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Objective To develop the optimal US scanning protocol for the diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Methods In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls 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 standardized scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from second to fifth 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 receiver operating characteristic curves. Results The number of participants enrolled was 204: 102 with CPPD disease and 102 disease controls [age, mean (s. d.): 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 [interquartile range (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 (s. d.): 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. [ABSTRACT FROM AUTHOR]

Objective To evaluate differences in nailfold videocapillaroscopy (NVC) findings between SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). Methods One hundred and ten SSc patients were enrolled in this cross-sectional, case–control, multicentre study. Patients were divided into cases (SSc-PAH confirmed by right heart catheterization) 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 a multivariate analysis, SSc-PAH patients, compared with non-PAH, had more non-specific abnormalities [27/55, 49.1% vs 10/55, 18.2%; adjusted odd ratio (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 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 a diagnosis of PAH. Conclusion 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives The aim was to explore the inter-reliability of a newly developed US scanning protocol (multimodal US) for the assessment of different aspects of sarcopenia-related muscle involvement, including muscle mass, muscle quality and muscle stiffness [using point shear-wave elastography (SWE)], in patients with rheumatic and musculoskeletal diseases (RMDs). Methods Quadriceps muscle mass (i.e. muscle thickness), muscle quality (i.e. muscle echogenicity evaluated with both a visual semi-quantitative scale and a dedicated software package for image analysis, ImageJ) and point SWE measurements were obtained by two rheumatologists (blinded to each other's evaluation) in consecutive RMD patients without previous/current myositis or neuromuscular disorders. Inter-reliability was assessed using the intraclass correlation coefficient (ICC) for continuous variables and Cohen's kappa (κ) for categorical variables. Results A total of 45 RMD patients were enrolled [mean age 54.5 (16.0) years, male-to-female ratio 1:1.5, mean BMI 24.6 (4.6) kg/m2], 10 with PsA, 7 RA, 5 AS, 5 PMR, 4 SLE, 4 gout, 4 OA, 3 FM and 3 SSc. The grade of inter-rater reliability was excellent for muscle mass [ICC = 0.969 (0.953 < ICC < 0.979)]. Regarding muscle echogenicity, the agreement was substantial/almost perfect using the visual semi-quantitative scale (weighted linear = 0.793, weighted squared = 0.878) and excellent using ImageJ analysis [ICC = 0.916 (0.876 < ICC < 0.944)]. Finally, a good agreement was obtained for point SWE measurements [ICC = 0.76 (0.712 < ICC < 0.8)]. Conclusion Multimodal US is a novel and reliable tool for the evaluation of different aspects of muscle involvement (muscle mass, muscle quality and muscle stiffness) in RMD patients. [ABSTRACT FROM AUTHOR]

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.   A video abstract is available for this article and can be viewed at https://doi.org/10.1093/rheumatology/keac479. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated prevalence and distribution of metacarpal head cartilage damage in patients with rheumatoid arthritis (RA) and hand osteoarthritis (OA). Topics explored include the clinical characteristics and manifestation of RA and OA, results of the image acquisition and radiographic examination performed, and the observed link between cartilage damage, patient's age, and disease duration.

Objectives The main objective of this study is to explore the prevalence and distribution of entheseal US changes in a cohort of SLE patients, taking as controls a group including both PsA patients and healthy subjects. The secondary objective is to investigate the correlation between the US findings and the clinical and serological data in SLE patients. Methods Clinical and US assessment of quadriceps, patellar and Achilles tendons, and plantar fascia entheses were performed by independent rheumatologists on 65 patients with SLE, 50 patients with PsA and 50 healthy subjects. US findings were identified according to the OMERACT definitions. In SLE patients, the correlation between the US changes and the clinical and laboratory findings was evaluated. Results US revealed one or more abnormalities in at least one enthesis in 44 out of 65 SLE patients (67.7%), 47 out of 50 PsA patients (94.0%) and 22 out of 50 healthy subjects (44.0%). In SLE patients, US findings indicating active inflammation were significantly more frequently detected than in healthy subjects (P < 0.001). The distal enthesis of the patellar tendon was the most commonly involved. The presence of power Doppler signal at the enthesis was an independent predictor of SLE disease activity (SLEDAI-2k P < 0.001, β = 0.52; musculoskeletal-BILAG P < 0.001, β = 0.56). Conclusion The burden of entheseal sonographic changes was significantly higher in SLE patients than in healthy subjects, especially as regards active inflammation. The presence of power Doppler signal at the enthesis may represent a potential biomarker of SLE disease activity. [ABSTRACT FROM AUTHOR]