Abstract Background Spondyloarthritis (SpA) is among the most frequent and impactful extraintestinal manifestations of inflammatory bowel diseases (IBD), often remaining subclinical and underdiagnosed.1 Accurate early recognition is vital for optimizing patient management. Musculoskeletal ultrasound (US) and gut microbiota profiling are promising approaches to capture extraintestinal activation along the gut–joint axis.2 Methods In a prospective design, 89 IBD patients were consecutively enrolled and underwent DETAIL questionnaire screening, full-joint and enthesis US, and faecal sampling for 16S rRNA gene microbiota profiling. The diagnostic accuracy of the DETAIL questionnaire (recommended cut-off ≥3) and a peripheral sub-score (≥2) was evaluated against the presence of US-confirmed inflammatory lesions and clinically classified peripheral SpA. Gut microbiota was compared in three groups: IBD, IBD with US-detected inflammatory lesions, and IBD with diagnosed peripheral SpA. Results Ultrasound detected at least one inflammatory lesion in 36% of patients, highlighting a considerable burden of subclinical musculoskeletal inflammation. Notably, 35.6% (total DETAIL negative) and 31% (peripheral DETAIL negative) of patients with negative questionnaires showed US-detected active lesions. The negative predictive value (NPV) of the peripheral DETAIL sub-score for ruling out SpA was excellent (NPV 96.6%), supporting the utility of US as a sensitive confirmatory tool following questionnaire screening. Microbiota analysis demonstrated significant differences in beta diversity among patients with and without musculoskeletal involvement (PERMANOVA Bray–Curtis p = 0.010; weighted UniFrac p = 0.024; unweighted UniFrac p = 0.035). Compositionally, Fusobacterium was markedly enriched in IBD patients with ultrasound-detected inflammation but not in those with established peripheral SpA, suggesting a role as an early microbial marker along the gut–joint axis. Other taxa characterising SpA included increased Lactobacillus and Prevotella and a decrease in commensal short-chain fatty acid producers. Conclusion A stepwise diagnostic strategy integrating symptom screening and universal musculoskeletal ultrasound uncovers a high rate of subclinical peripheral inflammation in IBD, which may precede clinical SpA. The excellent NPV of the peripheral DETAIL sub-score and the prevalence of US-detected lesions reinforce the role of imaging for early exclusion and detection. Microbiota profiling offers novel insights, identifying the enrichment of Fusobacterium, associated with early, asymptomatic musculoskeletal inflammation. These findings support the value of combined assessment for early risk stratification and pave the way towards personalised pathways in IBD–SpA. References: 1. Gordon H, Burisch J, Ellul P, et al. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(1):1-37. doi:10.1093/ecco-jcc/jjad108 2. Balint PV, Terslev L, Aegerter P, et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in Spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis. 2018;77(12):1730-1735. doi:10.1136/annrheumdis-2018-213609 3. Di Carlo M, Luchetti MM, Benfaremo D, et al. The DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire: development and preliminary testing of a new tool to screen patients with inflammatory bowel disease for the presence of Spondyloarthritis. Clin Rheumatol. 2018;37(4):1037-1044. doi:10.1007/s10067-017-3937-6 4. Hong M, Li Z, Liu H, et al. Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles. Cell Host Microbe. 2023;31(5):798-810.e7. doi:10.1016/j.chom.2023.03.018 Conflict of interest: Dr. Santagata, Fabrizio: No conflict of interest Ferrito, Matteo: No conflict of interest Ingrao, Luca: No conflict of interest Trignani, Giorgia: No conflict of interest Favalli, Ennio Giulio: No conflict of interest Caporali, Roberto: No conflict of interest De lucia, Orazio: No conflict of interest Hobcharyuk, Ivanna: No conflict of interest Panichi, Erica: No conflict of interest Conforti, Francesco: No conflict of interest Piazza O’ Sed, Nicole: No conflict of interest Spina, Luisa: No conflict of interest Amoroso, Chiara: No conflict of interest Federica, Facciotti: No conflict of interest Vecchi, Maurizio: No conflict of interest Caprioli, Flavio: No conflict of interest
Santagata et al. (Thu,) studied this question.