What is the treatment for extraglandular manifestations in patients with autoimmune diseases like Sjögren's syndrome?

Treatment of Extraglandular Manifestations in Sjögren's Syndrome

Systemic corticosteroids are the first-line treatment for extraglandular manifestations of Sjögren's syndrome, with specific immunosuppressive agents selected based on the organ system involved. 1, 2

General Approach to Extraglandular Manifestations

Treatment for extraglandular manifestations in Sjögren's syndrome is organ-specific and targeted based on the affected systems:

First-line Treatments:

• Mild systemic manifestations (fatigue, arthralgias): Hydroxychloroquine 200-400 mg daily 2
• Moderate to severe manifestations: Systemic corticosteroids (dosage based on severity) 1, 2
• Corticosteroid-sparing agents: Methotrexate, azathioprine, mycophenolate mofetil, or leflunomide 2

Specific Organ System Management

Pulmonary Manifestations:

• Small airway disease: Time-limited systemic steroids, nebulized/inhaled bronchodilators and/or corticosteroids, short course of macrolide antibiotics 2
• Interstitial lung disease (ILD):
  • Symptomatic/progressive ILD: Mycophenolate mofetil or azathioprine 2
  • Refractory ILD: Rituximab or cyclophosphamide 2

Vasculitis:

• Leukocytoclastic or cryoglobulinemic vasculitis: Immunosuppressive therapy with glucocorticoids 3
• Refractory/severe vasculitis: B-cell-targeted therapy with rituximab 3

Neurological Manifestations:

• Peripheral neuropathy: Corticosteroids with immunosuppressants
• Central nervous system involvement: High-dose corticosteroids and immunosuppression

Arthritis:

• Inflammatory arthritis: NSAIDs, hydroxychloroquine, low-dose corticosteroids
• Persistent/severe arthritis: Methotrexate or other DMARDs 1

Refractory Cases

For patients with severe or refractory extraglandular manifestations:

• Rituximab (anti-CD20) is recommended for refractory glandular and extraglandular manifestations 2, 3
• IL-6R inhibitors may be considered for refractory myositis 1
• TNF-α inhibitors if associated fasciitis is present 1
• IVIG and/or plasma exchange for severe manifestations with bulbar symptoms or myocarditis 1

Monitoring and Follow-up

• Use the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) to regularly monitor disease activity 2
• Complete pulmonary function testing and high-resolution CT imaging for patients with respiratory symptoms 2
• Regular ophthalmological evaluations to monitor ocular complications 2

Important Considerations

• Treatment should be initiated promptly for extraglandular manifestations to prevent organ damage
• Referral to a rheumatologist is recommended for corticosteroid-dependent or refractory cases 1
• The treatment approach differs significantly between patients with predominantly sicca features versus those with severe extraglandular disease 4
• B-cell-depleting therapies show more promise than TNF-α inhibitors, which have demonstrated limited efficacy in Sjögren's syndrome 4, 5

Pitfalls to Avoid

• Delay in treatment: Extraglandular manifestations can progress rapidly and cause permanent organ damage if not treated promptly
• Undertreatment: Using inadequate doses of immunosuppression for severe manifestations
• Overtreatment: Using aggressive immunosuppression for mild symptoms that could be managed with less toxic approaches
• Missing concurrent infections: Always rule out infections before initiating immunosuppressive therapy
• Inadequate monitoring: Failing to regularly assess disease activity and treatment response

Remember that while traditional anti-rheumatic agents show limited efficacy for systemic manifestations, newer biologic therapies targeting B-cell pathways appear more promising for managing extraglandular disease 4, 5.