Evaluation of Standard and Proposed Reference Values for Entheseal Thickening by Using Musculoskeletal Ultrasound

Abstract

ObjectiveUltrasound (US) is increasingly used to evaluate enthesitis. One of the US features of enthesitis is thickening. However, there is no consensus on how the entheseal thickening needs to be defined, and existing cut-off levels have been criticized for being frequently positive in healthy controls (HCs). Our objective was to determine the frequency of thickening of entheses on US using the existing cut-off values in HCs and in patients with axial spondyloarthritis (axSpA) and propose new values to improve discriminative value.MethodsEighty HCs and 100 patients with axSpA had US scans of 2160 entheses. Sensitivity, specificity, odds ratio (OR), and accuracy were calculated according to accepted cut-off levels from the literature and proposed cut-offs were calculated as the mean ± 2 SD.ResultsThickening according to current cut-off levels was found in 20.4% (196/960) of healthy participants' entheses and 33% (396/1200) of entheses of patients with axSpA. Thickening according to proposed cut-off levels decreased frequency of thickening in both groups, and therefore increased specificity at the cost of decreasing sensitivity. The only anatomical site where the thickness had a value to discriminate disease from health was seen at the triceps tendon enthesis with an OR of 13.4 (95% CI 4.0-44.8) according to the current cut-offs compared to 10.3 (95% CI 4.0-26.6) with the proposed cut-off levels.ConclusionAlthough using cut-offs appears to be an appealing method to evaluate entheseal thickness, the measurements may be affected by several confounding factors, leading to a low discriminative value, except for at the triceps tendon enthesis.

New Advances in the Knowledge of Elemental Enthesis Lesions: Doppler, Erosion, and Thickness

“…Even their discriminant validity between inflammatory patients and healthy subjects is poor. 25 The study by Keenan et al 13 is of interest due to the proposal of updated higher enthesis US thickening cut-off values in front of current margins 7,8 in patients with axial SpA. They found in both cases that only triceps tendon enthesis thickening discriminates healthy people from patients with SpA (cut-off > 4.2-4.3 mm).…”

“…In this issue of The Journal of Rheumatology, 2 new studies help deepen the knowledge and relevance of entheses in SpA and PsA. 12,13 Smerilli et al 12 share the results of a joint and entheses US study performed in 104 patients with PsA, exploring the association between enthesis involvement and peripheral joint damage measured by US joint erosions, demonstrating how enthesis US findings have become a biological marker of surrogate structural joint damage in PsA and reinforcing the central role of enthesis inflammation in PsA and its association with other outcomes and domains in this disease (joints, in this case). In this study, 12 joint erosions were found to be associated in the univariate and multi-variate model and in the logistic regression analysis with enthesis PD (β 0.51, P < 0.001 and odds ratio [OR] 1.74, 95% CI 1.17-2.59, P < 0.01), enthesis erosion (β 0.20, P = 0.02 and OR 3.17, 95% CI 1.30-7.77, P = 0.01), and greyscale joint synovitis (β 0.42, P = 0.03 and OR 2.59, 95% CI 1.16-5.78, P = 0.02).…”

“…Erosion appears in this study as the other elementary lesion of the enthesis related to joint damage in the multivariable analysis, which is very interesting since the evidence in this field is scarce but in agreement with previous studies. 21 The second article of interest related to enthesis is published by Keenan et al 13 in this issue of The Journal of Rheumatology. In this case, the topic is entheseal thickness, another OMERACT enthesis elemental lesion.…”

“…The problem is that in the aforementioned OMERACT reliability exercise, 5 thickening achieved the worst results, with a κ of 0.1 (95% CI 0-0.7), and this needs to be improved, highlighting the importance of the article by Keenan et al published in this issue. 13 Three options can be chosen to define entheseal thickening, as the authors mention 13 : comparing with the contralateral side (which does not seem appropriate in inflammatory patients, since the possibility of bilateral pathological findings increases), comparing the enthesis insertion with the body of the tendon, and using cut-off values (probably the most time-consuming option but increasing reliability and improving lesion assessment). The use of cut-offs has been the most employed method to date in the literature, but the accepted values were based on small sample studies, with heterogeneous cohorts (patients, healthy people, cadaveric samples), and most of the studies were published in the 1990s based on the low-quality US machines available at that time.…”

“…In summary, the study by Smerilli et al 12 adds to the previous studies a further step toward the confirmation of the association between enthesitis (based on enthesis PD) and peripheral radiographic damage in PsA, as well as an understanding of the connection of the enthesis with other distant domains, with a holistic explanation of interconnected PsA domains. The work by Keenan et al 13 will likely improve the reliability and demonstrate that having evaluation standards is highly desirable not only to improve knowledge in this field but also for the future accuracy of enthesis studies. Both studies published in this issue of The Journal of Rheumatology contribute new pieces to the complex puzzle of knowledge of the entheses.…”