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.

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.

Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis.

OBJECTIVES: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. METHODS: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. RESULTS: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. CONCLUSION: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra.

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Ultrasonography in the prediction of gout flares: a 12-month prospective observational study.

OBJECTIVES: To evaluate whether US findings indicating MSU deposits and US-detected inflammation (i.e. power Doppler signal) predict gout flares over 12 months. METHODS: Gout patients on urate-lowering therapy for at least the preceding 6 months were enrolled consecutively in this 12-month prospective, observational, single-centre study. A nested case-control analysis was performed. Cases were participants with at least one flare in the follow-up period, while controls did not self-report any gout flare. The US assessment included elbows, wrists, second MCP joints, knees, ankles, and first MTP joints. The US findings indicating MSU deposits [i.e. aggregates, double contour (DC) sign and tophi] were identified as present/absent according to the Outcome Measure in Rheumatology definitions. Power Doppler signal was scored semiquantitatively. Summated scores were calculated for each US finding. RESULTS: Eighty-one gout participants were enrolled, and 71 completed the study. Thirty (42.3%) of 71 participants experienced at least one flare over 12 months, with a median of 2.0 flares. Cases had a greater US burden of MSU deposits (6.7 ± 4.7 vs 2.9 ± 2.6, P = 0.01) and power Doppler signal (3.73 ± 3.53 vs 0.82 ± 1.44, P < 0.01) than controls, at baseline. The baseline US scores indicating MSU deposits and US-detected inflammation were significantly associated with the occurrence (total MSU score, adjusted odds ratio:1.75, 95% CI: 1.26, 2.43; power Doppler score, adjusted odds ratio: 1.63, 95% CI: 1.12, 2.40) and the number (total MSU score, adjusted incidence risk ratio: 1.17, 95% CI: 1.08, 1.26; power Doppler score, adjusted incidence risk ratio: 1.29, 95% CI: 1.19, 1.40) of flares over 12 months in multivariate analyses. CONCLUSIONS: Baseline US findings indicating MSU deposits and US-detected inflammation are independent predictors of gout flares over 12 months.

Significant nailfold capillary loss and late capillaroscopic pattern are associated with pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: To evaluate differences in nailfold videocapillaroscopy (NVC) findings between systemic sclerosis-SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). METHODS: 110 SSc patients were enrolled in this cross-sectional, case-control, multi-centre study. Patients were divided into cases (SSc-PAH confirmed by right hearth catheterization-RHC) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active, and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. RESULTS: SSc-PAH patients showed higher frequencies of late pattern (p < 0.01), non-specific abnormalities (p < 0.01), lower capillary density (p < 0.01), higher avascular areas (p < 0.01), and a higher mean NVC score (p < 0.01). Contrarily, the early/active pattern (p < 0.01) and a higher rate of micro-haemorrhages (p = 0.04) were more frequent in non-PAH patients. By the multivariate analysis, SSc-PAH patients, compared to non-PAH, had more non-specific abnormalities (27/55, 49.1% vs 10/55, 18.2%, adjusted OR: 16.89, 95%CI: 3.06-93.16), a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%, adjusted OR: 38.33, 95%CI: 2.34-367.80), and avascular areas (18/55, 32.7% vs 10/55, 18.2%, adjusted OR: 16.90, 95%CI: 2.64-44.35). A correlation was found between the mean pulmonary arterial pressure-mPAP and avascular areas (p < 0.01), capillary density (p < 0.01), and non-specific abnormalities (p < 0.01). A clinical model including the NVC variables may be able to predict the diagnosis of PAH. CONCLUSIONS: Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH.

In patients with acute mono/oligoarthritis, a targeted ultrasound scanning protocol shows great accuracy for the diagnosis of gout and CPPD.

OBJECTIVES: To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin. METHODS: Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. RESULTS: A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92-0.96) and CPPD (0.90-0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD. CONCLUSIONS: A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.

Diagnosis of calcium pyrophosphate crystal deposition disease by ultrasonography: how many and which sites should be scanned?

OBJECTIVE: To develop the optimal US scanning protocol for the diagnosis of CPPD disease. METHODS: In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls and with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardised scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from 2nd to 5th fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the ROC curves. RESULTS: 204 participants were enrolled: 102 with CPPD disease and 102 disease controls [age (mean±standard deviation) 71.3 ± 12.0 vs 71.1 ± 13.5 years, female: 62.8% vs 57.8%].The median number of joints with US evidence of CPPD was 5 (IQR: 4-7) and 0 (IQR: 0-1) in patients with CPPD disease and controls, respectively (p< 0 01).The detection of CPPD in ≥ 2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists, and hips) showed a sensitivity of 96.7% (95%CI: 82.8-99.9) and a specificity of 100 (95%CI: 88.8-100.0) for the diagnosis of CPPD disease and had good feasibility [(mean±standard deviation) 12.5 ± 5.3 min]. CONCLUSION: Bilateral US assessment of knees, wrists, and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease.

Predicting acupuncture efficacy in fibromyalgia: results of a pragmatic open-label study.

OBJECTIVES: To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM). METHODS: Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models. RESULTS: Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04). CONCLUSIONS: High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.

Sonographic assessment of cartilage damage at the metacarpal head in rheumatoid arthritis: qualitative versus quantitative methods.

OBJECTIVE: To test the validity of the OMERACT semi-quantitative score by comparing with a quantitative method in the US assessment of hyaline cartilage at the metacarpal head (MH) in patients with RA and healthy controls (HCs). METHODS: The hyaline cartilage from the second to fifth MHs of both hands was scanned. Hyaline cartilage was scored semi-quantitatively and quantitatively by measuring cartilage thickness and comparing with reference values. In RA patients, radiographic joint space narrowing (JSN) was scored on the same joints using the Simple Erosion Narrowing Score (SENS). RESULTS: A total of 408 MHs in 51 RA patients and 320 MHs in 40 HSs were evaluated. The OMERACT semi-quantitative score was quicker to perform than the quantitative method [6.0 min (s.d. 0.5) vs 8.0 (1.5); P < 0.01]. A significant correlation between the US scores (R = 0.68) and between the US scores and the JSN-SENS (R = 0.61 and R = 0.63 for the semi-quantitative and quantitative method, respectively) was found. The frequency of cartilage abnormalities was similar between the two US methods in RA patients (58.8% and 51.0% of RA patients for the semi-quantitative and quantitative method, respectively; P = 0.46), while the former revealed more abnormalities in HCs (27.5% and 7.5% of HCs; P = 0.02). CONCLUSION: The higher feasibility of the OMERACT semi-quantitative score suggests its use as a first-choice method in the evaluation of cartilage damage. However, despite its limits, the quantitative assessment of HCs, providing patient-tailored information with age- and sex-corrected cut-off values, may represent a valid supplement for optimizing the evaluation of cartilage damage in selected cases.

Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints.

OBJECTIVE: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD). METHODS: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or OA with CPPD), and age- and sex-matched controls with RA were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage and bone erosions were recorded. RESULTS: Sixty CPPD patients (33, 55.0% with OA with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (P <0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, eight (13.3%) double contour sign and five (8.3%) flexor digitorum tendons' deposits. CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with OA with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype. CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively. CONCLUSION: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes.

Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum.

OBJECTIVES: To investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted. METHODS: First, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis ('progressors') were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted >6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset. RESULTS: US subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7-60]}, in whom one or more scan was available, excluding those with a negative scan >6 months from inflammatory arthritis development (n = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0-112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P < 0.01]. CONCLUSIONS: In anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease.

Muscle involvement in systemic lupus erythematosus: multimodal ultrasound assessment and relationship with physical performance.

OBJECTIVES: The objectives of this study were (1) to explore US findings for muscle mass, muscle quality and muscle stiffness in SLE patients and healthy subjects; (2) to investigate the relationship between the US muscle findings and physical performance in SLE patients and healthy subjects. METHODS: Quadriceps muscle thickness was used for assessment of muscle mass, muscle echogenicity (using a visual semi-quantitative scale and grayscale analysis with histograms) for assessment of muscle quality, and point shear-wave elastography (SWE) for assessment of muscle stiffness in 30 SLE patients (without previous/current myositis or neuromuscular disorders) and 15 age-, sex- and BMI-matched healthy subjects. Hand grip strength tests and short physical performance battery (SPPB) tests were carried out in the same populations. RESULTS: No difference was observed between SLE patients and healthy subjects for quadriceps muscle thickness (35.2 mm ±s.d. 6.8 vs 34.8 mm ± s.d. 6.0, respectively, P = 0.79). Conversely, muscle echogenicity was significantly increased in SLE patients (visual semi-quantitative scale: 1.7 ± s.d. 1.0 vs 0.3 ± s.d. 0.5, respectively, P < 0.01; grayscale analysis with histograms: 87.4 mean pixels ± s.d. 18.8 vs 70.1 mean pixels ± s.d. 14.0, respectively, P < 0.01). Similarly, SWE was significantly lower in SLE patients compared with healthy subjects {1.5 m/s [interquartile range (IQR) 0.3] vs 1.6 m/s (IQR 0.2), respectively, P = 0.01}. Muscle echogenicity was inversely correlated with grip strength (visual semi-quantitative scale, Rho: -0.47, P = 0.01; grayscale analysis with histograms, Rho: -0.41, p < 0.01) and SPPB (visual semi-quantitative scale, Rho: -0.50, P < 0.01; grayscale analysis with histograms Rho: -0,46, P < 0.01). CONCLUSIONS: US assessment of muscle echogenicity and stiffness is useful for the early detection of muscle involvement in SLE patients.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

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 Reliability of Ultrasound in the Assessment of Hyaline Cartilage in Rheumatoid Arthritis and Healthy Metacarpal Heads.

PURPOSE: i) To assess the inter- and intra-observer reliability of ultrasound (US) in the evaluation of the hyaline cartilage (HC) of the metacarpal head (MH) in patients with rheumatoid arthritis (RA) and in healthy subjects (HS) both qualitatively and quantitatively. ii) To calculate the smallest detectable difference (SDD) of the MH cartilage thickness measurement. iii) To correlate the qualitative scoring system and the quantitative assessment. MATERIALS AND METHODS: US examination was performed on 280 MHs of 20 patients with RA and 15 HS using a very high frequency probe (up to 22 MHz). HC status was evaluated both qualitatively (using a five-grade scoring system) and quantitatively (using the average value of the longitudinal and transverse measures). The HC of MHs from II to V metacarpophalangeal joint of both hands were scanned independently on the same day by two rheumatologists to assess inter-observer reliability. All subjects were re-examined using the same scanning protocol and the same US setting by one sonographer after a week to assess intra-observer reliability. RESULTS: The inter-observer agreement and intra-observer agreement were moderate to substantial (k = 0.66 and k = 0.73) for the qualitative scoring system and high (ICC = 0.93 and ICC = 0.94) for the quantitative assessment. The SDD of the MH cartilage thickness measurement was 0.09 mm. A significant correlation between the two scoring systems was found (r = -0.35; p < 0.001). CONCLUSION: The present study describes the main methodological issues of HC assessment. Using a standardized protocol, both the qualitative and the quantitative scoring systems can be reliable.

Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout.

Importance: Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated. Objective: To investigate whether there is a transient increase in risk of cardiovascular events after a recent gout flare. Design, Setting, and Participants: A retrospective observational study was conducted using electronic health records from the Clinical Practice Research Datalink in England between January 1, 1997, and December 31, 2020. A multivariable nested case-control study was performed among 62 574 patients with gout, and a self-controlled case series, adjusted for season and age, was performed among 1421 patients with gout flare and cardiovascular event. Exposures: Gout flares were ascertained using hospitalization, primary care outpatient, and prescription records. Main Outcomes and Measures: The primary outcome was a cardiovascular event, defined as an acute myocardial infarction or stroke. Association with recent prior gout flares was measured using adjusted odds ratios (ORs) with 95% CIs in a nested case-control study and adjusted incidence rate ratios (IRRs) with 95% CIs in a self-controlled case series. Results: Among patients with a new diagnosis of gout (mean age, 76.5 years; 69.3% men, 30.7% women), 10 475 patients with subsequent cardiovascular events were matched with 52 099 patients without cardiovascular events. Patients with cardiovascular events, compared with those who did not have cardiovascular events, had significantly higher odds of gout flare within the prior 0 to 60 days (204/10 475 [2.0%] vs 743/52 099 [1.4%]; adjusted OR, 1.93 [95% CI, 1.57-2.38]) and within the prior 61 to 120 days (170/10 475 [1.6%] vs 628/52 099 [1.2%]; adjusted OR, 1.57 [95% CI, 1.26-1.96]). There was no significant difference in the odds of gout flare within the prior 121 to 180 days (148/10 475 [1.4%] vs 662/52 099 [1.3%]; adjusted OR, 1.06 [95% CI, 0.84-1.34]). In the self-controlled case series (N = 1421), cardiovascular event rates per 1000 person-days were 2.49 (95% CI, 2.16-2.82) within days 0 to 60; 2.16 (95% CI, 1.85-2.47) within days 61 to 120; and 1.70 (95% CI, 1.42-1.98) within days 121 to 180 after a gout flare, compared with cardiovascular event rates of 1.32 (95% CI, 1.23-1.41) per 1000 person-days within the 150 days before or the 181 to 540 days after the gout flare. Compared with 150 days before or the 181 to 540 days after a gout flare, incidence rate differences for cardiovascular events were 1.17 (95% CI, 0.83-1.52) per 1000 person-days, and adjusted IRRs were 1.89 (95% CI, 1.54-2.30) within days 0 to 60; 0.84 (95% CI, 0.52-1.17) per 1000 person-days and 1.64 (95% CI, 1.45-1.86) within days 61 to 120; and 0.38 (95% CI, 0.09-0.67) per 1000 person-days and 1.29 (95% CI, 1.02-1.64) within days 121 to 180 after a gout flare. Conclusions and Relevance: Among individuals with gout, those who experienced a cardiovascular event, compared with those who did not experience such an event, had significantly higher odds of a recent gout flare in the preceding days. These findings suggest gout flares are associated with a transient increase in cardiovascular events following the flare.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

In anti-CCP+ at-risk individuals, radiographic bone erosions are uncommon and are not associated with the development of clinical arthritis.

OBJECTIVES: To investigate the prevalence, distribution and predictive value for the development of inflammatory arthritis (IA) of conventional radiography (CR) bone erosions (BE) in anti-CCP positive (CCP+) at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis. METHODS: Baseline CR of the hands and feet of 418 CCP+ at-risk individuals were analysed. The presence of US-BE was explored in the anatomical areas in which CR-BE were reported. Hands and feet CR at the time of progression were analysed in a subset of individuals who developed IA (73/123, 59.3%). Logistic regression analyses were performed to calculate the predictive value of baseline CR-BE for the development of IA in 394 CCP+ individuals with ≥1 follow-up visit. RESULTS: BE were detected in 17/418 (4.1%) CCP+ at-risk individuals (median Simple Erosions Narrowing Score-BE = 2.0, IQR: 1.0-2.0; median Sharp van der Heijde score-BE = 4.0, IQR: 3.0-8.5), most frequently in the foot joints (11/17, 64.7% individuals). A total of 123/394 (31.2%) CCP+ at-risk individuals developed IA; 7/17 (41.2%) with, and 116/377 (30.8%) without BE on CR (P = 0.37). US-BE were found in 4/7 (57.1%) individuals with CR-BE who developed IA, but only in 1/10 (10.0%) who did not. At the time of progression, new BE were detected in 4/73 (5.5%) CCP+ individuals on repeated CR. In the regression analyses, baseline CR-BE were not predictive for the development of IA. CONCLUSIONS: In CCP+ at-risk individuals with MSK symptoms, CR-detected BE are uncommon and do not predict the development of IA.

Is the intima-media thickness of temporal and axillary arteries influenced by cardiovascular risk?

OBJECTIVES: To measure with US the intima-media thickness (IMT) of temporal (superficial, parietal and frontal branches) and axillary arteries in subjects without a diagnosis of GCA and/or PMR with different cardiovascular (CV) risk; and to assess the performance of previously proposed cut-off values for normal IMT. METHODS: Subjects ≥ 50 years without a diagnosis of GCA or PMR were included. Bilateral US of the temporal arteries, including the frontal and parietal branches, and axillary arteries was performed by two sonographers using a 10-22 MHz and 6-18 MHz probe. The following previously proposed cut-offs were considered: superficial temporal artery: 0.42 mm; frontal branch: 0.34 mm; parietal branch: 0.29 mm; axillary artery: 1.0 mm. RESULTS: A total of 808 arteries in 101 subjects were evaluated; of these, 31 (30.7%) were classified as very high CV risk, seven (6.9%) as high, 34 (33.7%) as moderate and 29 (28.7%) as low risk. Subjects with very high or high risk showed higher IMT than those with moderate or low risk in the superficial temporal arteries [0.23 (s.d. 0.07) vs 0.20 (s.d. 0.04), P < 0.01] and in the axillary arteries [0.54 (s.d. 0.17) vs 0.48 (s.d. 0.10), P = 0.002] . The IMT was higher than the reference cut-off in 13/808 (1.6%) arteries, in ≥1 artery in 10/101 subjects (10.1%). Of these 10 subjects, 8 (80%) were classified as having very high or high risk. CONCLUSION: Our results suggest that CV risk might influence the US-determined IMT of the temporal and axillary arteries in subjects without GCA. Therefore, in patients with suspected GCA, particular attention should be paid when measuring the IMT in those patients with very high/high CV risk.

Clinical efficacy of ultrasound-guided hyaluronic acid injections in patients with supraspinatus tendon tear.

OBJECTIVES: To evaluate the clinical efficacy of ultrasound (US)-guided soft tissue adapted biocompatible hyaluronic acid (STABHA) injections in the subacromial-subdeltoid bursa of patients with supraspinatus tendon tear. METHODS: In this prospective study, patients with a symptomatic partial-thickness or small full-thickness supraspinatus tendon tear, diagnosed by US, were consecutively enrolled. Patients received one injection at baseline visit and one after 2 weeks and performed rehabilitation therapy. Clinical assessment was performed with visual analogue scale (VAS) for pain, Constant-Murley Scale (CMS), and patient reported efficacy on a 0-4 Likert scale. Patients were examined at baseline, at week 2 and at week 12. RESULTS: Thirty patients were enrolled. Sixteen (53.3%) and 19 (63.3%) patients reported significant improvement at week 12 in pain and function, respectively. Reduction in VAS pain was statistically significant both at week 2 and at week 12 in comparison with baseline visit (mean-difference -27.2 and -36.8, respectively, p<0.01). The same trend was observed with CMS (mean-difference 17.7 and 19.8, respectively, p<0.01). At week 12, 18 patients (60.0%) reported a subjective improvement. At week 12, in non-responders (n=14) US detected inflammatory changes and/or progression of tendon tear in 7 (50.0%) patients and no relevant changes in 7 (50.0%). CONCLUSIONS: US-guided STABHA injections followed by rehabilitation therapy were found effective in improving both pain and shoulder function at the 12-week follow-up. In half of the non-responders, US allowed the detection of US findings responsible for treatment failure.