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Objectives To investigate the association between patient–physician discordance in the assessment of disease activity and residual US synovitis/tenosynovitis in a cohort of patients with RA in clinical remission. Methods A post hoc analysis of the STARTER study, promoted by the Musculoskeletal-US (MSUS) Study Group of the Italian Society for Rheumatology, was performed using data from 361 consecutive patients with RA in clinical remission. The global assessment of disease activity by each patient (PGA) and evaluator/physician (EGA) was recorded on a 100-mm visual analogue scale. The PGA-EGA discordance was classified as positive (PGA>EGA) or negative (PGA Results The mean (s.d.) PGA and EGA scores were 6.1 (7.1) and 8.8 (12) mm, respectively, with a median (IQR) absolute difference of 4 (0–10) mm. Positive and negative discordances were recorded in 39 (10.8%) and 65(18.0%) patients, respectively. The GS-S (adjOR 1.099) and PD-S (adjOR 1.167) scores were associated with positive discordance (P Conclusions Patient–physician discordance is associated with the lack of US remission in patients with RA and may represent a further indication for MSUS.

To develop definitions for imaging features being considered as potential classification criteria for calcium pyrophosphate deposition (CPPD) disease, additional to clinical and laboratory criteria, and to compile example images of CPPD on different imaging modalities.The American College of Rheumatology and European Alliance of Associations for Rheumatology CPPD classification criteria Imaging Advisory Group (IAG) and Steering Committee drafted definitions of imaging features that are characteristic of CPPD on conventional radiography (CR), conventional computed tomography (CT), dual-energy CT (DECT), and magnetic resonance imaging (MRI). An anonymous expert survey was undertaken by a 35-member Combined Expert Committee, including all IAG members. The IAG and 5 external musculoskeletal radiologists with expertise in CPPD convened virtually to further refine item definitions and voted on example images illustrating CR, CT, and DECT item definitions, with ≥90% agreement required to deem them acceptable.The Combined Expert Committee survey indicated consensus on all CR definitions. The IAG and external radiologists reached consensus on CT and DECT item definitions, which specify that calcium pyrophosphate deposits appear less dense than cortical bone. The group developed an MRI definition and acknowledged limitations of this modality for CPPD. Ten example images for CPPD were voted acceptable (4 CR, 4 CT, and 2 DECT), and 3 images of basic calcium phosphate deposition were voted acceptable to serve as contrast against imaging features of CPPD.An international group of rheumatologists and musculoskeletal radiologists defined imaging features characteristic of CPPD on CR, CT, and DECT and assembled a set of example images as a reference for future clinical research studies.

IntroductionCOVID-19 and autoinflammatory diseases, such as Adult-onset Still’s Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization.MethodsThis study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays.ResultsIn the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (pDiscussionPD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1β production.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition disease (CPPD) will facilitate clinical research on this common crystalline arthritis. We report on the first two phases of a four-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member Steering Committee. Item generation (Phase I) included a scoping literature review of five literature databases and contributions from a 35-member Combined Expert Committee and two Patient Research Partners. Item reduction and refinement (Phase II) involved a Combined Expert Committee meeting, discussions among Clinical, Imaging, and Laboratory Advisory Groups, and an item rating exercise to assess the influence of individual items toward classification. The Steering Committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The Advisory Groups eliminated items they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the Steering Committee recommended focusing on imaging of the knee, wrist, and one additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

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.

ObjectivesTo provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

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.

Objective: To summarize the published evidence in the literature on the role of ultrasound and elastography to assess skin involvement in systemic sclerosis (SSc).Methods: A systematic literature review (SLR) was performed within the "Skin Ultrasound Working Group" of the World Scleroderma Foundation, according to the Cochrane Handbook. A search was conducted in Pubmed, Cochrane Library and Embase databases from 1/1/1979 to 31/5/2021, using the participants, intervention, comparator and outcomes (PICO) framework. Only full-text articles involving adults, reported in any language, assessing ultrasound to quantify skin pathology in SSc patients. Two reviewers performed the assessment of risk of bias, data extraction and synthesis, independently.Results: Forty-six studies out of 3248 references evaluating skin ultrasound and elastography domains were included. B-mode ultrasound was used in 30 studies (65.2%), elastography in nine (19.6%), and both methods in seven (15.2%). The ultrasound outcome measure domains reported were thickness (57.8%) and echogenicity (17.2%); the elastography domain was stiffness (25%). Methods used for image acquisition and analysis were remarkably heterogeneous and frequently under-reported, precluding data synthesis across studies. The same applies to contextual factors and feasibility. Our data syntheses indicated evidence of good reliability and convergent validity for ultrasound thickness evaluation against mRSS and skin histological findings. Stiffness and echogenicity have limited evidence for validity against histological findings. Evidence for sensitivity to change, test-retest reliability, clinical trial discrimination or thresholds of meaning is limited or absent for reported ultrasound domains.Conclusion: Ultrasound is a valid and reliable tool for skin thickness measurement in SSc but there are significant knowledge gaps regarding skin echogenicity assessment by ultrasound and skin stiffness evaluation by elastography in terms of feasibility, validity and discrimination. Standardization of image acquisition and analysis is needed to foster progress. (c) 2022 Elsevier Inc. All rights reserved.

Supplemental material, sj-docx-1-tab-10.1177_1759720X221096382 for Ultrasound-detected inflammation is more common in clinically manifest hand osteoarthritis than in painless bony enlarged finger joints: subanalysis of the population-based Bruneck study by Nina Gasperi, Nikolaus Schreiber, Philipp Bosch, Antonella Adinolfi, Arnd Kleyer, Melanie Hagen, Christiane Gasperi, Martin Weger, Stefan Kiechl, Johann Willeit, Georg Schett, Annamaria Iagnocco, Arno Gasperi, Agnes Mayr and Christian Dejaco in Therapeutic Advances in Musculoskeletal Disease

Ultrasound has been widely explored in systemic sclerosis in the clinical and research settings. Ultrasound allows a non-invasive and ionising radiation-free ‘window’ into this complex disease and is well-suited to repeated examinations. Ultrasound provides novel insights into the pathogenesis and measurement of disease in systemic sclerosis, including early (preclinical) internal organ involvement. The purpose of this review is to describe the role of ultrasound to foster clinical and research advancements in systemic sclerosis relating to (1) musculoskeletal, (2) digital ulcer, (3) lung disease and (4) skin disease. We also highlight unmet needs which much be addressed for ultrasound to assume a central role in systemic sclerosis clinical care and research.

Background:Up to 30% of Psoriasis (PsO) patients are prone to develop Psoriatic Arthritis (PsA). Agreement on how to identify PsO patients at risk of developing PsA is still lacking (1).Objectives:To identify predictors of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA).Methods:MEDLINE, EMBASE and COCHRANE databases were searched (up to February 22nd, 2020). The PICO framework (population = PsO patients; intervention = clinical, environmental, imaging and genetic features; comparator = not applicable; outcome = PsA development) was used to design searches and define the eligibility of studies for inclusion. The MA focuses on 3 major features as possible predictors: i) PsO skin and nail involvement; ii) musculoskeletal (MSK) complaints; iii) inflammation and structural damage detected by imaging (Table 1). The sample estimates of the relative risk were pooled only when the studies were homogeneous in terms of cohort of patients, follow-up, study design and metrics.Results:4698 articles were screened for eligibility, 110 underwent a full reading and 29 were finally included. Figure 1 shows the study flow-chart for article selection. Though pooling was judge not appropriate, 5/7 prospective studies significantly support a predictive value of PsA development in patients with severe PsO (n=174635). While the predictive value of nail involvement is not well defined (n=2202), the pooled estimate from two cohort studies (n=474) supports nail pitting as predictor of PsA (RR=2.14 [1.32; 3.46]). Moving to the MSK complaints, the risk of developing PsA is about two times greater in PsO with than without arthralgia (pooled RR: 2.15 [1.16, 3.99]) within 2 years. Lastly, PsO patients with inflammation or structural damage detected by imaging are nearly four times more likely to develop PsA within 1-2 years (pooled RR from 4 cohort studies (n=247): 3.72 [2.12; 6.51]) (Table 1). The incidence rate of PsA varies from 1.34 to 5.9/100 p-ys in PsO and from 10.9 to 12.5/100 p-ys in PsOAr.Table 1.Studies reporting the major features as possible predictors of PsA development.PsO skin – severityPsO nail involvementPsO nail lesionsVariablesRelative Risk [95%CI]Follow-upWilson, 2009PsO nail involvementHRadjusted: 2.24 [1.26; 3.98]13.1±8.8 ysFaustini, 2015PASI score + PsO nail involvement/σ= -0.18[-0.84; 0.48] RR: 0.95 [0.37; 2.47]1.2±0.2 ysEder, 2016PASI score PsO nail involvement Type of PsO nail lesionsHR (>20vsHRunadjusted: 1.36 [0.76; 2.45] HRunadjusted: 2.21 [1.24; 3.92]4.1±2.1 ysEder, 2017PASI score + Type of PsO nail lesionsHRunadjusted: 1.05 [1.01; 1.09] HRunadjusted: 1.98 [0.83; 4.74]3.8±2.1 ysLewinson, 2017PsO severity defined from medicationsHRadjusted (moderate/severe vs mild): 5.02 [4.18; 6.04]5.1 ysEgeberg, 2018PsO severity defined from medicationsRR (severe vs mild): 1.31 [1.18; 1.46]18 ysElnady, 2019PASI score + PsO nail Involvement/σ= 0.79[-0.37; 1.95] RR: 1.43 [0.38; 5.31]2 ysGreen, 2020PsO severity defined from medicationRR (severe vs mild): 2.79 [2.49; 3.13]5.8 ysMSK-complaintsVariablesIncident-PsA casesFollow-upFaustini, 2015ArthralgiaRR: 1.98 [0.75; 5.19]1.2±0.2 ysEder, 2017ArthralgiaHRadjusted: 2.59 [1.15; 5.88]3.8±2.1 ysZabotti, 2019ArthralgiaRR: 4.44 [0.54; 36.72]1.6±0.5 ysSimon D, 2020ArthralgiaRR: 2.04 [0.86; 4.86]2.4±1.5 ysSub-clinical inflammation or structural damage detected by imagingVariablesIncident-PsA casesFollow-upFaustini, 2015MRIRR: 2.10 [0.75; 5.90]1.2±0.2 ysElnady, 2019MSK-USRR: 5.38 [1.17; 24.63]2 ysZabotti, 2019MSK-USRR: 6.86 [0.83; 56.63]1.6±0.5 ysSimon D, 2020HR-pQCTRR: 4.32 [1.96; 9.55]2.3±1.4 ysConclusion:Arthralgia and inflammation and/or structural damage detected by imaging are predictive features, likely prodromal, of PsA development. PsO severity and nail pitting are clinical manifestations related to PsA development.Figure 1.References:[1]Zabotti A, et al. Curr Rheumatol Rep. 2020 May 16;22(6):24. doi: 10.1007/s11926-020-00891-x.Disclosure of Interests:Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Orazio De Lucia Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Garifallia Sakellariou Consultant of: AbbVie, Novartis, Alberto Batticciotto Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Gilberto Cincinelli: None declared, Ivan Giovannini: None declared, Luca Idolazzi Speakers bureau: Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: UCB, Gabriella Maioli Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Ilaria Tinazzi Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Daniel Aletaha Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: Not relevant for this type of study, Antonio Marchesoni Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Josef S. Smolen Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Annamaria Iagnocco Speakers bureau: not relevant for this type of study, Paid instructor for: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Dennis McGonagle Speakers bureau: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Grant/research support from: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD

Background and aimStriving for harmonisation of specialty training and excellence of care in rheumatology, the European League Against Rheumatism (EULAR) established a task force to develop points to consider (PtCs) for the assessment of competences during rheumatology specialty training.MethodsA systematic literature review on the performance of methods for the assessment of competences in rheumatology specialty training was conducted. This was followed by focus groups in five selected countries to gather information on assessment practices and priorities. Combining the collected evidence with expert opinion, the PtCs were formulated by the multidisciplinary task force, including rheumatologists, medical educationalists, and people with rheumatic and musculoskeletal diseases. The level of agreement (LoA) for each PtC was anonymously voted online.ResultsFour overarching principles and 10 PtCs were formulated. The overarching principles highlighted the importance of assessments being closely linked to the rheumatology training programme and protecting sufficient time and resources to ensure effective implementation. In the PtCs, two were related to overall assessment strategy (PtCs 1 and 5); three focused on formative assessment and portfolio (PtCs 2–4); three focused on the assessment of knowledge, skills or professionalism (PtCs 6–8); one focused on trainees at risk of failure (PtC 9); and one focused on training the trainers (PtC 10). The LoA (0–10) ranged from 8.75 to 9.9.ConclusionThese EULAR PtCs provide European guidance on assessment methods throughout rheumatology training programmes. These can be used to benchmark current practices and to develop future strategies, thereby fostering continuous improvement in rheumatology learning and, ultimately, in patient care.

The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR’s standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.

BackgroundStructural damage in rheumatoid arthritis (RA) includes bone erosion, cartilage change, and joint malalignment; historically evaluated with conventional radiography. Ultrasound (US) has been shown to be a valid tool for evaluating both cartilage change and bone erosion.ObjectivesTo obtain agreement on definitions and develop semiquantitative scoring systems for assessing structural damage by US and to validate these in a web-based reliability exercise.MethodsA Delphi survey of statements was prepared by an OMERACT US Working Group task force (USWG) based on a previously published systematic literature review (1) and circulated between group members, including definitions on normal US appearance of joint components, definitions of elementary lesions and scoring systems for bone erosions and joint malalignment. Definitions and a US scoring system for scoring cartilage change were recently developed and validated by the USWG (2) After agreement was achieved (≥75% of grades 4-5 on 1-5 Likert scale) on the statements, still images of metacarpophalangeal and proximal interphalangeal joints 2-5 in healthy controls and in RA patients with varying degrees of pathology were acquired by the USWG members. A dataset of 100 anonymized images, representing various grades of the 3 components of structural damage was created and utilized in 2 rounds of a web-based exercise. Intra- and inter-reader reliability of the scoring systems was assessed by kappa statistics.Results19 USWG members needed 4 Delphi rounds to reach agreement on a total of 9 statements. 4/12 statements were approved in the first, 2/6 in the second, 1/5 in the third and 2/2 in the fourth round. Final scoring systems and representative images are shown in Table 1 & Figure 1. 22 members participated in the web-based reliability exercise. The intra-reader reliability was almost perfect for bone erosion (kappa: 0.87) and cartilage change (kappa: 0.83) and substantial for malalignment (kappa of 0.72). The inter-reader reliability was almost perfect for bone erosion (kappa: 0.85), and substantial for cartilage change (kappa: 0.79) and malalignment (0.62).Table 1.Final definitions of scoring systems of elementary lesions of structural damage in rheumatoid arthritisAgreementBone erosionA 4-grade semiquantitative scoring system can be used to score erosions as follows: grade 0. intact cortical bone; grade 1. single small erosion (diameter: ≤2mm); grade 2. single large erosion (diameter: >2mm) or 2 small erosions; grade 3. 2 large erosions or ≥3 erosions, regardless of size. Both longitudinal and transverse scans should be considered, and the largest measure chosen for each erosion.100%Cartilage changeA 3-grade semiquantitative scoring system can be used to grade hyaline cartilage change as follows: grade 0. normal cartilage; grade 1. minimal change: focal thinning or incomplete loss of cartilage; grade 2. severe change: diffuse thinning or complete loss of cartilage.80% (2)MalalignmentA 3-grade semiquantitative scoring system can be used to grade malalignment as follows: 0. normal alignment; 1. subluxation or partial dislocation, where the two bone endings are malaligned so that one bone ending is dislocated from its normal position, but still within the articulation; 2. luxation or total dislocation, where the luxated bone ending moves beyond the articulation and the opposing bone ending. Bone position may be compared with a contralateral or similar intact joint if available.94%Figure 1.Representative images of the scoring systems for bone erosion (A), cartilage change (B) and malalignment (C)ConclusionThis first attempt to create a composite US instrument based on scoring systems encompassing all aspects of structural damage, demonstrates that US is a reliable tool for evaluating and scoring bone erosion, cartilage change and malalignment in the finger joints of RA patients.References[1]Gessl I, et al. Semin Arthritis Rheum. 2021 Jun;51(3):627-39.[2]Mandl P, et al. Rheumatology (Oxford). 2019 Oct 1;58(10):1802-11.Disclosure of InterestsPeter Mandl Speakers bureau: AbbVie, Janssen, Lilly, Novartis, Consultant of: AbbVie, Janssen, Lilly, Novartis, Grant/research support from: AbbVie, BMS, Novartis, Janssen, Lilly, MSD, UCB, Irina Gessl: None declared, Georgios Filippou: None declared, Silvia Sirotti: None declared, Lene Terslev Speakers bureau: Novartis, Pfizer, UCB, Janssen, GE, Carlos Pineda: None declared, Helen Keen Speakers bureau: Roche, AbbVie, Janssen, Consultant of: Sanofi, Marina Backhaus: None declared, David Andrew Bong: None declared, Edoardo Cipolletta: None declared, PAZ COLLADO: None declared, Christian Dejaco Speakers bureau: Roche, AbbVie, Sanofi, Lilly, Pfizer, Novartis, Janssen, Galapagos, Consultant of: Roche, AbbVie, Sanofi, Lilly, Pfizer, Novartis, Janssen, Galapagos, Andrea Delle Sedie Speakers bureau: Abbvie, Amgen, Lilly, MSD, Novartis, UCB, Paid instructor for: Abbvie, Amgen, Lilly, MSD, Novartis, UCB, Consultant of: Abbvie, Amgen, Lilly, MSD, Novartis, UCB, Christina Duftner: None declared, Hilde Berner Hammer: None declared, Annamaria Iagnocco: None declared, Zunaid Karim: None declared, Ingrid Möller Speakers bureau: Bristol-Myers Squibb, Ibsa, Pfizer, Galapagos, Esperanza Naredo Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Janssen, Celgene GmbH, Paid instructor for: Novartis, Consultant of: Novartis, Lilly, Grant/research support from: Lilly, Pfizer, Wolfgang A. Schmidt: None declared, Marcin Szkudlarek: None declared, Giorgio Tamborrini: None declared, Priscilla C Wong: None declared, Emilio Filippucci Speakers bureau: AbbVie, Amgen, Bristol -Myers Squibb, Janssen-Cilag, Lilly, Novartis, Pfizer, Roche, Union Chimique Belge Pharma, Peter Balint Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Maria-Antonietta D’Agostino: None declared

BackgroundConventional radiography (CR) is widely used as the first-line investigation for calcium pyrophosphate deposition (CPPD) disease, given its widespread use and the low cost. Next to it a series of advanced imaging techniques have been evaluated for accuracy and reliability. Among them, ultrasound (US) has been thoroughly tested and demonstrated to be accurate and reliable for CPPD diagnosis. However, even if there are data on the diagnostic accuracy of US and CR alone, it is not clear if performing both diagnostic tests and in which sequential order provides an added value for the diagnosis of CPPD.ObjectivesThe aim of this study was to assess which diagnostic test performs better for the diagnosis of CPPD and if a combination of the two exams provides an additional value.MethodsThis is an ancillary study of the criterion validity of US in CPPD study1. Consecutive patients with knee osteoarthritis requiring total joint replacement were enrolled in 8 centres. Participants underwent US and CR of the affected knee prior to surgery. US was performed by experienced sonographers following the same scanning protocol described in the main study, while CR were performed in weight bearing AP and lateral views and were read by 2 experienced radiologists that reached a consensus on the presence/absence of CPPD. The evaluation of CPPD at the level of menisci and hyaline cartilage (HC) was based on the OMERACT definitions for US and on the new definitions developed by the ACR/EULAR CPPD classification criteria working group for CR [paper under submission]. Patients were classified as having CPPD considering histological examination as reference standard. Diagnostic indexes were calculated for US and CR alone and combined. Poisson models with robust estimation were used to estimate the best sequence of these diagnostic methods for a more accurate diagnosis of CPPD.Results51 pts were enrolled (63% F, mean age 74y ± 8). Diagnostic indexes of US and CR alone and combined are indicated in Table 1. Compared to histology, US demonstrated to be a sensitive tool for identification of CPPD at the knee, with a good sensitivity in all sites and in the overall evaluation. Instead, CR was less sensitive, but it was a highly specific exam for CPPD identification. Combining US and CR led to a higher sensitivity compared with CR alone, but a lower specificity compared to both CR and US alone, and it offered no additional increase in diagnostic accuracy. The Figure 1 shows the results of the appropriate sequence of use of US and CR in patients with suspected CPPD: in case of a positive CR at any of the 3 sites (menisci and HC) no additional exam is necessary, and the same in case of a positive US in at least two sites; however in case of a negative CR, US could help in a statistically significant way to identify CPPD patients, and further in case of a positive US in a single site CR can offer additional information.Table 1.diagnostic indexes of US, CR and US + CR in the identification of CPPD. MM: medial meniscus, LM: lateral meniscus, HC: hyaline cartilage, SN: sensitivity, SP: specificity, PPV: positive predictive value, NPV: negative predictive value, ACC: accuracy.USSNSPPPVNPVACCMM0.880.810.820.880.84LM0.880.730.760.860.80HC0.780.860.820.830.82Overall0.920.640.730.890.78CRMM0.32110.610.67LM0.400.960.910.630.69HC0.480.930.850.680.73Overall0.540.920.880.660.73US + CRMM0.880.810.820.880.84LM0.920.690.740.900.80HC0.870.820.800.890.84Overall0.920.560.670.880.75Figure 1.evaluation of sequence of US and CRConclusionUS confirmed a high diagnostic accuracy in identifying patients affected by CPPD at knee level, while CR demonstrated a high specificity but a low sensitivity. Performing both diagnostic tests could make sense in case of a negative CR or in case of an inconclusive US (only one positive site). To our knowledge, this is the first study that investigates the role of the combination of the two exams in CPPD. Further studies in a large number of patients and in different joints would be helpful to address this point.References[1]Filippou G. et al, Ann Rheum Dis, 2020Disclosure of InterestsNone declared

BackgroundMusculoskeletal ultrasonography (MSUS) is a useful tool for the diagnosis of several Rheumatic and Musculoskeletal Diseases (RMDs) but its role in the diagnostic pathways in clinical practice is still unclear as feasibility issues limit its application as a bed side technique.ObjectivesTo optimize the use of US in clinical practice, the MSUS Study Group of the Italian Society for Rheumatology aimed to develop an algorithm combining US with clinical and laboratory findings to improve the differential diagnosis among patients presenting with joint swelling.MethodsBased on a systematic literature review1 and experts’ opinion, MSUS Study Group Members attempt to identify a set of statements including the main US elementary lesions useful for US scanning in the suspicion of Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), Rheumatic Polymyalgia (PMR), Gout, Calcium Pyrophosphate Deposition Disease (CPPD), Osteoarthritis (OA). Then, the MSUS Study Group defined through a survey and ranked in a 1000minds exercise the most important clinical/laboratory findings for the differential diagnosis of those diseases. Higher-ranked items were fitted in an algorithm driving the differential diagnosis of RMDs to a reduced spectrum of 2 to 4 possible diseases. Finally, the algorithm supported the performance of US according to the established scans for those specific diseases. To assess the algorithm’s performance, a pilot study was conducted on 59 patients, comparing the algorithm-based diagnosis with the final diagnosis based on rheumatologist’s experience and/or on classification criteria.ResultsSets of elementary US lesions and a scanning protocol for each included pathology were created (Table 1), optimized towards high sensibility and specificity. Among the findings evaluated, the age (Table 1.Elementary ultrasound lesions and joints to be scanned for each included pathologyDiseaseSites to scanUS elementary lesionsRAII-IV MCPsSynovial Hypertrophy (SH), Power Doppler (PD), erosionsWristV MTPPsAII-III MCPsPeritendonitisPIPsEnthesitisSoft tissue oedemaFlexor tendons of the handsTenosynovitisSoft tissue oedemaAchille’s tendon enthesisPD, erosionsProximal patellar tendon enthesisCPPDKnees (menisci and Hyaline Cartilage)CPP depositsWrist (triangular fibrocartilage complex)Any involved sitesCPP deposits, SH, PDGoutKneesDouble contour, tophiI MTPInvolved sitesSHPDOAInvolved sitesOsteophytesCartilage changesPMRShouldersBursitisArthritisRotator cuff integrityFigure 1.The final algorithmConclusionThe diagnostic algorithm produced in this pilot study correctly classified patients with the most prevalent RMDs in clinical practice. A longitudinal study on a large sample size is ongoing to evaluate the added value of US when implemented in this algorithm regarding diagnostic certainty, accuracy and early diagnosis.References[1]Sakellariou G, Scirè CA, Adinolfi A, Batticciotto A, Bortoluzzi A, Delle Sedie A, et al. Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review. Front Med. 7 maggio 2020;7:141.Disclosure of InterestsNone declared

No abstract available.

The last decade witnessed the ascendancy of rheumatology to become one of the most dynamic and progressive across the fields of medicine. During the COVID-19 pandemic our discipline emerged at the forefront of molecular medicine with the rapid uptake of immune-modulatory therapeutics and depth of immune pathogenesis understanding contributing fundamentally to the COVID-19 response. The European Alliance of Associations for Rheumatology (EULAR) played a fundamental and vital role in this response in guiding rheumatic and musculoskeletal disease (RMD) therapeutics, vaccine use and even treatment innovations in the context of COVID-19 itself. Given this remarkable contribution, it is timely to reflect on EULAR—what is it and for what does it stand? At its core, EULAR represents people with RMDs, including their national societies, health professionals in rheumatology and scientific societies of rheumatology across the European nations. Our mission is to reduce the burden of RMDs on individuals and society and improve the treatment and prevention of RMDs. In this message from the new EULAR President and Steering Group, we present the most relevant activities of EULAR, its strategic aims and the concept of the EULAR family, a fantastic team of people working together across the three pillars of medical, health professional and patient societies.

OBJECTIVES: People who are exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop a potentially fatal disease with lung involvement and severe cytokine storm syndrome (CSS) - coronavirus disease 2019 (hereafter, COVID-19). Tocilizumab (TCZ) was administered to these subjects, despite the lack of randomised clinical trial data. Hence, summarising data on the mortality rate and related risks factors may help physicians to correctly administer TCZ. METHODS: We performed a systematic review and meta-analysis on mortality rate in TCZ- treated patients with COVID-19 according to the PRISMA guidelines. The pooled mortality rate in TCZ-treated persons was calculated and meta-regressions were done to investigate associated factors. RESULTS: We included 22 studies and 1520 TCZ-treated patients (mean age: 61 years, 95% CI: 59-64; male: 71%, 95% CI: 64-78%). The mortality estimated pooled prevalence was 19% (95% CI: 13-25, I2=100%, p

Objective The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. Methods Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). Results We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P Conclusion The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

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.

Purpose: The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C). Methods: This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0–3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved. Results: Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33). Conclusion: GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.

To systematically review the role of ultrasound (US) in the assessment of the joint-enthesial-nail apparatus in patients with psoriatic arthritis (PsA) or psoriasis (PSO) in terms of prevalence, diagnosis, prognosis, monitoring and treatment. A systematic literature review was conducted through medical databases (PubMed, Embase) and the grey literature up to February 2018. The main areas of application of nail US were first identified, allowing the development of research questions, which were rephrased following the PICOs methodology to develop inclusion criteria. Of the 585 studies produced by PubMed and Embase searches, 17 studies met the criteria for inclusion. Five additional studies were included: 1 from the hand search and 4 from the 2016–2017 ACR and EULAR congresses. The prevalence of nail plate changes varied from

Background/objectivesTo maintain and optimise the quality of care provided by health professionals in rheumatology (HPRs), adequate educational offerings are needed. This task force (TF) aimed to develop evidence-based recommendations for the generic core competences of HPRs, with specific reference to nurses, physical therapists (PTs) and occupational therapists (OTs) to serve as a basis for their postgraduate education.MethodsThe EULAR standardised operating procedures for the development of recommendations were followed. A TF including rheumatologists, nurses, PTs, OTs, patient-representatives, an educationalist, methodologists and researchers from 12 countries met twice. In the first TF meeting, 13 research questions were defined to support a systematic literature review (SLR). In the second meeting, the SLR evidence was discussed and recommendations formulated. Subsequently, level of evidence and strength of recommendation were assigned and level of agreement (LoA) determined (0–10 rating scale).ResultsThree overarching principles were identified and 10 recommendations were developed for the generic core competences of HPRs. The SLR included 79 full-text papers, 20 of which addressed the competences, knowledge, skills, attitudes and/or educational needs of HPRs from multiple professions. The average LoA for each recommendation ranged from 9.42 to 9.79. Consensus was reached both on a research and educational agenda.ConclusionEvidence and expert opinion informed a set of recommendations providing guidance on the generic core competences of HPRs. Implementation of these recommendations in the postgraduate education of HPRs at the international and national level is advised, considering variation in healthcare systems and professional roles.

BackgroundAging is a physiological, multidimensional, and irreversible process, occurring in humans over time. Interestingly, multiple lines of evidence have recently suggested that some diseases, generally affecting young adults, are nowadays described in the elderly, although possibly associated with different symptoms or complications. In this context, a possible occurrence of adult onset Still’s disease (AOSD) in elderly has been suggested. This is a rare inflammatory disorder of unknown origin usually observed in young adults [1-3].ObjectivesIn this study, we aimed at describing the clinical characteristics, life-threatening complications occurrence, and mortality of AOSD patients with an elderly onset. The manifestations of these patients were also compared with those with a younger onset. Furthermore, the predictive role of age was evaluated on clinical features and disease outcomes. Finally, in these patients, an assessment of associated comorbidities was also performed.MethodsA retrospective assessment of prospectively followed patients, from January 2001 to April 2021, was provided to analyse clinical features, life-threatening complications occurrence, and mortality in AOSD patients with onset in elderly. AOSD patients, who were included in multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort, were evaluated.ResultsOut of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over than 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (pAdditionally, our analysis showed that pleuritis and pericarditis positively correlated with age (coefficient=0.227, p=0.001; coefficient=0.213, p=0.001, respectively). Furthermore, the occurrence of parenchymal lung disease was significantly related with age (coefficient=0.168, p=0.012). The presence of comorbidities positively correlated with age (coefficient=0.443, pAge predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). No significant results were observed assessing the predictive role of age on occurrence of macrophage activation syndrome. Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012).ConclusionClinical features of AOSD patients with elderly onset were described in our multicentre cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a further negative prognostic factor in AOSD.References[1]Mollaeian A, Chen J, et al. BMC Rheumatol. 2021;5(1):12.[2]Maruyama A, et al. Mod Rheumatol. 2021;31(4):862-868.[3]Suzuki E, et al. Tohoku J Exp Med. 2021;255(3):195-202.Disclosure of InterestsNone declared

BackgroundUltrasound (US) has proven to be an excellent imaging technique for detecting calcium pyrophosphate (CPP) deposition disease (CPPD); it is also widely available and inexpensive and can be performed during the clinic visit making it the preferred imaging modality for many rheumatologists. However, no validated grading systems have yet been developed allowing for a quantification of the extent of crystal deposition in CPPD.ObjectivesThe aim of this study was to develop a scoring system for the quantification of CPP deposition at a patient level according to the OMERACT framework.MethodsAs part of the OMERACT methodology, we performed a systematic literature review (SLR) and meta-analysis aimed to estimate the prevalence of CPP deposition in peripheral joints by imaging, in order to identify relevant joints for CPPD monitoring. A preliminary survey was also circulated among the members of the OMERACT US – CPPD working group to collect their own suggestions according to their personal experience. Subsequently, a Delphi survey was prepared and circulated between members of the group, including statements that reflected both the results of the SLR and of the preliminary survey. In total, 32 statements were generated regarding the type of scoring for single structures, the sites to be included, the final scoring at patient level, and the scanning technique. Participants were asked to reply on a 5-point Likert scale (1, strongly disagree to 5, strongly agree) and agreement was achieved when 4 and 5 grades reached 75% or more of concordance. In case of disagreement, new statements were proposed according to the members’ suggestions and circulated for voting in a subsequent round. After agreement of a scoring system, the validation process began. Two rounds of a web-based exercise on static images were conducted on 120 images representing equally all sites under investigation and all degrees of crystal deposition, to assess the intra- and inter-reader reliability of the new scoring system. Representative images of the scoring system were visible throughout the entire exercise in order to facilitate the scoring of the lesions.ResultsThree Delphi rounds were needed to reach agreement on all items. 32/41 members of the OMERACT US-CPPD working group replied in the first round, 26/32 in the second, and 25/26 in the third round. Twenty statements were approved in the first round, 3 in the second, and 3 in the third round. Only the knees (menisci and hyaline cartilage) and the triangular fibrocartilage of the wrist were included in the final score, using a four-grade system (0-3). It was decided that each anatomical structure should be scored separately and then also summed in order to define the joint score. The sum of the assessed joints was the total score at patient level. The final scoring system with the definitions and the relative technical notes is represented in Figure 1. 33/41 members participated to the reliability exercise. The inter-reader reliability of the scoring was substantial (kappa of 0.72), and the intra-reader reliability was almost perfect (kappa of 0.82).ConclusionThis is the first study for developing a scoring system for the extent of CPP crystal deposition in patients with CPPD. The scoring system demonstrated to be reliable in static images. The next step of the validation process is to assess the reliability of the scoring system in a patient-based exercise. This study represents a fundamental step in the OMERACT process of validating US as an outcome measure instrument, and above proposed scoring system will hopefully provide a useful tool for clinical practice and research.Disclosure of InterestsNone declared

BackgroundAdult-onset Still’s disease (AOSD) is a rare multigenic autoinflammatory disease of unknown aetiology burdened by life-threatening, such as macrophage activation syndrome (MAS) [1]. Considering the poor outcome of MAS patients, previous works tried to assess predictive factors of its occurrence during AOSD [2-4]. However, an integrated evaluation of clinical features with biomolecules, more reflecting the pathogenic mechanisms of the disease and its complications, is still missing.ObjectivesTo multidimensionally characterise MAS complicating AOSD considering cytokine profile, inflammatory markers, and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing.MethodsThe present evaluation was designed to multidimensionally compare AOSD patients with or without MAS, considering cytokine profile, inflammatory markers, and multi-visceral involvement of the disease. Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterise circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues.ResultsIn this study, 40 consecutive AOSD patients (47.7±15.0 years, 50.0% male gender) were assessed at the time of diagnosis before the administration of any immunosuppressive therapy. Out of those, 14 (35%) patients were complicated by MAS. Paralleling with increases of systemic score and ferritin, MAS patients were characterised by an increased concentration of IL-1α, IL-1β, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α, SCF. Among these biomolecules, IL-1Ra, IFN-γ, MCP-1, and SCF were correlated with MAS.Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ, and IL-10. This model was characterised by AUC=0.99 (Standard error: 0.008; 95%CI: 0.976–1.000), sensitivity=100%, specificity=95.45%. By CyTOF analysis, AOSD patients, who were complicated or not with MAS were characterised by a significant increase of circulating “classical monocytes” (CD14+CD38+). MAS patients were characterised by a significant reduction of NK cells (CD45RA+CD56dim) than AOSD patients. Finally, the transcriptomic profile, by RNA-sequencing analysis, showed that 3477 among type I, II, and III IFN-related genes (IRGs) were significantly different in AOSD synovial tissues.ConclusionA multidimensional characterisation of AOSD patients was provided suggesting that IFN-γ, IL-10, ferritin, and systemic score discriminated MAS, thus identifying the occurrence of the cytokine storm syndrome. The inflammatory milieu of AOSD and MAS may be associated with a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these patients.References[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still’s disease. J Autoimmun. 2018;93:24-36.[2]Ruscitti P, et al. Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort. J Rheumatol. 2018;45:864-872.[3]Di Benedetto P, et al. Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still’s disease. Analysis of the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. PLoS One. 2020;15:e0235326.[4]Wan L, et al. Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still’s disease. Arthritis Res Ther. 2021;23:97.Disclosure of InterestsNone declared.

BackgroundUncontrolled systemic inflammation characterizes COVID-19 and autoinflammatory diseases such as adult-onset Still’s disease (AOSD). Biosynthesis of pro-resolving mediators (SPMs), i.e. lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR), ensures inflammation shutdown and tissue repair, limiting neutrophils recruitment and stimulating macrophages to remove apoptotic cells. Among protectins, reduction of PD1 was found in the lungs of mice infected with the H5N1 influenza virus and experimental treatment with PD1 resulted in increased animals’ survival (Morita M et al 2013).ObjectivesWe investigated the effects of SPMs in pathogenesis and clinical evolution of AOSD and compared these data with mild and severe COVID-19. Finally, we analyzed the potential role of PD1 in modulating the inflammatory response of macrophages obtained from AOSD patients, COVID-19 patients and healthy donors (HDs).Methods21 patients hospitalized for COVID-19 (10 ICU and 11 hospitalized in medical clinical unit) and 13 patients with AOSD were enrolled. Plasma PD1 levels from patients and controls were analyzed by ELISA, and monocytes-derived macrophages were polarized into M1 and M2 phenotype. We analyzed the effect of PD-1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Peripheral blood mononuclear cells (PBMCS) from 3 AOSD patients, 2 COVID-19 patients and 3 HDs were obtained. Next-generation deep sequencing was then performed to identify the differences in PBMCs transcripts profiles.ResultsAOSD patients with systemic scored (SS) ≥1 showed an increase of PD1 levels compared to AOSD patients with lower systemic score (p=0.04) (Figure 1A). Similarly, plasma levels of PD1 were increased in COVID-19 patients independently from their clinical subsets, compared to HDs (p=0.02). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (ppla2g15, pla2g12a, pla2g2d, involved in mobilization of SPMs precursors, were significant upregulated in patients compared to HDs (p1.2) (Figure 1D). The largest part of the genes involved in inflammation, lipid catabolism, and monocytes activation are less expressed in AOSD patients when compared to COVID19 patients, as reported in Table 1.Table 1.Gene symbolLog2 fold changepAdjusted pCounts COVID19Counts AOSDInflammation-related genesALOX50.980.0240.2116861.618562.92IL13RA11.280.0020.0537154.782938.95RTN30.720.0020.00699948.376045.92SSH21.056,78 E-70.0001618343.868848.67Lipid catabolism genesPLBD11.680.000110.008228051.888671.3CYP4F32.850.000340.0171996.63277.13STS1.530.0100.0361798.5623.9HADHA0.740.000140.009712766.447625.38Monocytes-related genesALDH21.462.48E-101.85E-079186.553340.87CD1632.379,99E-060.001466499.4512870.59MGST11.130.00260.0631385.54631.67RNASE42.480.00010.009286.6615.42Figure 1.ConclusionThe counterbalance by SPMs during inflammation is still a largely unexplored pathway. Our study suggests that an imbalance of SPMs in autoinflammatory diseases as well as COVID-19. The modulation of SPMs as observed in our experiments, might represent a new possible therapeutic strategy during AOSD and COVID-19.References[1]Morita M et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112-25.Disclosure of Interestsluca navarini Speakers bureau: AbbVie, Pfizer, MSD, UCB, GSK, BMS, Roche, Sanofi Aventis, Novartis, Janssen, Galapagos, Eli Lilly, Paid instructor for: AbbVie, Eli Lilly, Consultant of: Philogen, Grant/research support from: AbbVie, Marta Vomero: None declared, Onorina Berardiucrti: None declared, Damiano Currado: None declared, Annalisa Marino: None declared, Alice Biaggi: None declared, Stefano Di Donato: None declared, Francesco Ursini: None declared, Piero Ruscitti: None declared, Riccardo Meliconi: None declared, Paola Cipriani: None declared, Annamaria Iagnocco Speakers bureau: AbbVie, Pfizer, MSD, UCB, GSK, BMS, Roche, Sanofi Aventis, Novartis, Janssen, Galapagos, Eli Lilly, Antonella Afeltra Speakers bureau: AbbVie, Pfizer, MSD, UCB, GSK, BMS, Roche, Sanofi Aventis, Novartis, Janssen, Galapagos, Eli Lilly, Roberto Giacomelli Speakers bureau: AbbVie, Pfizer, MSD, UCB, GSK, BMS, Roche, Sanofi Aventis, Novartis, Janssen, Galapagos, Eli Lilly, SOBI, Consultant of: Philogen, Grant/research support from: AbbVie, SOBI

BackgroundThe transition from psoriasis (PsO) to psoriatic arthritis (PsA) is a focus of considerable scientific interest: is it possible to target pre-PsA and very early PsA, in particular for physiopathology and drug studies? Recently, a EULAR taskforce has been set up in this area (1).ObjectivesTo characterize the prodromal and the very early PsA through a systematic literature review (SLR).MethodsA SLR explored MEDLINE, EMBASE and CENTRAL, up to 22 October 2021. The objective was to identify the symptoms, objective signs, lab tests, imaging features and other characteristics of patients later diagnosed as “new onset” PsA in two key populations: 1) patients with PsO and 2) patients with early undifferentiated arthritis (UA). Studies of adult patients published in English were included, if they reported characteristics of pre-PsA or new onset PsA patients, and data were extracted by 2 readers. Meta-analysis was not done due to data heterogeneity (PsA classification criteria, outcome measures and length of observation). Results are reported semi-quantitatively.ResultsOf 31449 references, 22 studies were included of which 12 were prospective; 7 retrospective and 3 cross-sectional. Eighteen studies reported on patients with PsO (n=95828) later diagnosed as PsA (n=2136) with a mean duration of follow up of 5.2 (±3.9) years. Seven out of 18 (38.8%) studies were informative regarding the clinical features of the new onset PsA. Four studies on early UA patients (n=492) later diagnosed as PsA (n=49) were included. Progression to PsA was associated with the presence of musculoskeletal (MSK) complaints (mainly joint tenderness) and the presence of subclinical MSK inflammation detected by imaging. Peripheral oligo-arthritis was the prevalent clinical presentation of new onset PsA.ConclusionAs expected, joint pain and imaging evidence of MSK inflammation were associated with PsA development in PsO patients. The SLR highlights the lack of robust evidence regarding data associated with the development of PsA. More prospective studies focusing on transition from PsO to PsA are needed.Table 1.FeaturesTransition from PsO to PsA (n = 18 studies)Transition from UA to PsA (n = 4 studies)Clinical characterization of New Onset PsA (n = 5 studies)Patient reported symptomsVAS pain+++NAEntheseal pain+NAMorning stiffness+NAFatigue+NAHAQ more compromised++NAArthralgia+++NAClinical examinationJoint tenderness+++++++Swelling joints++++Entheseal tendernessMajor domain of pattern presentationPeripheral arthritis (more frequent)+++PolyarthritisMono-oligoarthritis++Inflammatory marker(s)CRP++ImagingMSK inflammation detected by imaging++++Radiographic evidence of specific damage++Legend:PsO = psoriasis (affecting skin); PsA = psoriatic arthritis; UA = undifferentiated inflammatory arthritis; VAS = visual-analogue scale; NA = not applicable; HAQ = health assessment questionnaire; CRP = C-reactive protein; MSK = musculoskeletal+ = 1 study for positive association; ++ = 2 studies for positive association; +++ >= 3 studies for positive associationReferences[1]https://www.eular.org/ongoing_initiatives.cfmDisclosure of InterestsAlen Zabotti Speakers bureau: Amgen, Lilly, Janssen, Novartis, UCB, Paid instructor for: Amgen, Janssen, Grant/research support from: Novartis, Gabriele De Marco: None declared, Laure Gossec Speakers bureau: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, Xenofon Baraliakos: None declared, Jenny Emmel: None declared, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Annamaria Iagnocco: None declared, Josef S. Smolen: None declared, Dennis McGonagle Speakers bureau: Janssen, Lilly, UCB, Abbvie, Pfizer, Celgene, Grant/research support from: Janssen

Ultrasound elastography (UE) is a non-invasive imaging method that allows the assessment of tissue elastic property. Different UE techniques are currently available (i.e. strain UE and acoustic radiation force impulse UE), with several potential clinical applications. Recent studies investigated the role of UE in two systemic rheumatic diseases and psoriasis. This research added interesting information to the already known applications of UE in the assessment of tendinopathies. In SS, acoustic radiation force impulse UE has shown a potential role in the diagnosis of the disease, with lower sensitivity than and similar specificity to salivary gland histology. In SSc, a potential use of UE in screening pre-clinical disease has been reported. In psoriasis, the use of strain UE in evaluating treatment response has been highlighted. UE is a promising tool in rheumatology, with a potential role in the evaluation of various tissues and pathologies.

Objectives Advanced therapies (AT), including biologics, biosimilars and Janus kinase inhibitors, have dramatically improved the quality of life of patients with RA, PsA and axial spondyloarthritis (axSpA). Evidence-based criteria for prescribing these drugs in England and Wales is formulated by the National Institute for Health and Care Excellence (NICE) through health technology appraisals and guidelines, with the aim of providing equitable access to AT for patients with severe or resistant disease. Similar bodies exist in some, but not all European countries, with disparities in AT access between countries for RA. We examined whether this disparity was mirrored in England for RA, PsA and axSpA despite the National Health Service in England and Wales being legally obliged to provide funding for AT recommended by NICE’s Health Technology Appraisal board, through the commissioning bodies, the clinical commissioning groups (CCGs). Methods We requested AT pathways from CCGs in England. Where these were not available, individual hospital Trusts were contacted using freedom of information requests. Results We found marked variability in the way that CCGs in England interpret NICE guidance. We found 41, 29 and 25 different pathways for RA, PsA and axSpA, respectively. Similar disparities existed with sequential prescribing where one AT did not work, with limits on the numbers of sequential AT in 54%, 59% and 59% of CCGs for RA, PsA and axSpA, respectively, and with these limits being different for the same condition between CCGs. Conclusion Although patients at identical stages of their disease course should have access to the same NICE-approved AT, we found this is not the case for large parts of England. Inequality of access was found between regions, mirroring the variability that occurs between countries throughout Europe. Harmonization of access needs to be addressed by policymakers to ensure fairness in the way that clinicians and patients can access AT.

Although synovitis is the pathological hallmark of rheumatoid arthritis (RA), many extra-articular manifestations (EMs) and comorbidities likely occur due to the complex, chronic, inflammatory, and autoimmune features of RA. Cardiovascular (CV) disease is the most common cause of death in patients with RA. Compared to the general population, patients with RA have twice the risk of myocardial infarction and up to 50% increased CV mortality risk. Severe and prolonged disease activity, genetics, and inflammation (e.g. CRP, ACPA, cytokines, matrix-degrading enzymes) play important roles in CV disease and atheroscleroticdamage. The second major cause of death in patients with RA is respiratory disease, which occurs in 30-40% of patients. RA may affect the lung interstitium, airways, and pleurae, while pulmonary vascular involvement is less frequent. Central and peripheral nervous system involvement is usually due to small vessel vasculitis, joint damage, or drug toxicity. There is also evidence that microvascular cerebral damage caused by systemic inflammation is associated with the development of Alzheimer's disease and vascular dementia. Some observational studies have hinted how Disease Modified Anti-Rheumatic Drugs and biologics could reduce the incidence of dementia. Primary gastrointestinal and renal involvements are rare and often relate to drug therapy. To minimize morbidity and mortality, physicians must manage RA disease activity (treat-to-target) and monitor risk factors and concomitant conditions (e.g. smoking cessation; weight regulation; monitoring blood pressure, lipids, thyroid hormone, folic acid and homocysteine; screening for depression, anxiety, atlantoaxial instability, and atherosclerosis). This article aims to provide an overview of the most prevalent and important EMs and comorbidities associated with RA.

Background:The UPSTREAM (NCT03330769) is a 24-month multi-center prospective cohort study that primarily aims to evaluate the additional value of musculoskeletal ultrasound (msk-US) over clinical examination in predicting 6-month minimal disease activity in Psoriatic Arthritis (PsA). (1)Objectives:To develop and preliminarily validate an activity msk-US score and a damage msk-US score for PsA using the UPSTREAM database.Methods:Patients classified with PsA according to CASPAR criteria and starting a new course of therapy for clinically active peripheral joint disease were eligible. The information regarding objectives, study design, clinical and US assessment has already been published (1). The msk-US examination was performed in 42 joints, 36 tendons, 12 entheses and 2 bursae defined through a web-based exercise (2). The sonographic elementary lesions were allocated to disease activity [i.e. synovitis (sy), tenosynovitis (ts), peritendinitis (pt), bursitis (bs) all evaluated both in Grey Scale (GS) and Power Doppler (PD) and active enthesitis (en)] and to damage (i.e. joint erosion, bone proliferation, tendon tear, enthesophyte, calcification and irregular enthesis bone profile). Hands and feet X-ray were assessed using the modified Sharp-Van der Heijde (mSVH) score. A principal component (PC) analysis (PCA) was performed for each score and the number of PCs was defined by means of parallel analysis using baseline data. Each PC was normalized (n) taking into account the proportion between the observed value (e.g. sy-GS count) and the maximum expected value (e.g. 42 for sy-GS). Spearman’ correlation was used to investigate the construct and discrimination validity of the new scores.Results:Between February 2017 and May 2020, 312 PsA patients (155 men), with a mean (SD) age of 52.8 13.4, were enrolled from 19 centers; 22 expert sonographers were involved with substantial agreement for US lesions evaluated (k ≥0.7). The median [IQR] disease duration was 1.3 [0.1-6.1] years and the median [IQR] tender joint and swollen joint counts were 6 [3-13] and 2 [1-5], respectively. The weight derived from PCA for each sonographic lesions and the final equation for calculating the scores are reported in Figure 1 (1A activity and 1B damage). The final msk-US activity score [n(ts-GS + ts-PD)*2.87] + [n(bs-GS + bs-PD)*1.76] + [n(pt-GS + pt-PD)*1.43] + [n(active en)*1.00] + [n(sy-GS)*0.83] + [n(sy-PD)*0.45] has the best construct and discrimination validities according to a significant correlation with all clinical variables usually related to clinical activity (Table 1). The msk-US damage score correlated with mSVH score, HAQ and other clinical variables (Table 1).Table 1.VariablesMsk-US activity scoreMsk-US damage scoreSpearman correlationP-valueSpearman correlationP-valueESR0.1960.0020.0750.235CRP0.2090.0680.254TJC0.3380.286SJC0.3380.0720.221Dactylitis count0.284-0.0610.306LEI0.1940.0010.214Physician GA0.150.0120.0160.793Patient GA activity0.1380.018-0.0730.221Patient GA pain0.1990.001-0.0270.648HAQ0.2380.1460.014BASDAI0.2370.1750.003PSAID-90.70.0040.1480.013DAPSA0.3920.228Sharp van Der Heijde score0.1150.20.2660.003Figure 1.Conclusion:These newly developed and preliminary validated msk-US activity and damage scores could be used in patients with PsA in the context of observational and controlled trials.References:[1]Canzoni M et al. BMJ Open. 2018;8:e021942.[2]Zabotti A et al. Ann Rheum Dis 2018;77:1537–1538.Acknowledgements:Alberto Batticciotto; Oscar Massimiliano Epis; Luisa Arcarese; Luca Navarini; Marta Caprioli; Mirco Magnani; Roberta Ramonda; Marco Amedeo CimminoDisclosure of Interests:Alen Zabotti: None declared, Matteo Piga: None declared, Anna Zanetti: None declared, Marco Canzoni: None declared, nicola boffini: None declared, valentina picerno: None declared, Giovanni Zanframundo: None declared, Ettore Silvagni: None declared, Ivan Giovannini: None declared, BERND RAFFEINER: None declared, Palma Scolieri: None declared, Paola Mancini: None declared, Simone Parisi: None declared, Alessandra Bortoluzzi Grant/research support from: GSK, Garifallia Sakellariou Consultant of: Consultant for Abbvie and Novartis, Orazio De Lucia: None declared, Ilaria Tinazzi: None declared, Fabiana Figus: None declared, Luca Idolazzi Speakers bureau: Received grants as speaker for Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: Paid instructor for UCB during Product specialist Meeting, Mariagrazia Lorenzin: None declared, Sara Zandonella Callegher: None declared, Alberto Cauli: None declared, Greta Carrara: None declared, Carlo Alberto Scirè: None declared, Annamaria Iagnocco: None declared

COVID-19, caused by infection of the novel coronavirus SARS-CoV-2, has caused a pandemic of enormous impact that has challenged healthcare and political system throughout the world. This new health emergency has occurred on top of the usual burden of diseases, including systemic sclerosis, and has led to many unanticipated consequences. An early consequence of the pandemic was postponement of the Sixth Systemic Sclerosis World Congress that was recently completed as a successful virtual congress with more than 1000 delegates. In this article, we summarise the relevance and impact of COVID-19 from the perspective of systemic sclerosis. Shared concepts of pathogenesis are considered, and the relevant literature emerging about COVID-19 and systemic sclerosis summarised. The specific impact of this pandemic on delivery of optimal scleroderma care is considered, together with the broader effect on rheumatic and musculoskeletal diseases and the activities of European League Against Rheumatism. As the World continues to struggle against this new infectious disease, it is notable that expertise and growing understanding of systemic sclerosis has been able to help tackle COVID-19. Moreover, the essential adjustments to deliver clinical care and establishment of new ways of working due to the pandemic have offered potential avenues for future improvement in systemic sclerosis care.

Objective Metalloproteinase (MMP)-3 and MMP-12 are proteolytic enzymes especially implicated in joint inflammation. This study aims to evaluate their association with arthritis features and hand MRI abnormalities in patients with SLE. Methods Fifty SLE patients, with a mean (s.d.) age of 48.1 (14.6) years were tested for MMP-3 and MMP-12 serum levels, then further classified according to the presence of X-ray erosions and joint deformities. Eighteen RA patients aged 47.9 (11.8) and 14 healthy people aged 46.0 (11.0) were enrolled as control groups. A subgroup of 28 SLE patients underwent a dominant-hand MRI; the detected changes were classified and semi-quantitatively scored as capsular swelling, synovitis, edematous or proliferative tenosynovitis, bone oedema, bone erosions. Statistical analysis was performed using multiple regression models. Results MMP-3 were significantly higher in patients with Jaccoud’s arthropathy (JA) (22.1 ng/ml, P < 0.05) and independently associated with hsCRP serum levels (B-coeff 0.50; r = 0.30; P < 0.05). MMP-12 serum levels were significantly lower in patients with JA (0.18 ng/ml, P < 0.05) and inversely associated with the prednisone daily dose (B-coeff –0.03; r = −0.44; P < 0.01). Capsular swelling and edematous tenosynovitis, the most prevalent hand MRI changes in patients with JA, associated with higher MMP-3 (B-coeff 0.12; r = 0.66; P < 0.01 and B-coeff 0.08; r = 0.59; P < 0.01, respectively) and lower MMP-12 serum levels (B-coeff –7.4; r = −0.50; P < 0.05 and B-coeff –5.2; r = −0.44; P = 0.05, respectively). Conclusion Imbalanced MMP-3 and MMP-12 serum levels are influenced by inflammation and glucocorticoids in SLE patients and associated with JA and distinctive hand MRI changes.

Background To assess the reliability of the consensually agreed US definitions of major salivary gland lesions and the US scoring system for salivary gland assessment in patients with SS. Methods Nine experienced sonographers scanned and read the US images of both parotid glands (PGs) and submandibular glands (SMGs) in eight patients with primary and secondary SS in two rounds. A consensually agreed four-grade semi-quantitative scoring was applied in B-mode for morphological lesions: grade 0, normal; grade 1, mild inhomogeneity without anechoic or hypoechoic areas; grade 2, moderate inhomogeneity with focal anechoic or hypoechoic areas; grade 3, severe inhomogeneity with diffuse an- or hypoechoic areas occupying the entire gland or fibrous gland. The presence or absence of typical SS lesions, i.e. the Sjögren’s signature, was scored binary. Intra- and interreader reliabilities were computed using weighted and unweighted Cohen’s and Light’s κ coefficients. Results The mean prevalence of grades 0–3 in PG were 43, 17, 23 and 31% and 28, 14, 33 and 32% for the SMGs, respectively. The weighted κ for intrareader reliability ranged from 0.44 to 1 for grading and 0.64 to 1 for the Sjögren’s signature of PG and 0.59 to 1 and −0.09 to 0.6 for SMGs, respectively. The interreader reliability κ for grading in PG was 0.62 (95% CI 0.47, 0.74) and for Sjögren’s signature it was 0.36 (95% CI 0, 0.43); in SMG it was 0.62 (95% CI 0.47, 0.72) and 0.03 (95% CI 0, 0.07) respectively. Conclusions The consensually agreed novel US scoring system for major salivary gland lesions showed substantial intra- and interreader reliability in patients with SS. The reliability of the Sjögren’s signature was moderate.

Polymyalgia rheumatica (PM) is an inflammatory rheumatic disorder characterised by pain and stiffness, mainly in the neck, shoulders, and pelvic girdle and possible association with giant cell arteritis. Currently, there is no diagnostic gold standard for PM, however, an extensive assessment of patients' inflammatory status aided by imaging evaluation is crucial for disease stratification. Many imaging techniques study PM features and their possible complications or associations with giant cell arteritis: radiography, ultrasound, scintigraphy, magnetic resonance imaging, and positron emission tomography/computed tomography. Each one has different advantages and disadvantages. The aim of this review is to clarify the current uses of imaging in PM for diagnosis and follow-up through a literature review of the last 10 years.

ObjectivesDactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score.MethodsAfter a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score.ResultsDACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score.ConclusionsThe novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

Objective To determine the intra- and inter-observer reliability of ultrasound (US)-detected age-related joint vascularization and ossification grading in healthy children. Methods Following standardized image acquisition and machine setting protocols, 10 international US experts examined four joints (wrist, second metacarpophalangeal joint, knee, and ankle) in 12 healthy children (divided into four age groups: 2–4, 5–8, 9–12, and 13–16 years). Grey-scale was used to detect the ossification grade, and power Doppler (PD) US was used to detect physiological vascularization. Ossification was graded from grade 0 (no ossification) to grade 3 (complete ossification). A positive PD signal was defined as any PD signal inside the joint. Kappa statistics were applied for intra- and inter-observer reliability. Results According to the specific joint and age, up to four solitary PD signals (mean, 1.5) were detected within each joint area with predominant localization of the physiological vascularization in specific anatomic positions: fat pad, epiphysis, physis, and short bone cartilage. The kappa values for ossification grading were 0.87 (range, 0.85–0.91) and 0.58 for intra- and inter-observer reliability, respectively. The bias-adjusted kappa values for intra- and inter-observer reliability were 0.71 (range, 0.44–1.00) and 0.69, respectively. Conclusion Detection of normal findings (i.e., grading of physiological ossification during skeletal maturation and identification of physiological vessels) can be highly reliable by using clear definitions and a standardized acquisition protocol. These data will permit development of a reliable and standardized US approach for evaluating paediatric joint pathologies. This article is protected by copyright. All rights reserved.

Although there has been an increase in the use of skin high frequency ultrasound for the evaluation of dermal thickness and skin impairment in systemic sclerosis, its role is still under debate and its use has not yet been fully validated. Herein we discuss the recent data from research and clinical practice on methods for sonographic evaluation of dermal thickness in systemic sclerosis.

Aim: To define and score finger soft tissue oedema in psoriatic dactylitis by ultrasound.Material and methods: A systematic literature review (SLR) on ultrasound-detected finger soft tissue oedema was performed. Subsequently, based on the SLR, a Delphi survey was developed and circulated among a group of 13 expert sonographers, in order to obtain agreement on detection, definition and scoring of finger oedema by B-mode and power Doppler ultrasound. Agreement was considered achieved when each statement was approved by >75% of participants.Results: At the first Delphi round, 91 % agreement was obtained for the scanning technique to adopt, including the most appropriate area to evaluate. At the second round, 76% agreement was achieved on the definition of soft tissue finger oedema. At the third round, 76% agreement was obtained for B-mode and power Doppler scores. The volar aspect of the finger and comparisons with the contralateral side were agreed to be the most appropriate in terms of scanning technique. Agreed ultrasound definition of finger soft tissue oedema was “abnormal hypoechoic/anechoic areas, diffused or localized within the subcutaneous tissue between the epidermidis and the tendon-related anatomic structures (i.e. flexor tendon sheath, peritenonium, tendon pulleys), with local thickening, with or without local abnormal Doppler signal, visualised in two perpendicular planes and not evident on the contralateral side”. Semiquantitative (0-3) scores for both B-mode and power Doppler were agreed to be the most appropriate to be used.Conclusion: Our work produced, for the first time, technical indications, definition and scoring for the ultrasound assessment of soft tissue oedema in psoriatic dactylitis

Summary Objective Ultrasonography (US) demonstrated to be a promising tool for the diagnosis of calcium pyrophosphate dihydrate deposition disease (CPPD). The aim of this systematic literature review (SLR) was to collect the definitions for the US elementary lesions and to summarize the available data about US diagnostic accuracy in CPPD. Methods We systematically reviewed all the studies that considered US as the index test for CPPD diagnosis without restrictions about the reference test or that provided definitions about US identification of CPPD. Sensitivity and specificity were calculated for each study and definitions were extrapolated. Subgroup analyses were planned by anatomical site included in the index text and different reference standards. Results Thirty-seven studies were included in this review. All the studies were eligible for the collection of US findings and all definitions were summarized. US description of elementary lesions appeared heterogeneous among the studies. Regarding US accuracy, 13 articles entered in the meta-analysis. Considering each joint structure, the sensitivity ranged between 0.77 (0.63–0.87) and 0.34 (0.16–0.58) while the specificity varies between 1.00 (0.89–1.00) and 0.92 (0.16–1.00). Considering the reference standards used, the sensibility ranged between 0.34 (0.02–0.65) and 0.87 (0.76–0.99) while specificity ranged between 0.84 (0.52–1.00) and 1.00 (0.99–1.00). Conclusion US is potentially a useful tool for the diagnosis of CPPD but universally accepted definitions and further testing are necessary in order to assess the role of the technique in the diagnostic process.

Background:Imaging has been extensively used for the Calcium Pyrophosphate Deposition Disease (CPPD) diagnosis but the prevalence of joint calcifications at imaging in CPPD patients has not been thoroughly assessed.Objectives:This systematic literature review (SLR) is aimed to estimate the prevalence of calcium crystal deposition in peripheral joints by imaging in suspected or definite CPPD patients to establish relevant joints for CPPD monitoringMethods:After defining PICOs, Pubmed and Embase were searched from inception to October 2020 for identifying studies that evaluated the use of Conventional Radiography (CR), Ultrasound (US), Computed Tomography (CT) and Dual Energy Computed Tomography (DECT) in detecting calcifications at peripheral joints in patients with defined or probable CPPD. Search strategies based on MeSH terms and free text were applied. Six reviewers independently screened titles and abstracts, eligible article full texts were evaluated for inclusion and data extraction.Results:The SLR identified 1149 manuscripts. 524 papers entered in the full text evaluation and 181 articles were finally included. Considering excluded abstracts and full texts, 23 and 17 were excluded as duplicate, 156 and 9 for language, 171 and 48 for population, 171 and 20 for intervention, 57 and 117 for outcome, 47 and 70 for study type and 76 for full text unavailability. Among included, 41 papers considered patients with definite CPPD with a total population of 1239 patients, 908 cases and 331 controls and 140 papers referred to patients with suspected CPPD with a total population of 26785 patients, 2896 affected by CPPD and 23889 controls. The results about all joints are summarized in the Table 1. In patients with definite diagnosis, knee and wrist are the joints with the highest prevalence of calcifications at all imaging types, followed by hip and acromion-clavicular joint while in patients with suspected CPPD, the knee is the most prevalent followed by the wrist, hip and ankle (only sites with more than 50 patients assessed considered). The hand joints are characterized by CPPD lowest prevalence at imaging. Bilateral imaging findings varies depending on the technique used, the site and the patient’s type.Table 1.Definite CPPD DiagnosisKNEEWRISTHANDELBOWSHOULDERACHIPANKLEFOOTTMXRImaging positive cases/all cases330/584 57%214/409 52%43/158 27%54/212 25%65/249 26%37/84 44%140/293 48%30/255 12%15/59 25%0Cases positivebilaterally99/146 68%30/79 38%0/104/12 33%2/2 100%9/17 53%7/10 70%7/10 70%00USImaging positive cases/all cases155/252 62%86/118 75%4/42 9%2/2 100%0/304/30 13%47/80 59%30/255 12%15/59 25%0Cases positivebilaterally83/96 86%33/47 70%1/ 4 25%003/ 4 75%29/47 62%7/10 70%00CTImaging positive cases/all cases41/50 82%22/28 78%00000000Cases positivebilaterally27/30 90%000000000DECTImaging positive cases/all cases8/10 80%9/10 90%1/1 100%0000000Cases positivebilaterally001/1 100%0000000Suspected CPPD diagnosisKNEEWRISTHANDELBOWSHOULDERACHIPANKLEFOOTTMXRImaging positive cases/all cases1989/2442 81%549/1024 54%98/602 16%29/72 40%75/185 41%27/31 87%322/887 36%56/116 48%24/42 57%0Cases positive bilaterally611/1068 57%209/334 63%64/85 75%22/23 96%41/46 89%0/294/196 48%44/53 83%18/19 95%0USImaging positive cases/all cases241/261 93%125/185 68%2/39 5%1/1 100%4/12 33%02/2 100%27/78 35%8/37 22%0Cases positivebilaterally4/9 44%74/93 80%00000000CTImaging positive cases/all cases019/23 83%002/2 100%02/2 100%001/1 100%Cases positivebilaterally0000000001/1 100%DECTImaging positive cases/all cases1/1 100%2/2 100%00000000Cases positivebilaterally1/1 100%000000000Table 1 For each joint, are summarized the ratio between positive joints and overall evaluated joints and the ratio between the joints positive bilaterally and overall joints evaluated bilaterally.AC Acromion Clavicular, TM temporo mandibularConclusion:According to the results of this SLR, knees and wrists could be the sentinel joints for CPPD detection by imaging.Disclosure of Interests:None declared.

Background:Synovial fluid analysis (SFA) via compensated polarized light microscopy is still considered the gold standard for the identification and diagnosis of Calcium Pyrophosphate Deposition disease (CPPD)-related arthropathies[1], but very few studies have been published about its diagnostic accuracy.Objectives:The aim of this study was to evaluate the accuracy of SFA in the identification of calcium pyrophosphate dihydrate (CPP) crystals compared to microscopic analysis of joint tissues as the reference standard.Methods:This is an ancillary study of an international, multicentre cross-sectional study performed by the CPPD subgroup of the OMERACT Ultrasound working group[2]. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres, Mexico and Romania. During surgical procedures synovial fluid (SF), menisci and hyaline cartilage were collected and analysed within 48 hours after surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of CPP crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/presence) was used for scoring both SF and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) of SFA in the identification of CPP crystals were calculated.Results:15 patients (53% female, mean age 68yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for CPP crystals at SFA and 14 (93%) at tissues microscopic analysis. Among 12 SFA positive patients, all were positive for CPP crystals in either medial or lateral meniscus, and 11 were positive in both; 10 patients were positive at the hyaline cartilage, and all 10 were also positive for at least one meniscus. Regarding the 3 SFA negative patients, only one had no crystals in the examined tissues, while the other 2 patients had CPP crystals in both menisci and hyaline cartilage. The overall diagnostic accuracy of SFA compared to histology analysis for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the PPV was 100% and the NPV was 33% (Table 1).Table 1.sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of synovial fluid analysis compared to the reference standard. CI: Confidential Interval. SF: synovial fluid, in parentheses: numerators and denominators for all percentages provided.SensitivitySpecificityPPVNPVAccuracySF analysis86% (12/14)100% (1/1)100% (12/12)33% (1/3)87% (13/15)(0.65-0.99) CI 95%(0.0-0.25) CI 95%(0.65-0.99) CI 95%(0.0-0.25) CI 95%Conclusion:SFA demonstrated to be an accurate test for the identification of CPP crystals in patients with advanced OA. However, is not always feasible and carries some risks for the patient. Considering the availability of validated imaging techniques for the detection of CPPD, such as US, SFA could be used in those patients where imaging and clinical data are not definitely confirmatory of the disease.References:[1]W. Zhang et al., ‘European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis’, Ann Rheum Dis, vol. 70, no. 4, pp. 563–570, Apr. 2011, doi: 10.1136/ard.2010.139105.[2]G. Filippou et al., ‘Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study’, Ann Rheum Dis, p. annrheumdis-2020-217998, Sep. 2020, doi: 10.1136/annrheumdis-2020-217998.Disclosure of Interests:None declared.

Background:Conventional Radiography (CR) has been widely used in the assessment of knee chondrocalcinosis (CC) and is still considered one of the most important diagnostic methods for the diagnosis. However, there are no studies on the reliability of CR for CC.Objectives:To assess the reliability of CR of the knee in the assessment of chondrocalcinosis (CC).Methods:This is an ancillary study of the Criterion Validity of Ultrasound in Calcium Pyrophosphate Deposition Disease (CPPD) study [1]. Consecutive patients with knee osteoarthritis (OA) that were planned for total knee replacement surgery were enrolled in 4 centres from Romania, Italy, USA and Mexico. All patients underwent CR of the knees taken maximum 6 months before surgery, in posterior-anterior weight baring and lateral projections. DICOM files of the radiographs were retrieved, anonymised and read independently by two musculoskeletal radiologists with experience in microcrystalline arthropathies. Each reader performed a second evaluation 3 weeks after the first one to calculate the inter- and intra-reader agreement. For each patient a dichotomic score was assigned (absence/presence of CC) at the level of the medial and lateral menisci, tibiofemoral hyaline cartilage, quadriceps and patella tendons, synovial membrane/joint capsule. The definitions of the ACR/EULAR taskforce for identification of CPPD in conventional radiography were used in this study [paper in preparation]. According to these definitions CPPD in CR appears as “linear or punctate opacities in the region of fibro- or hyaline articular cartilage/synovial membrane or joint capsule/within tendons or entheses that are distinct from denser, nummular radio-opaque deposits due to basic calcium phosphate deposition”. Cohen’s kappa was used to calculate the agreement between the two readers.Results:We enrolled 33 patients with knee OA (60.6% female, mean age 69yo ± 8). The kappa values of the inter-reader and intra-reader agreement in the various sites of the knee are indicated in Table 1. Inter-reader agreement was substantial at the level of both menisci but only moderate or fair at the other sites of assessment. This had a negative impact on the overall evaluation of the knee joint that proved to be unreliable (k of 0.16 – none to slight agreement) if all anatomical structures are included for assessment, and moderately reliable (kappa 0.41) when both menisci and hyaline cartilage are considered. On the other hand, intra-reader kappa values were substantial or higher in all sites (except for synovial membrane/joint capsule for one reader). The striking difference of the intra-reader compared to the inter-reader kappa values, highlight a different interpretation and application of the definitions used for most of the sites with the exception of the menisci.Table 1.kappa values for intra- and inter-reader agreement. Values from 0.01–0.20 are considered as none to slight agreement, 0.21–0.40 as fair, 0.41– 0.60 as moderate, 0.61–0.80 as substantial, and 0.81–1.00 as almost perfect agreement.Medial meniscusLateral meniscusHyaline cartilageQuadriceps tendonPatellar tendonCapsule/ synoviaMenisci + cartilageEntire jointInter-reader0.670.710.340.47NA0.370.400.17Intra-reader 1st assessor0.670.900.840.65NA(insufficient number of categories)0.530.710.76Intra-reader 2nd assessor10.801110.910.860.94Conclusion:CR has been extensively used for diagnosis of OA and CPPD. The results of our study raise some concerns on the reliability of CR in identification of CPPD. Assessment of calcium crystals at the menisci level should be used for identification of CC as other sites of the knee seem to present low reliability.References:[1]Filippou G et al. Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study. Ann Rheum Dis 2020. doi:10.1136/annrheumdis-2020-217998Disclosure of Interests:None declared.