What is Sjögren's syndrome and what are its symptoms and treatment options, particularly for a middle-aged woman presenting with dry eyes and dry mouth?

Sjögren's Syndrome and Sicca Syndrome Overview

Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands, resulting in the hallmark sicca symptoms of dry eyes (xerophthalmia) and dry mouth (xerostomia), predominantly affecting middle-aged women with a 20:1 female-to-male ratio. 1, 2

Definition and Core Pathophysiology

Sicca syndrome refers to the constellation of dryness symptoms—primarily dry eyes and dry mouth—that can occur from various causes. 3, 4

Sjögren's syndrome is the autoimmune disease that causes sicca symptoms through a specific mechanism: chronic inflammatory lymphocytic infiltration of exocrine glands (particularly lacrimal and salivary glands), leading to progressive destruction of functional epithelium and loss of secretory capacity. 2, 5, 3

The disease exists in two forms:

• Primary Sjögren's syndrome: Occurs as an isolated autoimmune condition 1, 2
• Secondary Sjögren's syndrome: Occurs alongside other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma 1, 2

Clinical Presentation

Primary Sicca Symptoms

Dry eyes (keratoconjunctivitis sicca) manifest as:

• Foreign body sensation in the eyes 2
• Eye irritation, itchiness, or pain 2
• Light sensitivity 2
• Frequent need for artificial tears 2

Dry mouth (xerostomia) presents with:

• Need for liquids to swallow dry foods 2
• Frequent sipping or drinking of water 2
• Burning sensation in the mouth 2
• Angular cheilitis (painful sores at mouth corners) 2
• Frequent dental cavities and gum disease 2

Systemic Manifestations Beyond Sicca

Musculoskeletal symptoms include joint pain (arthralgias) and muscle pain (myalgias). 2

Mucocutaneous involvement presents as vaginal dryness causing painful intercourse and dry, itchy, or flaking skin. 2

Neurological complications include peripheral neuropathy with numbness, altered sensation, or burning pain in extremities. 2

Constitutional symptoms feature extreme, debilitating fatigue. 2

Pulmonary manifestations affect approximately 38% of patients and include:

• Chronic dry cough (xerotrachea) 2
• Small airway disease (bronchiolitis) 2
• Bronchiectasis with chronic sputum production 2
• Interstitial lung disease developing in 10% within the first year, 20% after 5 years 2

Diagnostic Criteria

The current classification system uses a weighted scoring approach where a total score ≥4 establishes the diagnosis of primary Sjögren's syndrome. 1, 2

Scoring System (Need ≥4 Points)

High-value criteria (3 points each):

• Anti-SSA/Ro antibody positivity 1, 2
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² on minor salivary gland biopsy 1, 2

Standard criteria (1 point each):

• Abnormal ocular staining score ≥5 (or van Bijsterveld score ≥4) 1, 2
• Schirmer test result ≤5 mm/5 minutes without anesthesia 1, 2
• Unstimulated salivary flow rate ≤0.1 ml/minute 1, 2

When to Suspect Sjögren's Syndrome

Maintain high clinical suspicion in non-elderly women with intrinsic tear-production deficiency, especially if rapid in onset or marked in severity. 1

Approximately 10% of patients with clinically significant aqueous-deficient dry eye have underlying Sjögren's syndrome, warranting a low threshold for serological workup. 2, 5

Critical Complications and Prognosis

Lymphoma Risk

Patients with Sjögren's syndrome carry approximately a 5% lifetime risk of developing lymphoid malignancy, representing the strongest association between any rheumatic disease and lymphoma. 2, 6, 5

Decreased C4 complement levels at diagnosis identify patients at higher risk for lymphoma development. 1, 2, 6

Other Serious Complications

Ocular complications beyond dry eye include scleritis, sterile keratitis, and uveitis. 1

Life-threatening systemic complications include vasculitic disorders and lymphoproliferative disease. 1

Treatment Approach

First-Line Symptomatic Management

For dry eyes, the treatment hierarchy begins with:

• Topical lubricants (artificial tears and ointments) as first-line therapy 1, 2
• Topical anti-inflammatory therapy (cyclosporine) for moderate to severe dry eye 1
• Tear-conserving strategies (punctal plugs) 1

For dry mouth, initial management includes:

• Saliva substitutes for symptomatic relief 2
• Oral secretagogues (pilocarpine or cevimeline) are FDA-approved and demonstrate greater efficacy for oral dryness than ocular dryness 1, 7, 8

Systemic Therapy Considerations

For mild systemic manifestations:

• Hydroxychloroquine may be considered for fatigue and arthralgias, though evidence for dry eye efficacy is weak 1, 2
• NSAIDs for joint pain and inflammation 2

For severe, refractory systemic disease:

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

Important caveat: Anti-tumor necrosis factor agents have not demonstrated efficacy in Sjögren's syndrome. 1

Common Adverse Effects of Oral Secretagogues

Cevimeline side effects (occurring in >10% of patients) include excessive sweating (18.7%), nausea (13.8%), rhinitis (11.2%), and diarrhea (10.3%). 7

Pilocarpine carries similar cholinergic side effects. 8

Essential Management Principles

Co-management with a rheumatologist is mandatory for all patients with Sjögren's syndrome due to the risk of systemic complications and lymphoma. 1, 2, 6

Annual pulmonary function testing is recommended for patients with respiratory symptoms. 2

Regular monitoring for lymphoma development is essential, particularly in patients with decreased C4 levels or other risk factors. 2, 6

Patient education about disease nature, aggravating factors, and treatment goals is critical to successful management. 1

Key Clinical Pitfalls to Avoid

Do not overlook Sjögren's syndrome in younger patients or men despite the strong female and postmenopausal predominance, as the disease can occur in all demographics. 2

Do not dismiss chronic cough in Sjögren's patients—unexplained chronic cough with dry eyes led to Sjögren's diagnosis in 36% of previously undiagnosed patients. 2

Do not neglect screening for lymphoma in patients who develop unexplained hematologic abnormalities or persistent lymphadenopathy. 6

Maintain high suspicion when sicca symptoms occur following viral infections, particularly Epstein-Barr virus, hepatitis C, or HIV. 5