- •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
41 Other Biological Therapies in Primary Sjögren’s Syndrome |
595 |
by alefacept, it should be monitored on a regular basis to ensure it does not drop below 250 cells/mL. The reported side effects are minor and include: headache, nasopharyngitis, rhinitis, influenza, upper respiratory tract infections, pruritus, arthralgia, fatigue, nausea, and elevated liver enzymes. Severe infections and malignancies have not been linked to the use of alefacept, and few patients develop anti-alefacept antibodies. Alefacept seems to be a safe biological therapy for moderate-to-severe chronic plaque psoriasis with few side effects reported and will probably be tested in coming years in patients with systemic autoimmune diseases such as SLE, RA, and SS.
41.3.3Abatacept
Abatacept (Orencia®) is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) linked to the modified Fc portion of human IgG1. Specifically, abatacept blocks the CD80 and CD86 ligands on the surface of antigen-presenting cells that interface with the T cell’s CD28 receptor to activate T cells.
Abatacept has recently been approved for the treatment of rheumatoid arthritis refractory to other agents and seems to be more immunosuppressive than TNFalpha blockers. The combination of abatacept and a TNF-alpha-blocking agent does not seem to be more effective than either agent alone. Because abatacept has the ability to suppress T cell function, it is a potential treatment for psoriasis and other autoimmune conditions involving T cell driven pathologic processes. However, a recent controlled trial in patients with RA showed an increased rate of serious adverse events in patients receiving abatacept in combination with other biologic therapies [40], including a trend to a higher incidence of neoplasms (7% vs 2%). Therefore, abatacept should not be used in combination with other biologics to treat RA. Further long-term studies and postmarketing surveillance are required to assess for longer-term harms and sustained efficacy [41].
Recent evidence suggests that CTLA-4, an immune attenuator, contributes significantly to homeostatic control of T helper cell proliferation, and has a critical immunoregulatory role in the downregulation of T cell activation. Only two studies have been carried out in patients with primary SS. The first found no significant differences in the CTLA-4 polymorphisms of Tunisian patients with SS compared with the control group [42], while a recent study by Downie-Doyle et al. [43] described insignificant differences in haplotype frequencies of Australian SS patients compared with controls. A controlled trial of abatacept is under way in the Netherlands.
41.4Conclusion
New therapeutic approaches in primary SS using biological agents are centered on correcting lymphocytic dysfunction, with agents directed at modifying T cell dysfunction or diminishing B cell hyperactivity. B cell targeted therapies seem to be the most promising agents in primary SS, especially rituximab (anti-CD20). Rituximab
596 |
P. Brito-Zerón et al. |
has demonstrated therapeutic efficacy in the treatment of associated extraglandular and lymphoproliferative processes, although data from large randomized, doubleblind, placebo-controlled studies are not yet available. Other promising B cell targeted therapies include agents against CD22+ cells (epratuzumab) and therapies antagonizing Blys/BAFF (belimumab). It seems logical that these agents may play a role in modifying the etiopathogenic events of patients with primary SS, a disease characterized by B cell hyperactivity.
The excellent results of TNF targeted therapies in RA led to these agents being tested in patients with primary SS. However, controlled studies showed a lack of efficacy of infliximab and etanercept in primary SS. Strategies based on T cell targeted therapies (efalizumab, abatacept, alefacept) should be considered as possible future therapeutic options, although the poor response obtained with anti-TNF agents (which may be considered as partially directed against T cells) might suggest a similar limited response.
In the near future, biological agents will play key roles in the treatment of severe SS, broadening the therapeutic options for patients with this disease. However, the possible risks and benefits of using these agents should be balanced carefully. Assessments of the risk of serious adverse events versus the potential benefits of treatment must be made on a patient-by-patient basis.
References
1. Ramos-Casals M, Tzioufas AG, Stone JH, Sisó A, Bosch X. Treatment of primary Sjögren syndrome: a systematic review. JAMA. 2010;304:452–60.
2. Ramos-Casals M, Brito-Zerón P. Emerging biological therapies in primary Sjögren’s syndrome. Rheumatology (Oxford). 2007;46:1389–96.
3. Ramos-Casals M, Font J. Primary Sjögren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005;44:1354–67.
4. Steinfeld SD, Demols P, Salmon I, Kiss R, Appelboom T. Infliximab in patients with primary Sjögren’s syndrome: a pilot study. Arthritis Rheum. 2001;44:2371–5.
5.Steinfeld SD, Demols P, Appelboom T. Infliximab in primary Sjögren’s syndrome: one-year followup. Arthritis Rheum. 2002;46:3301–3.
6. Caroyer JM, Manto MU, Steinfeld SD. Severe sensory neuronopathy responsive to infliximab in primary Sjögren’s syndrome. Neurology. 2002;59:1113–4.
7. Pessler F, Monash B, Rettig P, Forbes B, Kreiger PA, Cron RQ. Sjogren syndrome in a child: favorable response of the arthritis to TNFalpha blockade. Clin Rheumatol. 2006;25:746–8.
8. Mariette X, Ravaud P, Steinfeld S, et al. Inefficacy of infliximab in primary Sjögren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren’s Syndrome (TRIPSS). Arthritis Rheum. 2004;50:1270–6.
9. Sankar V, Brennan MT, Kok MR, et al. Etanercept in Sjögren’s syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis Rheum. 2004;50: 2240–5.
10. Zandbelt MM, de Wilde P, van Damme P, Hoyng CB, van de Putte L, van den Hoogen F. Etanercept in the treatment of patients with primary Sjögren’s syndrome: a pilot study. J Rheumatol. 2004;31:96–101.
11.Moutsopoulos NM, Katsifis GE, Angelov N, Leakan RA, Sankar V, Pillemer S, et al. Lack of efficacy of etanercept in Sjögren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation. Ann Rheum Dis. 2008;67:1437–43.
41 Other Biological Therapies in Primary Sjögren’s Syndrome |
597 |
12. Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK. Augmented interferon-alpha pathway activation in patients with Sjögren’s syndrome treated with etanercept. Arthritis Rheum. 2007;56:3995–4004.
13. Mavragani CP, Crow MK. Activation of the type I interferon pathway in primary Sjögren’s syndrome. J Autoimmun. 2010;35(2):225–31. PubMed PMID:20674271.
14. Mariette X, Gottenberg JE. Pathogenesis of Sjögren’s syndrome and therapeutic consequences. Curr Opin Rheumatol. 2010;22:471–7.
15. Miceli-Richard C, Gestermann N, Ittah M, et al. The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren’s syndrome. Arthritis Rheum. 2009;60:1991–7.
16. Cummins MJ, Papas A, Kammer GM, Fox PC. Treatment of primary Sjögren’s syndrome with low-dose human interferon alfa administered by the oromucosal route: combined phase III results. Arthritis Rheum. 2003;49:585–93.
17. Ship JA, Fox PC, Michalek JE, Cummins MJ, Richards AB. Treatment of primary Sjögren’s syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group. J Interferon Cytokine Res. 1999;19:943–51.
18. Shiozawa S, Tanaka Y, Shiozawa K. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjögren’s syndrome. J Interferon Cytokine Res. 1998;18:255–62.
19. Roescher N, Tak PP, Illei GG. Cytokines in Sjögren’s syndrome: potential therapeutic targets. Ann Rheum Dis. 2010;69:945–8.
20. Smolen JS, Maini RN. Interleukin-6: a new therapeutic target. Arthritis Res Ther. 2006;8:407.
21. Llorente L, Richaud-Patin Y, Garcia-Padilla C, et al. Clinical and biologic effects of anti- interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum. 2000;43:1790–800.
22. Koenders MI, Joosten LA, van den Berg WB. Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis. Ann Rheum Dis. 2006;65 Suppl 3:iii29–33.
23. Isenberg D, Rahman A. Systemic lupus erythematosus – 2005 annus mirabilis? Nat Clin Pract Rheumatol. 2006;2:145–52.
24. Strand V, Singh JA. Newer biological agents in rheumatoid arthritis: impact on health-related quality of life and productivity. Drugs. 2010;70:121–45.
25. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst Rev. 2010;7:CD008331.
26. Nam JL, Winthrop KL, van Vollenhoven RF, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010;69:976–86.
27. Menter A. The status of biologic therapies in the treatment of moderate to severe psoriasis. Cutis. 2009;84(4 Suppl):14–24.
28. Kuhn A, Luger TA. Psoriasis: is ustekinumab superior to etanercept for psoriasis? Nat Rev Rheumatol. 2010;6:500–1.
29. Vosters JL, Landek-Salgado MA, Yin H, et al. Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren’s syndrome. Arthritis Rheum. 2009;60:3633–41.
30.Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleu- kin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. Am J Pathol. 2009;175:1167–77.
31. Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008;181:2898–906.
598 |
P. Brito-Zerón et al. |
32. Jois SD, Jining L, Nagarajarao LM. Targeting T cell adhesion molecules for drug design. Curr Pharm Des. 2006;12:2797–812.
33. Konttinen YT, Kasna-Ronkainen L. Sjögren’s syndrome: viewpoint on pathogenesis. One of the reasons I was never asked to write a textbook chapter on it. Scand J Rheumatol Suppl. 2002;116:15–22.
34. Mikulowska-Mennis A, Xu B, Berberian JM, Michie SA. Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/l-selectin, and lymphocyte function-associated antigen-1 adhesion pathways. Am J Pathol. 2001;159:671–81.
35. Bolstad AI, Eiken HG, Rosenlund B, Alarcon-Riquelme ME, Jonsson R. Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjögren’s syndrome. Arthritis Rheum. 2003;48:174–85.
36. Papp KA, Henninger E. Evaluation of efalizumab using safe psoriasis control. BMC Dermatol. 2006;6:8.
37. Gadzia J, Turner J. Progressive multifocal leukoencephalopathy in two psoriasis patients treated with efalizumab. J Drugs Dermatol. 2010;9(8):1005–9.
38. Papp KA. The long-term efficacy and safety of new biological therapies for psoriasis. Arch Dermatol Res. 2006;298:7–15.
39. Dunn LK, Feldman SR. Alefacept treatment for chronic plaque psoriasis. Skin Therapy Lett. 2010;15:1–3.
40. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, pla- cebo-controlled study. Arthritis Rheum. 2006;54:2807–16.
41. Maxwell LJ, Singh JA. Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010;37:234–45.
42. Hadj Kacem H, Kaddour N, Adyel FZ, Bahloul Z, Ayadi H. HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjögren’s syndrome. Rheumatology (Oxford). 2001;40:1370–4.
43. Downie-Doyle S, Bayat N, Rischmueller M, Lester S. Influence of CTLA4 haplotypes on susceptibility and some extraglandular manifestations in primary Sjögren’s syndrome. Arthritis Rheum. 2006;54:2434–40.