What are the treatment options for Sjögren's syndrome?

Treatment of Sjögren's Syndrome

Treatment of Sjögren's syndrome requires a stepwise approach that distinguishes between managing sicca symptoms and systemic disease manifestations, starting with topical therapies and muscarinic agonists for dryness, while reserving immunosuppression for severe extraglandular disease. 1

General Treatment Framework

A multidisciplinary approach coordinated by specialists in autoimmune diseases is essential, with clear distinction between treating dryness symptoms versus systemic manifestations. 1, 2 Regular assessment using the ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) guides therapeutic decisions and helps tailor treatment to organ-specific severity. 1, 3

Management of Ocular Dryness

First-Line Topical Therapy

• Artificial tears containing methylcellulose or hyaluronate should be applied at least twice daily as initial treatment. 1, 3
• Ocular gels and ointments are recommended for persistent cases, particularly for nighttime use. 1

Advanced Ocular Therapies

• Topical cyclosporine is effective for moderate to severe dry eye and provides anti-inflammatory benefits. 3
• For refractory cases, autologous serum drops (20% concentration) improve ocular irritation symptoms and corneal staining better than artificial tears. 4
• Allogeneic serum eye drops serve as an effective alternative when repeated blood sampling is not feasible. 4

Procedural Interventions for Severe Cases

• Punctal occlusion should follow a stepwise approach: trial with temporary silicone plugs first, then permanent thermal cautery of no more than one punctum per eye per session. 4
• Rigid gas-permeable scleral lenses successfully treat severe dry eye, though fitting difficulties, cost, and patient ability to manage insertion/removal may limit use. 4
• Limited tarsorrhaphy can decrease tear film instability in patients unresponsive to other therapies. 4

Common pitfall: Avoid permanent punctal cautery without first trialing temporary plugs to screen for potential epiphora. 4

Management of Oral Dryness

Mild Salivary Dysfunction

• Non-pharmacological stimulation with sugar-free gum and frequent water sips is recommended as first-line treatment. 1, 2
• Rigorous oral hygiene is essential to prevent infections and dental caries. 1

Moderate Dysfunction with Residual Glandular Function

• Muscarinic agonists (pilocarpine or cevimeline) are the therapy of choice for patients with residual salivary gland function. 1, 2
• Cevimeline is FDA-approved for dry mouth in Sjögren's syndrome and may have fewer systemic side effects than pilocarpine. 4
• Pilocarpine at 5 mg orally four times daily improves ability to focus during reading and blurred vision symptoms, though excessive sweating occurs in over 40% of patients. 4
• These medications bind muscarinic receptors to stimulate salivary and sweat gland secretion, with greater improvement typically seen in dry mouth than dry eye. 4

Severe Dysfunction Without Salivary Production

• Saliva substitutes are recommended when no residual glandular function remains. 1, 2

Management of Systemic Manifestations

Sequential Therapeutic Approach

Treatment should follow a severity-based algorithm: 1, 2, 3

1. Glucocorticoids at minimum effective dose and shortest duration necessary for active systemic disease
2. Immunosuppressive agents (azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide) as steroid-sparing options
3. Biologic therapies (rituximab) for severe, refractory disease

Musculoskeletal Symptoms

• Analgesics should be used according to pain severity, following the WHO analgesic ladder. 1
• Hydroxychloroquine may be prescribed for fatigue and arthralgias, though evidence for dry eye efficacy is limited. 3
• Short-term moderate-dose glucocorticoids may be considered for acute pain. 1

Pulmonary Involvement

• Baseline chest radiography is recommended for all patients to screen for pulmonary involvement. 3
• For interstitial lung disease, systemic corticosteroids at 0.5-1.0 mg/kg serve as first-line treatment, with mycophenolate mofetil or azathioprine as steroid-sparing agents. 1

Special Complications

• Filamentary keratitis can be debrided with moistened cotton-tip applicators and treated with topical N-acetylcysteine 10% to decrease mucinous tear film viscosity. 4
• Self-retaining or sutureless amniotic membrane insertion should be considered for refractory cases, recognizing the short-term effect. 4

Critical pitfall: Avoid prolonged glucocorticoid use without adequate steroid-sparing strategies. 1, 2, 3

Preventive Measures and Monitoring

• Smoking cessation should be strongly recommended for all patients. 1, 3
• Influenza and pneumococcal vaccination should be ensured. 1, 3
• Regular monitoring for lymphoma development (2-5% risk) through clinical examination for lymphadenopathy is recommended, with closer monitoring for patients with decreased C4 levels at diagnosis. 3
• Monitor potential side effects of immunosuppressive medications. 1

Evidence Considerations

The evidence base shows that traditional disease-modifying antirheumatic drugs demonstrate limited efficacy in Sjögren's syndrome overall, and TNF-alpha inhibitors have been disappointing. 5, 6 However, B-cell depleting therapies like rituximab appear more promising for severe systemic disease. 5 A meta-analysis found that while individual immunomodulatory drugs showed no consistent benefit for xerostomia and xerophthalmia, reducing inflammation potentially improves salivary gland function, with increased withdrawals due to adverse events (risk ratio 2.33). 6