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Summary Background Temporal artery biopsy is considered the diagnostic gold standard for giant cell arteritis, despite approximately 39% of patients who are negative for the condition by biopsy subsequently being given a clinical diagnosis of giant cell arteritis. We aimed to assess the diagnostic accuracy of ultrasound examination in patients with suspected giant cell arteritis. Methods In this prospective, multicentre, non-interventional, cohort study (evaluation of ultrasound's role in patients suspected of having extracranial and cranial giant cell arteritis; EUREKA), we consecutively recruited patients aged 50 years or older, with clinically suspected giant cell arteritis from three Danish hospitals (South West Jutland Hospital in Esbjerg, Silkeborg Regional Hospital, and Rigshospitalet, Glostrup). Participants had a bilateral ultrasound of the temporal, facial, common carotid, and axillary arteries. Ultrasounds were done by ultrasonographers who were systematically trained in vascular ultrasound using appropriate equipment and settings. Participants then had a temporal artery biopsy within 7 days of initiation of corticosteroid treatment. A blinded ultrasound expert assessed all ultrasound images. Ultrasound vasculitis was defined in cranial arteries as a homogeneous, hypoechoic, intimamedia complex thickness and a positive compression sign and as a homogeneous intimamedia complex of 1 mm in thickness or wider in the axillary arteries and of 1·5 mm thickness or wider in the common carotid artery. Participants were followed up at 6 months. During this 6 month period, clinicians were able to collect data from all clinical examinations to enable a full clinical diagnosis at 6 months. Clinical diagnosis was based on the expert opinion of the treating rheumatologist. The diagnostic criterion standard was diagnosis confirmed after 6 months of follow-up. We used logistic regression analyses to calculate the odds ratio and 95% CI of ultrasound as a predictor for giant cell arteritis. Findings Between April 1, 2014, and July 31, 2017, 118 patients were screened for inclusion, of whom 106 had both ultrasound examinations and an eligible temporal artery biopsy and were included in the intention-to-diagnose population. The mean age was 72·7 years (SD 7·9), 63 (59%) participants were women, and 43 (41%) were men. Temporal artery biopsy was positive in 46 (43%) of 106 patients, and 62 (58%) of 106 patients had a clinically confirmed diagnosis of giant cell arteritis at 6 months (temporal artery biopsy sensitivity 74% [95% CI 62–84], specificity 100% [95% CI 92–100]). Cranial artery ultrasound was positive in all patients who had a positive temporal artery biopsy, and seven (58%) of 12 patients who were positive by ultrasound and negative by temporal artery biopsy were confirmed to have large-vessel giant cell arteritis via other imaging methods. The sensitivity of ultrasound diagnosis of giant cell arteritis was 94% (84–98) and specificity was 84% (70–93). Logistic regression analysis confirmed that ultrasound was the strongest baseline predictor for a clinically confirmed diagnosis of giant cell arteritis at 6 months (crude odds ratio 76·6 [95% CI 21·0–280·0]; adjusted for sex and age 141·0 [27·0–743·0]). Interpretation Vascular ultrasound might effectively replace temporal artery biopsy as a first-line diagnostic method in patients suspected of having giant cell arteritis when done by systematically trained ultrasonographers using appropriate equipment and settings. Funding The Institute for Regional Research at Hospital of Southwest Jutland, Esbjerg, Denmark.

Objectives The role of musculoskeletal US (MSUS) in routine care for diagnosing arthritis is not fully elucidated, but US is more sensitive than clinical joint examination for detecting synovitis. Therefore, the use of US may facilitate diagnosis of arthritis. The aim of the study was to assess whether MSUS examination of hands and feet in relation to the first clinical visit had an impact on the time to reach a final diagnosis and the number of clinical follow-up visits needed after first consultation. Methods Two cohorts referred to the outpatient arthritis clinic with suspected arthritis were compared with each other, (i) MSUS (October 2017 to June 2018) of hands and feet performed prior to the first clinical visit and (ii) MSUS (November 2016 to June 2017) was performed ad hoc, for the following aspects: time to clinical diagnosis, number of clinical visits needed, and number of US examinations. Results In total, 163 and 109 patients were included in the MSUS and comparative cohorts, respectively. Adding MSUS to the first clinical visit reduced the time to diagnosis from mean 31 (32.2) days to 12 (17.3) days (P Conclusion In patients referred for suspected arthritis, routine MSUS in relation to the first clinical visit significantly reduces time to diagnosis and number of clinical visits needed to reach a final diagnosis.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

Objective To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. Methods Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0–3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. Results Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10–0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. Conclusion Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up—the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

AimTo describe salivary gland involvement in patients suspected of Sjögren’s syndrome (SS) using the OMERACT Ultrasound Scoring System for SS. Next, using different ultrasound cut-offs, to assess the performance of the scoring system for diagnosis and fulfilment of 2016 ACR/EULAR SS classification criteria.MethodsAll patients referred to our department with a suspicion of SS in a 12-month period were included. All underwent grey-scale ultrasound of the parotid and submandibular glands prior to clinical examination, Schirmer’s test, unstimulated salivary flow, blood samples including autoantibody analysis. Labial biopsy was performed according to clinicians’ judgement. Images of the four glands were scored 0–3 according to the scoring system and a consensus score was obtained using a developed ultrasound atlas.ResultsOf the 134 patients included in the analysis, 43 were diagnosed with primary SS (pSS) and all fulfilled the 2016 American College of Rheumatology (ACR)/EULAR classification criteria. More patients with pSS compared with non-pSS had score ≥2 in at least one gland (72% vs 13%; pConclusionThe OMERACT Ultrasound Scoring System showed good sensitivity (0.72) and excellent specificity (0.91) for fulfilling 2016 ACR/EULAR criteria using cut-off score >2 in at least one gland. Our data supports the use of ultrasound for diagnosing pSS and supports incorporation of ultrasound in the classification criteria.

The systemic large vessel vasculitides consist mainly of giant cell arteritis and Takayasu arteritis. Both diseases affect the large blood vessels and can lead to ischemia and end-organ damage. Ultrasound is an imaging technique that can depict inflammation of the vessel wall in large and medium vessel vasculitis. In this article, we critically review the current evidence for the clinical use of ultrasound for systemic large vessel vasculitides, regarding the clinical applicability, technical requirements, challenges, and cost. A roadmap for the development of a fast-track ultrasound clinic for giant cell arteritis is also provided.

Giant cell arteritis (GCA) is a medical and ophthalmological emergency due to risk of stroke and sudden irreversible loss of vision. Fast and accurate diagnosis is important to prevent complications and long-term high dose glucocorticoids toxicity. Temporal artery biopsy is gold standard for diagnosing GCA. However, temporal artery ultrasound is a fast and non-invasive procedure which may provide a supplement or an alternative to biopsy. This study assesses the diagnostic performance of ultrasound and biopsy in the diagnosis of GCA.Examination results of patients suspected of having GCA in the period from August 2018 to June 2019 were reviewed. Patients underwent clinical examination and blood tests. Within a few days of starting glucocorticoid treatment, temporal ultrasound and unilateral biopsy were performed. Experienced physicians established the final clinical diagnosis at 6-months follow-up.Seventy-eight patients underwent both ultrasound and biopsy. Thirty-five (45%) received the final clinical diagnosis of GCA. Compared with the final clinical diagnosis, biopsy had a sensitivity of 69% (51-83%) and a specificity of 100% (92-100%), and ultrasound a sensitivity of 63% (45-79%) and a specificity of 79% (64-94%). Area under the receiver operating characteristics curves were 0.84 and 0.71 for biopsy and ultrasound respectively (p = 0.048). False negative rate of ultrasound was 4 out of 78 (5%).Sensitivity of ultrasound is almost on par with that of biopsy although the overall diagnostic accuracy of ultrasound was slightly lower. We find that ultrasound is a reliable tool for first line diagnosis of GCA.

Background: Temporal artery biopsy (TAB) is considered the diagnostic gold standard for giant cell arteritis (GCA), despite up to 39% of biopsy-negative patients receiving a clinical diagnosis of GCA. This is a prospective, multicentre study assessing the diagnostic utility of ultrasound examination in patients with suspected GCA. Methods: Participants were recruited from three Danish centres among patients with clinically suspected GCA. Temporal (TA), facial (FA), common carotid (CC), and axillary arteries (AA) were examined by ultrasonographers, systematically trained in vascular ultrasound, using appropriate equipment and settings, before TAB. A blinded ultrasound expert evaluated all images. The primary outcome was the proportion of participants with clinically diagnosed GCA confirmed after 6-month follow-up. Ultrasound vasculitis was defined in cranial arteries as increased, hypoechoic intima-media thickness (IMT) and a positive compression sign, in large vessels as homogeneous IMT ≥ 1 mm in the AA and ≥1·5 mm in the CA. Findings: One hundred six patients were included in the intention-to-survey population. TAB was positive in 46 patients (43%), and 64 (60%) patients had a clinically confirmed diagnosis of GCA at 6-month follow-up (TAB sensitivity 74%, 95% CI 62–84%, specificity 100%, 95% CI 92–100%). Cranial artery ultrasound was positive in all TAB-positive patients. The sensitivity and specificity of the ultrasound diagnosis of clinical GCA were 94% (84–98%) and 84% (70–93%). Logistic regression analysis confirmed that ultrasound was the strongest baseline predictor for a clinically confirmed diagnosis of GCA at 6 months (crude: OR 76·6, 21·0–280·0; Adjusted for sex and age OR=141·0, 27·0–743). Interpretation: Vascular ultrasound can effectively replace TAB as a first-line diagnostic modality in patients suspected of having GCA when applied by systematically trained ultrasonographers using appropriate equipment and settings. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Written consent was obtained from all participating patients according to the Declaration of Helsinki. The study was approved by The Regional Committees on Health Research Ethics for Southern Denmark (reference number S-2014003) and the Danish Data Protection Agency (reference number 2008-58-0035).

Purpose The purpose of this study was to investigate seasonal variation in cases of biopsy-proven GCA in eastern Denmark in a 29-year period. Methods Pathology records of all temporal artery biopsies in eastern Denmark between 1990 and 2018 were reviewed. For each patient, data were collected which included age, sex, date of birth and biopsy result. Seasonality was evaluated using logistic regression and Poisson regression analysis. Lastly, an explorative pilot study was conducted to investigate a possible association between three weather parameters (average temperature, amount of rain and hours of sunshine) and the biopsy outcome. Results One thousand three hundred twenty-three biopsies were included of which 336 fulfilled objective criteria for GCA diagnosis. Mean age at diagnosis was 75.6 years (range 52-94 years). Among the biopsy-proven cases of GCA, there were 223 women (66.3%, mean age 76.2 years) and 113 men (33.7%, mean age 74.4 years) giving a female to male ratio of 1.97:1. The peak occurrence of GCA was in the 70-79 years age group. Statistical analysis of seasonal variation showed an increased risk of a positive biopsy during summer compared to autumn (p = 0.037). No association between the three weather parameters and the biopsy outcome was found. Conclusion In this study of biopsy-proven GCA in a large Danish patient cohort, the occurrence of GCA showed seasonal variation with higher occurrence in the summer months when compared to autumn. Future studies pooling all cases of GCA worldwide are needed to determine seasonality in the occurrence of GCA.

ObjectiveTo evaluate the impact of a standardised training programme including equipment adjustment for experienced musculoskeletal ultrasonographers without previous experience in vascular ultrasound (US) on the reliability of US in the diagnosis of giant cell arteritis (GCA).MethodsIn this prospective, non-interventional observational cohort study, patients suspected of GCA were evaluated by US by one of five rheumatologists with long-standing experience in musculoskeletal US (>8 years), trained using a standardised training programme including equipment adjustment. Images of cranial and large vessels were subsequently evaluated first by the performing ultrasonographer and thereafter by a blinded external expert (gold standard).ResultsIn three Danish centres, 112 patients suspected of GCA were included. According to the external expert, vasculitis changes were seen in 66 patients, in 45 of them with only cranial involvement, in 14 with both cranial and large vessel involvement, while in seven patients isolated large vessel vasculitis was found. The reliability was excellent between the local ultrasonographer and the US expert for the overall GCA diagnosis regarding the diagnosis of cranial and for large vessel GCA, with an interobserver agreement of 95–96%, mean kappa values of 0.88–0.92 (95% CI 0.78 to 0.99). Excellent reliability (mean kappa 0.86–1.00) was also found for the US examination of the individual arteries (temporal, facial, common carotid and axillary).ConclusionThe US training programme resulted in excellent agreement between trainees and an expert in patients suspected of GCA and may thus be applicable for implementation of vascular US in clinical practice.

Objectives: To investigate the anatomical distribution, morphological abnormalities and response to adalimumab therapy of ultrasound(US)-detected peripheral enthesitis in patients with axial spondyloarthritis (SpA). Methods: In a randomized, placebo-controlled, double-blinded, investigator-initiated trial (NCT01029847), patients with axial SpA according to the Assessment of Spondyloarthritis International Society criteria were randomized to subcutaneous adalimumab 40 mg every other week or placebo from baseline to week 6. From week 6 to 24, all patients received adalimumab 40 mg every other week. Of 49 patients enrolled, 21 patients participated in our observational US sub-study. US assessment applying the OMERACT US definitions for enthesitis of 10 peripheral entheseal regions of the upper and lower extremities and clinical examination were performed at baseline, weeks 6 and 24. US was performed by one experienced investigator. Hypo-echogenicity, increased thickness and Doppler activity of the enthesis were considered signs of active inflammation, whereas insertional bone erosions, intratendinous calcifications, and enthesophytes were regarded as signs of structural lesions. Results: Enthesitis on US was mostly present in the lower limbs, especially in the Achilles tendon (81%), the quadriceps tendon (62%), and the greater femoral trochanter (52%). Structural lesions were predominant (38 vs. 12% of examined entheses with inflammatory changes), particularly in the entheses of the lower limbs, and exhibited no change during treatment. Conclusion: US-detected structural lesions were common while inflammatory lesions were relatively rare in patients initiating adalimumab due to axial SpA. Structural lesions did not appear to change during 24 weeks follow-up, suggesting that these lesions may not be helpful outcome measures in short-term clinical trials.

Objective.To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.Methods.A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min.Results.In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments.Conclusion.OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

Background Ultrasound has been shown to be a promising tool in the evaluation of salivary glands for parenchyma changes with the potential to improve diagnosis. The changes range from mild inhomogeneity of the glandular tissue to large vesicular changes almost eliminating all normal glandular tissue. American-European Consensus Group (AECG) classification criteria for SS are often used diagnostically (1). Objectives To describe ultrasound findings in salivary glands (SGUS) in a cohort of patients with suspected Sjogren’s syndrome (SS) and assess their positive and negative predictive value for the diagnosis. Methods 191 consecutive patients with suspected SS (ocular and/or oral dryness) referred to the department of Rheumatology between March 2017 and March 2018 were evaluated by SGUS as part of the initial evaluation. All had unstimulated sialometry, Schirmer’s test and laboratory test done (including autoantibodies (ANA screening, Rheumatoid factor and anti-cyclic citrullinated peptide, anti-Ro/SSA and anti-La/SSB), and screenings test for hepatitis B+C). In doubtful cases, a minor salivary gland (MSG) biopsy was performed. SGUS was performed with a GE Logiq E9 equipped with a linear ML6-15 probe and included grey-scale evaluation of the submandibular and parotid gland bilaterally. SGUS was considered abnormal when moderate to severe inhomogeneity with anechoic or hypoechoic areas was present in at least one gland. Results 63 patients were diagnosed with SS according to the AECG classification criteria - 57 patients with primary SS, 6 with secondary SS. 128 patients with sicca symptoms did not fulfill AECG criteria for SS and none were diagnosed with SS based on other parameters. Demographic data for the cohort is shown in table 1. 55 patients had MSG biopsy performed. The SGUS examination and evaluation was performed in less than 15 min per patient. The sensitivity of SGUS is 0.51 and the specificity 0.88; the PPV of SGUS for the SS diagnosis was 0.68 and the NPV was 0.78 The sensitivity of SGUS for positive MSG biopsy was 0.29 and the specificity 0.82 – the PPV was 0.50 and the NPV was 0.65; for abnormal sialometry the sensitivity of SGUS was 0.32 and the specificity 0.82 - the PPV for SGUS was 0.64 and NPV was 0.55. Table 2 shows the association between SGUS and final diagnosis, MSG biopsy and sialometry, respectively. Conclusion SGUS has a high specificity but poor sensitivity for the SS diagnosis with a good NPV and a high specificity for positive MSG biopsy and positive sialometry. SGUS is a feasible method for the evaluation of structural changes in the salivary gland and may aid in the diagnosis and classification of SS. Reference [1] Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8. Disclosure of Interests Viktoria Fana: None declared, Uffe Moller Dohn Speakers bureau: Speakers fee from Eli Lilly, Novartis and Roche, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene

Objectives To develop and test the reliability of a new semiquantitative scoring system for the assessment of cartilage changes by ultrasound in a web-based exercise as well as a patient exercise of patients with RA. Methods A taskforce of the Outcome Measures in Rheumatology Ultrasound Working Group performed a systematic literature review on the US assessment of cartilage in RA, followed by a Delphi survey on cartilage changes and a new semiquantitative US scoring system, and finally a web-based exercise as well as a patient exercise. For the web-based exercise, taskforce members scored a dataset of anonymized static images of MCP joints in RA patients and healthy controls, which also contained duplicate images. Subsequently, 12 taskforce members used the same US to score cartilage in MCP and proximal interphalangeal joints of six patients with RA in in a patient reliability exercise. Percentage agreement and prevalence of lesions were calculated, as intrareader reliability was assessed by weighted kappa and interreader reliability by Light’s kappa. Results The three-grade semiquantitative scoring system demonstrated excellent intrareader reliability (kappa: 0.87 and 0.83) in the web-based exercise and the patient exercise, respectively. Interreader reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.48) in the patient exercise. Conclusion Our study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA.