What are the symptoms and diagnosis of Sjogren syndrome?

Sjögren Syndrome: Symptoms and Diagnosis

Primary Clinical Symptoms

Sjögren syndrome presents with characteristic sicca symptoms—dry eyes and dry mouth—along with systemic manifestations that can affect multiple organ systems. 1

Sicca Symptoms (Dryness)

Ocular manifestations include: 1

• Foreign body sensation in the eyes
• Eye irritation, itchiness, or pain
• Light sensitivity (photophobia)
• Frequent need for eye drops

Oral manifestations include: 1

• Xerostomia (dry mouth) requiring liquids to swallow dry foods
• Frequent sipping or drinking of water throughout the day
• Burning sensation in the mouth
• Angular cheilitis (painful sores or red patches at corners of mouth)
• Frequent dental cavities and gum inflammation or recession

Systemic Manifestations

Musculoskeletal symptoms include joint pain (arthralgias) and muscle pain (myalgias). 1

Mucocutaneous symptoms include: 1

• Vaginal dryness causing painful intercourse
• Dry skin with itchiness or flaking

Neurological symptoms include peripheral neuropathy presenting as numbness, altered sensation, or burning pain in feet, legs, or hands. 1

Constitutional symptoms include extreme fatigue, which is commonly reported. 1

Pulmonary involvement may manifest as dry, nonproductive cough (xerotrachea) and small airway disease. 1

Diagnostic Approach

Clinical Examination

The slit-lamp biomicroscopy evaluation should assess: 2

• Tear film: meniscus height, debris, viscosity, mucous strands, foam, break-up time and pattern
• Conjunctiva: punctate staining with rose bengal, lissamine green, or fluorescein dyes; hyperemia; localized drying; keratinization
• Cornea: interpalpebral drying, punctate epithelial erosions, filaments, epithelial defects, mucous plaques

Physical examination should evaluate: 2

• Adnexa: enlargement of lacrimal glands
• Hands: joint deformities characteristic of rheumatoid arthritis, Raynaud phenomenon
• Cranial nerve function: particularly cranial nerves V (trigeminal) and VII (facial)

Serological Testing

For patients with clinically significant dry eye and dry mouth, serological examination should include: 2

• Anti-Sjögren syndrome A antibody (SSA or anti-Ro)
• Anti-Sjögren syndrome B antibody (SSB or anti-La)
• Rheumatoid factor
• Antinuclear antibody (ANA)

A point-of-care test is now available that includes traditional serology plus additional biomarkers (salivary protein 1, carbonic anhydrase 6, and parotid secretory protein), though additional studies are needed to validate these markers. 2

Diagnostic Criteria (Weighted Scoring System)

The current classification criteria use a point-based system where ≥4 points confirms primary Sjögren syndrome: 1

• Anti-SSA/Ro antibody positivity: 3 points 1
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm²: 3 points 1
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point 1
• Schirmer test result ≤5 mm/5 minutes without anesthesia: 1 point 1
• Unstimulated salivary flow rate ≤0.1 ml/minute: 1 point 1

Histopathological Confirmation

Minor salivary gland biopsy remains the cornerstone for diagnosis, demonstrating characteristic focal infiltration of B- and T-lymphocytes, though it is not mandatory if other criteria are met. 3 The biopsy may also have prognostic value, as more complex infiltrates correlate with severe disease. 3

Important Clinical Considerations

Seronegative Disease

Approximately 20-30% of patients are "seronegative" for specific autoantibodies (ANA, anti-Ro/SSA, anti-La/SSB), and these patients may require alternative diagnostic approaches including mandatory biopsy or newer biomarkers. 3

Classification

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

Lymphoma Risk

Patients carry approximately a 5% risk of developing lymphoma, making this a critical consideration in diagnosis and follow-up. 1 Decreased C4 levels at diagnosis are associated with higher lymphoma risk. 1

Co-Management Requirements

Co-management with a rheumatologist is essential due to potential systemic complications, lymphoproliferative disorders, and the need for regular monitoring for lymphoma development. 1

Common Diagnostic Pitfalls

• Failing to maintain high suspicion for Sjögren syndrome in patients with clinically significant dry eye (approximately 10% have underlying Sjögren syndrome) 1
• Overlooking the diagnosis in seronegative patients who meet other clinical and histological criteria 3
• Not screening for associated autoimmune conditions in patients with confirmed Sjögren syndrome 4
• Misinterpreting salivary gland biopsy results due to incorrect biopsy technique or failure to determine average focus score 5