Diagnostic Testing for Sjögren's Syndrome
For patients with suspected Sjögren's syndrome, order a complete serological panel including anti-SSA/Ro, anti-SSB/La, rheumatoid factor (RF), and antinuclear antibody (ANA), combined with objective assessment of lacrimal and salivary gland function. 1, 2
Serological Testing
The diagnostic workup centers on autoantibody detection:
- Anti-SSA/Ro antibody is the most critical serological marker, scoring 3 points in the weighted diagnostic criteria 1
- Anti-SSB/La antibody provides additional diagnostic support when combined with other findings 3, 2
- Rheumatoid factor (RF) should be included in the initial panel 1, 3
- Antinuclear antibody (ANA) completes the traditional serological assessment 3, 2
Important caveat: Anti-Ro positivity alone is insufficient for diagnosis but becomes highly significant when combined with clinical manifestations 3. These traditional biomarkers have low specificity for Sjögren's and may be negative in early disease 4.
Objective Ocular Testing
Perform these tests to document dry eye objectively:
- Schirmer test without anesthesia: ≤5 mm/5 minutes scores 1 point in diagnostic criteria 1
- Ocular staining score using rose bengal, lissamine green, or fluorescein: ≥5 (or van Bijsterveld score ≥4) scores 1 point 1
- Tear film break-up time assessment during slit-lamp examination 1, 2
- Tear meniscus height evaluation 1, 3
The slit-lamp examination should specifically assess for punctate epithelial erosions, filaments, mucous plaques, and interpalpebral drying 1.
Objective Salivary Gland Testing
Document oral dryness through:
- Unstimulated whole saliva flow rate: ≤0.1 ml/minute scores 1 point 1
- Minor salivary gland biopsy from the lower lip: focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² scores 3 points 1, 5
The lip biopsy provides direct histological evidence of lymphocytic infiltration and is particularly valuable when serology is negative 6, 5.
Diagnostic Scoring System
A total score of ≥4 points meets criteria for primary Sjögren's syndrome in patients with suggestive signs/symptoms 1:
- Anti-SSA/Ro positive: 3 points
- Lip biopsy with focus score ≥1: 3 points
- Abnormal ocular staining: 1 point
- Schirmer test ≤5 mm: 1 point
- Salivary flow ≤0.1 ml/min: 1 point
Additional Diagnostic Considerations
Physical examination should specifically evaluate for:
- Parotid or submandibular gland enlargement 1, 6
- Joint deformities and Raynaud phenomenon 1
- Cranial nerves V and VII function 1
Emerging biomarkers include antibodies to salivary protein 1 (SP-1), carbonic anhydrase 6 (CA-6), and parotid secretory protein (PSP), which may appear earlier in disease and identify seronegative cases, though additional validation is needed 1, 4.
Critical Exclusions
Before diagnosing Sjögren's syndrome, exclude:
- Hepatitis C virus infection (can cause sicca syndrome without anti-SSA/SSB antibodies) 3, 6
- HIV infection 6, 5
- Pre-existing lymphoma 6
- Checkpoint inhibitor-induced sicca syndrome (only 20% anti-Ro positive with distinct histology) 3
Special Population Warnings
For women of childbearing age with positive anti-Ro/SSA antibodies: Counsel about risk of neonatal lupus and congenital heart block, consider hydroxychloroquine prophylaxis, and arrange serial fetal echocardiograms between weeks 16-26 of pregnancy 3.
Monitoring After Diagnosis
Once diagnosed, patients require:
- Regular monitoring for lymphoma development (approximately 5% lifetime risk, higher with decreased C4 levels at diagnosis) 1, 3
- Screening for systemic complications including pulmonary involvement, peripheral neuropathy, and vasculitis 1, 2
- Co-management with rheumatology due to potential life-threatening complications 1