OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

Azienda Ospedaliera Universitaria and University of Cagliari Monserrato Italy

Azienda Ospedaliero Universitaria di Parma Parma Italy

Carlo Urbani Hospital and Polytechnic University of Marche Ancona Italy

Carlo Urbani Hospital and Polytechnic University of Marche Ancona Italy and University of Leeds Leeds United Kingdom

Centro Hospitalar de Leiria Leiria Portugal and University of Beira Interior Covilhã Portugal

Centro Hospitalar e Universitário de Coimbra University of Coimbra Coimbra Portugal

Guangdong Provincial People's Hospital and Southern Medical University Guangdong China

Hacettepe University Ankara Turkey

Hokkaido Medical Center for Rheumatic Diseases Sapporo Japan

Hospital Italiano de Buenos Aires Buenos Aires Argentina

Hospital Juárez de México Mexico City Mexico

Hospital San Roque de Gonnet La Plata Argentina

Institución Prestadora de Salud Servicio Integral de Reumatología e Inmunología Doctor Orlando Villota and Fundación Hospital San Pedro Pasto Colombia

Institute of Psychophysical Rehabilitation Buenos Aires Argentina

IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Italy

Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca Romania

National Institute of Rehabilitation Luis Guillermo Ibarra Ibarra Mexico City Mexico

Reina Sofia University Hospital Cordoba Spain

University Hospital Motol Prague Czech Republic

University of Bari Bari Italy

University of Ioannina Ioannina Greece

University of Leeds NIHR Leeds BRC Leeds United Kingdom

University of Palermo Palermo Italy

Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

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Kehl AS, Corr M, Weisman MH. Review: enthesitis: new insights into pathogenesis, diagnostic modalities, and treatment. Arthritis Rheumatol 2016;68:312–322.

Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79:700–712.

Rudwaleit M, Landewé R, van der Heijde D, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009;68:770–776.

Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–783.

Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis 2024;83:706–719.

McGonagle DG, Helliwell P, Veale D. Enthesitis in psoriatic disease. Dermatology 2012;225:100–109.

Wu X, Liu D, Li Y, et al. A clinical practice guideline for the screening and assessment of enthesitis in patients with spondyloarthritis. Front Immunol 2022;13:978504.

Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum 2008;59:686–691.

Maksymowych WP, Mallon C, Morrow S, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis 2009;68:948–953.

Heuft‐Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003;62:127–132.

Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187–1193.

Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002;346:1349–1356.

Kaeley GS. Visualization of enthesitis by ultrasound: a key diagnostic tool in spondyloarthropathy diagnosis and management. Curr Rheumatol Rep 2020;22:48.

Filippucci E, Smerilli G, Di Matteo A, et al. Ultrasound definition of enthesitis in spondyloarthritis and psoriatic arthritis: arrival or starting point? Ann Rheum Dis 2021;80:1373–1375.

Smerilli G, Di Matteo A, Cipolletta E, et al. Enthesitis in psoriatic arthritis, the sonographic perspective. Curr Rheumatol Rep 2021;23:75.

Terslev L, Naredo E, Iagnocco A, et al. Defining enthesitis in spondyloarthritis by ultrasound: results of a delphi process and of a reliability reading exercise. Arthritis Care Res (Hoboken) 2014;66:741–748.

Balint PV, Terslev L, Aegerter P, et al. Reliability of a consensus‐based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis 2018;77:1730–1735.

Zabotti A, Bandinelli F, Batticciotto A, et al.; Musculoskeletal Ultrasound Study Group of the Italian Society of Rheumatology. Musculoskeletal ultrasonography for psoriatic arthritis and psoriasis patients: a systematic literature review. Rheumatology (Oxford) 2017;56:1518–1532.

Gouze H, Backhaus M, Balint P, et al. Ultrasound in the management of patients with psoriatic arthritis: systematic literature review and novel algorithms for pragmatic use. J Rheumatol Published online September 15, 2023. https://doi.org/10.3899/jrheum.2023-0091

Macchioni P, Salvarani C, Possemato N, et al. Ultrasonographic and clinical assessment of peripheral enthesitis in patients with psoriatic arthritis, psoriasis, and fibromyalgia syndrome: the ULISSE study. J Rheumatol 2019;46:904–911.

Di Matteo A, Smerilli G, Di Donato S, et al. Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study. Ann Rheum Dis Published online June 12, 2024. https://doi.org/10.1136/ard-2023-225443

Schoels M, Aletaha D, Funovits J, et al. Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis. Ann Rheum Dis 2010;69:1441–1447.

Lukas C, Landewé R, Sieper J, et al. Development of an ASAS‐endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24.

Gossec L, Portier A, Landewé R, et al. Preliminary definitions of “flare” in axial spondyloarthritis, based on pain, BASDAI and ASDAS‐CRP: an ASAS initiative. Ann Rheum Dis 2016;75:991–996.

Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21:2281–2285.

Jenkinson TR, Mallorie PA, Whitelock H, et al. Defining spinal mobility in ankylosing spondylitis: the Bath Ankylosing Spondylitis Metrology Index. J Rheumatol 1994;21:1694–1698.

Fries JF, Spitz P, Kraines G, et al. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137–145.

Di Matteo A, Filippucci E, Cipolletta E, et al. Entheseal involvement in patients with systemic lupus erythematosus: an ultrasound study. Rheumatology (Oxford) 2018;1;57:1822–1829.

Möller I, Janta I, Backhaus M, et al. The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology. Ann Rheum Dis 2017;76:1974–1979.

Di Matteo A, Filippucci E, Cipolletta E, et al. How normal is the enthesis by ultrasound in healthy subjects? Clin Exp Rheumatol 2020;38:472–478.

Di Matteo A, Filippucci E, Cipolletta E, et.al Reply to: High prevalence of ultrasound‐defined enthesitis in patients with metabolic syndrome. Clin Exp Rheumatol 2021;39:437.

de Miguel E, Cobo T, Munoz‐Fernandez S, et al. Validity of enthesis ultrasound assessment in spondyloarthropathy. Ann Rheum Dis 2009;68:169–174.

Kiris A, Kaya A, Ozgocmen S, et al. Assessment of enthesitis in ankylosing spondylitis by power Doppler ultrasonography. Skeletal Radiol 2006;35:522–528.

Freeston JE, Coates LC, Helliwell PS, et al. Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power Doppler ultrasound. Arthritis Care Res (Hoboken) 2012;64:1617–1621.

Di Matteo A, Cipolletta E, Destro Castaniti GM, et al. Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web‐based study. Rheumatology (Oxford) 2022;28;61:4863–4874.

Landis JR, Koch GG. An application of hierarchical kappa‐type statistics in the assessment of majority agreement among multiple observers. Biometrics 1977;33:363–374.

Zabotti A, Piga M, Canzoni M, et al; UPSTREAM study group. Ultrasonography in psoriatic arthritis: which sites should we scan? Ann Rheum Dis 2018;77:1537–1538.

McGonagle D, Aydin SZ, Marzo‐Ortega H, et al Hidden in plain sight: is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis? Semin Arthritis Rheum 2021;51:1147–1161.

Helliwell PS. Assessment of enthesitis in psoriatic arthritis. J Rheumatol 2019;46:869–870.

Fiorenza A, Bonitta G, Gerratana E, et al. Assessment of enthesis in patients with psoriatic arthritis and fibromyalgia using clinical examination and ultrasound. Clin Exp Rheumatol 2020;38 Suppl 123:31–39.

Aydin SZ, Bakirci S, Kasapoglu E, et al. The relationship between physical examination and ultrasonography of large entheses of the Achilles tendon and patellar tendon origin. J Rheumatol 2020;47:1026–1030.

Sapsford M, Evans J, Clunie G, et al. A comparison of clinical examination and ultrasound enthesitis indices in patients with psoriatic arthritis, adjusted for concomitant fibromyalgia. Ther Adv Musculoskelet Dis 2021;13:1759720X211003812.

Michelsen B, Diamantopoulos AP, Soldal DM, et al. Achilles enthesitis defined by ultrasound is not associated with clinical enthesitis in patients with psoriatic arthritis. RMD Open 2017;16;3:e000486.

Di Matteo A, Mankia K, Azukizawa M, et al. The role of musculoskeletal ultrasound in the rheumatoid arthritis continuum. Curr Rheumatol Rep 2020;22:41.

Eder L, Mathew AJ, Carron P, et al. Management of enthesitis in patients with psoriatic arthritis: an updated literature review informing the 2021 GRAPPA treatment recommendations. J Rheumatol 2023;50:258–264.

D'Agostino MA, Carron P, Gaillez C, et al. Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52‐week clinical and ultrasound results from the randomised, double‐blind ULTIMATE trial with open label extension. Semin Arthritis Rheum 2023;63:152259.

Elliott A, Wright G, Pendleton A, et al. Effects of TNF‐α inhibition versus secukinumab on active ultrasound‐confirmed enthesitis in psoriatic arthritis. Ther Adv Musculoskelet Dis 2023;15:1759720X231179524.

Smerilli G, Cipolletta E, Di Matteo A, et al. ‘Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis. Clin Exp Rheumatol 2024;42:626–632.

Aydin SZ, Mathew AJ, Koppikar S, et al. Imaging in the diagnosis and management of peripheral psoriatic arthritis. Best Pract Res Clin Rheumatol 2020;34:101594.

D'Agostino MA, Terslev L. Imaging evaluation of the entheses: ultrasonography, MRI, and scoring of evaluation. Rheum Dis Clin North Am 2016;42:679–693.

Maldonado RA, Ruta S, Valuntas ML, et al. Ultrasonography assessment of heel entheses in patients with spondyloarthritis: a comparative study with magnetic resonance imaging and conventional radiography. Clin Rheumatol 2017;36:1811–1817.

Felbo SK, Østergaard M, Sørensen IJ, et al. Ultrasound of the heel improves diagnosis‐tender entheses in the heel region rarely corresponds to inflammatory enthesitis in patients with peripheral spondyloarthritis. J Clin Med 2022;11:2325.

Polachek A, Cook R, Chandran V, et al. The association between sonographic enthesitis and radiographic damage in psoriatic arthritis. Arthritis Res Ther 2017;19:189.

Smerilli G, Cipolletta E, Destro Castaniti GM, et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol 2023;50:70–75.