The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites

The 2 major categories of idiopathic inflammatory arthritis are rheumatoid arthritis and the seronegative spondyloarthropathies. Whilst the synovium is the primary site of joint disease in the former, the primary site in the latter is less well defined. However, it has recently been proposed that enthesitis-associated changes in the spondyloarthropathies are primary and that all other joint manifestations are secondary. Nevertheless, some of the sites of disease localisation have not been adequately explained in terms of enthesitis. This article summarises current knowledge of the structure, function, blood supply, innervation, molecular composition and histopathology of the classic enthesis (i.e. the bony attachment of a tendon or ligament) and introduces the concept of 'functional' and articular 'fibrocartilaginous' entheses. The former are regions where tendons or ligaments wrap-around bony pulleys, but are not attached to them, and the latter are synovial joints that are lined by fibrocartilage rather than hyaline cartilage. We describe how these 3 types of entheses relate to other, and how all are prone to pathological changes in spondyloarthropathy. We propose that the inflammatory responses characteristic of spondyloarthropathies are triggered at these seemingly diverse sites, in genetically susceptible individuals, by a combination of anatomical factors which lead to higher levels of tissue microtrauma, and the deposition of microbes.