Entheseal Doppler signals in ultrasound are associated with vasodilator drugs and age in patients with radiographic axial spondyloarthritis

Abstract

Background: The ability of modern ultrasound machines to detect signs of enthesitis has increased, yet there is a lack of studies on patients with long-standing radiographic axial spondyloarthritis (r-axSpA). Hence, we aimed to investigate the prevalence and clinical significance of Doppler signals indicative of inflammation in peripheral entheses of patients with long-standing disease.

Methods: Patients fulfilling the modified New York criteria for ankylosing spondylitis were included in this cohort study. Peripheral entheses were examined clinically and the presence of focal pain was self-reported on a mannequin. Ultrasound examination of 1692 entheses was performed. Doppler signals were graded from 0 to 3 using color Doppler ultrasound and Smooth Microvascular Imaging. Multivariable linear regression was used to explore factors influencing Doppler signals.

Results: One hundred and forty-one patients were included with, age (mean (SD)) 60 (12) years, symptom duration 34 (12) years, males 57%, and HLA-B27 86%. Overall, 21.3% of patients presented with ≥ 1 active ultrasound enthesitis (Doppler signals combined with hypoechoic tissue). In 4.3% of patients these findings were tender on palpation. Isolated Doppler signals were found in 89.4-97.1% of patients, with the highest mean Doppler grades in the triceps entheses (0.88), and the lowest in the Achilles tendons (0.28). In multivariable linear regression analysis, age (B (95% CI)) (0.01 (0.00; 0.01), p = 0.004), daily NSAIDs (0.15 (0.00; 0.30), p = 0.048), vasodilator drugs 0.16 (0.01; 0.32, p = 0.041), but not AS disease activity score, were associated with total Doppler scores.

Conclusion: The prevalence of asymptomatic entheseal ultrasound Doppler findings was overall high. The use of vasodilator drugs and higher age increased the Doppler scores. No association between disease activity and Doppler scores was found in patients with long-standing disease.

Keywords: Ankylosing spondylitis; Axial spondyloarthritis; Diagnostic imaging; Doppler ultrasonography; Enthesopathy.

Fig. 1

Flowchart of the inclusion process of patients with radiographic axial spondyloarthritis. Legend: r-axSpA radiographic axial spondyloarthritis

Fig. 2

Mean color Doppler grade at six different anatomical sites in a total of 1692 entheses. Legend: Values are mean sum of semiquantitative grading between 0–3 on bilateral examinations at each anatomical location. Whiskers show 95% confidence interval. Wilcoxon signed-rank test with Bonferroni correction was used for pairwise comparisons. CDU color Doppler ultrasound, SMI smooth microvascular imaging, Enthesis (A) < 2 mm from cortical bone, Outside the enthesis (B) tendon proximal to the enthesis. **** p < 0.0001, * p < 0.05, ns non-significant

Fig. 3

Entheseal Doppler grades and relation to symptoms and signs of enthesitis. Legend: The combined columns in each cluster include a total of 141 patients. Doppler grades are based on maximum values measured in, or outside the enthesis (A or B) using color Doppler ultrasound (CDU). Tender positive clinical enthesitis test, Reporting pain patient-reported focal pain for more than three months registered on a mannequin. Asymptomatic absence of reported focal pain and negative clinical enthesitis test

Fig. 4

The effect of vasodilator therapy on entheseal Doppler scores. Legend: Total Doppler score is based on summarized Doppler grades measured in the entheses (A) in all examined locations using color Doppler ultrasound (CDU) and smooth microvascular imaging (SMI). Mann–Whitney U-test: p < 0.005 (CDU), p < 0.003 (SMI). Whiskers mark the lowest/highest value within the 1.5 interquartile range beneath/above quartiles 1 and 3. ** p < 0.01