The spondyloarthropathies (SpA) are characterized by asymmetrical arthritis especially affecting the lower limbs and inflammation at many other diverse locations, chief of which is axial skeleton involvement. Enthesitis, or inflammation of ligaments and tendons insertions to bone, is considered to be the unifying pathological hallmark of the disease but the link between enthesitis and how it may trigger a “secondary synovitis” was contentious. The microanatomical, functional biomechanics and immunopathogenic considerations pertaining to the enthesis led to the concept that the enthesis organ contained a unit termed a “synovio-entheseal complex” (SEC) . The SEC work together to dissipate load over a wider area and at the same time the adjacent synoviocytes function to lubricate and nourish the fibrocartilage via synovial fluid which in health maintains joint homeostasis. On the other hand, the SEC structure brings the synovium, a tissue lined with macrophages with considerable pro-inflammatory potential into close juxtaposition with mechanically stressed or injured adjacent avascular fibrocartilage tissue. It was hypothesized that these joint specific injurious/mechanical factors acted as danger signals thus triggering innate immune responses in the adjacent synovium. What could not be demonstrated at that time was the order of the events- e.g. the enthesitis being the initial manifestation; the triggering factors and why the enthesis is a target tissue in spondyloarthropathies.
Recent experimental studies supported the SEC concept. Jacques et al showed that biomechanical stress is a key component to trigger enthesitis, which subsequently spreads to the adjacent synovium with erosion and pannus formation, and that unloading by tail suspension suppresses the inflammation of the enthesis . Sherlock et al, showed that type II-collagen-specific antibody transfer resulted with severe enthesitis that was prominent before progression to the destructive synovitis and osteitis . This group also reported that disease was dependent on an enthesis resident population of RORΥt+ CD3+CD4–CD8– that were dependent on IL-23 stimulation with the elaboration of inflammatory mediators such as IL-17 that are mechanistically associated with synovitis. Prior work has also shown that TNF overexpression is also associated with arthritis that starts at the enthesis before spreading to the adjacent synovium . The current evidence shows that the mechanical stress in mice that are prone to spondyloarthropathies may cause to enthesitis initially which is then followed by synovitis.
With respect to the SEC in man, imaging studies in SpA have shown that findings indicative of inflammation may not be evident at the enthesis insertion per se but may manifest in the adjacent bursae in some cases supporting the idea of integrated SEC related disease rather than inflammation spreading from the more distal parts of the enthesis. Finally, the well-known association of psoriatic nail disease with adjacent distal interphalangeal arthritis has been carried one step further and it has been demonstrated that the inflammation can also distribute to the skin and the extensor tendon enthesis supporting the idea of an elaborate SEC organ around the DIP joint . The recognition of increased vascularity in aymptomatic enthesis of patients with psoriatic arthritis compared to both psoriasis and healthy controls led to the hypothesis that a vascular phenotype at insertions may be an important step to switch from psoriasis to psoriatic arthritis .
In conclusion since the first introduction of SEC, evidence has accumulated from different approaches including animal models, molecular biology and imaging which are all supportive of SEC.
McGonagle D et al. The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 2007; 56:2482-2491
Jacques P et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis 2014; 73:437-445
Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med 2012; 18:1069-1076
Armaka M et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med 2008; 205:331-337
Aydin SZ et al. Ultrasonographic assessment of nail in psoriatic disease shows a link between onychopathy and distal interphalangeal joint extensor tendon enthesopathy. Dermatology 2012; 225:231-235
Aydin SZ et al. The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development. Ann Rheum Dis 2012
Disclosure of Interest None declared