- •Sjögren’s Syndrome
- •Foreword
- •Contents
- •Contributors
- •1.1 Primary Sjögren’s Syndrome
- •1.1.1 Diagnostic Criteria
- •1.1.2 Incidence
- •1.1.3 Prevalence
- •References
- •2.1 Introduction
- •2.2 Genetic Epidemiology of SS
- •2.3 Key Concepts in Genetics, Transcriptomics, and Proteomics
- •2.4 Candidate Genes and SS Pathogenesis
- •2.5 Gene Expression Studies in SS
- •2.6 Protein Expression Studies in SS
- •2.7 Future Directions
- •References
- •3.1 Introduction
- •3.2 Characteristics of Autoimmune Lesions
- •3.3 Epithelial Cells as Key Regulators of Autoimmune Responses
- •3.4 Tissue Injury and Repair
- •3.4.1 Functional Impairment of Glands and Autonomic Nervous System Involvement
- •3.4.2 Extracellular Matrix and Tissue Damage
- •3.5 Pathogenetic Factors
- •3.5.1 Genetic Predisposition
- •3.5.2 Environmental Factors
- •3.5.3 Hormonal
- •3.6 Conclusions/Summary
- •References
- •4.1 Hepatitis C Virus
- •4.2 Hepatitis B Virus
- •4.5 Coxsackieviruses
- •4.6 Herpes Viruses
- •4.7 Human Parvovirus B19
- •4.8 Conclusion
- •References
- •5.1 The Role of T Cells in SjS
- •5.2 The Role of B Cells in SjS
- •5.2.1 The Impact of B Cell Cytokines
- •5.2.2 Ontogeny of B Lymphocytes
- •5.2.3 Subpopulations of B Cells
- •5.2.4 B Cell Monoclonal Expansion
- •5.3 B Cells Are Not Dispensable
- •5.3.1 B Cell Chemokines and Antibody Production
- •5.3.2 Peculiarities of B Cell Products: Cytokines and IgA Autoantibodies
- •5.3.3 Intrinsic Abnormalities of B Cells in Primary SjS
- •5.4 Conclusion
- •References
- •6.1 Introduction
- •6.3 Objective Determination of Salivary Flow
- •6.4 Etiology of Xerostomia
- •6.5 Orofacial Manifestations in SS
- •6.5.1 Salivary Involvement
- •6.5.2 Neurological Involvement
- •6.6 Sialochemical Changes in SS
- •6.7 Hyposalivation: Clinical Features and Complications
- •6.7.1 Clinical Features
- •6.7.2 Examination
- •6.7.3 Clinical Signs of Hyposalivation
- •6.7.4 Effect of Hyposalivation on Quality of Life
- •6.7.5 Management of Hyposalivation
- •6.7.6 Chronic Complications of Hyposalivation
- •Box 6.1: Chronic Complications of Hyposalivation
- •6.7.6.1 Dental Caries
- •Box 6.2: Strategies for Reducing Dental Caries in Patients with Sjögren’s Syndrome
- •6.7.6.2 Periodontal Health
- •6.7.6.3 Oral Functional Impairments
- •6.7.6.4 Oral Infections
- •Box 6.3: Factors Predisposing to Oral Candidiasis
- •6.7.6.6 Angular Stomatitis
- •6.7.6.7 Candidiasis
- •6.7.6.8 Bacterial Sialadenitis
- •6.7.6.9 Oral Ulceration
- •6.8 Salivary Gland Enlargement
- •6.8.1 Box 6.5: Non-Salivary Causes of Salivary Gland Enlargement
- •6.9 Salivary Swelling in SS
- •References
- •Key Websites (Accessed Dec 19, 2009)
- •7.1 Sjögren’s Syndrome: A Disease of the Lacrimal Functional Unit
- •7.2 Components of the Lacrimal Functional Unit
- •7.3 Lacrimal Gland
- •7.4 Conjunctiva
- •7.5 Cornea
- •7.6 Meibomian Glands and Eyelids
- •7.7 Neural Innervation
- •7.8 Mechanisms of Dysfunction
- •7.8.1 Lacrimal Gland
- •7.8.2 Ocular Surface
- •7.9 Diagnosis of Ocular Involvement in Sjögren’s Syndrome
- •7.10 Treatment of LFU Dysfunction
- •References
- •8.1 Introduction
- •8.2 Otologic Manifestations
- •8.3 Sinus and Nasal Manifestations
- •8.4 Laryngopharyngeal and Tracheal Manifestations
- •References
- •9.1 Epidemiology of Fatigue
- •9.2 Assessing Fatigue
- •9.4 Relationship of Fatigue to Cognitive Symptoms and to Depression
- •9.5 Fatigue Viewed From the Physiological Perspective: Relationships Between Fatigue, Sleep Quality, and Neuroendocrine Function
- •9.6 Relationship Between Fibromyalgia and SS
- •9.7 Management of Pain and Fatigue
- •9.8 Summary
- •References
- •10.1 Introduction
- •10.2 Arthralgias and Arthritis
- •10.3 Arthritis: Patterns of Expression
- •10.4 Differential Diagnosis: RA, SLE, and Other Arthropathies
- •References
- •11.1 Introduction
- •11.2 Epidemiology
- •11.3 Skin Changes Encountered in Primary SjS
- •11.3.1 Pruritus
- •11.3.2 Annular Erythema of SjS
- •11.3.3 Eyelid Dermatitis
- •11.3.4 Panniculitis
- •11.3.5 Primary Nodular Cutaneous Amyloidosis
- •11.3.6 B Cell Lymphoma
- •11.4 Skin Changes Encountered in Secondary SjS
- •11.4.1 Skin Changes Associated with Lupus Erythematosus
- •References
- •12.1 Introduction
- •12.2 Epidemiology
- •12.3 Histopathology
- •12.4 Laboratory Findings
- •12.5 Pathogenesis
- •12.6 Clinical Findings
- •12.7 Skin
- •12.8 Peripheral and Central Nervous System
- •12.9 Other Organs
- •12.10 Vasculitis and Mortality
- •12.11 Treatment
- •References
- •13.1 Introduction
- •13.2 Pericarditis
- •13.3 Myocarditis
- •13.4 Valvular Abnormalities
- •13.5 Diastolic Dysfunction
- •13.6 Atrioventricular Block
- •13.7 Subclinical Atherosclerosis
- •13.8 Pulmonary Arterial Hypertension
- •13.9 Autonomic Cardiovascular Dysfunction
- •13.10 Therapeutic Management
- •13.11 Conclusion
- •References
- •14.1 Introduction
- •14.2 Airway Disease
- •14.2.1 Overview
- •14.2.2 Pathology
- •14.2.3 Imaging Studies
- •14.3 Interstitial Lung Disease
- •14.3.1 Overview
- •14.3.2 Pathology
- •14.3.4 Usual Interstitial Pneumonia
- •14.3.5 Follicular Bronchiolitis
- •14.3.6 Lymphocytic Interstitial Pneumonia
- •14.3.7 Cryptogenic Organizing Pneumonia
- •14.3.8 Clinical Features
- •14.3.9 Imaging Studies
- •14.4 Pleuritis
- •14.5 Diagnosis and Management
- •References
- •15.1 Evaluation of the Sjögren’s Syndrome and Raynaud’s Phenomenon
- •15.2 Management of Raynaud’s Phenomenon
- •15.2.1 Vasodilator Therapy
- •15.2.2 Calcium Channel Blockers
- •15.2.3 Adrenergic Blockers
- •15.2.4 Nitrates
- •15.2.5 Phosphodiesterase Inhibitors
- •15.2.6 Prostacyclins
- •15.2.7 Other Agents
- •15.3 Surgical Options
- •15.3.1 Sympathectomies
- •15.3.2 Management of Critical Digital Ischemia
- •References
- •16.1 Dysphagia
- •16.3 Chronic Gastritis
- •16.5 Association with Celiac Disease
- •16.6 Intestinal Vasculitis
- •16.7 Other Intestinal Diseases
- •16.8 Conclusion
- •References
- •17.1 Introduction
- •17.2 Primary Biliary Cirrhosis (PBC)
- •17.2.2 Similarities, Differences, and Overlap Among SS and PBC
- •17.2.3 Epithelium Involvement
- •17.2.4 Animal Models
- •17.2.5 Histology and Serology
- •17.3 Autoimmune Hepatitis (AIH)
- •17.4 Hepatitis C Virus (HCV) Infection and Sicca Syndrome
- •17.5 Algorithm for the Diagnosis of Liver Involvement in SS
- •References
- •18.1 Introduction
- •18.3 Involvement of the Pancreas in SjS
- •18.3.1 Clinical Presentation
- •18.3.2 Autoantibodies
- •18.3.3 Pancreatic Enzymes
- •18.3.4 Pathology
- •18.3.5 Imaging Studies of the Pancreas
- •18.4 Autoimmune Pancreatitis
- •18.4.1 Introduction
- •18.4.2 Clinical Features
- •18.4.3 Imaging
- •18.4.4 Serology
- •18.4.5 Pathology
- •18.4.6 Diagnostic Criteria
- •18.5.1 Introduction
- •18.5.2 Nomenclature
- •18.5.3 Clinical Manifestations
- •18.5.4 Serological Issues
- •18.5.5 Pathology
- •18.5.6 Diagnostic Criteria
- •18.6 Conclusions
- •References
- •19.1 Introduction
- •19.2 Interstitial Nephritis in Primary Sjögren’s Syndrome
- •19.2.1 Historical Aspects
- •19.2.2 Clinical Features
- •19.2.3 Histology
- •19.2.4 Pathogenesis
- •19.2.5 Differential Diagnosis
- •19.2.6 Treatment
- •19.3 Glomerulonephritis in Primary Sjögren’s Syndrome
- •19.3.1 Historical Aspects
- •19.3.2 Clinical Features
- •19.3.3 Histology
- •19.3.4 Pathogenesis
- •19.3.5 Differential Diagnosis
- •19.3.6 Treatment
- •19.4 Painful Bladder Syndrome/Interstitial Cystitis and Primary Sjögren’s Syndrome
- •19.4.1 Historical Aspects
- •19.4.2 Clinical, Cytoscopic, and Histologic Features
- •19.4.3 Pathogenesis and Association with Sjögren’s Syndrome
- •19.4.4 Differential Diagnosis
- •19.4.5 Treatment
- •References
- •20.2 Cerebral Lesions
- •20.3 Differential Diagnosis with Multiple Sclerosis, Neuromyelitis Optica, and Antiphospholipid Syndrome
- •20.4 Cranial Nerve Involvement
- •20.5 Diagnostic Algorithm of SS Patient with CNS Lesions, Myelitis, Meningitis
- •References
- •21.3 Sensorimotor Demyelinating Polyneuropathy (CIDP)
- •21.4 Multiple Mononeuropathy or Mononeuritis Multiplex
- •21.5 Sensory Ataxic Neuronopathy
- •21.6 Small Fiber Painful Sensory Neuropathy
- •21.7 Restless Leg Syndrome
- •References
- •22.1 Introduction
- •22.2 Pathogenesis of Autonomic Dysfunction in pSS
- •22.3 Diagnostic Tests
- •22.4 Parasympathetic and Sympathetic Disorders
- •22.4.1 Secretomotor Disorder
- •22.4.2 Urinary Disorder
- •22.4.3 Gastrointestinal Disorder
- •22.4.4 Pupillomotor Disorder
- •22.4.5 Orthostatic Intolerance
- •22.4.6 Vasomotor Disorder
- •22.5 Diagnostic Algorithm of pSS Patient with Autonomic Dysfunction
- •22.6 Treatment
- •References
- •23.1 Introduction
- •23.5 Prolactin and Sjögren Syndrome
- •23.7 Perspectives of Hormonal Treatment on Sjögren Syndrome
- •23.8 Conclusions
- •References
- •24.1 Introduction
- •24.2 Gynecological Manifestations in Sjögren’s Syndrome
- •24.3.1 Epidemiology and Clinical Features of NLS and Congenital Heart Block (CHB)
- •24.3.2 Maternal and Fetal Outcomes in NLS
- •24.3.3 Diagnosis
- •24.3.4 Risk Factors
- •24.3.5 Pathogenesis of Congenital Heart Block
- •References
- •25.1 Introduction
- •25.2 Serum Proteins
- •25.2.1 Acute Phase Reactants
- •25.2.2 Gammaglobulins
- •25.2.2.1 Polyclonal Hypergammaglobulinemia
- •25.2.2.3 Circulating Monoclonal Immunoglobulins
- •25.3 Hematological Abnormalities
- •25.3.1 Normocytic Anemia
- •25.3.2 Autoimmune Hemolytic Anemia
- •25.3.3 Aplastic Anemia
- •25.3.4 Pure Red Cell Aplasia
- •25.3.5 Myelodysplasia
- •25.3.6 Pernicious Anemia
- •25.3.7 Leukopenia
- •25.3.8 Lymphopenia
- •25.3.9 Neutropenia
- •25.3.10 Eosinophilia
- •25.3.11 Thrombocytopenia
- •25.4 Conclusions
- •References
- •26.2 Questionnaires
- •26.3 Ocular Tests
- •26.3.1 Schirmer Test
- •26.3.2 Vital Dyes
- •26.3.3 Rose Bengal
- •26.3.4 Fluorescein
- •26.3.5 Lissamine Green
- •26.3.7 Tear Osmolarity
- •26.3.8 Tear Meniscus
- •26.3.9 Tear Proteins
- •26.3.10 Ferning Test
- •26.3.11 Ocular Cytology
- •26.4 Oral Tests
- •26.4.1 Wafer Test
- •26.4.2 Whole Saliva Flow Collection
- •26.4.3 Saxon Test
- •26.4.5 Impression Cytology
- •26.5 Conclusion
- •References
- •27.1 Salivary Scintigraphy
- •27.2 Sialography
- •27.3 Ultrasound
- •27.4 Tomography
- •27.5 Magnetic Resonance
- •27.6 Salivary Gland Biopsy
- •27.6.1 Labial Gland Biopsy
- •27.6.2 Daniels’ Technique
- •27.6.3 Punch Biopsy
- •27.6.4 Major Salivary Gland Biopsy
- •27.6.5 Lacrimal Gland Biopsy
- •27.6.6 Focus Score
- •27.7 Is There an Alternative to Labial Salivary Gland Biopsy?
- •References
- •28.1 Antinuclear Antibodies
- •28.3 Antibodies Against Nonnuclear Antigens
- •28.7 Antiphospholipid Antibodies
- •28.9 Anticentromere Antibodies
- •28.12 Rheumatoid Factor and Cryoglobulins
- •28.13 Complement
- •28.14 Conclusion
- •References
- •29.1 Introduction
- •29.2 Historical Overview and Sets of Criteria
- •29.3 Preliminary European Criteria
- •References
- •30.1 Introduction
- •30.2 Clinical and Serological Peculiarities of Sjögren’s Syndrome
- •30.3 Assessment of Disease Activity or Damage in Systemic Autoimmune Diseases
- •30.4 Methodological Procedures to Develop Disease Status Criteria
- •30.5 Development of Disease Status Indices for Sjögren’s Syndrome
- •30.5.1 The Italian Approach
- •30.5.2 The British Approach
- •30.5.3 The EULAR Initiative
- •References
- •31.1 Introduction
- •31.3 Other Generic QoL/HRQoL Measures
- •31.6 Predictors of QoL and HRQoL (WHOQoL) in PSS
- •31.7 Therapeutic Interventions
- •31.8 Conclusions and Summary
- •References
- •32.1 Introduction
- •32.2 SS Associated with Systemic Lupus Erythematosus (SLE)
- •32.3 SS Associated with Rheumatoid Arthritis (RA)
- •32.5 SS Associated with Other Systemic Autoimmune Diseases
- •32.5.1 Mixed Connective Tissue Disease
- •32.5.2 Systemic Vasculitis
- •32.5.3 Antiphospholipid Syndrome (APS)
- •32.5.4 Sarcoidosis
- •32.6.1 SS Associated with Autoimmune Thyroiditis
- •32.6.2 SS Associated with Autoimmune Liver Disease
- •32.6.3 Association of SS with Coeliac Disease
- •32.7 Conclusions
- •References
- •33.1 Introduction
- •33.2 Methodological Considerations
- •33.3 Primary Sjögren’s Syndrome and Lymphoma
- •33.3.1 Risk Levels
- •33.3.2 Lymphoma Subtypes
- •33.4 Prediction of Lymphoma
- •33.4.1 Can We Tell Who Will Develop Lymphoma and When This May Occur?
- •33.4.2 Established Risk Factors
- •33.4.3 Recently Proposed Newer Risk Factors
- •33.5 Pathogenetic Mechanisms
- •33.6 Medication and Risk of Lymphoma in SS
- •33.7 Associated Sjögren’s Syndrome and Lymphoma
- •33.8 Other Cancers in SS
- •33.9 Conclusion
- •References
- •34.1 Introduction
- •34.2 Mortality and Causes of Death in pSS
- •34.4 Conclusions
- •References
- •35.1 Introduction
- •35.2 General Considerations
- •35.3.1 Keratoconjunctivitis Sicca
- •35.3.2 Xerostomia
- •35.3.3 Systemic Dryness
- •35.3.4 Extraglandular Manifestations
- •35.4 Diagnosis
- •35.4.2 Diagnostic Methods
- •35.4.2.1 Keratoconjunctivitis Sicca
- •35.4.2.2 Xerostomia
- •35.4.2.3 Salivary Gland Biopsy
- •35.4.2.4 Immunological Tests
- •35.4.2.5 Other Laboratory Findings
- •35.5 Comorbidities and Occupational Disability
- •35.6 Treatment
- •35.6.1 Keratoconjunctivitis Sicca
- •35.6.2 Xerostomia
- •35.6.3 Management of Extraglandular Features
- •35.7 When to Refer to a Specialist
- •References
- •36.1 Background
- •36.2 General Approach to Dry Mouth
- •36.3 Additional Dental Needs of the SjS Patient
- •36.3.1 Background
- •36.4 Particular Oral Needs of the SjS Patient to Be Assessed by the Rheumatologist
- •36.5 Use of Secretagogues
- •36.5.1 Other Cholinergic Agonists
- •36.5.2 Additional Topical Treatments
- •36.5.3 Systemic Therapy
- •36.6 Oral Candidiasis
- •36.7 Treatment and Management of Cutaneous Manifestations
- •36.7.1 Treatment of Dry Skin in SjS Is Similar to Managing Xerosis in Other Conditions
- •36.7.2 Vaginal Dryness
- •36.7.3 Special Precautions at the Time of Surgery
- •References
- •37.1 Introduction
- •37.2 Marginal Zone (MZ) Lymphomas
- •37.2.1 Extranodal Marginal Zone Lymphomas of MALT Type
- •37.2.2 Therapeutic Approaches of MALT Lymphomas
- •37.2.4 Managing NMZL
- •37.3.1 Histology and General Considerations
- •37.3.2 Treatment of DLBCL
- •37.4 Conclusions
- •References
- •38.1 Introduction
- •38.2 Antimalarials
- •38.4 Glucocorticoids
- •38.5 Azathioprine
- •38.6 Cyclophosphamide
- •38.7 Methotrexate
- •38.8 Cyclosporine
- •38.9 Conclusion
- •References
- •39.3 Mycophenolic Acid
- •39.4 Mizoribine
- •39.5 Rebamipide
- •39.6 Diquafosol
- •39.7 Cladribine
- •39.8 Fingolimod
- •References
- •40.1.2.1 Serum BAFF in SS
- •40.1.3 BAFF Is Secreted by Resident Cells of Target Organs of Autoimmunity
- •40.2 Rituximab in SS
- •40.2.1 The Different Studies Assessing Rituximab in SS
- •40.2.2 Safety of Rituximab
- •40.2.3 Increase of BAFF After Rituximab Therapy
- •40.3.1 Epratuzumab
- •40.4 Conclusion
- •References
- •41.1 Introduction
- •41.2 Cytokine Targeted Therapies
- •41.2.2 Etanercept
- •41.2.3 Interferon Alpha
- •41.2.4 Emerging Anticytokine Therapies
- •41.3 T Cell Targeted Therapies
- •41.3.1 Efalizumab
- •41.3.2 Alefacept
- •41.3.3 Abatacept
- •41.4 Conclusion
- •References
- •42.1 Introduction
- •42.2 Progression and Disease Activity in SjS
- •42.2.1 Saliva
- •42.2.2 Serum
- •42.2.3 Labial or Parotid Tissue
- •42.3 Molecular Targets for Potential Therapeutic Interventions
- •42.3.1 Interferons
- •42.3.2 Cytokines
- •42.3.3 B Cell Activating Factors
- •42.3.4 B and T Cell Receptors
- •42.3.4.1 Rituximab
- •42.3.4.2 Epratuzumab
- •42.3.4.3 Abatacept
- •42.4 Gene Therapy
- •42.5 Stem Cell Therapy
- •42.6 Conclusion
- •References
- •Index
Foreword
We are poised on the verge of major breakthroughs in the understanding and treatment of Sjögren’s syndrome (SjS). Though this complex, multi-organ system disorder has been little understood, poorly described, and relatively ignored for decades, successful collaboration on an international scale, careful epidemiologic studies, basic research on the immunological dimensions of this condition, clinical trials, and other investigations have led us to the brink of meaningful advances for patients. As we move forward into an era of individualized medicine for patients with SjS more rational, mechanism-based therapies, it is timely and appropriate to gather collected knowledge from SjS experts around the world on this condition.
This book is divided into four major sections: (I) Scientific Basis; (II) Clinical Manifestations; (III) Diagnosis and Prognosis; and (IV) Therapeutic Aspects. The Scientific Basis chapters address the epidemiology, genetics, proteomics, and immunopathogenesis of SjS. They also discuss the potential roles of viruses in causing SjS, and consider the emerging understanding of the importance of B lymphocytes in the inflammatory symphony of this condition. Within these chapters are themes that promise advances in therapies based upon fundamental understanding of the disease mechanisms of SjS. As the book’s editors, we have attempted to carry those themes forward through subsequent sections of the book.
The Clinical Manifestations chapters extend far beyond the sicca symptoms to describe in detail the features of this disorder in virtually every organ system. For example, three separate chapters are devoted to the neurological manifestations of SjS – one each to the central, peripheral, and autonomic nervous system complications of this condition. Similarly, both the vasculitic and non-vasculitic cutaneous features of SjS are given proper attention in separate, well-illustrated chapters. New understandings of pancreatic disease in SjS are elaborated in light of an emerging disease long confused with SjS; namely, autoimmune pancreatitis and IgG4-related disease. Raynaud’s phenomenon, the pulmonary complications, and obstetrical/ gynecological issues are also given thorough treatments, along with the rest of the organs touched by this protean disorder.
Diagnosis and Prognosis, areas to which the world’s SjS have expended much collaborative energy over the past 30 years, are given full consideration with ample reference to consensus documents and evidence-based studies. The lengthy, sometimes contentious, but ultimately fruitful efforts at consensus in the American and
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Foreword |
European Classification Criteria are described lucidly. Thorough and practical discussions of the approaches to diagnosis for clinical purposes, an area often confusing for practitioners, are also provided. Aspects of malignancy as they relate to SjS and its prognosis are given appropriate weight in this section, and then considered further in Therapeutic Approaches.
Finally, the growing number of treatment options for SjS are considered in nonoverlapping chapters that address the therapy of sicca features; the treatment of B-cell lymphoma; classic immunosuppressive and immunomodulatory drugs for extra-glandular disease; new immunosuppressive and immunomodulatory drugs; B-cell targeted therapies; and experimental treatments.
As co-editors of this book on SjS we would like to thank the 100 contributors who participated as experts in the assembly of this work. You have enabled the creation of a body of knowledge related to SjS not seen on such a scope before. We have learned much from your writing, wisdom, and experience. Our readers will, too.
Finally, two of us – M.R.-C. and J.H.S. – thank the third, H.M.M., for his remarkable contributions to the field of SjS investigation and clinical care that now span more than 30 years. Much of the progress outlined in these pages has stemmed directly from his vision and devotion to fostering new understandings of SjS and to mentoring the next generation of SjS researchers and clinicians. We hope that this book will do the same.
Manel Ramos-Casals
John H. Stone
Haralampos M. Moutsopoulos
Contents
Part I Scientific Basis |
|
|
1 |
Epidemiology ........................................................................................... |
3 |
|
Yannis Alamanos and Alexandros A. Drosos |
|
2 |
Genetics, Genomics, and Proteomics of Sjögren’s Syndrome............. |
11 |
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Christopher J. Lessard, John A. Ice, Jacen Maier-Moore, |
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Courtney G. Montgomery, Hal Scofield, and Kathy L. Moser |
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3 |
Pathogenetic Aspects of Primary Sjögren’s Syndrome ....................... |
33 |
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Athanasios G. Tzioufas, Efstathia K. Kapsogeorgou, |
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Menelaos N. Manoussakis, and Haralampos M. Moutsopoulos |
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4 |
Primary Sjögren’s Syndrome and Viruses............................................ |
55 |
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Manuel Ramos-Casals, Albert Bové, Rafael Belenguer, |
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Xavier Forns, and Salvatore deVita |
|
5 |
Etiopathogenic Role of B Cells in Primary Sjögren’s Syndrome ....... |
67 |
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Jacques-Olivier Pers, Sophie Hillion, Gabriel Tobón, |
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Valérie Devauchelle, Alain Saraux, and Pierre Youinou |
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Part II Clinical Manifestations
6 |
Oral Involvement..................................................................................... |
85 |
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Crispian Scully and Eleni A. Georgakopoulou |
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7 |
Ocular Involvement................................................................................. |
107 |
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Stephen C. Pflugfelder, Karyn Siemasko, and Michael E. Stern |
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8 |
Ear, Nose, and Throat Manifestations of Sjögren’s Syndrome........... |
121 |
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Rohan R. Walvekar and Francis Marchal |
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9 |
Fatigue in Primary Sjögren’s Syndrome............................................... |
129 |
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Barbara M. Segal |
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10 |
Musculoskeletal Involvement ................................................................. |
149 |
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Guillermo J. Pons-Estel, Bernardo A. Pons-Estel, |
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and Graciela S. Alarcón |
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x |
Contents |
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11 |
Non-Vasculitic Cutaneous Involvement ................................................ |
157 |
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Hobart W. Walling and Richard D. Sontheimer |
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12 |
Vasculitis and Sjögren’s Syndrome........................................................ |
173 |
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George E. Fragoulis, Haralampos M. Moutsopoulos, |
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and John H. Stone |
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13 |
Cardiovascular Involvement .................................................................. |
185 |
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George E. Tzelepis, Clio P. Mavragani, and Haralampos M. Moutsopoulos |
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14 |
Pulmonary Involvement.......................................................................... |
195 |
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Clio P. Mavragani, George E. Tzelepis, and Haralampos M. Moutsopoulos |
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15 |
Raynaud’s Phenomenon and Sjögren’s Syndrome .............................. |
209 |
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Fredrick M. Wigley |
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16 |
Gastrointestinal Involvement in Primary Sjögren’s Syndrome.......... |
227 |
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Manuel Ramos-Casals, José Rosas, Roser Solans, |
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Margit Zeher, and Peter Szodoray |
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17 |
Liver Involvement in Sjögren’s Syndrome............................................ |
237 |
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George E. Fragoulis, Fotini N. Skopouli, Carlo Selmi, |
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and M. Eric Gershwin |
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18 |
Pancreatic Disease in Sjögren’s Syndrome |
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and IgG4-Related Disease....................................................................... |
247 |
|
Arezou Khosroshahi, John H. Stone, and Vikram Deshpande |
|
19 |
Nephro-Urological Involvement............................................................. |
265 |
|
Andreas V. Goules and Haralampos M. Moutsopoulos |
|
20 |
Central Nervous System Involvement ................................................... |
281 |
|
Stanley R. Pillemer, Aaron B. Mendelsohn, and Katrin E. Morgen |
|
21 |
Peripheral Neuropathy ........................................................................... |
293 |
|
Pantelis P. Pavlakis and Marinos C. Dalakas |
|
22 |
Autonomic Neuropathy........................................................................... |
303 |
|
Thomas Mandl and Lennart Jacobsson |
|
23 |
Endocrine Involvement........................................................................... |
321 |
|
Luis J. Jara, Gabriela Medina, Carmen Navarro, Olga Vera-Lastra, |
|
|
and Miguel A. Saavedra |
|
24 |
Gynecological and Reproductive Complications |
|
|
in Primary Sjögren’s Syndrome ............................................................ |
333 |
|
Andreas Goules and Athanasios G. Tzioufas |
|
25 |
Laboratory Abnormalities in Primary Sjögren’s Syndrome .............. |
347 |
|
Pilar Brito-Zerón, Roberto Pérez-Alvarez, Marta Pérez-de-Lis, |
|
|
Carmen Hidalgo-Tenorio, and Manuel Ramos-Casals |
|
Contents |
xi |
|
Part III Diagnosis and Prognosis |
|
|
26 |
Diagnostic Procedures (I): Ocular and Oral Tests ............................... |
369 |
|
Gabriela Hernández-Molina, Francisco Cárdenas-Velazquez, |
|
|
Claudia Recillas-Gispert, and Jorge Sánchez-Guerrero |
|
27 |
Diagnostic Procedures (II): Parotid Scintigraphy, Parotid Ultrasound, |
|
|
Magnetic Resonance, Salivary Gland Biopsy ....................................... |
383 |
|
Gabriela Hernández-Molina, Eric Kimura-Hayama, |
|
|
María del Carmen Ávila-Casado, and Jorge Sánchez-Guerrero |
|
28 |
Immunological Tests in Primary Sjögren Syndrome........................... |
401 |
|
Soledad Retamozo, Pilar Brito-Zerón, Myriam Gandía, |
|
|
Lucio Pallarés, and Manuel Ramos-Casals |
|
29 |
Classification Criteria ............................................................................. |
417 |
|
Chiara Baldini, Rosaria Talarico, and Stefano Bombardieri |
|
30 |
Measurement of Chronicity and Activity in Sjögren’s Syndrome...... |
429 |
|
Claudio Vitali |
|
31 |
Measurement of Quality of Life in Primary Sjögren’s Syndrome...... |
441 |
|
Simon J. Bowman and Wan-Fai Ng |
|
32 |
Sjögren’s Syndrome and Associations with Other Autoimmune |
|
|
and Rheumatic Diseases ......................................................................... |
455 |
|
James E. Peters and David A. Isenberg |
|
33 |
Cancer ...................................................................................................... |
477 |
|
Elke Theander and Eva Baecklund |
|
34 |
Prognostic Factors and Survival ............................................................ |
493 |
|
Andreas V. Goules and Fotini N. Skopouli |
|
35 |
Primary Sjögren Syndrome in Primary Health Care.......................... |
501 |
|
Antoni Sisó-Almirall, Jaume Benavent, Xavier Bosch, Albert Bové, |
|
|
and Manuel Ramos-Casals |
|
Part IV Therapeutic Aspects |
|
|
36 |
Therapy of Oral and Cutaneous Dryness Manifestations |
|
|
in Sjögren’s Syndrome............................................................................ |
517 |
|
Robert I. Fox and Carla M. Fox |
|
37 |
Treatment of B-Cell Lymphoma ............................................................ |
547 |
|
Michael Voulgarelis and Haralampos M. Moutsopoulos |
|
38 |
Classic Immunosuppressive and Immunomodulatory Drugs............. |
565 |
|
Clio P. Mavragani and Stuart S. Kassan |
|
xii |
|
Contents |
39 |
New Immunosuppressive Agents for the Treatment |
|
|
of Sjögren’s Syndrome............................................................................ |
571 |
|
Steven Carsons |
|
40 |
B-Cell-Targeted Therapies in Sjögren’s Syndrome ............................. |
579 |
|
Xavier Mariette |
|
41 |
Other Biological Therapies in Primary Sjögren’s Syndrome ............. |
589 |
|
Pilar Brito-Zerón, Cándido Diaz-Lagares, M. Jose Soto-Cárdenas, |
|
|
Manuel Ramos-Casals, and Munther A. Khamashta |
|
42 |
Experimental Therapies in Sjögren’s Syndrome ................................. |
599 |
|
Arjan Vissink, Hendrika Bootsma, Fred K.L. Spijkervet, |
|
|
and Cees G.M. Kallenberg |
|
Index................................................................................................................ |
617 |
|