What is the association between ankylosing spondylitis and acute anterior uveitis, including prevalence, HLA‑B27 risk, typical presentation, and recommended management?

Relationship Between Ankylosing Spondylitis and Uveitis

Acute anterior uveitis (AAU) is the most common extra-articular manifestation of ankylosing spondylitis, occurring in 20-40% of AS patients, with a particularly strong association in HLA-B27 positive individuals. 1, 2, 3

Epidemiology and Prevalence

• Approximately 20-30% of patients with ankylosing spondylitis will develop acute anterior uveitis during their disease course 2
• More recent data suggests the prevalence may be as high as 40% of AS patients experiencing at least one episode of AAU 3
• About 50% of all acute anterior uveitis cases are associated with HLA-B27 positivity 2, 4
• In many cases (57% in one cohort), uveitis is diagnosed before the spondyloarthritis, making it a critical opportunity for early AS diagnosis 5

HLA-B27 Association and Risk

• HLA-B27 positive AAU represents a distinct clinical entity with specific characteristics 4
• The relative risk of having ankylosing spondylitis is 6.8 times higher in HLA-B27 positive AAU patients compared to HLA-B27 negative patients 6
• HLA-B27 positive AAU shows a 9.9-fold increased association with systemic inflammatory diseases overall 6
• Male predominance is more pronounced in HLA-B27 positive AAU (relative risk 1.2) 6

Clinical Presentation Patterns

HLA-B27 positive AAU typically presents as unilateral or alternating bilateral episodes, whereas simultaneous bilateral involvement suggests HLA-B27 negative disease. 6, 5

• Unilateral involvement is significantly more common in HLA-B27 positive cases (relative risk 1.1) 6, 5
• Alternating bilateral pattern (switching eyes between episodes) has a relative risk of 2.2 in HLA-B27 positive patients 6
• Simultaneous bilateral AAU is more characteristic of HLA-B27 negative disease (relative risk 0.3 for HLA-B27 positive) 6
• Typical symptoms include sudden onset eye pain, blurred vision, photophobia, and eye redness 7

Distinctive Clinical Features of HLA-B27 AAU

• Hypopion (layered white blood cells in anterior chamber) occurs 5.5 times more frequently in HLA-B27 positive AAU 6
• Fibrinous anterior chamber reaction is characteristic of HLA-B27 positive disease 6
• Papillitis shows a 7.7-fold increased risk in HLA-B27 positive AAU 6
• Interestingly, elevated intraocular pressure and glaucoma are actually less common in HLA-B27 positive AAU (relative risk 0.6) compared to HLA-B27 negative disease 6

Management Approach for AS Patients with Uveitis

Acute Episode Treatment

All acute uveitis episodes require urgent ophthalmology evaluation within 2 days, with topical prednisolone acetate 1% as first-line therapy. 8, 7

• Prednisolone acetate 1% eyedrops should be initiated at 1-2 drops per eye daily or more frequently based on inflammation severity 7
• Cycloplegic agents must be added to prevent posterior synechiae formation and reduce pain 7
• The goal is to discontinue topical corticosteroids within 3 months due to risks of glaucoma and cataracts 7
• Most HLA-B27 associated AAU episodes are self-limiting and respond well to topical therapy alone 7, 3

Prevention of Recurrent Episodes

For AS patients with recurrent uveitis requiring systemic therapy, adalimumab or infliximab must be used instead of etanercept. 1, 8

• Adalimumab and infliximab significantly reduce uveitis recurrence rates, with adalimumab showing rates of 13.6 per 100 patient-years compared to 60.3 for etanercept 1
• Infliximab demonstrates rates of 27.5 per 100 patient-years 1
• Etanercept should never be used in AS patients with a history of uveitis, as it may paradoxically worsen or trigger new uveitis episodes 1, 8, 9
• Certolizumab or golimumab may also be considered, though supporting data are less substantial 1

Indications for Systemic Therapy

• Requiring more than 1-2 drops per day of prednisolone acetate 1% at 3 months to maintain control 7
• Recurrent flares during topical steroid taper 7
• Bilateral disease 7
• Presence of complications such as posterior synechiae or cystoid macular edema 7

Refractory Disease Management

• Methotrexate is the preferred initial disease-modifying agent for refractory AAU, achieving remission in approximately 52% of patients 8, 7
• For methotrexate-refractory cases, monoclonal TNF inhibitors (adalimumab or infliximab) should be used, with complete remission in 30-85% of patients 8, 7

Critical Clinical Pitfalls

• All HLA-B27 positive AAU patients must be referred to a rheumatologist because approximately 50% have undiagnosed ankylosing spondylitis or related spondyloarthritis 4, 5
• The Dublin Uveitis Evaluation Tool (DUET) algorithm identified undiagnosed spondyloarthritis in approximately 40% of patients presenting with idiopathic AAU, with 96% sensitivity and 97% specificity 3
• Regular ophthalmologic monitoring is essential even when asymptomatic, as posterior uveitis can progress to irreversible vision loss without symptoms 8
• Secukinumab was not efficacious for panuveitis or posterior uveitis and has been associated with new onset or exacerbation of inflammatory conditions 1
• Ixekizumab also shows increased risks of inflammatory complications 1