Acute Anterior Uveitis: Etiologic investigation and its relationship with HLA-B27

Acute anterior uveitis (AAU) requires prompt recognition, control of intraocular inflammation, and etiologic assessment proportionate to its clinical phenotype. HLA-B27-associated AAU is particularly relevant because ocular attacks may precede recognition of axial or peripheral spondyloarthritis. This critical narrative review examines how HLA-B27 modifies diagnostic reasoning, which clinical findings justify targeted investigations, and how recognition of systemic disease influences management and recurrence prevention. Literature available through 2026 was assessed through PubMed/MEDLINE, relevant full-text journal sources, and professional recommendations, with emphasis on classification studies, diagnostic cohorts, longitudinal outcomes, and therapeutic evidence. A sudden, painful, unilateral or alternating, nongranulomatous episode is suggestive but not specific for HLA-B27-associated disease. Genotyping supports phenotypic interpretation but neither establishes causation nor excludes spondyloarthritis when negative. Infectious and alternative inflammatory etiologies remain important, especially with elevated intraocular pressure, iris atrophy, granulomatous inflammation, posterior involvement, or atypical persistence. Rheumatologic assessment is valuable when inflammatory musculoskeletal symptoms or other spondyloarthritis features are present, regardless of HLA-B27 status. Topical corticosteroids and cycloplegia control most isolated attacks; systemic recurrence prevention requires individualized risk assessment. A phenotype-directed, interdisciplinary approach avoids both missed systemic disease and unnecessary investigations.