Kawasaki Disease

Contents
Introduction and History of Kawasaki Disease
Epidemiology
Is Kawasaki Disease an Infectious Disease?
Is Kawasaki Disease a Genetic Disease?
Is Kawasaki Disease an Immune-Mediated Disease?
References
Clinical Symptoms of Kawasaki Disease
Clinical Symptoms of Classic KD
Fever
Extremity Changes
Skin Rash
Conjunctivitis
Oropharyngeal Changes
Cervical Lymphadenopathy
Incomplete (Atypical) KD
Unusual Manifestation of KD
KD, KDSS (Kawasaki Disease Shock Syndrome), and Multisystem Inflammatory Syndrome in Children (MIS-C)
References
Diagnosis of Kawasaki Disease and Development of New Biomarkers
Clinical Features and Diagnosis of Kawasaki Disease
Diagnosis of Incomplete (or Atypical) Kawasaki Disease
Echocardiographic Findings That Aid in the Diagnosis of Kawasaki Disease
Development of New Biomarkers to Aid in the Diagnosis of Kawasaki Disease
Conclusion
References
Treatment of Kawasaki Disease
Intravenous Immunoglobulin
Acetylsalicylic Acid
Adjuvant Therapy: Corticosteroids
Adjuvant Therapy: Biologics
Adjuvant Treatments: Cyclosporin
Adjuvant Treatments: Clarithromycin
Second-Line Therapy of Refractory Kawasaki Disease
References
Precision Medicine and Big Data Research of Kawasaki Disease
Big Data and Precision Medicine
Using Big Data for Kawasaki Disease Incidence Estimation
The Validity of Claim Data
Complication Rate Estimation
Recurrence Rates
How to Estimate the Incidence Accurately by Big Data
Head-to-Head Comparison of Different Immunoglobulins from Big Data Research
Comparing Timing of Immunoglobulin Therapy by Big Data
Genetic Predisposition to Kawasaki Disease from the Perspective of Big Data
Future Perspectives for Precision Medicine for Kawasaki Disease
References
Complication of Kawasaki Disease
CAA
IVIG Resistance
References
How to Prevent Complication of KD
Introduction
Precise Diagnosis (How to Identify Typical or Atypical Kawasaki Disease)
Clinical Diagnosis Criteria (Kuo Mnemonic: 1-2-3-4-5 for Rapid Memory)
Bacillus Calmette–Guerin (BCG) Site Induration
Consulting a Kawasaki Disease Expert
AHA Supplemental Criteria
COVID-19 and Kawasaki Disease
Treating Kawasaki Disease and IVIG Resistance with Precision Medicine
IVIG (Intravenous Immunoglobulin or Intravenous Gamma-Globulin)
Aspirin
IVIG Resistance (Nonresponsiveness or Failure)
Preventing Coronary Artery Lesion Formation
Other Off-Label Treatments
Potential Role of Molecular Hydrogen Gas (H2) in KD [59]
Promoting Kawasaki Disease Awareness
Conclusion
References
Imaging of Coronary Artery Abnormalities in Kawasaki Disease with Emphasis on Multimodalities
Introduction
Noninvasive Evaluation of Coronary Artery Abnormalities in Kawasaki Disease
Transthoracic Echocardiography
FOCUS Methodology
Measurement of Coronary Lumen Size at Different Cardiac Cycles
Coronary Computed Tomography Angiography
Coronary CTA in the Patients with Possible Regression in a Chronic Phase of KD
Cardiac Magnetic Resonance Imaging
Invasive Evaluation of Coronary Artery Abnormalities in Kawasaki Disease
Invasive Selective Coronary Angiography
Intravascular Ultrasound
Virtual Histology Intravascular Ultrasound
Optical Coherence Tomography (OCT)
Near-Infrared Spectroscopy Intravascular Ultrasound
Giant Coronary Aneurysm Regression Validated by Transthoracic Echocardiography and Coronary CTA
Summary (Take Home Message)
References
Clinical Research of Kawasaki Disease
Fever
Conjunctivitis
Oral Mucosa Manifestations
Lymphadenopathy
Skin Manifestations
Changes in the Extremities
Incomplete Kawasaki Disease
Kawasaki Disease Shock Syndrome
Refractory Kawasaki Disease
Infant Kawasaki Disease
Kawasaki Disease in Adolescents
Laboratory Tests for KD
References
Laboratory Research and Scoring System of Kawasaki Disease
Laboratory Data for Distinguishing Kawasaki Disease from Fever in Children
Clinical Features Differentiating Children with Fever Suspected of Kawasaki Disease (Do Not Fit KD Diagnosis Upon Admission, But Fit Diagnosis During Follow-Up) [16]
Nomogram Model for Predicting Kawasaki Disease
The Importance of Eosinophils in Kawasaki Disease
Neutrophil-to-Lymphocyte Ratio in Kawasaki Disease
Prognostic Nutrition Index (PNI) in Kawasaki Disease
C-Reactive Protein-to-Albumin Ratio (CRP/Alb) in Kawasaki Disease
References
Genetic Study of Kawasaki Disease
Introduction
Genetics and KD
B Lymphoid Tyrosine Kinase (BLK)
Caspase-3 (CASP3)
Cluster of Differentiation 40 (CD40) and CD40 Ligand (CD40L)
Fc Fragment of IgG Receptor IIa (FCGR2A)
HLA Complex 5 (HCP5)
Human Leukocyte Antigen (HLA)
Immunoglobulin Heavy Chain (IGH) Variable (IGHV)
Interleukin (IL)-4 and the IL-4 Receptor (IL-4R)
Inositol-Triphosphate 3-Kinase C (ITPKC)
Multidrug Resistance Protein 4 (MRP4)
Nicotinamide Mononucleotide Adenylyl Transferase 2 (NMNAT2)
SMAD3
High-Mobility Group Box 1 (HMGB1)
Interleukin (IL)-16
Purinergic Receptor P2Y12 (P2RY12)
Sterile Alpha Motif Domain-Containing Protein 9-Like (SAMD9L)
Prediction of Intravenous Immunoglobulin Resistance Using a Genetic Risk Score (GSC)
Conclusions
References
Epigenetics in Kawasaki Disease
Methylation in KD
MicroRNA Alteration in KD
References
Transcriptomics in Kawasaki Disease
Introduction
Transcriptomics to Unravel Mechanisms of KD
mRNA Transcripts in Patients’ Blood
mRNA Transcripts in KD Patients’ Heart Tissues
mRNA Transcripts in KD-Like Mouse Models
Noncoding Transcripts Biosignatures in KD
Emerging Applications of Transcriptomics in Kawasaki Disease
Immune Receptor Repertoire
Neutrophil-Associated Genes as Potential Targets in Kawasaki Disease
Perspective of Transcriptomics in Kawasaki Disease
Conclusion
References
Immune Responses in Kawasaki Disease
A Postinfectious Autoimmune Disease of Kawasaki Disease
Kinetic Progress on the Immunopathogenesis of Kawasaki Disease
Immune Responses of Different KD Variants
Genetic and Epigenetic Immunoregulation of KD with and Without Complications
Immunotherapies Based on Immune Response of KD
References
Anemia in Kawasaki Disease
Kawasaki Disease Is the Most Common Vasculitis of the Coronary Arteries in Children
Anemia in Patients with Kawasaki Disease
Hepcidin Expression Is Associated with the Prognosis of Kawasaki Disease
Iron Deficiency Caused by Hepcidin Is Related to Transient Hypoferremia and Anemia in KD Patients
HAMP Promoter Hypomethylation and Elevated Hepcidin Levels Are Biomarkers of Kawasaki Disease
Other Studies on Hepcidin in Kawasaki Disease
Conclusion
References
Psychological or Mental Issues in Kawasaki Disease
Background
KD and Cognition
KD and ADHD
KD and Autism Spectrum Disorders
KD and Caregiver Pressure
Conclusion
References
Infection or not in Kawasaki Disease
What Is Infection?
Clinical and Epidemiological Evidence
Clinical Presentation of Vasculitis
Age Distribution
Gender
Seasonality
Tropospheric Wind
Intra-Family Transmission
Recurrence
Cluster Phenomenon
Laboratory Evidence
Pathological Discovery
Bacterial Infections and Superantigens
Viral Infections
SARS-CoV-2 Infection
Conclusion
References
Kawasaki Disease Shock Syndrome and Mild KD
Introduction
Definition of KDSS
Interracial Incidence
Etiology (Shock Mechanism)
Cardiogenic Shock Component (Hypokinesia)
Cardiogenic Shock Component (Valvular Insufficiency)
Distributive Shock Component
Clinical Manifestations (Database Limitation Is Addressed in the End of the Section)
Database Limitation
Conditions that Mimic Kawasaki Disease Shock Syndrome
Toxic Shock Syndrome
Septic Shock
Adverse Effect of IVIG
Treatment
Mortality
Significant Difference between KDSS and Mild KD
Conclusion (Take Home Message)
References
Gut Microbiota in Kawasaki Disease
Introduction
Gut Microbiota in Childhood Diseases
Gut Microbiota and Risk of Cardiovascular Diseases
Proposed Infectious Causes of KD
The Complex Relationship Between Gut Microbiota and Kawasaki Disease
Conclusion
References
Allergic Diseases and Association with Kawasaki Disease
Allergy-Related Biomarkers in Kawasaki Disease
Allergic Diseases and Association with Kawasaki Disease
Allergic Diseases Before Kawasaki Disease
Asthma and Kawasaki Disease
References
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