What are the diagnostic criteria and treatment options for Sjögren’s syndrome?

Sjögren's Syndrome Diagnosis

Diagnose Sjögren's syndrome using the 2016 ACR/EULAR classification criteria, which require a weighted score of ≥4 points from five objective measures: anti-SSA/Ro positivity (3 points), focal lymphocytic sialadenitis with focus score ≥1 foci/4mm² (3 points), abnormal ocular staining score ≥5 (1 point), Schirmer test ≤5mm/5 minutes (1 point), and unstimulated salivary flow ≤0.1 mL/minute (1 point). 1, 2

When to Suspect Sjögren's Syndrome

Maintain high clinical suspicion in the following scenarios:

• Non-elderly women with rapid-onset or severe intrinsic tear production deficiency 1
• Patients with clinically significant dry eye AND dry mouth symptoms occurring together 1
• Approximately 10% of patients with significant dry eye have underlying Sjögren's syndrome 2
• Female-to-male ratio is 20:1, making middle-aged women the highest-risk population 1, 2

Diagnostic Algorithm

Step 1: Initial Serological Testing

Order the following autoantibody panel when Sjögren's is suspected: 1, 3

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

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

Step 2: Objective Ocular Assessment (1 point each)

Perform Schirmer test without anesthesia: 1, 2

• Abnormal result: ≤5 mm in 5 minutes

Perform ocular surface staining: 1, 2

• Abnormal ocular staining score ≥5 (using lissamine green or fluorescein)
• OR van Bijsterveld score ≥4

Step 3: Salivary Gland Assessment (1 point)

Measure unstimulated salivary flow rate: 1, 2

• Abnormal result: ≤0.1 mL/minute

Step 4: Histopathological Confirmation (3 points)

Minor salivary gland biopsy showing: 1, 2

• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm²
• This remains the most helpful diagnostic test alongside serology 4

Step 5: Calculate Total Score

• Anti-SSA/Ro positive: 3 points 1, 2
• Focal lymphocytic sialadenitis (≥1 foci/4mm²): 3 points 1, 2
• Abnormal ocular staining: 1 point 1, 2
• Abnormal Schirmer test: 1 point 1, 2
• Abnormal salivary flow: 1 point 1, 2

Total score ≥4 = Primary Sjögren's syndrome diagnosis 1, 2

Critical Pitfalls to Avoid

Do not rely on symptoms alone - the diagnosis requires objective criteria, as dry eye and dry mouth are extremely common complaints in the general population. 1

Do not skip rheumatology referral - all patients with confirmed or suspected Sjögren's syndrome should be co-managed with a rheumatologist due to serious systemic complications. 1, 2, 5

Screen for lymphoma risk factors - patients with decreased C4 levels at diagnosis have higher risk of developing lymphoma, which occurs in approximately 5% of Sjögren's patients. 1, 2, 3, 5

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Treatment Approach for Sjögren's Syndrome

Begin with topical symptomatic therapies (artificial tears for eyes, saliva substitutes for mouth) as first-line treatment, escalating to systemic immunomodulation only for significant systemic manifestations or severe glandular disease. 2

Treatment Algorithm by Disease Severity

Mild Disease: Sicca Symptoms Only

Ocular dryness management: 1

• Topical lubricants (artificial tears and ointments)
• Topical anti-inflammatory therapy (cyclosporine) for moderate-to-severe dry eye
• Tear-conserving strategies (punctal plugs)

Oral dryness management: 1, 2

• Saliva substitutes
• Oral secretagogues (pilocarpine or cevimeline) - more effective for oral than ocular dryness
• Frequent water sipping
• Sugar-free gum or lozenges

Moderate Disease: Mild Systemic Manifestations

For joint pain and mild systemic symptoms: 2

• Hydroxychloroquine (antimalarial)
• NSAIDs for arthralgias

Important caveat: Evidence for hydroxychloroquine efficacy specifically for dry eye is weak, though it is commonly prescribed for fatigue and arthralgias. 1

Severe Disease: Refractory Systemic Involvement

For severe, refractory systemic disease: 2

• B-cell targeted therapies may be considered
• Sequential approach: glucocorticoids → immunosuppressive agents → biologics
• Evidence for anti-TNF agents is not strong 1
• Evidence for rituximab remains insufficient 1

Pulmonary Manifestations Management

Chronic dry cough (present in ~38% of patients): 1

• First exclude: gastroesophageal reflux, postnasal drip, asthma
• Then consider: humidification, secretagogues, guaifenesin

Small airway disease/bronchiolitis: 1

• Short course systemic steroids (2-4 weeks) with repeat spirometry
• Inhaled bronchodilators and/or corticosteroids if obstruction present
• Empiric macrolide antibiotics (azithromycin 250mg 3 days/week for 2-3 months)

Bronchiectasis: 1

• Mucolytic agents/expectorants
• Nebulized saline or hypertonic saline
• Airway clearance techniques
• Chronic macrolides (if no non-tuberculous mycobacterium)

Smoking cessation is mandatory in all Sjögren's patients. 1

Essential Monitoring and Co-Management

Rheumatology co-management is non-negotiable due to: 1, 2, 5

• 5% risk of lymphoma development
• Risk of vasculitic disorders
• Potential for other ocular manifestations (scleritis, sterile keratitis, uveitis)
• Association with other autoimmune diseases

Patient education is critical regarding disease nature, aggravating factors, and treatment goals. 1

Regular monitoring for lymphoproliferative disorders, especially in patients with low C4 levels at diagnosis. 1, 2, 5