Immune-Mediated Myopathies and Neuropathies: Current Trends and Future Prospects

Description

The book covers all aspects of immune-mediated diseases of the muscle and nerve, which are a group of complex diseases, whose diagnosis needs a team of specialists in the field of neuropathology, immunopathology, neurology, and rheumatology. Nerve and muscle biopsy evaluation is invaluable in distinguishing immune-mediated from etiologies and therefore, despite being invasive, pathological evaluation of nerve and muscle has stood the test of time. Chapters cover all the essential aspects of each disease entity viz. the pathogenesis, clinical features, diagnostic armamentarium, and guidelines for diagnosis and management. It is supplemented with full-colorful illustrations and photomicrographs for better comprehension. It includes a chapter highlighting the current progress in the field of immune-mediated myopathies and neuropathies as it is a rapidly evolving field with the addition of many new entities. This clinically oriented book serves as a primer for general histopathologists as well as a practice guide for neuropathologists. It is also relevant for neurologists and rheumatologists and encourages young medical students, residents, and research scholars in the field of neuropathology, neurology, and rheumatology to get involved in active research. Acknowledgments Contents About the Author Part I: Immune-Mediated Myopathies 1: Introduction to Immune-Mediated Myopathies 1.1 Normal Skeletal Muscle 1.2 Immunometabolism of Skeletal Muscle 1.3 Immune Cells and Inflammatory Myopathies 1.4 Interferons in Inflammatory Myopathies 1.5 Conclusion References 2: Diagnostic Evaluation of Immune-Mediated Myopathies 2.1 Introduction 2.2 Clinical Features 2.3 Serum Muscle Enzymes 2.4 Electrodiagnostic Studies 2.4.1 Nerve Conduction Studies 2.4.2 Electromyography 2.5 Muscle Imaging 2.5.1 Muscle MRI and Muscle Biopsy for IIM Diagnosis 2.6 Autoantibodies in Myositis 2.7 Muscle Biopsy 2.8 Conclusion References 3: Classification of Immune-Mediated Myopathies 3.1 Introduction 3.2 Dermatomyositis 3.3 Sporadic Inclusion Body Myositis 3.4 Immune-Mediated Necrotizing Myopathy 3.5 Antisynthetase Syndrome 3.6 Overlap Myositis 3.7 Antimitochondrial M2-Associated Myopathy 3.8 Anti-Program Cell Death 1/PD-1 Ligand Inhibitor-Associated Myositis 3.9 Polymyositis 3.10 Conclusion References 4: Idiopathic Inflammatory Myopathies 4.1 Introduction 4.2 Dermatomyositis 4.2.1 Introduction 4.2.2 Pathological Criteria for DM 4.2.3 Pathophysiology of DM 4.2.4 Juvenile Manifestations of DM and Inherited Interferonopathies 4.2.5 Treatment in DM 4.2.6 Cancer and DM 4.2.7 Conclusion 4.3 Sporadic Inclusion Body Myositis 4.3.1 Introduction 4.3.2 Nomenclature 4.3.3 Epidemiology 4.3.4 Clinical Features of sIBM 4.3.5 Anti-cN1A Autoantibody 4.3.6 Microscopic Pathology 4.3.7 Diagnostic Criteria 4.3.8 Associated Disorders and Comorbidities 4.3.9 Progression 4.3.10 sIBM Therapeutics 4.3.11 Pathogenesis of sIBM 4.3.12 Conclusion 4.4 Polymyositis 4.5 Conclusion References 5: Specific Forms of Immune-Mediated Necrotizing Myopathies 5.1 Introduction 5.2 Diagnostic Criteria for IMNM 5.2.1 General Features of IMNM 5.2.2 Anti-SRP Autoantibodies 5.2.3 Anti-HMGCR Autoantibodies 5.3 Epidemiology 5.3.1 Prevalence, Incidence, and Risk Factors 5.3.2 Anti-SRP-Positive IMNM 5.3.3 Anti-HMGR-Positive IMNM 5.3.4 Seronegative IMNM 5.4 Clinical Features 5.4.1 Muscular Phenotype 5.4.1.1 Seropositive IMNM 5.4.1.2 Seronegative IMNM 5.4.2 Extramuscular Phenotype 5.4.2.1 Anti-SRP-Positive IMNM 5.4.2.2 Anti-HMGCR-Positive IMNM 5.4.2.3 Seronegative IMNM 5.5 Microscopic Pathology 5.5.1 General Pathology of IMNM 5.5.2 Immunohistochemistry of IMNM 5.6 Disease Course and Prognosis 5.6.1 Seropositive IMNM 5.6.2 Seronegative IMNM 5.7 Pathogenesis of Seropositive IMNM 5.7.1 Targets of Autoantibodies 5.7.2 Effects of Autoantibodies In Vitro 5.8 Treatment Recommendations for IMNM 5.9 Conclusions 5.10 Antisynthetase Syndrome 5.10.1 Introduction 5.10.2 Epidemiology 5.10.3 Pathogenesis 5.10.4 Diagnosis 5.10.5 Clinical Symptoms 5.10.6 Myositis 5.10.7 Extramuscular Manifestations 5.10.8 Outcome and Prognosis 5.10.9 Overview of Treatment Possibilities 5.10.10 Conclusion 5.11 IIMs that Mimic IMNM References 6: Overlap Myositis References 7: Vasculitic Myopathy 7.1 Introduction 7.2 Large Vessel Vasculitis 7.3 Medium Vessel Vasculitis 7.4 Small-Vessel Vasculitis 7.4.1 ANCA-Associated/Pauci-Immune Vasculitis 7.4.2 Immune-Complex Mediated Vasculitis 7.4.3 Anti-glomerular Basement Membrane Disease 7.4.4 Cryoglobulinemic Vasculitis 7.4.5 IgA Vasculitis (Henoch–Schönlein Purpura) 7.4.6 Hypocomplementemic Urticarial Vasculitis (Anti-C1q Vasculitis) 7.4.7 Variable Vessel Vasculitis 7.4.8 Single-Organ Vasculitis 7.5 Skeletal Muscle Vasculitis 7.5.1 Takayasu Arteritis 7.5.2 Giant Cell Arteritis 7.5.3 Polyarteritis Nodosa 7.5.4 Kawasaki Disease 7.5.5 Granulomatosis with Polyangiitis 7.5.6 Microscopic Polyangiitis 7.5.7 Eosinophilic Granulomatosis with Polyangiitis 7.5.8 Cryoglobulinemic Vasculitis 7.5.9 IgA Vasculitis 7.5.10 Anti-C1q Vasculitis 7.5.11 Cogan’s Syndrome 7.5.12 Behçet’s Disease 7.5.13 Single-Organ Vasculitis 7.5.14 Vasculitis Associated with Systemic Disease 7.6 Conclusion References 8: Sarcoid Myopathy and Other Immune-Mediated Granulomatous Myopathies 8.1 Introduction 8.2 Sarcoid Myopathy 8.2.1 Introduction 8.2.2 Clinical Features 8.2.3 Non-invasive Investigations 8.2.4 Muscle Biopsy 8.2.5 Management and Prognosis 8.3 Idiopathic Granulomatous Myositis 8.4 Giant Cell Myositis 8.5 Conclusion References 9: Paraproteinemia Associated Myopathy 9.1 Introduction 9.2 Amyloid Myopathy 9.3 Sporadic Late-Onset Nemaline Myopathy (SLONM) 9.4 Conclusion References 10: AntiAMA-M2 Myopathy 10.1 Introduction 10.2 Pathogenesis 10.3 Clinical and Laboratory Findings 10.4 Muscle Biopsy 10.5 Conclusion References 11: Paraneoplastic Myopathy 11.1 Introduction 11.2 Dermatomyositis (DM) 11.3 Sporadic Inclusion Body Myositis (sIBM) 11.4 Immune-Mediated Necrotizing Myopathy (IMNM) 11.5 Conclusions References 12: Mimics of Immune-Mediated Myopathy 12.1 Introduction 12.2 Muscular Dystrophies 12.2.1 Facioscapulohumeral Muscular Dystrophy 12.2.2 Dysferlinopathy 12.2.3 Calpainopathy 12.2.4 Role of MHC Staining 12.3 Metabolic Myopathies 12.3.1 Acid Maltase Deficiency (Pompe Disease) 12.3.2 McArdle’s Disease 12.3.3 Mitochondrial Myopathies 12.4 Endocrine Myopathies 12.4.1 Thyroid Myopathies 12.4.2 Other Endocrine Myopathies 12.5 Nervous System Disease 12.6 Focal Disease 12.7 Conclusions References 13: Current Concepts and Future Prospects in Immune-Mediated Myopathies 13.1 Introduction 13.2 Interferons in Muscle Disease 13.2.1 IFN-I 13.2.2 IFN-II 13.2.3 IFN-III 13.2.4 Genetic Interferonopathies Share Common Features with DM 13.2.5 Skin Manifestations 13.2.6 Muscle Manifestations 13.2.7 IFN Pathway and DM-Specific Autoantibodies 13.2.8 IFN Pathway Is Activated in DM 13.2.8.1 Muscle Tissue 13.2.8.2 Skin Tissue 13.2.8.3 Blood 13.2.9 IFN Production in DM 13.2.9.1 Immune Cells and IFN Production 13.2.9.2 Muscle Cells 13.2.9.3 Keratinocytes 13.2.10 IFNs Induce Muscle Damage 13.2.11 Interferon Pathway Activation in ASS 13.2.11.1 IFN-II Pathway in Muscle of ASS 13.2.11.2 IFN-II Pathway in Lungs of ASS Patients 13.2.11.3 IFN Pathways in the Blood of ASS Patients 13.2.12 Interferon Pathway Activation in sIBM 13.2.12.1 IFN-II Pathway in Muscle Tissue of sIBM 13.2.12.2 IFN-II Pathway in the Blood of sIBM 13.2.12.3 IFN-II Pathway and Muscle Degeneration 13.2.13 IFN and IMNM 13.2.14 Conclusion 13.3 Myositis Associated with Graft-Versus-Host Disease 13.3.1 Introduction 13.3.2 Pathophysiology of GVHD Myositis 13.3.3 Incidence and Onset of GVHD Myositis 13.3.4 Clinical Features 13.3.5 Muscle Enzymes and Autoantibodies 13.3.6 Imaging 13.3.7 Pathology 13.3.8 Association with GVHD 13.3.9 GVHD vs De Novo Myositis 13.3.10 Treatment 13.3.11 Outcome 13.3.12 Conclusion 13.4 SARS-CoV-2 Myopathy 13.4.1 Muscle Biopsy 13.4.2 Conclusion 13.5 Immune Checkpoint Inhibitors Associated Myopathy 13.5.1 Introduction 13.5.2 Epidemiology 13.5.3 Treatment Options for ICI-Induced Musculoskeletal Manifestations 13.5.4 Immunotherapy Type and Musculoskeletal Manifestations 13.5.5 Conclusion References Part II: Immune-Mediated Neuropathies 14: Introduction to Immune-Mediated Neuropathies: A Brief Overview of the Nervous System 14.1 Neurons 14.2 Synapse 14.3 Types of Neurons 14.3.1 Multipolar 14.3.2 Bipolar 14.3.3 Unipolar 14.4 Peripheral Nerve 14.5 Immune-Mediated Neuropathies References 15: Diagnostic Evaluation of Immune-Mediated Neuropathies 15.1 Introduction 15.2 Initial Steps 15.3 Clinical History 15.4 Neurological Examination 15.4.1 Type of Nerve Fiber Involvement 15.4.2 Distribution of Symptoms 15.5 Electrodiagnostic Studies 15.6 Laboratory Testing 15.6.1 Examination of the Cerebrospinal Fluid 15.6.2 Genetic Testing 15.6.3 Nerve Biopsy 15.6.4 Peripheral Nerve Imaging 15.6.5 Other Examinations 15.7 Conclusion References 16: Classification of Immune-Mediated Neuropathies 16.1 Classification 17: Immune-Mediated Demyelinating Neuropathies 17.1 Introduction 17.2 Guillain-Barré Syndrome 17.2.1 Pathogenesis 17.2.2 Clinical Features 17.2.3 Electrophysiological Findings 17.2.4 Laboratory Investigations 17.2.5 Role of Nerve Biopsy in GBS 17.2.6 Treatment 17.2.7 Paraneoplastic GBS 17.3 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) 17.3.1 Introduction 17.3.2 Clinical Features of Typical CIDP 17.3.3 Electrodiagnostic Features and Ancillary Testing 17.4 Patterns Suggestive of Atypical CIDP or Disease Mimickers 17.4.1 Rapid Clinical Progression by Definition 17.4.2 Length-Dependent Sensory-Greater-Than-Motor, Axonal-Predominant Peripheral Neuropathy 17.4.3 Non-Length-Dependent Sensory Ganglionopathy/Neuronopathy 17.4.4 Upper-Limb-Predominant Neuropathy 17.4.5 Sensory and Motor Demyelinating Neuropathy 17.4.6 Sensory and Motor Axonal Polyradiculoneuropathy 17.4.7 CIDP with a Paraprotein 17.4.8 Paraneoplastic CIDP 17.5 Conclusions References 18: Immune-Mediated Axonal Neuropathies 18.1 Introduction 18.2 Vasculitic Neuropathy 18.2.1 Introduction 18.2.2 Classification 18.2.3 Clinical Features 18.2.4 Nonsystemic Vasculitic Neuropathy with Proximal Involvement (Nondiabetic Lumbosacral Radiculoplexus Neuropathy) 18.2.5 Subtypes 18.2.6 Imaging 18.2.7 Conclusion 18.3 Connective Tissue Disorders 18.4 Sarcoidosis 18.4.1 Neurosarcoidosis Consortium Consensus Group Definition and Consensus Diagnostic Criteria for Neurosarcoidosis 18.5 Immune-Mediated Gastrointestinal Disorders 18.5.1 Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis 18.5.2 Celiac Disease 18.6 Paraprotein-Associated Neuropathy 18.6.1 Epidemiology 18.6.2 Pathogenesis 18.6.3 IgM Paraproteinaemic Disorders 18.6.4 IgG or IgA Paraproteinaemic Disorders 18.6.5 IgM, IgG, or IgA Paraproteinaemic Disorders 18.6.6 Investigations 18.6.7 Nerve Biopsy 18.6.7.1 Endoneural Immunoglobulin Deposits 18.6.8 Conclusion 18.7 Paraneoplastic Disease 18.7.1 Types of Neuropathy 18.7.2 Diagnosis 18.7.3 Conclusion 18.8 Axonal GBS 18.9 Idiopathic Perineuritis References 19: Mimics of Immune-Mediated Neuropathy 19.1 Introduction 19.2 Diagnosis of Peripheral Neuropathies 19.3 Acquired Neuropathies 19.3.1 Metabolic Neuropathies 19.3.1.1 Endocrine 19.3.1.2 Vitamin Deficiencies 19.3.2 Toxic Neuropathies Metals 19.3.3 Drugs 19.3.4 Chemicals and Plants 19.3.5 Neurolymphomatosis 19.3.6 Hansen’s Neuritis 19.3.7 Cholesterol Emboli Neuropathy 19.4 Conclusions References 20: Current Concepts and Future Prospects in Immune-Mediated Neuropathies 20.1 Immune Checkpoint Inhibitors 20.1.1 Introduction 20.1.2 Approach to Differential Diagnosis 20.1.2.1 Clinical Features 20.1.3 Conclusions 20.2 Coronavirus Disease 19 (COVID-19)/Coronavirus 2 (SARS-CoV-2) Associated Peripheral Neuropathy 20.2.1 Introduction 20.2.2 Peripheral Nervous System Manifestations and Complications 20.3 Humoral Immune Endoneurial Microvasculopathy 20.3.1 Introduction 20.3.2 Conclusion References