Treatment of Sjögren's Syndrome
Treatment of Sjögren's syndrome should follow a structured, symptom-based approach starting with topical therapies for sicca features, followed by muscarinic agonists for patients with residual gland function, and escalating to systemic immunosuppression only for active systemic disease with ESSDAI score >5. 1, 2
Management Framework
The therapeutic approach must clearly distinguish between treating sicca symptoms versus systemic disease—these require fundamentally different strategies. 1, 2 Treatment decisions should be guided by the ESSDAI (European League Against Rheumatism Sjögren's Syndrome Disease Activity Index) for systemic manifestations. 1
Ocular Dryness Management
First-Line Therapy
- Artificial tears containing methylcellulose or hyaluronate at least twice daily (increase frequency up to hourly as needed based on symptoms). 1, 2
- Use preservative-free formulations if applying ≥4 times daily to avoid toxicity. 1
- Apply ophthalmic ointments at bedtime for overnight symptom control (causes blurred vision, so nighttime use only). 1
Refractory Ocular Dryness Algorithm
For patients failing standard artificial tears with OSS (Ocular Staining Score) >3:
- Topical cyclosporine 0.05% for moderate-to-severe keratoconjunctivitis sicca 1, 3
- Topical corticosteroids or NSAIDs for short-term use only (2-4 weeks maximum) due to risk of corneal melts, perforation, increased intraocular pressure, and cataracts 1
- Autologous serum eye drops for severe refractory cases 1, 2
- Punctal plugs as rescue therapy 1
Critical caveat: Refractory cases must be managed by an ophthalmologist experienced in corneal disease, as complications can be vision-threatening. 1
Oral Dryness Management
Stratified by Residual Gland Function
Mild dysfunction (residual salivary flow present):
- Non-pharmacological stimulation: sugar-free gum, frequent water sips, avoid anticholinergic medications 2, 4
- Rigorous oral hygiene to prevent caries and candidiasis 4
Moderate dysfunction (some residual function):
- Pilocarpine 5mg three to four times daily or cevimeline 30mg three times daily 1, 3, 5
- These muscarinic agonists showed 61-76% improvement in dry mouth versus 24-37% with placebo 3
- Common side effects: sweating, nausea, urinary frequency 3
Severe dysfunction (no salivary output):
Constitutional Symptoms (Fatigue and Pain)
Evaluation First
- Rule out contributing conditions: hypothyroidism, anemia, depression, fibromyalgia, sleep disorders 1, 2
- Distinguish inflammatory versus non-inflammatory pain 1
Pain Management
For inflammatory musculoskeletal pain:
- Analgesics following WHO pain ladder 1, 2
- Short-term moderate-dose glucocorticoids (e.g., prednisone 10-20mg daily for 2-4 weeks) for acute flares 1, 2
- Avoid repeated NSAIDs or prolonged glucocorticoids for chronic non-inflammatory pain 1
For chronic non-inflammatory pain:
- Physical activity and aerobic exercise as first-line intervention 1
- Consider gabapentin, pregabalin, or amitriptyline for neuropathic pain (caution: may worsen dryness) 1
- Never use opioids 1
Fatigue Management
- Non-pharmacological approaches preferred 1
- No biologic agents (anakinra, epratuzumab, abatacept) have proven efficacy for fatigue alone 1
Systemic Disease Management
Systemic therapies should be restricted to patients with active systemic disease defined as ESSDAI score >5 or at least moderate activity in one clinical domain. 1, 2
Sequential Treatment Algorithm
Step 1: Glucocorticoids for Initial Control
- Use minimum effective dose and shortest duration necessary 1, 4
- Typical dosing: prednisone 0.5-1.0 mg/kg for severe manifestations 2
Step 2: Immunosuppressive Agents as Steroid-Sparing Therapy
- Options include: mycophenolate mofetil, azathioprine, methotrexate, leflunomide, or cyclophosphamide 1, 2
- No head-to-head trials exist comparing these agents; choice based on organ involvement, comorbidities, and safety profile 1
- Evidence quality is modest (all studies <50 patients with 41-100% adverse event rates) 1
Step 3: Biologic Therapies for Refractory Disease
- Rituximab for severe, refractory systemic manifestations 1
- Anti-TNF agents (infliximab, etanercept) have failed to show efficacy and should not be used 1, 3
- Abatacept and belimumab remain investigational 1
Organ-Specific Considerations
Interstitial Lung Disease (ILD):
- First-line: Systemic corticosteroids 0.5-1.0 mg/kg 2
- Maintenance: Mycophenolate mofetil or azathioprine as steroid-sparing agents 1, 2
- Second-line for progressive fibrotic ILD: Nintedanib (antifibrotic therapy) 1, 2
- Rapidly progressive/acute respiratory failure: IV methylprednisolone plus rituximab or cyclophosphamide 1
Critical warning: Multiple medications used in Sjögren's can cause drug-induced ILD (rituximab, cyclophosphamide, methotrexate, leflunomide, sulfasalazine, TNF-inhibitors)—maintain high suspicion if patients worsen on therapy. 1
Common Pitfalls to Avoid
Failing to distinguish sicca treatment from systemic disease treatment—these require completely different approaches 2, 4, 6
Prolonged glucocorticoid use without steroid-sparing agents—always add immunosuppressive agents for maintenance 1, 4, 6
Using immunosuppression for sicca symptoms alone—topical therapies and muscarinic agonists are appropriate; systemic immunosuppression is not 1
Prescribing anti-TNF biologics—these have consistently failed in clinical trials and should not be used 1, 3
Overlooking drug-induced complications—particularly drug-induced ILD and infections with immunosuppression 1
Essential Preventive Measures
- Smoking cessation strongly recommended for all patients 2, 4
- Vaccinations: Ensure influenza and pneumococcal immunization 2, 4
- Pneumocystis jirovecii prophylaxis when using cyclophosphamide 1
- Hepatitis B screening before rituximab due to reactivation risk 1