What is Sjogren syndrome?

Sjögren's Syndrome

Sjögren's syndrome is a chronic systemic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, particularly the lacrimal and salivary glands, leading to gland dysfunction, dry eyes and dry mouth, with potential systemic manifestations and increased risk of lymphoma development. 1, 2

Definition and Epidemiology

• Sjögren's syndrome affects approximately 0.4% of the general population, with a strong female predominance (female-to-male ratio of 20:1) 2
• Annual incidence is approximately 3.9-5.3 per 100,000 people, with a prevalence of 92.8 cases per 100,000 2
• About 10% of patients with clinically significant dry eye have an underlying Sjögren's syndrome 2

Classification

• Primary Sjögren's syndrome occurs as a distinct entity without association with other autoimmune diseases 2
• Secondary Sjögren's syndrome occurs in association with other autoimmune diseases such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 2

Pathophysiology

• The condition is characterized by infiltration of the lacrimal and salivary glands with lymphocytes, resulting in secondary compromise of gland function 1, 2
• Abnormal B cell and T cell responses to autoantigens, particularly Ro/SSA and La/SSB, lead to destruction of the epithelium of the exocrine glands 3
• The inflammatory process is central to the disease mechanism, involving both innate and adaptive immune systems 4

Clinical Manifestations

Glandular Symptoms

• Dry eyes (keratoconjunctivitis sicca) - sensation of dryness, irritation, foreign body sensation, and light sensitivity 5
• Dry mouth (xerostomia) - need for liquids to swallow dry foods, frequent sipping of water, burning sensation in mouth, and frequent dental cavities 5
• Parotid gland enlargement may occur 2

Extraglandular Manifestations

• Systemic manifestations beyond sicca symptoms include arthralgia, myalgia, and fatigue 1
• Potential involvement of multiple organs including the lungs, kidneys, liver, nervous system, and vasculature 1
• Other ocular manifestations may include scleritis, sterile keratitis, and uveitis 2
• Potentially life-threatening vasculitic or lymphoproliferative disorders may occur 2

Diagnostic Criteria

The latest classification criteria for Sjögren's syndrome are based on a weighted scoring system:

• Anti-SSA/Ro antibody positivity (3 points) 2
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (3 points) 2
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4 (1 point) 2
• Schirmer test result ≤5 mm/5 minutes without anesthesia (1 point) 2
• Unstimulated salivary flow rate ≤0.1 ml/minute (1 point) 2
• A total score of ≥4 meets the criteria for primary Sjögren's syndrome in individuals with signs/symptoms suggestive of the condition 2

Complications and Associated Risks

• Patients with Sjögren's syndrome have approximately a 5% risk of developing lymphoma, representing a significant increase compared to the general population 1, 2
• Primary Sjögren's syndrome is the rheumatic disease most strongly associated with lymphoma development 1
• Decreased C4 levels at diagnosis are associated with a higher risk of developing lymphoma 1, 2
• Sjögren's syndrome is associated with excess mortality, mainly related to systemic involvement and lymphoma development 3

Management

Ocular Manifestations

• Tear substitutes are the mainstay of therapy for keratoconjunctivitis sicca 6
• Local and systemic stimulators of tear secretion may be used 6
• Supportive surgical procedures may be considered in severe cases 6

Oral Manifestations

• Intense oral hygiene, prevention and treatment of oral infections 6
• Saliva substitutes to manage xerostomia 6
• Local and systematic stimulation of salivary secretion 6

Systemic Therapy

• Cholinergic agents such as pilocarpine and cevimeline are the cornerstone of current therapy for stimulating secretions 6
• Corticosteroids, cyclophosphamide, and nucleoside analogues are reserved for severe extraglandular manifestations 6
• Anti-B-cell therapy is a promising option for both glandular and extraglandular manifestations 6

Important Considerations

• Co-management with a rheumatologist is essential due to potential systemic complications 1, 2
• Regular monitoring for signs of lymphoma development is recommended, especially in patients with risk factors like decreased C4 levels 1, 2
• Screening for other autoimmune conditions may be warranted 2
• Patient education about the nature of the problem, aggravating factors, and goals of treatment is critical to successful management 2

Key Pitfalls to Avoid

• Overlooking medication-induced hematologic abnormalities in patients on immunosuppressive therapy 1
• Neglecting to screen for lymphoma in patients who develop unexplained hematologic abnormalities 1
• Failing to maintain a high index of suspicion for Sjögren's syndrome in patients with clinically significant dry eye 1
• Missing the diagnosis due to the heterogeneous clinical presentation, which can vary from sicca symptoms to systemic disease 3