What is the management approach for a patient with a history of uveitis, positive HLA-B27 (Human Leukocyte Antigen B27), negative Antinuclear Antibody (ANA), negative Rapid Plasma Reagin (RPR), normal Erythrocyte Sedimentation Rate (ESR), normal C-Reactive Protein (CRP), negative Rheumatoid Factor (RF), and negative Cyclic Citrullinated Peptide (CCP)?

Management of HLA-B27 Positive Uveitis with Negative Inflammatory Markers

This patient requires immediate ophthalmologic evaluation for uveitis management with topical corticosteroids, education about warning signs of acute anterior uveitis recurrence, and rheumatology referral to evaluate for underlying spondyloarthritis. 1

Immediate Ophthalmologic Management

First-Line Treatment

• Initiate topical prednisolone acetate 1% with cycloplegics as first-line therapy for the uveitis. 1, 2 This is the standard approach for HLA-B27 associated anterior uveitis, which is typically episodic and self-limiting. 1, 3
• Limit topical corticosteroid use to ≤3 months due to significant risk of elevated intraocular pressure and cataract formation. 1, 2
• Monitor ophthalmologically every 3 months while on stable therapy. 1, 2

Critical Patient Education

• Strongly educate the patient about warning signs of acute anterior uveitis recurrence: eye pain, redness, and photophobia. 2, 4 This education is essential to decrease delay in treatment and prevent complications such as posterior synechiae, cataracts, glaucoma, and vision loss. 2

Rheumatologic Evaluation

Assessment for Spondyloarthritis

• Refer to rheumatology for evaluation of underlying spondyloarthritis, even with negative inflammatory markers. 1, 2 The negative ESR, CRP, RF, and CCP do not rule out spondyloarthritis. 2
• Specifically assess for inflammatory back pain characteristics: morning stiffness >30 minutes, nocturnal/early morning pain, improvement with exercise, and onset before age 45. 4, 2
• Approximately 25% of HLA-B27 positive individuals with uveitis will develop axial spondyloarthritis over time. 2

Important Diagnostic Pitfall

• Do not rule out spondyloarthritis based solely on negative laboratory results. 2 HLA-B27 associated conditions can occur with normal inflammatory markers, and axial spondyloarthritis occurs equally in HLA-B27 positive and negative individuals. 2

Imaging Considerations

• Consider radiography of sacroiliac joints if the patient has a mature skeleton and symptoms suggestive of axial involvement. 2
• If radiography does not meet modified New York criteria or cannot be performed, MRI can be utilized to detect early sacroiliitis. 2, 4

Systemic Treatment Algorithm

If Uveitis Becomes Refractory to Topical Therapy

1. Screen for latent/active tuberculosis, HIV, and hepatitis before initiating systemic immunomodulatory therapy. 1
2. Initiate methotrexate 0.5-1 mg/kg/week (maximum 30 mg) as first-line systemic agent. 1
3. If inadequate response to methotrexate, add monoclonal antibody TNF inhibitors (adalimumab or infliximab). 1, 2
4. Avoid etanercept specifically in HLA-B27 associated uveitis due to risk of severe, atypically chronic bilateral uveitis with cystoid macular edema. 1, 5

If Associated Spondyloarthritis is Confirmed

• First-line treatment is NSAIDs at full dose. 4, 2
• Higher NSAID doses are associated with increased cardiovascular risk (ischemic heart disease, stroke, congestive heart failure), requiring careful monitoring. 2
• If inadequate response to NSAIDs, TNF inhibitors (adalimumab, infliximab) are recommended as first-line biologics. 4

Monitoring Schedule

• Every 3 months for stable, controlled uveitis. 1, 2
• Within 1 month after any change in topical glucocorticoids. 2
• Within 2 months after any change in systemic therapy. 2

Red Flags Requiring Immediate Reassessment

• If the uveitis develops granulomatous features, this should raise concern for misdiagnosis or masquerade syndrome (malignancy, infection) and requires diagnostic vitrectomy, CSF cytology, and brain MRI. 1
• Chronic bilateral uveitis or posterior segment involvement is atypical for HLA-B27 associated disease and warrants investigation for alternative diagnoses. 3, 5
• Before escalating therapy, always rule out treatment nonadherence, infections, and masquerade syndromes. 1