Textbook of Pediatric Rheumatology

Description

Offering up-to-date, comprehensive coverage of disease progression, diagnosis, management, and prognosis, Textbook of Pediatric Rheumatology is the definitive reference in the field. For physicians caring for children with rheumatic diseases, this revised 8th Edition is an unparalleled resource for the full spectrum of rheumatologic diseases and non-rheumatologic musculoskeletal disorders in children and adolescents. Global leaders in the field provide reliable, evidence-based guidance, highlighted by superb full-color illustrations that facilitate a thorough understanding of the science that underlies rheumatic disease. Offers expanded coverage of autoinflammatory diseases, plus new chapters on Takayasu Arteritis and Other Vasculitides, Mechanistic Investigation of Pediatric Rheumatic Diseases, Genetics and Pediatric Rheumatic Diseases, and Global Issues in Pediatric Rheumatology.  Reflects the changes in diagnosis, monitoring, and management that recent advances have made possible.  Covers the latest information on small molecule treatment, biologics, biomarkers, epigenetics, biosimilars, and cell-based therapies, helping you choose treatment protocols based on the best scientific evidence available today.  Features exhaustive reviews of the complex symptoms, signs, and lab abnormalities that characterize these clinical disorders.  Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices. cover Front Matter Textbook of PEDIATRIC RHEUMATOLOGY Copyright Copyright Dedication Dedication Preface PREFACE Contributors CONTRIBUTORS 1 - Structure and Function 1 - Structure and Function Bone Structure and Function 1 Joints Tendons Ligaments and fascia Entheses Bursae Skeletal muscle Classification of Skeletal Muscles Based on Shape The Function of Skeletal Muscle Online References 2 - Genetics and Pediatric Rheumatic Diseases 2 - Genetics and Pediatric Rheumatic Diseases Genetics and Pediatric Rheumatic Diseases Introduction Genes, Variation, and the Human Genome Sequence in Biomedical Research Gene Structure, Function, and the Central Dogma of Molecular Biology Noncoding RNA Gene Regulation Genetic Variation SNP Genotyping Conventional DNA Sequencing Massively Parallel High-Throughput Sequencing Approaches for Investigating Monogenic Pediatric Rheumatic Disease Linkage Analysis High-Throughput Sequencing-Based Studies Approaches for Investigating Polygenic Pediatric Rheumatic Disease Family Studies (Twins, Siblings, Registries) Association Studies Candidate Gene Studies in Pediatric Rheumatology Transmission Disequilibrium Testing Genome-Wide Association Studies Genome Editing Online References 3 - Mechanistic Investigation of Pediatric Rheumatic Diseases 3 - Mechanistic Investigation of Pediatric Rheumatic Diseases Mechanistic Investigation of Pediatric Rheumatic Diseases Introduction The Essence of a Test Essentials Normal Ranges Absolute Versus Relative Measurement Hypothesis Generating versus Hypothesis Testing Omic Resources Genetic and Epigenetic Investigations Cell Separation Flow Cytometry Fluorescence-Activated Cell Sorting Cytometry by Time-of-Flight Cytometry in Disease Protein Quantitation and Proteomics General Aspects of Proteomics in Juvenile Rheumatic Diseases Protein Localization Protein Quantitation Challenges in Proteomics Proteomics in Pediatric Rheumatic Diseases Quantitating RNA General Aspects Transcriptomics Assessment of Microbial Populations Traditional Techniques Summary Online References 4 - Inflammation and Its Mediators 4 - Inflammation and Its Mediators Phagocytes Inflammation and Its Mediators 4 Dendritic Cells Natural Killer Cells Innate Lymphoid Cells Fibroblasts Molecules of Innate Immunity The Inflammatory Response The Recruitment of Leukocytes into Inflamed Tissue Online References 5 - Adaptive Immunity and Autoimmunity 5 - Adaptive Immunity and Autoimmunity T Cells T-Cell Development Adaptive Immunity and Autoimmunity 5 Antigen-Induced T-Cell Activation Effector T-Cell Differentiation T Cells in Autoimmunity T-Cell Subsets in Autoimmunity B Cells B-Cell Development Antibody Production by B Cells Antibody-Independent Effector Mechanisms Antigen Presentation HLA Genes, Proteins, and Functions Peptide Loading Pathways for HLA Class I and Class II Molecules Functional Specialization of Antigen Presentation Mechanisms Antigen Presentation by HLA Molecules and Disease Therapeutic Targeting of Antigen Presentation Conclusions Online References 6 - Understanding Clinical Investigations 6 - Understanding Clinical Investigations Understanding Clinical Investigations 6 Basic Concepts Exposures and Outcomes Observational Versus Experimental Studies Controlled Versus Uncontrolled Studies Association Versus Causation Formalizing a Research Question Study Design Descriptive Studies Case-Control Studies Cohort Studies Randomized Controlled Studies Comparative Effectiveness Studies Cluster Randomized Studies Decision Analysis and Cost-Effectiveness Studies Systematic Reviews and Meta-Analysis Studies Describing Data Measures of Central Tendency and Variance Z Scores Describing Nonnormal or Nonparametric Distributions Paradigms of Inference Hypothesis Testing Sample Size Determinations Concepts and Terminology for Communicating Study Results Confidence Intervals Disease Frequency: Incidence and Prevalence Communicating Risk Assessing Predictive Ability Reproducibility of Results Basic Tests of Association Selecting the Appropriate Statistical Test One-Sample Tests Two-Sample Tests K-Sample Tests Correlations and Analyses of Association Advanced Data Analyses Regression Analyses Analysis of Covariance Survival Analysis Measures of Agreement Among and Within Raters Multivariate Analyses Factor Analysis Item Response Theory and Rasch Analysis Assessing and Interpreting Results Missing Data Bias Assessing the Quality of Clinical Investigations Assessing Individual Studies Online References 7 – Clinical Outcome Measures in Pediatric Rheumatic Diseases 7 - Clinical Outcome Measures in Pediatric Rheumatic Diseases Juvenile Idiopathic Arthritis American College of Rheumatology Pediatric Response Criteria Criteria for Clinically Inactive JIA Clinical Outcome Measures in Pediatric Rheumatic Diseases Criteria for Low (or Minimal) Disease Activity Juvenile Arthritis Disease Activity Score (JADAS) Systemic JADAS Juvenile Arthritis Damage Index Systemic Lupus Erythematosus British Isles Lupus Assessment Group The Pediatric Rheumatology International Trials Organization Preliminary Core Set of Outcome Variables and Definition of Improve... ACR Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents with Childhood-Onset Systemic Lupus Ery... Juvenile Dermatomyositis Manual Muscle Testing Childhood Myositis Assessment Scale Hybrid MMT/CMAS (hMC) Cutaneous Assessment Tool Disease Activity Score Myositis Damage Index The PRINTO and International Myositis Assessment and Clinical Studies Group Core Sets and Definitions of Improvement Criteria for Inactive Disease Scleroderma Modified Localized Scleroderma Skin Severity Index Juvenile Systemic Sclerosis Severity Score Modified Rodnan Skin Score Systemic Vasculitis Pediatric Vasculitis Activity Score Vasculitis Damage Index Parent- and Child-Reported Outcomes Childhood Health Assessment Questionnaire Child Health Questionnaire Pediatric Quality of Life Inventory (PedsQL) Juvenile Arthritis Quality of Life Questionnaire Conclusions Online References 8 - Pain and Its Assessment 8 - Pain and Its Assessment Pain and Its Assessment Introduction Biopsychosocial Model of Pain Biological Factors Psychological Factors Social/Environmental Factors Implications for Assessment and Treatment Assessment of Pain Self-Report Pain Measures Electronic Pain Diaries Observational Behavioral Measures Treatment of Pain Future Directions Online References 9 - Imaging in Pediatric Rheumatic Diseases 9 - Imaging in Pediatric Rheumatic Diseases Imaging Modalities: Technical Aspects Radiography Sonography Computed Tomography Imaging in Pediatric Rheumatic Diseases 9 Cone Beam Computed Tomography Magnetic Resonance Imaging Arthrography Bone Scintigraphy Physiological Findings, Normal Variants, and Reference Standards Radiography Sonography Magnetic Resonance Imaging Imaging in Joint Disease Inflammatory Arthritis Juvenile Idiopathic Arthritis Imaging in the Assessment of Response to Therapy Transient Synovitis of the Hip Joint Injections Enthesitis-Related Arthritis/Spondylarthopathies Appendicular Skeleton Axial Skeleton Psoriatic Arthritis Radiography Sonography Magnetic Resonance Imaging Axial Skeleton Online References 10 - Laboratory Investigations 10 - Laboratory Investigations Laboratory Methods Immunofluorescence Enzyme-Linked Immunosorbent Assay (ELISA) Laboratory Investigations 10 Radioimmunoassay Immunoblotting (Western Blotting) Immunodiffusion and Counterimmunoelectrophoresis Turbidimetry and Nephelometry Laser Microbead Arrays Tests Antinuclear Antibodies Immunofluorescence Patterns Antibodies to Extractable Nuclear Antigens Detection Anti-DNA Antibodies Detection Antinucleosome Antibodies Antineutrophil Cytoplasmic Antibodies Antiglomerular Basement Membrane Antibodies Rheumatoid Factor Anticitrullinated Peptide Antibodies Antiphospholipid Antibodies Complement Other Laboratory Investigations Measures of the Acute Phase Response Synovial Fluid Urinalysis Genetic Assessment of Rheumatic Diseases The Future Online References 11 - Principles in the Management of Patients with Rheumatic Disease 11 - Principles in the Management of Patients with Rheumatic Disease General Approach to Management Scope of Disease Long-Term Goals and Functioning Approach Principles in the Management of Patients with Rheumatic Disease 11 Family and Education Other Important Topics Financial and Insurance Issues Complementary and Alternative Therapies Future Endeavors Treat to Target Summary Organizations Online References 12 – Global Issues in Pediatric Rheumatology 12 - Global Issues in Pediatric Rheumatology EPIDEMIOLOGY Juvenile Idiopathic Arthritis Systemic Lupus Erythematosus Juvenile Dermatomyositis Vasculitis Acute Rheumatic Fever Challenges in Diagnosis and Management Socioeconomic Challenges Challenges Related to Comorbidities Shortage of Specialized Manpower Strategies to Improve Outcomes Increasing Knowledge About Pediatric Rheumatology Other Options Development of Guidelines and Consortia for the Management of Rheumatic Disease in Low-Resource Settings Enhancement of Research in Diseases Prevalent in Less-Resourced Countries Online References 13 - Therapeutics- Nonbiologics 13 - Therapeutics: Nonbiologics Drug Absorption and Bioavailability Volume of Distribution Half-Life and Clearance Therapeutics: Nonbiologics 13 Drug Biotransformation Precision Medicine and Individualized Drug Therapy Antirheumatic Drugs Nonsteroidal Antiinflammatory Drugs Salicylates Disease-Modifying Antirheumatic Drugs Other Disease-Modifying Drugs Therapeutics for Amplified Pain Online References 14 - Therapeutics- Biologics and Small Molecules 14 - Therapeutics: Biologics and Small Molecules Therapeutics: Biologics and Small Molecules 14 Intravenous Immunoglobulin Inhibition Of T Cell Costimulation CTLA-4 Ig (Abatacept) B-Cell Targeted biological Dmards Rituximab Belimumab Interference With Cytokines Tumor Necrosis Factor Inhibitors Etanercept Infliximab Adalimumab Golimumab Certolizumab IL-1 Inhibitors IL-6 Inhibitors IL-17 and IL-23 Inhibition Kinase Inhibitors Tofacitinib Baricitinib and Others Other JAK Inhibitors Online References 15 - Nonmedical Therapies in Pediatric Rheumatic Diseases 15 - Nonmedical Therapies in Pediatric Rheumatic Diseases Epidemiology of Joint and Muscle Health in Pediatric Rheumatic Conditions Juvenile Idiopathic Arthritis Juvenile Dermatomyositis Nonmedical Therapies in Pediatric Rheumatic Diseases 15 Juvenile Systemic Lupus Erythematosus Juvenile Scleroderma Examining Joint and Muscle Health Assessment of Muscle Function and Muscle Strength Improving Joint and Muscle Health Joint and Muscle Pain Joint and Muscle Exercise Motor Development and Motor Performance Motor Behavior as a Diagnostic Tool for Musculoskeletal Conditions in Early Life Early Motor Milestones, Motor Proficiency at School Age, Physical Literacy, Sports, and Athletic Skills at Adolescence Physical Activity Level and Exercise Tolerance Physical Activity Level Aerobic and Anaerobic Fitness Psychosocial and Occupational Health Psychosocial Development Daily Living: Pain and Pain Relief Daily Living: Fatigue, Sleep, Energy Conservation, and Pacing Strategies Play, School, and Social Inclusion Long-Term Considerations Additional Aspects of Health Patient and Family Education Effects of Uveitis on Function Summary Acknowledgements Online References 16 - Juvenile Idiopathic Arthritis - Classification and Basic Concepts 17 - Systemic Juvenile Idiopathic Arthritis 17 - Systemic Juvenile Idiopathic Arthritis Systemic Juvenile Idiopathic Arthritis Epidemiology Etiology and Pathogenesis Clinical Manifestations Fever Rash Musculoskeletal Disease Myalgia and Myositis Cardiac Disease Pleural Disease Lymphadenopathy and Splenomegaly Hepatic Disease Central Nervous System Disease Other sJIA Features Complications of sJIA Diagnosis and Differential Diagnosis Adult-Onset Still Disease Pathology Laboratory Examination Radiological Examination Treatment Approach to Management Pharmacological Therapy Course of the Disease and Prognosis Online References 18 - Polyarticular Juvenile Idiopathic Arthritis 18 - Polyarticular Juvenile Idiopathic Arthritis Polyarticular Juvenile Idiopathic Arthritis Definitions RF-Negative Polyarticular JIA Epidemiology Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Laboratory Testing Treatment Course of the Disease and Prognosis Rheumatoid Factor Positive Polyarthritis Epidemiology Etiology and Pathogenesis Genetic Background Clinical Manifestations Differential Diagnosis Laboratory Investigations Treatment Course of the Disease and Prognosis Online References 19 - Oligoarticular Juvenile Idiopathic Arthritis 19 - Oligoarticular Juvenile Idiopathic Arthritis Epidemiology Incidence Prevalence Age at Onset Sex Ratio Genetics Oligoarticular Juvenile Idiopathic Arthritis 19 HLA Genes Non-HLA Genes Etiology and Pathogenesis Environmental Factors Immunological Factors Clinical Manifestations Laboratory Evaluation Radiographic Evaluation Pathology Diagnosis Treatment General Management Medical Management Physical Therapy Surgery Disease Course and Prognosis Perspective Online References 20 - Enthesitis-Related Arthritis 20 - Enthesitis-Related Arthritis Enthesitis-Related Arthritis Definition and Classification Epidemiology Incidence and Prevalence Age at Onset Sex Ratio Geographical and Racial Distribution Etiology Genetic Background Pathogenic Mechanisms Clinical Manifestations Enthesitis Arthritis Peripheral Joint Arthritis Axial Skeleton Uveitis Gastrointestinal Disease Cardiopulmonary Disease Nervous System Disease Renal Disease Pathology Differential Diagnosis Laboratory Examination Radiological Examination Sacroiliac Joints Spine Entheses Whole-Body MRI Treatment General Management Medications Physical and Occupational Therapy Surgery Course of the Disease and Prognosis ONLINE References 21 - Psoriatic Juvenile Idiopathic Arthritis 21 - Psoriatic Juvenile Idiopathic Arthritis Psoriatic Juvenile Idiopathic Arthritis Definition and Classification Epidemiology Incidence and Prevalence Age at Onset and Sex Ratio Etiology, Pathology, and Pathogenesis Pathology Synovial Pathology Entheseal Pathology Pathogenesis Genetic Contribution Cytokines and Other Mediators The Microbiota Environmental Contribution Clinical Manifestations Subgroups within PsJIA Laboratory Examination Radiologic Examination Treatment Peripheral Arthritis Spondylitis Course and Prognosis Online References 22 – Uveitis in Juvenile Idiopathic Arthritis 22 - Uveitis in Juvenile Idiopathic Arthritis CLASSIFICATION OF UVEITIS UVEITIS IN JUVENILE IDIOPATHIC ARTHRITIS Uveitis in Juvenile Idiopathic Arthritis History: The Association of Arthritis and Uveitis Epidemiology Etiology and Pathogenesis Genetic Background Clinical Manifestations Differential Diagnosis Uveitis in Other Diseases LABORATORY EXAMINATION Investigations MANAGEMENT Medical Management of Chronic Uveitis Associated with JIA Surgical Management DISEASE COURSE AND PROGNOSIS ONLINE REFERENCES 23 – Systemic Lupus Erythematosus, Mixed Connective Tissue Disease, and Undifferentiated Connective Tissue Disease 23 - SYSTEMIC LUPUS ERYTHEMATOSUS, MIXED CONNECTIVE TISSUE DISEASE, AND UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE EPIDEMIOLOGY CLINICAL DISEASE PRESENTATION APPROACH TO THE CHILD WITH SLE MORBIDITY AND MORTALITY 24 - Antiphospholipid Syndrome 24 - Antiphospholipid Syndrome Antiphospholipid Syndrome Definition and Classification Epidemiology Primary Antiphospholipid Syndrome Secondary Antiphospholipid Syndrome Healthy Children Etiology and Pathogenesis Pathophysiology Characteristics that Influence Pathogenicity of APLA Prothrombotic Effects of APLA on Cells Genetic Background Genetic Studies Clinical Manifestations Thrombosis Hematological Manifestations Skin Manifestations Neurological Manifestations Other Manifestations Catastrophic Antiphospholipid Syndrome Perinatal Complications Associated with APLA Pathology Diagnosis and Differential Diagnosis Laboratory Examination Radiologic Examination Treatment Primary Thromboprophylaxis Other Drugs Catastrophic Antiphospholipid Syndrome Course of the Disease and Prognosis Online References 25 - Neonatal Lupus Erythematosus Neonatal Lupus Erythematosus Neonatal Lupus Erythematosus Etiology and Pathogenesis Autoantigens Calcium Channels Autoantibodies Maternal Factors Environmental Factors Immunological Factors Genetic Background Clinical Features Cardiac NLE Cutaneous Neonatal Lupus Erythematosus Liver Disease Hematological Disease Neurological Involvement Chondrodysplasia Punctata Other Manifestations Long-Term Risk of Autoimmune Disease Children Mothers Online References 26 - Juvenile Dermatomyositis and Other Inflammatory Muscle Diseases 26 - Juvenile Dermatomyositis and Other Inflammatory Muscle Diseases Epidemiology Causes and Pathogenesis Genetic Background Environmental Factors Immunological Mechanisms Chimerism Clinical Manifestations Constitutional Symptoms and Signs Musculoskeletal Disease Mucocutaneous Disease Cardiopulmonary Involvement Gastrointestinal Disease Rare Manifestations Classification and Diagnostic Criteria Laboratory Examination/Investigations Muscle Enzymes Other Biomarkers Autoantibodies Electromyography Muscle Biopsy Radiological Examination Differential Diagnosis Amyopathic Dermatomyositis Juvenile Polymyositis Infectious Inflammatory Myopathies Noninflammatory Myopathies Malignancy-Associated Dermatomyositis Cutaneous Lesions without Muscle Involvement Treatment Pharmacological Treatment Nonpharmacological Treatment Management of Calcinosis Management of Lipodystrophy and Metabolic Syndrome Clinical Assessment Course of the Disease and Prognosis Course of the Disease Mortality Rate and Cause of Death Prognosis and Long-term Outcome Complications Calcinosis Lipodystrophy Osteoporosis Online References 27 - Juvenile Systemic Sclerosis 27 - Juvenile Systemic Sclerosis Demographics and Epidemiology Etiology and Pathogenesis Genetics Juvenile Systemic Sclerosis 27 Overview of Pathogenesis Immunological Factors Fibroblasts and Endothelium Clinical Features Cutaneous Vascular Musculoskeletal Gastrointestinal Cardiopulmonary Renal Neurological Overall Disease Monitoring Patient Reported Outcomes Systemic Sclerosis Treatment Renal Disease Pulmonary Arterial Hypertension Raynaud Phenomenon Medical Treatment of Raynaud Phenomenon Digital Ulcers Treatment of SSc-Associated Interstitial Lung Disease Hematopoietic Stem Cell Therapy Cardiac Disease Gastrointestinal Disease Cutaneous Disease Musculoskeletal Disease Prognosis Online References 28 – Localized Scleroderma and Eosinophilic Fasciitis 28 - Localized Scleroderma and Eosinophilic Fasciitis HISTORICAL REVIEW DEFINITION AND CLASSIFICATION Associated Conditions EPIDEMIOLOGY ETIOLOGY AND PATHOGENESIS Clinical Manifestations PATHOLOGY DIFFERENTIAL DIAGNOSIS LABORATORY EXAMINATION Disease Monitoring TREATMENT OF LOCALIZED SCLERODERMA Skin Directed Therapies Systemic Treatment Other Treatments and Multiprofessional Team Care COURSE OF THE DISEASE AND PROGNOSIS ONLINE REFERENCES 29 - Sjögren Syndrome and Immunoglobulin-G4 Disease 29 - Sjögren Syndrome and Immunoglobulin-G4 Disease Definition And Epidemiology Classification Sjögren Syndrome and Immunoglobulin-G4 Disease 29 Clinical Manifestations Oral Manifestations Ocular Manifestations Other Glandular Involvement Extraglandular Manifestations Skin Manifestations Arthritis Pulmonary Involvement Renal Involvement Neurological Involvement Pathology Pathogenesis Autoantibodies Immunopathological Mechanism of Disease Laboratory Examination Imaging Studies Minor Salivary Gland and Parotid Biopsy Management Outcome Measures Prognosis and Outcome Progression to Lymphoma IGG4-Related Diseases Online References 30 - Raynaud Phenomenon and Vasomotor Syndromes 30 - Raynaud Phenomenon and Vasomotor Syndromes Clinical Presentation Epidemiology Etiology/Pathogenesis Raynaud Phenomenon and Vasomotor Syndromes 30 Diagnosis History Clinical Criteria Nailfold Capillary Microscopy Laboratory Testing Differential Diagnosis Treatment of Raynaud Phenomenon General Measures Behavioral Therapy Pharmacological Measures Other Measures Chemical or Surgical Sympathectomy Summary Management of Digital Ischemia Erythromelalgia Summary and Future Directions Key References Online References cover 31 - Inflammatory Central Nervous System Disorders Inflammatory Central Nervous System Disorders Specific Inflammatory Brain Conditions Primary Angiitis of the CNS Antibody-Associated Encephalopathies Rasmussen Encephalitis Multiple Sclerosis Neuromyelitis Optica Spectrum Disorder Acute Disseminated Encephalomyelitis Immune Dysregulation/Autoinflammatory CNS Disorders Deficiency of Adenosine Deaminase 2 (DADA2) Acute Necrotizing Encephalopathy Pediatric Acute-Onset Neuropsychiatric Syndrome Summary Online References 32 - Vasculitis and Its Classification 32 - Vasculitis and Its Classification Classification Vasculitis and Its Classification 32 Evaluation of Vasculitis Epidemiology General Clinical Aspects of Vasculitis Online References 33 - Immune Complex Small-Vessel Vasculitis- IgA Vasculitis (Henoch–Schönlein) and Hypersensitivity Vasculitis 33 - Immune Complex Small-Vessel Vasculitis: IgA Vasculitis (Henoch–Schönlein) and Hypersensitivity Vasculitis Immune Complex Small-Vessel Vasculitis: IgA Vasculitis (Henoch–Schönlein) and Hypersensitivity Vasculitis Iga Vasculitis (Henoch–SchÖnlein Purpura) Definition and Classification Epidemiology Etiology and Pathogenesis Genetic Background Clinical Manifestations Pathology Differential Diagnosis Laboratory Examination Radiological Examination Treatment Course of the Disease and Prognosis Hypersensitivity Vasculitis Online References 34 – Polyarteritis Nodosa 34 - Polyarteritis Nodosa Polyarteritis Nodosa (Systemic) Definitions and Classification Criteria Epidemiology Etiology and Pathogenesis Clinical Features Laboratory Investigations Radiological and Other Investigations Management Outcome Cutaneous Polyarteritis Nodosa Treatment Summary Online References 35 - Kawasaki Disease 35 - Kawasaki Disease Definition and Diagnostic Criteria Epidemiology Kawasaki Disease 35 Etiology and Pathogenesis Genetic Background Clinical Manifestations Disease Course Other Clinical Manifestations of Kawasaki Disease Differential Diagnosis Pathology Laboratory Evaluation Treatment General Approach Goals of Therapy Aspirin Intravenous Immunoglobulin Prediction of IVIG Resistance Corticosteroids Treatment of IVIG Resistance Monitoring Cardiac Status Disease Course and Prognosis Online References 36 - Antineutrophil Cytoplasmic Antibody Associated Vasculitis 36 - Antineutrophil Cytoplasmic Antibody Associated Vasculitis Antineutrophil Cytoplasmic Antibody Associated Vasculitis Antineutrophil Cytoplasmic Antibodies Granulomatosis With Polyangiitis Classification Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Examination Pathology Imaging Treatment Remission Maintenance Localized Disease Refractory Vasculitis Disease Measurement Tools Clinical Course and Outcome Microscopic Polyangiitis Definition and Disease Classification Epidemiology Pathogenesis Clinical Manifestations Pathology Diagnosis and Differential Diagnosis Laboratory Examination Treatment Course of the Disease and Prognosis Definition and Disease Classification Epidemiology Pathogenesis Clinical Manifestations Pathology Diagnosis and Differential Diagnosis Laboratory Examination Imaging Treatment Course of the Disease and Prognosis Online References 38 - Behçet Disease 38 - Behçet Disease Behçet Disease Introduction and Historical Review Definitions and Classifications Epidemiology Incidence and Prevalence Sex Ratio and Age at Onset Genetic Background Etiology and Pathogenesis Clinical Manifestations Mucocutaneous Disease Ocular Disease Central Nervous System Disease Musculoskeletal Disease Vascular Disease Gastrointestinal Disease Renal Disease Other Uncommon Manifestations Pathology Laboratory Investigations Radiological Examinations Differential Diagnosis Treatment Oral and Genital Ulcers Ocular Inflammation Treatment of Other Manifestations Course of Disease and Prognosis Online References 39 - Periodic Fever Syndromes and Other Inherited Autoinflammatory Diseases 39 - Periodic Fever Syndromes and Other Inherited Autoinflammatory Diseases Familial Mediterranean Fever Periodic Fever Syndromes and Other Inherited Autoinflammatory Diseases 39 Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Mevalonate Kinase Deficiency NLRP3-Associated Autoinflammatory Disease FCAS (NLRP3-AID Mild) Muckle–Wells Syndrome (NLRP3-AID Moderate) NOMID/CINCA (NLRP3-AID Severe) Periodic Fever Resulting from Cyclic Hematopoiesis Deficiency of the Interleukin-1 Receptor Antagonist Deficiency of Interleukin Thirty-Six Receptor Antagonist STING-Associated Vasculopathy with Onset in Infancy Haploinsufficiency of A20 NLRC4 Macrophage Activation Syndrome/Syndrome of Enterocolitis and Autoinflammation Associated with Mutation in NLRC4 Deficiency of Adenosine Deaminase 2 The Future of Autoinflammatory Diseases Online References 40 - Autoinflammatory Bone Diseases 40 - Autoinflammatory Bone Diseases Autoinflammatory Bone Diseases Autoinflammatory Bone Diseases Autoinflammatory Bone Diseases Autoinflammatory Bone Diseases Overview Chronic Recurrent Multifocal Osteomyelitis Overview Nomenclature Incidence, Geographical, and Racial Distribution Age at Onset and Sex Ratio Etiology and Pathogenesis Clinical Manifestations of CNO/CRMO Diagnostic Imaging Studies Histology Associated Inflammatory Conditions Serum Biomarkers Differential Diagnosis Treatment Genetic Autoinflammatory Syndromes With Bone Inflamation Majeed Syndrome Deficiency of the Interleukin-1 Receptor Antagonist Cherubism Summary Online References 41 - Pediatric Sarcoidosis 41 - Pediatric Sarcoidosis Etiopathogenesis Pediatric Sarcoidosis 41 Pathology Clinical Features Sarcoidosis Associated with NOD2 Mutation Sarcoidosis Without NOD2 Mutation Secondary Granulomatous Inflammatory Diseases Diagnosis Laboratory Parameters Pathology Genetic Testing Differential Diagnosis Prognosis Treatment Online References 42 - Macrophage Activation Syndrome 42 - Macrophage Activation Syndrome Epidemiology Triggers Macrophage Activation Syndrome 42 Genetic Background Pathophysiology Clinical Features Tissue Histology Diagnosis Differential Diagnosis Treatment Prognosis Online References 43 - Primary Immunodeficiencies and Rheumatic Diseases 43 - Primary Immunodeficiencies and Rheumatic Diseases Overview of the Inborn Errors Of Immunity Infection-Driven Approach Primary Immunodeficiencies and Rheumatic Diseases 43 Antibody Deficiencies T-Cell Deficiencies Complement Deficiencies Myeloid Immunodeficiencies Natural Killer Cell Deficiencies Somatic Tissue Immune Deficiencies Arthritis SLE and SLE-Like Phenotype Inflammatory Skin Disorders and Vasculitis/Vasculopathy Complex, Multiorgan Autoimmune/Autoinflammatory Phenotype Conclusion Online References 44 - Infectious Arthritis and Osteomyelitis 44 - Infectious Arthritis and Osteomyelitis Definition and Classification Epidemiology Pathogenesis and Risk Factors 44 Infectious Arthritis and Osteomyelitis Causative Agents Clinical Manifestations Diagnosis Treatment Neonatal Septic Arthritis Septic Hip Joint Gonococcal Arthritis Mycobacterial Arthritis Arthritis Associated with Brucellosis Arthritis Associated with Mycoplasma Infection Arthritis Associated with Bartonella Infection Whipple Disease Arthritis Caused by Viruses Rubella Virus Parvovirus Hepatitis B Virus Hepatitis C Virus Arboviruses Herpes Viruses Mumps Virus Human Immunodeficiency Virus Other Viruses Arthritis Associated With Other Organisms Fungi Spirochetes Parasites Arthritis and Systemic Bacterial Infections Course and Prognosis of Septic Arthritis Osteomyelitis Definition and Classification Epidemiology Etiology Pathogenesis Clinical Manifestations Diagnosis Treatment Course and Prognosis of Osteomyelitis Pyogenic Diskitis and Spondylodiskitis References 45 - Lyme Disease 45 - Lyme Disease Lyme Disease Epidemiology Geographical Distribution Incidence and Prevalence Sex Ratio and Age at Onset Genetic Background Etiology and Pathogenesis Etiology Microbiology Pathogenesis Pathogenesis of Post-Antibiotic Lyme Arthritis Clinical Manifestations Cutaneous Disease Nervous System Disease: Neuroborreliosis Musculoskeletal Disease Other Manifestations Laboratory Examination Nonspecific Abnormalities Confirmation of Infection with Borrelia burgdorferi Diagnosis Treatment Early Disease Arthritis Treatment Outcomes Coinfections Prevention References 46 - Reactive Arthritis 46 - Reactive Arthritis Epidemiology Genetic Background Pathogenesis Reactive Arthritis 46 Clinical Manifestation Characteristics of the Primary Infection Musculoskeletal Manifestations Constitutional Signs and Symptoms Mucocutaneous and Ocular Disease Laboratory Examination Imaging Studies Differential Diagnosis Treatment Prevention Treatment of the Precipitating Infection Treatment of Reactive Arthritis Physical Therapy and Rehabilitation Orthopedic Surgery Course of the Disease and Prognosis Reactive Arthritis After Streptococcal Infection Acute Rheumatic Fever Epidemiology Clinical Manifestations Major Manifestations Pathology Diagnosis: 2015 Criteria Differential Diagnosis Treatment Poststreptococcal Reactive Arthritis Definition and Classification Epidemiology Etiology and Pathogenesis Genetic Background Clinical Manifestations Diagnosis and Differential Diagnosis Laboratory Evaluation Treatment Course of the Disease and Prognosis Online References 47 - Skeletal Malignancies and Related Disorders 47 - Skeletal Malignancies and Related Disorders Primary Malignant Disease of Bone Marrow Leukemia Skeletal Malignancies and Related Disorders 47 Tumors of Bone Benign Tumors of Bone Malignant Tumors of Bone Tumors of Cartilaginous Origin Benign Cartilage Tumors Malignant Cartilage Tumors Tumors of Fibrous Tissue Benign Fibrous Tissue Tumors Malignant Tumors of Fibrous Tissue Tumors of Musculoskeletal Soft Tissues Benign Tumors of Soft Tissues Malignant Tumors of Soft Tissue Malignant Diseases Metastasizing to Bone Neuroblastoma Hypertrophic Pulmonary Osteoarthropathy Benign Tumors of Miscellaneous Origin Unicameral Bone Cysts Aneurysmal Bone Cysts Giant Cell Tumors Langerhans Cell Histiocytosis Summary Online References 48 - The Impact of Rheumatic Diseases and Their Treatment on Bone Strength Development in Childhood 48 - The Impact of Rheumatic Diseases and Their Treatment on Bone Strength Development in Childhood The Impact of Rheumatic Diseases and Their Treatment on Bone Strength Development in Childhood Normal Skeletal COMPOSITION Physiology of the Developing Skeleton Genetic Determinants of Bone Mass Calcium-Regulating Hormones Osteoporosis in Pediatric Rheumatic Disorders: Clinical Manifestations and Risk Factors Mechanisms of Bone Strength Loss in Pediatric Rheumatic Disorders Disease-Specific Clinical Manifestations Diagnosis and Monitoring of Osteoporosis in Pediatric Rheumatic Disorders Definition and Diagnosis of Osteoporosis in Childhood Diagnostic Techniques Impact of Medical Therapies on Skeletal Health in Childhood The Prevention and Treatment Effect of Medical Therapies Used for JIA Future Directions Online References 49 - Skeletal Dysplasias 49 - Skeletal Dysplasias Background Skeletal Dysplasias 49 History and Physical Examination Diagnostic Imaging Biochemical Investigations Cartilage Histology Molecular Basis Conclusion Online References 50 - Noninflammatory Musculoskeletal Pain 50 - Noninflammatory Musculoskeletal Pain Generalized Hypermobility Noninflammatory Musculoskeletal Pain 50 Pes Planus Pain Associated with Hypomobility Common Overuse Injuries Lower Extremity Upper Extremity Disorders of the Trunk Developmental Conditions Legg–Calvé–Perthes Disease Slipped Capital Femoral Epiphyses Bipartite Patella Sesamoid Pathology Accessory Bones of the Foot Miscellaneous Traumatic Arthritis Chondrolysis Femoral Acetabular Impingement Growing Pains Restless Legs Syndrome Carpal Tunnel Syndrome Cervical Neuropraxia Neuralgic Amyotrophy Online References 51 - Musculoskeletal Manifestations of Inflammatory Bowel Disease 51 - Musculoskeletal Manifestations of Inflammatory Bowel Disease Musculoskeletal Manifestations of Inflammatory Bowel Disease Definition and Classification Epidemiology Etiology and Pathogenesis Genetic Background Gut Inflammation and the Microbiome Clinical Manifestations Peripheral Arthropathies Axial Arthropathy Other Rheumatic Manifestations in IBD Ibd Diagnostic Clues Treatment and Disease Course Concluding Remarks Online References 52 - Musculoskeletal Manifestations of Systemic Disease 52 - Musculoskeletal Manifestations of Systemic Disease Rickets and Osteomalacia Musculoskeletal Manifestations of Systemic Disease 52 Scurvy Hypervitaminosis A Kashin–Beck Disease Mseleni Joint Disease Fluorosis Metabolic Diseases Abnormalities of Uric Acid Metabolism Glucose-6-Phosphatase Deficiency Calcium Pyrophosphate Deposition Disease Ochronosis Hyperlipoproteinemia Sphingolipidoses Hematological Disorders Hemoglobinopathies Hemophilia Endocrine and Exocrine Glands Diabetes Mellitus Pancreatitis with Arthritis Disorders of Other Endocrine Glands Cystic Fibrosis Celiac Disease Hyperostosis Primary Hyperostosis Secondary Hyperostosis Online References 53 - Pain Amplification Syndromes 53 - Pain Amplification Syndromes Pain Amplification Syndromes Evaluation of Musculoskeletal Pain History and Physical Examination Laboratory Examination Amplified Musculoskeletal Pain Historical Review Definition and Classification Epidemiology Age at Onset Sex Ratio Geographical and Racial Distribution Etiology and Pathogenesis Genetic Background Clinical Manifestations General Features Associated Symptoms and Signs The Impact of Chronic Musculoskeletal Pain on the Child and Family Pathology Laboratory Examination in Amplified Pain Radiographic Examination in Amplified Pain Treatment Education Psychological Therapies Physical and Occupational Therapies Pharmacotherapy Miscellaneous Sleep Natural History and Long-Term Outcomes Conclusion Online References 54 - Primary Disorders of Connective Tissue 54 - Primary Disorders of Connective Tissue Primary Disorders of Connective Tissue Introduction Syndromes Associated with Joint Hypermobility Syndromes Associated with Joint Hypomobility Disorders That May Mimic Arthritis Disorders Characterized by Lytic Bone Lesions Online References