The enthesis, the site where tendons, ligaments, or joint capsules attach to bone, represents a central lesion in the pathophysiology of SpA. Enthesitis, or inflammation at the enthesis, is a key feature of SpA and occurs much more frequently than in other rheumatic diseases. Functionally, entheses act as biomechanical shock absorbers, dispersing forces during movement. Their anatomical complexity, which includes adjacent bone, bursae, and nearby synovium, collectively referred to as the “enthesis organ,” allows efficient load distribution but also makes them prone to inflammation under repetitive stress.
Pathological processes often begin at the enthesis, influenced by mechanical stress and genetic factors such as HLA-B27, as shown in both human and experimental studies. The enthesis contains a specialized immune environment where mechanical strain, microbial triggers, and genetic susceptibility interact to activate local immune responses, particularly through the IL-23 and IL-17 pathway. This leads to the recruitment of innate immune cells and the release of cytokines including IL-17, TNF, and IL-22.
Microtrauma at these sites induces prostaglandin E2 and cytokine signaling, promoting enthesitis that may extend to nearby synovium and subchondral bone, explaining its overlap with synovitis. Persistent inflammation at the enthesis also activates mesenchymal cells, resulting in abnormal new bone formation such as enthesophytes and syndesmophytes, which are distinctive features of SpA and differ from the bone erosions commonly seen in RA.
REFERENCE
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