What is the recommended workup and treatment for a patient suspected of having Sjögren's syndrome?

Workup for Sjögren's Syndrome

Begin with a detailed symptom assessment focusing on sicca manifestations (dry eyes, dry mouth) and systemic features, followed by serologic testing for anti-SSA/Ro and anti-SSB/La antibodies, ANA, and RF, combined with objective assessment of lacrimal and salivary gland function. 1, 2

Initial Clinical Assessment

Key Symptom Screening

Oral symptoms to specifically query: 3

• Persistent daily dry mouth for >3 months
• Need for liquids to swallow dry foods
• Frequent sipping/drinking of water throughout the day
• Burning sensation in the mouth
• Angular cheilitis (painful sores or red patches at mouth corners)
• Frequent dental cavities, particularly gumline cavities
• Teeth chipping, cracking, or erosion
• Gum inflammation or receding gums

Ocular symptoms to specifically query: 3

• Daily dry, irritated, itchy, or painful eyes
• Foreign body sensation in the eyes
• Light sensitivity
• Frequent use of eye drops for dryness
• Blurry vision or unexplained vision changes

Systemic manifestations to assess: 3

• Parotid or submandibular gland swelling
• Vaginal dryness causing painful intercourse
• Peripheral neuropathy (numbness, burning pain in extremities)
• Extreme fatigue
• Joint or muscle pain (arthralgias, myalgias)
• Raynaud's phenomenon (fingers turning pale/blue in cold)

Physical Examination Findings

Focus on these specific findings: 4

• Lacrimal gland enlargement
• Parotid or submandibular gland swelling
• Joint deformities
• Raynaud's phenomenon in hands
• Cranial nerve V and VII function assessment

Serologic Testing

Order the following antibodies as first-line testing: 1, 2

• Anti-SSA/Ro antibodies (most important—scores 3 points toward diagnosis)
• Anti-SSB/La antibodies
• Antinuclear antibodies (ANA)
• Rheumatoid factor (RF)

Note that anti-SSA/Ro positivity alone can meet diagnostic threshold when combined with minimal objective findings, but approximately 30-40% of Sjögren's patients may be seronegative. 4

Objective Ocular Testing

Perform these standardized assessments: 1, 4

• Schirmer test without anesthesia: ≤5 mm/5 minutes scores 1 point toward diagnosis 4
• Ocular surface staining: Ocular staining score ≥5 (or van Bijsterveld score ≥4) scores 1 point 4
• Tear film osmolarity measurement using FDA-approved commercial devices 4
• Point-of-care matrix metalloproteinase-9 testing to confirm inflammatory dry eye 4
• Tear break-up time assessment and tear meniscus height evaluation 4

Slit-lamp biomicroscopy should specifically assess: 4

• Tear film meniscus height, debris, viscosity
• Mucous strands, foam, break-up time and pattern
• Punctate staining patterns with rose bengal, lissamine green, or fluorescein
• Conjunctival hyperemia, localized drying, keratinization
• Corneal punctate epithelial erosions, filaments, epithelial defects

Salivary Gland Assessment

Measure unstimulated whole salivary flow rate: ≤0.1 mL/minute scores 1 point toward diagnosis 4

Consider minor salivary gland biopsy when: 4, 5

• Clinical suspicion remains high despite negative or equivocal serology
• Looking for focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (scores 3 points)
• Avoid biopsy if patient has been on immunosuppression >6 weeks, as this significantly reduces diagnostic yield 5
• Patients with both sicca symptoms AND positive serology have 75% likelihood of positive biopsy, making biopsy potentially unnecessary in this subset 5

Pulmonary Evaluation (If Respiratory Symptoms Present)

Baseline chest imaging and pulmonary function testing are mandatory: 3, 1, 2

• Baseline chest radiography for all suspected Sjögren's patients 1
• High-resolution CT (HRCT) with expiratory views if respiratory symptoms present or if lymphoproliferative disease suspected 3, 4
• Complete pulmonary function tests (PFTs) including:
  • Spirometry
  • Lung volumes by body plethysmography
  • Diffusing capacity (DLCO)
  • Oxygen saturations at rest and with exercise 3

Specific indications for pulmonary workup: 3, 4

• Chronic cough >8 weeks duration (affects 38% of Sjögren's patients)
• Unexplained dyspnea on exertion
• Dry, nonproductive cough suggesting xerotrachea

If pulmonary involvement confirmed, repeat PFTs every 3-6 months initially for at least 1 year to establish disease trajectory. 3, 1

Lymphoma Surveillance

Actively monitor for these red flags requiring further investigation: 3

• Unexplained weight loss
• Fevers or night sweats
• Head and neck lymphadenopathy
• Persistent or progressive parotitis
• Pulmonary nodules >8 mm
• Growing lung nodules or progressive cystic lung disease

If lymphoproliferative disease suspected: 3

• PET scan for pulmonary lesions (nodules >8 mm, consolidations, lymphadenopathy)
• Biopsy for lymphadenopathy, growing nodules, or progressive cystic disease
• Note that PET-avid parotitis (SUV ≥4.7) with lung nodules is particularly concerning

Risk stratification: Approximately 5% lifetime lymphoma risk, with decreased C4 levels at diagnosis indicating higher risk. 4

Diagnostic Scoring System

A total score of ≥4 points meets criteria for primary Sjögren's syndrome: 4

• Anti-SSA/Ro antibody positive: 3 points
• Focal lymphocytic sialadenitis (focus score ≥1 foci/4 mm²): 3 points
• Ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point
• Schirmer test ≤5 mm/5 minutes: 1 point
• Unstimulated salivary flow ≤0.1 mL/minute: 1 point

Essential Referrals

Mandatory rheumatology consultation for all confirmed or highly suspected cases due to: 4

• 5% lifetime lymphoma risk (320 cases per 100,000 patient-years increased incidence)
• Need for systemic disease monitoring using ESSDAI (systemic activity) and ESSPRI (patient-reported symptoms) 1
• Potential need for systemic immunosuppression

Ophthalmology referral for ongoing management of ocular complications and monitoring for corneal damage. 2

Pulmonology referral if respiratory symptoms, abnormal PFTs, or concerning chest imaging findings. 1, 2

Common Pitfalls to Avoid

• Do not rely solely on serology—approximately 30-40% of Sjögren's patients are anti-SSA/Ro negative but can still meet diagnostic criteria with objective testing 4
• Avoid lip biopsy in patients on immunosuppression >6 weeks—significantly reduces diagnostic yield 5
• Do not order plain chest X-ray when lymphoproliferative disease suspected—HRCT is superior and recommended 3
• Do not delay rheumatology referral—systemic complications including lymphoma require specialist monitoring 4
• Avoid anticholinergic medications in confirmed Sjögren's patients as they worsen sicca symptoms 3