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Objectives: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population., Methods: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas)., Results: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses., Conclusions: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA., Competing Interests: Competing interests: ADM has received speaking fees from Janssen and has received support for attending meetings by Galapagos outside the submitted work. GS has received speaking fees and support for attending meetings by Novartis outside the submitted work. EC has received speaking fees from Novartis outside the submitted work. EDD has received speaking fees from Novartis and has received support for attending meetings by AbbVie outside the submitted work. MF has received speaking fees from Galapagos, AbbVie, Boehringer Ingelheim, Lilly and GSK and has received support for attending meetings by Pfizer outside the submitted work. XM has received speaking fees from AbbVie, Lilly Novartis, UCB and Janssen and has received support for attending meetings by UCB and Janssen outside the submitted work. MGR has received speaking fees from AbbVie, Raffo and Tecnofarma outside the submitted work. HM-O has received research grants from Janssen, Novartis, Pfizer and UCB and honoraria/speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB non-relevant to the submitted work. WG has received speaking fees from Accademia di Medicina, Janssen, Angelini Ethos, Galapagos, Biopharma and UVET outside the submitted work. EF has received speaking fees from AbbVie, Amgen, BMS, Janssen, Lilly, Novartis, Pfizer and Union Chimique Belge Pharma outside the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases., Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients., Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively)., Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases., Competing Interests: SA received honoraria from AbbVie, Celgene, UCB, Novartis, Janssen, Pfizer, and Sanofi. AB served as a speaker for AbbVie, Amgen, Sanofi-Genzyme, and UCB, outside the submitted work. EF had received speaking fees from AbbVie, Amgen, BMS, Janssen, Lilly, Novartis, Roche, Pfizer, and UCB, outside the submitted work. WG had received speaking fees from Celltrion and Pfizer, outside the submitted work., (Copyright © 2023 Di Matteo, Moscioni, Lommano, Cipolletta, Smerilli, Farah, Airoldi, Aydin, Becciolini, Bonfiglioli, Carotti, Carrara, Cazenave, Corradini, Cosatti, de Agustin, Destro Castaniti, Di Carlo, Di Donato, Di Geso, Elliott, Fodor, Francioso, Gabba, Hernández-Díaz, Horvath, Hurnakova, Jesus, Marin, Martire, Mashadi Mirza, Massarotti, Musca, Nair, Okano, Papalopoulos, Rosa, Rosemffet, Rovisco, Rozza, Salaffi, Scioscia, Scirè, Tamas, Tanimura, Ventura-Rios, Villota-Eraso, Villota, Voulgari, Vreju, Vukatana, Hereter, Zanetti, Grassi and Filippucci.)

Objectives: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA., Methods: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs., Results: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation., Conclusions: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: The authors declare no conflict of interest.

Introduction: Musculoskeletal findings in MPS can progress after enzyme replacement. Our aim was to examine synovial recesses, tendons, retinacula and pulleys using ultrasonography for structural and inflammatory changes., Material and Methods: The wrist, metacarpophalangeal (MCP), proximal and distal interphalangeal (PIP and DIP) joints, the finger flexor tendons and the knee including entheses of quadriceps and patella tendons were assessed clinically. Ultrasonography of the various synovial recesses of the wrist as well as the extensor retinaculum, carpal tunnel, MCP, PIP and DIP joints of the second finger, extensor and flexor tendons, A1-5 pulleys and the knee joint including relevant entheses followed. Significance of differences between patient values and available normative data were assessed using t-tests., Results: Ultrasonography showed significant abnormal intraarticular material in the wrist without a clear distribution to synovial recesses and without effusions. Doppler signals were found in a perisynovial distribution and not intrasynovial as expected in in inflammatory arthritis. Findings were similar in the knee but not the fingers. Flexor and extensor tendons were also mostly normal in their structure but significant thickening of retinaculae and the flexor tendon pulleys was seen (p<0.0001 compared to normal)., Conclusion: MPS I patients showed intraarticular deposition of abnormal material in the wrist and knee but not in the finger joints where significant thickening of retinaculae/pulleys controlling tendon position was dominant. No ultrasound findings of inflammatory pathology were demonstrated but rather a secondary reaction to abnormal deposition and direct damage of GAG., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Ultrasonography might be an important imaging method for assessing the pediatric enthesis. To diagnose pathology, knowledge of physiological findings is essential but limited., Objective: To provide a detailed ultrasonographic assessment of four lower-extremity entheses in healthy adolescents as a reference for the correct interpretation of findings in children with rheumatic diseases., Materials and Methods: The quadriceps tendon, proximal and distal patella tendon, and Achilles enthesis were examined in B-mode, Power and color Doppler in 41 boys and girls ages 11-14 years in neutral position and 30° flexion. We assessed Doppler signals at various distances from the enthesis and analyzed the data using a marginal logistic regression model with generalized estimating equation. We assessed agreement between observers using weighted kappa and we determined agreement on repeat scans using prevalence- and bias-adjusted kappa., Results: Doppler signals were predominantly in the quadriceps and distal patella tendon with odds ratios of 50.85 and 21.35 (P<0.001) compared to the Achilles tendon. They were within 2 mm or 5 mm of the enthesis (odds ratios [ORs] of 4.58 and 4.24, P<0.001), without significant difference between flexion and neutral position and between the right and the left legs. Agreement between first and second assessment was good, with aggregate kappas from 0.79 to 0.90. The inter-reader agreement was also good, with aggregate kappas ranging from 0.75 to 0.95., Conclusion: We found a differential Doppler pattern in lower-extremity entheses, with signals present mostly in the quadriceps and distal patella entheses.

To validate the clinical applicability and feasibility of an automated ultrasound (US) method in measuring the arterial stiffness of patients with chronic inflammatory rheumatic diseases, comparing automated measurements performed by a rheumatologist without experience in vascular sonography with those obtained by a sonographer experienced in vascular US, using a standardized manual method. Twenty subjects affected by different chronic inflammatory rheumatic disorders were consecutively recruited. For each patient, the arterial stiffness of both common carotids was manually calculated. Subsequently, the measure of the pulse wave velocity (PWV) was obtained using an US device called Radio Frequency - Quality Arterial Stiffness (RF-QAS), provided by the same US system (ie, My Lab 70 XVG, Esaote SpA, Genoa, Italy) equipped with a 4-13 MHz linear probe. The reliability comparison between the two US methods was calculated using the intraclass correlation coefficient (ICC). ICC between the values obtained with the two methods for calculating the arterial stiffness resulted 0.789. A significant positive correlation between the two methods was also established with Pearson's (r=0.62, p<0.0001) and Spearman's analysis (r=0.66, p=0.001). A significant performance comparison was seen using Bland-Altman plot. The acquisition of the arterial stiffness parameter with the automated method required about 2 min for each patient. Clinical applicability of this US automated method to assess PWV at common carotid level by a rheumatologist is reliable and feasible in comparison with a conventional manual method., Competing Interests: Competing interests: EMZ, AA, DMZ, CG, FS, MC declare no competing interests. LDG has received speaking fees from Esaote Spa. EF has received speaking fees from AbbVie, UCB Pharma, Bristol-Myers Squibb, Merck Sharp & Dohme. WG has attended advisory board meetings and scientific consultancies and has received speaking fees from General Electric Medical System, Esaote Spa, Bristol-Myers Squibb, Merck Sharp & Dohme, Schering Plough, UCB Pharma, AbbVie, Savient, Pfizer, Menarini, Wyeth and Fidia., (© American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: The main aim of this study was to investigate the relationship between ultrasound (US) findings indicative of joint inflammation and US features characterising bone erosions at joint level in patients with rheumatoid arthritis (RA) in clinical remission., Methods: Twenty-four consecutive patients with RA in clinical remission according to EULAR criteria (DAS28<2.6) underwent a complete clinical assessment. An experienced sonographer blind to the clinical data performed the US examinations to detect and score signs of joint inflammation and bone erosions from second to fifth metacarpophalangeal (MCP) joints of both hands. All joints were scanned both on dorsal and volar aspects. The second and fifth MCP joints were scanned also in lateral aspects., Results: The patients were mainly female (79.2%), with a mean age of 63.2 years ±12.3 standard deviation (SD) and a mean disease duration of 114.5 months ±53.9 SD. Half of the patients were rheumatoid factor positive and 45.8% were anti-citrullinated protein antibody positive. A total of 192 MCP joints and 480 aspects were assessed. Of these joints, 105 (54.7%) were found inflamed by grey-scale US, 57 (29.7%) were power Doppler (PD) positive, and bone erosions were detected in 42 (21.7%) joints. PD signal was found in 30 (53.6%) of the 56 eroded aspects and in only 41 (9.7%) out of the 424 aspects without bone erosions. Both the GS and PD mean scores were statistically higher in the joints with US bone erosions compared to those without erosions., Conclusions: A higher prevalence of PD signal was found in the joints where bone erosions were detected. This is the first study providing evidence supporting the association between US bone erosions and the persistence of subclinical inflammation in RA patients in clinical remission.

Recent advances in imaging technology are dramatically changing the approach to patients with inflammatory arthritis. Conventional radiography is still the major imaging modality used to evaluate patients with rheumatoid arthritis in daily clinical practice. In the last decade, several investigations have shown the diagnostic ability of MRI and ultrasound to rectify the traditional approach to early diagnosis and disease activity monitoring. This review will summarize the options, uses and optimization of these imaging modalities with a special focus on ultrasound, which is currently the most promising tool to change the paradigms in both early diagnosis and therapy monitoring of rheumatoid arthritis.

For decades, diagnostic imaging in rheumatology has used conventional radiography. Over the past 10 years, MRI and ultrasonography have clearly shown their potential in diagnostic imaging in rheumatology and their use is revolutionizing the management of chronic arthritis, revealing subclinical inflammation and predicting progression of joint damage. Although validation processes for these imaging modalities are still ongoing, several investigations have now established the positive correlation between subclinical synovitis and radiographic progression of joint damage. Despite the available evidence and the diagnostic potential, there remains a substantial proportion of rheumatologists for whom MRI and ultrasonography findings do not influence their clinical decision-making. This Perspectives will discuss the key issues related to diagnostic imaging in patients with chronic arthritis, outlining how new imaging techniques have evolved over the past two decades and presenting the most attractive technological advances in this field.

Objective: The objective of this study was to determine the prevalence and distribution of bone erosions detectable by US in patients with early RA (ERA) in comparison with long-standing RA (LSRA), other erosive diseases and healthy controls., Methods: Thirty patients with ERA and 80 patients with LSRA were consecutively recruited. Thirty patients with PsA, 15 with primary OA, 10 with gout and 20 healthy subjects were included as controls. Bone erosions were investigated at the following anatomical sites: the second and fifth metacarpal heads, the ulnar head and the first and fifth metatarsal heads, bilaterally. Dorsal, volar and lateral aspects were explored on longitudinal and transverse views., Results: At least one US bone erosion was found in 20 (66.7%) of 30 patients with ERA and in 10 (33%) of them it was found on the fifth metatarsal head. Bone erosions were most frequently found on the lateral quadrants of all scanned anatomical sites. If the second and fifth metacarpal heads and the fifth metatarsal head were scanned, an erosive disease could be found in 60% of ERA patients. The first metatarsal head was most frequently involved in the disease control group., Conclusion: This study found a high percentage of ERA patients with US bone erosions, with the fifth metatarsal head and the lateral aspects the most frequently involved site and quadrants. US scanning for bone erosions on a few target joints was found feasible and provided information not obtainable with clinical examination.

Objective: The objective of this study was to draw up a set of recommendations for the format and content of the musculoskeletal ultrasonography (MSUS) report in rheumatology., Methods: A panel of rheumatologists, members of the MSUS Study Group of the Italian Society of Rheumatology, met in order to identify the main discrepancies in the MSUS report. A set of 15 recommendations was then defined, aimed at resolving the main discrepancies. They consisted of information about the motivations for the MSUS examination, the equipment, the US modalities and scanning technique, a list of the examined structures and findings, the scoring/grading systems, the number of images and main findings to include and conclusions. Subsequently a Delphi-based procedure was started in order to obtain agreement on a core set of recommendations. Consensus for each recommendation was considered achieved when the percentage of agreement was >75%., Results: Three complete rounds were performed. The response rate was 85.2% for the first round, 78.3% for the second and 88.9% for the third. Finally, consensus was obtained for 14 of 15 statements. These 14 statements represent the recommendations of the group for the format and content of the report and documentation in MSUS in rheumatology., Conclusion: To the best of our knowledge, our group has produced the first recommendations for the format and content of the report and documentation in MSUS in rheumatology. The report is an integral part of the MSUS examination and its use in a homogeneous form can help in the correct interpretation of the findings.

In the last decade, an increasing number of rheumatologists have been using ultrasound (US) for assessing patients with gout and calcium pyrophosphate deposition (CPPD) disease. The high reflectivity of the crystalline aggregates and the ability of US to detect even minimal crystal deposits explain the high sensitivity of this imaging technique. Furthermore, the peculiar distribution within the target tissues results in the generation of typical US patterns and explains the excellent specificity of some US findings. The large spectrum of US findings and their wide combination generate different scenarios in different patients and also in the same subject. Such a high variety impaired the standardisation of the definitions of each US finding. This review presents the main US findings indicative of crystal deposits, discusses the available evidence supporting the use of US in patients with gout and CPPD disease, and provides a research agenda to guide further investigations. The combined US examination of the target tissues and the clinically involved sites represents the key issue to obtain the best compromise between accuracy and feasibility, in the daily US assessment of patients with crystal-related arthropathies. Moreover, the US guided aspiration of synovial fluid may enhance the possibility to reach a crystal-proven diagnosis, making US a complementary tool, not in contrast, with microscopy, which rests the current gold standard. Finally, even if at moment other US findings are not included among the typical ones for crystal-related arthropathies, it is possible that in the future, thanks to continuous technological advances, we will be able to identify other specific patterns of pathology.

Objective: To determine the sensitivity, specificity, and accuracy of ultrasound (US) in the detection of cartilage calcification at knee level in patients with calcium pyrophosphate deposition disease (CPDD) and to assess the interobserver reliability., Methods: Seventy-four CPDD patients and 83 controls with other chronic arthritis were included. All patients underwent a clinical examination, synovial fluid analysis, and radiographic assessment of the knee. US examinations were performed in order to detect hyperechoic spots within the hyaline cartilage layer and hyperechoic areas within the meniscal fibrocartilage. Twenty patients were assessed by 2 operators in order to calculate the interobserver reliability., Results: A total of 314 knees in 157 patients (74 with CPDD, 19 with rheumatoid arthritis, 17 with spondyloarthritis, 32 with osteoarthritis, and 15 with gout) were assessed. In the 74 patients with CPDD, hyaline cartilage spots were detected by US in at least 1 knee in 44 patients (59.5%), whereas radiography detected hyaline cartilage spots in 34 patients (45.9%) (P < 0.001). Meniscal fibrocartilage calcifications were detected by US in 67 of the 74 CPDD patients (90.5%), whereas conventional radiography detected calcifications in 62 patients (83.7%) (P = 0.011). The criterion validity expressed as percentage of sensitivity, specificity, and accuracy of US in the detection of articular cartilage calcification was high. Both kappa values and overall agreement percentages showed moderate to excellent agreement., Conclusion: US is an accurate and reliable imaging technique in the detection of articular cartilage calcification at knee level in patients with CPDD., (Copyright © 2014 by the American College of Rheumatology.)

Objectives: This study was aimed at determining the prevalence of ultrasound (US) morpho-structural changes in the shoulders of patients with crystal-related arthropathies, and at investigating the relationship between them and the clinical findings., Methods: Eighty-eight patients with a crystal proven diagnosis of gout or calcium pyrophosphate dihydrate (CPPD) disease attending the in-patient and the out-patient clinics of four Italian Rheumatology Departments were consecutively enrolled in this multi-centre study. All patients were clinically examined by an expert rheumatologist who recorded clinical and laboratory data in addition to the presence/absence of spontaneous shoulder pain and performed the Hawkins, Jobe, Patte, Gerber, and Speed tests. In each centre, US examinations were carried out by a rheumatologist expert in musculoskeletal US blinded to clinical data, using a MyLab TWICE XVG machine (Esaote SpA, Genoa, Italy) equipped with a linear probe operating at 4-13 MHz, and a Logiq 9 machine (General Electrics Medical Systems, Milwaukee, WI, USA) with a linear probe operating at 9-14 MHz. Shoulders were scanned to detect peri-articular inflammation, rotator cuff pathology and joint involvement, and to reveal US signs indicative of crystal deposits., Results: A total of 88 patients, 39 with gout, 46 with CPPD disease, and 3 with both gout and CPPD disease, were enrolled. In total, 176 shoulders were clinically assessed, of which 54/176 (30%) were painful and 74/176 (42%) were clinically normal shoulders. All US findings indicative of peri-articular synovial inflammation were more frequently detected in patients with CPPD disease than in gouty patients. In 50 out of 176 (28.4%) shoulders, US allowed the detection of at least one finding indicative of synovial inflammation. Chronic tendinopathy was a frequent US finding both in gout patients and in patients with CPPD disease and the supraspinatus tendon was the most frequently involved one. In CPPD disease the supraspinatus tendon was found ruptured in a number of shoulders seven times higher than in gouty patients. The osteophytes were found at acromion-clavicular joint in nearly 80% of the shoulders in CPPD disease and in 60% in the gouty patients., Conclusions: The results of this study confirm the high specificity of US findings indicative of crystal deposits at hyaline cartilage level and indicate that the supraspinatus tendon and the fibrocartilage of the acromion-clavicular joint are the most frequently affected structures of the shoulders in patients with crystal-related arthropathies.