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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.

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.

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

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

Dear Editor, We read with interest the correspondence by Chen et al 1 about our recent article on the comparison of clinical, laboratory and artificial intelligence–radiological findings in patients with lung involvement either from macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis (HLH) or severe coronavirus disease 2019 (COVID-19).2 Age is one of the most common confounding factors in any observational study since it is associated with an increased risk of comorbidities, which may influence the outcome. In our study, the matching for age was not reliable because of higher prevalence of severe COVID-19 in elderly patients, who were admitted to intensive or subintensive care units of our hospital. These results mirror what was already observed in other observational studies,3 4 in which the incidence and severity of COVID-19 are generally higher in elderly patients due to higher frequency of comorbidities, increased frailty and immunosenescence.5 Conversely, MAS complicating adult-onset Still’s disease (AOSD), as patients assessed in our study, usually affects young adults.6 Considering the scientific debate behind our study,2 about the possibility that severe COVID-19 could be considered or not part of HLH spectrum, the age of occurrence may further differentiate the clinical pictures between these diseases. Furthermore, Chen et al 1 questioned the use of Yamaguchi criteria in classifying AOSD patients .7 Although …