Amyloidosis and Fabry Disease: A Clinical Guide

Description

This book presents a multispecialty and multidisciplinary approach on Amyloidosis and Fabry disease. These two “rare” diseases are underdiagnosed and have systemic peculiarities that should be emphasized for diagnosis. In both cases, early diagnosis is important for initiating treatment sooner, achieving better prognosis, and improving patients’ quality of life. The history of these patients, in general, involves a long journey among health professionals to obtain a diagnosis. Even after a patient is diagnosed, there are still difficulties in understanding these complex diseases, managing complications, and defining specific treatment. Therefore, this work will be a valuable resource for many healthcare professionals, including physicians of various specialties, nurses, physiotherapists, and medical students. It will also be of interest to patients who would like to understand Amyloidosis and Fabry disease. The content will give healthcare professionals a clinical perspective and provide insights on proper care. Readers will be able to recognize the symptoms related to each disease and will be guided during diagnosis and treatment. Chapters include an overview on clinical course, and will address neurological, ophthalmological, dermatological, gastrointestinal, hematological and cardiology manifestations, orthopedic care, mutations, expressiveness according to epigenetics and multidisciplinary treatment. Chapter authors from around the world will contribute sharing their experience in managing these diseases. Preface Acknowledgments Contents Contributors Chapter 1: Introduction References Part I: Amyloidosis Chapter 2: Neurological Manifestations in ATTRv Amyloidosis 2.1 Introduction 2.2 Historical Notes 2.3 ATTRv-PN Genetic Aspects of Neural Damage 2.4 Clinical Findings 2.4.1 Early Onset ATTRv 2.4.2 Late-Onset ATTRv 2.4.3 Other Clinical Manifestations Associated with ATTRv 2.5 ATTRv-PN Diagnosis 2.6 Neurophysiology (EMG) of ATTRV-PN References Chapter 3: Neurological Manifestations in AL and Wild-Type ATTR Amyloidosis 3.1 Introduction 3.2 AL Amyloidosis 3.3 ATTRwt 3.4 Conclusions References Chapter 4: Amyloidosis and Dysautonomia 4.1 Introduction 4.1.1 The Autonomic Nervous System—Basic Physiology 4.1.2 Autonomic Failure and Changes in Amyloidosis 4.2 Clinical Manifestations of Dysautonomia in Amyloidosis 4.3 Diagnosis of Dysautonomia in Amyloidosis 4.3.1 Autonomic Assessment May Include the Following Methods 4.3.1.1 Tilt Table Test 4.3.1.2 24-h Ambulatory Blood Pressure Monitor 4.3.1.3 Valsalva Maneuvere 4.3.1.4 Isometric Exercise (Handgrip) 4.3.1.5 Respiratory Maneuveres 4.3.1.6 Exercise Test 4.3.1.7 Carotid Sinus Compression 4.3.1.8 Heart Rate Variability/Spectral Analysis Time Domain Spectral Analysis 4.3.1.9 Biochemical Tests 4.3.1.10 Imaging Techniques Used to Assess Autonomic Innervation 4.4 Treatment 4.4.1 Pharmacological Interventions 4.4.2 Physical Maneuveres 4.4.3 Prevention and Treatment of Supine Hypertension 4.5 Conclusions References Chapter 5: Cardiologic Manifestation in Amyloidosis 5.1 Introduction 5.2 Clinical Presentation References Chapter 6: Syncope, Arrhythmia, and Cardiac Devices in Amyloidosis 6.1 Introduction 6.2 Syncope 6.2.1 Definition 6.2.2 Pathophysiology 6.2.3 Syncope in Amyloidosis 6.2.4 Treatment 6.3 Arrhythmias 6.3.1 Pathophysiological Mechanisms of Cardiac Arrhythmias in CA 6.3.2 Heart Conduction System Diseases 6.3.3 Atrial Arrhytmias 6.3.4 Ventricular Arrhythmias 6.3.5 Sudden Cardiac Death and Cardioverter Defibrillator in CA 6.3.6 Definitive Pacemaker in CA References Chapter 7: Urological and Kidney Involvements in Amyloidosis 7.1 Introduction 7.2 Renal Amyloidosis 7.2.1 Types of Renal Amyloidosis 7.2.1.1 Immunoglobulin Amyloidosis 7.2.1.2 Amyloid Protein A Amyloidosis 7.2.1.3 Leukocyte Chemotactic Factor 2 Amyloidosis Hereditary Amyloidosis 7.2.1.4 Fibrinogen A-α Chain Amyloidosis 7.2.1.5 Transthyretin Amyloidosis 7.2.1.6 Lysozyme Amyloidosis 7.2.1.7 Apolipoprotein Amyloidosis 7.2.1.8 Gelsolin Amyloidosis 7.2.2 Histological Diagnosis in Renal Amyloidosis 7.2.3 Course and Prognosis of Renal Amyloidoses 7.3 Urinary and Sexual Dysfunction in Hereditary TTR Amyloidosis 7.4 Localized Amyloidosis of the Genitourinary Tract 7.5 Conclusion References Chapter 8: Ophthalmological Manifestations in ATTRv Amyloidosis 8.1 Retinal and Vitreous Alterations 8.2 Chronic Open-Angle Glaucoma 8.3 Orbital and Adnexal Amyloidosis and Conjunctival Amyloidosis 8.4 d. Keratoconjunctivitis Sicca and Neurotrophic Kerathopathy 8.5 Pupillary and Lens Abnormalities References Chapter 9: Ophthalmological Manifestations in AL and Wild-Type ATTR Amyloidosis 9.1 AL Amyloidosis 9.2 Wild-Type Amyloidosis References Chapter 10: Dermatological Manifestations 10.1 Introduction 10.2 Localized Cutaneous Amyloidosis 10.2.1 Primary Localized Cutaneous Amyloidosis 10.2.1.1 Clinical Features 10.2.1.2 Histopathology 10.2.1.3 Diagnosis 10.2.1.4 Differential Diagnosis 10.2.1.5 Treatment 10.2.1.6 Clinical Features 10.2.1.7 Histopathology 10.2.1.8 Diagnosis 10.2.1.9 Differential Diagnosis 10.2.1.10 Treatment 10.2.2 Secondary Localized Cutaneous Amyloidosis 10.2.3 Rare Variants of Primary Cutaneous Amyloidosis 10.3 Systemic Amyloidosis with Cutaneous Involvement 10.3.1 Immunoglobulin Light Chain Amyloidosis (AL Amyloidosis) 10.3.2 Secondary (AA) Amyloidosis 10.3.3 Dialysis-Related Amyloidosis (Beta-2 Microglobulin Amyloid) 10.3.4 Heredofamilial Amyloidosis References Chapter 11: Gastrointestinal Symptoms 11.1 Introduction 11.2 Clinical Syndromes 11.3 Special Situations 11.3.1 Inflammatory Bowel Disease and AA Amyloidosis 11.3.2 - Celiac Disease and Secondary Amyloidosis 11.3.2.1 Diagnosis 11.3.2.2 Treatment 11.4 Summary References Chapter 12: Hematological Associations in Amyloidosis 12.1 Introduction 12.2 Epidemiology 12.3 Incidence of AL Amyloidosis 12.4 Clinical Manifestations—Signs and Symptoms 12.5 Diagnosis 12.6 MGUS and ATTR Amyloidosis References Chapter 13: Orthopedic Care 13.1 Carpal Tunnel Syndrome 13.1.1 Diagnosis 13.2 Tendinopathy 13.2.1 Trigger Finger 13.3 Distal Biceps Tendon Rupture 13.4 Rotator Cuff Disease 13.5 Lumbar Spinal Stenosis References Chapter 14: Serum Amyloid A Amyloidosis 14.1 Serum Amyloidosis (AA Amyloidosis): General Principles 14.2 Clinical Presentation 14.3 Diagnosis 14.4 Treatment References Chapter 15: Diagnostic Workflow of Cardiac Amyloidosis 15.1 Question 1: Is Cardiac Amyloidosis a Rare Disease? 15.2 Question 2: Can Amyloidosis Masquerade as Other Cardiac Diseases? 15.3 Question 3: What Are the Clinical Clues to Raise the Suspicion of Cardiac Amyloidosis? 15.4 Question 4: What Is the Next Step When Tests Are Suggestive of Cardiac Amyloidosis? 15.5 Question 5: When Laboratorial Tests Are Positive What Should Be Done? 15.6 Question 6: When and How Should Tissue Biopsy Be Undertaken? 15.7 Question 7: What Is the Hematologist’s Participation? 15.8 Question 8: After the Tissue Biopsy, Is the Diagnostic Work Done? 15.9 Cardiological Route References Chapter 16: The Echocardiogram in Amyloidosis 16.1 Introduction 16.2 Light Chain Cardiac Amyloidosis 16.3 Transthyretin (ATTR) Cardiac Amyloidosis 16.4 Echocardiography for the Diagnosis of Cardiac Amyloidosis 16.4.1 General Findings 16.4.2 Role of Myocardial Deformation Analysis for the Diagnosis of Amyloidosis 16.4.3 Role of 3D Echocardiography for Volumetric Analysis in Amyloidosis 16.4.4 Use of Contrast Echocardiography in Amyloidosis 16.4.5 Cardiac Elastography in Amyloidosis 16.5 Potential Role of Echocardiography in the Evaluation of Therapeutic Responsiveness 16.5.1 Conventional Parameters 16.5.2 Advanced Techniques 16.6 Prognostic Value of Echocardiography in Amyloidosis 16.7 Conclusion References Chapter 17: The Role of MRI in Amyloidosis 17.1 Introduction 17.2 Evaluation of Cardiac Morphology 17.3 Ventricular Function Analysis 17.4 Myocardial Characterization—Delayed Enhancement 17.5 Myocardial Characterization—T1 Mapping and Extracellular Volume 17.6 Practical Contribution of CMR in Clinical Scenarios 17.6.1 Screening of Family Members of Patients with Cardiac Amyloidosis 17.6.2 Differential Diagnosis of Myocardial Hypertrophy 17.6.3 Heart Failure with Preserved Ejection Fraction 17.6.4 Equivocal Results of Other Noninvasive Tests 17.6.5 Elderly Patients with Aortic Stenosis 17.6.6 Prognostic Evaluation and Treatment Monitoring 17.7 Conclusion References Chapter 18: Proteomics by Mass Spectrometry in the Typing of Amyloidosis 18.1 Introduction 18.2 What Is Proteomics 18.3 Technical Aspects of Proteomics by Mass Spectrometry—Specimen Preparation, Microdissection, Proteomic Analysis, and Results Interpretation References Chapter 19: The Role of Nuclear Medicine in the Diagnosis of Amyloidosis 19.1 Introduction 19.2 Imaging Targets in Cardiac Amyloidosis 19.3 Cardiac SPECT in the Diagnosis of Amyloidosis 19.4 Imaging Protocols 19.5 99mTc-DPD Imaging Protocol and Interpretation 19.6 99mTc-PYP Imaging Protocol and Interpretation 19.7 Critical Points Concerning 99mTechnetium-Labeled Cardiac Scintigraphy for Suspected Amyloidosis 19.8 False-Positive and False-Negative Scenarios in Bone-Seeking Scintigraphy [2–4, 31] 19.9 Role of Cardiac SPECT in the Context of Multimodality Imaging for Cardiac Amyloidosis Diagnosis 19.10 Myocardial Innervation Evaluation in CA 19.11 Diagnostic Algorithms of Cardiac Amyloidosis 19.12 Quantitative Studies to Assess Disease Activity and Response to Therapy 19.13 Myocardial Blood Flow Evaluation in CA 19.14 PET Tracers for Amyloid Detection and to Evaluate Disease Progression 19.14.1 18F-Sodium Fluoride 19.14.2 Amyloid PET Tracers 19.15 Future Perspectives References Chapter 20: Genetics and Epigenetics of Transthyretin Amyloidosis 20.1 Genetics 20.1.1 TTR Structure and Function 20.1.2 Clinical and Populational Features of Amyloidosis 20.1.3 Epidemiology and types of variants 20.1.4 Inheritance and Penetrance Patterns 20.1.5 Family screening 20.1.6 Clinical Applicability of Genetic Testing 20.2 Epigenetics References Chapter 21: Cardiopulmonary Exercise Testing and Cardiac Rehabilitation in Amyloidosis 21.1 Cardiopulmonary Exercise Testing 21.2 Cardiac Rehabilitation 21.3 Healthy Lifestyle 21.4 Physical Activity 21.5 Conclusion References Chapter 22: Treatment of Transthyretin Amyloidosis 22.1 Introduction 22.2 Pathophysiology 22.3 Treatment of Heart Failure in ATTR 22.3.1 Diuretics 22.3.2 Digoxin 22.3.3 Levosimendan 22.3.4 Sodium Glucose Cotransporter 2 (SGLT2i) Inhibitors 22.3.5 Calcium Antagonists 22.3.6 Angiotensin-Converting Enzyme (ACEi) Inhibitors and Angiotensin II Receptor Blockers (ARB) 22.3.7 Beta Blockers 22.4 Symptomatic Treatment of Dysautonomic Manifestations 22.4.1 Erectile Dysfunction 22.4.2 Urinary Dysfunction 22.4.3 Gastrointestinal Dysfunction 22.4.4 Orthostatic Hypotension 22.5 Specific Treatment of ATTR 22.6 Antisense Oligonucleotide 22.6.1 Inotersen 22.6.2 Eplontersen 22.7 Interference RNA (siRNA) 22.7.1 Patisiran 22.7.2 Revusiran 22.7.3 Vutrisiran 22.8 Transthyretin Stabilizers 22.8.1 Tafamidis 22.8.2 Other Transthyretin Stabilizers 22.8.3 Diflunisal 22.8.4 Acoramidis (AG10) 22.8.5 Tolcapone (Tasmar®) 22.9 Amyloid Fibril Disruption Therapy 22.9.1 Doxycycline and Tauroursodeoxycholic Acid (TUDCA) or Ursodeoxycolic Acid (UDCA) 22.9.2 Green Tea Extracts (EGCG) 22.10 Emerging Therapies 22.10.1 Gene Editing Therapy 22.10.2 Immunotherapeutic Agents 22.11 Treatment Response and Disease Progression Markers 22.11.1 Treatment Response Markers 22.11.2 Disease Progression Markers References Chapter 23: Treatment of AL Amyloidosis 23.1 Treatment of Light Chain Amyloidosis: General Principles 23.2 Intensive Treatment Strategy: High-Dose Chemotherapy and Autologous Stem Cell Transplantation 23.3 Standard Chemotherapy Treatment in Patients Not Eligible for ASCT 23.4 Response Assessment 23.5 Treatment of Relapsed/Refractory AL Amyloidosis 23.6 Supportive Treatment References Chapter 24: Ilustrative Cases in Amyloidosis 24.1 Case Report 01 24.1.1 Summary 24.1.2 Case Presentation 24.1.3 Past Medical History 24.1.4 Physical Exam 24.1.5 Laboratory Analysis 1 24.1.6 Imaging and Endoscopic Exams 24.1.7 First Diagnosis 24.1.8 First Treatment 24.1.9 Laboratory Analysis 2 24.1.10 Imaging Exams 24.1.11 Second Diagnosis 24.1.12 Second Treatment 24.1.13 Upper Endoscopy 24.1.13.1 Gastric Biopsy 24.1.13.2 Kidney Biopsy 24.1.14 Screening for Monoclonal Gammopathy 24.1.15 Cardiac Assessment: Imaging (Echo and MRI) 24.1.16 Cardiac Assessment: Biomarkers 24.1.17 Neurologic Assessment 24.1.18 Hepatic Assessment 24.1.19 Conclusion 24.2 Case Report 02 24.2.1 Summary 24.2.2 History of Presentation 24.2.3 Past Medical History 24.2.4 Laboratory Exams 24.2.5 Conclusion 24.3 Case Report 03 24.3.1 Summary 24.3.2 History of Presentation 24.3.3 Past Medical History 24.3.4 Differential Diagnoses 24.3.5 Investigations 24.3.6 Discussion 24.3.7 Management 24.3.8 Conclusion References Part II: Fabry Disease Chapter 25: Neurological Manifestations of Fabry Disease 25.1 Introduction 25.2 PNS-Related Manifestations in FD 25.3 CNS-Related Manifestations in FD 25.4 Cochleovestibular Manifestations in FD 25.5 Enzyme Replacement Therapy and Neurological Manifestations 25.6 Conclusions References Chapter 26: Cardiac Manifestations in Fabry Disease 26.1 Introduction 26.2 Epidemiology 26.3 Differential Diagnosis 26.4 Molecular Genetics 26.5 Pathophysiology of Cardiac Involvement in Fabry Diseases 26.6 Clinical Presentation 26.7 Cardiomyopathy 26.8 Electrophysiological Abnormalities 26.9 Valvular Disease 26.10 Coronary Manifestations 26.11 Conclusion References Chapter 27: Fabry Nephropathy 27.1 Introduction 27.2 Pathophysiology 27.3 Clinical Manifestations and Natural History of Fabry Nephropathy 27.4 Morphological Alterations in Fabry Nephropathy 27.5 Laboratory Findings 27.6 Fabry Nephropathy Diagnosis 27.7 Therapeutic Aspects of Fabry Nephropathy References Chapter 28: Ophthalmological Manifestations of Fabry Disease 28.1 Ophthalmological Manifestations of Fabry Disease References Chapter 29: Dermatological Manifestations in Fabry Disease 29.1 Introduction 29.2 Dermatological Manifestations 29.2.1 Angiokeratomas 29.2.1.1 Differential Diagnoses of Angiokeratomas 29.2.2 Sweating Changes 29.2.2.1 Differential Diagnoses of Sweating Disorders 29.2.3 Acroparesthesias 29.2.3.1 Differential Diagnoses of Acroparesthesias 29.2.4 Lymphedema 29.2.4.1 Differential Diagnoses of Lymphedema Alterations 29.2.5 Facial Dysmorphia 29.3 Treatment References Chapter 30: Diagnostic Flowchart in Fabry Disease 30.1 When to Suspect the Diagnosis of Fabry Disease? 30.2 What Is an Important Exam to Diagnose FD? 30.3 Is It Common to Use Tissue Biopsy to Aid the Diagnosis? 30.4 Are There Particularities for the Diagnosis of Atypical FD or Pediatric Forms? 30.5 Is There a Genetic Diagnosis in FD Prenatal Care? 30.6 Conclusion References Chapter 31: Genetics in Fabry Disease 31.1 Introduction 31.2 An X-Linked Recessive Disease? 31.3 X-Chromosomal Inactivation and FD 31.4 GLA Mutations and Genetic Diagnosis of FD 31.4.1 Genetic Diagnosis in FD Male Patients 31.4.2 Genetic Diagnosis in FD Female Patients 31.5 Types of GLA Mutations References Chapter 32: Echocardiography in Fabry References Chapter 33: Cardiac Magnetic Resonance Imaging in Fabry Disease 33.1 Introduction 33.2 Fabry Diagnosis and Its Imposing Challenges 33.2.1 Electrocardiogram 33.2.2 Echocardiogram 33.3 Role of Cardiovascular Magnetic Resonance in Fabry 33.3.1 Traditional Methods for Tissue Characterization 33.3.1.1 Late Gadolinium Enhancement 33.3.2 Advanced Methods for Tissue Characterization 33.3.2.1 T1 Mapping and Extracellular Volume Fraction 33.3.2.2 Myocardial Strain 33.3.2.3 T2 and T2* Mapping 33.4 Conclusions References Chapter 34: Pharmacological Therapy in Fabry Disease 34.1 Introduction 34.1.1 Classes of Recommendation 34.2 Enzyme Replacement Therapy for FD Treatment 34.2.1 Consensus Criteria for Initiation of ERT 34.2.2 Consensus Criteria to Stop or Not Start ERT 34.3 Chaperone Oral Therapy for FD 34.4 Symptomatic Therapies 34.5 Monitoring FD Patients References Chapter 35: A Case Report of Fabry Disease 35.1 Case Report of Fabry Disease 35.2 Main Complaint and Duration 35.3 Previous History 35.4 Clinical Course 35.5 Evaluation at the Present Consultation 35.6 Family History 35.7 Cardiac Tests 35.8 Kidney Biopsy 35.9 CT Scan 35.10 Genetic Analysis 35.11 Enzymatic Study 35.12 Specific Treatment 35.13 Symptomatic Treatment 35.14 Follow-Up of Patients with Fabry Disease 35.15 Conclusion Part III: Miscellany Chapter 36: Clinical and Genetic Screening in ATTR and Fabry Disease in Children and Adolescents 36.1 Fabry Disease (FD) 36.1.1 Pediatric Clinical Manifestation 36.1.2 Diagnosis 36.1.3 Clinical Monitoring of Children Diagnosed with Fabry Disease 36.2 Hereditary Transthyretin Amyloidosis (ATTR Amyloidosis) 36.2.1 Pediatric Manifestations 36.2.2 Genetic Counseling References Chapter 37: History and Clinical Research 37.1 History of Amyloidosis 37.2 History of Fabry Disease 37.3 Creation of Clinical Research Centers 37.4 Clinical Research and Treatment of a Patient with Rare Disease References Chapter 38: Misdiagnosis and Clinical Reasoning in Cardiac Amyloidosis 38.1 Introduction 38.2 Understanding Misdiagnosis and Clinical Reasoning: Important Concepts 38.3 Amyloidosis Patient Journey 38.4 Challenges in Diagnosing the Disease 38.5 Strategies for Reducing Diagnostic Error 38.6 Conclusions References Chapter 39: Multidisciplinary Approach in Fabry Disease and Amyloidosis 39.1 Introduction 39.2 Nutritional Approach in Fabry Disease 39.3 Nutritional Approach in Amyloidosis 39.4 Nurse Approach in Amyloidosis and Fabry Disease 39.5 Physiotherapy Performance References Chapter 40: Chronic Pain and Quality of Life 40.1 Introduction 40.1.1 Mind Body Therapies 40.1.2 Acupuncture 40.2 Other Options 40.3 Palliative Care References Index