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The synovio-entheseal complex in enthesoarthritis

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Abstract

The group of diseases classified as seronegative spondyloarthritis or enthesoarthritis is characterized by typical osteoarticular and extra-articular manifestations. Diverse patterns of disease can affect different members of the same family and may show different features in the same patient, with clinical overlaps thwarting the differential diagnosis. An anatomo-pathological hallmark in enthesoarthritis is the inflammatory process in the synovio-entheseal sites. The inflammatory microenvironment of synovio-entheseal complex, named enthesitis, is characterized, after an initial inflammatory/erosive phase, by a subsequent phase of neobone apposition, which seems to progress independently from the previous erosive phase, suggesting that the physiopathogenetic mechanisms that underlay the two phases are driven by different pivots. The structural damage is characterized by excessive neobone formation, with the syndesmophyte as a typical lesion. The process underlying their formation is not fully understood, although there are many useful information to clarify the physiopathogenetic puzzle. The primum movens of the enthesitic process is the micro-trauma to which entheses are subject, especially in the lower limbs, for biomechanical reasons. The inflammatory process is facilitated by the sequential structure of the organ enthesis, constitutionally devoid of sub-enthesitic cortical bone and closely related to the underlying trabecular bone and the medullary vascular system. The reparative attempt from the vascular system, thanks to the activating action of certain loco-regional cytokines, such as TNF α, conditions the possible deposit in the enthesis of molecules derived from other organic sites and able, especially in HLA-B27+ subjects, to activate and self-renew an immune-mediated inflammatory process following the initial mechanical process.

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Acknowledgments

We apologize for not citing many important references that have contributed to this review due to space limitations. The authors are grateful for support to their research from the “5 × 1000” voluntary contribution. None of the authors received any funding related to the writing of this manuscript, and the funding bodies did not play any role in the writing of the manuscript or decision to submit the manuscript for publication.

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The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Division of Internal Medicine, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, FG, Italy

    Angelo De Cata, Michele Inglese, Rosa Rubino, Francesca Molinaro & Gianluigi Mazzoccoli

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  1. Angelo De Cata
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  2. Michele Inglese
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  3. Rosa Rubino
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  4. Francesca Molinaro
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  5. Gianluigi Mazzoccoli
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Correspondence to Gianluigi Mazzoccoli.

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De Cata, A., Inglese, M., Rubino, R. et al. The synovio-entheseal complex in enthesoarthritis. Clin Exp Med 16, 109–124 (2016). https://doi.org/10.1007/s10238-015-0341-x

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  • DOI: https://doi.org/10.1007/s10238-015-0341-x

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