Abstract
A characteristic feature of the spondyloarthropathies is inflammation at tendon or ligament attachment sites. This has traditionally been viewed as a focal abnormality, even though the inflammatory reaction intrinsic to enthesitis may be quite extensive. We argue that the diffuse nature of the pathology is best understood in the context of an ‘enthesis organ conceptrs. This highlights the fact that stress concentration at an insertion site involves not only the enthesis itself, but neighbouring tissues as well. The archetypal enthesis organ is that of the Achilles tendon where intermittent contact between tendon and bone immediately proximal to the enthesis leads to the formation of fibrocartilages on the deep surface of the tendon and on the opposing calcaneal tuberosity, but similar functional modifications are widespread throughout the skeleton. Many entheses have bursae and fat near the insertion site and both of these serve to promote frictionless movement. Collectively, the fibrocartilages, bursa, fat pad and the enthesis itself constitute the enthesis organ. However, it also includes both the immediately adjacent trabecular bone networks and in some cases deep fascia.
The concept of a synovio-entheseal complex (SEC) and of a ‘functional enthesis’ are complimentary to that of an enthesis organ and also have important implications for understanding spondyloarthropathy. The SEC concept emphasizes the interdependence between synovial membrane and entheses within enthesis organs. It draws attention to the fact that one component (the enthesis) is prone to microdamage and the other (the synovium) to inflammation. If an enthesis is damaged, any ensuing inflammatory reaction is likely to occur in the synovium. The concept of a ‘functional enthesis’ serves to emphasise anatomical, biomechanical and pathological features that are shared between true fibrocartilaginous entheses and regions proximal to the attachment sites themselves where tendons or ligaments wrap around bony pulleys. Such ‘wrap-around regions’ are well documented sites of pathology in SpA—for tenosynovitis is a recognized feature.
Stress concentration at the enthesis itself is dissipated at many sites by fibrous connections between one tendon or ligament and another, close to the insertion site. At a microscopic level, enthesis fibrocartilage is of paramount importance in ensuring that fibre bending of the tendon or ligament is not focused at the hard tissue interface. Normal enthesis organs are avascular in their fibrocartilaginous regions, but tissue microdamage to entheses is common and appears to be associated with tissue repair responses and vessel ingrowth. This makes the enthesis organ a site where adjuvant molecules derived from bacteria may be preferentially deposited. This microdamage and propensity for bacterial molecule deposition in the context of genetic factors such as HLA-B27 appears to lead to the characteristic inflammatory changes of AS.
Understanding the enthesis organ concept helps to explain synovitis and osteitis in spondy-loarthropathy. An appreciation of the complex anatomy of ‘articular enthesis organs’ (e.g., that associated with the distal interphalangeal joints) is helpful in understanding disease patterns in psoriatic arthritis. In this chapter, we review the extent and types of enthesis organs and show how a patho-anatomic appreciation of these structures leads to a new platform for understanding the pathogenesis of SpA.
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References
Woo SL, Buckwalter JA. AAOS/NIH/ORS workshop. Injury and repair of the musculoskeletal soft tissues. Savannah Georgia 1987. J Orthop Res 1988; 6:907–931.
Benjamin M, McGonagle D. The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J Anat 2001; 199:503–526.
Benjamin M, Moriggl B, Brenner E et al. The “enthesis organ” concept: Why enthesopathies may not present as focal insertional disorders. Arthritis Rheum 2004; 50:3306–3313.
Huber LC, Moritz F, Gay S. Spondylarthritides and related entities: Entheses and hypotheses. Arthritis Rheum 2007; 56:4–8.
McGonagle D, Khan MA, Marzo-Ortega H et al. Enthesitis in spondyloarthropathy. Curr Opin Rheumatol 1999; 11:244–250.
McGonagle D, Gibbon W, Emery P. Spondyloarthropathy. Lancet 1999; 353:1526–1527.
Alvarez-Nemegyei J, Canoso JJ. Heel pain: Diagnosis and treatment, step by step. Cleve Clin J Med 2006; 73:465–471.
Ritchlin CT. Pathogenesis of psoriatic arthritis. Curr Opin Rheumatol 2005; 17:406–412.
Leung YY, Tam LS, Kun EW et al. Psoriatic arthritis as a distinct disease entity. J Postgrad Med 2007; 53:63–71.
Benjamin M, Bydder GM. Magnetic resonance imaging of entheses using ultrashort TE (UTE) pulse sequences. J Magn Reson Imaging 2007; 25:381–389.
Canoso JJ. The premiere enthesis. J Rheumatol 1998; 25:1254–1256.
Benjamin M, Ralphs JR. Fibrocartilage in tendons and ligaments—An adaptation to compressive load. J Anat 1998; 193:481–494.
Vogel KG, Koob TJ. Structural specialization in tendons under compression. Int Rev Cytol 1989; 115:267–293.
Rufai A, Ralphs JR, Benjamin M. Structure and histopathology of the insertional region of the human Achilles tendon. J Orthop Res 1995; 13:585–593.
de Palma L, Marinelli M, Meme L et al. Immunohistochemistry of the enthesis organ of the human Achilles tendon. Foot Ankle Int 2004; 25:414–418.
Theobald P. Biomechanical Analysis of the Achilles Tendon Enthesis Organ. PhD Thesis, Cardiff University, 2006: 32–76.
Sella EJ, Caminear DS, McLarney EA. Haglund’s syndrome. J Foot Ankle Surg 1998; 37:110–114.
Theobald P, Bydder G, Dent C et al. The functional anatomy of Kager’s fat pad in relation to retrocalcaneal problems and other hindfoot disorders. J Anat 2006; 208:91–97.
Canoso JJ, Liu N, Traill MR et al. Physiology of the retrocalcaneal bursa. Ann Rheum Dis 1988; 47:910–912.
Shaw HM, Santer RM, Watson AHD et al. Adipose tissue at entheses: The innervation and cell composition of the retromalleolar fat pad associated with the Achilles tendon. J Anat 2007; J Anat 2007: 211:436–443.
Wood Jones F. Structure and Function as Seen in the Foot. London: Bailliere, Tindall and Cox, 1944:60.
Benjamin M, Theobald P, Suzuki D et al. The anatomy of the Achilles tendon. In: Maffulli N, Almekinders L, eds., The Achilles Tendon. Berlin: Springer-Verlag, 2007; 5–16.
Standring S. Gray’s Anatomy: The Anatomical Basis of Clinical Practice. 38 ed, 2004:881.
Yamamoto T, Mizuno K, Soejima T et al. Bicipital radial bursitis: CT and MR appearance. Comput Med Imaging Graph 2001; 25:531–533.
Olivieri I, Barozzi L, Padula A et al. Retrocalcaneal bursitis in spondyloarthropathy: Assessment by ultrasonography and magnetic resonance imaging. J Rheumatol 1998; 25:1352–1357.
Schweitzer TP, Rayan GM. The terminal tendon of the digital extensor mechanism: Part I, anatomic study. J Hand Surg (Am) 2004; 29:898–902.
Shum C, Bruno RJ, Ristic S et al. Examination of the anatomic relationship of the proximal germinal nail matrix to the extensor tendon insertion. J Hand Surg [Am] 2000; 25:1114–1117.
Tan AL, Benjamin M, Toumi H et al. The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis—A high-resolution MRI and histological study. Rheumatology (Oxford) 2007; 46:253–256.
Moriggl B, Kumai T, Milz S et al. The structure and histopathology of the “enthesis organ” at the navicular insertion of the tendon of tibialis posterior. J Rheumatol 2003; 30(3):508–517.
McGonagle D, Lories RJU, Benjamin M. The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 2007; 56:2482–2491.
Benjamin M, Toumi H, Suzuki D et al. Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders. Arthritis Rheum 2007; 56:224–233.
McGonagle D, Gibbon W, O’Connor P et al. Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum 1998; 41:694–700.
Benjamin M, Kumai T, Milz S et al. The skeletal attachment of tendons-tendon ‘entheses’. Comp Biochem Physiol A Mol Integr Physiol 2002; 133:931–945.
Milz S, Rufai A, Buettner A et al. Three-dimensional reconstructions of the Achilles tendon insertion in man. J Anat 2002; 200:145–152.
Maksymowych WP. Ankylosing spondylitis—At the interface of bone and cartilage. J Rheumatol 2000; 27:2295–2301.
Baker H, Golding DN, Thompson M. The nails in psoriatic arthritis. Br J Dermatol 1964; 76:549–554.
Cohen MR, Reda DJ, Clegg DO. Baseline relationships between psoriasis and psoriatic arthritis: analysis of 221 patients with active psoriatic arthritis. Department of Veterans Affairs Cooperative Study Group on Seronegative Spondyloarthropathies. J Rheumatol 1999; 26:1752–1756.
Jones SM, Armas JB, Cohen MG et al. Psoriatic arthritis: Outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol 1994; 33:834–839.
Wright V, Roberts MC, Hill AG. Dermatological manifestations in psoriatic arthritis: A follow-up study. Acta Derm Venereol 1979; 59:235–240.
Tan AL, Grainger AJ, Tanner SF et al. A high-resolution magnetic resonance imaging study of distal interphalangeal joint arthropathy in psoriatic arthritis and osteoarthritis: Are they the same? Arthritis Rheum 2006; 54:1328–1333.
Toumi H, Higashiyama I, Suzuki D et al. Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis. J Anat 2006; 208:47–57.
Benjamin M, Toumi H, Ralphs JR et al. Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load. J Anat 2006; 208:471–490.
Benjamin M, Kumai T, Milz S et al. The skeletal attachment of tendons—Tendon “entheses”. Comp Biochem Physiol A Mol Integr Physiol 2002; 133:931–945.
Benjamin M, Evans EJ, Copp L. The histology of tendon attachments to bone in man. J Anat 1986; 149:89–100.
Schneider H. Zur Struktur der sehnenansatzzonen. Z Anat Entwicklung 1956; 119:431–456.
Benjamin M, Evans EJ, Rao RD et al. Quantitative differences in the histology of the attachment zones of the meniscal horns in the knee joint of man. J Anat 1991; 177:127–134.
Benjamin M, Newell RL, Evans EJ et al. The structure of the insertions of the tendons of biceps brachii, triceps and brachialis in elderly dissecting room cadavers. J Anat 1992; 180:327–332.
Evans EJ, Benjamin M, Pemberton DJ. Fibrocartilage in the attachment zones of the quadriceps tendon and patellar ligament of man. J Anat 1990; 171:155–162.
Knese K-H, Biermann H. Die Khochenbildung an sehnen-und Bandsatzen im beriech ursprunglich chondraler apophysen. Z Zellforsch 1958; 49:142–187.
Waggett AD, Ralphs JR, Kwan AP et al. Characterization of collagens and proteoglycans at the insertion of the human Achilles tendon. Matrix Biol 1998; 16:457–470.
Milz S, Schluter T, Putz R et al. Fibrocartilage in the transverse ligament of the human atlas. Spine 2001; 26:1765–1771.
Zou J, Zhang Y, Thiel A et al. Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis. Rheumatology (Oxford) 2003; 42:846–855.
Glant T, Csongor J, Szucs T. Immunopathologic role of proteoglycan antigens in rheumatoid joint disease. Scand J Immunol 1980; 11:247–252.
Haines RW, Mohuiddin A. Metaplastic bone. J Anat 1968; 103:527–538.
Evans EJ, Benjamin M, Pemberton DJ. Variations in the amount of calcified tissue at the attachments of the quadriceps tendon and patellar ligament in man. J Anat 1991; 174:145–151.
Myerson M, Solomon G, Shereff M. Posterior tibial tendon dysfunction: Its association with seronegative inflammatory disease. Foot Ankle 1989; 9:219–225.
McGonagle D, Marzo-Ortega H, Benjamin M et al. Report on the second international enthesitis workshop. Arthritis Rheum 2003; 48:896–905.
McGonagle D, Marzo-Ortega H, O’Connor P et al. The role of biomechanical factors and HLA-B27 in magnetic resonance imaging-determined bone changes in plantar fascia enthesopathy. Arthritis Rheum 2002; 46:489–493.
McGonagle D, Stockwin L, Isaacs J et al. An enthesitis based model for the pathogenesis of spondyloar-thropathy. additive effects of microbial adjuvant and biomechanical factors at disease sites. J Rheumatol 2001; 28:2155–2159.
Lories RJ, Derese I, Luyten FP. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest 2005; 115:1571–1579.
McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 3:e297.
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Benjamin, M., McGonagle, D. (2009). The Enthesis Organ Concept and Its Relevance to the Spondyloarthropathies. In: López-Larrea, C., Díaz-Peña, R. (eds) Molecular Mechanisms of Spondyloarthropathies. Advances in Experimental Medicine and Biology, vol 649. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0298-6_4
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