What is Sjogren's syndrome?

What is Sjögren's Syndrome

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

Definition and Core Pathophysiology

• The disease fundamentally involves chronic inflammatory cellular infiltration of exocrine glands by lymphocytes, particularly targeting the lacrimal and salivary glands, leading to progressive glandular dysfunction 1, 2
• This lymphocytic infiltration causes secondary compromise of gland function, manifesting as the hallmark sicca symptoms (dryness) 1
• The condition represents a multifactorial autoimmune process caused by the interplay of genetic susceptibility, environmental triggers (particularly viral infections like Epstein-Barr virus), and hormonal factors 2

Epidemiology and Demographics

• Women are overwhelmingly affected with a 20:1 female-to-male ratio, suggesting strong hormonal influences 1, 2
• The disease affects approximately 0.4% of the general population, with an annual incidence of 3.9-5.3 per 100,000 people 1
• It predominantly affects middle-aged women, though it can occur in children, men, and the elderly 3
• Approximately 10% of patients with clinically significant dry eye have underlying Sjögren's syndrome 1

Classification

• Primary Sjögren's syndrome occurs alone as a distinct autoimmune entity 1
• Secondary Sjögren's syndrome occurs in association with other autoimmune diseases such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 1, 4

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 1
• Dry mouth (xerostomia): need for liquids to swallow dry foods, frequent water sipping, burning mouth sensation, angular cheilitis, frequent dental cavities, and gingivitis 1

Systemic Manifestations

• Joint pain (arthralgias) and muscle pain (myalgias) are common musculoskeletal symptoms 1
• Extreme fatigue is a prominent constitutional symptom 1
• Vaginal dryness causing painful intercourse and dry skin causing itchiness or flaking 1
• Peripheral neuropathy manifesting as numbness, changed sensation, or burning pain in extremities 1

Pulmonary Involvement

• Chronic cough affects approximately 38% of patients 1
• Dry, nonproductive cough (xerotrachea) and small airway disease 1
• Bronchiolitis, bronchiectasis, and interstitial lung disease can develop, with ILD prevalence increasing to 20% after 5 years 1

Other Serious Complications

• Ocular manifestations including scleritis, sterile keratitis, and uveitis 1
• Potentially life-threatening vasculitic or lymphoproliferative disorders 1

Diagnostic Approach

Serological Markers

• Anti-SSA/Ro antibody positivity is the most specific marker, scoring 3 points in diagnostic criteria 1, 2
• Anti-SSB/La antibodies, rheumatoid factor, and antinuclear antibodies are also evaluated 1, 5
• Novel early biomarkers (salivary protein 1, carbonic anhydrase 6, parotid secretory protein) may detect disease earlier 1, 5

Diagnostic Criteria (Weighted Scoring System)

• Anti-SSA/Ro antibody positivity: 3 points 1
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² on minor salivary gland biopsy: 3 points 1
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point 1
• Schirmer test result ≤5 mm/5 minutes: 1 point 1
• Unstimulated salivary flow rate ≤0.1 ml/minute: 1 point 1
• A total score of ≥4 meets criteria for primary Sjögren's syndrome in individuals with suggestive signs/symptoms 1

Objective Testing

• Tear film osmolarity measurement and matrix metalloproteinase-9 testing confirm inflammatory dry eye 1
• Slit-lamp biomicroscopy evaluation assessing tear film, conjunctiva, cornea, meniscus height, and punctate staining 1
• Minor salivary gland biopsy if clinical suspicion remains high despite negative initial testing 1

Lymphoma Risk and Monitoring

• Patients have approximately a 5% risk of developing lymphoma, making Sjögren's syndrome the rheumatic disease most strongly associated with lymphoid malignancy 1, 6
• Decreased C4 levels at diagnosis are associated with higher lymphoma risk 1, 6
• Regular monitoring for signs of lymphoma development is essential 1, 6

Management Principles

First-Line Symptomatic Treatment

• Artificial tears and ointments for dry eyes 1
• Saliva substitutes for dry mouth 1
• Cholinergic agents (pilocarpine, cevimeline) are the cornerstone of current therapy 7

Systemic Disease Management

• Antimalarials (hydroxychloroquine) and NSAIDs for mild systemic manifestations with joint pain 1
• For severe, refractory systemic disease, B-cell targeted therapies may be considered 1
• Sequential use of glucocorticoids, immunosuppressive agents, and biologics for organ-specific involvement 1

Critical Management Considerations

• Co-management with a rheumatologist is essential due to potential systemic complications and lymphoma risk 1, 6
• Annual pulmonary function tests for patients with respiratory symptoms 1
• Neurology consultation mandatory when neurological symptoms develop 1

Important Clinical Pitfalls

• Do not overlook Sjögren's syndrome in younger patients or men despite the strong female predominance 2
• Maintain high suspicion when dry eye occurs with systemic symptoms like fatigue, arthralgia, or recurrent parotid swelling 2
• Unexplained chronic cough with dry eyes led to Sjögren's diagnosis in 36% of previously undiagnosed patients 1
• Ophthalmologists and dentists are often the first point of medical contact and should maintain low threshold for serological workup 1, 5