What is the treatment approach for patients with granulomatous uveitis and HLA (Human Leukocyte Antigen) B27?

Treatment of Granulomatous Uveitis with HLA-B27 Positivity

Critical Diagnostic Consideration

This clinical presentation is atypical and requires immediate reassessment of the diagnosis, as HLA-B27 associated uveitis is characteristically non-granulomatous, not granulomatous. 1, 2

The combination of granulomatous uveitis with HLA-B27 positivity should raise concern for:

• Misdiagnosis or masquerade syndrome (malignancy such as lymphoma, infection, or other conditions mimicking inflammation) 3
• Coexisting conditions where HLA-B27 positivity is incidental
• Atypical presentation requiring further investigation

Before proceeding with treatment, you must rule out infections and masquerade syndromes through diagnostic vitrectomy, cerebrospinal fluid cytology, and brain MRI if indicated 3.

Typical HLA-B27 Uveitis Characteristics (What You Should Expect)

HLA-B27 associated uveitis typically presents as:

• Acute anterior non-granulomatous uveitis in 87% of cases 1
• Unilateral or unilateral alternating involvement in 93% of patients 1
• Episodic and self-limiting attacks with median duration of 6 weeks 1

Initial Treatment Approach (If Diagnosis Confirmed)

For Acute Anterior Uveitis Component

Topical corticosteroids are first-line treatment for HLA-B27 associated anterior uveitis, as it is typically episodic and self-limiting. 4, 5

• Start topical prednisolone with cycloplegics 4
• Limit topical prednisolone to ≤3 months due to significant risk of elevated intraocular pressure and cataract formation 5
• Monitor for posterior synechiae, which are associated with increased risk of cataracts, elevated intraocular pressure, and cystoid macular edema 1

Monitoring Schedule

• Every 3 months for patients with controlled uveitis on stable therapy 4, 5
• Within 1 month after each change in topical glucocorticoid therapy 4, 6
• Within 2 months after changes in systemic therapy 4, 6

Escalation to Systemic Therapy

Indications for Noncorticosteroid Systemic Immunomodulatory Therapy (NCSIT)

Initiate NCSIT if:

• Corticosteroid therapy fails or causes intolerable side effects 5
• Disease requires prolonged control beyond 3 months 5
• Active uveitis while taking ≥30 mg or ≥0.5 mg/kg prednisone daily 5
• Relapse when oral corticosteroid dose reduced to <7-10 mg/day 5
• Sight-threatening disease, visual acuity worse than 20/100, or cystoid macular edema 5

Pre-Treatment Screening (Mandatory)

Before initiating systemic immunomodulatory therapy:

• Screen for latent or active tuberculosis (interferon-gamma release assay, chest CT) 3, 5, 7
• Test for HIV and hepatitis 3, 5
• Assess baseline vital organ function (liver, kidney) 3, 5
• Evaluate for history of malignancy and family history 3, 5

First-Line Systemic Therapy

Methotrexate is the recommended first-line systemic agent for refractory non-infectious uveitis. 4, 5

• Dose: 0.5-1 mg/kg/week, maximum 30 mg 5
• Alternative first-line options include mycophenolate mofetil or azathioprine 5

Second-Line: TNF Inhibitors

If inadequate response to methotrexate, add monoclonal antibody TNF inhibitors (adalimumab or infliximab). 4, 5

• Adalimumab is FDA-approved for non-infectious intermediate, posterior, and panuveitis 8
• Dosing: 80 mg initial dose, then 40 mg every other week starting one week after initial dose 8
• For patients ≥30 kg: 40 mg every other week; <30 kg: 20 mg every other week 8

Critical warning: Screen for tuberculosis and hepatitis before initiating TNF inhibitors 5, 8. There is risk of hepatosplenic T-cell lymphoma, particularly when combined with azathioprine in adolescent/young adult males with inflammatory bowel disease 5.

Special Consideration: Etanercept

Avoid etanercept in HLA-B27 associated uveitis. A case report documented severe, atypically chronic bilateral uveitis with cystoid macular edema in an HLA-B27 positive patient with ankylosing spondylitis treated with etanercept, which improved only after switching to infliximab 9. This suggests etanercept may be ineffective or potentially harmful in this population.

Treatment Failure Algorithm

If patient not responding adequately to therapy:

1. First, rule out: 3

   • Treatment nonadherence
   • Infections (tuberculosis, syphilis, viral)
   • Masquerade syndromes (lymphoma, retinal degeneration)

2. Then consider: 3, 5

   • Dose escalation to maximum tolerated therapeutic dose
   • Transition to alternative or additional agent

3. Assess disease activity using: 3

   • Visual acuity
   • Anterior chamber cells and flare
   • Vitreous haze
   • Macular or optic nerve involvement

Associated Systemic Disease Evaluation

58% of HLA-B27 positive uveitis patients have an associated spondyloarthropathy, frequently undiagnosed before uveitis onset. 1

Refer to rheumatology if patient has:

• Inflammatory back pain (onset before age 45, lasting >3 months) 3
• Morning stiffness, nocturnal pain, improvement with exercise 3, 6
• Enthesitis, peripheral arthritis, or psoriasis 3
• First-degree family member with spondyloarthritis (present in 30% of cases) 1

First-line treatment for associated spondyloarthritis is NSAIDs at full dose. 3, 6

Key Pitfalls to Avoid

• Do not assume all HLA-B27 positive uveitis is granulomatous - this is atypical and warrants investigation for alternative diagnoses 1, 2
• Do not use systemic corticosteroids as monotherapy for posterior uveitis - must combine with immunosuppressive agents 5
• Do not continue topical prednisolone >3 months without escalating to systemic therapy due to risk of glaucoma and cataracts 5
• Do not start TNF inhibitors without tuberculosis screening - risk of reactivation 5, 8