Non-B27 HLA-B alleles lack diagnostic value, necessitating composite clinical indices to distinguish axial spondyloarthritis from radiographic mimics in Japanese patients.

Objective: To assess whether extended HLA-B typing, together with simple clinical indices, distinguishes axial spondyloarthritis (axSpA) from radiographic mimics in Japanese population.

Methods: We retrospectively reviewed 127 patients who underwent HLA-B typing at a single centre between 2008 and 2024. Ankylosing spondylitis met the 1987 modified New York criteria, and non-radiographic axSpA met the 2009 ASAS criteria. Diffuse idiopathic skeletal hyperostosis (DISH), palmoplantar pustulosis arthritis (PAO) and osteitis condensans ilii (OCI) were identified by characteristic imaging and clinical findings. Two rheumatologists reassigned final diagnoses. HLA-B phenotypes, age at onset, sex and initial C-reactive protein (CRP) were compared across groups.

Results: Twenty-five patients satisfied axSpA criteria; 80% were HLA-B27-positive. DISH, PAO and OCI showed apparent enrichment of common Japanese alleles (B52, B61/B62, B39). DISH and PAO presented later than axSpA (54.0 y and 42.5 y versus 25.2 y) and DISH had lower CRP (0.31 versus 1.51 mg/dL, p = 0.003). OCI occurred exclusively in women and was CRP-negative.

Conclusion: In Japanese practice, no single non-B27 allele reliably separates axSpA from its mimics; instead, early age at onset, male sex and raised CRP provide the most practical safeguards against diagnostic error and unnecessary therapy.