Enthesitis: from pathophysiology to treatment

Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of enthesitis remains limited. This Review provides an insight into the pathophysiology of enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of enthesitis, and the role of clinical and imaging instruments in detecting enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents.