How to evaluate for Sjogren's syndrome?

Evaluation for Sjögren's Syndrome

The comprehensive evaluation for Sjögren's syndrome requires assessment of sicca symptoms, physical examination for glandular involvement, specific serologic testing, and objective measures of gland function to establish diagnosis and guide treatment decisions. 1

Initial Clinical Assessment

Key Symptoms to Evaluate

Oral Symptoms

• Dry mouth (xerostomia)
• Need for liquids to swallow dry foods
• Frequent water sipping
• Burning sensation in the mouth
• Angular cheilitis (painful sores/red patches at mouth corners)
• Frequent dental cavities, particularly at gumline
• Teeth chipping, cracking, or surface erosion
• Gum inflammation/receding gums

Ocular Symptoms

• Dry, irritated, itchy, or painful eyes
• Foreign body sensation
• Light sensitivity
• Frequent use of eye drops
• Blurry vision or unexplained vision changes

Other Key Symptoms

• Gland swelling in face or along jawline (parotid/submandibular)
• Vaginal dryness or skin dryness
• Peripheral neuropathy (numbness, tingling, burning pain in extremities)
• Extreme fatigue
• Joint or muscle pain (arthralgias, myalgias)
• Raynaud's phenomenon (fingers turning pale/blue in cold)
• Chronic dry cough 1

Diagnostic Testing Algorithm

Step 1: Serologic Evaluation

• Traditional biomarkers:

  • Anti-SSA/Ro antibodies
  • Anti-SSB/La antibodies
  • Antinuclear antibody (ANA) titers
  • Rheumatoid factor (RF) 2

• Consider newer biomarkers (may appear earlier in disease course):

  • Antibodies to SP-1 (salivary gland protein-1)
  • Antibodies to PSP (parotid secretory protein)
  • Antibodies to CA-6 (carbonic anhydrase VI) 2

Step 2: Objective Assessment of Gland Function

Ocular Tests

• Schirmer's test (measures tear production; ≤5 mm/5 min is positive)
• Rose bengal or lissamine green staining (evaluates corneal and conjunctival damage)
• Tear film break-up time 3

Oral Tests

• Unstimulated whole saliva flow rate
• Stimulated parotid flow rate (≤1 cc/5 min/gland is abnormal)
• Sialography (if available)
• Salivary gland ultrasonography 3, 4

Step 3: Histopathologic Examination

• Minor salivary gland biopsy (lower lip):
  • Focal lymphocytic sialadenitis with focus score ≥1 (defined as ≥50 lymphocytes per 4 mm² of glandular tissue)
  • This is considered the gold standard for diagnosis 3, 4

Step 4: Evaluation for Systemic Manifestations

• Complete blood count
• Comprehensive metabolic panel
• Erythrocyte sedimentation rate and C-reactive protein
• Immunoglobulin levels (to assess for hypergammaglobulinemia)
• Complement levels (C3, C4)
• Cryoglobulins
• Urinalysis 4

Pulmonary Assessment (if respiratory symptoms present)

• Pulmonary function tests (PFTs)
• High-resolution CT (HRCT) imaging
• Consider expiratory views if small airway disease is suspected 1

Diagnostic Criteria

Current American College of Rheumatology criteria require:

• Signs/symptoms suggestive of Sjögren's syndrome
• At least two objective factors:
  1. Positive traditional biomarkers
  2. Positive salivary gland biopsy findings
  3. Presence of keratoconjunctivitis sicca 2

Important Clinical Pitfalls to Avoid

1. Delayed diagnosis - The non-specific and variable nature of symptoms often leads to diagnostic delays. Maintain high clinical suspicion when sicca symptoms are present 2

2. Overlooking systemic manifestations - Sjögren's is not just a disease of dryness; it can affect virtually any organ system 4

3. Missing early disease - Traditional biomarkers may be negative in early disease; consider newer biomarkers or repeat testing if clinical suspicion is high 2

4. Failure to differentiate primary vs. secondary Sjögren's - Always evaluate for other autoimmune conditions (especially rheumatoid arthritis, systemic lupus erythematosus) 4

5. Inadequate biopsy technique - Ensure adequate tissue sampling (4-6 minor salivary glands) and proper histopathologic evaluation 3

6. Overlooking medications that cause sicca symptoms - Always review medications that may cause dryness (antihistamines, antidepressants, antihypertensives) 3

7. Not considering lymphoma risk - Sjögren's patients have increased risk of lymphoma; persistent glandular enlargement requires evaluation 4

By following this systematic approach to evaluation, clinicians can establish an accurate diagnosis of Sjögren's syndrome, allowing for appropriate treatment and monitoring to improve morbidity, mortality, and quality of life outcomes.