medial layer and vascular endothelium of KD mice. Masitinib (Mas) is an oral tyrosine kinase inhibitor of numerous targets, which can selectively target PDGFR signaling. We set out to explore whether Mas could regulate coronary pathology in KD. Mas administration significantly reduced the VEGF-induced endothelial cells migration. NOX4 was activated in vascular endothelial cells to produce more ROS. Mitochondrial dysregulated fission and mitophagy caused by DRP-1 overexpression precipitated the arterial endothelial cells injury. Here, mitophagy seemed to work as the driving force of DRP-1/Bak/BNIP3-dependent endothelial cells apoptosis. In summary, how mitophagy is regulated by DRP-1 under pathologic status is critical and complex, which may contribute to the development of specific therapeutic interventions in cardiovascular diseases patients, for example Masatinib, the inhibitor of PDGFRβ. FACTS AND QUESTIONS: Kawasaki disease causing systemic vasculitis, affects infants and toddlers. Coronary artery injury remains the major causes of morbidity and mortality. DRP-1 overexpression induces DRP-1/Bak/BNIP3-dependent endothelial cells apoptosis. PDGFRβ was high-expressed in the thickened medial layer of CAWS-induced KD mice. Inhibition of PDGFRβ signaling alleviates arterial endothelial cells injury.
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Affiliation(s)
- Xiaohong An
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd, Kunming, 650106, China
| | - Xiao Ma
- Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd, Kunming, 650106, China
| | - Heng Liu
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, 671000, China
| | - Jing Song
- Laboratory Animal Center, Xiamen University, Xiamen, 361102, China
| | - Tiange Wei
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
| | - Rongzhan Zhang
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
| | - Xiao Zhan
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
| | - Hongyang Li
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
| | - Jia Zhou
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
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17
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Bhatt MC, Singhal M, Pilania RK, Bansal SC, Khandelwal N, Gupta P, Singh S. Radiation dose analysis of computed tomography coronary angiography in Children with Kawasaki disease. World J Clin Pediatr 2023; 12:230-236. [PMID: 37753492 PMCID: PMC10518747 DOI: 10.5409/wjcp.v12.i4.230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/12/2023] [Accepted: 08/09/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND There is evolving role of computed tomography coronary angiography (CTCA) in non-invasive evaluation of coronary artery abnormalities in children with Kawasaki disease (KD). Despite this, there is lack of data on radiation dose in this group of children undergoing CTCA. AIM To audit the radiation dose of CTCA in children with KD. METHODS Study (December 2013-February 2018) was performed on dual source CT scanner using adaptive prospective electrocardiography-triggering. The dose length product (DLP in milligray-centimeters-mGy.cm) was recorded. Effective radiation dose (millisieverts-mSv) was calculated by applying appropriate age adjusted conversion factors as per recommendations of International Commission on Radiological Protection. Radiation dose was compared across the groups (0-1, 1-5, 5-10, and > 10 years). RESULTS Eighty-five children (71 boys, 14 girls) with KD underwent CTCA. The median age was 5 years (range, 2 mo-11 years). Median DLP and effective dose was 21 mGy.cm, interquartile ranges (IQR) = 15 (13, 28) and 0.83 mSv, IQR = 0.33 (0.68, 1.01) respectively. Mean DLP increased significantly across the age groups. Mean effective dose in infants (0.63 mSv) was significantly lower than the other age groups (1-5 years 0.85 mSv, 5-10 years 1.04 mSv, and > 10 years 1.38 mSv) (P < 0.05). There was no significant difference in the effective dose between the other groups of children. All the CTCA studies were of diagnostic quality. No child required a repeat examination. CONCLUSION CTCA is feasible with submillisievert radiation dose in most children with KD. Thus, CTCA has the potential to be an important adjunctive imaging modality in children with KD.
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Affiliation(s)
- Mahesh Chandra Bhatt
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Manphool Singhal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kumar Pilania
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Subhash Chand Bansal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Niranjan Khandelwal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Pankaj Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Surjit Singh
- Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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18
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Miao Y, Qian G, Zhang R, Yuan Y, Zuo Y, Ding Y, Li X, Tang Y, Zheng H, Lv H. Linear ubiquitination improves NFAT1 protein stability and facilitates NFAT1 signalling in Kawasaki disease. FEBS J 2023; 290:4224-4237. [PMID: 36779231 DOI: 10.1111/febs.16749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 01/08/2023] [Accepted: 02/09/2023] [Indexed: 02/14/2023]
Abstract
NFAT1 is known for its roles in T cell development and activation. So far, the phosphorylation of NFAT1 has been extensively studied, but the other post-translational modifications of NFAT1 remain largely unknown. In this study, we reported that NFAT1 is a linearly ubiquitinated substrate of linear ubiquitin chain assembly complex (LUBAC). LUBAC promoted NFAT1 linear ubiquitination, which in turn inhibited K48-linked polyubiquitination of NFAT1 and therefore increased NFAT1 protein stability. Interestingly, the linear ubiquitination levels of NFAT1 in patients with the Kawasaki disease were upregulated. Further studies demonstrated that the patients with the Kawasaki disease had increased mRNA levels of HOIL-1L. These findings revealed a linearly ubiquitinated substrate of LUBAC and an important biological function of NFAT1 linear ubiquitination in the Kawasaki disease and therefore may provide a novel strategy for the treatment of the Kawasaki disease.
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Affiliation(s)
- Ying Miao
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
| | - Guanghui Qian
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China
| | - Renxia Zhang
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
| | - Yukang Yuan
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
| | - Yibo Zuo
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
| | - Yueyue Ding
- Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China
| | - Xuan Li
- Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China
| | - Yunjia Tang
- Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China
| | - Hui Zheng
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China
| | - Haitao Lv
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China
- Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China
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19
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Hébert S, Schmidt M, Topf G, Rieger D, Klinge J, Vermehren J, Fusch C, Grillhösl C, Schroth M, Toni I, Reutter H, Morhart P, Hanslik G, Mulzer L, Woelfle J, Hohberger B, Hoerning A. "Multisystem Inflammatory Syndrome in Children" (MIS-C) after COVID-19 Infection in the Metropolitan Area of Nuremberg-Erlangen, Germany-Expectations and Results of a Two-Year Period. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1363. [PMID: 37628362 PMCID: PMC10453116 DOI: 10.3390/children10081363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 07/11/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND Multisystemic Inflammatory Syndrome in children (MIS-C) is a rare autoimmune disorder occurring after a latency period following acute SARS-CoV-2 infection. The therapeutic regime of MIS-C is adapted to the therapy of the Kawasaki disease, as clinical symptoms are similar. Since the Kawasaki disease can potentially result in severe symptoms, which may even affect long-term health, it is essential to gain further knowledge about MIS-C. Thus, we aimed to investigate the incidence, symptoms, therapeutical procedure and outcome of MIS-C patients in the metropolitan area of Nuremberg-Erlangen during the SARS-CoV2 pandemic. MATERIAL AND METHODS Retrospective analysis of clinical charts of MIS-C patients was carried out at three children's hospitals covering the medical care of the metropolitan area of Nuremberg-Erlangen in Germany. Demographic characteristics and symptoms at first visit, their clinical course, therapeutic regime and outcome were recorded within the time period January 2021-December 2022. RESULTS Analysis of 10 patients (5 male, 5 female) with MIS-C resulting in an incidence of 2.14/100.000 children. The median time between COVID-19 infection and admission to hospital was 5 weeks. The median age was 7 years. Symptoms comprised fever (100%), rash (70%), bilateral non-purulent conjunctivitis (70%) and urticaria (20%). At the time of presentation, diagnosis-defining inflammation parameters were increased and the range for C-reactive protein was 4.13 mg/dL to 28 mg/dL, with a median of 24.7 mg/dL. Procalcitonin was initially determined in six patients (1.92 ng/mL to 21.5 ng/mL) with a median value of 5.5 pg/mL. Two patients displayed leukocytosis and two displayed leukopenia. None of the patients presented coronary pathologies. Nine of the ten patients received intravenous immunoglobulin (IVIG) therapy. In addition, patients received intravenous steroids (80%) and acetylsalicylic acid (80%). CONCLUSION SARS-CoV virus may rarely exert multiorgan manifestations due to hyperinflammatory immunological processes. Within two years of the COVID-19 pandemic, we identified ten patients with COVID-induced MIS-C in the metropolitan area Nuremberg-Erlangen. In the description of the patient collective, we can confirm that MIS-C is distinguished from the Kawasaki disease by the lack of coronary manifestations. Interestingly, although having monitored all pediatric facilities in the investigated area, we find lower incidences of MIS-C compared to findings in the literature. In conclusion, an overestimation of incidences in the upcoming MIS-C during the pandemic needs to be considered.
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Affiliation(s)
- Steven Hébert
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Marius Schmidt
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Georg Topf
- Hospital for Children and Adolescents Furth, 90766 Furth, Germany
| | - Daniel Rieger
- Hospital for Children and Adolescents Furth, 90766 Furth, Germany
| | - Jens Klinge
- Hospital for Children and Adolescents Furth, 90766 Furth, Germany
| | - Jan Vermehren
- Pediatrics—Children’s Department Nuremberg Hospital South, 90471 Nuremberg, Germany
| | - Christoph Fusch
- Pediatrics—Children’s Department Nuremberg Hospital South, 90471 Nuremberg, Germany
| | - Christian Grillhösl
- Cnopf Children’s Hospital, Diakoneo Klinikum Hallerwiese Nuremberg, 90419 Nuremberg, Germany
| | - Michael Schroth
- Cnopf Children’s Hospital, Diakoneo Klinikum Hallerwiese Nuremberg, 90419 Nuremberg, Germany
| | - Irmgard Toni
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Heiko Reutter
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Patrick Morhart
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Gregor Hanslik
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Linda Mulzer
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Joachim Woelfle
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
| | - Bettina Hohberger
- Department of Ophthalmology, University Hospital Erlangen, 90766 Erlangen, Germany
| | - André Hoerning
- Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
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20
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Yamazaki T, Okada S, Saito Y, Kitahara H, Kobayashi Y. ST-Segment Elevation Myocardial Infarction in a 32-Year-Old Man With a History of Incomplete Kawasaki Disease. JACC Case Rep 2023; 15:101851. [PMID: 37283836 PMCID: PMC10240282 DOI: 10.1016/j.jaccas.2023.101851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 03/30/2023] [Indexed: 06/08/2023]
Abstract
The role of the incomplete form of Kawasaki disease in future cardiovascular risk is unknown. The present case demonstrates that even a healthy young man with only a history of incomplete Kawasaki disease can develop endothelial dysfunction and suffer myocardial infarction. We did not obtain ethical/institutional review board approval for our submission because this is not a clinical study, but the patient gave written informed consent to publish the case. (Level of Difficulty: Advanced.).
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Affiliation(s)
| | - Sho Okada
- Address for correspondence: Dr Sho Okada, Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8677, Japan.
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21
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Kasem Ali Sliman R, van Montfrans JM, Nassrallah N, Hamad Saied M. Retropharyngeal abscess-like as an atypical presentation of Kawasaki disease: a case report and literature review. Pediatr Rheumatol Online J 2023; 21:34. [PMID: 37046311 PMCID: PMC10099679 DOI: 10.1186/s12969-023-00812-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 03/26/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Kawasaki disease (KD) is a systemic inflammatory condition primarily affecting young children. Although 90% of KD patients present with variable head and neck manifestations, especially cervical lymphadenopathy, peritonsillar, retropharyngeal and parapharyngeal involvement are uncommonly reported as initial manifestations of KD. CASE REPORT Eight-year-old girl with prolonged fever, clinical and a radiological picture suggestive of retropharyngeal abscess, unresponsive to three changes in the antibiotic regimen and surgical drainage. The disease progressed with the development of additional signs and symptoms as non-purulent conjunctivitis (with uveitis), mucosal involvement (strawberry tongue and cracked lips), edema of her hands and feet, and arthritis. A diagnosis of Kawasaki disease was reached with complete remission after Intravenous Immunoglobulin (IVIG) treatment. In addition, we present a literature review of similar cases reported in the last thirty years. CONCLUSION Kawasaki disease requires a high index of suspicion and awareness of unusual presentations. It should be kept in mind as one of the differential diagnosis of patients with febrile inflammation of the retropharyngeal and parapharyngeal spaces who do not respond to antibiotic treatment in the relevant clinical context.
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Affiliation(s)
- Rim Kasem Ali Sliman
- Pediatric Department, Carmel Medical Center, Michal 7 St., 3436212, Haifa, Israel.
- Technion Faculty of Medicine, Haifa, Israel.
| | - Joris M van Montfrans
- Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center, Utrecht, The Netherlands
| | - Najwan Nassrallah
- Technion Faculty of Medicine, Haifa, Israel
- Department of Radiology, Carmel Medical Center, Michal 7 St., 3436212, Haifa, Israel
| | - Mohamad Hamad Saied
- Pediatric Department, Carmel Medical Center, Michal 7 St., 3436212, Haifa, Israel
- Technion Faculty of Medicine, Haifa, Israel
- Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center, Utrecht, The Netherlands
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22
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Li H, Xing H. Interleukin-35 Enhances Regulatory T Cell Function by Potentially Suppressing Their Transdifferentiation into a T Helper 17-Like Phenotype in Kawasaki Disease. Immunol Invest 2023:1-16. [PMID: 37052682 DOI: 10.1080/08820139.2023.2201283] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
Interleukin-35 (IL-35) modulates immune cell activity in inflammation and autoimmune disorders. However, its specific effects on regulatory T cells (Tregs) in Kawasaki disease remain ambiguous. We enrolled 37 patients with Kawasaki disease and 20 healthy controls in this study. The percentages of CD4+CD25+CD127dim/- Tregs and CD4+IL-17A+ T helper 17 (Th17) cells were determined via flow cytometry. Tregs were enriched and stimulated by recombinant IL-35. Immunosuppressive activity of Tregs was via co-culture with autologous CD4+CD25- T cells. Purified Tregs were cultured for Th17 polarization, and the influence of IL-35 on Tregs transdifferentiation into a Th17-like phenotype was determined. The percentage of Tregs was elevated in patients with Kawasaki disease and positively correlated with C-reactive protein levels. There was no significant difference in the percentage of Th17 cells between the two groups. IL-35 stimulation increased the percentage of Tregs in both groups, but decreased the percentage of Tregs Th17 cells in affected patients. IL-35 enhanced the immunosuppressive activity of Tregs in both groups, resulting in decreased cellular proliferation and increased IL-35 subunit mRNA relative levels in co-culture system. IL-35 did not affect the immune checkpoint molecule expression in Tregs, but inhibited the transdifferentiation of Tregs into a Th17-like phenotype in affected patients, indicating by the down-regulations of C-C motif chemokine receptor-4/6 expression, retinoid-related orphan nuclear receptor γt mRNA levels, and IL-17 secretion. IL-35 contributes to the immunosuppressive function of Tregs by inhibiting the cellular proliferation and transdifferentiation of Tregs into a Th17-like phenotype, which may be a protective mechanism against Kawasaki disease.
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Affiliation(s)
- Hua Li
- Department of Disease Prevention and Control, Xi'an Children's Hospital, The Children's Hospital Affiliated to Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Haijian Xing
- Department of General Internal Medicine, Xi'an Children's Hospital, The Children's Hospital Affiliated to Xi'an Jiaotong University, Xi'an, Shaanxi, China
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23
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Kattner AA. When it doesn't run in the blood(vessels) - events involved in vascular disorders. Biomed J 2023; 46:100591. [PMID: 37059363 DOI: 10.1016/j.bj.2023.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 03/28/2023] [Indexed: 04/16/2023] Open
Abstract
In the current issue of the Biomedical Journal the underlying pathology of hemodynamic compromise in acute small subcortical infarction are elucidated. A follow-up study in patients with childhood Kawasaki disease is presented, as well as an insight into the gradually decreasing antigen expression in cases of acute myeloid leukemia. Furthermore this issue provides an exciting update concerning COVID-19 and the use of CRISPR-Cas, a review about computational approaches in the research of kidney stone formation, factors connected to central precocious puberty, and why a rock star of paleogenetics recently received a Nobel Prize. Additionally, this issue contains an article proposing the repurposing of the lung cancer drug Capmatinib, a study of how the gut microbiome develops in neonates, an impulse about the role of the transmembrane protein TMED3 in esophageal carcinoma, and the revelation about how competing endogenous RNA influences ischemic stroke. Lastly, genetic reasons for male infertility are discussed, as well as the relation between non-alcoholic fatty liver disease and chronic kidney disease.
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24
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Spratt F, Eilbert W. Child with fever and a rash. J Am Coll Emerg Physicians Open 2023; 4:e12932. [PMID: 36960352 PMCID: PMC10028413 DOI: 10.1002/emp2.12932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 03/01/2023] [Indexed: 03/24/2023] Open
Affiliation(s)
- Faith Spratt
- Department of Emergency MedicineUniversity of Illinois at Chicago, College of MedicineChicagoIllinoisUSA
| | - Wesley Eilbert
- Department of Emergency MedicineUniversity of Illinois at Chicago, College of MedicineChicagoIllinoisUSA
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25
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Tahir M, Mehmood R, Ahmad MS. Complete Kawasaki disease after COVID-19 infection in an infant. Pak J Med Sci 2023; 39:616-618. [PMID: 36950447 PMCID: PMC10025724 DOI: 10.12669/pjms.39.2.6359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 11/17/2022] [Accepted: 11/29/2022] [Indexed: 01/29/2023] Open
Abstract
Kawasaki disease is a generalized systemic vasculitis that affects blood vessels throughout the body. The aetiology of Kawasaki disease is still unknown but is thought to be related to the combined effects of the immune response, genetic susceptibility, and infections including COVID-19. In this case report, we present a seven months old male infant who presented to us with fever, swollen lips, ulcers in the mouth, enlarged tonsils, strawberry tongue, conjunctivitis and generalised non-blanchable maculopapular rash. The detailed workup fulfilled the criteria of Kawasaki disease. The COVID-19 IgM antibodies were positive. The patient was treated with IV Immunoglobulins, IV methylprednisolone and Aspirin. The repeat echocardiography on six weeks follow-up turned out normal. In conclusion, there should be a high index of suspicion of Kawasaki disease while evaluating pediatric patients with COVID-19 infection so that timely intervention can be made to prevent complications. Prospective studies are needed to evaluate the relationship between Kawasaki Disease and COVID-19 infection.
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Affiliation(s)
- Maliha Tahir
- Dr. Maliha Tahir, MBBS., King Edward Medical, University, Lahore, Pakistan. Medical Officer Pediatric, Department of Paediatrics Fazl-e-Omar Hospital, Chenab Nagar, District Chiniot, Pakistan
| | - Ramlah Mehmood
- Dr. Ramlah Mehmood, MBBS, FCPS (Pediatrics)., Consultant Pediatrician, Department of Paediatrics Fazl-e-Omar Hospital, Chenab Nagar, District Chiniot, Pakistan
| | - Mirza Sultan Ahmad
- Dr. Mirza Sultan Ahmad, MBBS, DCH, FCPS (Pediatrics)., Head of Department, Pediatrics, Department of Paediatrics Fazl-e-Omar Hospital, Chenab Nagar, District Chiniot, Pakistan
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26
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Singhal M, Pilania RK, Jindal AK, Gupta A, Sharma A, Guleria S, Johnson N, Maralakunte M, Vignesh P, Suri D, Sandhu MS, Singh S. Distal coronary artery abnormalities in Kawasaki disease: experience on CT coronary angiography in 176 children. Rheumatology (Oxford) 2023; 62:815-823. [PMID: 35394488 DOI: 10.1093/rheumatology/keac217] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 03/18/2022] [Accepted: 03/18/2022] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Precise evaluation of coronary artery abnormalities (CAAs) in Kawasaki disease (KD) is essential. The aim of this study is to determine role of CT coronary angiography (CTCA) for detection of CAAs in distal segments of coronary arteries in patients with KD. METHODS CTCA findings of KD patients with distal coronary artery involvement were compared with those on transthoracic echocardiography (TTE) during the period 2013-21. RESULTS Among 176 patients with KD who underwent CTCA (128-Slice Dual Source scanner), 23 (13.06%) had distal CAAs (right coronary-15/23; left anterior descending-14/23; left circumflex-4/23 patients). CTCA identified 60 aneurysms-37 proximal (36 fusiform; 1 saccular) and 23 distal (17 fusiform; 6 saccular); 11 patients with proximal aneurysms had distal contiguous extension; 9 patients showed non-contiguous aneurysms in both proximal and distal segments; 4 patients showed distal segment aneurysms in absence of proximal involvement of same coronary artery; 4 patients had isolated distal CAAs. On TTE, only 40 aneurysms could be identified. Further, distal CAAs could not be identified on TTE. CTCA also identified complications (thrombosis, mural calcification and stenosis) that were missed on TTE. CONCLUSIONS CAAs can, at times, occur in distal segments in isolation and also in association with, or extension of, proximal CAAs. CTCA demonstrates CAAs in distal segments of coronary arteries, including branches, in a significant number of children with KD-these cannot be detected on TTE. CTCA may therefore be considered as a complimentary imaging modality in children with KD who have CAAs on TTE.
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Affiliation(s)
| | - Rakesh Kumar Pilania
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ankur Kumar Jindal
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Aman Gupta
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Avinash Sharma
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sandesh Guleria
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nameirakpam Johnson
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Pandiarajan Vignesh
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Deepti Suri
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Surjit Singh
- Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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27
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Cem E, Böncüoğlu E, Kıymet E, Şahinkaya Ş, Yılmaz Çelebi M, Gülderen M, Kaçar P, Akaslan Kara A, Aydın A, Murat M, Yılmazer MM, Bayram N, Devrim İ. Which Findings Make multisystem Inflammatory Syndrome in Children Different from the Pre-Pandemic Kawasaki Disease? Pediatr Cardiol 2023; 44:424-432. [PMID: 35804239 PMCID: PMC9282145 DOI: 10.1007/s00246-022-02961-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/22/2022] [Indexed: 02/07/2023]
Abstract
Multisystem Inflammatory Syndrome in Children associated with COVID-19 infection attracted attention because some features overlapped with Kawasaki disease. And due to these overlapping features with Kawasaki disease, it has become difficult to diagnose both disorders. Therefore, this study focused on the differences between the patients diagnosed with MIS-C after COVID-19 and Kawasaki patients analyzed, particularly during the pre-pandemic period. In this way, it is aimed to reduce the dilemmas experienced in Diagnosis. In this descriptive study, 98 patients diagnosed with MIS-C throughout the pandemic were compared to 37 patients diagnosed with Kawasaki Disease during the pre-pandemic period.The patients in the MIS-C group were older children and clinically suffered from more headaches, vomiting, diarrhea, abdominal pain, and chest pain than Kawasaki patients. Signs of shock such as hypotension and tachycardia were more remarkable. Also, myocarditis and mitral regurgitation were detected at a higher rate in the MIS-C group. Besides, in the laboratory, lymphopenia, hypoalbuminemia, and creatinine elevation were more apparent.In conclusion, our present study findings support that although the MIS-C and Kawasaki share common features, they present with different clinical and laboratory features. And these differences are thought to be supportive in treatment and patient management.
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Affiliation(s)
- Ela Cem
- Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children's Hospital, İzmir, Turkey.
| | - Elif Böncüoğlu
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Elif Kıymet
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Şahika Şahinkaya
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Miray Yılmaz Çelebi
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Mustafa Gülderen
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Pelin Kaçar
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Aybüke Akaslan Kara
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Ayşenur Aydın
- grid.414112.30000 0004 0419 2150Department of Paediatrics, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Mehmet Murat
- grid.414112.30000 0004 0419 2150Department of Paediatric Cardiology Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Murat Muhtar Yılmazer
- grid.414112.30000 0004 0419 2150Department of Paediatric Cardiology Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Nuri Bayram
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - İlker Devrim
- grid.414112.30000 0004 0419 2150Department of Paediatric Infectious Diseases, University of Health Sciences Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
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28
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Martínez-García JJ, López-Acosta JR, Arce-Cabrera D, León-Sicairos N, Hernández-Parra AC, Cuen-Diaz HM, Zatarain-Lopez R, Canizalez-Roman A. Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease. Front Pediatr 2023; 11:1167828. [PMID: 37138560 PMCID: PMC10149839 DOI: 10.3389/fped.2023.1167828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/24/2023] [Indexed: 05/05/2023] Open
Abstract
Background Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1 An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2 A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.
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Affiliation(s)
- Jesús Javier Martínez-García
- Pediatric Intensive Care Unit, Pediatric Hospital of Sinaloa, Culiacan, Mexico
- School of Medicine, Autonomous University of Sinaloa, Culiacan, Mexico
| | | | | | - Nidia León-Sicairos
- School of Medicine, Autonomous University of Sinaloa, Culiacan, Mexico
- Research Department, Pediatric Hospital of Sinaloa, Culiacan, Mexico
| | | | | | | | - Adrian Canizalez-Roman
- School of Medicine, Autonomous University of Sinaloa, Culiacan, Mexico
- Research Department, The Women’s Hospital, Secretariat of Health, Culiacan, Mexico
- Correspondence: Adrian Canizalez Roman
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张 维, 沈 捷, 张 亚, 焦 富. [Clinical details in the diagnosis of Kawasaki disease]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2022; 24:1307-1310. [PMID: 36544408 PMCID: PMC9785088 DOI: 10.7499/j.issn.1008-8830.2208124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 11/01/2022] [Indexed: 12/24/2022]
Abstract
Kawasaki disease (KD) is one of the leading causes of acquired heart diseases in children aged under 5 years. The clinical manifestations of KD include fever, changes in the extremities, rash or redness at the site of bacille Calmette-Guérin vaccination, bilateral bulbar conjunctival hyperemia, changes in lips and mouth, nonsuppurative cervical lymphadenopathy, and other systemic manifestations. There are difficulties in the diagnosis of KD due to its asynchronous clinical manifestations. With reference to the latest case reports and research advances in KD, this article summarizes the clinical details in the diagnosis of KD, so as to improve the level of clinical diagnosis of KD.
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Affiliation(s)
| | - 捷 沈
- 上海儿童医学中心/上海交通大学附属儿童医院上海200120
| | | | - 富勇 焦
- 陕西省川崎病诊疗中心/陕西省人民医院儿童病院，陕西西安710068
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30
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Navarro FB, Mulinari L. Kawasaki disease: Surgical treatment. J Card Surg 2022; 37:4340-4341. [PMID: 36183393 DOI: 10.1111/jocs.16991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 01/06/2023]
Abstract
Kawasaki disease (KD) is a systemic vasculitis of small and medium arteries, preferably affecting coronary arteries. It is one of the most frequent causes of acquired heart disease in children. Despite being comprehensively studied, its etiopathogenesis is not totally explained. The surgical procedures usually become necessary during the late follow-up and may be coronary artery bypass grafting, cardiac defibrillator implantation with or without cardiac resynchronization therapy, or cardiac transplantation.
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Affiliation(s)
- Fabio B Navarro
- Cardiothoracic Surgery, Hospital Pequeno Principe, Curitiba, Paraná, Brazil
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31
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Li X, Sun Y, Cai Y, Zhang X, Zhang X. Identification of miRNA profile in the peripheral blood and clinical significance of miR-355 and miR-2911 expression in children with Kawasaki disease. Am J Transl Res 2022; 14:7820-7830. [PMID: 36505330 PMCID: PMC9730091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 04/12/2022] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To identify the abnormal expression profile of miRNA in peripheral blood of children with Kawasaki disease (KD) and explore its diagnostic value for Kawasaki disease. METHODS From January 2020 to June 2021, 62 children with KD (KD group) and 158 children with febrile disease (Con group) were selected as subjects. Peripheral blood was collected before treatment, and differentially expressed miRNAs in peripheral blood were identified by next generation sequencing, and the identified targets were verified by RT-PCR. The diagnostic value of miRNAs in KD was analyzed by ROC curves and linear SVM model. RESULTS Compared to Con group, a total of 163 differentially expressed miRNAs were detected in peripheral blood of children in the KD group, including 126 up-regulated miRNAs and 37 down-regulated miRNAs. Hierarchical clustering showed that miRNA profiles of children in the KD group and Con group were significantly different, among which 3 miRNAs wereup-regulated and 3 miRNAs were down-regulated (P<0.05). The results of miRanda and TargetScanS software showed that a total of 17159 target genes were predicted. GO function and KEGG signal pathway enrichment analysis showed that target genes were involved in a wide range of biological functions; ROC curve results showed that the sensitivity of miR-355 and miR-2911 in diagnosing KD were 73.8% and 71.2%, the specificity was 72.4% and 73.9%, and the AUC was 0.793 and 0.757, respectively. The AUC for combined detection of miR-355 and miR-2911 was increased to 0.806. A linear SVM model further verified the diagnostic value of joint detection of miR-355 and miR-2911. CONCLUSION Expression levels of miR-355 and miR-2911 were significantly up-regulated in peripheral blood of children with Kawasaki disease. miR-355 and miR-2911 could serve as biomarkers for diagnosis of Kawasaki disease.
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32
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Yang Y, Hu X. The Predictive Values of MMP-9, PLTs, ESR, and CRP Levels in Kawasaki Disease with Cardiovascular Injury. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:6913315. [PMID: 36159562 PMCID: PMC9492360 DOI: 10.1155/2022/6913315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/01/2022] [Accepted: 08/06/2022] [Indexed: 11/18/2022]
Abstract
Objective To explore the levels of matrix metalloproteinase-9 (MMP-9), platelets (PLTs), C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) and their predictive values in Kawasaki disease (KD) with cardiovascular injury. Methods 128 children were diagnosed with KD in the Lanzhou University Second Hospital. 75 patients had coronary artery lesion (CAL), while 53 patients did not. The levels of MMP-9, PLTs, and CRP and ESR in the two groups were determined. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve and the Youden index (YI) were used to evaluate the efficacy of MMP-9, PLTs, ESR, and CRP for predicting CALs in KD. Results The mean age of the patients was 2.7 ± 2.03 years (range, 2 months to 11 years). There were 87 boys (67.97%) and 41 girls (32.03%). In contrast to the NCAL group, the CAL group had obviously higher levels of MMP-9, PLTs, and CRP and an obviously higher ESR (P < 0.05). MMP-9 showed a linear positive correlation with ESR (P < 0.05) and CRP (P < 0.05). The AUC of the combined detection of the four indicators was 0.877, the sensitivity was 85.07% and the specificity was 78.95%. Conclusion MMP-9, PLTs, ESR, and CRP are important indicators for a CAL in KD. The efficacy of the combined detection of MMP-9, PLTs, ESR and CRP is better than that of any single indicator for predicting a CAL in KD.
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Affiliation(s)
- Yinan Yang
- Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu, China
| | - Xiaobin Hu
- Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, China
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Castaldo A, D’Anna C, Gelzo M, Giannattasio A, Maglione M, Muzzica S, Raia M, Scalia G, Tripodi L, Castaldo G, Tipo V, Grieco D, Grieco M. Immunophenotyping of peripheral blood cells allows to discriminate MIS-C and Kawasaki disease. TRANSLATIONAL MEDICINE COMMUNICATIONS 2022; 7:22. [PMID: 36093039 PMCID: PMC9440857 DOI: 10.1186/s41231-022-00128-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 08/09/2022] [Indexed: 06/12/2023]
Abstract
BACKGROUND The pathogenesis of the novel described multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) is still debated as it is not clear if they are the same or different nosological entities. However, for both the diseases a rapid and unequivocal diagnosis is mandatory to start the therapy before the onset of severe complications. In this study, we aimed to evaluate the white cell populations in MIS-C and KD as potential markers to discriminate between the two diseases. METHODS We studied white cell populations by flow cytometry in 46 MIS-C and 28 KD patients in comparison to 70 age-matched healthy children. RESULTS MIS-C patients had a significant lymphopenia that involved both B and T populations while KD patients showed a significant neutrophilia and thrombocythemia. Granulocyte/lymphocyte ratio helped to diagnose both MIS-C and KD with a high diagnostic sensitivity, while a multivariate analysis of granulocyte and T lymphocyte number contributed to discriminate between the two diseases. CONCLUSIONS The relevant lymphopenia observed in MIS-C patients suggests that the disease would be a post-infectious sequel of COVID-19 immunologically amplified by a massive cytokine release, while the significant neutrophilia and thrombocythemia observed in KD confirmed that the disorder has the genesis of a systemic vasculitis. The analysis of a panel of circulating cells may help to early diagnose and to discriminate between the two diseases. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1186/s41231-022-00128-2.
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Affiliation(s)
- Alice Castaldo
- Dipartimento Di Scienze Mediche Traslazionali, Sezione Di Pediatria, Università Di Napoli Federico II, Naples, Italy
| | - Carolina D’Anna
- Dipartimento Di Emergenza, AORN Santobono-Pausilipon, Naples, Italy
| | - Monica Gelzo
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
- Dipartimento Di Medicina Molecolare E Biotecnologie Mediche, Università Di Napoli Federico II, Naples, Italy
| | | | - Marco Maglione
- Dipartimento Di Emergenza, AORN Santobono-Pausilipon, Naples, Italy
| | - Stefania Muzzica
- Dipartimento Di Emergenza, AORN Santobono-Pausilipon, Naples, Italy
| | - Maddalena Raia
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
| | - Giulia Scalia
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
| | - Lorella Tripodi
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
| | - Giuseppe Castaldo
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
- Dipartimento Di Medicina Molecolare E Biotecnologie Mediche, Università Di Napoli Federico II, Naples, Italy
| | - Vincenzo Tipo
- Dipartimento Di Emergenza, AORN Santobono-Pausilipon, Naples, Italy
| | - Domenico Grieco
- CEINGE-Biotecnologie Avanzate, via Gaetano Salvatore 486, 80145, scarl, Naples, Italy
| | - Michela Grieco
- Dipartimento Di Emergenza, AORN Santobono-Pausilipon, Naples, Italy
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Lu Z, Zheng Z, Xu Y, Wang C, Lin Y, Lin K, Fu L, Zhou H, Pi L, Che D, Gu X. The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population. J Inflamm Res 2022; 15:5053-5062. [PMID: 36081762 PMCID: PMC9448350 DOI: 10.2147/jir.s378080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/05/2022] [Indexed: 11/23/2022] Open
Abstract
Background Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported. Methods A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance. Results Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06–3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10–2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62–4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37–3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22–2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24–2.27, p = 0.0008). Conclusion Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.
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Affiliation(s)
- Zhaojin Lu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Zepeng Zheng
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Yufen Xu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Chenlu Wang
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Yueling Lin
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Kun Lin
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - LanYan Fu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Huazhong Zhou
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Lei Pi
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Di Che
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
- Correspondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076562, Email
| | - Xiaoqiong Gu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
- Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China
- Xiaoqiong Gu, Department of Clinical Biological Resource Bank, Department of Clinical Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076561, Email
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Wen H, Hun M, Zhao M, Han P, He Q. Serum ferritin as a crucial biomarker in the diagnosis and prognosis of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease: A systematic review and meta-analysis. Front Med (Lausanne) 2022; 9:941739. [PMID: 36035423 PMCID: PMC9399505 DOI: 10.3389/fmed.2022.941739] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/11/2022] [Indexed: 12/15/2022] Open
Abstract
Background Early identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase. Methods The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervals (CIs) were applied to compute the pooled assessments of the outcomes. Results A total of 11 eligible articles were included in this meta-analysis, including twenty studies for diagnosis and five studies for prognosis. In terms of diagnostic values, SF could identify KD patients in the overall studies with a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.76 (95% CI: 0.69-0.82), 0.82 (95% CI: 0.76-0.88), 4.33 (95% CI: 3.07-6.11), 0.29 (95% CI: 0.22-0.38), 15.0 (95% CI: 9.00-25.00), and 0.86 (95% CI: 0.83-0.89), respectively. In studies comparing KD patients and controls, there were a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.79 (95% CI: 0.72-0.84), 0.84 (95% CI: 0.79-0.91), 4.61 (95% CI: 3.27-6.51), 0.26 (95% CI: 0.20-0.34), 20.82 (95% CI: 11.83-36.64), and 0.89 (95% CI: 0.86-0.91), respectively. For the prognostic values, we found poor survival outcomes based on KD patients (HR = 1.31, 95% CI: 1.07-1.59, P = 0.008). Conclusion Our meta-analysis suggests that SF may be used as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs. Systematic review registration [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].
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Affiliation(s)
- Huai Wen
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Marady Hun
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Mingyi Zhao
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Phanna Han
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qingnan He
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
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Ultrasound Comparative Analysis of Coronary Arteries before and after Immune Blocking Therapy with Gamma Globulin in Children with Kawasaki Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2900378. [PMID: 35966739 PMCID: PMC9371854 DOI: 10.1155/2022/2900378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 05/26/2022] [Accepted: 06/29/2022] [Indexed: 11/21/2022]
Abstract
Objective To investigate the ultrasound characteristics and clinical efficacy of coronary arteries before and after immune blocking therapy with gamma globulin in children with Kawasaki disease. Methods A total of 64 children with Kawasaki disease who were treated in our hospital from January 2018 to October 2021 were selected. All the children were given immune blocking therapy with gamma globulin on the basis of conventional treatment. The disappearance time of related symptoms and signs (fever, mucosal congestion, cervical lymphadenopathy, and swelling of the hands and feet) in children were counted. The white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), and procalcitonin (PCT) levels of the children before and after treatment were compared, and the characteristics of coronary echocardiography before and after treatment were observed for analysis and discussion, to carefully observe whether the coronary artery involvement of the children was improved. Results The inner diameter of the left and right coronary arteries significantly decreased (P < 0.05), and the levels of leukocytes, platelets, CRP, erythrocyte sedimentation rate, vascular endothelial growth factor (VEGF), and endostatin were significantly decreased compared with those before treatment, with a statistical difference (P < 0.05). Conclusion The effect of gamma globulin in the treatment of Kawasaki disease is remarkable, which can improve the blood indexes, VEGF, and endostatin levels in children, significantly reduce coronary dilatation, and reduce the incidence of coronary artery disease. Echocardiography is of high value in the examination of children with Kawasaki disease, which can accurately detect the size, location, and inner diameter of coronary artery lesions, and can effectively evaluate the treatment effect on children.
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Lee H, Eun Y, Hwang JY, Eun LY. Explainable deep learning algorithm for distinguishing incomplete Kawasaki disease by coronary artery lesions on echocardiographic imaging. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2022; 223:106970. [PMID: 35772231 PMCID: PMC9214709 DOI: 10.1016/j.cmpb.2022.106970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 04/30/2022] [Accepted: 06/19/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND AND OBJECTIVE Incomplete Kawasaki disease (KD) has often been misdiagnosed due to a lack of the clinical manifestations of classic KD. However, it is associated with a markedly higher prevalence of coronary artery lesions. Identifying coronary artery lesions by echocardiography is important for the timely diagnosis of and favorable outcomes in KD. Moreover, similar to KD, coronavirus disease 2019, currently causing a worldwide pandemic, also manifests with fever; therefore, it is crucial at this moment that KD should be distinguished clearly among the febrile diseases in children. In this study, we aimed to validate a deep learning algorithm for classification of KD and other acute febrile diseases. METHODS We obtained coronary artery images by echocardiography of children (n = 138 for KD; n = 65 for pneumonia). We trained six deep learning networks (VGG19, Xception, ResNet50, ResNext50, SE-ResNet50, and SE-ResNext50) using the collected data. RESULTS SE-ResNext50 showed the best performance in terms of accuracy, specificity, and precision in the classification. SE-ResNext50 offered a precision of 81.12%, a sensitivity of 84.06%, and a specificity of 58.46%. CONCLUSIONS The results of our study suggested that deep learning algorithms have similar performance to an experienced cardiologist in detecting coronary artery lesions to facilitate the diagnosis of KD.
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Affiliation(s)
- Haeyun Lee
- Department of Electrical Engineering and Computer Science
| | - Yongsoon Eun
- Department of Electrical Engineering and Computer Science; The Interdisciplinary Studies of Artificial Intelligence
| | - Jae Youn Hwang
- Department of Electrical Engineering and Computer Science; The Interdisciplinary Studies of Artificial Intelligence.
| | - Lucy Youngmin Eun
- Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, South Korea.
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Upregulated Expression of IL2RB Causes Disorder of Immune Microenvironment in Patients with Kawasaki Disease. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2114699. [PMID: 35924269 PMCID: PMC9343205 DOI: 10.1155/2022/2114699] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/11/2022] [Indexed: 11/18/2022]
Abstract
Aims. The clinical diagnosis of Kawasaki disease (KD) is not easy because of many atypical manifestations. This study is aimed at finding potential diagnostic markers and therapeutic targets for KD and analysing their correlation with immune cell infiltrations. Methods. First, we downloaded the KD dataset from the Gene Expression Omnibus (GEO) database and used R software to identify differentially expressed genes (DEGs) and perform functional correlation analysis. Then, CIBERSORT algorithm was used to evaluate immune cell infiltrations in samples. Coexpression analysis between DEGs and infiltrating immune cells was performed to screen the main infiltrating immune cells. Subsequently, the least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to screen the core genes related to KD. Finally, correlation analysis between the core genes and the main infiltrating immune cells was performed. Results. 327 DEGs were screened out in this study. Among them, 72 shared genes were the category of genes most likely to be disease-causing for they did not change before and after treatment. After analysis, it was found that expression level of IL2RB in KD tissues was significantly upregulated, the number of resting CD4+ memory T cells was decreased, and the decrease was significantly negatively correlated with the upregulated expression of IL2RB. Therefore, it was speculated that the upregulated expression of IL2RB disrupted Th1/Th2 cell differentiation balance, which led to a decrease of resting CD4+ memory T cells and finally caused disorder of immune microenvironment in patients with KD. Conclusions. Upregulated expression of IL2RB leads to disorder of immune microenvironment in patients with KD and eventually causes the occurrence and development of KD. Therefore, IL2RB may serve as a diagnostic marker and potential therapeutic target for KD.
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Madan D, Maheshwari A, Mahto D, Mendiratta V, Sharma S. Kawasaki Disease with Peripheral and Facial Gangrene: A Case report and review of literature. Trop Doct 2022; 52:449-452. [PMID: 35345947 DOI: 10.1177/00494755221081598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
With the onset of the SARS-CoV-2 pandemic, Kawasaki Disease (KD) has come to the fore with its many atypical manifestations. Atypical clinical neurological, ophthalmological, musculoskeletal, gastrointestinal and pulmonary manifestations in a febrile child with raised markers should prompt the clinician to think of Kawasaki disease. Peripheral gangrene is a rare atypical manifestation of KD reported in infancy. We present a three-and-a-half-year-old boy with extensive gangrene all four limbs and face along with purpura fulminans. He was successfully treated with two doses of intravenous immunoglobulin (IVIG) and infliximab, with no residual gangrene. This case highlights that very severe forms of Kawasaki disease require IVIG, pulse steroids as well as infliximab for adequate control and complete resolution of the disease.
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Affiliation(s)
- Dolly Madan
- Department of Pediatrics, Kalawati Saran Children's Hospital and Lady Hardinge Medical College, New Delhi, India
| | - Anu Maheshwari
- Department of Pediatrics, Kalawati Saran Children's Hospital and Lady Hardinge Medical College, New Delhi, India
| | - Deonath Mahto
- Department of Pediatrics, Kalawati Saran Children's Hospital and Lady Hardinge Medical College, New Delhi, India
| | - Vibhu Mendiratta
- Department of Dermatology, Lady Hardinge Medical College, New Delhi, India
| | - Sunita Sharma
- Department of Pathology, Lady Hardinge Medical College, New Delhi, India
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Çakmak F, Demir F, Çakan M, Sonmez HE, Çağlayan Ş, Karadağ ŞG, Varlı YZ, Otar Yener G, Öztürk K, Sözeri B, Aktay Ayaz N. Is it all about age? Clinical characteristics of Kawasaki disease in the extremely young: PeRA research group experience. Postgrad Med 2022; 134:429-434. [PMID: 35324413 DOI: 10.1080/00325481.2022.2058206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES : In the evaluation of children with Kawasaki disease (KD), the age of onset is important and complications may occur if the distinctive features are not assessed accordingly. The objective of the study is to define the clinical and laboratory presentations and treatment outcomes of KD in infants ≤6 months of age compared to those >6 months multicentrically. METHODS : This retrospective study reviewed the medical records of the patients diagnosed with KD and followed up between January 2009 and January 2019. RESULTS : A total of 204 KD patients were enrolled and grouped according to age as Group I (≤6 months, n=31) and Group II (>6 months, n=173). Except for cervical adenopathy (19.3% vs. 47.4%, p=0.03), the major clinical manifestations of KD were similar between groups I and II. However, the frequency of incomplete and atypical KD was higher in Group I (38.7% vs. 24.8%, p=0.04, 38.7% vs. 8.1% p<0.001, respectively). Clinical features such as vomiting/diarrhea (19.3% vs. 1.1% p<0.001), aseptic meningitis (19.3% vs. 2.3%, p=0.001) were more common in Group I. Percentage of neutrophils (45.5 vs. 36, p=0.004) and hemoglobin levels (8 vs. 10.5 gr/dL, p=0.02) were statistically lower and platelet count (737000 vs 400000/mm3, p=0.004) was statistically higher in group I. Coronary artery lesions (CALs) were more common in Group I (48% vs. 20 %, p<0.001). Harada and Kobayashi scores appear to be effective in predicting coronary artery lesions (CALs) and IVIG resistance in the entire cohort. There was no diagnostic delay in group I (5.5 vs 6.5 days, p=0.88). CONCLUSIONS : Since clinical presentations and laboratory features of KD may vary with age, and the frequency of atypical and incomplete presentations is high, awareness of KD in young children should be raised among pediatricians.
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Affiliation(s)
- Figen Çakmak
- Department of Pediatric Rheumatology, Istanbul University Faculty of Medicine, Fatih, Istanbul, Turkey
| | - Ferhat Demir
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Mustafa Çakan
- Department of Pediatric Rheumatology, Zeynep Kamil Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Hafize Emine Sonmez
- Department of Pediatric Rheumatology, Kocaeli University Medical School, Kocaeli, Turkey
| | - Şengül Çağlayan
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Şerife Gül Karadağ
- Department of Pediatric Rheumatology, Erzurum Training and Research Hospital, Erzurum, Turkey
| | - Yusuf Ziya Varlı
- Department of Pediatrics, Istanbul Basaksehir City Hospital, Istanbul, Turkey
| | - Gülçin Otar Yener
- Department of Pediatric Rheumatology, Sanliurfa Training and Research Hospital, Sanlıurfa, Turkey
| | - Kübra Öztürk
- Department of Pediatric Rheumatology, Goztepe Prof. Dr Suleyman Yalcın City Hospital,Istanbul Medeniyet University, Istanbul, Turkey
| | - Betül Sözeri
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Nuray Aktay Ayaz
- Department of Pediatric Rheumatology, Istanbul University Faculty of Medicine, Fatih, Istanbul, Turkey
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Choi J, Chang S, Kim E, Min SY. Integrative treatment of herbal medicine with western medicine on coronary artery lesions in children with Kawasaki disease. Medicine (Baltimore) 2022; 101:e28802. [PMID: 35363167 PMCID: PMC9281920 DOI: 10.1097/md.0000000000028802] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/24/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Kawasaki disease (KD) is a major cause of coronary artery lesions (CALs) in children. Approximately 10% to 20% of children treated with intravenous immunoglobulin are intravenous immunoglobulin-resistant. This study evaluated the efficacy and safety of adding herbal medicine to conventional western medicines versus conventional western medicines alone for CALs in children with KD. METHODS This study searched 9 electronic databases until August 31, 2021. The inclusion criteria were the randomized controlled trials (RCTs) that assessed the CALs in children with KD and compared integrative treatment with conventional western treatments. Two authors searched independently for RCTs, including eligible articles that fulfilled the inclusion criteria, extracted data, and assessed the methodological quality using the Cochrane risk of bias tool. Meta-analysis was conducted using Cochrane Collaboration's Review Manager 5.4 software. The effect size was presented as the risk ratio (RR), and the fixed-effect models were used to pool the results. RESULTS The finally selected 12 studies included a total of 1030 KD patients. According to a meta-analysis, the integrative treatment showed better results than the conventional treatment in the CAL prevalence rate (RR = 2.00; 95% confidence interval [CI], 1.49-2.71; P < .00001), CAL recovery rate (RR = 1.27; 95% CI, 1.05-1.54; P = .02), and total effective rate (RR = 1.17; 95% CI, 1.11-1.23; P < .00001). Only 2 studies referred to the safety of the treatment. The asymmetrical funnel plot of the CAL prevalence rate indicated the possibility of potential publication bias. CONCLUSIONS This review found the integrative treatment to be more effective in reducing the CAL prevalence rate and increasing the CAL recovery rate and total effective rate in KD patients than conventional western treatment. However, additional well-designed RCTs will be needed further to compensate restrictions of insufficient trials on safety, methodological quality, and publication bias.
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Affiliation(s)
- Jungyoon Choi
- Department of Pediatrics of Korean Medicine, Graduate School of Dongguk University, Pildong-ro 1-Gil 30, Jung-gu, Seoul, Republic of Korea
| | - Seokjoo Chang
- Department of Pediatrics of Korean Medicine, Graduate School of Dongguk University, Pildong-ro 1-Gil 30, Jung-gu, Seoul, Republic of Korea
| | - Eunjin Kim
- Department of Pediatrics of Korean Medicine, Korean Medicine Hospital, Dongguk University Bundang Medical Center, 268, Buljeong-ro, Bun-dang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Sang Yeon Min
- Department of Pediatrics of Korean Medicine, Graduate School of Dongguk University, Pildong-ro 1-Gil 30, Jung-gu, Seoul, Republic of Korea
- Department of Pediatrics of Korean Medicine, Korean Medicine Hospital, Dongguk University Ilsan Medical Center, Dongguk-ro 27, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea
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Bakutenko IY, Haurylchyk ID, Nikitchenko NV, Sechko E, Kozyro IA, Tchitchko AM, Batyan GM, Sukalo AV, Ryabokon NI. Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile-onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children. Mol Genet Genomic Med 2022; 10:e1859. [PMID: 34971477 PMCID: PMC8801135 DOI: 10.1002/mgg3.1859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 11/08/2021] [Accepted: 12/17/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non-synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. METHODS In order to test this hypothesis, we conducted a pilot case-control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real-time polymerase chain reaction was used for genotyping. RESULTS The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18-5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. CONCLUSION Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD.
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Affiliation(s)
- Ivan Y. Bakutenko
- Laboratory of Molecular Basis of Genome StabilityInstitute of Genetics and CytologyNational Academy of Sciences of BelarusMinskBelarus
| | - Irena D. Haurylchyk
- Laboratory of Molecular Basis of Genome StabilityInstitute of Genetics and CytologyNational Academy of Sciences of BelarusMinskBelarus
| | - Natalia V. Nikitchenko
- Laboratory of Molecular Basis of Genome StabilityInstitute of Genetics and CytologyNational Academy of Sciences of BelarusMinskBelarus
| | - Elena V. Sechko
- 1st Department of Childhood DiseasesBelarusian State Medical UniversityMinskBelarus
| | - Inna A. Kozyro
- 1st Department of Childhood DiseasesBelarusian State Medical UniversityMinskBelarus
| | - Alexei M. Tchitchko
- 1st Department of Childhood DiseasesBelarusian State Medical UniversityMinskBelarus
| | - Galina M. Batyan
- 1st Department of Childhood DiseasesBelarusian State Medical UniversityMinskBelarus
| | - Alexander V. Sukalo
- 1st Department of Childhood DiseasesBelarusian State Medical UniversityMinskBelarus
| | - Nadezhda I. Ryabokon
- Laboratory of Molecular Basis of Genome StabilityInstitute of Genetics and CytologyNational Academy of Sciences of BelarusMinskBelarus
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Mauro A, Di Mari C, Casini F, Giani T, Sandini M, Biondi L, Calcaterra V, Zuccotti GV, Bernardo L. Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities. Front Pediatr 2022; 10:1088773. [PMID: 36683824 PMCID: PMC9849814 DOI: 10.3389/fped.2022.1088773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 12/02/2022] [Indexed: 01/07/2023] Open
Abstract
Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosis.
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Affiliation(s)
- A Mauro
- Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy
| | - C Di Mari
- Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy
| | - F Casini
- Pediatric Department, "Vittore Buzzi" Children's Hospital, Milan, Italy
| | - T Giani
- Department of Pediatrics, Anna Meyer Children's Hospital, Florence, Italy
| | - M Sandini
- Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy
| | - L Biondi
- Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy
| | - V Calcaterra
- Pediatric Department, "Vittore Buzzi" Children's Hospital, Milan, Italy.,Department of Pediatrics, Anna Meyer Children's Hospital, Florence, Italy.,Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - G V Zuccotti
- Pediatric Department, "Vittore Buzzi" Children's Hospital, Milan, Italy
| | - L Bernardo
- Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy
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Rahmati Y, Mollanoori H, Najafi S, Esmaeili S, Alivand MR. CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study. BMC Pediatr 2021; 21:566. [PMID: 34895171 PMCID: PMC8665509 DOI: 10.1186/s12887-021-03003-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 11/13/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Kawasaki disease (KD) is a pediatric inflammatory disorder causes coronary artery complications. The disease overlapping manifestations with a set of symptomatically like diseases such as bacterial and viral infections, juvenile idiopathic arthritis, Henoch-Schönlein purpura, infection of unknown etiology, group-A streptococcal and adenoviral infections, and incomplete KD could lead to misdiagnosis of the disease. METHODS In the present study, we applied weighted gene co-expression network analysis (WGCNA) to identify network modules of co-expressed genes in GSE73464 and also, limma package was used to identify the differentially expressed genes (DEGs) in KD expression arrays composed of GSE73464, GSE18606, GSE109351, and GSE68004. By merging the results of WGCNA and limma, we detected hub genes. Then, analyzed the peripheral blood mononuclear cells (PBMCs) of 16 patients and 8 control subjects using Real-Time Polymerase Chain Reaction (RT-PCR) to evaluate the previous results. RESULTS We assessed the diagnostic potency of the screened genes by plotting the area under curve (AUC). We finally identified 2 genes CASP5(Caspase 5) and CR1(Complement C3b/C4b Receptor 1) which were shown to potentially discriminate KD from other similar diseases and also from healthy people. CONCLUSIONS The results of RT-PCR and AUC confirmed the diagnostic potentials of two suggested biomarkers for KD.
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Affiliation(s)
- Yazdan Rahmati
- Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hasan Mollanoori
- Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sajad Najafi
- Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sajjad Esmaeili
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Reza Alivand
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Peters AA, Abbuehl H, Spano G, Graeni C, Huber AT. Chronic occluded coronary aneurysm as a complication of Kawasaki disease: a long-term follow-up. J Cardiovasc Med (Hagerstown) 2021; 22:e47-e48. [PMID: 34494604 DOI: 10.2459/jcm.0000000000001244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Alan A Peters
- Department of Diagnostic, Interventional and Pediatric Radiology
| | - Heidi Abbuehl
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Giancarlo Spano
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Christoph Graeni
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Adrian T Huber
- Department of Diagnostic, Interventional and Pediatric Radiology
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Carotid Intima-Media Thickness and Ankle-Brachial Index and Their Correlation with Coronary Artery Dilatation in Children with Kawasaki Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:7372424. [PMID: 34737783 PMCID: PMC8563121 DOI: 10.1155/2021/7372424] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022]
Abstract
Objective To investigate the correlation between carotid intima-media thickness (IMT), ankle-brachial index (ABI), and coronary artery dilatation (CAD) in children with Kawasaki disease (KD) and to evaluate the effectiveness of CAD. Methods A total of 68 children diagnosed with KD from January 2019 to January 2021 in our hospital were included. According to the results of cardiac color Doppler ultrasound, the children with KD were divided into a noncoronary artery dilation group (NCAD), with 41 children with KD who did not have coronary artery lesions, and a coronary artery dilation group (CAD), with 27 children with KD who had coronary artery dilation. 27 healthy children undergoing physical examination in our hospital at the same time were selected as the normal control group. Laboratory index of all subjects was measured individually. The carotid IMT, ABI, and coronary artery diameter of all subjects were measured and compared. Pearson correlation was used to analyze the correlation between carotid IMT, ABI, and the severity of coronary artery disease. The ROC curve was used to evaluate the efficacy of carotid IMT and ABI in predicting coronary artery disease. Results The ALB of children in the CAD group was lower than that in the NCAD group (P < 0.05). The IMT of carotid artery and the diameter of coronary artery in children of the CAD group and the NCAD group were higher than those of the normal control group, and the IMT of the CAD group was higher than that of the NCAD group. The ABI of children in the CAD group and the NCAD group was lower than that of the normal control group, and the ABI of children in the CAD group was lower than that of the NCAD group (P < 0.05). Correlation analysis showed that carotid artery IMT of children with KD was positively correlated with coronary artery diameter, while ABI was negatively correlated with coronary artery diameter. The AUC of carotid IMT for CAD in children with KD was 0.668 (95% CI: 0.538–0.797), that of ABI for CAD in children with KD was 0.646 (95% CI: 0.513–0.780), and that of the combination of carotid IMT and ABI for CAD was 0.874 (95% CI: 0.785–0.963). Conclusion The changes of carotid artery IMT and ABI in children with KD have a certain correlation with CAD, and the joint detection of carotid artery IMT and ABI can provide clinical reference value for predicting the degree of coronary artery disease in children with KD.
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Abstract
ABSTRACT Multisystem inflammatory syndrome in children is a previously unrecognized and potentially catastrophic illness that appears in children who have been exposed to or diagnosed with COVID-19. As healthcare agents and members of the community, nurses are positioned to assist in identifying children who may experience previously unrecognized complications of infection from the SARS-CoV-2 virus.
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Affiliation(s)
- Andrew Greenway
- Andrew Greenway is a clinical nurse specialist, burn/trauma, at NewYork-Presbyterian Hospital in Piermont, N.Y. At NewYork-Presbyterian/Weill Cornell Medical Center in New York, N.Y., Holly Macklay is a family NP, burn unit; Kevin Xuereb is a clinical manager, women's health; and Linda Gibbons is director of nursing, women's health, and burn services
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Beitzke D. [Acute and chronic cardiac involvement in COVID-19]. Radiologe 2021; 61:896-901. [PMID: 34529127 PMCID: PMC8444505 DOI: 10.1007/s00117-021-00913-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2021] [Indexed: 11/28/2022]
Abstract
Hintergrund Neben pulmonalen Manifestationen ist eine COVID-19-Infektion (Coronavirus-Krankheit 2019) häufig mit kardiovaskulären Komplikationen bzw. einer kardiovaskulären Beteiligung assoziiert. Das Herz kann im Rahmen einer Infektion sowohl direkt im Rahmen einer Myokarditis oder Perikarditis und auch im Rahmen von Hypoxie, Fieber, Volumenbelastungen oder thrombembolischer Komplikationen involviert werden. Bestehende kardiovaskuläre Grunderkrankungen haben zudem einen maßgeblichen Einfluss auf die Prognose von COVID-19-infizierten Patienten. Methode Diese Übersichtsarbeit basiert auf einer umfassenden Literaturrecherche in der PubMed-Datenbank zu kardialen Beteiligungen und kardialen Komplikationen einer COVID-19-Infektion sowie deren Abgleich mit eigenen Erfahrungen. Ergebnisse und Schlussfolgerung Je nach Schweregrad der Infektion werden kardiale Beteiligungen im Rahmen einer COVID-19-Infektion mit bis zu 50 % durchaus häufig beobachtet. Neben der Echokardiographie als Untersuchungsmethode der ersten Wahl stellen die kardiale Magnetresonanztomographie (MRT) zur Beurteilung der myokardialen Struktur und die kardiale Computertomographie (CT) zur Beurteilung der Koronararterien bzw. zum Ausschluss eines intrakardialen Thrombus bedeutende Untersuchungsmodalitäten dar. Die wichtigsten kardialen Manifestationen einer COVID-19-Infektion sind entzündliche und ischämische Pathologien. Deren bildgebende Diagnostik spielt sowohl im akuten als auch im postinfektiösen Stadium eine bedeutende Rolle.
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Affiliation(s)
- Dietrich Beitzke
- Universitätsklinik für Radiologie und Nuklearmedizin, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.
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Shioji N, Aoyama K, Englesakis M, Annich G, Maynes JT. Multisystem inflammatory syndrome in children during the coronavirus disease pandemic of 2019: a review of clinical features and acute phase management. J Anesth 2021; 35:563-570. [PMID: 34052944 PMCID: PMC8164829 DOI: 10.1007/s00540-021-02952-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 05/22/2021] [Indexed: 11/30/2022]
Abstract
The current coronavirus disease of 2019 (COVID-19) pandemic has presented unique health challenges in the pediatric population. Compared to adults, the most significant change in viral disease manifestation is encompassed by the multisystem inflammatory syndrome in children (MIS-C). MIS-C is a new inflammatory syndrome which develops 2-4 weeks after COVID-19 exposure, with evidence suggesting it is a post-infectious immune reaction. We describe its epidemiology, pathophysiology, diagnosis (which varies based on definition used) and treatment options based on published recommendations. A systematic literature search we conducted through MEDLINE yielded 518 abstracts and identified five studies that reported more than 100 cases of MIS-C and their mortality. Most cases developed multiorgan dysfunction, including cardiovascular, dermatologic, neurological, renal, and respiratory issues, and required intensive care unit (ICU) admission. Many patients admitted to the ICU needed inotrope support and invasive mechanical ventilation, and the most severe cases required extracorporeal membrane oxygenation support. Most clinicians treated MIS-C with intravenous immunoglobulin, systemic steroids, and biological therapies. Overall mortality was low (2-3%) in all studies. Further research is needed to: understand if early intervention can prevent its progression; optimize its treatment; and improve outcomes of this new syndrome for the patients who develop MIS-C.
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Affiliation(s)
- Naohiro Shioji
- Department of Critical Care Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada
- Department of Critical Care Medicine, Okayama University Hospital, Okayama, Japan
| | - Kazuyoshi Aoyama
- Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
- Program in Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Canada.
| | - Marina Englesakis
- Library and Information Services, University Health Network, Toronto, Canada
| | - Gail Annich
- Department of Critical Care Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Jason T Maynes
- Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada
- Program in Molecular Medicine, SickKids Research Institute, Toronto, Canada
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Banday AZ, Mondal S, Barman P, Sil A, Kumrah R, Vignesh P, Singh S. What Lies Ahead for Young Hearts in the 21 st Century - Is It Double Trouble of Acute Rheumatic Fever and Kawasaki Disease in Developing Countries? Front Cardiovasc Med 2021; 8:694393. [PMID: 34250047 PMCID: PMC8263915 DOI: 10.3389/fcvm.2021.694393] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/01/2021] [Indexed: 12/19/2022] Open
Abstract
Rheumatic heart disease (RHD), the principal long-term sequel of acute rheumatic fever (ARF), has been a major contributor to cardiac-related mortality in general population, especially in developing countries. With improvement in health and sanitation facilities across the globe, there has been almost a 50% reduction in mortality rate due to RHD over the last 25 years. However, recent estimates suggest that RHD still results in more than 300,000 deaths annually. In India alone, more than 100,000 deaths occur due to RHD every year (Watkins DA et al., N Engl J Med, 2017). Children and adolescents (aged below 15 years) constitute at least one-fourth of the total population in India. Besides, ARF is, for the most part, a pediatric disorder. The pediatric population, therefore, requires special consideration in developing countries to reduce the burden of RHD. In the developed world, Kawasaki disease (KD) has emerged as the most important cause of acquired heart disease in children. Mirroring global trends over the past two decades, India also has witnessed a surge in the number of cases of KD. Similarly, many regions across the globe classified as “high-risk” for ARF have witnessed an increasing trend in the incidence of KD. This translates to a double challenge faced by pediatric health care providers in improving cardiac outcomes of children affected with ARF or KD. We highlight this predicament by reviewing the incidence trends of ARF and KD over the last 50 years in ARF “high-risk” regions.
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Affiliation(s)
- Aaqib Zaffar Banday
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjib Mondal
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Prabal Barman
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Archan Sil
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajni Kumrah
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pandiarajan Vignesh
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Surjit Singh
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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