دانلود کتاب Dubois' Lupus Erythematosus and Related Syndromes

فهرست مطالب :

Cover
Inside front cover
Front matter
Dubois’ Lupus Erythematosus and Related Syndromes
Copyright
Dedication
Preface
Acknowledgments
Contributors
Contents
Section 1 What is lupus?
Section 2 Pathogenesis
Section 3 Mechanisms of tissue injury
Section 4 Autoantibodies
Section 5 Clinical aspects of lupus erythematosus
Section 6 Assessment of lupus
Section 7 Management of lupus
Section 8 Outcomes
1 History of lupus
Prescientific period
Differentiation from tuberculosis
Recognition of systemic lupus erythematosus
Systemic lupus erythematosus and “collagen disease”
Serologic aspects
Pathogenesis: Some breakthroughs
Epidemiology
Classification criteria and disease indices
Management: Some breakthroughs
Related diseases
Antiphospholipid syndrome
Neonatal lupus
Lupoid hepatitis
Prognosis: Just a few comments
References
2 Definition and classification of lupus and lupus-related disorders
Systemic lupus erythematosus
Definition of systemic lupus erythematosus
Development of the american college of rheumatology systemic lupus erythematosus classification criteria
Constraints of the american college of rheumatology systemic lupus erythematosus classification criteria
Systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus
2019 European league against rheumatism/american college of rheumatology classification criteria for systemic lupus erythematosus
Chronic cutaneous lupus
Drug-induced lupus erythematosus
Mixed connective tissue disease
Undifferentiated connective tissue disease and overlap syndromes
Antiphospholipid antibody syndrome
Neonatal lupus
Summary
References
3 The epidemiology of lupus
Introduction
The fundamentals of epidemiology
Case definition
Case ascertainment
Population at risk
Pediatric systemic lupus erythematosus
Cutaneous lupus erythematosus
Other considerations
Conclusion
References
4 Overview of lupus pathogenesis
Phases of SLE: Evolution of disease in susceptible persons
Overview: The major pathways favoring development of SLE
Stimulation of innate and adaptive immune responses by foreign and autoantigens
Autoantibodies and immune complexes of SLE
Regulatory mechanisms fail to control autoimmune responses
Abnormalities in T and B lymphocytes in SLE
Cytokines/chemokines and SLE
Genetics and epigenetics
Gender influences
Environmental factors
Complement activation and tissue damage in SLE
Current approved and investigational therapies for SLE4
Suggested reading
5 Genetics of SLE
Genetic studies on SLE
Early days of SLE genetic studies
Genome-wide association studies
SLE susceptibility genes in cell death and clearance of self-antigens
Complements and nucleases
NCF1 and NCF2
ITGAM and SLC29A3
Other genes involved in cell death and clearance
Fc gamma receptors
SLE genes in toll-like receptor and IFN-I signaling
TLR7
IRF5 and IRF3
IRF7
IFN-α
miR-146a and USP18
TASL and SLC15A4
IFIH1
STIM1
IFN-II (IFN-γ) and IFN-III signaling
NF-κB signaling
TNFAIP3 and TNIP1
UBE2L3
RELA
IKBKB and IKBKE
B-cell signaling in SLE genetics
LYN
TNFSF13B
TACI
PTPN22
CSK
TRAF3
CD40 and FCRL5
TAOK3
RASGRP1 and RASGRP3.
IL7R
SLE genes in T cell signaling
HLA class II genes
TNFSF4
PTPRC (CD45)
CTLA4 and CD80
DEF6
DUSP22
CXCR5 and RGS1
GRB2 and PDCD5
WDFY4
CD37
IL12 and JAK/STAT signaling
IL12A and IL12RB2
STAT4, JAK2, and TYK2
Transcription factors and epigenetic modifiers in SLE
IKZF1
BACH2 and PRDM1
ETS1
TET3
Applications of the genetic findings
Future directions
References
6 Single gene defects and autoinflammation
Introduction
Type I interfons and their role in autoimmune disease
Interferonopathies and associated molecular defects
Aicardi-Goutières syndrome
STING-associated vasculopathy with onset in infancy
COPA syndrome
Spondyloenchondrodysplasia
Informing monogenic lupus
Ultraviolet sensitivity and cGAS-STING
Complement protein defects driving monogenic lupus
Therapeutic implications of RNA/DNA sensing in monogenic autoimmune disease and future directions
References
7 Epigenetics of lupus
DNA methylation in SLE
Introduction to DNA methylation
Dysregulated DNA methylation and gene expression in SLE
Mediators and factors contributing to dysregulated DNA methylation in SLE
Histone modification in SLE
Introduction to histone modification
Dysregulated histone modification in SLE
Mediators and factors contributing to dysregulated histone modification in SLE
3D genome and SLE
Introduction of 3D genome
Genetic variants and 3D genome
Identification of 3D genome associated with functional variants
Dysfunctional enhancers in SLE
3D genome as targets for SLE therapy
RNA modification
m6A modification
A-to-I editing
C-to-U editing
miRNA in SLE
Introduction to miRNA
miRNA biogenesis
miRNA regulation
Roles of miRNAs in SLE
Functions of miRNAs in the immune system
Regulating the development of immune cells
Regulating innate and adaptive immune responses
Dysfunctional miRNAs in lupus
Dysfunctional miRNAs in innate immunity
Dysfunctional miRNAs in adaptive immunity
Dysfunctional miRNAs in resident cells of target tissues
Roles of lncRNAs in SLE
Functions of lncRNA in the immune system
Dysfunctional lncRNAs in lupus
Roles of circrnas in SLE
Translational application of epigenetics in lupus
Prospective epigenetic biomarkers
Epigenetic therapeutic targets
References
8 The role of the environment and microbiome in lupus
Interplay between environmental, genetic, and epigenetic factors
Dietary influences on SLE
Gut microbiome and SLE
Environmental exposures and SLE
Silica exposure
Smoking
Smoking and the role of gene-environment interactions
Epstein-Barr virus exposure
Vitamin D status and ultraviolet radiation exposure
Metals
Pesticides and persistent organic pollutants
Air pollution
Other environmental agents and SLE
Methodologic considerations
The SLE exposome
Future considerations
References
9 The innate immune system in SLE
Cellular components of the innate immune system
Monocytes, macrophages, and dendritic cells
Neutrophils
Plasmacytoid dendritic cells
Natural killer cells
Platelets
Innate lymphoid cells
Extracellular components of the innate immune system
Pattern recognition receptors: Pamps, damps, and pathways of innate immune stimulation in SLE
Toll-like receptors
TLR7 and TLR9 in SLE
Cytosolic sensors
Ligands responsible for stimulating IFN-I and other inflammatory cytokines
Innate immune detection of self versus nonself nucleic acid
Therapeutic approaches
References
10 B cells and generation of antibodies
Structure of the antibody molecule
Generation of antibody diversity
Class switch recombination
Somatic hypermutation
Posttranscriptional modifications of antibodies
Pathogenic autoantibodies
Genetic and molecular analysis of anti-DNA antibodies
B-cell subsets: Implications for SLE
Innate B cells
Follicular B cells
Memory B cells
Plasma cells
Age/autoimmune-associated B cells
Regulatory B cells
B-cell activation
B-cell receptor signaling
Toll-like receptors in B-cell function
Cytokine activation
Plasma cell differentiation
Germinal center and extrafollicular activation of B cells
B-cell tolerance
Apoptosis and autoimmunity
Autoantibody induction
Triggers
Regulation of autoantibody production in the germinal center
Therapeutic interventions
Depleting autoreactive B cells
Interfering with T-cell help
Antiinflammatory therapies
Antigen-based therapies
Summary
References
11 T cells
Role of T cells in autoimmunity and inflammation
B cell help
Inflammation
CD8 and double negative T cells
Regulatory function
Intrinsic T cell defects
Assembly and selection of the T cell repertoire
T cell activation and signaling
Regulation of gene expression
Metabolic dysfunction
Apoptosis induction
Acquired defects
Concluding remarks
References
12 Immunoregulatory cells and networks in lupus
T-regulatory cells
CD4⁺ T-regulatory cells
CD4⁺ Tregs and SLE
CD8⁺ Tregs
CD8⁺ Tregs and SLE
B-regulatory cells
B-regulatory cells and SLE
Myeloid-derived suppressor cells
Myeloid-derived suppressor cells and SLE
Dendritic cells
Dendritic cells and SLE
Natural killer cells
NK cells and SLE
NKT cells
iNKT cells and SLE
Conclusions
References
13 Cytokines in lupus
Properties of cytokines and their receptors
Assessment of cytokine production
Use of gene expression to study cytokine effects
Activation of the immune response in systemic lupus erythematosus
Cytokines of the innate immune response
Type I interferons in immune responses
Type I interferons in the pathogenesis of systemic lupus erythematosus
Tumor necrosis factor
Osteopontin
Interleukin-1
Interleukin-10
B-lymphocyte stimulator
Interleukin-6
Other cytokines
Cytokines of the adaptive immune response
Cytokines generated in the adaptive immune response: T-cell–derived cytokines
T helper cell cytokines
Interleukin-2
Interferon-γ
T helper 2 cytokines
Transforming growth factor-β
Other T-cell–derived cytokines
Cytokines generated in the adaptive immune response: B-cell–derived cytokines
Cytokines in preclinical lupus
Summary
References
14 Metabolic control of immunopathogenesis in systemic lupus erythematosus
Metabolic pathways regulate proinflammatory immune cell lineage specification via MTOR activation in SLE
Mitochondrial oxidative stress underlie MTOR activation in SLE
Mechanistic checkpoints of metabolic pathways represent targets for treatment in SLE
Conclusions
Acknowledgement
References
15 Animal models of systemic lupus erythematosus (SLE)
Multigenic spontaneous SLE
NZB/BL (NZB) mice
Clinical characteristics and autoantibodies
B cells, T cells, and other factors
Genetics
Summary
New Zealand White mice
Clinical characteristics and autoantibodies
Genetics
(NZB x NZW) F1 mice (BWF1)
Autoantibodies
Nephritis in BWF1 females: Autoantibodies, infiltrating cells, and predisposing glomerular structures
Neurologic tissue
Lymphoproliferation
Sex influences
Hematopoietic cell abnormalities
Interferons and TGF-β
Abnormalities of dendritic cells in BWF1 mice
Abnormalities of monocytes/macrophages
Other abnormalities
Genetic predisposition
Summary
New Zealand mixed mice
Clinical and immunologic characteristics of NZM2410
NZM2328: Clinical and immune characteristics
NZM triple congenics (C57BL/6.NZM.Sle1.Sle2.Sle3), clinical manifestations, and immunologic features
(SWR x NZB) F1 (SNF1) mice
Characteristics
Genetics
Summary
MRL-lpr mice and MRL/Mp (MRL⁺/⁺)
Clinical characteristics
Immune cell characteristics
Genetics
Summary
Nonfunctional Fas ligand in GLD mice
BXSB mice
Clinical manifestations and autoantibodies
Genetics
Summary
(NZW×BXSB) F1 model of antiphospholipid syndrome and coronary artery disease
Disease characteristics and autoantibodies
Other disease features
Genetics
Summary
BXD2 RI model of spontaneous lupus nephritis and erosive polyarthritis (“rhupus”)
Genetics
Summary
Monogenic spontaneous SLE
Fcgr2b−/− mice
Lyn−/− mice
TLR7.1 mice
Induced lupus-like disease in nonautoimmune strains
Chronic GVHD (cGVHD) model
Lupus induced by injection of hydrocarbon oil
Xenobiotic-induced autoimmunity
TLR7 agonist-induced autoimmunity
Other induced models
Lupus in genetically manipulated mice
Modified genes in nonautoimmune strains
Modified genes in lupus mice
Therapeutic interventions in mouse models of lupus
Immunosuppressive therapies
Therapies targeting B cells
Therapies targeting T cells
Activation of suppressor networks
Treatments targeting complement, cytokines, chemokines and their activation pathways
Treatments targeting innate immunity
Stem cell replacement
Diet, gut inflammation, and the microbiome
Manipulating sex hormones
Target organ protection
Lupus in domestic animals
Spontaneous canine SLE
SLE in cats, monkeys, and horses
References
16 Abnormalities in clearance of immune complexes and dying cells in lupus
Introduction
Defective apoptotic cell clearance mechanisms in autoimmunity
Phosphatidylserine receptors
Role of “don’t eat me” receptors in systemic lupus erythematosus
Role of scavenger receptors in apoptotic cell clearance
Role of efferosome maturation in apoptotic cell clearance
Abnormalities in immune complex clearance
Tissue clearance mechanisms
Complement receptors
Role of C1q
Fcγ receptors
Genetic abnormalities of Fcγ receptors
Other cell types involved in immune complex interactions
Other tissue clearance mechanisms
Acknowledgments
Disclosures of interest
Summary
References
17 Complement and systemic lupus erythematosus
Historical overview
Biology of the complement system
Complement activation pathways
Regulators of complement activation
Receptors for complement proteins
Effector functions of complement
Complements as a bridge between innate immunity and adaptive immunity
Novel roles for complement
Complement dysregulation and SLE
Immune complex abnormalities, complement activation, and tissue injury
Other potential mechanisms of complement dysregulation in SLE
Complement defiency and SLE
Hereditary complement deficiency and SLE
Acquired complement deficiency and anticomplement autoantibodies
Deficiency and dysfunction of complement regulatory proteins
Possible mechanisms underlying the complement deficiency–SLE association
Analyses of complement
Measurement of complement functional activity
Measurement of complement proteins
Measurement of complement activation products
Genetic testing
Diagnostic considerations for complement dysregulation and deficiency
Soluble complement components as biomarkers for SLE
Soluble complement components and SLE diagnosis and activity monitoring
Problems associated with measurement of soluble complement components
Cell-bound complements as biomarkers for SLE
Cell-bound complement activation products as diagnostic biomarkers
Cell-bound complement activation products as biomarkers of disease activity
Cell-bound complement activation products as biomarkers for predicting the development of SLE
Complement-targeted therapeutics for SLE
Conclusion
References
18 Apoptosis and inflammatory forms of cell death
Introduction and definitions
Biochemistry of apoptosis
Caspases
Intrinsic apoptosis: Bcl-2 proteins and the mitochondria
Abnormalities in the expression of Bcl-2 family members cause lupus-like autoimmunity in mice
Intrinsic death pathways from cellular damage or stress
Metabolic stress
Genotoxic stress
Endoplasmic reticulum stress
Extrinsic signaling through death receptors
Regulation of death receptors
Function in immune regulation
Deficiencies in death receptor signaling lead to systemic autoimmunity
Removal of dead and dying cells: Tolerance versus autoimmunity
Receptors and ligands implicated in the removal of intact dead cells by phagocytes
How a cell dies affects the immune response
Apoptotic cell death leads to a lack of immune response or immune suppression and tolerance.
Defective clearance of apoptotic cells predispose to lupus-like disease in mice
Cells that die by necrosis, pyroptosis, necroptosis, netosis or ferroptosis, stimulate inflammation and, in some cases, au ...
The critical role of nucleases and the degradation of extracellular and intracellular nucleic acids.
Cell death abnormalities in human SLE
Apoptosis, clearance of apoptotic cells, and necrosis
The pivotal role of nucleic acids in stimulation of IFN-I in SLE
Cell death and treatment of SLE
Conclusions
Acknowledgments
References
19 Tissue damage in lupus
Introduction
Overview of reactive oxygen and nitrogen intermediates
Regulation of oxidant stress
Mechanisms through which ROI can modify DNA and change transcription
Association of ROI and RNI with SLE disease activity
Autoantibodies
T-cell regulation and function
Apoptosis
Autophagy regulation and induction
Neutrophil net formation
Podocyte dysfunction induced by RNI
Fibrosis
The role of NO• in vascular homeostasis
Conclusion
References
20 Lupus nephritis
Renal anatomy and physiology
Glomerular structure and function
Glomerular filtration barrier
Podocytes
Mesangium
Glomerular endothelial cells
The renal tubules and the kidney interstitium
Renal tubular epithelial cells
Renal interstitial fibroblasts
Resident renal immune cells
Histologic classification of lupus nephritis
Genetic risk for lupus nephritis
Mouse models of lupus nephritis
NZB/W F1 and inbred strains
Mice overexpressing TLR7
Fas overexpression
Inducible models of lupus nephritis
Mechanisms for immune complex deposition in the kidneys
Site of immune complex deposition in SLE
The characteristics of pathogenic autoantibodies
Mechanisms of tissue deposition of immune complexes
Pauci-immune glomerulonephritis
Dissociation of immune complex deposition and/or glomerular injury from end-stage renal disease
Effector mechanisms in the kidney
Complement
Fc receptors
Innate immune receptors
Immune cell influx
T cells
B cells
Myeloid cells
Soluble mediators of tissue injury
Chemokines
Cytokines
Lipid mediators
Hypoxia and other metabolic disturbances
The renin-angiotensin system
MMPs and tissue repair
Blood vessels and endothelium
Integrin ligands
Heparan sulfate proteoglycan
Progression to fibrosis and sclerosis
Natural history of progressive lupus nephritis
Pathways that contribute to or protect from fibrosis
TGFβ
Hepatocyte growth factor
PPARγ and obesity
LCN2 and KIM-1
Systems biology of lupus nephritis
Serum and urine biomarkers
Modular signatures
Insights from molecular profiling and single-cell RNA sequencing
Future directions in lupus nephritis
References
21 Pathogenesis of accelerated atherosclerosis and vascular injury in systemic lupus erythematosus
Epidemology of cardiovascular disease in systemic lupus erythematosus
Major adverse cardiovascular events
Subclinical and clinical vascular damage in SLE
Pathogenesis of atherosclerosis in the general population
Pathogenesis of premature atherosclerosis in SLE
The role of altered immune cell subtypes in SLE atherosclerosis
Dysregulation of innate immune responses and SLE-related cardiovascular disease
Monocytes/macrophages
Plasmacytoid dendritic cells and type I interferons
Neutrophils and low-density granulocytes
Dysregulation of adaptive immune responses and SLE-related cardiovascular disease
CD4+ T cells
Th1 cells and interferon-γ
Th17s and IL-17A
Tregs
Follicular helper T cells
B cells
Autoantibodies and immune complexes
Cytokines and other soluble mediators
Alarmins S100A8, S100A9, and S100A8/A9
Tumor necrosis factor-aymor nex
Monocyte chemotactic protein-1
B cell activating factor/B lymphocyte stimulator
The role of inflammatory lipids
Oxidized low-density lipoproteins
High-density lipoprotein structure and function
Other factors associated with cardiovascular disease in SLE
Homocysteine
The PREDICTS model
Vitamin D deficiency
Genetic risk factors
Potential treatments to mitigate cardiovascular disease in SLE
Statins
Antihypertensives
Treatment of disease activity
Antimalarials
Mycophenolate mofetil
Peptidylarginine deiminase inhibitors
Methotrexate
Anti–B cell therapies
Antiinterferon therapies
Conclusions
Acknowledgments
Key points
References
22 Pathogenesis of cutaneous lupus
Introduction
Clinical considerations
Epidemiology
Triggers of cutaneous lupus erythematosus
Ultraviolet light
Medications
Smoking
Etiopathogenesis
Genetics
Contribution of sex bias
Microbiome
The importance of interferons
Etiology of the interferon signature
Other type II and type III interferons
Cell death
Immune cell populations in cutaneous lupus erythematosus
How understanding pathogenesis is changing treatment
References
23 Pathogenesis of neuropsychiatric lupus
Introduction
Neuroimmune interfaces
Blood-brain barrier
Blood–cerebrospinal fluid barrier
Cell-mediated inflammation
Autoantibodies
Autoantibody-mediated vasculopathy
Brain-reactive autoantibodies
Cytokines and chemokines
Complement-mediated immunity
Glial cells
Summary
References
24 Pathogenesis of Sjögren syndrome
Introduction
Disease triggers
Viruses
Neuroendocrine axis
Sex hormones
Smoking
Diet and microbiome
Genetics
Epigenetics
Autoimmune epithelitis
Salivary glands and immune system
Innate immunity and salivary glands epithelium
Adaptive immunity and salivary gland epithelium
Stromal cells of salivary glands
Mechanisms of dryness
From a gland disease to a systemic disease
B-cell hyperactivity
Tertiary lymphoid structures
Autoantibodies
Lymphoma
Research tools
Animal models
OMICs
From pathogenesis to targeted treatment
Major knowledge gaps
Fatigue
Environmental factors
Chronic inflammation
Conclusions
References
25 Antinuclear antibodies, antibodies to DNA, histones, and nucleosomes
Antinuclear antibody overview
History
Choice of substrate
Patterns of immunofluorescence and links to target antigen
Clinical interpretation
New methods for antinuclear antibody detection
Identification of lupus-related antibodies
Antinuclear antibody–negative lupus
Summary
Antibodies to DNA, histones, and nucleosomes
Measurement of anti-dsDNA antibodies
Work from experimental models that emphasized the potential importance of anti-dsDNA antibodies
How pathogenic anti-dsDNA antibodies bind to tissues: The importance of binding to nucleosomes
Cross-reaction of anti-DNA antibodies with intracellular antigens
Cell-penetrating anti-DNA antibodies in SLE
Antihistone antibodies
Structure and origin of pathogenic anti-dsDNA and antinucleosome antibodies
Can measuring anti-dsDNA levels help manage patients with SLE?
Acknowledgments
Summary
References
26 Antibodies against extractable nuclear antigens (RNP, Sm, SS-A/RO, and SS-B/La)
Structure of the antigens
Sm and RNP complexes
SS-A/RO and SS-B/La ribonucleoprotein complexes
Assays for measuring anti-ENA antibodies
Prevalence and clinical associations in SLE
Origins of anti-ENA autoimmunity
Viral infections as trigger for autoimmunity
Sequential presentation of anti-ENA antibodies and relationship of anti-ENA to other SLE-specific autoantibodies
Role of apoptosis for the generation of anti-ENA antibodies
Toll-like receptors as key molecules for the generation of anti-ENA antibodies
Genetic risks and anti-ENA antibodies
Pathogenic importance of anti-RNP and anti-Sm antibodies
Pathogenic role of anti–SS-A/Ro and anti–SS-B/La antibodies
Autoantibodies against other ENA
Anti–proliferating cell nuclear antigen antibodies/anti-cyclin antibodies
References
27 Other autoantibodies
Introduction
Anti-C1q antibodies
Antilipoprotein antibodies
Antiendothelial cell antibodies
References
28 Pathogenesis of antiphospholipid antibody syndrome
The clinical importance of antiphospholipid antibodies
Epidemiology of aPL and APS
Which aPL tests should be done and how should they be interpreted?
Standard laboratory “criteria” assays
Noncriteria assays
Antiphospholipid antibody–induced mechanisms of disease
Mechanisms of thrombosis
Animal models
Interactions with cell surface receptors
Cell activation and signaling pathways leading to thrombosis
Endothelial cells.
Monocytes.
Platelets.
Neutrophils.
Dysregulation of coagulation and complement pathways.
Mechanisms of pregnancy morbidity
Animal models
Mechanisms of cellular activation leading to obstetric APS
Dysregulation of coagulation and complement pathways
Coronavirus disease 2019 and antiphospholipid antibodies
Conclusions
References
29 Drug-induced lupus
Introduction
Etiology
Implicated drugs
Genetic contributions to idiopathic and drug-induced lupus
Roles of age and gender in idiopathic and drug-induced lupus
Summary
Pathogenesis
Genetic predisposition
Drug biotransformation
Epigenetics and gene expression
Epigenetics, chromatin structure, and gene expression
Histone modification
DNA methylation
T cells, DNA methylation, and drug-induced lupus
T cells, DNA methylation, and idiopathic lupus
T cells, DNA methylation, and the environment
Innate immune system
Role of cytokines—evidence from biologic agents
Interferon α (IFN-α)
Tumor necrosis factor α (TNF-α) inhibitors
Summary
Clinical aspects
Comparison of drug-induced versus idiopathic lupus
Patient characteristics
Hydralazine.
Procainamide.
Tnf-α inhibitors.
Drug-induced subacute cutaneous lupus erythematosus
Laboratory findings
Clinical course
Summary
References
30 Overview and clinical presentation
Clinical manifestations and racial disparities
Chief complaint, autoantibody development, and immunologic changes
Variations in clinical presentation
Incomplete lupus
Late-onset lupus
Male lupus
Categorization of lupus symptoms
Fatigue
Brain fog
Fever
Lymphadenopathy
Weight loss
References
31 Skin disease in cutaneous lupus erythematosus
Epidemiology
Triggers of cutaneous lupus erythematosus
Clinical features
Classification of cutaneous lupus erythematosus
Lupus-specific skin lesions
Acute cutaneous lupus erythematosus
Subacute cutaneous lupus erythematosus
Chronic cutaneous lupus erythematosus
Discoid lupus erythematosus.
Hypertrophic/verrucous DLE.
Lupus panniculitis/lupus profundus.
Lupus erythematosus tumidus.
Chilblain LE.
Lichen planus–lupus erythematosus overlap.
Bullous SLE.
Relationship with systemic disease features
Pathology
Immunopathology
Laboratory findings
Differential diagnosis
Lupus-nonspecific skin lesions
Photosensitivity
Mucosal ulceration
Nonscarring alopecia
Cutaneous vascular reactions
Vasculitis
Vasculopathy
Raynaud phenomenon
Antiphospholipid antibodies
Cryoglobulins
Other cutaneous vascular reactions
Urticaria
Periungual telangiectasias
Erythromelalgia and palmar erythema
Other LE-nonspecific skin lesions
Papulonodular mucinosis
Calcinosis cutis
Nail changes
Anetoderma
Interstitial granulomatous dermatitis
Conclusion
References
32 The musculoskeletal system and bone metabolism
Introduction
Arthritis
Arthritis definition by classification criteria
Diagnosis
Imaging
Synovial fluid analysis and synovial tissue pathology
Immunologic profiles in erosive arthritis in SLE arthritis
Jaccoud arthropathy
Rhupus: Revisiting concepts of erosive arthritis
Treatment
Muscle involvement
Lupus myositis
Orbital myositis
Drug-induced myopathies in SLE
Infection-related myopathies
Soft tissue disorders and other pain syndromes
Musculoskeletal infections
Avascular necrosis
Osteoporosis
Joint replacement in SLE
Musculoskeletal features in outcome measures
SLE disease activity measures
British isles lupus assessment group
European consensus lupus activity measurement
Lupus activity index
SLE activity index score
Systemic lupus activity measure
SLE disease activity index
SLE damage indices
SLICC/ACR damage index
Lupus damage index questionnaire
Brief index of lupus damage
Summary
References
33 Lupus and the cardiovascular system
Introduction
Epidemiology
Pericardium
Pericarditis
Pericardial effusion
Chronic pericarditis
Myocardium
Myocarditis
Cardiomyopathy
Endocardium
Endocarditis
Congenital heart block
Adult conduction abnormalities
Vasculature
Atherosclerosis and coronary artery disease
References
34 Pulmonary manifestations of systemic lupus erythematosus
Introduction
Pleural disease
Pathogenesis
Diagnosis
Clinical presentation
Imaging
Pleural fluid analysis
Management
Parenchymal disease
Acute parenchymal disease
Acute lupus pneumonitis
Diffuse alveolar hemorrhage
Management of ALP and DAH
Uncommon forms of acute parenchymal involvement in SLE
Chronic parenchymal disease
Interstitial lung disease
Treatment of SLE-ILD
Vascular disease
Pulmonary hypertension
Treatment of SLE-PH
Pulmonary vasculitis
Thromboembolic disease
Acute reversible hypoxemia
Diseases of the mediastinum and musculature
Shrinking lung syndrome
Treatment of shrinking lung syndrome
Uncommon pulmonary involvement in SLE
Airway disease
Miscellaneous pulmonary disease
Lung transplantation in SLE
Novel treatment targets
Summary
References
35 Lupus and the nervous system
Classification of NPSLE
Attribution of neuropsychiatric events in patients with SLE
Etiopathogenesis
Epidemiology of NPSLE
Risk factors for neuropsychiatric manifestations of SLE
Clinical presentation of NPSLE
Diffuse central nervous syndromes—neurologic
Acute confusional state
Aseptic meningitis
Cognitive dysfunction
Demyelinating syndrome
Headache
Diffuse central nervous system syndromes—psychiatric
Anxiety disorders
Mood disorders
Psychosis
Focal central nervous system syndromes
Cerebrovascular disease
Movement disorders
Myelopathy
Seizures
Peripheral nervous system manifestations
Acute inflammatory demyelinating polyneuropathy
Autonomic disorders
Cranial neuropathies
Mononeuropathy
Myasthenia gravis and related disorders
Plexopathy
Polyneuropathy
Neuropsychiatric SLE in children
Diagnostic evaluation
Clinical laboratory tests
Autoantibodies
Antiphospholipid antibodies
Anti-ribosomal P antibodies
Anti-aquaporin 4 antibodies
Anti-NMDAR antibodies
Cerebrospinal fluid examination
Electroencephalography
Electromyography and nerve conduction studies
Neuropsychometric tests
Neuroimaging studies in NPSLE
Computed tomography
Magnetic resonance imaging
Positron-emission tomography and single-photon emission computed tomography
Advanced magnetic resonance imaging techniques
Magnetization transfer imaging
Magnetic resonance spectroscopy
Diffusion tensor imaging
Dynamic contrast-enhanced magnetic resonance imaging
Functional magnetic resonance imaging
Transcranial color doppler sonography
Angiography
Treatment of NPSLE
Inflammatory pathway therapies
Ischemic pathway therapies
Prognosis of NPSLE
References
36 Gastrointestinal and hepatic manifestations
Gastrointestinal involvement
Introduction
Incidence and prevalence
Manifestations
Oral-pharyngeal ulceration, dysphagia, and esophagitis
Anorexia, nausea, vomiting, and diarrhea
Abdominal pain and acute abdomen
Ascites and peritonitis
Peptic ulcer disease
Helicobacter pylori infection in systemic lupus erythematosus
Pancreatitis
Prevalence
Clinical presentation and etiopathogenesis
Management
Motility disorders
Mesenteric and intestinal vasculitis, melena, and bowel hemorrhage
Prevalence
Clinical presentation and etiopathogenesis
Laboratory, radiographic, and histologic findings
Treatment and outcome
Mesenteric insufficiency, thromboembolism, and intestinal infarction
Inflammatory bowel disease
Collagenous colitis
Celiac disease in association with systemic lupus erythematosus
Protein-losing enteropathy and malabsorption
Irritable bowel syndrome
Liver manifestations of systemic lupus erythematosus
Liver function test abnormalities: Clinicopathologic correlates
Autoimmune liver disease in lupus
Lupus hepatitis: Is there a distinct entity of lupus hepatitis?
Autoimmune hepatitis and its relationship to lupus
Overlapping syndromes in autoimmune hepatitis
PBC and PSC overlap with SLE
Other causes of hepatitis in systemic lupus erythematosus
Hepatitis B infection
Hepatitis C
Drug-induced autoimmune hepatitis
Biliary abnormalities: Cholecystitis, cholangitis, and biliary cirrhosis
Hepatobiliary and pancreatic malignancies
References
37 The gut microbiome and lupus pathogenesis
Introduction
Microbiome dysbiosis and the etiopathogenesis of systemic lupus disease
Linking gut microbes with lupus etiopathogenesis
Changes in microbial diversity
Gut barrier impairment
Clarifying differences between beneficial versus harmful bacteria by considering immune effects of bacterial toxins, metabolites, and antigen molecular mimicry
Limitations of current approaches and future considerations
Methodologic limitations and future directions
Can we consider targeting gut microbiome dysbiosis or barrier dysfunction for therapeutic benefit in lupus disease?
Key points and conclusions
References
38 Hematologic and lymphoid abnormalities in SLE
Anemia
Anemia of chronic disease
Iron-deficiency anemia
Immune-mediated hemolytic anemias
Autoimmune hemolytic anemia
Diagnosis
Antigen specificity of antierythrocyte antibodies
Treatment
General considerations
First-line therapies
Second-line therapies
Third-line therapies
Novel treatment approaches
Bone marrow and immune-mediated hematopoietic failure in SLE
Reactive hemophagocytic syndrome
Diagnosis
Treatment of autoimmune-associated hemophagocytic syndrome
Thrombocytopenia and qualitative platelet disorders
Pathogenesis of thrombocytopenia in SLE
Acquired abnormalities of platelet function
Treatment of thrombocytopenia in SLE
Evans syndrome
Thrombotic thrombocytopenic purpura
White blood cell disorders
Lymphadenopathy in SLE
Spleen in SLE
Bonus content for this chapter can be found online at
References
39 Neonatal lupus
History
Epidemiology
Pathogenesis
Candidate biomarkers and new theories relating to pathogenesis
Clinical manifestations
Cardiac
Dermatologic
Gastrointestinal
Neurologic
Hematologic and skeletal
Diagnosis
Management
Monitoring anti-SSA/Ro–exposed pregnancies and treatment approach
Management of first-degree block
Management of second-degree block
Management of third-degree block
Prevention strategies
Postnatal assessment and treatment of neonatal lupus
Prognosis
References
40 Pregnancy and reproductive health issues in systemic lupus erythematosus
Introduction
Hormones and reproductive immunology
Gonadal hormones and the immune system
Female hormones and inflammatory mediators
Complex effects of sex hormones on inflammation
Sex hormones, immune system, and the vascular system
Maternal–fetal immunology
Embryologic development of the immune system
Contraception
Contraception use by SLE patients
Estrogen-progestin contraception
Progestin-only contraception
Intrauterine devices
Barrier methods
Emergency contraception
Medication interactions
Infertility and protection against premature ovarian failure
Preservation of fertility with cyclophosphamide therapy
Assisted reproductive technologies
Pregnancy in SLE
Disease activity in pregnancy
Diagnosing SLE flare during pregnancy
Pregnancy outcomes
Pregnancy loss
Preterm birth
Preeclampsia
Offspring outcomes
Long-term outcomes of SLE offspring
Maternal mortality
Antiphospholipid syndrome and pregnancy
Etiologic and pathophysiologic characteristics
Pregnancy outcomes
Maternal outcomes
Medications for antiphospholipid antibodies during pregnancy
Medications in SLE pregnancy
Nonsteroidal antiinflammatory drugs and acetaminophen
Corticosteroids
Hydroxychloroquine
Azathioprine
Mycophenolate mofetil
Calcineurin inhibitors
Cyclophosphamide
Intravenous immunoglobulin
Rituximab
Belimumab
Anifrolumab
Menopause and SLE
Postmenopausal hormone therapy
Effect of menopausal hormone therapy on cardiovascular disease and thrombosis risk
Effect of menopausal hormone replacement on disease activity
Bone health and osteoporosis
Prevention of osteoporosis
Reproductive health care and screening
References
41 Systemic lupus erythematosus in childhood and adolescence
Introduction
Epidemiology
Diagnosis of SLE in children
Clinical manifestations of SLE
Renal disease
Neuropsychiatric disease
Pulmonary manifestations
Musculoskeletal manifestations
Dermatologic manifestations
Cardiac manifestations
Gastrointestinal manifestations
Infection and vaccinations
Hematologic manifestations
Laboratory evaluation
Clinical differences between adults and childhood-onset SLE
Genetics of cSLE
Standards of care of childhood-onset SLE as opposed to adult-onset SLE
Common medications in cSLE therapy
Other psychosocial concerns
Summary
References
42 Clinical aspects of antiphospholipid syndrome
Introduction
Epidemiology
Risk factors for thrombosis in those with antiphospholipid antibodies
Diagnosis and laboratory testing
Laboratory testing
Clinical features
Thrombotic manifestations
Obstetric antiphospholipid syndrome
Neurologic manifestations
Ocular manifestations
Cardiovascular manifestations
Renal manifestations
Hematologic abnormalities
Pulmonary involvement
Gastrointestinal involvement
Cutaneous manifestations of antiphospholipid syndrome
Catastrophic antiphospholipid syndrome
Management strategies in antiphospholipid syndrome
Treatment of patients with prior thrombosis
Primary thromboprophylaxis
Obstetric antiphospholipid syndrome
Catastrophic antiphospholipid syndrome
Other therapies in antiphospholipid syndrome
Hydroxychloroquine
Statins
Rituximab
Eculizumab
Conclusion
References
43 Lupus and infections
Prevalence of infections in SLE
Infections as a cause of morbidity and mortality in SLE
Risk factors for infections and serious infections in SLE
Protean spectrum of infection in SLE
Viruses
Mycobacteria
Bacteria
Fungi
Parasites and protozoa
Intrinsic immune dysfunction increasing infection susceptibility in SLE
Therapeutic toxicities
Glucocorticoids
Other immunosuppressive therapies
Biologic therapies
Hydroxychloroquine use and protection from infection
Select genetic defects and risk of infection
Can biomarkers be used to differentiate between infection and disease flare?
Clinical approach to SLE patients with a suspected infection
Acknowledgments
Summary
References
44 Ocular, aural, and oral manifestations of lupus
Systemic lupus erythematosus and the eye
Retinal vascular disease
Subclinical retinal vascular disease
Choroidal vascular disease
Optic neuropathy
Episcleritis and scleritis
Conjunctival or corneal disease and keratitis
Uveitis
Orbital inflammation
Chloroquine and hydroxychloroquine toxicity
Antiphospholipid antibody retinopathy
Lupus and the mouth
Oral manifestations of lupus
Pathology
Treatment
Malignant transformation
Conditions associated with lupus
Sjögren syndrome
Infectious complications
Medication toxicity
Common oral conditions mimicking lupus
Oral lichen planus
Recurrent aphthous stomatitis
Lupus and the nose
Intranasal manifestations
Conditions associated with lupus
Pernio
Relapsing polychondritis
Lupus and the larynx
Lupus and the ear
Sensorineural hearing loss
Vertigo
Acknowledgments
References
45 Clinical aspects of Sjögrens disease
Introduction and epidemiology
History
Clinical presentation
Overview
Glandular manifestations
Dry eye disease
Salivary hypofunction
Glandular enlargement
Other glandular manifestations
Extraglandular manifestations
Skin manifestations
Ear, nose, and throat manifestations
Pulmonary manifestations
Joint and muscle manifestations
Gastrointestinal manifestations
Gynecologic and urologic manifestations
Pregnancy
Kidney manifestations
Neurologic manifestations
Vasculitis
Cardiovascular manifestations
Hematologic manifestations
Lymphoma development
Paraclinical examinations
Serologic findings
Salivary gland ultrasonography (SGUS)
Clinical forms
Men with Sjögren’s
Childhood Sjögren’s
Sjögren’s in systemic lupus erythematosus
Classification and diagnosis of Sjögren’s
Outcome measures
Prognosis
Acknowledgment
References
46 Clinical presentations of lupus in the kidney and urogenital system
Introduction
Lupus nephritis epidemiology and risk factors
Clinical presentation and diagnosis of lupus nephritis
Differential diagnosis of lupus nephritis
Histopathologic classification of lupus nephritis
Lupus nephritis biomarkers
Lupus nephritis during pregnancy
References
47 The endocrine system and hormones in lupus
Introduction
Role of the hypothalamic-pituitary-adrenal axis in the pathogenesis of SLE
Role of stress in SLE
Does prolactin function as an inflammatory cytokine?
Sex hormones and their role in SLE
Specific endocrine disorders in SLE
Thyroid disease in SLE
Epidemiology
Hypothyroidism
Hyperthyroidism
Auto-immune thyroid disease
Thyroid cancer
Thyroid nodules
Diabetes mellitus and SLE
Prolactin in SLE
Parathyroid disease in SLE
Hypoparathyroidism
Adrenal disease in SLE
Addison disease
Cushing syndrome
Acknowledgements
References
48 Clinical application of serologic tests, serum protein abnormalities, and other laboratory tests in systemic lupus erythematosus
Diagnosis of SLE
Monitoring disease activity in SLE
Clinical significance of anti-dsDNA antibodies
Diagnostic value
Clinical tests for dsDNA antibodies
Preemptive treatment of serologically active SLE
Summary
Anti-Sm antibodies
Prevalence
Anti-Sm association with organ involvement
Anti-Sm antibodies and disease activity
Anti–U1 ribonucleoprotein
Clinical association of anti–U1-ribonucleoprotein antibodies
Anti–SS-A
Diagnostic specificity and associations
Serial measurement of anti–SS-A antibody titer
Summary
Anti–SS-B antibodies
Antihistone antibodies
Clinical association
Summary
Antinucleosome antibodies in SLE
Summary
Anti-C1Q antibodies
Anti–ribosomal P antibodies
Summary
Anti-centromere and anti–SCL-70 antibodies
Summary
Erythrocyte sedimentation rate
C-reactive protein and the immune system
Clinical significance of C-reactive protein in SLE
C-reactive protein and cardiovascular risk in SLE
Serum complements
Complement activation products
Cell-bound complement activation products
Plasma proteins
Globulins
Albumin
Serum immunoglobulins
Immunoglobulin G
Immunoglobulin M
Immunoglobulin A
Immunoglobulin E
Common variable immunodeficiency
Drug-related hypogammaglobulinemia
Other serologic abnormalities in SLE
Rheumatoid factor
Anti–cyclic citrullinated protein antibodies
Summary
Cryoglobulins
Anti–endothelial cell antibodies
Antineutrophil cytoplasmic antibodies
Anti-N-methyl-d-aspartate receptors
Clustering of autoantibodies
References
49 Differential diagnosis and disease associations
When to suspect SLE
Laboratory evaluation of suspected systemic lupus erythematosus
Routine studies
Serologic testing
Classification criteria
Diagnostic challenges
Incomplete or preclinical lupus erythematosus
Rhupus
Undifferentiated connective tissue disease
Mixed connective tissue disease
Attribution to disease activity
Differential diagnosis
Other autoimmune diseases
Sjögren syndrome.
Dermatomyositis.
Rheumatoid arthritis.
Systemic sclerosis.
Sarcoidosis.
Multiple sclerosis.
Infections
Chronic infections.
Acute infections.
Malignancy
Noninflammatory conditions
Myalgic encephalomyelitis/chronic fatigue syndrome.
Fibromyalgia.
Conclusion
References
50 Incomplete lupus, undifferentiated connective tissue disease, and mixed connective tissue disease
Introduction and historical background
Undifferentiated connective tissue disease and incomplete lupus syndromes
Clinical findings in incomplete lupus erythematosus and undifferentiated connective tissue disease
Autoantibodies and immunologic findings
Treatment strategies
Mixed connective tissue disease
Historical perspective and definition
Clinical features
Mucocutaneous
Joints
Muscles
Pulmonary system
Gastrointestinal system
Cardiac system
Nervous system
Renal disease
Hematologic disorders
Children
Pregnancy
Serologic and immunologic studies
Pathogenesis
Genetic factors
Environmental factors
B cells in pathogenesis
T cells in pathogenesis
Innate immunity in pathogenesis
Course and prognosis
Treatment
References
51 Clinical markers, metrics, indices, and clinical trials
Introduction
Principles and approaches for assessing patients with lupus
Disease activity indices
Global indices
SLE disease activity index and its versions
SLEDAI-2000 (2K).
SLEDAI-2K: 30-day version.
Safety of estrogens in lupus erythematosus national assessment.
Systemic lupus erythematosus disease activity index (SELENA-SLEDAI).
Mexican version of SLEDAI (Mex-SLEDAI).
Adjusted mean SLEDAI-2K (AMS).
Practical considerations of SLEDAI and its modifications.
Systemic lupus activity measure
European consensus lupus activity measurement
Lupus activity index
SLE activity index score (SIS)
SLE-disease activity score (SLE-DAS)
Organ-specific indices
British isles lupus assessment group index
Renal outcome measures
Cutaneous lupus erythematosus disease area and severity index (CLASI)
Disease activity assessment in special circumstances
Disease activity in childhood
Disease activity in pregnancy
Clinically meaningful states of disease activity
Improvement/response
Flare
Remission and low disease activity
Outcome measures in clinical trials in SLE
Improvement and response
SLE responder index.
British isles lupus assessment group based combined lupus assessment (BICLA).
Damage assessment
Health-related quality of life
Generic questionnaires
Disease-specific questionnaires
References
52 Principles of therapy, local measures, and NSAIDs
Formulation overview
Patient education
General therapeutic considerations
Rest, sleep, and the treatment of fatigue
Exercise, physical therapy, and rehabilitation
Tobacco smoke and alcohol
Weather and seasons
Pain management
Diet
Role of stress and trauma
Can stress induce lupus?
Can stress exacerbate preexisting SLE?
Can physical trauma cause or exacerbate SLE?
Compliance and adherence
Nonsteroidal antiinflammatory drugs for the treatment of SLE
Mechanisms of action
Clinical efficacy in SLE
Cyclooxygenase-2 inhibition
Adverse reactions of nonsteroidal antiinflammatory drugs in SLE
Renal system
Gastrointestinal system
Nervous system
Cutaneous reactions
Respiratory tract and infections
Cardiovascular system
Hematologic complications
Bone healing
Pregnancy
Drug interactions and monitoring
References
53 Antimalarial medications
Antimalarials
Pharmacokinetics
Mechanism of action
Molecular effects
Inhibition of lysosomal activity and autophagy
Inhibition of signaling pathways
Efficacy of antimalarials
Effects of AMs in pregnancy (Table 53.1)
Effect on cardiovascular events (Table 53.2)
Effect on diabetes mellitus
Protective effects on infections
Effects on damage accrual and survival
Effects on cancer
Adverse effects of antimalarials
Gastrointestinal
Cutaneous and pigmentary adverse events
Ocular
Screening for ocular toxicity
Neurologic, muscular, and cardiac
Dosage
Summary
References
54 Systemic glucocorticoid therapy for SLE
Therapeutic use of glucocorticoids in sle
Tapering of glucocorticoids
Optimizing nonglucocorticoid therapies in lupus
Molecular mechanisms of glucocorticoid action
Nongenomic effects of glucocorticoids
Genomic effects of glucocorticoids
Antiinflammatory and immunosuppressive effects of glucocorticoids
Mechanisms of glucocorticoid insensitivity
Adverse effects of glucocorticoids
Bone toxicity of glucocorticoids
Glucocorticoid-induced diabetes
Cardiovascular risk
Infections
Neuropsychiatric adverse effects
Is there a safe dose of glucocorticoids in SLE?
Conclusions and the future of glucocorticoid therapy in SLE
References
55 Immunosuppressive drug therapy
Historical perspective
Alkylating agents
Chlorambucil
Cyclophosphamide
Adverse effects of cyclophosphamide
Hemorrhagic cystitis and carcinomas of the bladder
Other malignancies
Hematologic toxicity
Gastrointestinal toxicity
Pulmonary toxicity
Gonadal toxicity and teratogenicity
Infections
Induction therapy with cyclophosphamide in lupus nephritis
Oral cyclophosphamide
Intravenous cyclophosphamide in nonrenal lupus
Neuropsychiatric lupus
Cyclophosphamide use in children
Aggressive cyclophosphamide-containing regimens
Azathioprine
Mycophenolate mofetil
Nonrenal lupus
Calcineurin inhibitors
Calcineurin inhibitor induction therapy of nephritis
Cyclosporin A
Tacrolimus
Combined tacrolimus and mycophenolate mofetil therapy
Voclosporin, a calcineurin inhibitor for lupus nephritis
Calcineurin inhibitors in nonrenal lupus
Methotrexate
Leflunomide
Conclusion
References
56 Complementary and integrative health approaches
Introduction
Prevalence of use
Nutritional approaches
Diet
Dietary supplements
Vitamin D
Omega 3 fatty acids
Herbs
Psychological approaches
Mindfulness
Meditation
Physical approaches
Massage
Combination approaches
Yoga
Acupuncture
Conclusions
References
57 Specialized and niche therapies
Treatment of patients with SLE and end-stage renal disease
Incidence and prevalence
Uremia and its reversibility
Prognosis of end-stage renal disease
Hemodialysis versus peritoneal dialysis
Transplantation
Prevalence
Graft and patient survival
Serologic features and disease recurrence
Pregnancy
Laser therapy
Apheresis and related technologies
Plasmapheresis and plasma exchange
Basic science and clinical rationale
Clinical studies in SLE
Lupus nephritis.
Antiphospholipid syndrome and congenital heart block.
Other potential indications.
Pulse synchronization therapy.
Membrane technologies.
Summary
Lymphocyte depletion: Thoracic duct drainage, lymphocytapheresis, and total lymphoid irradiation
Photopheresis
Ultraviolet-1 radiation
Should radiation therapy be avoided?
Niche therapies for lupus subsets
Antileprosy drugs
Dapsone
Thalidomide and lenalidomide
Novel immunosuppressive agents
Mizoribine
Antilymphocyte globulin
β-carotene and retinoids
Intravenous, subcutaneous, and intramuscular immune globulin
References
58 Adjunctive and preventive measures
Infection prevention in lupus
Immunizations in SLE
Are there vaccinations that should be avoided with SLE?
SARS-CoV-2 vaccination in SLE
Should patients with SLE receive the herpes zoster (shingles) vaccine?
Should patients with SLE receive the human papillomavirus vaccine?
What is the risk of vaccination triggering an SLE flare or being ineffective?
Antibiotic prophylaxis in lupus
Are there antibiotics that patients with SLE should avoid?
Drug allergies in patients with lupus
Should patients with SLE and allergies consider immunotherapy?
Vitamin D supplementation in lupus
Should all patients with SLE be screened for vitamin D deficiency?
What are the consequences of vitamin D deficiency for patients with SLE?
What are the current vitamin D intake recommendation for patients with SLE?
Management and prevention of osteoporosis
Adherence issues in lupus
What strategies have been shown to improve adherence?
References
59 Management of cutaneous lupus erythematosus
Introduction
Photoprotection
Topical medications
Intralesional therapy
Antimalarials
Oral/intravenous corticosteroids
Mycophenolate mofetil
Methotrexate
Azathioprine
Cyclophosphamide
Oral retinoids
Dapsone
Thalidomide
Lenalidomide
Intravenous immunoglobulin
Biologic therapies
Belimumab
Rituximab
Anifrolumab
Anti-plasmacytoid dendritic cell therapies
References
60 Targeted therapies in SLE
Introduction
B cell directed therapies
Belimumab
Perspectives on clinical use
Rituximab
Perspectives on clinical use
Obinutuzumab
T cell directed therapeutic approaches
Abatacept
Perspectives on clinical use
Cytokine inhibition
Anifrolumab
Perspectives on clinical use
Interleukin-6
Tumor necrosis factor-α
JAK inhibitors
Perspectives on clinical use
Summary
References
61 Management of lupus nephritis
Introduction
Clinical manifestations of lupus nephritis
Laboratory assessment of lupus nephritis
Proteinuria
Urine sediment
Assessment of kidney function
Biomarkers of lupus nephritis
Kidney biopsy in the management of lupus nephritis
Histopathologic classification of lupus nephritis
Management of lupus nephritis
Class 1 and 2 lupus nephritis
Class 3 and 4 (“proliferative”) lupus nephritis
Glucocorticoids
Cyclophosphamide
Mycophenolate mofetil
Combination of calcineurin inhibitors and mycophenolate mofetil
B-cell–directed therapies
Other drugs for initial therapy
Class 5 (membranous) lupus nephritis
Class 6 lupus nephritis
Renoprotective nonimmunosuppressive interventions
Antimalarial drugs in lupus nephritis
Expected results of the initial therapy
Maintenance therapy
Nonimmune complex-mediated kidney injury in SLE
Resistant disease
Long-term monitoring of lupus nephritis patients
Pregnancy in lupus nephritis
Progression to end-stage kidney disease
References
62 Management of Sjögren disease syndrome
Introduction
Sjögren disease
Nonmedical therapy of dryness
Treatment of symptoms of mild-to-moderate dry eye
Treatment of moderate-to-severe dry eye
Blepharitis
Topical immunomodulatory agents
Topical steroids
Topical lifitegrast
Overview of treatment of dry mouth
Saliva substitutes
Indications for the use of sialagogues: Drugs that promote salivation
Dose
Choice of medication
Pilocarpine efficacy
Cevimeline efficacy
Adverse effects and precautions
Lack of benefit from sialagogues
Treatment of systemic and extraglandular manifestations of Sjögren disease
Cutaneous
Arthralgia
Cardiopulmonary manifestations
Renal disease
Gastrointestinal disorders
Endocrine disorders
Neurologic manifestations
Peripheral neuropathies
Autonomic neuropathy59-62
Central nervous system manifestations64-66
Treatment with biologic agents
Rituximab, epratuzumab, and abatacept
Fatigue67-71
Endocrine factors
Emerging therapies for the management of Sjögren disease
Summary
References
Suggested reading
63 Socioeconomics, disparities, and disability
Introduction
Physical health and quality of life
Measuring functional status in systemic lupus erythematosus
Mental health and well-being
Effect of illness on school and social support systems
Employment and long-term disability
Economic costs of systemic lupus erythematosus
Direct costs
Indirect costs
Effects of adverse social determinants of health
Interventions
Conclusion
Key take-away points
References
64 Prognosis and mortality of systemic lupus erythematosus
Survival rates in SLE
Ethnic and racial variation in mortality
Causes of death in SLE
Prognosis and predictors of overall mortality in SLE
Cardiovascular disease
Renal disease
Demographics: Sex, age, and socioeconomic status
Disease severity, activity, and organ involvement
Role of SLE medications
Mortality in pediatric-onset SLE
Evidence of improved survival in pediatric-onset SLE
Long-term survival in pediatric-onset SLE
Causes of death and risk factors for death in pediatric-onset SLE
Strategies for improved mortality outcomes in SLE
Acknowledgments
References
65 Future directions
Introduction
Innate immune system targets
Type I interferons
Complement
Adaptive immune system targets
B cells
T cells
Plasma cells
Cytokines
Signaling pathways
Cellular therapies
Combination therapies
Repurposed drugs
Miscellaneous strategies
Summary
References
66 Expanding the opportunities to effectively treat patients
Classification criteria and treatment guidance documents
The relevance of lupus subsets
Identifying relevant biomarkers and clinical determinants for precision medicine
Preventing lupus
Role of lupus advocacy groups
Summary
References
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Inside back cover