Enthesitis: Much More Than Focal Insertion Point Inflammation

Abstract

Purpose of review: Recognition of the importance of enthesitis as the pivotal pathological process underpinning spondyloarthropathies (SpA) has increased in recent years. Thus, we summarized the current knowledge on the pathogenic role of enthesitis on SpA shown by both animal models and human studies in vivo.

Recent findings: Experimental models have shown several SpA-like diseases that commence at entheses and are linked to nail disease as well as dactylitis, two important entheseal-associated conditions in humans. Frequently, enthesitis is not the primary outcome measure in studies of peripheral PsA and SpA although arguably it is the key parameter being indirectly assessed in spinal disease in ankylosing spondylitis. The use of different agents including JAK, IL-17, and IL-23 inhibitors contributes significantly to our understanding of enthesitis in terms of involved immune pathways. Enthesitis and enthesis organ inflammation may be the primary pathological process underlying SpA associated skeletal inflammation. Emergent studies are beginning to elucidate the molecular basis for this type of joint inflammatory response.

Keywords: Entheses; Enthesitis; IL-12; IL-17; IL-23; JAKi.

Fig. 1

Lymphocyte populations defined at the human enthesis. Thus far, two lymphocyte populations have been defined at the human enthesis. Innate lymphoid cells are part of the IL-23-responsive T cells which are residents of the healthy enthesis. Gamma delta T cells are also resident at the enthesis. The activation of resident T cells within the enthesis by IL-23 may promote inflammation, osteogenesis, and bone loss and remodeling. These lymphocyte populations may release different cytokines including IL-17 and IL-22 and TNF-α

Fig. 2

Magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) showing bilateral ischial tuberosity enthesitis in a patient with newonset PsA. The site of soft tissue entheseal inflammation is depicted by arrowheads. In this case, there is sparing of the bony attachment.

Fig. 3

Magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) showing bilateral sacral joint bone marrow edema on in a patient with early psoriatic arthritis. The Bone marrow edema is more florid at the anterior part of the joint adjacent to the capsular enthesis. It remains to be determined whether the patterns of inflammation at entheses in soft tissue or in the bone may influence responses to therapy