The Rose and Mackay Textbook of Autoimmune Diseases, 7e (Aug 9, 2024)_(0443239460)_(Academic Press).pdf

The Rose and Mackay Textbook of Autoimmune Diseases
Copyright
Dedication
Contents to Volume 1
prelims1-volume2.pdf
	Contents to Volume 2
List of contributors
List of editors and section editors
	Editors
	Section editors
		Basic science
		Ear nose and throat
		Dermatology
		Endocrinology
		Hematology
		Hepatobiliary and gastroenterology
		Nephrology
		Neurology
		Ophthalmology
		Pulmonary
		Rheumatology
Preface
1 Development of adaptive immune cells
	Self versus nonself
	Adaptive immune cell development
	Lymphocyte progenitors
	T cell development
	Altered mechanisms of T cell tolerance as promoters of autoimmunity
	B cell development
	Antibody diversity
	Self-reactive B cells are inherently part of the peripheral B cell pool
	Altered mechanisms of B cell tolerance and autoimmunity
	Conclusion
	Acknowledgment
	References
2 Revision to the origins of the mononuclear phagocyte
	Key points
	Overview
	Steady-state development of macrophages
	Transcriptional regulation of tissue-resident macrophages
	Common macrophage transcriptional profiles
		Adipose tissue macrophages
		Cardiac tissue macrophages
		Intestinal macrophages
		Kupffer cells
		Langerhans cells
		Peritoneal macrophages
		Lung macrophages
		Brain macrophages
		Nerve-associated macrophages
		Osteoclasts
		Splenic macrophages
		Synovial macrophages
	M1 and M2 paradigm revisited
	Future directions
	References
3 Tolerance and activation of peripheral B and T cells
	B cell central tolerance “checkpoints” in humans
		Tonic signaling at the immature B cell stage
		Receptor editing is likely a dominant tolerance mechanism at the immature B cell stage in mice and humans
		The special case of immature B cell deletion in response to DNA-protein complexes
	T cell activation, T-B collaboration, and peripheral B cell tolerance
		Self-reactive B cells at the transitional B cell stages are likely most susceptible to receptor downregulation and subseque...
		Late transitional and mature follicular B cells are anergized by selective downregulation of IgM, but anergic B cells are a...
		An overview of T cell tolerance and peripheral T cell activation
		The simultaneous generation of CD4+ T cell subsets and the induction of the extrafollicular response
		The transient extrafollicular induction of autoimmunity after infection likely reflects the major contribution of self-reac...
		The extrafollicular response, tolerance, and common autoimmune disorders
		Regulatory T cells in the maintenance of B cell tolerance
		Autoantibodies in common variable immunodeficiency likely reflect altered T effector/T reg ratios that allow anergic B cell...
		Germinal center B cell tolerance may reflect a default process and a break in tolerance at this location may lead to frank ...
	Conclusion
	Acknowledgments
	References
4 Genetic alterations leading to autoimmunity
	Introduction
	The genetics of autoimmunity before development of the genome-wide association study
		Evidence supporting the role of genetics in autoimmune diseases
		Linkage studies in autoimmune diseases
		Candidate gene studies identify the first non-HLA associated autoimmune disease risk genes
		The genome-wide association study
		Genome-wide association study discover a trove of autoimmune disease associations
		Fine mapping autoimmune disease loci with the Immunochip
	Moving from genetic association to functional mechanism in the post-GWAS era
	The next technology advance: single cell sequencing
	Leveraging polygenic risk scores to predict disease
	Summary
	References
5 Microbiome in autoimmunity
	Introduction
	Alterations in the gut microbiome in autoimmune diseases
		Inflammatory bowel diseases
		Type 1 diabetes
		Multiple sclerosis
		Rheumatoid arthritis
		Systemic lupus erythematosus
	Mechanisms
		Metabolites
		Molecules mimicry
		Microbiota translocation
	Interventions
		Diet and metabolites
		Fecal microbiota transplantation
			Inflammatory bowel diseases
			Type 1 diabetes
			Multiple sclerosis
			Rheumatoid arthritis
			Systemic lupus erythematosus
	Conclusion
	References
6 Metabolic control of pathogenesis in autoimmune diseases
	Short summary
	Introduction
	Systemic lupus erythematosus
	Mitochondrial oxidative stress underlies mTOR activation in SLE
	Rheumatoid arthritis
		Autoimmune spondyloarthritis
		Scleroderma and systemic sclerosis
		Metabolic control of organ-specific autoimmune diseases
	Conclusions
	Acknowledgments
	References
7 Triggers for autoimmunity
	Introduction
	Self-antigens that escape tolerance
		Neoantigens
		Breaking tolerance to existing autoantigens
			Enhanced presentation of posttranslationally modified epitopes
			Cryptic epitopes
			Sequestered antigens
	Environmental triggers of autoimmunity
		Viral-induced autoimmunity
			Epstein–Barr virus
			Enterovirus
			Hepatitis C virus
			Herpes simplex virus
			SARS-CoV-2
		Drug-induced autoimmunity
			Drug-induced lupus
			Potential mechanisms of drug-induced lupus
			Cellular autoimmunity
			Neutrophil extracellular traps
			Immune checkpoint inhibitor-induced autoimmunity
			Potential mechanisms of immune checkpoint inhibitor-induced autoimmunity
			Cellular autoimmunity
			Humoral autoimmunity
			Cytokine production
	Conclusion
	References
8 Organ damage in autoimmune disease
	Introduction
	Initiation of tissue injury
		Antibody-mediated tissue injury
			Organ-specific diseases initiated by autoantibodies
			Autoantibodies of unknown function
			Antibodies directed at ubiquitous self-antigens
			B cells as organizers of local inflammation
			B cell-directed therapies
		T cell-mediated tissue injury
			T cells as inflammatory effector cells
			Antigen-specific T cells
			T cells as B cell helpers or regulatory cells
			T cell-directed therapies
		Innate immune mechanisms
			Macrophages
			Neutrophils
			Innate lymphoid cells
			Soluble inflammatory mediators
			Soluble mediators of resolution
	Chronic tissue injury
		Hypoxia
		Immune senescence
		Cell death
		Fibrosis
			Fibroblasts
			Pro-fibrotic and antifibrotic soluble mediators
			Targeting fibrosis
		Failed resolution
	Genetics of tissue injury
	Loss of function
	Implications for therapy
	References
9 Therapeutic strategies for treating autoimmune disease
	Immunosuppression versus targeted therapy
	B cell depletion
	T cell-directed therapy
	Cytokine blockade
	Small molecule immune inhibitors
	Immunoablation and reconstitution
	Antigen-specific therapy
	Conclusion
	References
10 Systemic lupus erythematosus
	Introduction
	History
	Disease diagnosis and classification
	Epidemiology, genetics, and the environment
	Pathogenesis
		Adaptive immunity
		Innate immunity
	Clinical features
		Clinical presentation
			Mucocutaneous manifestations
			Arthritis
			Renal involvement
			Neuro-psychiatric disease
			Hematologic manifestations
			Pulmonary and cardiovascular manifestations
			Other clinical manifestations
			Infections
		Clinical laboratory findings
		Treatment
			Outcome measures
			General therapeutic schema
			Therapeutic agents
				Antimalarials
				Corticosteroids
				Biologics
				Immunosuppressive medications
				Calcineurin inhibitors
				Cyclophosphamide
				Supportive treatments
	Future directions
	References
11 Systemic sclerosis (scleroderma)
	Definition and classification
	Epidemiology and etiology
	Sex bias, ethnic background and mortality trends
	Environmental factors
	Pathogenesis
	Genetic associations
		Preclinical disease models
		Microvascular disease in systemic sclerosis
		Inflammation and autoimmunity
			Cellular immunity
			Humoral autoimmunity
		Fibrosis
	Pathology
		Skin
		Lungs
		Gastrointestinal tract
		Kidneys
		Heart
		Pathology in other organs
	Clinical features
		Overview
		TABLE 11.5 Clinically significant organ involvement in systemic sclerosis.
		Initial clinical presentation
		Organ involvement
			Raynaud’s phenomenon
		Skin features
	Pulmonary features
		Interstitial lung disease
	Gastrointestinal involvement
		TABLE 11.6 Systemic sclerosis related autoantibodies and their demographic and clinical correlates.
	Renal involvement: scleroderma renal crisis
	Cardiac involvement
		It can be
		outcomes
		may be affected
		detecting preclinicalheart involvement in SSc
	Musculoskeletal complications
	Less recognized disease manifestations
	Biomarkers and autoantibodies in systemic sclerosis
	Screening and follow-up evaluation
	Management of patients with systemic sclerosis
		General principles
		Disease-modifying immunomodulatory therapy
			Immunosuppressive agents
			glucocorticoids
			cyclosporine, azathioprine, plaquenil,thalidomide, and rapamycin
			cyclophosphamide
			Mycophenolate mofetil
			Tocilizumab
			Extracorporeal photochemotherapy (photopheresis)
			cellulartherapies
			Therapy targeting fibrosis
				in patients with idiopathic pulmonary fibrosis
		Vascular therapy
			The goal of vascular therapy is to
			Raynaud’s
				ACE inhibitors
				Angiotensin II receptor blockers
				Patients unresponsive tothese therapies may require
				in severe cases
				adjunctiveagents
				Patients with nonhealing ischemic digitalulcerations may respond to
				statins and antioxidants
				often used for atrial arrhythmias
				for improving myocardial perfusionand left ventricular systolic function
		Treatment of gastrointestinal complications
			Gastroesophagealreflux
				Patientsshould be instructed to
				Prokinetic agents
				Surgical antireflux procedures
			Recurrent episodic bleeding from GAVE
		Treatment of interstitial lung disease
		Management of renal crisis
		Treatment of pulmonary arterial hypertension
	Natural history and prognosis
	References
12 Antiphospholipid syndrome
	Historical perspective
	Geoepidemiology
	Pathogenesis
		Double-hit model
		Thrombosis
			Activation of endothelial cells, platelets and immune cells
			Complement activation
			Resistance to activated protein C
		Pregnancy complications
			Proliferation and migration of trophoblasts
			Inflammation
			Complement activation
	Genetics
	Diagnosis, screening, and prevention
		Antiphospholipid antibody assays
			Lupus anticoagulant
			Antibodies against β2GPI and anticardiolipin antibodies
			Antibody profile
			Noncriteria antiphospholipid antibodies
		Clinical manifestations
			Thrombosis
			Obstetrical morbidity
			Neurological manifestations
			Cardiac manifestations
			Thrombocytopenia
			Pulmonary manifestations
			Skin manifestations
			Renal involvement
			Catastrophic antiphospholipid syndrome
	Management
		Primary thromboprophylaxis
		Prevention of recurrent thrombosis
		Alternative therapies for refractory and difficult cases
		Other therapies
	Pregnancy
		Recurrent early miscarriage
		Fetal death
		Management of pregnancy in patients with antiphospholipid syndrome and previous thrombosis
		Management of refractory obstetric antiphospholipid syndrome
		Postpartum period
	Risk assessment in antiphospholipid syndrome
	Future directions
	References
13 Sjögren’s disease
	Historical perspectives
	Establishing classification criteria for the disease
	Epidemiology
	Clinical presentation
		Introduction
			Nonspecific manifestations
			Periepithelial manifestations
				Glandular
				Extraglandular
			Extraepithelial manifestations
				Skin
				Nervous system
				Kidney
				Vasculitis
				Lymphoma [117–119]
	Disease course and prognosis
	Pathophysiology of Sjögren’s syndrome
		The normal salivary gland (structure and function)
		Genetic and environmental factors predisposing to Sjögren’s syndrome development
			Genetic factors
				The X chromosome
				Major histocompatibility complex genes and nonmajor histocompatibility complex genes
			Epigenetic modifications
			Environmental factors
				Biological factors
					Infections and vaccinations
				Organic chemical factors (smoking, alcohol, organic solvents)
			Hormonal factors
				Sex hormones
				Stress hormones and the growth hormone-insulin-like growth factor 1 axis
	Autoimmune epithelitis
		Initiation of the disease
			Autoantibodies
			Epithelial activation and immune sensing
		Establishment and perpetuation of the disease
			Cytokine—chemokine release
			Antigen presentation
			Immune cell activation and infiltration
			T cells
			B cells
			Macrophages
			Dendritic cells—plasmacytoid dendritic cells
			Natural killer cells
			Autoantigen fueling
		Mechanisms of tissue injury
			Periepithelial lesions
			Extraepithelial injury
			Lymphomagenesis
	The use of mouse models in the study of Sjögren’s syndrome
	Diagnosis and management
		Diagnosis
			Imaging modalities for evaluation of salivary glands
			Salivary gland ultrasonography
			Magnetic resonance imaging
			Autoantibodies related to Sjögren’s syndrome
			Minor labial salivary gland biopsy
		Differential diagnosis
		Management
			Nonpharmacologic interventions and preventive measures
			Local treatments
			Systemic and organ-based treatment
			Targeted treatments
	References
14 Rheumatoid arthritis
	Introduction
	Clinical, pathologic, and epidemiologic features
	Autoimmune features
	Genetic characteristics
	In vivo models
	Pathogenetic effector mechanisms
	Concluding remarks—future prospects
	References
15 Juvenile idiopathic arthritis
	Introduction
	Definition and classification
	Epidemiology
	Pathogenesis
		Genetic susceptibility
		Environmental factors
		Effector mechanism
	Clinical features
		Oligoarthritis
		Rheumatoid factor-positive polyarthritis
		Rheumatoid factor-negative polyarthritis
		Enthesitis-related arthritis
		Psoriatic arthritis
		Undifferentiated arthritis
		Systemic arthritis
		Macrophage activation syndrome
		Biomarkers
		Histopathology
		Morbidity/mortality
		Treatment
	Future directions
	References
16 Spondyloarthritis
	Introduction
		Disease history
		Definition of the disease and classification criteria
		Geoepidemiology
		Pathogenesis
			Genetics
				The role of HLA-B27
		The role of non-MHC genes in spondyloarthritis
		Spondyloarthritis: an autoimmune or an autoinflammatory disease?
		Animal models
	Clinical features and treatment
		Clinical manifestations and the diagnostic approach
		Biomarkers
		Pathology with histology
		Morbidity/mortality
		Treatment
	References
17 Autoimmune myositis
	Defining autoimmune myositis
	Clinical and pathological descriptions of different phenotypes, including immune-mediated necrotizing myopathy
	Characteristic pathology, but significant overlap between phenotypes
	Epidemiological clues into mechanism
	Specific autoantibodies are strongly associated with phenotype, making them useful probes of disease mechanism
		Myositis-specific autoantibodies
		HMGCR autoantibodies in statin-associated immune-mediated necrotizing myopathy
	Mechanisms of disease
		The association of malignancy with autoimmunity: insights into disease initiation
		Enhanced expression of myositis autoantigens in regenerating muscle cells to focus propagation on muscle
		Modification of autoantigen expression or structure by immune effector pathways to generate a self-sustaining phenotype
	Therapeutic insights
	Concluding remarks
	References
18 Relapsing polychondritis
	Introduction
	Historical note
	Epidemiology
	Genetics and pathogenesis
	Clinical features and diagnosis
	Systemic manifestations
	Clinical evaluation
	Ear and nose manifestations
	Laryngotracheal and pulmonary manifestations
	Musculoskeletal manifestations
	Ocular manifestations
	Cutaneous manifestations
	Renal involvement
	Cardiovascular manifestations
	Neurological manifestations
	Association with other diseases
	Laboratory findings
	Imaging
	Differential diagnosis
	Assessment of disease activity and damage
	Treatment
	Nonsteroidal anti-inflammatory agents, colchicine and dapsone
	Corticosteroids
	Second-line therapies
	Biologic agents
	Surgical intervention
	Prognostic factors
	Summary
	References
19 IgG4-related disease
	Introduction
	Historical aspects
	Epidemiology
	Pathology
		Histological features
		Immunostaining
	Pathophysiology
		B cells
		T cells
	Serum IgG4 concentrations
	Autoimmune features
		Does the immunoglobulin G4 molecule participate in autoimmunity?
		Evidence for autoimmunity in immunoglobulin G4-related disease
			Galectin-3
	Genetics
	An animal model
	Clinical features and disease associations
		Lymphadenopathy
		Lacrimal and salivary glands
		Orbits
		Ear/nose/throat
		Pancreas
		Immunoglobulin G4-related sclerosing cholangitis and cholecystitis
		Lung
		Kidney
		Thoracic aorta and coronary lesions
		Chronic periaortitis and retroperitoneal fibrosis
		Nervous system
		Other immunoglobulin G4-related disease lesions
	Classification criteria
	Treatment
		B cell-targeted treatments
		Costimulatory blockade
		CD4+ cytotoxic T lymphocytes
	Perspectives
	References
20 Necrotizing arteritis and small-vessel vasculitis
	Introduction
	Historical background
		Necrotizing arteritis
		Purpura and small-vessel vasculitis
	Polyarteritis nodosa
		Definition
		Epidemiology
		Clinical features
		Pathological features
		Clinical features and disease association
			Pathogenesis
		Environmental influences and genetic features
		Autoimmune features
		Animal models
		Diagnostic procedures
		Treatment
	Kawasaki’s disease
		Epidemiology
		Clinical features and disease associations
		Pathological features
		Pathogenesis
		Genetic features and environmental influences
		Autoimmune features
		Animal models
		Diagnostic procedures
		Treatment
	Anti-neutrophil cytoplasmic autoantibody vasculitis
		Definition
		Epidemiology
		Clinical features and disease associations
		Pathological features
		Pathogenesis
		Genetic features and environmental influences
		Autoimmune features
		Immunological non-responsiveness
		Animal models
		Diagnostic procedures
		Treatment
	Cryoglobulinemic vasculitis
		Definition
		Epidemiology
		Clinical features and disease associations
		Pathological features
		Pathogenesis
		Genetic features and environmental influences
		Autoimmune features
		Animal models
		Diagnostic procedures
		Treatment
	IgA Vasculitis (Henoch-Schonlein purpura)
		Definition
		Epidemiology
		Clinical features and disease associations
		Pathological features
		Pathogenesis
		Genetic features and environmental influences
		Autoimmune features
		Animal models
		Diagnostic procedures
		Treatment
	Concluding remarks—future prospects
	References
21 Large and medium vessel vasculitides
	Vasculitides of large and medium-sized blood vessels
	Giant cell arteritis
	Historic background
	Clinical, pathologic, and epidemiologic features
	The vascular lesion
	Epidemiology
	Genetic features
	Pathogenic mechanisms
		T cells and antigen-presenting cells in giant cell arteritis
	Macrophages (M&e_2C77;) in giant cell arteritis
	Neoangiogenesis of microvascular networks and intimal hyperplasia
		Immuno-stromal interactions in vasculitis
		Extravascular giant cell arteritis
	Treatment, monitoring, and outcome
	Takayasu arteritis
	Historic background
		Clinical, pathologic, and epidemiologic features
		Genetic predisposition
		Pathogenic mechanisms
		Treatment and outcome
	Concluding remarks – future perspectives
	Acknowledgment
	References
22 Autoimmune diseases of the kidney
	Introduction
	Historical perspective
	Definition of disease
		Nephrotic syndrome
			Minimal change disease
			Membranous nephropathy
			Focal segmental glomerulosclerosis
		Nephritic syndrome
			IgA nephropathy
			Rapidly progressive glomerulonephritis (RPGN)
	Lupus nephritis (covered extensively in chapter 10)
		Overlap nephrotic/nephritic syndrome
			Membranoproliferative glomerulonephritis (MPGN)
				Complement-mediated membranoproliferative glomerulonephritis (C-MPGN); complement factor 3 glomerulopathy (C3G)
				Immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN)
		Tubulointerstitial disease
	Geoepidemiology
	Pathogenesis
	Clinical features, disease associations, treatment, and outcomes
		Minimal change disease (MCD)
		Membranous nephropathy (MN)
		Focal segmental glomerulosclerosis (FSGS)
		IgA nephropathy (IgAN)
		Rapidly progressive glomerulonephritis (RPGN)
		Complement factor 3 glomerulopathy (C3G)
		Tubulointerstitial nephritis (TIN)
	Summary
	References
23 Autoimmune hemolytic anemia
	Introduction
	Historical background
	Classification
	Diagnostic pathway
	Warm-antibody autoimmune hemolytic anemia
		Primary and secondary warm-antibody autoimmune hemolytic anemia
			Epidemiology
			Pathogenesis
			Underlying or associated disorders
			Clinical features
			Therapy
		Drug-induced immune hemolytic anemia
	Cold-antibody autoimmune hemolytic anemia
		Cold agglutinin disease
			Epidemiology
			Pathogenesis
			Clinical features
			Diagnosis
			Therapy
		Secondary cold agglutinin syndrome
		Paroxysmal cold hemoglobinuria
	Atypical autoimmune hemolytic anemia
		Mixed warm and cold-antibody autoimmune hemolytic anemia
		Direct antiglobulin test-negative autoimmune hemolytic anemia
	Autoimmune hemolytic anemia in pregnancy
	Supportive therapeutic measures
		Transfusion
		Plasma exchange
		Vitamin and iron supplementation
		Thrombosis prophylaxis
		Measures against adverse effects of corticosteroids
	The future
	References
24 Acquired aplastic anemia
	Introduction
	Disease history
	Definition and classification
	Epidemiology
	Pathogenesis
		The immune pathogenesis of acquired aplastic anemia
	Triggers and predisposing factors for acquired aplastic anemia
		Genetic associations
		Medications and toxins
		Immunizations
		Association of acquired aplastic anemia with other disorders
		Potential role of telomere dysfunction
	Clinical manifestations
		Natural history & prognosis
		Clonal evolution in acquired aplastic anemia
	Diagnostic evaluation
	Treatment
		Supportive care
		Allogeneic hematopoietic stem cell transplant
			Patient selection
			Donor choice
			Graft choice
			Conditioning regimen
		Nontransplant therapy
			Immunosuppressive therapy
			Eltrombopag
			Androgens
			Cyclophosphamide
		Salvage therapy
	Conclusions and future directions
	References
25 Autoimmune clotting dysfunction
	Introduction
	Prothrombotic disorders
		Autoimmune inhibitors to protein C and protein S
		Autoimmune inhibitors to protein Z
	Anticoagulant disorders
		Autoimmune inhibitors to fibrinogen (factor I)
		Autoimmune inhibitors to prothrombin (factor II) and thrombin
		Autoimmune inhibitors to factor V
		Autoimmune inhibitors to factor VII
		Autoimmune inhibitors to factor VIII
		Autoimmune inhibitors to factor IX
		Autoimmune inhibitors to factor X
		Autoimmune inhibitors to factor XI
		Autoimmune inhibitors to factor XII
		Autoimmune inhibitors to factor XIII
		Autoimmune inhibitors to Van Willebrand factor
		Autoimmune inhibitors to further proteins
	Conclusion and future aspects
	COVID-19 and hypercoagulability
	References
26 Immune thrombocytopenia
	Introduction
	Disease history
	Definition and classification
	Geoepidemiology
	Pathogenesis
		Genetics backgrounds
		Environmental factors
		Autoimmune mechanisms
		Animal models for disease phenotype development
	Treatment
		First-line therapy
			Glucocorticoids
			Intravenous immunoglobulin
			Anti-D therapy
		Second-line therapy
			Thrombopoietin receptor agonist
			Rituximab
			Splenectomy
		Other agents
	Future directions
	References
27 Thrombotic thrombocytopenic purpura
	Introduction
	Disease history
	Epidemiology
	Definition, classification, and terminology
	Pathogenesis
		Genetics
		Environment
		Mechanism of thrombotic thrombocytopenic purpura
			von Willebrand factor and ADAMTS13
			Autoimmunity
			Other mechanisms
	Animal models
	Clinical and laboratory features
		Clinical manifestation
			Microangiopathic hemolytic anemia and thrombocytopenia
			Organ involvements
		Pathohistology
		Laboratory biomarkers
			ADAMTS13 activity levels
			Anti-ADAMTS13 antibody detection
			Emerging biomarkers
	Evaluation and diagnosis
		Initial evaluation
		Differential diagnosis
			Systemic disorders that induce microangiopathic hemolytic anemia and thrombocytopenia
			Other primary thrombotic microangiopathies
		Presumptive diagnosis
		Confirmed diagnosis
		Evaluation for organ injury
	Treatment for immune-mediated thrombotic thrombocytopenic purpura
		Therapeutic plasma exchange
		Immunosuppressive agents
			Glucocorticoids
			Rituximab
			Other immunosuppressive agents
		Therapies targeting von Willebrand factor
			Caplacizumab
			N-acetylcysteine
		Splenectomy
		Emerging therapies
	Therapy for congenital thrombotic thrombocytopenic purpura
	Special populations
		Thrombotic thrombocytopenic purpura during pregnancy
		Jehovah’s Witnesses
	Future directions
	Glossary
	References
28 Macrophage activation syndrome
	Introduction
		History of macrophage activation syndrome
		Definition and classification criteria for macrophage activation syndrome
		Geoepidemiology of macrophage activation syndrome
	Environmental factors and triggers
		Clinical features
			Natural history and mortality
			Biomarkers
			Pathology findings in macrophage activation syndrome
			Animal models
	Immunology and genetics
	Hormonal influences
	Treatment
	Future directions
	References
29 Autoimmune leukopenia
	Introduction
	Autoimmune neutropenia
		Epidemiology
		Pathophysiology
		Clinical features
		Diagnosis
		Management and treatment
		Conclusion and future directions
	Lymphopenia and antilymphocyte antibodies in autoimmune diseases
	References
30 Autoimmune thyroid diseases
	Introduction
	Chronic autoimmune thyroiditis
		Historic background
		Definition and classification
		Epidemiology
		Pathogenesis
			Autoimmune features
				Antigen presentation
				Autoantibodies
				T-cell responses
			Genetic factors
			Existential and environmental risk factors
				Sex
				Pregnancy
				Infections
				Stress
				Iodine
				Smoking and alcohol
				Vitamin D
				Selenium
				Drugs
				Microbiota
	In vivo models
		Pathologic effector mechanisms
	Clinical features
		Natural history
		Biomarkers
		Histopathology
	Morbidity and mortality
		Treatment
		Perspectives
	Graves’ disease
		Historic background
		Definition and classification
		Epidemiology
		Pathogenesis
			Autoimmune features
				Autoantibodies
				Immune mechanisms
			Genetic factors
			Existential and environmental risk factors
				Sex
				Pregnancy
				Infections
				Stress
				Iodine
				Vitamin D
				Smoking
				Radiation
				Immune-modulating drugs
				Microbiota
		In vivo models
		Pathologic effector mechanism
			Clinical features
				Natural history
				Biomarkers
				Histopathology
				Morbidity and mortality
				Treatment
				Graves’ orbitopathy and thyroid dermopathy
		Perspectives
	Acknowledgments
	Conflict of interest
	References
31 Autoimmune (Type 1) diabetes
	Introduction
	Epidemiology
		Asymptomatic islet autoimmunity
		Symptomatic autoimmune (type 1) diabetes
	Diagnostic criteria and classification of diabetes
	Etiology
		Genetic etiology of islet autoimmunity
		Environmental factors associated with first appearing autoantibodies
		Beta cell-related factors and islet autoimmunity
	Pathogenesis
		Pathophysiology
		Genetic factors
		Environmental factors
		Cellular mechanisms
		Humoral biomarkers
		Pathology
	Preclinical models of type 1 diabetes
	Primary prevention
	Secondary prevention
	Intervention
	Conclusions and future directions
	References
32 Adrenalitis
	Historical notes
	Anatomy and physiology of the adrenals
	Epidemiology of Addison’s disease and of autoimmune adrenalitis
	Autoimmune Addison’s disease (adrenalitis)
		Histopathology
		Animal models
			Induced immunity
			Spontaneous models
		Family history and genetic predisposition
		Cellular immunity
		Environmental factors
		Serological autoimmunity
			Adrenal cortex autoantibodies
			Steroid-producing cells autoantibodies
			Autoantigens recognized by adrenal cortex autoantibodies
			Techniques to detect 21-hydroxylase autoantibodies
			Autoantigens recognized by steroid-producing cells autoantibodies
			Techniques for determination of autoantibodies to other steroidogenic enzymes (17α-OHAbs and P450sccAbs)
			Other autoantibodies detected in patients with autoimmune Addison’s disease in the context of autoimmune polyglandular syndrome
		Pathogenesis
		Natural history of autoimmune Addison’s disease
		Diagnosis of autoimmune Addison’s disease
			Clinical manifestations
			General biochemical indices
			Hormonal tests
			Imaging
			Different clinical presentations of autoimmune Addison’s disease
			Association with other autoimmune disorders
		Therapy
			Conventional glucocorticoid therapy
			Conventional mineralocorticoid therapy
			Dehydroepiandrosterone therapy
			New therapies
			Regenerative therapy
			Steroid replacement during surgery, other illness, medical procedures, physical activity, and pregnancy
		Acute adrenal failure (adrenal crisis)
		Emergency Card
		Quality of life
		Autoimmune Addison’s disease and SARS-CoV-2 infection
		Mortality
		Osteoporosis
	Acknowledgments
	References
33 Autoimmune polyendocrine syndromes
	Historic background
	Autoimmune polyendocrine syndromes type1 (APS-1)
		Autoimmune polyendocrine syndrome type-2
	Immumodys; regulation polyendocrinopathy enteropathy X-linked (IPEX)
	Autoantibodies in diagnosis of autoimmune polyendocrine syndromes
	Genetics of autoimmune polyendocrine syndromes
	Pathogenic mechanisms
	Concluding remarks – future prospects
	References
34 Autoimmune gastritis and pernicious anemia
	Introduction
	Epidemiology and clinical presentation
		Epidemiology
		Gastric atrophy, hypochlorhydria and clinical consequences
			Pernicious anemia
			Autoimmune gastritis
			Autoimmune comorbidities
	Genetic features
	Pathogenesis
		Experimental models
		Studies on humans
	Diagnosis
		Laboratory tests
		Endoscopy
		Histopathology
	Assessing the neoplastic risk
		Staging of atrophic gastritis and surveillance strategies of autoimmune gastritis patients
	Concluding remarks – future prospects
	References
35 Autoimmune hypophysitis
	Definition and classification
	Historical notes
	Epidemiology and body of literature
	Clinical features
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	Pathological features
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	Autoimmune features
	Genetic and environmental influences
	Animal models
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	Diagnosis
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	Treatment
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	Outcome
		Primary hypophysitis
		Hypophysitis secondary to immune checkpoint inhibitors
	A comparison between primary hypophysitis and hypophysitis secondary to immune checkpoint inhibitors
	Concluding remarks – future perspectives
	References
36 Autoimmune primary ovarian insufficiency
	Introduction
	Ovarian autoimmunity and primary ovarian insufficiency
	Diagnosis of autoimmune primary ovarian insufficiency
	Treatment of primary ovarian insufficiency
	Conclusions
	References
37 Endometriosis as an autoimmune disease
	Introduction
	Disease history
	Disease definition and classification criteria
	Geoepidemiology
	Pathogenesis
		Genetics
		Hormonal influences
	The immunology of endometriosis
		Inflammatory pathways
		The role of immune cells in the pathogenesis of endometriosis
			Macrophages
			Uterine natural killer cells
			Mast cells
			Neutrophils
			Lymphocytes
		Humoral immune factors in endometriosis
			Cytokines and growth factors
			Complement
	Animal models
	Clinical features
		Natural history
		Biomarkers
	Pathology
		Peritoneal endometriosis
		Ovarian endometrioma
		Deep infiltrative endometriosis
	Diagnosis
		Nonsurgical approaches to the diagnosis of endometriosis
		Surgical approaches to the diagnosis of endometriosis
	Treatment
	Morbidity
	Future directions in endometriosis
	References
38 Primary hypoparathyroidism or non-surgical hypoparathyroidism
	Biological effect of parathyroid hormone
	Classification and etiopathology of non-surgical hypoparathyroidism
		Autoimmune hypoparathyroidism
		Nongenetically determined autoimmune hypoparathyroidism
		Significance of calcium sensing receptor and NACTH leucine-rich-repeat protein 5 antibodies
		Genetic hypoparathyroidism
			Disorders of parathyroid gland formation
		Disorders of parathyroid gland secretion
	Epidemiology of non-surgical-IpoPTH
	Clinical presentation of hypoparathyroidism
	Complications of chronic hypoparathyroidism
		Cataract
		Cardiovascular complications
		Chronic kidney disease
		Skeletal complications
		Basal ganglia calcifications or Fahr’s syndrome
		Infections
		Neuropsychiatric complications
	Diagnosis of hypoparathyroidism
	Initial assessment
	Treatment and follow-up
		Parathyroid hormone treatment versus standard treatment
	Hypoparathyroidism in pregnancy
	References
39 Celiac disease
	Introduction
	Disease history
	Geoepidemiology
	Clinical diagnosis
	Maintenance after diagnosis
	Celiac disease as an autoimmune disease
	Pathogenesis of celiac disease
	In vitro and in vivo models of celiac disease
		In vitro models of celiac disease
		Organoids
		In vivo models of celiac disease (nontransgenic)
		In vivo models of celiac disease (transgenic)
	Novel therapies for celiac disease
	Future directions for celiac research
	References
40 Inflammatory bowel disease
	Introduction
	History of inflammatory bowel disease
	Epidemiology
	Clinical features
		Crohn’s disease
		Ulcerative colitis
		Extraintestinal manifestations
		Musculoskeletal system
		Mucocutaneous system
		Ocular manifestations
		Hepatobiliary manifestations
		Extraintestinal complications of inflammatory bowel diseases
		Hypercoagulability
		Urolithiasis
		Osteopenia and osteoporosis
		Depression and anxiety
		Cancer
		Immune-mediated diseases associated with inflammatory bowel diseases
	Histopathologic features
	The etiology of inflammatory bowel disease
		Innate and adaptive immune mechanisms of disease
		Microbiome and disease
		Intestinal epithelium, barrier dysfunction, and disease
		Metabolism, cellular stress, and disease
	Genetics
	Diagnostics
		Inflammatory bowel diseases serologies and blood-based disease surveillance
		Stool-based tests of intestinal inflammation
		Detection of intestinal inflammation with imaging studies
	Treatment
		Aminosalicylates
		Corticosteroids
		Thiopurines
		Methotrexate
		Calcineurin inhibitors
		Anti-TNFα therapies
		Anti IL12/23
		Antiintegrins
		Janus kinase (JAK) inhibitors
		Sphingosine-1-phosphate receptor modulators
		Fecal microbiota transplantation
		Mesenchymal stem cells for perianal disease
		Nutritional support
		Surgical treatment
	Future directions
	References
41 Autoimmune gastrointestinal dysmotility
	Introduction
	Disease history and etiologies
		Immune-mediated and paraneoplastic gastrointestinal dysmotility
		Systemic autoimmune and inflammatory disorders
		Systemic diseases
		Infectious diseases
	Pathophysiology
		The enteric nervous system and autoantibodies
		Gut microbiome and autoimmune gastrointestinal dysmotility
		Clinical presentation
		Diagnosis
		Treatment
		Botulinum toxin (Botox) injections
		Gastric electrical stimulation
	Conclusion
	Future directions
	Acknowledgments
	Disclosures
	References
42 Autoimmune pancreatitis
	Introduction
	Disease definition
	Epidemiology
	Pathogenesis
	Pancreatitis
	Type 1 autoimmune pancreatitis
		Mechanisms in adaptive cellular and humoral immunity
		Mechanisms in innate immunity
	Genetics
	Clinical features
	Clinical features and disease course
	Serologic features
	Imaging features
	Pediatric presentation
	Checkpoint inhibitor related autoimmune pancreatitis
	Diagnostic criteria
	International Consensus Diagnostic Criteria
	Japanese criteria
	Treatment
	Induction
	Maintenance
	Relapse
	Procedural intervention
	Treatment of special populations
		Children
		Immune checkpoint inhibitor autoimmune pancreatitis
	Prognosis
	Future directions
	Acknowledgment
	References
43 Primary sclerosing cholangitis and IgG4-associated cholangitis
	Introduction
	History of primary sclerosing cholangitis and IgG4-associated cholangitis
	Definition of primary sclerosing cholangitis and IgG4-associated cholangitis
	Geoepidemiology
	Pathogenesis
	Genetics
	Environmental factors
	Dysbiosis
	Infectious and antigenic factors
	Immune responses
	Lymphocyte trafficking
	Biliary epithelial cells
	Toxic bile
	Clinical features
	Natural history
	Biomarkers
	Pathology with histology
	Morbidity/mortality
		Treatment
		Medical treatment of primary sclerosing cholangitis
	Stricture management
	Liver transplantation
	Future directions
	References
44 Autoimmune hepatitis
	General introduction
	Historical aspects
	Epidemiology
	Clinical features, diagnostic procedures and disease associations
	Pathological features
	Noninvasive fibrosis assessment
	Autoimmune features
	Genetics
	Pathogenic mechanisms
	Animal models
	The severe acute respiratory syndrome coronavirus 2 pandemic
	Treatment
		Standard treatment
		Alternative first-line treatments
		Second-line treatments
		Third-line treatments
		Duration of treatment
		Liver transplantation
		Future treatment approaches
	Perspectives
	References
45 Primary biliary cholangitis
	Introduction
	Historical perspective: changing nomenclature from primary biliary “cirrhosis” to primary biliary “cholangitis”
	Epidemiology
	Etiology
		Antimitochondrial autoantibody epitopes
		CD4+ and CD8+ T-cell epitopes
		Why biliary epithelial cells? The “ABC” of primary biliary cholangitis
		Genetic predisposition
		Environmental triggering factors
		Hormonal influences
	Animal models of primary biliary cholangitis
		Spontaneous murine models
		Xenobiotics-triggered animal models
		Infection-triggered murine models
		Adenylate uridine-rich element Del−/− mice
	Diagnosis
		Serum biochemistry and imaging studies
		Serological testing
			Antimitochondrial antibodies (AMA)
			Primary biliary cholangitis-specific antinuclear antibodies (ANA)
		Histopathology
	Symptoms and extrahepatic complications
		Fatigue
		Pruritus
		Sicca syndrome
		Osteopenia and osteoporosis
		Hyperlipidemia
		Fat-soluble vitamin deficiencies
	Variant syndromes of primary biliary cholangitis
		Primary biliary cholangitis with overlapping features of autoimmune hepatitis
		Premature ductopenic variant
	Treatment
		First-line therapy
			Ursodeoxycholic acid
		Second-line therapy
			Obeticholic acid
		Fibrates
	Management of symptoms of primary biliary cholangitis
		Fatigue
		Pruritus
	Risk stratification
		Monitoring and risk stratification during treatment
	Hepatocellular carcinoma
	Liver transplantation
	Future directions
	Acknowledgments
	References
46 Rheumatic fever and rheumatic heart disease
	Clinical, pathological, and epidemiologic features
	Autoimmune features
	Genetic features
	Genetic features
		Innate immune response
			MBL2 gene
			TLR-2 gene
			Ficolin gene
			FcγRIIA gene
			Masp2 gene
			MIF gene
			IGHV4-61 gene
		Adaptive immune response
		Major histocompatibility complex: DRB1, DRB3, DQB1, DQA1 genes
		CTLA4 gene
		Both innate and adaptive immune response
	In vivo and in vitro models
		In vivo model of myocarditis and valvulitis
		In vitro model of rheumatic heart disease autoimmune reactions
	Pathologic effector mechanisms
	Autoantibodies as potential immunologic markers
	Concluding remarks—future prospects
	References
47 Myocarditis and dilated cardiomyopathy
	Historical background
	Myocarditis—clinical, pathologic, and epidemiologic features
	Treatment
	Dilated cardiomyopathy—clinical, pathologic, and epidemiologic features
	Treatment
	Autoimmune features
	Genetic features
	Animal models
	Perspectives
	References
48 Autoimmune interstitial lung disease
	Introduction
	Historical background and classification criteria
	Epidemiology
	Pathogenesis
		Genetics
		Epigenetics
			Role of histone deacetylases
			DNA methylation
			MicroRNA
		Environmental factors
			Lung microbiome
			Occult occupational
			Air pollution
		Inflammation
			Epithelial damage and transforming growth factor-β activation
			Epithelial-to-mesenchymal transition
			Effector cells
			Innate and adaptive immune system response
			Autoantibodies
	Radiological patterns
		Nonspecific interstitial pneumonia
		Usual interstitial pneumonia
		Organizing pneumonia
		Lymphoid interstitial pneumonia
		Diffuse alveolar damage
	Pathological patterns
		Nonspecific interstitial pneumonia
		Usual interstitial pneumonia
		Organizing pneumonia
		Lymphoid interstitial pneumonia
		Diffuse alveolar damage
	Natural history
	Clinical features
		Systemic sclerosis
		Rheumatoid arthritis
		Sjögren’s syndrome
		Idiopathic inflammatory myopathies
		Systemic lupus erythematosus
		Small-vessel vasculitis
	Diagnostic biomarkers
	Treatment
		Nonpharmacological
		Major clinical trials on immunosuppressive agents for interstitial lung diseases
		Major clinical trials on antifibrotics for interstitial lung diseases
		Recommendations for the management of interstitial lung diseases secondary to autoimmune diseases
			Systemic sclerosis
			Rheumatoid arthritis
			Sjögren’s syndrome
			Idiopathic inflammatory myopathies
			Small vessel vasculitis
	Future directions
	Summary
	Glossary
	References
49 Sarcoidosis—a multisystemic disease
	Introduction
	Disease history
	Definition of the disease and classification criteria
	Geoepidemiology
	Pathogenesis
		Genetics
		Environmental factors
		Hormonal influences
		Immunology/inflammation/metabolism—effector mechanisms
		Animal models
	Clinical presentation
		Natural history
		Biomarkers
		Pathology and histology
		Organ involvement
	Differential diagnosis
	Comorbidities
	Morbidity/mortality
	Diagnosis
	Treatment
	Future directions
	References
50 Autoimmune inner ear disease
	Introduction
	Disease history
	Definition of the disease
	Epidemiology
	Pathogenesis
		Animal models used to study pathogenesis of disease
		Human studies used to identify pathogenesis of disease
	Genetics
	Environmental factors
		Immunology/inflammation/metabolism–effector mechanisms
		Clinical features
			Natural history
			Overlap with other autoimmune diseases
			Commercially available biomarkers
			Pathology with histology
			Imaging
			Morbidity/mortality
			Treatment
	Future directions: gaps/voids
	References
51 Meniere disease
	Definition
	Epidemiology
	Histopathology
		Anatomical considerations
		Endolymph production and regulation
		Histopathology
	Pathophysiology
		Genetics
		Autoimmunity
		Allergy/autoinflammation
	Clinical course
	Clinical variants
	Diagnosis
		Physical examination
		Audiological evaluation
			Pure tone audiometry
			Electrocochleography
			Auditory brainstem response, brainstem evoked response audiometry, and brainstem auditory evoked potential tests
		Vestibular evaluation
			Caloric test
			Video head impulse test
			Vestibular-evoked myogenic potentials
		Neuroimaging
			Computed tomography
			Magnetic resonance imaging
			Genetic testing
	Differential diagnosis
	Treatment
		Acute treatment
		Preventive treatment
			Lifestyle and dietary modifications
			Betahistine
			Steroids
			Gentamicin
			Other drugs
			Surgical treatment
			Future perspectives
	Acknowledgment
	Funding
	References
52 Autoinflammatory inner ear disease (AID)
	Introduction
	Disease history
	Geoepidemiology
	Definitions of the disease
		Familial cold autoinflammatory syndrome (FCAS)
		Muckle-Wells syndrome (MWS)
		Neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA)
		Autosomal dominant non-syndromic hearing loss (DFNA34)
	Clinical manifestations
		Otolaryngologic manifestations
		Cutaneous manifestations
		Neurologic manifestations
		Ophthalmologic manifestations
		Rheumatologic manifestations
		Other systemic manifestations
	Morbidity/mortality
	Pathogenesis
		Mechanism of nod-like receptor family pyrin domain 3-mediated inflammation
		Nod-like receptor family pyrin domain 3-mediated Autoinflammation in autoinflammatory inner ear disease
	Biomarkers/diagnostics
		Laboratory testing
		Histopathology
		Radiographic imaging
		Genetic testing
	Genetics
		Genetics of cryopyrin-associated periodic syndrome (CAPS)
	Animal models
	Treatment
		Anakinra
		Rilonacept
		Canakinumab
		VX-765
			Efficacy of treatment on auditory outcomes
		Cochlear implant
	Future directions
	References
53 Episcleritis and scleritis
	Introduction
	Anatomy and definition of episcleritis/scleritis
	Causes and morbidity of episcleritis
	Classification of episcleritis
		Simple episcleritis
		Nodular episcleritis
	Episcleritis laboratory evaluation
	Episcleritis treatment
	Epidemiology
	Pathogenesis of scleritis
	Causes and morbidity of scleritis
	Classification of scleritis
		Anterior scleritis
		Diffuse anterior scleritis
		Nodular anterior scleritis
		Necrotizing scleritis with inflammation
		Necrotizing scleritis without inflammation
		Posterior scleritis
	Animal models
	Scleritis workup
	Treatment for scleritis
	Current clinical trials
	References
54 Anterior uveitis
	Introduction
	Disease history
	Geo-epidemiology
	Genetic and autoimmune
	Infectious causes
		Viral
		Bacterial
		Parasitic
		Medication-induced
		Other
	Clinical picture
	Management
		Future directions
	References
55 Pediatric uveitis
	Introduction
	Disease history
	Disease definition and classification
		Standardization of uveitis nomenclature descriptors of uveitis
		Standardization of uveitis nomenclature anatomic classification of uveitis
	Geoepidemiology
	Pathogenesis
		Immunology
		Genetic factors
		Biomarkers
		Environmental factors
			Vitamin D
			Microbiome
	Clinical features
		Juvenile idiopathic arthritis
		Tubulointerstitial nephritis and uveitis syndrome
		Pars planitis
		Blau syndrome
	Masquerades
	Treatment
		Corticosteroids
		Conventional immunosuppressants
		Biologic therapy
			Tumor necrosis factor alpha inhibitors
			Other biologic agents
			Withdrawing therapy
	Future directions
	References
56 Intermediate uveitis
	Introduction
	Disease history
	Classification criteria
	GeoEpidemiology
	Pathogenesis
	Systemic associations
		Multiple sclerosis
		Sarcoidosis
		Tubulointerstitial nephritis and uveitis
	Infectious associations
		Syphilis
		Tuberculosis
		Lyme
		Human T-lymphotrophic virus 1
		Other
	Clinical features
	Morbidity and mortality
	Treatment
	Medical
		Local therapy
		Systemic therapy
	Surgery
	Future directions
	References
57 White dot syndromes
	Introduction
	Disease history
	Definition of the disease
	GeoEpidemiology
	Pathogenesis
	Genetics
	Clinical features
	Natural history
	Symptoms
	Pathology with histology
	Morbidity/mortality
	Treatment
	Future directions
	References
58 Panuveitis
	Introduction
	Sympathetic ophthalmia
		Disease history
		Geoepidemiology
		Pathogenesis
		Clinical features
			Natural history
			Pathology
			Morbidity and mortality
			Treatment
	Vogt–Koyanagi–Harada disease
		Disease history
		Diagnostic criteria
		Geoepidemiology
		Pathogenesis
		Clinical features
			Natural history
			Pathology
			Morbidity and mortality
			Treatment
	Behçet’s disease
		Disease history
		Diagnostic criteria
		Geoepidemiology
		Pathogenesis
		Clinical features
			Natural history
			Pathology
			Morbidity and mortality
			Treatment
	Sarcoidosis
		Disease history
		Diagnostic criteria
		Geoepidemiology
		Clinical features
			Natural history
			Pathology
			Morbidity and mortality
			Treatment
	Conclusion
	Acknowledgments
	References
59 Regional corticosteroid therapy for noninfectious uveitis
	Introduction
	Anatomic classification of uveitis
	Regional corticosteroid treatment by route of administration
		Topical
		Intravitreal
		Suprachoroidal
		Periocular
		Surgically implanted
	Summary
	References
60 Autoimmune bullous skin disorders
	Introduction
61 Pemphigus
	Disease history, definition, and classification
	Geoepidemiology
	Pemphigus vulgaris
		Pathogenesis
			Autoimmune features
				Autoantibodies
				T-cell activation
			Genetic features
		In vivo and in vitro models
			In vitro models
			Autoantibody passive transfer model
			Murine models of pemphigus vulgaris
		Pathologic effector mechanisms
			Pathogenic role of autoantibodies
		Autoantibodies as potential immunologic markers
			Clinical features
		Histopathology and immunopathology
		Treatment
	Pemphigus foliaceus
		Pathogenesis
			Autoimmune features
				Autoantibodies and T-cell activation
			Genetic features
			In vivo and in vitro models
			Pathologic effector mechanisms
			Autoantibodies as potential immunologic markers
			Environmental factors involved in fogo selvagem
		Clinical features
		Histopathology
		Treatment
		Other subtypes of pemphigus
			PNP
			Drug-induced pemphigus
			IgA pemphigus
			Pemphigus herpetiformis
	Concluding remarks
62 Bullous pemphigoid
	Disease history
	Definition
	Geoepidemiology
	Pathogenesis
		Genetics and epigenetics
		Environmental factors
		Hormonal influences
		Immunology/inflammation/metabolism—effector mechanisms
		Animal models/other ways for the studies of bullous pemphigoid
	Clinical features
		Natural history
		Biomarkers
		Pathology
		Morbidity/mortality
		Treatment
	References
63 Dermatitis herpetiformis
	Introduction and disease history
		Geoepidemiology
		Pathogenesis
	Clinical features and diagnosis
		Treatment
	References
64 Cutaneous lupus erythematosus
	Introduction
	Disease history
	Definition and classification criteria
	Geoepidemiology
		Pathogenesis
			Genetics
			Environmental factors
			Immunology/inflammation/metabolism
	Animal models
		Clinical features
			Natural history
			Biomarkers
			Pathology with histology
	Morbidity/mortality
		Treatment
	Topical and localized therapies
		Topical and intralesional use of corticosteroids
		Calcineurin inhibitors
		Topical application of retinoids
		Pulsed-dye laser
	Systemic treatment for cutaneous lupus erythematosus
		Antimalarials
		Systemic corticosteroids
		Thalidomide, retinoids, dapsone, and methotrexate
		Mycophenolate mofetil and other immunosuppressants
		Belimumab
	Surgical treatment for cutaneous lupus erythematosus
	Future directions
	References
65 Vasculitis from the dermatologist’s perspective
	Overview of vasculitis
		Introduction
		Features suggestive of systemic involvement
		Skin biopsy
	Small vessel vasculitis
		Cutaneous small vessel vasculitis
			Introduction
			Epidemiology
			Clinical features
		Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	IgA vasculitis
		Introduction
			Epidemiology
		Clinical features
		Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Urticarial vasculitis
		Introduction
			Epidemiology
		Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Acute hemorrhagic edema of infancy
	Erythema elevatum diutinum
	Granuloma faciale
	Small to medium vessel vasculitis
	Cryoglobulinemias
		Epidemiology
			Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Antineutrophilic cytoplasmic antibody-associated vasculitides
	Granulomatosis with polyangiitis
		Introduction
		Epidemiology
		Clinical features
			Antineutrophilic cytoplasmic antibody associations
			Pathology
		Diagnostic workup
		Prognosis and treatment
	Microscopic polyangiitis
		Introduction
		Epidemiology
		Clinical features
		Antineutrophilic cytoplasmic antibody association
			Pathology
		Diagnostic workup
		Treatment
	Eosinophilic granulomatosis with polyangiitis
		Introduction
		Epidemiology
		Clinical features
		Antineutrophilic cytoplasmic antibody association
			Pathology
		Diagnostic workup
		Treatment
	Medium vessel vasculitis
		Polyarteritis nodosa
			Introduction
			Epidemiology
			Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Kawasaki’s disease
		Introduction
		Epidemiology
		Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Large vessel vasculitis
	Temporal arteritis (giant cell arteritis)
		Introduction
		Epidemiology
		Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Takayasu arteritis
		Introduction
		Epidemiology
		Clinical features
			Etiology and pathogenesis
			Pathology
		Diagnostic workup
		Treatment
	Vasculitis associated with systemic disease
	Conclusion
	References
66 Psoriasis
	Introduction
	History of psoriasis
	Defining psoriasis
	Geo-epidemiology of psoriasis
		Prevalence and incidence
		Sex bias and age of onset
		Epidemiology of psoriatic arthritis
	Genetics of psoriasis
		Twin studies
		Heritability of psoriasis
		Susceptibility genes in psoriasis
		Epigenetics of psoriasis
		Environmental effects on psoriasis
			Infection
			Skin trauma
			Body habitus
			Diet
			Smoking
			Acute stress
			Medications
			Microbiome
	Animal models of psoriasis
		Spontaneous
		Xenograft
		Transgenic/knockout
		Intradermal cytokine injections
		Topical imiquimod application
	Immunopathogenesis
		Histological features of psoriasis
		Antigen presentation in psoriasis
		T cell activating self-antigens of psoriasis
		T cells in psoriasis
		Effect of IL-17 secreting cells
		Neutrophils in psoriasis
		IL-36 family cytokines and autoinflammation
		Other pustular psoriasis risk factors
		Spectrum of psoriasis
	Clinical features of psoriasis
		Clinical subtypes of psoriasis
			Chronic plaque
			Inverse
			Palmoplantar
			Sebopsoriasis
			Nail
			Guttate
			Erythrodermic
			Pustular
		Psoriatic arthritis
	Treatment
		Topical therapy
		Phototherapy
		Oral systemic therapy
		Biologic therapy
		Summary
	References
67 Cutaneous graft-versus-host disease
	Introduction and historical aspects
	Definition and classification of graft-versus-host disease
		Epidemiology
		Risk factors
		Pathogenesis
			Genetics factors
			Pathogenesis of acute graft-versus-host disease
			Pathogenesis of chronic graft-versus-host disease
			In vitro and in vivo models
	Clinical manifestations of graft-versus-host disease
		Acute cutaneous graft-versus-host disease
		Histopathology of acute graft-versus-host disease
		Differential diagnosis of acute graft-versus-host disease
		Chronic cutaneous graft versus-host disease
		Extracutaneous manifestations in graft-versus-host disease
		Histopathology of chronic cutaneous graft-versus-host disease
		Biomarkers
		Treatment
			Treatment of acute graft-versus-host disease
				Systemic treatment
				Topical treatment
			Treatment of chronic graft-versus-host disease
				Systemic treatment
				Topical treatment
	References
68 Vitiligo
	Introduction
	Disease history
		Definition, classification, and clinical manifestation
		Geoepidemiology
	Pathogenesis
		Genetics
		Epigenetics
	Environmental factors
		Chemical triggers
		Ultraviolet irradiation
		Skin injury
		Drugs
		Virus infection
		Vaccines
		Microbiome
	Hormonal influences
	Effector mechanisms
		Inflammation
		Immunology
		Metabolism
	Animal models
	Clinical features
		Natural history
		Biomarkers
		Histopathology
		Morbidity/mortality
		Treatment
			Treatment principles and objectives
			The goal treatment
			The principle of treatment
		Segmental vitiligo
	Nonsegmental vitiligo
		Topical therapies
			Topical corticosteroids
			Topical immunomodulators
		Systemic therapies
			Oral corticosteroids
			Methotrexate
			JAK inhibitors
			Ruxolitinib
			Tofacitinib citrate
			Minocycline
			Ginkgo biloba extract
			Afamelanotide
		Phototherapy
			Narrowband ultraviolet B
			308nm excimer laser
			Surgical treatment
			Depigmenting treatment
			Cosmetic: camouflage
	Future direction (what is still needed)
	References
69 Alopecia areata
	Introduction
	Disease history
	Definition and classification of alopecia areata
	Geoepidemiology
	Pathogenesis
		Genetics
		Immunology
		Other factors
		Animal models
			Spontaneous animal models
			Constructed animal models
	Clinical features
		Clinical manifestation
		Natural history
		Biomarkers
		Trichoscopy
		Pathology
		Morbidity/mortality
	Treatment
		Traditional treatments
			Corticosteroids
			Immunosuppressants
			Contact immunotherapy
		Treatment options in development
			Janus kinase inhibitors
			Biologics
			Other treatments
	Future directions
	References
70 Chronic spontaneous urticaria
	Introduction
	Disease history
	Definition
	Epidemiology
	Etiology
		Genetics
		Environmental factors
			Helicobacter pylori infection
			Staphylococcus aureus enterotoxins
			Gut microbiota
			Viral infection
			Parasite infestation
			Vitamin D
			Food intolerance
			Psychological factors
		Hormonal influences
			Sex hormones
			Thyroid-related hormones
			Hypothalamic–pituitary–adrenal axis
	Pathogenesis
		Immunology
			Type I autoimmunity of chronic spontaneous urticaria
			Type IIb autoimmunity of chronic spontaneous urticaria
			Overlap of type I and type IIb autoimmunity
			Downstream mechanism involved in autoimmunity of chronic spontaneous urticaria
		Coagulation cascade
		Inflammation
		Allergy
	Clinical features
		Natural history
		Biomarkers
			Biomarkers associated with chronic spontaneous urticaria diagnosis, activity, and severity
			Biomarkers associated with response to treatment for chronic spontaneous urticaria
		Histopathology
		Comorbidity
		Mortality
	Diagnostic strategies
	Treatment
		Identifying possible causative or predisposing factors and eliminating or avoiding them
		Symptomatic pharmacotherapy
			Second generation H1-antihistamines (sgAHs)
			Omalizumab
			Cyclosporine
			Other alternative treatments
	Future directions
	Acknowledgments
	Glossary
	References
71 Skin involvement in other autoimmune diseases
	Adult-onset Still’s disease
		Introduction
		Disease history
		Definition and classification criteria
		Geoepidemiology
		Pathogenesis
		Genetic factors
		Environmental factors
		Immunology/inflammation/metabolism
		Clinical features
		Fever
		Arthralgia or arthritis
		Skin rashes
		Other clinical symptoms
		Increased leukocyte and neutrophil counts
		Other biological abnormalities
		Natural history
		Biomarkers
		Treatment
		Traditional therapies
		Colchicine
		Tumor necrosis factor-α inhibitors
		IL-1β inhibitors
		IL-18 inhibition
		IL-6 inhibitor
		Other treatments
		Future directions
	Eosinophilic fasciitis
		Introduction
		Disease history
		Definition and classification criteria
		Diagnostic procedures
		Geoepidemiology
		Pathogenesis
		Genetics
		Thrombotic manifestations
		Antiphospholipid antibodies and the coagulation cascade
		Antiphospholipid antibodies cellular interactions
		Obstetric manifestations
		The complement system in antiphospholipid syndrome
		Clinical features
		Risk assessment in antiphospholipid syndrome
		Biomarkers
		Obstetric antiphospholipid syndrome
		Thrombotic antiphospholipid syndrome
		Noncriteria antiphospholipid syndrome manifestations
		Neurological antiphospholipid syndrome
		Hematologic antiphospholipid syndrome
		Dermatologic antiphospholipid syndrome
		Cardiac antiphospholipid syndrome
		Pulmonary antiphospholipid syndrome
		Renal antiphospholipid syndrome
		Catastrophic antiphospholipid syndrome
		The antiphospholipid antibodies
			Criteria-relevant antiphospholipid antibodies
			Lupus anticoagulant
			Anticardiolipin
			Anti-b2-glycoprotein-I antibody
			Noncriteria antiphospholipid antibodies
			Antiphospholipid antibodies of the IgA isotype
			Low-level antiphospholipid antibodies
			Autoantibodies to domain 1 of b2-glycoprotein-I antibody
			Antiphosphatidylethanolamine antibodies
			Antiphosphatidylserine antibodies
			Antiprothrombin antibodies
			Antiphosphatidylserine/prothrombin antibodies
			Antiannexin A5 antibodies
			Metaanalysis: prevalence of different noncriteria antiphospholipid antibodies
		Seronegative antiphospholipid syndrome
		Morbidity/mortality
		Treatment
		Future directions
	Behcet’s syndrome
		Disease history
		Definition and classification criteria
		Pathergy test
		Other
		Diagnosis
		Assessment of disease activity
		Differential diagnosis
		Geoepidemiology
		Pathogenesis
		Genetics
		Hormonal influences
		Immunology/inflammation/metabolism
		Others
		Animal models
		Clinical features
			Oral ulcers
			Cutaneous lesions
			Vasculitis
			Genital ulcers
			Ocular involvement
			Neurologic involvement
			Joint involvement
			Gastrointestinal involvement
		Other features
		Biomarkers
		Pathology with histology
		Treatment
		Oral and genital ulcers
		Cutaneous lesions
		Gastrointestinal involvement
		Ocular involvement
		Deep venous thrombosis
		Aneurysm
		Neurologic involvement
		Arthritis
		Prognosis
		Future directions
	Dermatomyositis
		Disease history
		Definition and classification criteria
		Diagnostic criteria
		Classification and clinical manifestation of dermatomyositis
		Classic dermatomyositis
		Amyopathic dermatomyositis
		Hypomyopathic dermatomyositis
		Geoepidemiology
		Specific and associated antibodies in dermatomyositis
		Myositis-specific autoantibodies
		Mechanism of disease
		The association of malignancy with autoimmunity
		Modification of autoantigen expression or structure by immune effector pathways to generate a self-sustaining phenotype
		Treatment
		Rituximab
		Abatacept
		Janus kinase inhibitors
		Antitumor necrosis factor agents
		Future directions
	Eosinophilic fasciitis
		Introduction
		Disease history
		Definition and classification criteria
		Geoepidemiology
		Pathogenesis
			Genetics
			Environmental factors
			Hormonal influences
			Immunology/inflammation/metabolism
		Clinical features
			Natural history
		Biomarkers
		Pathology with histology
		Treatment
		Future directions
	Rheumatoid arthritis
		Disease history
		Definition and classification criteria
		Diagnosis
		Assessment of disease activity
		Geoepidemiology
		Pathogenesis
		Genetics
		Hormonal influences
		Environmental factors
		Others
		Immunology/inflammation/metabolism
			The synovium
			Bone erosion
			Cytokine and signaling networks
		Animal models
		Clinical features
			Natural history
		Joint manifestations
			Typical rheumatoid arthritis
			Others
		Systemic manifestations
			Constitutional and systemic symptoms
			Osteopenia
				Systemic
				Periarticular
				Periodontal
			Muscle weakness
				Synovial inflammation
				Myositis
				Drug-induced myopathy
			Skin disease
				Rheumatoid nodules
				Skin ulcers
				Neutrophilic dermatoses
				Medication-induced skin changes
				Other
			Hematologic abnormalities
			Other
		Biomarkers
		Autoantibodies
		Acute-phase response
		Investigational markers
		Pathology with histology
		Morbidity/mortality
		Treatment
		Future directions
	Sjogren’s syndrome
		Introduction
		Disease history
		Definition and classification criteria
		Geoepidemiology
		Pathogenesis
			Genetics
			Environmental factors
			Hormonal influences
			Immunology/inflammation/metabolism
			Animal models
		Clinical features
			Natural history
		Eyes
		Oral cavity
		Lungs
		Kidney
		Gastrointestinal tract
		Nervous system
		Genitourinary
		Vascular system
		Musculoskeletal and constitutional symptoms
		Lymphoma and other hematological manifestations
		Biomarkers
		Pathology with histology
		Morbidity/mortality
		Treatment
		Future directions
	Systemic sclerosis
		Disease history
		Definition and classification criteria
		Geoepidemiology
		Pathogenesis
		Genetics
		Clinical features
			Cutaneous manifestation
		Digital vasculopathy
		Musculoskeletal manifestations
		Gastrointestinal involvement
		Pulmonary involvement
		Cardiac involvement
		Scleroderma renal crisis
		Genitourinary involvement
		Management
			Baseline assessment and classification
			Long-term organ-specific management, follow-up, and outcomes
			Skin and musculoskeletal disease
			Interstitial lung disease
			Pulmonary hypertension
			Gastrointestinal manifestations
			Scleroderma renal crisis
			Cardiac disease
			Hemopoietic autologous stem-cell transplantation
		Future directions
	References
72 Multiple sclerosis
	Introduction and historical background
	Clinical features and disease phenotypes
	Clinically isolated syndrome
	Relapsing remitting multiple sclerosis
		Primary progressive multiple sclerosis
		Secondary progressive multiple sclerosis
	Radiologically isolated syndrome
	Silent progression
	Diagnostic criteria
	Epidemiology and causes of multiple sclerosis
	Geographic and environmental factors
	Genetic factors
	Viral factors
	Immunology and pathology
	Immunology
	Imaging
	Management of multiple sclerosis
		Acute relapses
	Disease modifying treatments
		Interferons
		Glatiramer acetate
		Teriflunomide
		Fumarates
		Sphingosine-1-phosphate receptor modulators
		Cladribine
		Natalizumab
	Anti-CD20 agents
		Alemtuzumab
		Mitoxantrone
		Hematopoietic stem cell transplant
		New treatments currently in trials
	Symptomatic management of multiple sclerosis
	Pregnancy and hormonal influences in multiple sclerosis
	Biomarkers
	Diagnostic biomarkers
	Treatment associated biomarkers
	Disease activity biomarkers
	Future directions
	Conclusions
	References
73 Neuromyelitis optica spectrum disorder and other central nervous system inflammatory diseases
	Introduction
	Aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder
		Disease history
		Definition and diagnostic criteria
		Epidemiology
		Pathogenesis
		Clinical features
			Optic neuritis
			Acute myelitis
			Area postrema syndrome
			Acute brainstem syndrome
			Symptomatic narcolepsy or acute diencephalic syndrome
			Symptomatic cerebral syndrome
		Neuroimaging findings
			Brain and orbit magnetic resonance imaging
			Spinal cord magnetic resonance imaging
		Laboratory findings
			Aquaporin4 IgG detection
			Cerebrospinal fluid
			Glial fibrillary acidic protein—a potential biomarker for disease activity monitoring
			Coexisting autoimmune diseases and related biomarkers
		Treatment and outcome
			Acute attack treatment
			Attack prevention
				Moving toward targeted treatment in AQP4+NMOSD
				Depletion of B-cells and its lineage
				IL-6 antagonists
				Monoclonal antibodies targeting complement
				Other treatment options
				Future therapies
	Myelin oligodendrocyte glycoprotein antibody associated disease
		Disease history
		Definition and diagnostic criteria
		Epidemiology
		Pathogenesis
		Clinical features
			Optic neuritis
			Acute myelitis
			Acute disseminated encephalomyelitis
			Brainstem and cerebellar attack
			Cerebral cortical encephalitis and other cerebral attacks
		Neuroimaging findings
			Brain and orbit magnetic resonance imaging
			Spinal cord magnetic resonance imaging
			T2-lesion evolution
		Laboratory findings
			MOG IgG detection
			Cerebrospinal fluid
			Coexisting autoimmune diseases and related biomarkers
		Treatment
			Acute
			Attack prevention
	Glial fibrillary acidic protein autoimmunity
		Disease history
		Definition and diagnostic criteria
		Epidemiology
		Pathogenesis
		Clinical features
		Neuroimaging findings
		Laboratory finding
			GFAP IgG detection
			Cerebrospinal fluid
			Coexisting autoimmune diseases and related biomarkers
		Oncologic associations
		Treatment
	References
74 Pediatric multiple sclerosis and acute disseminated encephalomyelitis
	History of pediatric multiple sclerosis and other acquired demyelinating disorders
		Acute demyelinating syndromes
	Acute disseminated encephalomyelitis
		Overview
	Acute disseminated encephalomyelitis secondary to MOGAD
	Additional clinical presentations in pediatric MOGAD
	When ADEM is not associated with MOG
	ADEM prognosis and treatment
	Pediatric multiple sclerosis
		Pathogenesis
		Genetics
		Environment
		Physiology
	Epidemiology
	Gender, age, ethnicity
		Age
		Gender
		Puberty
		Ethnicity
	Radiologically isolated syndrome
	Pediatric relapsing-remitting multiple sclerosis
	Prognosis/long-term outcomes
	Psychosocial issues in pediatric multiple sclerosis
		Psychiatric disorders
		Self-reported depressive symptoms, anxiety, fatigue, coping
		Quality of life
		Cognition
		Academics
	Neuroimaging
	Multiple sclerosis treatment
		Acute relapse management
		Disease modifying therapies for pediatric multiple sclerosis
			Interferon/glatiramer acetate
			Natalizumab
			Dimethyl fumarate
			Fingolimod
			Teriflunomide
			Monoclonal antibodies
		Disease modifying therapy in pediatric multiple sclerosis—current perspectives
		Other management recommendations
	References
75 Paraneoplastic neurological syndromes
	Introduction
		Definition and historical background
	Diagnostic criteria: paraneoplastic neurological syndromes-care score
	Epidemiology
	Antibody and antigenic targets: distribution and functions
	Clinical features
	High-risk phenotypes
		Rapidly progressive cerebellar syndrome
		Limbic encephalitis
		Encephalomyelitis
		Opsoclonus-myoclonus
		Sensory neuronopathy
		Gastroparesis
		Lambert–Eaton myasthenic syndrome
	Intermediate-risk phenotypes
	Considerations regarding antibody testing
	Cancer screening
	Pathophysiology
		Triggers of immune tolerance breakdown
			Tumors
			Host predisposition
			Infections
	Effector mechanisms of the immune response
		The role of antibodies
		The role of T cells
		Neuropathological findings
	The role of immune checkpoint inhibitors
	Treatment and prognosis
	Future directions
	References
76 Autoimmune encephalitis
	Introduction
	Historical background
	Epidemiology
	Clinical features and specific neuronal autoantibodies
		Disease definition
		Clinical features
		Other specific immune-mediated neurological syndromes
			Morvan’s syndrome
			Stiff person spectrum disorders: stiff person syndrome and progressive encephalomyelitis with rigidity and myoclonus
		Clinical autoimmune encephalitis criteria
	Diagnostics
		Medical history and clinical examination
		Brain MRI
		Electroencephalography
		CSF analysis and neuronal antibody studies
		Brain fluorodeoxyglucose positron emission tomography
		Tumor screening
	Pathogenesis
	Treatment
		Tumor removal
		Immunotherapy
		Symptomatic treatment
	Future directions
	References
77 Central nervous system manifestations of systemic autoimmune diseases
	Introduction
	Immune-mediated inflammatory diseases: systemic lupus erythematosus, scleroderma, rheumatoid arthritis, and Sjogren’s syndrome
		Systemic lupus erythematosus
			Epidemiology
			Pathogenesis
			Inflammatory pathway
			Autoantibodies
			Breakdown of the blood–brain barrier
			Cytokines
			Ischemic pathway
			Antiphospholipid antibodies
			Vasculopathy
			“Secondary” NPSLE or non-SLE-related NP symptoms
			Clinical features
				Natural history
				Biomarkers and diagnostics
				Serum biomarkers
				Brain imaging
				Electroencephalogram
				Histopathology
				Morbidity/mortality
				Treatment
			Gaps in diagnosis and treatment
				Diagnostic gaps
				Treatment gaps
		Scleroderma
			Epidemiology
			Pathogenesis
			Clinical features
				Natural history
				Biomarkers
				Histopathology
				Morbidity/mortality
				Treatment
				Gaps in diagnosis and treatment
		Rheumatoid arthritis
			Epidemiology
			Pathogenesis
			Clinical features
				Natural history
				Biomarkers
				Histopathology
				Morbidity/mortality
				Treatment
				Gaps in diagnosis and treatment
		Sjogren’s syndrome
			Epidemiology
			Pathogenesis
			Clinical features
				Natural history
				Biomarkers
				Histopathology
				Morbidity/mortality
				Treatment
			Gaps in diagnosis and treatment
		Summary
	Neurosarcoidosis
		Introduction
		Definition and overview
		Epidemiology
		Pathogenesis
			Genetics
			Environmental factors
			Effector mechanisms
		Clinical features
			Cranial nerve palsies
			Meningitis
			Intraparenchymal brain lesions
			Myelopathy
			Hypothalamic–pituitary axis dysfunction
			Peripheral neuropathy
			Myopathy
			Nongranulomatous syndromes associated with sarcoidosis
		Natural history
		Evaluation and diagnosis
			Evaluation for central nervous system disease
			Evaluation for systemic disease
		Biomarkers
			Pathology
		Morbidity and mortality
		Treatment
			Corticosteroids
			Cytotoxic drugs
			Tumor necrosis factor-alpha blockers
		Future directions
	Systemic vasculitides: small vessel vasculitis, medium vessel vasculitis, large vessel vasculitis, and variable vessel vasc...
		Small vessel vasculitis
			Introduction
			Definition and overview
			Pathogenesis
			Biomarkers
			Neurologic manifestations
			Granulomatosis with polyangiitis
			Microscopic polyangiitis
			Eosinophilic granulomatosis with polyangiitis
			Evaluation and diagnosis
			Treatment
			Summary
		Medium vessel vasculitis
			Introduction
			Definition and overview
			Pathogenesis
			Biomarkers
			Disease manifestations and central nervous system manifestations
			Evaluation and diagnosis
			Treatment
			Summary
		Large vessel vasculitis
			Introduction
			Definition and overview
			Pathogenesis
			Epidemiology
			Genetics
		Disease manifestations and central nervous system manifestations
			Giant cell arteritis
			Takayasu arteritis
			Evaluation and diagnosis
				Giant cell arteritis
			Takayasu arteritis
			Treatment
			Summary
		Variable vessel vasculitis
			Introduction
			Definition and overview
			Pathogenesis
			Genetics
			Disease manifestations and central nervous system manifestations
			Evaluation and diagnosis
			Treatment
	Immunoglobulin G4-related disease
		Introduction
		Pathogenesis
		Epidemiology
		Clinical features
		Central nervous system manifestations
		Treatment
	Miscellaneous conditions
	Summary
	Acknowledgments
	References
78 Peripheral neuropathies
	Introduction
	Acute neuropathies: the Guillain–Barré syndrome
		Historical background
		Epidemiology
		Clinical features and subtypes of Guillain–Barré syndrome
			Acute inflammatory demyelinating polyradiculoneuropathy
			Acute motor axonal neuropathy
			Acute motor and sensory neuropathy
		Miller Fisher syndrome
		Autoimmune features
			Molecular mimicry
			Antiganglioside antibodies in Guillain–Barré syndrome variants
			Gangliosides in peripheral nerve
			Functional effects of antibodies
		Environmental effects
		Animal models of disease
		Cellular mechanisms
		Cellular and humoral immune elements are synergistic
		Genetic aspects of Guillain–Barré syndrome
		Treatment and outcomes
	Chronic neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy
		History
		Epidemiology and clinical features
			Multifocal motor neuropathy with conduction block
			Multifocal-acquired demyelinating sensory and motor neuropathy
			Paraproteinemic demyelinating peripheral neuropathy
		Autoimmune features
		Immunogenetic features
		Environmental influences
		Animal models
		Pathogenic mechanisms
		Treatment and outcome
	Concluding remarks and future prospects
	Patient support and education
	Acknowledgments
	References
79 Autoimmune disorders of the neuromuscular junction
	Introduction
	Historical background
	Definition of autoimmune neuromuscular junction disorders
	Epidemiology of autoimmune neuromuscular junction disorders
	Myasthenia gravis
		Pathophysiology
			Neuromuscular transmission defect
			Antibody effector mechanisms
			Thymic immunopathology
			Autoreactive T and B cells
			Micro RNA in myasthenia gravis pathogenesis
			Differential involvement of muscles by myasthenia gravis
		Animal and cell-based models
		Clinical features
		Natural history, mortality, and morbidity
		Biomarkers
		Treatment
	Lambert-Eaton syndrome
		Pathophysiology
		Clinical features
		Natural history
		Serology and biomarkers
		Treatment
	Neuromyotonia
	Future directions
	References
80 The autoimmune myopathies
	Introduction
	Disease history and classification
		Polymyositis: a diagnosis of exclusion
	Epidemiology
	Pathogenesis and genetic predisposition
		Genetic factors
		Environmental factors
			Smoking
			Ultraviolet light
			Infections
			Microbiome in myositis
			Medications
		Animal models
		Further insights into the pathogenesis of inclusion body myositis
		Further insights into the pathogenesis of immune-mediated necrotising myopathy
		Further insights into the pathogenesis of dermatomyositis
		Nonimmune aspects of autoimmune myopathies
	Clinical presentation of autoimmune myopathies except inclusion body myositis
		Skin involvement
		Arthritis
		Pulmonary involvement
		Cardiac involvement
		Gastrointestinal involvement
		Association with malignancy
	Clinical presentation of inclusion body myositis
	Differential diagnosis of autoimmune myopathy/myositis
	Investigations
		Blood tests
			Autoantibodies used in the laboratory assessment of patients with idiopathic inflammatory myositis
			Antinuclear antibodies (ANA) in immune-mediated inflammatory myopathy
			Antiextractable nuclear antigen (ENA) antibodies and antidouble stranded DNA antibodies in immune-mediated inflammatory myo...
			Assays for the detection of myositis-specific antibodies (MSA) and myositis associated antibodies (MAA)
			Immunoprecipitation
			Line/dot immunoassay (LIA/DIA)
			ELISA and similar immunoassays
			Other methods
			Prevalence of myositis antibodies in immune-mediated inflammatory myopathy
			Clinical associations of serologic subgroups of IIM – myositis specific antibodies
				Anti-MDA5 antibodies
			Anti-TIF1gamma antibodies
			Anti-NXP2 antibodies
			Anti-SAE antibodies
			Anti-Mi2 antibodies
			Antisynthetase antibodies
			Anti-SRP antibodies
			Anti-HMGCR antibodies
			Clinical associations of serologic subgroups of immune-mediated inflammatory myopathy – myositis associated antibodies
				Anti-Ro52 antibodies
				Anti-PM-Scl antibodies
				Anti-Ku antibodies
				Anti-U1RNP antibodies
				Anti-CN1A antibodies
			Mutual exclusivity of myositis specific antibodies
			Myositis antibodies among patients with juvenile myositis
		Neurophysiology
		Imaging in myositis
			Muscle biopsy
				Selecting a muscle biopsy site
				Specimen stains and their clinical utility
				General histopathological findings in immune-mediated inflammatory myopathy
				Histopathological features in specific immune-mediated inflammatory myopathy subtypes
		Investigations directed at excluding an underlying malignancy in immune-mediated inflammatory myopathy except inclusion bod...
	Treatments
		Approach to treatment of idiopathic inflammatory myopathies except inclusion body myositis [215,216]
			Glucocorticoids
			Non-biologic disease modifying antirhematic drugs (DMARDs)
			Intravenous immunoglobulin
			Rituximab
			Abatacept
			Tofacitinib
			Treatment of inclusion body myositis
			Arimoclomol
			Sirolimus
			Bimagrumab
		Exercise treatment
		Treatment of dysphagia
	Prognosis
	Concluding remarks
	References
Index for Volumes 1 and 2