- •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
Index
A
ACA. See Anticentromere antibodies Acetylcholine (ACh)
increased degradation, cholinesterase, 316 neuronal release, 316
parasympathetic nervous system, 316 signal, secretion, 322
ACh. See Acetylcholine
ACTH. See Adrenocorticotrophin hormone AD. See Autonomic dysfunction
Adie’s syndrome, 315 Adrenocorticotrophin hormone (ACTH)
CRH, 332–333 HPA axis, 333
IL–6 stimulation, 333
AECG. See American-European consensus group
AIHA. See Autoimmune hemolytic anemia Alefacept
biological therapy, 619
treatment, chronic plaque psoriasis, 618 American-European consensus criteria
(AECC), 4, 6 American-European consensus
group (AECG) defined, 432
excessive stringency, 439–440 scientific community, 440 tool, patient classification, 439
ANA. See Antinuclear antibodies ANCA. See Anti-neutrophil cytoplasmic
antibodies Angular stomatitis, 97
ANS. See Autonomic nervous system Anticentromere antibodies (ACA), 419 Anti-neutrophil cytoplasmic antibodies (ANCA), 177, 420
Antinuclear antibodies (ANA) diagnosis, 414–415
and RF, 334 SjS, 179
Antiphospholipid antibodies (aPL) coexistence, 418–419 description, 418
detection, classification, 418 Antiphospholipid syndrome (APS), 296, 489 APS. See Antiphospholipid syndrome ARTs. See Autonomic reflex tests
ASP. See Autonomic symptom profile Atrioventricular (AV) block
CHB, 346
first-degree, 348–349, 351 second-degree, 351
Autoimmune diseases, pSjS APS, 489 cryoglobulinemia, systemic
vasculitis, 489 MCTD, 488 organ-specific
coeliac disease, 492 liver disease, 491 thyroiditis, 490–491
sarcoidosis, 489–490
Autoimmune hemolytic anemia (AIHA) causes, primary SjS, 364 description, 364
etiopathogenesis, 365
low prevalence, hemolytic assays, 363, 365 PRCA, 365
Autoimmune hepatitis (AIH), 248 Autoimmune pancreatitis (AIP) radiologic abnormalities, 259
serum IgG4, 259 type 1 and 2, 260
M. Ramos-Casals et al. (eds.), Sjögren’s Syndrome, |
617 |
DOI 10.1007/978-0-85729-947-5, © Springer-Verlag London Limited 2012 |
|
618
Autonomic dysfunction (AD) description, 313 pathogenesis, pSS, 315–318
pSS patient diagnostic algorithm, 325–326 Autonomic nervous system (ANS)
ARTs, activity, 321 cardiovascular tests, 321
Autonomic neuropathy AD pathogenesis, pSS
factors, M3R reduced stimulation, 316–318
immunological mechanisms, 315 secretory process and immune system
interaction, 316, 317 serological factor, IgG fraction, 318
anti-M3R antibodies, 314–315 diagnostic tests
ANS, 318, 321
ASP, 321–322
finger skin blood flow, 320 HRV and ARTs, 321
orthostatic blood pressure, 318, 319 parasympathetic and sympathetic disorders
AD, 322 gastrointestinal, 324
orthostatic intolerance, 324–325 pupillomotor, 324 secretomotor, 322–323
urinary, 323 vasomotor, 325
patient autonomic nervous function, pSS, 313, 314
pSS patient diagnostic algorithm, AD, 325–326
treatment, 326–327 Autonomic reflex tests (ARTs)
advantages, 321, 326
ANS activity measurement, 321 cardiovascular, 322
uses, 313, 318
Autonomic symptom profile (ASP) AD, 315
pSS, 321
AV block. See Atrioventricular block
B
B and T cell receptors abatacept, 634 epratuzumab, 634 rituximab
proliferation, 633 retreatment, 634
Index
Baroreceptor sensitivity (BRS)
baroreflex sensitivity measurement, 321 and HRV, 321, 326
B-cell hyperactivity, increase in BAFF B-lymphocyte stimulator (BLyS), 604 Serum BAFF in SS, 604–605
B cell lymphoma (Bcl) chemotherapeutic agents, 585 DLBCL, 582–584 hematopathology, 572
marginal zone (MZ) lymphomas B-cell maturation, peripheral lymph
nodes., 572, 574
extranodal, MALT type, 573–578 histology, differential diagnosis, 581 NMZL management, 581–582 splenic lymphoid follicle, 572, 573 therapeutic approaches, 578–581
non-Hodgkin’s, 168, 169 non-Hodgkin’s lymphoma (NHL), 571 parotid, 169
types, SS patients, 169 B cells, primary SjS
chemokines and antibody production antimuscarinic receptor antibody, 75 organ-specific inflammation, 74
cytokines
BAFF and APRIL, 70 ELISA, 70–71
Th–17 lymphocyte subpopulation, 71 IgA autoantibodies and cytokines
BAFF, 75 sialic acid, 76
intrinsic abnormalities, 76 monoclonal expansion, 74 ontogeny, lymphocytes
activation-induced cytidine deaminase (AID), 72
BAFF, 72
bone marrow (BM), 71 subpopulations
Bm homeostasis, 72
relative expression, CD 38 and IgD, 73 B-cell-targeted therapies in Sjögren’s syn-
drome BAFF-targeted therapy
A Proliferation-Inducing Ligand (APRIL), 608
tolerance, belimumab, 609 treatment strategies, 608, 609
epratuzumab, 608 hyperactivity
autoimmunity, 605
Index |
619 |
efficacy lack, TNF inhibition, 605 |
differential diagnosis |
evidence, 604 |
cognitive and affective disorders, 295 |
increase, BAFF, 604–605 |
MS, 295–296 |
rituximab |
NMO, 296 |
open and controlled studies, 605–606 |
PML, 297 |
safety, 607 |
“T1 black holes”, 296 |
therapy, BAFF increase, 607–608 |
and peripheral, 182–183 |
visual analogic scale (VAS), 607 |
prevalence and classification |
unequivocal evidence, 609 |
pSS, 291–292 |
Bcl. See B cell lymphoma |
theories, 292 |
Biological therapies, pSjS |
SS patient diagnostic algorithm |
B cell hyperactivity, 620 |
aseptic meningitis/myelitis, 298 |
cytokine targeted therapies |
MRI, 298–299 |
emerging anticytokine, 617 |
viruses, 298 |
etanercept, 616–617 |
Cerebrospinal fluid (CSF) |
infliximab, 614–615 |
MS, 296 |
interferon alpha, 617 |
PCR, 299 |
lymphocytic dysfunction, 619 |
CHB. See Congenital heart block |
systemic lupus erythematosus (SLE), 614 |
Chronicity and activity measurement, |
T cell targeted |
primary SjS |
abatacept, 619 |
British approach, 454 |
alefacept, 618–619 |
clinical and serological peculiarities |
efalizumab, 618 |
B cell hyperactivity and proliferation, |
initiation, autoimmune process, 618 |
446 |
Bronchial hyperresponsiveness (BHR), 202 |
focal lymphocytic infiltration, 446 |
|
heterogeneity, 447 |
|
defined, activity, 446 |
C |
development, disease status, 448 |
Candidiasis, 97–98 |
disease activity/damage assessment, |
Carbonic anhydrase (CA), 278 |
autoimmune disease, 447 |
Cardiovascular involvement |
disease severity, 446 |
atrioventricular block, 189 |
EULAR initiative, 454–457 |
autonomic cardiovascular dysfunction, 191 |
immunologic and inflammatory |
complications, pSS, 187–188 |
process, 445 |
diastolic dysfunction, 189 |
Italian approach |
myocarditis, 188 |
ESSDAI, 450–453 |
PAH, 190 |
multivariate models, 448 |
pericarditis, 188 |
SSDDI and SSDAI, 448, 449 |
subclinical atherosclerosis, 189–190 |
Classification criteria, primary SjS |
symptomatic, 193 |
AECG, 432 |
therapeutic management |
American-European |
cardiac complications, pSS, 192 |
analysis, ROC curve, 437 |
pSS treatment algorithm, PAH, 192, |
classification, 438, 439 |
193 |
defined, 439 |
valvular abnormalities, 189 |
drawbacks, 439 |
Central nervous system (CNS) |
prevalence, 440 |
cerebral lesions |
salivary biopsy, heavy reliance, 440 |
focal neurological deficits, 294 |
disease heterogeneity, 431–432 |
MRI, 292–293 |
hallmark, xerostomia and KCS, 431 |
MS and SLE, 294 |
historical overview |
patient white matter damage, pSS, 293 |
awareness, 434 |
cranial nerve involvement, 297–298 |
Copenhagen and San Francisco |
cutaneous involvement, 180 |
criteria, 432 |
620
Classification criteria, primary SjS (cont.) diagnostic tests and ranges, 432–433 importance, focal sialoadenitis, 434 “probable” and “definite”, 432
sets, 432
similarities and dissimilarities, 433 tests, diagnosis, 433–434
preliminary European characteristics, 436–437 classification, 436 disorders and controls, 435 EEC-COMAC, 434–435
methodology and statistics, RA, 435 monovariate, multivariate analyses and
stepwise multiple regression, 435 Congenital heart block (CHB)
NLS epidemiology and clinical features, 345–347
pathogenesis, 350–351 Conjunctival-associated lymphoid tissue
(CALT), 110 Connective tissue disorders (CTDs)
ILD, 202
UIP, 204
Corticotropin releasing hormone (CRH) ACTH, 332–333
cytokines, 332
IL–6 stimulation, 333 C-reactive protein (CRP)
ESR, 358
testing levels, 358
CRH. See Corticotropin releasing hormone CRISP–3 gene. See Cysteine-rich secretory
protein–3 gene CRP. See C-reactive protein
Cryptogenic organizing pneumonia (COP), 206
Cysteine-rich secretory protein–3 (CRISP–3) gene
activation, 334 expression, 335
Cytokines
anti-cytokine therapies, 632–633 IL–6
acute phase reactions, 630 chronic inflammation, 630–632 systemic autoimmunity, 632
IL–7, 632
IL–17, 632
IL–12, IL–18, and IL–23, 632 TNF-a, 630
Index
D
Dehydroepiandrosterone sulphate (DHEAS) and DHEA, 335, 337
serum, 338 Dental caries, 94–95
Denture-induced stomatitis, 96–97 Diagnostic procedures II, primary SjS
MRI, 401–404
salivary gland biopsy, 404–409 salivary gland involvement, 395 salivary scintigraphy
abnormalities, 398 description, 396, 398
percentage, sensitivity and specificity, 396
qualitative and non-invasive measures, 396
system, Shall’s grading, 397 sialography, 398, 399 tomography, CT scans, 401 ultrasound
diagnosis and longitudinal follow-up, 398
Frankfurt horizontal plane, 399 parenchymal inhomogenicity, 400 sensitivity, hypoechoic zones and echo-
genic lines, 399–400 substantial drawbacks, 398–399 ultrasonographic findings, 399, 400 ultrasonographic grading, 400 ultrasonographic images, 401
Diagnostic procedures I, primary SjS definitions, 381
eye and mouth dryness, conditions, 380 ocular (see Ocular tests, primary SjS) oral (see Oral tests, primary SjS) prevalence, xerostomia, 380 questionnaires, 381
symptoms evaluation, 381
Diffuse large B-cell lymphomas (DLBCL) histology
lymph node biopsy, 583, 584
nodal and extranodal dissemination, 583
MALT, 503 MZBCL, 502–503
SS diagnosis and lymphoma, 508 treatment, 584
Distal RTA (dRTA)
and IN, 275 latent, 274
Index
pathogenesis, pSS, 278 SS patients, 278
DLBCL. See Diffuse large B-cell lymphomas Dry mouth, SjS
acidic beverages, 545 anticholinergic side effects, 542 “burning mouth” syndrome, 542 cevimeline effects, 555–556
chemoprophylaxis and polyol sweeteners, 550
cholinergic agonists, 556 dry skin treatment, 559–560
evaluation and treatment, rheumatologist, 551
fluoride, 550 functional circuit, 542
home products, safety, 551 lip balms, 543
measures, 544 oral
candidiasis, 557–559 hygiene, 551–553
pH maintenance, 545 pilocarpine benefit, 554 radiation therapists, 545 recommendations, 543–544
saliva content and stimulation, 546–547 salivary glands, 542
terminology, oral medicine, 547–549 time of surgery, 562–563 TNF-alpha blockers
anti-CD20 antibody, 557 B-cells, 557
treatments, 556–557 vaginal dryness
and dyspareunia, 553
estrogen replacement, 561–562 sexual considerations, 561 yeast infection, 561
Dysphagia
esophageal candidiasis, 234, 235 peristaltic velocity, 234
E
Ear, nose and throat manifestations audiometric evaluation, 124 hearing loss, 123–124 laryngopharyngeal and tracheal
bamboo node, 127 crusting, 128
621
dry mouth and xerostomia, 126 granulomatous and nongranulomatous
nodules, 127
hoarseness and dsyphonia, 127 vocal cord lesions, 128
sensorineural hearing loss, 124 sinus and nasal
epistaxis, 126 hypofunctioning, 125 nasal dryness, 126
Technetium 99m scan (99mTc), 125 UPSIT test, 126
Endocrine involvement axis
HPA, 333 HPG, 333–336 HPT, 338
description, 332
hormonal treatment, SS, 338–339 immune-neuroendocrine system, SS
impact, stress, 333 proinflammatory cytokines, 332
prolactin and SS hyperprolactinemia, 336–337 role, 337
Epidermal nerve fiber biopsy (EFNB), 143 Erythrocyte sedimentation rates (ESRs)
circulating gammaglobulins, 358 CRP, 358
primary SjS, 358
ESSDAI. See EULAR SS disease activity index
Etanercept effect, 616
interferon (IFN)-alpha activity, 617 T cell adhesion molecules, 616
EULAR SS disease activity index (ESSDAI), 450–453, 455, 456
European league against rheumatism (EULAR) initiative, pSjS
indices, 455
multiple regression model, 456 poles, SS spectrum, 454
relationship, curves and plots, 456–457 symptoms, patients, 455–456
Experimental therapies, Sjögren’s syndrome gene therapy, 634–635
lacrimal and salivary glands, 623 molecular targets, therapeutic interventions
B and T cell receptors, 633–634 B cell activating factors, 633
622
Experimental therapies, Sjögren’s syndrome (cont.)
B cell depletion, 627, 629 cytokines, 630–633
development, cytokine-directed drugs, 627, 628
interferons, 627–630 rheumatoid arthritis (RA), 627
phase I and II trials, 636 progression and disease activity
labial/parotid tissue, 627 saliva, 624–626
serum, 626–627
stem cell therapy, 635–636 Eye-associated lymphoid tissue (EALT), 110
F
Fatigue, primary Sjögren’s syndrome assessment
FACIT, 132
FSS, 132, 135 helplessness, 135 MCID, 132
Profile of Fatigue and Discomfort (PROFAD-SSI), 132
questionnaires, measurement, 133–134 cognitive symptoms and depression
affective disorder, 137 “brain fog”, 138
brain imaging studies, 138–139 cerebral perfusion abnormalities, 138
epidemiology “neurasthenia”, 131
persistent and abnormal, 132 fibromyalgia (FM)
dysregulation, stress response system, 141
EFNB, 143 features, 140
nociceptive and neuropathic pain, 142 pain mechanisms, 141 polysymptomatic distress, 141 small-fiber neuropathy, 142
management, 143
prevalence and impact, primary SS hypothesized individual risk factors,
136
oral sicca severity, 137
seropositive and seronegative patients, 135
SF–36, 136–137
sleep quality, and neuroendocrine function adrenal axis hypofunction, 139
animal models, 140
Index
cardiovascular reflexes, 139–140 IL–6, 140
polysomnography and actigraphy, 139 Fibromyalgia (FM)
dysregulation, stress response system, 141 EFNB, 143
features, 140
nociceptive and neuropathic pain, 142 pain mechanisms, 141 polysymptomatic distress, 141 small-fiber neuropathy, 142
FM. See Fibromyalgia
G
Gammaglobulin, primary SjS hypogammaglobulinemia and
immunoglobulin deficiency, 360 monoclonal immunoglobulins
clinical significance, 361 detection, monoclonal B-cell
population, 360 IgMk and IgGk, 361, 362
peripheral monoclonal expression, 361–362
prevalence, 361
polyclonal hypergammaglobulinemia classification and parameters,
prevalence, 359, 360 description, 359 immunological marker, 359
Gastroesophageal reflux (GER), 234–235 Gastrointestinal involvement, primary
Sjögren’s syndrome celiac disease, 237 chronic gastritis
anti-PCA antibodies, 235, 236 prevalence, 235
diseases, 234 dysphagia
esophageal candidiasis, 234, 235 peristaltic velocity, 234
GER (see Gastroesophageal reflux)
Helicobacter pylori infection gastric lymphomagenesis, 237 seroprevalence, dyspeptic
patients, 236
inflammatory mucosal response, 238 intestinal vasculitis
biopsy-proven vasculitis, 238 cryoglobulins, 238
Gene therapy
exocrine component, SjS, 635 restore normal function, 634
GER. See Gastroesophageal reflux
Index |
623 |
Glomerulonephritis (GN), pSS |
High-resolution computed tomography |
clinical features, 279–280 |
(HRCT) |
description, 279 |
features, 209 |
differential diagnosis, 282 |
ILD pattern, 208 |
histology, 280–281 |
lung determinations, 201 |
pathogenesis, 281–280 |
parenchymal lung abnormalities |
treatment, 282–283 |
detection, 206 |
Granulocyte colony-stimulating factor |
pSS patients, 208 |
(G-CSF), 369 |
HPA axis. See Hypothalamus-pituitary- |
Gynecological and reproductive |
adrenal axis |
complications, pSS |
HPG axis. See Hypothalamus-pituitary- |
description, 343 |
gonadal axis |
NLS |
HPT axis. See Hypothalamus- |
epidemiology and clinical features |
pituitary-thyroid |
and CHB, 345–347 |
Human leukocyte antigen (HLA) |
maternal and fetal outcomes, 347–348 |
HLA-DR3, 362, 369 |
pathogenesis, CHB, 350–351 |
light chain, 362 |
pregnancy management, anti-Ro/La |
Human T-lymphotropic virus type I |
autoantibodies, 351–352 |
(HTLV-I), 61 |
risk factors, 349–350 |
Hyposalivation |
SS, 344–345 |
chronic complications |
|
angular stomatitis, 97 |
|
bacterial sialadenitis, 98 |
H |
candidiasis, 97–98 |
Health-related quality of life (HRQoL), pSjS |
dental caries, 94–95 |
measures, “disease-specific” |
denture-induced stomatitis, 96–97 |
correlations, 466 |
oral functional impairments, 95 |
domains, EQ–5D, 464 |
oral infections, 95–96 |
domains, OHIP, 465 |
oral ulceration, 98–99 |
importance, 465 |
periodontal health, 95 |
NHP and SIP, 465 |
clinical features, 91–92 |
rheumatoid arthritis, 464 |
defined, 86 |
predictors, SF–36, 464–466 |
examination, 92 |
predictors, WHOQoL |
management, 94 |
measures, global and objective, 467 |
oral complaints, 91 |
stepwise regression analysis, 469 |
quality of life, effect, 93–94 |
symptomatic measures, 468 |
reduced salivary output, 92 |
total damage score, 467 |
signs, clinical |
variables, correlation analysis, 468 |
dry mouth, food residues, 92, 93 |
SF–36 questionnaire |
lobulated tongue, 93 |
difference and comparison, 463–464 |
Hypothalamus-pituitary-adrenal |
domains, 463 |
(HPA) axis |
therapeutic interventions |
basal ACTH and cortisol levels |
androgen deficiency, 470 |
creation, 333 |
cyclosporine ophthalmic emulsion, 469 |
hormonal alterations, SS, 338 |
efficacy, rituximab, 469 |
Hypothalamus-pituitary-gonadal |
non-pharmacologic approach, 470 |
(HPG) axis |
Heart rate variability (HRV) |
androgens and estrogens role, |
and BRS, 321, 326 |
333–334 |
cardiovascular autonomic function, 321 |
DHEA and DHEAS, 335 |
Hepatitis C virus (HCV) |
dihydrotestosterone, estrogen and |
infection, 361–362 |
testosterone, 334 |
and parvovirus B19, 368 |
interaction, CRISP–3 gene, 335, 336 |
Highly active antiretroviral treatments |
Hypothalamus-pituitary-thyroid (HPT) |
(HAART), 60–61 |
axis, 338 |
624
I
Immunological tests, primary SjS ACA, 419
ANA, 414–415 ANCA, 420
antibodies, anti-SSA/Ro and-SSB/La, 415 anti-citrullinated antibodies
and anti-keratin, 421 defined, CCP, 420
anti-DNA antibodies, 415–416 anti-RNP antibodies, 417–418 anti-Scl70 antibodies, 419 anti-Sm antibodies, 417
aPL, 418–419
B-lymphocyte hyperactivation, 413 clinical significance, 414 complement, 421–423
evaluation, 414 nonnuclear antigens
antimitochondrial and anti-parietal cell antibodies, 415
prevalence and clinical significance, 416
rheumatoid factor and cryoglobulins, 421 Immunosuppressive agents, Sjögren’s
syndrome interferon-a
cladribine, 600–601 diquafosol, 600 fingolimod, 601 mizoribine, 599
mycophenolic acid (MPA), 598 neurological symptoms, 598 refamipide, 599–600
restore salivary gland function, 597 leflunomide (LEF), 595
oral agents, disease modifying activity, 595, 596
Immunosuppressive and immunomodulatory drugs
antimalarials, 590 azathioprine, 591 cyclophosphamide, 591–592 cyclosporine, 592
effect, 589–590 glucocorticoids, 591 methotrexate, 592 NSAID, 591
SS management, 592
symptoms, Sjögren’s syndrome (SS), 589 Inclusion body myositis (IBM)
and SS, 154
vacuolar myopathic degeneration, 155
Index
Infliximab
therapeutic approaches, 614, 615 TNF-alpha blockers, 615
Interferons
immunomodulating properties, 627 intracellular pathogens, 630, 631 visual analogue scale (VAS), 629
Interstitial lung disease (ILD) clinical features, 206 COP, 206
CTD, 202
follicular bronchiolitis, 205 imaging studies
parenchymal bullae and cysts, 208 respiratory involvement HRCT patterns
frequency, pSS, 206, 207 LIP, 205–206
NSIP, 203–204 pathology, 203
pulmonary function tests, pSS-associated, 208
UIP, 204–205
Interstitial nephritis (IN), pSS
clinical and laboratory determinations, 275, 276
description, 274 differential diagnosis, 278 and dRTA, 275
histology, 277 pathogenesis, 277–278
patient plain abdominal film, 275, 276 treatment, 278–279
K
KCS. See Keratoconjunctivitis sicca Keratoconjunctivitis sicca (KCS)
Bijsterveld score, 384 defined, 380, 381 dry eyes, 525–526
fluorescein staining, 385, 386 rose bengal staining, 383 schirmer test, 529
treatment, 531 validation, DEQ, 381
L
Laboratory abnormalities, primary Sjögren’s Syndrome
description, 358 hematological
AIHA, 364–365
Index |
625 |
aplastic anemia, 365 |
LFU. See Lacrimal functional unit |
eosinophilia, 370 |
Linkage disequilibrium (LD) |
leukopenia, 366–367 |
description, 16 |
lymphopenia, 367–368 |
SNPs, human genome, 17 |
MDS, 366 |
variable patterns, 16 |
neutropenia, 368–370 |
Liver involvement, Sjögren’s syndrome |
normocytic anemia, 363–364 |
AIH, 248 |
pernicious anemia, 366 |
algorithm, diagnosis, 249–250 |
PRCA, 365–366 |
HCV Infection and sicca syndrome, |
thrombocytopenia, 370 |
248–249 |
serum proteins |
LFT, 244 |
acute phase reactants, 358 |
PBC (see Primary biliary cirrhosis) |
b2-microglobulin, 362–363 |
Lymphocytic interstitial pneumonia |
gammaglobulins, 359–362 |
(LIP), 205–206 |
Laboratory abnormalities, pSS |
Lymphoma, SS |
cytopenias, 371 |
B-cell subsets, 509 |
hematological |
British SS cohort, 510–511 |
AIHA, 364–365 |
chemokine expression, 504 |
aplastic anemia, 365 |
disease activity, 509 |
eosinophilia, 370 |
MALT and DLBCL, 502–503 |
leukopenia, 366–367 |
medication, 510 |
lymphopenia, 367–368 |
NHL development, 504 |
MDS, 366 |
RA and SLE, 510 |
neutropenia, 368–369 |
risk factors |
normocytic anemia, 363–364 |
B cell transformation, 505–508 |
pernicious anemia, 366 |
CD4+ T-lymphocytopenia, 505 |
PRCA, 365–366 |
DLBCL and MALT, 508–509 |
thrombocytopenia, 370 |
dose effect, 504 |
serum proteins |
lip biopsies, germinal centers, |
acute phase reactants, 358 |
506 |
gammaglobulins, 359–362 |
risk levels |
b2-microglobulin, 362–363 |
pSS population and cohort, 502 |
SjS, 358 |
sicca syndrome, 501 |
Lacrimal functional unit (LFU) |
SIR and NHL, 501–502 |
components, 108 |
serum immunoglobulins, 504 |
dysfunction treatment |
Lymphopenia, primary SjS |
artificial tears, 114 |
prevalence, CD4+, 367 |
consensus and evidence-based algo- |
viral infections, 368 |
rithms, 113 |
|
dry eye severity grading scheme, 114, |
|
115 |
M |
management recommendation, dry eye, |
Magnetic resonance cholangiography |
116 |
(MRCP), 255 |
ocular surface prosthesis, 114 |
Magnetic resonance imaging (MRI) |
punctal occlusion, 114 |
APS, 297 |
LD. See Linkage disequilibrium |
axial CT image, 402 |
Leflunomide (LEF) |
cerebral changes, 292 |
immunosuppressive agent, 595 |
classification, 404 |
liver function test abnormalities, 596 |
CNS lesions, 299 |
therapy, 596 |
comparison, findings, 402 |
Leukopenia, primary SjS |
defined, 401 |
positive autoantibodies vs. cytopenias, 367 |
modalities, 402 |
prevalence, 366–367 |
MS lesions, 296 |
626
Magnetic resonance imaging (MRI) (cont.) T2-weighted, 293, 294 ultrasonography, 403
MALT. See Mucosa-associated lymphoid tissue
Marginal zone B-cell lymphoma (MZBCL), 502–503
MCTD. See Mixed connective tissue disease MDS. See Myelodysplasia
Meibomian glands and eyelids, 110 b2-Microglobulin, pimary SjS
dTRA, 363
and extraglandular involvement, 362 levels, 362
transmembrane glycoproteins, 362
Mixed connective tissue disease (MCTD), 488 Mucosa-associated lymphoid tissue (MALT)
lymphomas
extranodal marginal zone lymphomas hashimoto thyroiditis, 573 international prognostic index, 578 lactate dehydrogenase (LDH), 575 lymphoepithelial lesion, 573, 574 neoplastic marginal zone cells, 576 neoplastic process, 575, 576 staging, 575, 577
histological transformation, 583 low-grade lymphomas, 509 pSS, 502
salivary glands, 503 therapeutic approaches
alkylating agents, 579 anti-CD20 treatments, 579 chemotherapy, 578–579
management, SS-associated MZ lymphomas, 580
Multiple sclerosis (MS) CNS damage, 294 diagnosis, 295 disability cause, 295 and PML, 297
and SLE, 294, 297 Musculoskeletal involvement
arthralgias and arthritis, 152 description, 151 differential diagnosis
patients diagnostic algorithm, arthritis and sicca symptoms, 153
sarcoidosis, 154
expression patterns, arthritis, 152 myalgias and myositis
classification, pSS, 155 SS and IBM, 154, 155
Index
Myelodysplasia (MDS), 366 Myoepithelial sialadenitis (MESA), 103
MZBCL. See Marginal zone B-cell lymphoma
N
Neonatal lupus syndrome (NLS) CHB pathogenesis, 350–351 diagnosis, 348–349
epidemiology and clinical features and CHB
classic periorbital rash consistent, 345, 346
defined, 345
dilated cardiomyopathy, 346 heart involvement, 346, 347 skin disease, 345
maternal and fetal outcomes autoimmune disease, 347–348 children prognosis, 348 evolution, 347, 348
pregnancy management, anti-Ro/La autoantibodies
glucocorticoids, 351
intrauterine and postnatal, CHB, 351, 352
IVIG administration, 352 risk factors
anti-Ro/SSA and anti-La/SSB, 349, 350 CHB, 349, 350
idiotypic-anti-idiotypic network, 350 Nephro-urological involvement
IN
clinical features, 275–276 differential diagnosis, 278 histology, 277 pathogenesis, 277–278 treatment, 278–279
GN
clinical features, 279–280 differential diagnosis, 282 histology, 280–281 pathogenesis, 281–282 treatment, 282–283
PBS/IC, 283–285 Neuromyelitis optica (NMO)
MRI, 294 MS, 296, 298
Neutropenia cytopenias, 368 description, 368
high frequency, immunological markers, 368
Index
immune granulocytopenia/ agranulocytosis, 369
primary SjS, 368
significant predictive factor, 369 treatment, agranulocytosis, 368 NHL. See Non-Hodgkin lymphoma NLS. See Neonatal Lupus Syndrome
Nodal MZ lymphomas (NMZL) histology, differential diagnosis, 581 management
bone marrow transplantation, 582 therapeutic dilemma, 581
Non-Hodgkin lymphoma (NHL) CD4+ T-lymphocytopenia, 505 development, primary SS, 504, 508 sicca syndrome, 501
SS cohorts, 502 Non-specific interstitial
pneumonia (NSIP) characterization, 203 UIP and LIP, 204
Nonsteroidal anti-inflammatory drugs (NSAIDs), 591
Non-vasculitic cutaneous involvement description, 159
epidemiology, 162–163 primary SjS, skin changes
annular erythema, 164–166 Bcl, 168–170
eyelid dermatitis, 166–167 panniculitis, 167
PNCA, 167–168 pruritus, 164 xerosis, 163
skin changes, secondary SjS lupus erythematosus, 170–171
RA, SSc and idiopathic inflammatory myopathies, 171
skin change types classification, SjS patients, 160–161
Normocytic anemia, primary SjS cause, patients, 364
cell membrane expression, 364 defined, 363
and extraglandular manifestations, 363–364
O
Ocular involvement conjunctiva
conjunctival-associated lymphoid tissue (CALT), 110
627
Goblet cells, 109 topographic zones, 109
cornea, 110 dysfunction mechanism
lacrimal gland, 111 ocular surface, 111–112
lacrimal functional unit MUC5AC, 108
tear film instability and corneal epithelial disease, 108
lacrimal gland
mucosal-associated lymphoid tissue (MALT), 109
sympathetic nerves, 109 meibomian glands and eyelids, 110 neural innervation, 110–111 Sjögren’s syndrome
corneal epithelial filaments, 113 diffuse punctate staining, 112–113 fluorescein tear breakup time, 112 lissamine green and rose bengal dyes,
113, 114 Schirmer test, 112
Ocular tests, primary SjS cytology, 388
destruction, lacrimal gland, 382 ferning test, 387
fluorescein, 385, 386 lissamine green, 385, 386
methods, dry eye evaluation, 382 rose bengal, 384–385
Schirmer, 383–384
tear break-up time, 385, 387 tear meniscus, 387
tear osmolarity, 387 tear proteins, 387 vital dyes, 384
Oral involvement hyposalivation
chronic complications, 94–99 clinical features, 91–92 examination, 92 management, 94
quality of life, effect, 93–94 signs, clinical, 92–93
orofacial manifestations neurological involvement, 89 salivary involvement, 87, 89
salivary flow Saxon test, 86 USFR, 86
salivary gland enlargement causes, 100
628
Oral involvement (cont.) facial palsy, 99, 102 swelling, 101
salivary swelling forms, 103 MESA, 103 parotid glands, 102
sialochemical changes, SS prostaglandin PGE–2, saliva, 90 proteins, minor salivary glands, 91 unstimulated whole saliva (UWS)
flow, 89
xerostomia (see Xerostomia) Oral tests, primary SjS
determination, salivary gland function, 388
impression cytology, 390 reaction, iodine-starch, 390 Saxon, 389–390 sialometry, 388
wafer, 389
whole saliva flow collection, 389
P
PAH. See Pulmonary arterial hypertension Painful bladder syndrome/interstitial cystitis
(PBS/IC) and pSS
clinical, cytoscopic and histologic features, 283
differential diagnosis, 284 ESSIC, 283
pathogenesis and association, SS, 284 treatment, 285
PBC. See Primary biliary cirrhosis
PCNA. See Primary cutaneous nodular amyloidosis
Peripheral neuropathy
axonaly polyneuropathies, 305 electrophysiologic determination, SS, 305 multiple mononeuropathy/mononeuritis
multiplex, 306 prevalence and classification
description, 303 patterns, SS, 304
sensory neuropathies subsets, 304 restless leg syndrome, 309
SAN, 307–308
sensorimotor demyelinating polyneuropathy, 305–306
small fiber painful sensory description, 308 patterns, 309
Index
PNCA. See Primary nodular cutaneous amyloidosis
Polymerase chain reaction (PCR), 299 Polymorphonuclear leukocytes (PMN)
activation, 369 serum counts, 369
PRCA. See Pure red cell aplasia Primary biliary cirrhosis (PBC)
animal models NOD.c3c4 mouse, 246 Treg cells, 247 xenobiotics, 247
definition and diagnosis, 245 epithelium involvement, 246 histology and serology
anti-pyruvate dehydrogenase complex, 248
autoantibody profiles, 247 serum ANA, 247
similarities, differences and overlap, 245–246
Primary cutaneous nodular amyloidosis (PCNA)
immunoglobin light chains deposition, 167
SjS-associated, 167–168
Primary nodular cutaneous amyloidosis (PNCA)
immunoglobulin, 167, 168 leg, 167, 168
Primary Sjögren’s syndrome (pSjS). See also Laboratory abnormalities, pSS
IN, 274–279
AD pathogenesis, 315–318 arthritis, 154
arthropathy, 152
articular involvement, extra-glandular manifestation, 152
autoimmune epithelitis, 515 autoimmune exocrinopathy, 524 autoimmune lesions, characteristics
BAFF, 37
IgG concentrations, 37 incidence, inflammatory cells, 35 lymphocytic infiltrates, 34
mononuclear cell types, incidence, 36 T and B lymphocytes, 36
T cell receptor (TCR) repertoire, 36–37 autonomic dysfunction, 191
cardiac involvement, 187
comorbidities and occupational disability adverse effects, 530
non adults, 530–531
Index |
629 |
diagnosis
classification criteria, 528–529 immunological tests, 530 keratoconjunctivitis sicca, 529 laboratory features, 530 salivary gland biopsy, 529 xerostomia, 529
diagnostic criteria
and classification, 4 variations, occurrence, 4
ECG study, 189
epithelial cells, autoimmune response regulators
exosomes, 40
immunoactive molecules, 39, 40 molecules and cellular products, 38, 39 salivary glands, 38
TLR signaling, 40 etiopathogenic factors, 34 extraepithelial manifestations, 516 extraglandular organ involvement, 34 fatigue and myalgias, 154 glucocorticoids, 516
GN, 279–283 hyperprolactinemia, 336–337 incidence
adult populations, 4
age and sex distribution, Greek study, 5 population-based study, Olmsted
County, 5
information, family doctor, 532–533 key recommendations, practice, 532 mild synovitis, 153
model, SjS pathogenesis, 47 mortality and causes, deaths
cyclophosphamide and glucocorticoids, 517–518
Geek patients, 517 hemodialysis, 517
lymphoproliferative disorders, 516 MALT, 516
musculoskeletal manifestations, 151 non-sicca manifestations, 525 ocular dryness, 524
PAH, 190 pathogenetic factors
environmental factors, 44–46 genetic predisposition, 44 hormonal, 46
patient diagnostic algorithm, AD, 325–326 PBS/IC, 283–285
prevalence
adult populations, 6
ethnic differences role, 7 systematic recording, diagnosed
cases, 6
tricyclic antidepressants and antipsychotic agents, 7
prognostic factors
cryoglobulins evaluation, 519 lymphoproliferative disorders, 518–519 parotid gland enlargement, 519–520 rheumatoid factors (RF), 518
serum monoclonality, 518 pulmonary function tests
airway disease, 202 ILD, 208
stress impact, 333 symptoms
joint disease, 527 keratoconjunctivitis sicca, 525–526 systemic dryness, 527
vascular disease, 527 xerostomia, 526–527
symptoms, impaired autonomic nervous function, 313
tissue injury and repair
extracellular matrix and tissue damage, 42–44
functional impairment and autonomic nervous system, 41–42
treatment hydroxychloroquine, 532
keratoconjunctivitis sicca, 531 xerostomia, 530–531
Primary SS (pSS). See also Primary Sjögren’s syndrome (pSjS)
CNS, 292, 294
MRI, 292, 293
peripheral nervous system, 291 Progressive multifocal leukoencephalopathy
(PML) and MS, 297
viral neurologic disease, 297 pSS. See Primary Sjögren’s syndrome
Pulmonary arterial hypertension (PAH) description, 190
management, pSS, 192
pSS treatment algorithm, 192, 193 Pulmonary involvement
airway disease
imaging studies, 201 mucus secretion, 200–201 pathology, 201 pulmonary function tests,
pSS-associated, 202
630
Pulmonary involvement (cont.) diagnosis and management, 208–209 ILD, 202–208
pleuritis, 208
respiratory system type, SS, 200 Pure red cell aplasia (PRCA)
description, 365
erythropoietic-inhibitor IgG and cytotoxic lymphocytes, 365–366
Q
QoL measurement, primary SjS autoantibodies, blood, 461–462 concept, 462
HRQoL
measures, “disease-specific”, 464–466 predictors, SF–36, 464–466 predictors, WHOQoL, 467–469 SF–36 questionnaire, 463–464 therapeutic interventions, 469–470
SF–36, patients, 463 uses, 462–463
R
RA. See Rheumatoid arthritis Raynaud’s phenomenon (RP), 325 Renal tubular acidosis (RTA)
dRTA, 274, 275, 278–279 patients, proximal, 279 patient, SS, 274
Rheumatoid arthritis (RA) disease activity, 509 KCS, 481
lymphoproliferative disease, 510 prevalence, sicca symptoms, 482 pSS and RA-SS
clinical and serological difference, 482–484
genetic difference, 484 seronegative, 152
skin changes, SSc and idiopathic inflammatory myopathies, 171
SLE and arthropathies, 153–154 Tarpley’s classification, 482
Rheumatoid factor (RF) and ANA, 334
and anti-Ro/SS-A antibody, 359, 366–367 patients, elevated ESRs, 358
Index
S
Saliva
autoimmune process, 624 intervention therapy, 626
mean salivary flow rates, 624, 625 submandibular/sublingual (SM/SL) flow
rates, 626
Salivary gland biopsy, primary SjS Daniels’ technique, 405
focus score
cigarette smoking, 408 defined, 406
histopathologic classification, 407 multiple tissue levels, 408
nodular lymphocytic infiltration, 407 sensitivity and specificity, 406 standardization, 406–407
labial
biopsy results, 409 description, 404
symptoms and positive serology, 408 lacrimal, 406
punch and major, 405 Schirmer test, 112
SCLE. See Subacute cutaneous lupus erythematosus
Sensory ataxic neuronopathy (SAN) causes, 307, 308
defined, 307
diagnostic and therapeutic algorithm, SS, 308
paraneoplastic, 307 treatment regimens, 308
Serum proteins
acute phase reactants, 358
circulation, monoclonal immunoglobulins HCV infection, 361–362
prevalence, 360, 361 hypogammaglobulinemia and immuno-
globulin deficiency, 360 b2-microglobulin
HLA, 362 levels, 362–363
polyclonal hypergammaglobulinemia, 359–360
Sialadenitis, 98, 99
SICCA. See Sjögren’s international collaborative clinical alliance
Single photon emission computerized tomography (SPECT), 293
Index |
631 |
SIR. See Standardized Incidence Ratio |
genetics, transcriptomics and proteomics |
Sjögren’s international collaborative clinical |
central dogma, information flow, 14 |
alliance (SICCA), 440 |
DNA sequence variation, 15 |
Sjögren’s syndrome (SjS). See also Ocular |
genome-wide association (GWA) |
involvement |
scans, 17, 18 |
arguments, “T-cell disease”, 68 |
human genome, 14, 15 |
axonaly polyneuropathies, 305 |
imprecision, allele frequency, 18 |
B cells |
linkage disequilibrium (LD), 16, 17 |
chemokines and antibody production, |
mapping genetic effects, 17 |
74–75 |
SNPs, 15–16 |
cytokines, 70–71 |
variant association calculation, 16 |
IgA autoantibodies and cytokines, |
gynecological manifestations |
75–76 |
dyspareunia and pruritus, 344 |
intrinsic abnormalities, 76 |
problems, patients, 344, 345 |
monoclonal expansion, 74 |
HCV-SjS patients, 362 |
ontogeny, lymphocytes, 71–72 |
hormonal treatment, 338–339 |
subpopulations, 72–73 |
identification and treatment, skin |
B lymphocytes, 68 |
changes, 159 |
cancer |
lymphocytes, 68 |
associated disorder, SLE, 500 |
mean prevalence, skin disorders, 162 |
autoimmune disease, 500 |
patient, diagnostic algorithm, |
disease activity, 509 |
298–299 |
lymphoma, 501–510 |
peripheral neuropathy, 303 |
malignancy and types, 500–501 |
primary, 3–7, 163–170 |
reverse causality, 501 |
and prolactin, 336–337 |
candidate genes and pathogenesis |
protein expression studies, 27–28 |
allele frequencies, 23 |
restless leg syndrome, 309 |
antibody responses, 24–25 |
reticulosarcoma development, 360 |
BAFF influences, 26 |
secondary, 170–171 |
components, immune system, 18 |
small fiber neuropathy patterns, 309 |
early B cell factor 1 (EBF1), 26 |
T-cell infiltrates, 68 |
FAM167A and BLK, 25 |
T cells |
HLA association, 22 |
germinal center evolution, 69 |
interferon (IFN) activation, 23 |
Th–1 and Th–2 cells, 70 |
multifunctional proteins, 22 |
T lymphocytes, 69 |
non-HLA association studies, 19–22 |
Sjögren’s syndrome and associations |
plasmacytoid dendritic cells |
autoimmune diseases, 488–492 |
(pDCs), 24 |
classification, 476 |
STAT4 protein, 24 |
nomenclature, 476 |
TNFSF4, 25 |
RA (see Rheumatoid arthritis (RA)) |
description, 3, 291, 343, 358 |
SLE, 476–481 |
gene expression profiling (GEP), 12 |
SS-SSc, 485–487 |
gene expression studies |
symptoms, sicca, 476 |
cytokine and chemokine signaling, 27 |
systemic/extraglandular, 475 |
“IFN signature”, 27 |
Sjögren’s syndrome (SjS) and IgG4-related |
mRNA, 26–27 |
disease (IgG4-RD) |
genetic epidemiology |
autoimmune pancreatitis |
candidate genes, 12 |
AIP, 257–258 |
human leukocyte antigen (HLA), 13 |
clinical features, 258–259 |
twin concordance rate, 13 |
diagnostic criteria, 261 |
632
Sjögren’s syndrome (SjS) and IgG4-related disease (IgG4-RD) (cont.)
imaging, 259 pathology, 259–260 serology, 259
chronic pancreatitis, 254 clinical characteristics, 254, 255 clinical manifestations
CT, 262, 264
submandibular, parotid and lacrimal glands, 262, 263
diagnostic criteria, 266
exocrine and endocrine portions, 254 nomenclature, 261
pancreas involvement autoantibodies, 256
clinical presentation, 255–256 imaging studies, 257 pancreatic enzymes, 256 pathology, 256–257
pancreatic injury and exocrine dysfunction, 266–267
pathogenesis, 266 pathology
lymphoplasmacytic infiltrate, 263, 265
positive staining, IgG4-bearing plasma cells, 265
serological issues, 263 SjS. See Sjögren’s syndrome
SLE. See Systemic lupus erythematosus SS associated with systemic sclerosis
(SS-SSc) comparison, patients, 487 cryoglobulinemia, 486 ENA testing, 487
extra glandular features, 486 patient, RA, 485
prevalence and parotid enlargement, 485 salivary gland biopsy, 486
symptoms, sicca, 487 SSc. See Systemic sclerosis
SS disease activity index (SSDAI), 448, 449, 454–456
SS disease damage index (SSDDI), 448–450
SS-SSc. See SS associated with systemic sclerosis
Standardized Incidence Ratio (SIR) malignancy, 510 non-hematological tumors, 510–511 patient cohort, 502
primary SS, 501–502
Index
Stem cell therapy
submandibular gland function, 636 tissue formation, 635
Subacute cutaneous lupus erythematosus (SCLE)
annular lesions, 170 and RP, 162
Systemic lupus erythematosus (SLE) anti-Ro and-La antibodies, 479 aplastic anemia, 365
associated disorder, 500 and CNS, 337 comparison, 477 diseases
autoimmune, 509 lymphoproliferative, 510
exposure, mothers, 347–348, 352 hormonal and reproductive factors, 511 immune-neuroendocrine communication,
332
lymphocytic filtration, 478 b2-microglobulin, increased serum levels,
362
and MS, 294, 299 perivascular infiltration, 481 PML, 297
pSS, systemic autoimmune diseases, 187
RA and arthropathies, 153–154 Raynauds phenomenon and CNS involvement, 481
salivary duct dilatation and acinar tissue destruction, 479
serological difference, 481 sicca, clinical expression, 480 and SS, 333–334
and SS, relationship, 476 Systemic sclerosis (SSc)
PBC, 246
skin changes, 171
T
Tissue injury and repair, SjS
extracellular matrix and tissue damage cytokines, 43–44
Fas/Fas-ligand apoptotic pathway, 43
IFNg, 43
matrix metalloproteinase, 43 functional impairment and autonomic
nervous system involvement animal models, 41–42
Index |
633 |
aquaporins (AQP), 42 |
Viruses, SS |
exocrine secretion, 41 |
coxsackieviruses |
M3 muscarinic receptors, 42 |
cross-reaction, 62 |
peripheral tissue, 41 |
lymphocytes, 61 |
|
hepatitis B virus (HBV) |
|
lymphotropism and sialotropism, |
U |
59, 60 |
University of Pennsylvania Smell Identifica- |
prevalence, 59–60 |
tion Test, 126 |
systemic autoimmune diseases, 59 |
Usual interstitial pneumonia (UIP) |
hepatitis C virus (HCV) |
characterization, 204 |
autoimmune features, 57 |
NSIP, 204 |
B-cell hyperactivity, 59 |
|
chronic infection, 59 |
V |
lymphotropism, 58 |
sicca syndrome, 58 |
|
Vasculitis and Sjögren’s syndrome (SS) |
herpes viruses, 62 |
clinical determinations, 180 |
HTLV-I, 61 |
description, 175–176 |
human immunodeficiency virus (HIV) |
epidemiology, 176–177 |
HAART, 60–61 |
histopathology |
salivary gland infiltration, 60 |
acute necrotizing, 178, 179 |
human parvovirus B19 |
endarteritis obliterans, 179 |
B19-DNA, 63 |
leukocytoclastic, 177, 178 |
leukopenia and thrombocytopenia, 62 |
lymphocytic, 178 |
|
laboratory determinations, 179 |
|
and mortality, 183–184 |
X |
other organs, 183 |
Xerostomia |
pathogenesis, 179–180 |
causes, 88–89 |
peripheral and CNS |
dry mouth and maxillofacial |
biopsy specimens, 183 |
diseases, 90 |
neuropathy, 182–183 |
dry mouth symptoms, 526–527 |
skin |
hyposalivation, 86 |
nodules, 180, 181 |
measurement, salivary flow, 529 |
palpable purpura, hyperpigmentation, |
older patients, 87 |
180, 181 |
pilocarpine and cevilimine, 531–532 |
urticaria, 182 |
|
treatment, 183–184 |
|