- •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
Contributors
Yannis Alamanos, M.D. Department of Public Health, Medical School, University of Patras, Rio, Greece
Graciela S. Alarcón, M.D., M.P.H. Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
María del Carmen Ávila-Casado, M.D., Ph.D. Department of Pathology, Instituto Nacional de Cardiología Ignacio, Chávez, Mexico City, Mexico
Eva Baecklund, M.D., Ph.D. Rheumatology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Chiara Baldini, M.D., Ph.D. Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy
Rafael Belenguer, M.D., Ph.D. Rheumatology Unit, Hospital 9 d’Octubre, Valencia, Spain
Jaume Benavent, M.D. Research Group on Primary Care, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),
CAP Les Corts, GesClínic, University of Barcelona, Barcelona, Spain
Stefano Bombardieri, M.D., Ph.D. Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy
Hendrika Bootsma, M.D., Ph.D. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Xavier Bosch, M.D., Ph.D. Department of Internal Medicine, University of Barcelona, ICMiD, Hospital Clínic, Barcelona, Spain
Albert Bové, M.D., Ph.D. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain
xiii
xiv |
Contributors |
Simon J. Bowman, Ph.D., F.R.C.P Rheumatology Department, University Hospital Birmingham (Selly Oak), Birmingham, UK
Pilar Brito-Zerón, M.D., Ph.D. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain
Francisco Cárdenas-Velazquez, M.D. Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Steven Carsons, M.D. Division of Rheumatology, Allergy and Immunology, Winthrop-University Hospital, Mineola, NY, USA
Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY, USA
Marinos C. Dalakas, M.D., F.A.A.N. Neuroimmunology Unit, Department of Pathophysiology, Medical School, University of Athens, Athens, Greece
Vikram Deshpande, M.D. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
Valérie Devauchelle, M.D., Ph.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, the European University of Brittany and the University of Brest, and the Brest University Medical School Hospital, Brest, France
Cándido Diaz-Lagares, M.D. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Alexandros A. Drosos, M.D., F.A.C.R. Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
Xavier Forns, M.D., Ph.D. Liver Unit, Ciberehd, IDIBAPS, Hospital Clínic, Barcelona, Spain
Robert I. Fox, M.D., Ph.D. Chief, Rheumatology Clinic, Scripps Memorial Hospital and Research Foundation, La Jolla, CA, USA
Carla M. Fox, R.N. Cheif, Rheumatology Clinic, Scripps Memorial Hospital and Research Foundation, La Jolla, CA, USA
George E. Fragoulis, M.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Myriam Gandía, M.D. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain
Rheumatology Department, Hospital Puerta del Mar, Cadiz, Spain
Contributors |
xv |
Eleni A. Georgakopoulou, M.D., D.D.S., M.Sc. First Department of Dermatology and Venereology, A. Syggros Hospital, School of Medicine, University of Athens, Athens, Greece
M. Eric Gershwin, M.D. Division of Rheumatology, Allergy and Clinical Immunology, Genome and Biomedical Sciences Facility,
University of California at Davis, Davis, CA, USA
Andreas V. Goules, M.D. Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece
Gabriela Hernández-Molina, M.D., M.S. Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Carmen Hidalgo-Tenorio, M.D., Ph.D. Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain
Sophie Hillion, M.D., Ph.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, The European University of Brittany and The University of Brest, and The Brest University Medical School Hospital, Brest, France
John A. Ice, Ph.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
David A. Isenberg, M.D., F.R.C.P., F.A.M.S. Department of Rheumatology, University College London Hospital, London, UK
Lennart Jacobsson, M.D., Ph.D. Department of Rheumatology, Skane University Hospital, Malmö, Sweden
Luis J. Jara, M.D. Direction of Education and Research, Hospital de Especialidades, Centro Médico La Raza, IMSS, Universidad Nacional Autónoma de México, Mexico City, DF, Mexico
Cees G.M. Kallenberg, M.D., Ph.D. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Efstathia K. Kapsogeorgou, Ph.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Stuart S. Kassan, M.D., F.A.C.P. University of Colorado Health Sciences Center, Denver, CO, USA
Munther A. Khamashta, M.D., Ph.D., F.R.C.P. Lupus Research Unit, The Rayne Institute, King’s College London School of Medicine at Guy’s, King’s and St Thomas’ Hospitals, St Thomas’ Hospital, London, UK
Arezou Khosroshahi, M.D. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA
xvi |
Contributors |
Eric Kimura-Hayama, M.D. Tomography Department, Instituto Nacional de Cardiología Ignacio, Chávez, Mexico City, Mexico
Christopher J. Lessard, Ph.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Jacen Maier-Moore, Ph.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Thomas Mandl, M.D., Ph.D. Department of Rheumatology,
Skane University Hospital, Malmö, Sweden
Menelaos N. Manoussakis, M.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Francis Marchal, M.D., Ph.D. Department of Otolaryngology Head and Neck Surgery, Sialendoscopy Unit, European Sialendoscopy Training Center (ETSC), University Hospital of Geneva, Geneva, Switzerland
Xavier Mariette, M.D., Ph.D. Service de Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
Institut Pour la Santé et la Recherche Médicale (INSERM), Paris, France
Clio P. Mavragani, M.D. Department of Pathophysiology, University of Athens Medical School, Laiko University Hospital, Athens, Greece
Department of Experimental Physiology, School of Medicine,
University of Athens, Athens, Greece
Gabriela Medina, M.D., Ph.D. Clinical and Epidemiology Research Unit, Hospital de Especialidades Centro Médico La Raza, IMSS,
Mexico City, DF, Mexico
Aaron B. Mendelsohn, Ph.D., M.P.H. School of Health Sciences, Walden University, Minneapolis, MN, USA
Courtney G. Montgomery, Ph.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Katrin E. Morgen, M.D. Department of Psychiatry, Central Institute of Mental Health (CIMH), Mannheim, Germany
Kathy L. Moser, Ph.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Haralampos M. Moutsopoulos, M.D., F.A.C.P., F.R.C.P., Master ACR
Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Carmen Navarro, M.D., Ph.D. Deputy Director of Clinical Research, Instituto Nacional de Enfermedades Respiratorias, SSA, Mexico City, DF, Mexico
Contributors |
xvii |
Wan-Fai Ng, M.D., Ph.D. Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
Roberto Pérez-Alvarez, M.D. Department of Internal Medicine, Hospital Meixoeiro, Vigo, Spain
Marta Pérez-de-Lis, M.D., Ph.D. Department of Internal Medicine, Hospital Meixoeiro, Vigo, Spain
Lucio Pallarés, M.D., Ph.D. Autoimmune Diseases Unit, Hospital Son Espases, Palma de Mallorca, Spain
Pantelis P. Pavlakis, M.D. Neuroimmunology Unit, Department of Pathophysiology, Medical School, University of Athens, Athens, Greece
Jacques-Olivier Pers, M.D., Ph.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, the European University of Brittany and the University of Brest,
and the Brest University Medical School Hospital, Brest, France
James E. Peters, M.D., Ph.D. Department of Rheumatology, University College London Hospital, London, UK
Stephen C. Pflugfelder, M.D. Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA
Stanley R. Pillemer, M.D. American Biopharma Corporation,
Gaithersburg, MD, USA
Guillermo J. Pons-Estel, M.D. Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatologia, Hospital Clínic, Barcelona, Catalonia, Spain
Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
Bernardo A. Pons-Estel, M.D. Department of Rheumatology, Instituto Cardiovascular de Rosario, Rosario, Argentina
Manuel Ramos-Casals, M.D., Ph.D. Spanish Group of Autoimmune Diseases (GEAS), Spanish Society of Internal Medicine (SEMI), Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, ICMD Hospital Clínic, Barcelona, Spain
Claudia Recillas-Gispert, M.D. Ophthalmology Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Soledad Retamozo, M.D. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain
xviii |
Contributors |
José Rosas, M.D., Ph.D. Department of Rheumatology, Hospital de la Vila-Joiosa, Alicante, Spain
Jorge Sánchez-Guerrero, M.D., M.S. Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Miguel A. Saavedra, M.D., Ph.D. Department of Rheumatology, Hospital de Especialidades Centro Médico La Raza, Universidad Nacional Autónoma de México, Mexico City, DF, Mexico
Alain Saraux, M.D., Ph.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, The European University of Brittany and The University of Brest, and The Brest University Medical School Hospital, Brest, France
Hal Scofield, M.D. Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Crispian Scully Division of Maxillofacial Diagnostic, Medical and Surgical Sciences, University College London (UCL) – Eastman Dental Institute, London, UK
Barbara M. Segal, M.D. Division of Rheumatic and Autoimmune Disorders, University of Minnesota Medical School, Minneapolis, MN, USA
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN, USA
Carlo Selmi, M.D., Ph.D. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA
Department of Translational Medicine, IRCCS Istituto Clinico Humanitas, University of Milan, Rozzano (MI), Italy
Karyn Siemasko, M.D. Biological Sciences, Allergan, Inc, Irvine, CA, USA
Antoni Sisó-Almirall, M.D., Ph.D. Research Group on Primary Care, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CAP Les Corts, GesClínic, University of Barcelona, Barcelona, Spain
Fotini N. Skopouli, M.D., F.R.C.P. Department of Dietetics and Nutritional Science, Harokopio University of Athens, Athens, Greece
Roser Solans, M.D., Ph.D. Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Spain
Richard D. Sontheimer, M.D. Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA
M. Jose Soto-Cárdenas, M.D., Ph.D. Department of Medicine, University of Cadiz, Department of Internal Medicine, Hospital Puerta del Mar, Cadiz, Spain
Fred K.L. Spijkervet, D.M.D., Ph.D. Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Contributors |
xix |
Michael E. Stern, M.D., Ph.D. Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA
John H. Stone, M.D., M.P.H. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA
Peter Szodoray, M.D., Ph.D. Medical and Health Science Center, Clinical Immunology Division, University of Debrecen, Debrecen, Hungary
Rosaria Talarico, M.D. Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy
Elke Theander, M.D., Ph.D. Department of Rheumatology,
Skåne University Hospital, Malmö, Sweden
Gabriel Tobón, M.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, the European University of Brittany and the University of Brest, and the Brest University Medical School Hospital, Brest, France
George E. Tzelepis, M.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Athanasios G. Tzioufas, M.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Olga Vera-Lastra, M.D., Ph.D. Department of Internal Medicine, Hospital de Especialidades, Centro Médico Nacional La Raza, IMSS, Universidad Nacional Autónoma de México, Mexico City, DF, Mexico
Arjan Vissink, M.D., Ph.D. Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Salvatore deVita, M.D., Ph.D. Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero-Universitaria,
S Maria della Misericordia, Udine, Italy
Claudio Vitali, M.D. Department of Internal Medicine and Section of Rheumatology, ‘Villamarina’ Hospital, Piombino, Italy
Michael Voulgarelis, M.D., Ph.D. Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece
Hobart W. Walling, M.D., Ph.D. Private Practice of Dermatology, Coralville, IA, USA
Rohan R. Walvekar, M.D. Department of Otolaryngology Head and Neck Surgery, LSU Health Sciences Center, Salivary Endoscopy Service
and Clinical Research, New Orleans, LA, USA
Fredrick M. Wigley, M.D. Johns Hopkins University, Department of Medicine, Division of Rheumatology, Baltimore, MD, USA
xx |
Contributors |
Pierre Youinou, M.D., Ph.D. EA 2216 “Immunology and Pathology” and IFR 148 ScInBioS, the European University of Brittany and the University of Brest, and the Brest University Medical School Hospital, Brest, France
Laboratory of Immunology, Brest University Medical School Hospital,
Brest, France
Margit Zeher, M.D., Ph.D. Medical and Health Science Center, Clinical Immunology Division, University of Debrecen, Debrecen, Hungary
Part I
Scientific Basis