What is Sjogren's disease?

What is Sjögren's Syndrome?

Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands, causing dry eyes and dry mouth, with potential for serious systemic complications including a 5% risk of lymphoma. 1, 2

Definition and Core Pathophysiology

• The American College of Rheumatology defines Sjögren's syndrome as an autoimmune disorder marked by chronic inflammatory cellular infiltration of exocrine glands, particularly the lacrimal and salivary glands, resulting in diminished tear and saliva production 1
• This lymphocytic infiltration leads to secondary compromise of gland function, manifesting as the hallmark sicca symptoms (dryness) 2

Epidemiology

• Affects approximately 0.4% of the general population with an annual incidence of 3.9-5.3 per 100,000 people 2
• Women are disproportionately affected with a female-to-male ratio of 20:1 2, 3
• About 10% of patients with clinically significant dry eye have underlying Sjögren's syndrome 2

Classification Types

Primary Sjögren's Syndrome

• Occurs alone as a distinct entity without other autoimmune diseases 1, 2

Secondary Sjögren's Syndrome

• Develops in association with other autoimmune conditions such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 1, 2

Clinical Manifestations

Primary Sicca Symptoms

• Dry eyes (keratoconjunctivitis sicca): sensation of foreign body, eye irritation, itchiness, pain, light sensitivity, and frequent need for eye drops 2
• Dry mouth (xerostomia): need for liquids to swallow dry foods, frequent water sipping, burning mouth sensation, angular cheilitis, frequent dental cavities, and gingivitis 2

Systemic Manifestations Beyond Glands

• Joint pain (arthralgias) and muscle pain (myalgias) are common musculoskeletal features 1, 2
• Extreme fatigue is a prominent constitutional symptom 1, 2
• Peripheral neuropathy causing numbness, altered sensation, or burning pain in extremities 2
• Vaginal dryness and dry skin with itchiness or flaking 2
• Pulmonary involvement including dry nonproductive cough and small airway disease 2
• Potential involvement of kidneys, liver, nervous system, and vasculature 1

Diagnostic Approach

Key Serological Markers

• Anti-SSA/Ro and anti-La/SSB autoantibodies are key diagnostic markers 1

Classification Criteria (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 criteria for primary Sjögren's syndrome in individuals with suggestive signs/symptoms 2

Serious Complications and Risks

Lymphoma Risk

• Approximately 5% of patients will develop lymphoid malignancy, representing the highest lymphoma risk among all rheumatic diseases 1, 2
• Primary Sjögren's syndrome has an incidence rate of lymphoma of 18.9% (95% CI, 9.4–37.9) in meta-analysis 1
• Decreased C4 levels at diagnosis are associated with higher lymphoma risk and require closer monitoring 1, 2, 3

Other Serious Manifestations

• Potentially life-threatening vasculitic disorders 2
• Other ocular manifestations including scleritis, sterile keratitis, and uveitis 2

Associated Autoimmune Conditions

• Thyroid dysfunction or autoimmune thyroiditis 3
• Primary biliary cholangitis (8% in limited cutaneous systemic sclerosis with anti-centromere antibodies) 3

Management Principles

First-Line Symptomatic Treatment

• The European League Against Rheumatism recommends topical therapies as first-line treatment: artificial tears and ointments for dry eyes, saliva substitutes for dry mouth 2

Mild Systemic Disease

• Consider antimalarials such as hydroxychloroquine 2
• NSAIDs for joint pain and inflammation 2

Severe Refractory Systemic Disease

• B-cell targeted therapies may be considered 2
• Sequential use of glucocorticoids, immunosuppressive agents, and biologics for organ-specific involvement 2

Cholinergic Agents

• Pilocarpine and cevimeline are helpful in patients with residual salivary function 2, 4

Essential Management Considerations

• Co-management with a rheumatologist is essential due to potential systemic complications and lymphoma risk 1, 2, 3
• Regular monitoring for signs of lymphoma development is recommended 2, 3
• Screening for other autoimmune conditions may be warranted 2, 3
• Ophthalmologists should maintain high index of suspicion for Sjögren's syndrome in patients with clinically significant dry eye and have low threshold for serological workup 1

Critical 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, especially with decreased C4 levels 1
• Failing to recognize that about 10% of patients with significant dry eye have underlying Sjögren's syndrome 2