The at-risk-to-early continuum of enteropathic spondyloarthritis.

Abstract

Enteropathic spondyloarthritis is a common, under-recognised musculoskeletal manifestation of inflammatory bowel disease and a potentially preventable contributor to long-term disability. Epidemiological, imaging, and biomarker data support a continuum from at-risk states (ie, high-risk inflammatory bowel disease phenotypes with early extraintestinal manifestations and non-specific pain), through subclinical MRI-defined or ultrasound-defined sacroiliac and entheseal inflammation, to early clinical enteropathic spondyloarthritis with overt synovitis, enthesitis, and inflammatory back pain, often after prolonged diagnostically ambiguous symptoms. This transition unfolds within a gut-derived inflammatory milieu shaped by type-3 immunity, dysbiosis, epithelial barrier dysfunction, gut-homing and tissue-resident lymphocyte circuits, and polygenic susceptibility, with only partial synchrony between intestinal and musculoskeletal trajectories. Clinically, these mechanisms yield phase-specific signatures in which faecal calprotectin, C-reactive protein, and HLA-B27 act as probabilistic modifiers, and power Doppler ultrasound and sacroiliac or spinal MRI enable recognition of inflammation before irreversible structural change. In this Review, we synthesise mechanistic and clinical evidence across the at-risk-to-early articular continuum (this term refers to individuals at-risk of enteropathic spondyloarthritis, individuals with subclinical musculoskeletal disease, and patients with early clinical articular disease). We propose a precision, dual-compartment strategy addressing both gut and joint involvement, integrating structured musculoskeletal screening, probability-guided imaging, and timely use of therapies with proven gut-joint efficacy into inflammatory bowel disease care, aiming to prevent diagnostic delay, limit structural damage, and reframe enteropathic spondyloarthritis as an interceptable, treat-to-target phenotype along the gut-joint axis.