Amyloidosis and Fabry Disease: A Clinical Guide

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