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In psoriatic arthritis (PsA), ultrasonography (US) plays a growing role in the differential diagnosis and in monitoring treatment response.1 PsA is a heterogeneous disease with different domains and peculiar sites involved.2 Therefore, a dedicated US composite score is needed to monitor disease activity and to identify structural damage progression. A recently published Systematic Literature Review (SLR) identified only two US scores specifically developed for PsA (ie, 5TPD and PsA-Son) and, although these had a good sensitivity to detect inflammation and a good feasibility, they have not been validated in other series.1 3 4 Recently, the Study Group for US of the Italian Society of Rheumatology promoted the Ultrasound in PSoriatic Arthritis TREAtMent (UPSTREAM) study (registered at ClinicalTrial.gov, NCT03330769). UPSTREAM is a multicentre observational prospective cohort study and it represents the first …

Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory. CA extern

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Objective To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). Methods Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). Results 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p Conclusion The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different. Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus

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

Objective: To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals deposition disease (CPPD). DESIGN: A systematic search of electronic databases (PubMed, Embase, and Cochrane), conference abstracts and reference lists was undertaken. Studies which evaluated the accuracy of CR and/or US in the diagnosis of CPPD, using synovial fluid analysis (SFA), histology or classification criteria as reference tests were included. Subgroup analyses by anatomic site and by reference test were performed. Results: Twenty-six studies were included. Using SFA/histology as reference test, CR and US showed an excellent (CR AUC = 0.889, 95%CI = 0.811–0.967) and an outstanding (US AUC = 0.954, 95%CI = 0.907–1.0) diagnostic accuracy (p < 0.01), respectively. Furthermore, US showed a higher sensitivity (0.85, 95%CI = 0.79–0.90 vs 0.47, 95%CI = 0.40–0.55) and only a little lower specificity (0.87, 95%CI = 0.83–0.91 vs 0.95, 95%CI = 0.92–0.97) than CR. A considerable heterogeneity between the studies was found, with adopted reference test being the main source of heterogeneity. In fact, subgroup analysis showed a significant change in the diagnostic accuracy of CR, but not of US, using Ryan and McCarty criteria or SFA/histology as reference test (CR: AUC = 0.956, 95%CI = 0.925–1.0 vs AUC = 0.889, 95%CI = 0.828–0.950, respectively, p < 0.01) (US: AUC = 0.922, 95%CI = 0.842–1.0 vs AUC = 0.957, 95%CI = 0.865–1.0, respectively, p = 0.08) Conclusions: Although US is more sensitive and a little less specific than CR for identifying CPP crystals, both these two techniques showed a great diagnostic accuracy and should be regarded as complementary to each other in the diagnostic work-up of patients with CPPD.

ObjectiveAs part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe.MethodsTwo cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0–10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0–100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementationResultsOverall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients.ConclusionsMany problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.

Background There is no agreement on the prevalence of anti-phospholipid antibodies (aPLs) and the correlation with atherosclerosis and cardiovascular (CV) events in the general population. Methods We performed a cross-sectional study on 1712 randomly enrolled subjects from a Northern Italian city to investigate the presence of aPLs and the association with subclinical atherosclerosis (using the carotid artery intima media thickness measured as inter-adventitia common carotid artery diameters - ICCAD) and retrospectively collected CV factors and events (i.e. acute myocardial infarction, stroke, and peripheral obliterans arterial vasculopathy) using physician-assisted questionnaires. We tested serum IgG, IgM, and IgA anti-cardiolipin, anti-beta2glycoprotein I (aGPI), and anti-phosphatidylserine-prothrombin antibodies. Results Positive aPLs were found in 15.1% of the subjects, with no differences between sex but with higher rates in older subjects. Carotid subclinical atherosclerosis was more frequent in aPL positive subjects; more specifically, aGPI IgA were associated with higher ICCAD average (adjusted beta 0.51, 95% confidence interval (CI)0.17–0.84; p = 0.003). A positive history of CV events was also more frequent in aPL positive subjects (odds ratio (OR) 1.67, 95%CI 1.08–2.54; p = 0.012), particularly peripheral obliterans arterial vasculopathy ( OR 2.02 ; 95%CI 1.14–3.57; p = 0.015). Among subjects with a Framingham risk score >20, and/or diabetes, and/or body mass index >3 5 kg/m 2 , aPL positivity was associated to the highest risk of CV events (OR 2.52, 95%CI 1.24–5.11; p = 0.011). Conclusions APL prevalence in the general population is higher than previously reported. CV events and subclinical atherosclerosis are more frequent in the presence of aPL, particularly when a high CV risk coexists.

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan–Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Objectives Although neuropsychiatric involvement in SLE (NPSLE) is one of the most complex and troubling manifestations of the disease, validated outcome instruments to be used as sensitive endpoints in controlled clinical trials are lacking. We performed a systematic literature review (SLR) to identify outcome measurement instruments and domains used to assess NPSLE. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. Articles available in English (1967–2020), listed in PubMed, Embase, PsycINFO, Cochrane Library and the EULAR outcome measures library were screened. All domains and outcome measurement instruments were characterized according to the OMERACT Filter 2.1, considering core areas (manifestations/abnormalities, life impact, death/lifespan, societal/resource use) and contextual factors. Results Of 3392 abstracts evaluated, 83 studies were included in the SLR (15 974 patients, females 89.9%). Eligible studies included domains and instruments pertinent to all core areas defined by the OMERACT, except for ‘societal/resource use’. The most common core areas were ‘manifestations/abnormalities’, covering 10 domains pertinent to laboratory and instrumental markers, indexes and neuropsychiatric dimension (cognitive, neurologic and psychiatric field), and ‘life impact’, covering 7 domains related to physical function (from both the perspective of the patient and the physician), pain and quality of life. Conclusion Our study revealed great heterogeneity in the instruments derived from populations with NPSLE and none of these had high-quality evidence. This supports the need to develop and further validate a core domain set and outcome measurement instruments to promote clinical research in this field, enhancing comparability across studies.

Background: Rheumatoid arthritis (RA) is associated with an increase in cardiovascular (CV) risk. This issue maybe not only explained by a genetic component, as well as by the traditional CV risk factors, but also by an underestimation and undertreatment of concomitant CV comorbidities.Method: This was a retrospective matched-cohort analysis in the Italian RA real-world population based on the healthcare-administrative databases to assess the CV risk factors and incidence of CV events in comparison with the general population. Persistence and adherence to the CV therapy were also evaluated in both groups.Results: In a RA cohort (N = 21,201), there was a greater prevalence of hypertension and diabetes with respect to the non-RA subjects (N = 249,156) (36.9 vs. 33.4% and 10.2 vs. 9.6%, respectively), while dyslipidemia was more frequent in the non-RA group (15.4 vs. 16.5%). Compared with a non-RA cohort, the patients with RA had a higher incidence of atrial fibrillation (incidence rate ratio, IRR 1.28), heart failure (IRR 1.53), stroke (IRR 1.19), and myocardial infarction (IRR 1.48). The patients with RA presented a significantly lower persistence rate to glucose-lowering and lipid-lowering therapies than the controls (odds ratio, OR 0.73 [95% CI 0.6–0.8] and OR 0.82 [0.8–0.9], respectively). The difference in the adherence to glucose-lowering therapy was significant (OR 0.7 [0.6–0.8]), conversely no statistically significant differences emerged regarding the adherence to lipid-lowering therapy (OR 0.89 [95% CI 0.8–1.0]) and anti-hypertensive therapy (OR 0.96 [95% CI 0.9–1.0]).Conclusion: The patients with RA have a higher risk of developing CV events compared with the general population, partially explained by the excess and undertreatment of CV risk factors.

Fibromyalgia or fibromyalgia syndrome (FMS) is defined as a central sensitization syndrome characterized by the dysfunction of neurocircuits detecting, transmitting and processing nociceptive stimuli; the prevalent manifestation is musculoskeletal pain. In addition to pain, there are multiple accompanying symptoms, in common with other algo-dysfunctional syndromes, which are reflected in a broad spectrum of somatic, neurocognitive and neuro-vegetative manifestations. An evidence-based approach is essential in FMS management, in order to improve patient health and to reduce its social burden. Since in the last ten years new international guidelines for clinical practice (Clinical Practice Guidelines or CPGs) concerning FMS diagnosis and pharmacological/ non-pharmacological management have been published, the Italian Society of Rheumatology (SIR) has decided to adapt them to the Italian national setting. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the most recent CPGs on FMS to the needs of the Italian healthcare context. A working group of rheumatologists from SIR epidemiology unit and FMS experts identified relevant clinical questions to guide the systematic review of the literature. The target audience of these CPGs included physicians and healthcare professionals who manage FMS. The adapted recommendations were finally assessed by an external multidisciplinary panel. From the systematic search in databases (Pubmed/Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. The combination of the scientific evidence underlying the original CPGs with expert opinion lead to the development of 17 recommendations. The quality of evidence for each recommendation was reported and their potential impact on clinical practice was assessed. These SIR recommendations are expected to be a valuable aid in the diagnosis and treatment of FMS, as they will contribute to disseminate the best practice on the basis of the current scientific evidence.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

© 2021 Elsevier Ltd. All rights reserved, Background: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management. Methods: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237. Findings: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7-6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4-4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05-1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02-1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32-0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic. Interpretation: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic., Pfizer, Sanofi, Amgen, Galapagos, and Lilly funded this study through unrestricted grants.

ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

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Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

To estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08-5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51-3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for.

Background and aims Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). Approach and results We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84–2.35, p, Highlights • Methotrexate is widely prescribed for psoriatic arthritis with different dosages. • The risk of non adherence is 2 times lower for oral compared to subcutaneous or intramuscular methotrexate. • Maximising methotrexate efficacy and retention is crucial to reach disease remission.

Objectives: To investigate opinion and routine practice of specialists from different disciplines on imaging techniques for interventional procedures related to rheumatic and musculoskeletal diseases (RMDs).Methods: An English-language questionnaire was developed by an international working group and distributed to health care providers of various disciplines involved in the care of people with RMDs via an online survey tool (SoSci Survey®) from December 2019 to May 2020.Results: A total of 1,105 respondents from 56 countries completed the survey, over 60% of participants were rheumatologists. The majority of respondents (88%) performed interventional procedures in RMDs patients and 90% of them used imaging guidance. Ultrasonography was the most frequently used technique, particularly among rheumatologists. X-ray and computed tomography were mainly used by radiologists. A discrepancy emerged between the importance assigned to certain items such as the availability of a second operator and their actual implementation in clinical practice. Local barriers, lack of resources and facilities were mentioned as the most relevant obstacles in this regard. Lack of training on imaging and/or imaging guided procedures did not emerge as a barrier to perform such interventions; in fact, 19% of respondents performing the procedures indicated not to have received adequate training in this field.Conclusions: This is the first multinational multidisciplinary survey exploring in detail the opinions and practice on imaging guidance for interventional procedures in RMDs. A harmonization of protocols based on international guidelines, along with adequate training programmes and interventions on barriers at national/local levels are the main unmet needs requiring attention.

The aim of this study was to evaluate the accuracy of synovial fluid analysis in the identification of calcium pyrophosphate dihydrate crystals compared to microscopic analysis of joint tissues as the reference standard. This is an ancillary study of an international, multicentre cross-sectional study performed by the calcium pyrophosphate deposition disease (CPPD) subgroup of the OMERACT Ultrasound working group. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres in Mexico and Romania. During the surgical procedures, synovial fluid, menisci and hyaline cartilage were collected and analysed within 48 hours from surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of calcium pyrophosphate crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/ presence) was used for scoring both synovial fluid and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values of synovial fluid analysis in the identification of calcium pyrophosphate crystals were calculated. 15 patients (53% female, mean age 68 yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for calcium pyrophosphate crystals at the synovial fluid analysis and 14 (93%) at the tissue microscopic analysis. The overall diagnostic accuracy of synovial fluid analysis compared with histology for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the positive predictive value was 100% and the negative predictive value was 33%. In conclusion synovial fluid analysis proved to be an accurate test for the identification of calcium pyrophosphate dihydrate crystals in patients with advanced OA.

Objective To assess the effect of optimal management of pregnancy on a composite outcome of miscarriage and complicated birth among women with rheumatoid arthritis (RA). Methods Data were extracted from health care databases of the Lombardy Region, Italy (2004-2013) as a part of the Record-Linkage on Rheumatic Diseases Study. Analyses included women with RA identified through a copayment exemption code (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) and controls from the general population, ages 18-50 years. Seven health care quality indicators (HCQI) were constructed and summarized in 3 pathway indicators: diagnostic, therapeutic, and prenatal follow-up. Complicated birth or miscarriage were used to identify the adverse pregnancy outcome (APO). The relationship between HCQI and APO was analyzed using logistic models, and the results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Data from the study cohort included the first pregnancy observed in 443 patients with RA compared with 6,097 women belonging to the general population. In the RA population, patients who followed the 3 pathway indicators had a reduced risk of overall APO, with an OR of 0.60 (95% CI 0.39-0.94), and reduced risk of miscarriage/perinatal death, with an OR of 0.40 (95% CI 0.24-0.69), compared to those who did not follow the pathway indicators. Compared with the general population, patients with RA who met all HCQI during pregnancy displayed a risk of APO with an OR of 0.92 (95% CI 0.61-1.38) and miscarriage/perinatal death with an OR of 0.77 (95% CI 0.47-1.29). Conclusion The adherence to an ideal clinical pathway of pregnancy management in women with RA restored the risk of APO to that expected for the general population.

The objective of this study was to determine the correlation between functional and radiological longitudinal change in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), and to test the OMERACT definition of clinically meaningful progression of pulmonary function tests (PFTs) for the prediction of ILD radiological evolution. We retrospectively retrieved high-resolution computed tomography (HRCT) studies and PFTs including DLco, both available at two time-points and performed within 6 months of each other, in SSc patients. A subset of patients was selected using a 12-24-month clinically oriented interval (n = 58). The extent of ILD at HRCT was scored according to a visual semi-quantitative method (SQCT). The correlation of absolute change (Δ) in the SQCT score with change in FVC and DLco was examined using Pearson's correlation coefficient. The concordance between the OMERACT criteria (≥ 10% FVC relative decline; or 5-10% FVC and ≥ 15% DLco relative decline) and SQCT categorical change (5% and 10%) was investigated. A total of 129 patients were enrolled. During 12-24-month follow-up, ΔSQCT was negatively correlated with ΔFVC (r = - 0.487, p = 0.0001) and ΔDLco (r = - 0.298, p = 0.023). Ten patients demonstrated CT progression ΔSQCT > 5%, among whom 5 with ΔSQCT > 10%. OMERACT criteria identified 25 patients with progressive SSc-ILD, of whom only 5 presented ΔSQCT > 5 and 3 presented ΔSQCT > 10%. In conclusion, change in radiological extent of SSc-ILD was correlated to functional decline in a limited time-frame. Repeated HRCT after 12-24 months may be useful for the longitudinal characterization of ILD evolution in patients with stable pulmonary function. Conversely, functional changes are suggestive of a concurrent radiological progression only after this interval. Key Points • In SSc patients, chest HRCT performed every 12-24 months can detect minimal but significant changes in ILD extent, even in subjects with stable pulmonary function. • PFT changes in 12-24 months are related to the radiological ILD progression. • OMERACT criteria might overlook patients with radiological progression. • Repeated chest HRCT may be useful for monitoring SSc-ILD when performed within 12 to 24 months from baseline in order to promptly detect progression and possibly impact on prognosis.

International audience; Objective: This study aimed to develop (1) a new ultrasound definition for aggregates and (2) a semi-quantitative ultrasound scoring system (0–3) for tophus, double contour and aggregates. Furthermore, the intra- and inter-reader reliabilities of both the re-defined aggregates and the semi-quantitative scoring system were assessed using static image exercises. Methods: Thirty-seven rheumatologists were invited. A Delphi process was used for re-defining aggregates and for selecting a semi-quantitative scoring system with >75% agreement obligate for reaching consensus. Subsequently, a web-based exercise on static ultrasound images was conducted in order to assess the reliability of both the re-defined aggregates and the semi-quantitative scoring system. Results: Twenty rheumatologists contributed to all rounds of the Delphi and image exercises. A consensual re-definition of aggregates was obtained after three Delphi rounds but needed an overarching principle for scoring aggregates in patients. A consensus-based semi-quantitative ultrasound scoring system for gout lesions was developed after two Delphi rounds. The re-definition of aggregates showed good intra- and inter-reader reliability (κ-values 0.71 and 0.61). The reliabilities of the scoring system were good for all lesions with slightly higher intra-reader (κ-values 0.74–0.80) than inter-reader reliabilities (κ-values 0.61–0.67). Conclusion: A re-definition of aggregates was obtained with a good reliability when assessing static images. The first consensus-based semi-quantitative ultrasound scoring system for gout-specific lesions was developed with good inter- and intra-reader reliability for all lesions when tested in static images. The next step is to assess the reliabilities when scoring lesions in patients.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA). Methods: Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared. Results: 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012). Conclusions: Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA.

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease with a burdensome impact on quality of life and substantial healthcare costs. To date, pharmacological interventions with different mechanisms of action, including conventional synthetic (cs), biological (b), and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), have been proven efficacious, despite a relevant proportion of failures. The current approach in clinical practice and research is typically “predictive”: the expected response is based on stratification according to clinical, imaging, and laboratory data, with a “heuristic” approach based on “trial and error”. Several available therapeutic options target the TNF-α pathway, while others are directed against the IL-23/IL-17A axis. Janus kinase inhibitors (JAKis), instead, simultaneously block different pathways, endowing these drugs with a potentially “broad-spectrum” mechanism of action. It is not clear, however, whether targeting a specific pathway (e.g., TNF-α or the IL-23/IL-17 axis) could result in discordant effects over other approaches. In particular, in the case of “refractory to a treatment” patients, other pathways might be hyperactivated, with opposing, synergistic, or redundant biological significance. On the contrary, refractory states could be purely resistant to treatment as a whole. Since chronic synovitis is one of the primary targets of inflammation in PsA, synovial biomarkers could be useful in depicting specific biological characteristics of the inflammatory burden at the single-patient level, and despite not yet being implemented in clinical practice, these biomarkers might help in selecting the proper treatment. In this narrative review, we will provide an up-to-date overview of the knowledge in the field of psoriatic synovitis regarding studies investigating the relationships among different activated proinflammatory processes suitable for targeting by different available drugs. The final objective is to clarify the state of the art in the field of personalized medicine for psoriatic disease, aiming at moving beyond the current treatment schedules toward a patient-centered approach.

ObjectiveTo evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard.MethodsConsecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0–3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other’s findings.Results11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%—sensitivity of 91% (range 71%–87% in single sites) and specificity of 59% (range 68%–92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation.ConclusionUltrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Over the last few years, the landscape of treatments for axial spondyloarthritis (SpA) has been rapidly evolving, urging international scientific societies to draft or update existing clinical practice guidelines (CPGs) on the management of axial SpA. The Italian Society for Rheumatology (SIR) committed to provide revised and adapted evidence- and expert-based recommendations for the management of patients with axial SpA in Italy. A systematic approach to the adaptation of existing CPGs - the ADAPTE methodology - was adopted to obtain updated recommendations suitable for the Italian context. A systematic literature search was performed in Medline and Embase databases to find international CPGs and consensus statements with recommendations for the management of axial SpA published in the previous five years. A working group composed of rheumatologists with proven experience in the management of axial SpA and methodologists identified the key research questions which guided study selection and data extraction. Guideline quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The Italian recommendations were developed by endorsing or adapting and rewording some existing recommendations. The draft of the recommendations was sent to a multidisciplinary group of external reviewers for comment and rating. Six original CPGs were selected and used to create this SIR CPG, which includes a final set of 14 recommendations covering the management of patients with axial SpA across the following domains: assessment, pharmacological and non-pharmacological treatment, and follow-up. The dissemination and implementation of these SIR recommendations are expected to support an evidencebased clinical approach to the management of patients with axial SpA in Italy.

ObjectiveTo describe the adherence to quality of care indicators in early rheumatoid arthritis (RA) and to evaluate its impact on the risk of hospitalisation in a real-world setting.DesignRetrospective cohort study.SettingPatients with early-onset RA identified from healthcare regional administrative databases by means of a validated algorithm between 2006 and 2012 in the Lombardy region (Italy).ParticipantsThe study cohort included 14 203 early-onset RA (71% female, mean age 60 years).Outcome measuresFor each patient, a summary adherence score was calculated starting from the compliance to six quality indicators: (1–2) methotrexate or sulfasalazine or leflunomide with/without glucocorticoids, (3–4) other disease-modifying antirheumatic drugs (DMARDs) with/without glucocorticoids, (5) early interruption of glucocorticoids, (6) early clinical assessment.The relationship between low, intermediate and high categories of the summary score and the 12-month risk of hospitalisation for all causes and for RA was assessed.ResultsDuring a follow-up of 1 year, 2609 hospitalisations occurred, of which 704 were for RA (main or secondary diagnosis) and 252 primarily for RA. In a 7-year period (2006–2012), early DMARDs and timely clinical monitoring treatment increased (from 52% to 62% p trend Intermediate and high summary adherence score categories (compared with the low category) were related significantly with a lower risk of hospitalisation (adjusted HR 0.85 (95% CI 0.77 to 0.93), pConclusionIn early RA, adherence to quality standards of care is associated with a lower risk of hospitalisation. Future interventions to improve the adherence to quality standards of care in this setting should decrease the risk of hospitalisation with a significant impact on individual and population health.

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

Background Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. A simple multisource comorbidity score (MCS) has been recently developed and validated. A very large real-world investigation was conducted with the aim of measuring inequalities in the MCS distribution across Italy. Methods Beneficiaries of the Italian National Health Service aged 50–85 years who in 2018 were resident in one of the 10 participant regions formed the study population (15.7 million of the 24.9 million overall resident in Italy). MCS was assigned to each beneficiary by categorizing the individual sum of the comorbid values (i.e. the weights corresponding to the comorbid conditions of which the individual suffered) into one of the six categories denoting a progressive worsening comorbidity status. MCS distributions in women and men across geographic partitions were compared. Results Compared with beneficiaries from northern Italy, those from centre and south showed worse comorbidity profile for both women and men. MCS median age (i.e. the age above which half of the beneficiaries suffered at least one comorbidity) ranged from 60 (centre and south) to 68 years (north) in women and from 63 (centre and south) to 68 years (north) in men. The percentage of comorbid population was lower than 50% for northern population, whereas it was around 60% for central and southern ones. Conclusion MCS allowed of capturing geographic variability of multimorbidity prevalence, thus showing up its value for addressing health policy in order to guide national health planning.

Background: Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. Methods: In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. Results: For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Conclusions: Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.

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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.

Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

ObjectiveTo compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis.MethodsIn a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists.ResultsResponses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients’ preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK.ConclusionsOverall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

OBJECTIVE: The language currently used to describe gout lacks standardisation. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n=130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labelling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. RESULTS: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of eight disease elements through the Delphi exercise; the remaining three labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were: monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion and podagra. The face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label 'chronic gout' should not be used. CONCLUSION: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout aetiology, pathophysiology and clinical presentation. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) recommends the use of these labels when describing the basic disease elements of gout. This article is protected by copyright. All rights reserved.

ObjectiveThere is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout.MethodsA content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions.ResultsThe content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: ‘asymptomatic hyperuricaemia’, ‘asymptomatic monosodium urate crystal deposition’, ‘asymptomatic hyperuricaemia with monosodium urate crystal deposition’, ‘gout’, ‘tophaceous gout’, ‘erosive gout’, ‘first gout flare’ and ‘recurrent gout flares’. There was consensus agreement that the label ‘gout’ should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus).ConclusionConsensus agreement has been established for the labels and definitions of eight gout disease states, including ‘gout’ itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.

Objective.To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease.Methods.We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non–anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody–negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures.Results.NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP.Conclusion.NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

ObjectiveTo evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients with osteoarthritis (OA) of the foot.MethodsAfter a systematic literature review, a Delphi survey was performed to test definitions of US lesions in OA of the foot, including inflammatory lesions (ie, synovial hypertrophy [SH], joint effusion [JE], power Doppler signal [PD]), and structural abnormalities (ie, cartilage damage [CD] and osteophytes). Subsequently, the reliability of US in assessing the aforementioned lesions was tested on static images as well as during a live exercise. Reliability was assessed by kappa analyses and prevalence-adjusted bias-adjusted kappa (PABAK) on a dichotomous and an ordinal scale.ResultsIntraobserver and interobserver reliability for SH and JE evaluated by binary scoring was good for both components, while the intraobserver reliability for semiquantitative scoring of SH ranged from moderate in the web-based exercise (PABAK 0.49) to good (PABAK 0.8) in the live exercise. Reliability for CD and PD assessments were respectively good and excellent in all exercises (ranged from PABAK 0.61 to 0.79 for CD and 0.88 to 0.95 for PD). The interobserver reliability for the semiquantitative scoring of osteophytes was fair in the live exercise (PABAK 0.36) and moderate in the static exercise (PABAK 0.60).ConclusionsConsensual US definitions were found to be reliable for assessing inflammatory lesions in OA of the foot, while the use of US to assess structural damage requires further studies.

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing–remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids.In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD.With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.

The opportunity of a multidisciplinary evaluation for the diagnosis of interstitial pneumonias highlighted a major change in the diagnostic approach to diffuse lung disease. The new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guidelines for the diagnosis of idiopathic pulmonary fibrosis have reinforced this assumption and have underlined that the exclusion of connective tissue disease related lung involvement is mandatory, with obvious clinical and therapeutic impact. The multidisciplinary team discussion consists in a moment of interaction among the radiologist, pathologist and pulmonologist, also including the rheumatologist when considered necessary, to improve diagnostic agreement and optimize the definition of those cases in which pulmonary involvement may represent the first or prominent manifestation of an autoimmune systemic disease. Moreover, the proposal of classification criteria for interstitial lung disease with autoimmune features (IPAF) represents an effort to define lung involvement in clinically undefined autoimmune conditions. The complexity of autoimmune diseases, and in particular the lack of classification criteria defined for pathologies such as anti-synthetase syndrome, makes the involvement of the rheumatologist essential for the correct interpretation of the autoimmune element and for the application of classification criteria, that could replace clinical pictures initially interpreted as IPAF in defined autoimmune disease, minimizing the risk of misdiagnosis. The aim of this review was to evaluate the available evidence about the efficiency and efficacy of different multidisciplinary team approaches, in order to standardize the professional figures and the core set procedures that should be necessary for a correct approach in diagnosing patients with interstitial lung disease.

ObjectivesThis multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease—ILD, emphysema or neither).MethodsChest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. PResultsWe enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (pConclusionsCPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD.

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes. info:eu-repo/semantics/publishedVersion

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterised by chronic joint inflammation, leading to functional disability and increased risk of premature death. Clinical practice guidelines (CPGs) are expected to play a key role in improving management of RA, across the different phases of the disease course. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2011 recommendations on management of RA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing RA CPGs to the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Research Unit and a committee with experience in RA identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage RA in practice, and the target population includes adult patients diagnosed as having RA. An external multi-disciplinary committee rated the final version of the CPGs. From the systematic search in databases (Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 8 (Management) +6 (Safety) recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the management of RA and to disseminate the best evidence-based clinical practices for this disease.

Background: Patients in the terminal phase of chronic illnesses are often admitted to acute care wards, with the risk of receiving inappropriate intensive treatments as opposed to necessary palliative care (PC). Objective: To assess patient features and possible service biases in the activation of PC pathways, or lack thereof, for those dying in acute care. Design and setting: This was a prospective observational study of all patients admitted to our acute medical ward from the emergency department during 6 months. Measurements: Need for palliation was evaluated for all patients by a physician and a nurse of the Internal Medicine ward. Those proposed for PC were re-evaluated by a consultant and a nurse of the PC unit. Clinical and epidemiological data were obtained for those selected for PC, and those deceased in the acute ward without having received PC. Results: A total of 781 patients were admitted to the acute care ward and screened during the study period. Of the 56 patients assigned to the PC pathway, those that died in hospital (n = 30) had significantly poorer Karnofsky, Braden, and ECOG scores compared to those alive at discharge (n = 26). Forty-eight more patients died on the ward without having received PC. The prevalence of cardiopulmonary diseases was significantly higher in this group, while more oncologic patients died in the PC cohort. Conclusions: Palliative treatment needs to be augmented and better targeted in acute care settings. Special attention should be given to patients with cardiopulmonary illnesses, a possible bias preventing the activation of this type of care, and those at high risk of developing pressure ulcers. Further education and training in this field are crucial for healthcare professionals working in acute wards.

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.

Objectives. To identify from a patient's perspective, difficulties and differences in the comprehension of five global presenteeism measures in patients with inflammatory arthritis and OA across seven countries. Methods. Seventy patients with a diagnosis of inflammatory arthritis or OA in paid employment were recruited from seven countries across Europe and Canada. Patients were randomly allocated to be cognitively debriefed on 3/5 global measures [Work Productivity Scale - Rheumatoid Arthritis, Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index, Quality and Quantity questionnaire, and WHO Health and Work Performance Questionnaire (HPQ)], with the WPAI debriefed in all patients as a standard measure of comparison between countries and patients. NVivo was used to code the data into four themes: construct and anchor, time recall, reference frame, and attribution. Results. Discrepancies were found in the interpretation of the word performance (HPQ) between countries, with Romania and Sweden relating performance to sports rather than work. Seventy percent of patients considered that a 7-day recall (WPAI) can accurately represent how their disease affects work productivity. The compared to normal reference (Quality and Quantity questionnaire) was reportedly too ambiguous, and the comparison with colleagues (HPQ), made many feel uncomfortable. Overall, 29% of patients said the WPAI was the most relevant to them, making it the most favoured measure. Conclusion. Overall, patients across countries agree that the construct of work productivity in the last 7 days can accurately reflect the impact of disease while at work. Some current constructs to assess at-work productivity are not interchangeable between languages.

Objective.To determine the frequency of adverse events of diagnostic arthrocentesis in patients with possible gout.Methods.Consecutive patients underwent arthrocentesis and were evaluated at 6 weeks to determine adverse events. The 95% CI were obtained by bootstrapping.Results.Arthrocentesis was performed in 910 patients, and 887 (97.5%) were evaluated for adverse events. Any adverse event was observed in 12 participants (1.4%, 95% CI 0.6–2.1). There was 1 case (0.1%, 95% CI 0–0.34) of septic arthritis.Conclusions.Diagnostic arthrocentesis is associated with a low frequency of adverse events. Septic arthritis rarely occurs.

Objective.Several global measures to assess at-work productivity loss or presenteeism in patients with rheumatic diseases have been proposed, but the comparative validity is hampered by the lack of data on test-retest reliability and comparative concurrent and construct validity. Our objective was to test-retest 5 global measures of presenteeism and to compare the association between these scales and health-related well-being.Methods.Sixty-five participants with inflammatory arthritis or osteoarthritis in paid employment were recruited from 7 countries (UK, Canada, Netherlands, France, Sweden, Romania, and Italy). At baseline and 2 weeks later, 5 global measures of presenteeism were evaluated: the Work Productivity Scale–Rheumatoid Arthritis (WPS-RA), Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index (WAI), Quality and Quantity questionnaire (QQ), and the WHO Health and Performance Questionnaire (HPQ). Agreement between the 2 timepoints was assessed using single-measure intraclass correlations (ICC) and correlated between each other and with visual analog scale general well-being scores at followup by Spearman correlation.Results.ICC between measures ranged from fair (HPQ 0.59) to excellent (WPS-RA 0.78). Spearman correlations between measures were moderate (Qquality vs WAI, r = 0.51) to strong (WPS-RA vs WPAI, r = 0.88). Correlations between measures and general well-being were low to moderate, ranging from −0.44 ≤ r ≤ 0.66.Conclusion.Test-retest results of 4 out of 5 global measures were good, and the correlations between these were moderate. The latter probably reflect differences in the concepts, recall periods, and references used in the measures, which implies that some measures are probably not interchangeable.