What is the recommended autoimmune workup for a patient with episcleritis or scleritis who only responds to prednisolone acetate (1% ophthalmic solution) 1 drop four times a day?

Autoimmune Workup for Episcleritis/Scleritis in Patients Dependent on Prednisolone Acetate 1%

A comprehensive autoimmune workup is strongly recommended for patients with episcleritis or scleritis who only respond to prednisolone acetate 1% ophthalmic drops, as up to 50% of these cases are associated with underlying systemic autoimmune disease.

Rationale for Autoimmune Workup

Patients requiring ongoing topical steroid therapy for episcleritis or scleritis often have underlying systemic conditions that need identification and treatment. The American College of Rheumatology guidelines emphasize that:

• Prolonged topical steroid therapy (>3 months) increases risk of complications including elevated intraocular pressure and cataracts 1
• Patients requiring 1-2 drops/day of prednisolone acetate 1% for ≥3 months should be considered for systemic therapy 2
• Systemic disease is associated with up to 50% of all patients with scleritis or episcleritis 3

Recommended Autoimmune Workup

First-Line Laboratory Testing:

• Complete blood count (CBC) with differential
• Comprehensive metabolic panel
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Rheumatoid factor (RF)
• Anti-nuclear antibody (ANA)
• Anti-neutrophil cytoplasmic antibodies (ANCA)
• Anti-cyclic citrullinated peptide (anti-CCP) antibodies

Second-Line Testing (Based on Clinical Suspicion):

• HLA-B27 (especially if concurrent anterior uveitis)
• Angiotensin-converting enzyme (ACE) level
• Serum protein electrophoresis
• Tuberculosis testing (QuantiFERON-TB Gold or PPD)
• Syphilis serology (RPR/VDRL and specific treponemal tests)
• Lyme disease serology (in endemic areas)

Imaging Studies:

• Chest X-ray (to evaluate for sarcoidosis, tuberculosis, or granulomatosis with polyangiitis)
• Consider chest CT if sarcoidosis is suspected

Management Algorithm

1. Initial Assessment:

   • Determine if episcleritis or scleritis (more severe, deeper inflammation)
   • Document response to prednisolone acetate 1%
   • Assess for signs of complications (elevated IOP, cataract formation)

2. Treatment Pathway:

   • If requiring prednisolone acetate 1% for <3 months: Continue topical therapy with close monitoring
   • If requiring prednisolone acetate 1% for ≥3 months: Initiate autoimmune workup and consider systemic therapy 1, 2

3. Based on Autoimmune Workup Results:

   • Positive findings: Refer to rheumatology for management of underlying condition
   • Negative findings but continued steroid dependence: Consider systemic immunomodulatory therapy

4. Systemic Therapy Options (in consultation with rheumatology):

   • First-line: Methotrexate (subcutaneous preferred over oral for ocular inflammation) 1, 2
   • Second-line: TNF inhibitors (adalimumab or infliximab, NOT etanercept) 2
   • Alternative for steroid-resistant cases: Consider tacrolimus (topical or systemic) 4

Important Clinical Considerations

• Differentiation: Episcleritis is typically more benign and self-limited compared to scleritis, which can lead to permanent vision loss if untreated 3
• Warning Signs: Recurrence of inflammation during steroid tapering may indicate underlying systemic disease, as seen in cases of polymyalgia rheumatica 5
• Monitoring: Regular ophthalmologic follow-up is essential to assess treatment response and monitor for complications of both the disease and therapy
• Infectious Causes: Rule out infectious etiologies before initiating immunosuppressive therapy, as some cases of scleritis can be post-traumatic or infectious in nature 6

Treatment Efficacy Considerations

• Topical steroid therapy alone fails in over 50% of scleritis cases, though it may spare some patients from systemic therapy and its side effects 7
• The goal of systemic therapy is to control inflammation while minimizing the need for long-term topical steroids 1, 2
• Patients with nodular episcleritis may be particularly resistant to conventional therapy and might benefit from alternative agents like tacrolimus 4

By following this structured approach to autoimmune workup and management, you can identify underlying systemic conditions and implement appropriate therapy to prevent vision-threatening complications while reducing dependence on topical steroids.