What underlying systemic disease is most associated with recurrent scleritis?

Rheumatoid Arthritis is the Most Common Systemic Disease Associated with Recurrent Scleritis

Rheumatoid arthritis is the most common systemic disease associated with recurrent scleritis, followed by ANCA-associated vasculitis, particularly granulomatosis with polyangiitis. 1, 2

Systemic Associations with Scleritis

Scleritis is a severe inflammatory condition of the sclera that can lead to significant ocular complications including vision loss. While scleritis can occur in isolation, it is associated with systemic diseases in up to 50% of cases 3. The major systemic associations include:

1. Rheumatoid arthritis (RA)

   • Most common systemic association overall 2
   • Particularly associated with necrotizing scleritis without inflammation in advanced disease 4

2. ANCA-associated vasculitis

   • Granulomatosis with polyangiitis (formerly Wegener's granulomatosis) is the most common vasculitis associated with scleritis 2
   • Often presents with a more aggressive form of scleritis

3. Other autoimmune conditions

   • Inflammatory bowel disease (IBD) 5
   • Systemic lupus erythematosus 6
   • Spondyloarthropathies 4
   • IgG4-related disease (recently identified association) 1

Clinical Presentation and Classification

Scleritis can be classified into:

• Anterior scleritis

  • Diffuse anterior (generally better prognosis)
  • Nodular anterior
  • Necrotizing with inflammation (often associated with autoimmune disease)
  • Necrotizing without inflammation (scleromalacia perforans, often in advanced RA)

• Posterior scleritis

  • Often more difficult to diagnose due to subtle clinical signs 2

Diagnostic Approach

When evaluating a patient with recurrent scleritis:

1. Exclude infectious causes (particularly herpetic infections) 4
2. Comprehensive rheumatologic evaluation to identify underlying systemic disease
3. Laboratory testing should include:
   • Rheumatoid factor and anti-CCP antibodies
   • ANCA testing
   • ANA and specific autoantibodies
   • Inflammatory markers (ESR, CRP)

Management Considerations

Treatment of recurrent scleritis should address both the ocular inflammation and any underlying systemic disease:

1. Mild to moderate scleritis

   • NSAIDs (first-line for non-necrotizing forms) 6
   • Topical corticosteroids for symptomatic relief

2. Moderate to severe scleritis

   • Systemic corticosteroids
   • Immunomodulatory agents (methotrexate, azathioprine, mycophenolate mofetil)
   • Biologic therapies (particularly rituximab for refractory disease) 1

3. Treatment of underlying systemic disease

   • Collaboration between ophthalmologists and rheumatologists is essential 4
   • Controlling systemic disease activity often helps manage ocular inflammation

Prognosis and Monitoring

• Necrotizing scleritis carries the worst prognosis and highest risk of complications
• Regular ophthalmologic monitoring is essential for patients with systemic autoimmune diseases
• Early diagnosis and aggressive treatment improve outcomes and reduce risk of vision loss

Clinical Pearls

• Scleritis can precede the diagnosis of systemic autoimmune disease, particularly vasculitis 1
• Pain is a distinguishing feature between episcleritis (mild pain) and scleritis (moderate to severe pain) 5
• Necrotizing scleritis has an increased risk of complications and is more commonly associated with anterior uveitis and peripheral ulcerative keratitis 2
• Mortality risk is increased in RA patients who develop scleritis 3

Understanding the strong association between recurrent scleritis and systemic autoimmune diseases, particularly rheumatoid arthritis, is crucial for proper diagnosis, management, and prevention of vision-threatening complications.