What is the appropriate autoimmune workup for a patient presenting with uveitis?

Autoimmune Workup for Uveitis

Initial Diagnostic Approach

The autoimmune workup for uveitis should be targeted and limited, as extensive serologic testing leads to false-positives given the low prevalence of many conditions—only 30-45% of uveitis cases have an underlying systemic disease. 1

Essential First-Line Testing

• Syphilis serology and chest radiography are the only universally recommended tests for all patients with uveitis of unclear etiology, screening for syphilis, sarcoidosis, and tuberculosis 1
• HLA-B27 typing should be performed specifically for patients with recurrent anterior uveitis, as this identifies seronegative spondyloarthropathy risk 2, 1
• Screen for latent or active tuberculosis, HIV, and hepatitis before initiating any systemic immunomodulatory therapy 2

Tests to AVOID Routinely

• Do not routinely order Lyme serology, antinuclear antibody (ANA) tests, serum angiotensin-converting enzyme, serum lysozyme, or tuberculin skin tests, as these produce false-positives due to low disease prevalence 1
• The exception is ANA testing in children, as ANA positivity, oligoarthritis, and early-onset arthritis are predominant risk factors for chronic anterior uveitis in juvenile idiopathic arthritis (JIA) 3

Critical Exclusions Before Labeling as Autoimmune

Rule Out Masquerade Syndromes

• Granulomatous uveitis with HLA-B27 positivity should immediately raise concern for misdiagnosis or masquerade syndrome (malignancy, infection) and requires diagnostic reassessment 2
• Masquerade syndromes occur in up to 2.5% of noninfectious uveitis cases and require diagnostic vitrectomy, cerebrospinal fluid cytology, and brain MRI when suspected 2, 4
• Consider primary ocular lymphoma in patients over 50 years with persistent intermediate or posterior uveitis unresponsive to anti-inflammatory therapy 1

Rule Out Infectious Causes

• Toxoplasmosis, herpes, tuberculosis, and HIV comprise 11-21% of infectious cases in high-income countries and 50% in low- and middle-income countries 5
• Perform sampling and culturing of intraocular fluids in immunosuppressed patients, those with indwelling catheters, or systemic sepsis 4

Targeted Workup Based on Clinical Patterns

Anterior Uveitis Pattern

• HLA-B27 testing for recurrent cases to identify axial spondyloarthritis 2, 1
• Refer to rheumatology if inflammatory back pain, morning stiffness, or family history of spondyloarthritis present 2
• In children with anterior uveitis: ANA testing as positivity predicts JIA-associated uveitis risk 3

Posterior or Panuveitis Pattern

• Chest radiography for sarcoidosis and tuberculosis 1
• Syphilis serology universally 1
• Consider systemic autoimmune diseases including Behçet's disease, sarcoidosis, and granulomatosis with polyangiitis based on clinical context 6, 7

When Autoimmune Disease is Identified

• Only 5% of uveitis cases are truly autoimmune in origin (distinct from auto-inflammatory), with rheumatoid arthritis and granulomatosis with polyangiitis being most common 7
• 15% are auto-inflammatory (including Behçet's disease, sarcoidosis) and 14% are mixed 7
• Patients with classical autoimmune connective tissue disease predominantly exhibit scleritis (53%) rather than isolated uveitis 7

Common Pitfalls to Avoid

• Avoid shotgun serologic testing—the low prevalence of many conditions in uveitis populations makes broad autoimmune panels counterproductive 1
• Do not assume all noninfectious uveitis is autoimmune—only 5% truly are, with most being idiopathic (27-51%) or auto-inflammatory 5, 7
• Always exclude infection and masquerade syndromes before attributing uveitis to autoimmune disease, especially in atypical presentations 2, 4