Laboratory Evaluation for Scleritis
All patients with scleritis require a comprehensive laboratory workup to identify underlying systemic autoimmune disease, which is present in 30-40% of cases and may be life-threatening if undiagnosed. 1, 2
Initial Mandatory Laboratory Panel
Autoimmune Screening
- Complete blood count (CBC) to assess for cytopenias and hematologic abnormalities 3
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers 3, 2
- Antinuclear antibody (ANA) by immunofluorescence as the initial autoimmune screening test 3
- Rheumatoid factor (RF) - rheumatoid arthritis is the most common systemic association with scleritis 1, 2, 4
Vasculitis-Specific Testing
- Anti-neutrophil cytoplasmic antibodies (ANCA) - granulomatosis with polyangiitis is the most common vasculitis causing scleritis and may present with scleritis as the initial manifestation 1, 2, 4
- Both c-ANCA and p-ANCA should be tested 5
Complement Levels
- C3 and C4 to assess for complement consumption in autoimmune disease 3
Extended Autoantibody Panel (If ANA Positive or High Clinical Suspicion)
Lupus-Specific Antibodies
- Anti-double stranded DNA (anti-dsDNA) - highly specific for systemic lupus erythematosus 3, 6
- Anti-Smith (anti-Sm) antibodies - highly specific for SLE 3
- Anti-Ro/SSA and anti-La/SSB antibodies for Sjögren syndrome overlap 3
- Anti-RNP antibodies 3
Additional Autoimmune Markers
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-beta-2 glycoprotein I) 3
- Anti-Scl-70/topoisomerase-1 and anti-centromere if systemic sclerosis suspected 5
Specialized Testing Based on Clinical Presentation
If Necrotizing Scleritis or Severe Disease
- Serum IgG4 levels - IgG4-related disease is an emerging systemic association with scleritis 5, 4
- Chest imaging (CT chest) to evaluate for sarcoidosis or granulomatosis with polyangiitis 5
- Serum angiotensin-converting enzyme (ACE) if sarcoidosis suspected 5
Infectious Disease Screening (Before Immunosuppression)
- HIV, hepatitis B and C serology - required before initiating immunosuppressive therapy 5, 3
- Tuberculosis screening according to local guidelines before starting immunosuppression 5, 3
Renal Function Assessment
- Serum creatinine and urinalysis with microscopy - essential as many associated systemic diseases affect the kidneys 3, 6
- Urine protein-to-creatinine ratio if urinalysis abnormal 3
Clinical Context and Pitfalls
The presence of necrotizing scleritis significantly increases the likelihood of finding an underlying systemic disease and warrants more aggressive systemic workup. 2 Scleritis may precede the diagnosis of systemic autoimmune disease, particularly vasculitis, by months to years 1, 4. Therefore, even if initial workup is negative, patients with idiopathic scleritis require ongoing surveillance for development of systemic disease 2, 4.
Active SLE disease (SLEDAI score >4) is commonly present when scleritis develops in lupus patients, and the workup should assess for multi-organ involvement including complement consumption and anti-dsDNA elevation 6.
The laboratory evaluation should be performed urgently as timely identification of underlying systemic disease and prompt immunosuppressive treatment reduces both ocular and systemic morbidity and mortality 1, 4. A multidisciplinary approach with rheumatology consultation is essential for patients with positive serologies or clinical features suggesting systemic disease 2, 7.