Enthesitis and Enthesopathy

Psoriatic Arthritis - Overview

In experimental models of inflammatory arthritis with features of Psoriatic Arthritis it has been demonstrated that the disease process clearly starts at the enthesis [1, 2, 3].

These models support the original imaging observation in humans that suggested that Psoriatic Arthritis and the related Spondyloarthropathies might start at the enthesis [4, 5].

McGonagle et al Lancet 1998. In Rheumatoid Arthritis it is considered that inflammation starts in the joint lining which is called the synovium. In Psoriatic Arthritis it is recognised that the inflammaton may start at the enthesis and then spread to the adjacent bone and synovium and other tissues

However, it is difficult to prove this theory beyond doubt in man due to the obvious limitations in sampling tissues early in the disease course to unequivocally show this.

Enthesopathy as measured by ultrasound is very common subjects with psoriasis who do not have clinical arthritis further suggesting that it is the primary abnormality [6].

The presence of clinically silent enthesopathy in psoriasis appears to be associated with the subsequent evolution of Psoriatic Arthritis [7].

Synovitis or joint swelling in Psoriatic Arthritis may be linked to dysfunction of the enthesis where it forms tissue structures called synovio-entheseal complexes (SECs) [8].

Osteitis or bone inflammation is common throughout the skeleton in some patients with Psoriatic Arthritis. The enthesis and underlying bone are functionally integrated with the enthesis being anchored to the underlying bone like the roots of a tree.

Nail disease in patients with psoriasis is a predictor of subsequent Psoriatic Arthritis. It has now being demonstrated that the nail is anchored directly to the skeleton by ligament and tendon entheses [9]. This offers a new explanation for the link between nail disease and arthritis.

Collectively, these observations support the idea that Psoriatic Arthritis starts at insertions and then spreads to other sites.

Since entheseal insertions are so ubiquitous throughout the skeleton this theory offers a simple explanation for the highly varied distribution of Psoriatic Arthritis.

This page represents a general overview of the key role of the enthesis in Psoriatic Arthritis. The following link explains the different manifestations of Psoriatic Arthritis in more detail.

References

1. Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Lories RJ, Matthys P, de Vlam K, Derese I, Luyten FP. Ann Rheum Dis. 2004 May;63(5):595-8.
2. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, Gorman DM, Bowman EP, McClanahan TK, Yearley JH, Eberl G, Buckley CD, Kastelein RA, Pierce RH, Laface DM, Cua DJ. Nat Med. 2012 Jul 1;18(7):1069-76. doi: 10.1038/nm.2817.
3. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. Armaka M, Apostolaki M, Jacques P, Kontoyiannis DL, Elewaut D, Kollias G. J Exp Med. 2008 8;205(2):331-7.
4. Classification of inflammatory arthritis by enthesitis. McGonagle D, Gibbon W, Emery P. Lancet. 1998;352(9134):1137-40
5. Psoriatic arthritis: a unified concept twenty years on. McGonagle D, Conaghan PG, Emery P. Arthritis Rheum. 1999 Jun;42(6):1080-6.
6. High prevalence of ultrasonographic synovitis and enthesopathy in patients with psoriasis without psoriatic arthritis: a prospective case-control study. Naredo E, Möller I, de Miguel E, Batlle-Gualda E, Acebes C, Brito E, Mayordomo L, Moragues C, Uson J, de Agustin JJ, Martinez A, Rejon E, Rodriguez A, Dauden E; Rheumatology (Oxford). 2011 Oct;50(10):1838-48.
7. Preliminary evidence that subclinical enthesopathy may predict psoriatic arthritis in patients with psoriasis. Tinazzi I, McGonagle D, Biasi D, Confente S, Caimmi C, Girolomoni G, Gisondi P. J Rheumatol. 2011 Dec;38(12):2691-2.
8. The concept of a "synovio-entheseal complex" and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. McGonagle D, Lories RJ, Tan AL, Benjamin M. Arthritis Rheum. 2007 Aug;56(8):2482-91.
9. The nail as a musculoskeletal appendage--implications for an improved understanding of the link between psoriasis and arthritis. McGonagle D, Tan AL, Benjamin M. Dermatology. 2009;218(2):97-102.