How is Sjogren's syndrome diagnosed in a patient with Rheumatoid Arthritis (RA) and symptoms of dry eyes and burning mouth pain?

Diagnosis of Sjögren's Syndrome

Sjögren's syndrome is diagnosed using a weighted scoring system requiring ≥4 points from objective criteria: anti-SSA/Ro antibody positivity (3 points), focal lymphocytic sialadenitis on minor salivary gland biopsy with focus score ≥1 foci/4 mm² (3 points), abnormal ocular staining score ≥5 (1 point), Schirmer test ≤5 mm/5 minutes (1 point), or unstimulated salivary flow rate ≤0.1 ml/minute (1 point). 1

Clinical Suspicion and Initial Assessment

Maintain high suspicion for Sjögren's syndrome in any patient with both clinically significant dry eye and dry mouth symptoms. 2 Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren's syndrome. 1

Key Symptoms to Elicit:

Dry Eye Manifestations:

• Foreign body sensation, eye irritation, itchiness, or pain 1
• Light sensitivity 1
• Frequent use of eye drops for irritation or dryness 1

Dry Mouth Manifestations:

• Need for liquids to swallow dry foods 1
• Frequent sipping/drinking of water 1
• Burning sensation in mouth 1
• Angular cheilitis (painful sores or red patches at corners of mouth) 1
• Frequent dental cavities and gum inflammation 1

Systemic Symptoms:

• Joint pain (arthralgias) and muscle pain (myalgias) 1
• Extreme fatigue 1
• Peripheral neuropathy (numbness, burning pain in extremities) 1
• Dry, nonproductive cough 1

Physical Examination Findings

Slit-Lamp Biomicroscopy:

• Reduced tear meniscus height along inferior eyelid 2
• Abnormal tear break-up time and pattern 2
• Punctate staining with fluorescein, lissamine green, or rose bengal dyes on conjunctiva and cornea 2
• Lissamine green staining of conjunctiva may aid in early diagnosis 2

External Examination:

• Enlargement of lacrimal glands 2
• Joint deformities characteristic of rheumatoid arthritis (ulnar deviation of fingers) 2
• Raynaud phenomenon 2

Serological Testing

Order a complete serological panel when Sjögren's syndrome is suspected: 1, 3

• Anti-SSA/Ro antibody (most important—scores 3 points if positive) 1
• Anti-SSB/La antibody 3
• Rheumatoid factor (RF) 2, 3
• Antinuclear antibody (ANA) 3

Critical Note: Anti-SSA/Ro antibody positivity is the single most valuable serological marker, but a negative result does NOT exclude Sjögren's syndrome—diagnosis can still be made with ≥4 points from other objective criteria. 1

Objective Diagnostic Tests

Ocular Surface Testing:

• Schirmer test without anesthesia: ≤5 mm/5 minutes scores 1 point 1
• Ocular staining score: ≥5 (or van Bijsterveld score ≥4) scores 1 point 1
• Tear film osmolarity measurement using FDA-approved devices 1
• Point-of-care matrix metalloproteinase-9 testing for inflammatory dry eye 1

Salivary Gland Assessment:

• Unstimulated whole salivary flow rate: ≤0.1 ml/minute scores 1 point 1
• Minor salivary gland biopsy if clinical suspicion remains high: focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² scores 3 points 1

Point-of-Care Salivary Biomarkers:

• Salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP) may indicate early Sjögren's syndrome, though additional validation studies are needed 1

Classification: Primary vs. Secondary Sjögren's Syndrome

• Primary Sjögren's syndrome: Occurs alone as a distinct entity 1
• Secondary Sjögren's syndrome: Occurs with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma 1, 4

In your patient with RA and dry eyes/burning mouth, you are evaluating for secondary Sjögren's syndrome. 5

Mandatory Rheumatology Referral

Co-management with a rheumatologist is essential due to: 1

• Approximately 5% lifetime risk of developing lymphoma (320 cases per 100,000 patient-years increased incidence) 1
• Decreased C4 levels at diagnosis indicate higher lymphoma risk 1, 3
• Potential for life-threatening vasculitic or lymphoproliferative disorders 1
• Need for systemic immunosuppressive therapy for extraglandular manifestations 1

Important Caveats

Differential Diagnoses to Consider:

• HCV-related sicca syndrome (differentiated by absence of anti-SSA/SSB antibodies) 3
• Checkpoint inhibitor-induced sicca syndrome (only 20% anti-Ro positive with distinct histological patterns) 3
• Medication-induced dry eyes/mouth (antihistamines, diuretics, antidepressants, anticholinergics) 2

Special Considerations:

• In women of childbearing age with positive anti-Ro/SSA antibodies, counsel about risk of neonatal lupus and congenital heart block 3
• Anti-Ro/SSA antibodies can be present in systemic lupus erythematosus, not just Sjögren's syndrome 3

Pulmonary Evaluation if Respiratory Symptoms Present

If the patient reports chronic cough or dyspnea: 1

• High-resolution CT chest with expiratory views 1
• Baseline pulmonary function tests 1
• Oximetry testing at rest and with exercise 1

Chronic cough affects approximately 38% of patients with Sjögren's syndrome, and unexplained chronic cough with dry eyes led to Sjögren's diagnosis in 36% of previously undiagnosed patients. 1