Molecular mechanisms of spondyloarthropathies

Benjamin M, McGonagle D, Michael Benjamin, Dennis McGonagle, Benjamin, Michael, McGonagle, Dennis

A characteristic feature of the spondyloarthropathies is inflammation at tendon or ligament attachment sites. This has traditionally been viewed as a focal abnormality, even though the inflammatory reaction intrinsic to enthesitis may be quite extensive. We argue that the diffuse nature of the pathology is best understood in the context of an 'enthesis organ concept'. This highlights the fact that stress concentration at an insertion site involves not only the enthesis itself, but neighbouring tissues as well. The archetypal enthesis organ is that of the Achilles tendon where intermittent contact between tendon and bone immediately proximal to the enthesis leads to the formation of fibrocartilages on the deep surface of the tendon and on the opposing calcaneal tuberosity, but similar functional modifications are widespread throughout the skeleton. Many entheses have bursae and fat near the insertion site and both of these serve to promote frictionless movement. Collectively, the fibrocartilages, bursa, fat pad and the enthesis itself constitute the enthesis organ. However, it also includes both the immediately adjacent trabecular bone networks and in some cases deep fascia. The concept of a synovio-entheseal complex (SEC) and of a 'functional enthesis' are complimentary to that of an enthesis organ and also have important implications for understanding spondyloarthropathy. The SEC concept emphasizes the interdependence between synovial membrane and entheses within enthesis organs. It draws attention to the fact that one component (the enthesis) is prone to microdamage and the other (the synovium) to inflammation. If an enthesis is damaged, any ensuing inflammatory reaction is likely to occur in the synovium. The concept of a 'functional enthesis' serves to emphasise anatomical, biomechanical and pathological features that are shared between true fibrocartilaginous entheses and regions proximal to the attachment sites themselves where tendons or ligaments wrap around bony pulleys. Such'wrap-around regions' are well documented sites of pathology in SpA-for tenosynovitis is a recognized feature. Stress concentration at the enthesis itself is dissipated at many sites by fibrous connections between one tendon or ligament and another, close to the insertion site. At a microscopic level, enthesis fibrocartilage is of paramount importance in ensuring that fibre bending of the tendon or ligament is not focused at the hard tissue interface. Normal enthesis organs are avascular in their fibrocartilaginous regions, but tissue microdamage to entheses is common and appears to be associated with tissue repair responses and vessel ingrowth. This makes the enthesis organ a site where adjuvant molecules derived from bacteria may be preferentially deposited. This microdamage and propensity for bacterial molecule deposition in the context of genetic factors such as HLA-B27 appears to lead to the characteristic inflammatory changes of AS. Understanding the enthesis organ concept helps to explain synovitis and osteitis in spondyloarthropathy. An appreciation of the complex anatomy of 'articular enthesis organs' (e.g., that associated with the distal interphalangeal joints) is helpful in understanding disease patterns in psoriatic arthritis. In this chapter, we review the extent and types ofenthesis organs and show how a patho-anatomic appreciation of these structures leads to a new platform for understanding the pathogenesis of SpA.