Is there a relationship between scleritis and connective tissue disease, such as rheumatoid arthritis (RA), lupus, or scleroderma, in patients with a history of autoimmune disorders?

Scleritis and Connective Tissue Disease: A Strong Clinical Association

Yes, there is a well-established relationship between scleritis and connective tissue diseases, with approximately 50% of scleritis cases occurring in the context of systemic autoimmune conditions, most notably rheumatoid arthritis and ANCA-associated vasculitis. 1, 2

Prevalence and Key Associations

The connection between scleritis and autoimmune disease is clinically significant:

• Up to half of all scleritis patients have an underlying immune-mediated systemic inflammatory condition, making this one of the most important associations to recognize 2
• Rheumatoid arthritis is the most common systemic association, requiring particular vigilance from clinicians 1
• ANCA-associated vasculitis (including Wegener's granulomatosis) represents another critical association that rheumatologists must actively screen for 1

Specific Connective Tissue Disease Associations

Rheumatoid Arthritis

• In a prospective study of 32 scleritis patients, rheumatoid arthritis was the most frequent systemic association (9 of 14 patients with systemic disease) 3
• Scleritis in rheumatoid arthritis patients confers an increased risk of mortality, making this a prognostically important finding 2

Systemic Lupus Erythematosus

• SLE is associated with scleritis, though less commonly than rheumatoid arthritis 3
• Overlap syndromes between scleroderma and SLE are reported, though SLE rarely occurs with scleroderma 4

Scleroderma (Systemic Sclerosis)

• Scleroderma can present with overlap features including other autoimmune conditions 4
• Antibodies thought to be specific for scleroderma (like Scl-70) can be present in up to 25% of SLE patients, indicating immunologic overlap 4
• Scleroderma overlap with polymyositis is frequently anti-PM Scl antibody positive 4

Other Associations

• IgG4-related disease has recently been recognized as a systemic association with scleritis 1
• Additional reported associations include Crohn's disease, Behçet's disease, and gout 3

Serologic Evidence of Autoimmunity

Patients with scleritis associated with systemic rheumatoid disease demonstrate significantly higher rates of autoantibodies (64.3%) compared to those with isolated scleritis (27.8%), providing objective laboratory evidence of the autoimmune connection 3

Clinical Implications and Diagnostic Approach

When Scleritis Precedes Systemic Diagnosis

Scleritis can precede a systemic autoimmune disease diagnosis, especially in the case of vasculitis, making it a potential sentinel finding 1

Ocular Manifestations

• Nodular anterior scleritis is the predominant presentation in both isolated and systemic disease-associated cases 3
• Scleral thinning is the most frequent complication regardless of systemic association 3
• The disease is often extremely painful and can lead to vision-threatening complications, including involvement of other ocular tissues 2

Treatment Considerations

Therapeutic Response Patterns

Patients with scleritis associated with systemic rheumatoid disease achieved 100% treatment success compared to 88.9% in isolated scleritis, though both groups required similar immunosuppressive regimens 3

Treatment Intensity

• In the systemic disease group, 50% required corticosteroids with one immunosuppressive drug, and 22.2% required pulse immunosuppressive therapy 3
• Aggressive systemic therapy is often required to obtain favorable outcomes, particularly when systemic disease coexists 2
• Oral prednisone is the mainstay of treatment but is usually combined with a steroid-sparing immunosuppressive drug 2
• Rituximab shows increasing evidence for refractory disease 1

Critical Clinical Pitfalls

Do not dismiss scleritis as an isolated ocular condition without thorough systemic evaluation, as missing an underlying vasculitis or rheumatoid arthritis can have serious prognostic implications including increased mortality risk 1, 2

Prompt recognition and adequate therapy are needed to avoid serious ocular complications including vision loss, making early rheumatologic consultation essential 1

Be aware that vasculitis may not be universally present at the microscopic level despite typical presentation with scleral vessel engorgement, so clinical suspicion should remain high even with negative biopsy findings 2