Clinical significance of spondyloarthritis-attended enthesites: from pathophysiology to treatment (review)

Abstract

The article presents the latest views on enthesites’ anatomy and pathogenesis, clinical features, diagnostic and thera­peutic options. The enthesis lesions are considered an outstan­ding pathologic and clinical manifestation of spondyloarthritis group; this symptom is included into the classification criteria by the Assessment of SpondyloArthritis International Society for the peripheral and axial forms. The typical spondyloarthritis-atten­ded enthesites’ localizations are: the site of Achilles tendon and plantar aponeurosis’ attachment to the calcaneus, the lateral condyle of the humerus, the medial condyle of the femur, the upper edge of the patella, the upper edge of the iliac bones, trochanters of the femoral bones, spinous processes of the vertebrae. The structures focused in the entheses’ sites have anatomical, functional and physiological interactions and constitute a single synovial-entheseal complex. Unlike the rheumatoid arthritis with a key pathological process occurring in the synovial lining, the spondyloarthritis is mainly provoking the morphological modifications, namely enthesites, while the developing arthritis (synovitis) appears secondary to enthesites. The enthesitis is detected in 30–50 % of spondyloarthritis patients and associated with a higher activity, higher pain indices and a compromised life qua­lity. The presence of enthesites in the psoriatic arthritis patients is associated with axial and peripheral joint lesions, a high chance of ankylosation, a high disease activity, pronounced pains, a compromised life quality and functional state, sleeping disorders. Furthermore, the enthesitis is considered a precursor of the negative disease outcome, and may forecast a lower probability of remission and a low activity. The entheseal inflammation occurs as a result of mechanical and/or infection-originating stress, resulting in the prostaglandin E2 and interleukin-23 activation with a further vasodilatation, and T-cell and Group 3 innate lymphoid cell (ILC3) activation. The innate immunity-generated inflammation is characterized by a release of tumor necrosis factor and interleukin-17, resulting in the immune cell influx, namely the polymorphonuclear neutrophils. Under the influence of interleukin-17 and interleukin-22, the mesenchymal proliferation is characte­rized by an activation and proliferation of resident mesenchymal stem cells in the periosteum. The enthesitis treatment strategies remain undefined; however, the ones most commonly used are the nonsteroidal anti-inflammatory drugs (NSAIDs), localized glucocorticoid injections, Apremilast, as well as targeted medications, namely the tumor necrosis factor, interleukin-17 and interleukin-23 inhibitors.

Keywords

• enthesitis, spondyloarthritis, psoriatic arthritis, synovial-enthesial complex, prostaglandin e2, inflammation, pathogenesis, treatment