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COVID-19; Registries; Vaccination COVID-19; Registros; Vacunación COVID-19; Registres; Vacunació Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups. HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

Objectives The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. Methods An online self-reported questionnaire (March–December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. Results Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. Conclusion Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Objectives To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin. Methods Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. Results A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92–0.96) and CPPD (0.90–0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD. Conclusions A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis. A video abstract is available for this article and can be viewed at https://doi.org/10.1093/rheumatology/keac479.

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (

Some case reports and small case series of patients with silicone breast implant (SBI) have reported the development of systemic sclerosis (SSc) many years later, despite conflicting evidence of this association in the literature. Recently, patients with SSc and anti-RNA polymerase III antibodies positivity have been associated with previous silicone implants and/or breast cancer, showing clinical features that differ from the classic SSc, such as rapid and diffuse cutaneous involvement and scleroderma renal crisis (SRC). The specific autoimmune reaction is not yet fully understood, although knowledge in this regard is increasing. We describe a case that can support these previous observations, strengthening this association which must be taken into account. Clinicians should be aware of this new clinical entity, given the widespread use of silicone implants.

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune-system alterations, fibrosis involving the skin and internal organs and diffuse microangiopathy. Pulmonary arterial hypertension (PAH) is a severe complication of SSc affecting about 10–15% of the patients and it is a leading cause of mortality. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. Nail fold videocapillaroscopy (NVC) studies have shown a more severe peripheral microvascular dysfunction in SSc patients with PAH suggesting that abnormalities in peripheral microcirculation may correlate with pulmonary microangiopathy. This is a cross-sectional study involving four tertiary University Rheumatology Units in the Center-North of Italy. Seventy patients, 35 adults with SSc and PAH confirmed by RHC (F/M 34/1; median age 65.2 ± 8.9 SD yrs), and 35 SSc patients without PAH were enrolled (F/M 3471; median age 63.3 ± 10.3 SD yrs). Clinical, laboratoristic and instrumental data were collected and NVC was performed in all patient. Specific NVC parameters were evaluated and a semi-quantitative rating scale was adopted to score these changes. Finally, patients were distributed into the suitable NVC pattern belonging to the scleroderma pattern. Our aim was to compare the peripheral microangiopathy changes in SSc patients with and without PAH, and to investigate the relationship between NVC findings and the main hemodynamic parameters of pulmonary vasculopathy. Patients with SSc-PAH+ showed a significant higher frequency of interstitial lung disease (ILD). No significant differences regarding clinical and laboratoristic parameters were observed. NVC abnormalities, avascular areas were more frequent in SSc patients with PAH, respect to those without (p = 0.03), and capillary density was significantly lower when considering grade 3 (p = 0.02). A higher NVC semiquantitative mean was found in SSc-PAH+ patients and a greater rate of the “late” pattern was detected in SSc-PAH+ subjects in respect to PAH- (57.1% vs. 25.7%) (p = 0.03). A significant correlations between pulmonary pressure values (sPAP by TTE and mPAP by RHC) and the capillary density (Spearman's rho 0.35, p = 0.04 for both). Our findings provide additional evidence to the literature data, confirming that a higher degree of peripheral nailfold microangiopathy is more common in SSc-PAH patients, and further strengthening the concept that NVC changes may run parallel with similar abnormalities inside pulmonary microcirculation.

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.

In the past months, mass vaccination represented the turning point of the global battle against the COVID-19 pandemic, an unprecedented challenge for physicians, healthcare professionals, health systems and pharmaceutical companies. More than 6 billion doses of vaccine have been administered to date, covering nearly 50% of the world’s population. Although the vaccination campaign is still thwarted by spread of fake news disseminated by a ubiquitous antivaxxer movement, accumulating real-life data1 confirm the favourable safety profile already demonstrated in phase III clinical trials.2 Despite the lack of a steady literature evidence,3 the potential role of vaccines in promoting autoimmunity continues to intrigue many researchers. The theoretical basis of this association relies on the possible molecular mimicry between macromolecular components of the vaccine and specific human proteins and the exuberant immune response elicited by adjuvants contained in vaccines.4 Adverse events (AEs) associated with COVID-19 vaccines are usually mild and mainly restricted to injection site reactions. Interestingly, among systemic AEs, arthralgia is one of the most common.2 To the best of our knowledge, only isolated cases5 of arthritis developed after COVID-19 …

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Objectives The objectives of this study were (1) to explore US findings for muscle mass, muscle quality and muscle stiffness in SLE patients and healthy subjects; (2) to investigate the relationship between the US muscle findings and physical performance in SLE patients and healthy subjects. Methods Quadriceps muscle thickness was used for assessment of muscle mass, muscle echogenicity (using a visual semi-quantitative scale and grayscale analysis with histograms) for assessment of muscle quality, and point shear-wave elastography (SWE) for assessment of muscle stiffness in 30 SLE patients (without previous/current myositis or neuromuscular disorders) and 15 age-, sex- and BMI-matched healthy subjects. Hand grip strength tests and short physical performance battery (SPPB) tests were carried out in the same populations. Results No difference was observed between SLE patients and healthy subjects for quadriceps muscle thickness (35.2 mm ±s.d. 6.8 vs 34.8 mm ± s.d. 6.0, respectively, P = 0.79). Conversely, muscle echogenicity was significantly increased in SLE patients (visual semi-quantitative scale: 1.7 ± s.d. 1.0 vs 0.3 ± s.d. 0.5, respectively, P Conclusions US assessment of muscle echogenicity and stiffness is useful for the early detection of muscle involvement in SLE patients.

Purpose of Review To highlight the potential uses and applications of imaging in the assessment of the most common and relevant musculoskeletal (MSK) manifestations in systemic lupus erythematosus (SLE). Recent Findings Ultrasound (US) and magnetic resonance imaging (MRI) are accurate and sensitive in the assessment of inflammation and structural damage at the joint and soft tissue structures in patients with SLE. The US is particularly helpful for the detection of joint and/or tendon inflammation in patients with arthralgia but without clinical synovitis, and for the early identification of bone erosions. MRI plays a key role in the early diagnosis of osteonecrosis and in the assessment of muscle involvement (i.e., myositis and myopathy). Conventional radiography (CR) remains the traditional gold standard for the evaluation of structural damage in patients with joint involvement, and for the study of bone pathology. The diagnostic value of CR is affected by the poor sensitivity in demonstrating early structural changes at joint and soft tissue level. Computed tomography allows a detailed evaluation of bone damage. However, the inability to distinguish different soft tissues and the need for ionizing radiation limit its use to selected clinical circumstances. Nuclear imaging techniques are valuable resources in patients with suspected bone infection (i.e., osteomyelitis), especially when MRI is contraindicated. Finally, dual energy X-ray absorptiometry represents the imaging mainstay for the assessment and monitoring of bone status in patients with or at-risk of osteoporosis. Summary Imaging provides relevant and valuable information in the assessment of MSK involvement in SLE.

Nailfold capillaroscopy is currently the best method to investigate microvascular abnormalities in systemic sclerosis and related conditions, and in other rheumatic conditions in which there is a clinical suspicion of microangiopathy. Although easy to perform, it is essential that the operators have been properly trained about correct method of images acquisition and interpretation. There are some parameters to indicate a normal/healthy capillaroscopic picture, but it is important to consider that there is a great variability in the capillary structure both interindividual and intraindividual. The early differential diagnosis between primary and secondary RP is the best advantage that the technique may offer. Remarkable capillaroscopic alterations are found in the majority of cases of systemic sclerosis and the so-called “scleroderma spectrum disorders” (dermatomyositis, mixed connective tissue disease, undifferentiated connective tissue disease). Nevertheless, some capillaroscopic changes have been observed in systemic lupus erythematosus, Sjogren’s syndrome, psoriatic and rheumatoid arthritis. Discussion about controversies on this topic should be encouraged, leading to a progressive development of capillaroscopy as a routine investigation in rheumatology.

We read with great interest the letter recently published in Annals of the Rheumatic Diseases by Priori et al ,1 who carried out an online survey among patients with rheumatic diseases to explore their willingness to receive the SARS-CoV-2 vaccination. An alarming high hesitancy was observed in nearly half of these patients. This is particularly concerning as patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are regarded as at higher risk for developing severe COVID-19 and, for this reason, they should be vaccinated with priority.2 3 To date, four vaccines have been approved in Italy for COVID-19 but only three are currently available (ie, Pfizer/BioNTech, Moderna and AstraZeneca). Importantly, the European Alliance of Association for Rheumatology stated that all these vaccines can be used safely in patients with AIIRDs as well as in patients receiving immunosuppressive treatment.4 Similarly, the Italian Society of Rheumatology (Societa Italiana di Reumatologia) produced a document (last update: 13 March 2021) to confirm the safety of all the SARS-CoV-2 vaccines for patients with AIIRDs.5 In recent weeks, AstraZeneca vaccine is undergoing an unprecedented media firestorm following reports on its possible association with venous thromboembolism.6 With this regard, the European Medicines Agency has stated that the overall benefits of AstraZeneca vaccine in preventing COVID-19 outweigh the risks of side effects in the general population.7 Our aim was to explore the willingness to receive SARS-CoV-2 vaccines among …

Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Background Frailty is a construct recently introduced in the context of inflammatory joint diseases. To date, it is not clear if frailty can act as a negative factor in the achievement of comprehensive disease control (CDC) in patients suffering from rheumatoid arthritis (RA). Aim To verify whether frailty is a factor hindering the achievement of CDC in patients with RA starting a biologic drug. Methods RA patients requiring a treatment with a biologic drug were included. Patients were classified as achieving or not achieving CDC after 12 months of treatment. Patients were classified as non-frail, mildly frail, moderately frail and severely frail according to the Comprehensive Rheumatologic Assessment of Frailty (CRAF). Frailty was tested using the Mann–Whitney or Kruskal-Wallis test for continuous variables and chi-square test or Fisher’s exact test for comparison with categorical variables. A multivariable logistic regression was performed to identify factors associated with prediction of CDC achievers. Results A total of 214 RA patients were followed for 12 months, 14.5% achieved CDC. Eighty-four (39.3%) patients were non-frail, 57 (26.6%) were mildly frail, 14 (6.5%) were moderately frail and 59 (27.6%) were severely frail. The multivariable logistic regression analysis identified the CRAF score at baseline as an independent variable for CDC achievement at 12 months (p = 0.0040). Discussion Frailty is a frequent condition in RA patients and reduces the chances of achieving CDC. Conclusions Frailty, measured by CRAF, reduced the likelihood of CDC achievement in RA patients treated with a biologic agent. Key Points• Frailty is an under-researched condition in rheumatoid arthritis affecting more than 60% of patients.• Frailty is a condition that hinders the achievement of comprehensive disease control after 1 year of treatment with biological drugs in patients with rheumatoid arthritis.

Large cohort studies demonstrated that a sizeable proportion of patients with acute COVID-19 present with symptoms or signs of rheumatological interest such as arthralgia/myalgia, inflammatory skin lesions and/or autoantibodies positivity.1 Subsequent clinical observations disclosed the existence of a post-acute COVID-19 syndrome, characterised by a large constellation of manifestations including fatigue, arthralgia and myalgia.2 The potential role of viruses in the development of rheumatic diseases is well recognised, either as causative agents or antigenic triggers for the ensuing development of autoimmunity.3 Consistent with these premises, from the earliest phases of the pandemic, inflammatory musculoskeletal manifestations following COVID-19 have been described in isolated case reports although no systematically collected cohorts are still available to unveil the clinical spectrum of post-COVID-19 arthritis.4 To contribute to shed light on this field, in December 2020, we built a web-based survey platform and invited all members of our study group to submit cases of inflammatory …

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05046-4.

Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.

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Contains fulltext : 219902.pdf (Publisher’s version ) (Open Access) Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a 'mainstream' investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.

The Internal Medicine section, from the origins in the seventies with Carlo De Martinis to Riccardo Sarzani today, has been involved in cardiovascular medicine integrated with metabolic aspects. The research has been focused on many aspect of hypertension, from basic and experimental research with a translational approach up to clinical studies even in the elderly, with special focus on obesity and natriuretic peptides. Our main results have been confirmed by many independent groups and our key papers are highly cited. Collaborations with three U.S. groups, from Boston University in the eighties to the Mayo Clinic today, have consolidated our research efforts. The research activity of Rheumatology Clinic was mainly devoted to develop a core set of knowledge which endorsed worldwide the use of ultrasound in daily rheumatologic practice. Moreover, our group firstly introduced the capillaroscopy technique in Italy to study the microcirculation in connective tissue diseases. Another clinical area of research was dedicated on patient-reported outcomes in inflammatory arthritides and fibromyalgia. The results obtained over the years have allowed us to keep a widely recognized role not only in research, but also in teaching, proven by the publication of more than 300 studies in high quality peer-reviewed international scientific journals.

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Background Belimumab is the unique biologic therapy available for patients with SLE. Objectives To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression (SPSS, version 22.0). Results Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort. Disclosure of Interests Luca Iaccarino: None declared, Francesca Saccon: None declared, Alessandro Mathieu: None declared, Matteo Piga: None declared, Angela Ceribelli: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Paolo Cardinaletti: None declared, Armando Gabrielli: None declared, Andrea Di Matteo: None declared, Rossella De Angelis: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Micaela Fredi: None declared, Francesca Regola: None declared, Laura Andreoli: None declared, Giulia Pazzola: None declared, Carlo Salvarani: None declared, Francesco Puppo: None declared, Simone Negrini: None declared, Marcella Prete: None declared, Vito Racanelli: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Maria Gerosa: None declared, Tania Ubiali: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Fabrizio Conti: None declared, Fulvia Ceccarelli: None declared, Elena Bartoloni Bocci: None declared, Roberto Gerli: None declared, Antonio Lobasso: None declared, Amato De Paulis: None declared, Ginevra De Marchi: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche, Alessandra Bortoluzzi: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Benvenuti: None declared, Margherita Zen: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Chiara Tani: None declared, Maurizio Rossini: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Mariele Gatto: None declared, Salvatore Scarpato: None declared, Enrico Brunetta: None declared, Aurora Zumbo: None declared, Gabriele Valentini: None declared, SERENA FASANO: None declared, Giacomo Emmi: None declared, Maria Letizia Urban: None declared, Giacomo Tanti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Andrea Doria: None declared

Background: The European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases is a non-profit international network of expert centres. Its main research focus is to investigate the morphology and function of the microcirculation with different non-invasive techniques such as nailfold videocapillaroscopy (NVC). NVC is of paramount importance for the differential diagnosis of primary and secondary Raynaud’s phenomenon [1], and is part of the 2013 ACR/EULAR classification criteria for systemic sclerosis. As there is a wide variety of non-scleroderma patterns, the categorisation of capillaroscopic images as non-scleroderma patterns may be a challenge to the capillaroscopist. Objectives: This study was designed to propose a simple fast track algorithm to differentiate scleroderma patterns from non-scleroderma patterns and to assess its interobserver reliability. Methods: During the 8th EULAR course on capillaroscopy held in Genoa, September 2018, a lecture on teaching the fast tract algorithm to categorise an image as non-scleroderma (category 1) or scleroderma pattern (category 2) (see figure) was given to all attendees (from 43 different countries): 6 experts, 68 novices, 53 moderately experienced ( 5 years of experience with capillaroscopy). Immediately after training, an examination was performed on 30 images. Classification of the images was defined by the presenter (VS) as the gold standard. Interobserver reliability was assessed by the calculation of kappa coefficients and proportion of agreement versus the gold standard. Results: The light kappa was 1 for the independent experts (n=6) and 0.92 for the attendees (n=135). When comparing with the gold standard, an equal mean kappa of 0.96 (95%CI 0.95 – 0.98) was found for both independent experts and attendees. Analyses according to the reported level of experience on capillaroscopy revealed a mean index of reliability of 0.98 (95%CI 0.96 – 0.99) for novices, 0.96 (95%CI 0.93 – 0.99) for moderately experienced raters and 0.93 (95%CI 0.85 – 1.01) for experienced raters. Conclusion: For the first time a fast track algorithm has been developed that was trainable within an hour to non-experienced capillaroscopists and has an excellent reliability to discern a non-scleroderma from a scleroderma pattern by medical doctors with varying levels of expertise in capillaroscopy. Reference [1] Koenig M, et al. Arthritis Rheum. 2008;58(12):3902-12. Disclosure of Interests: Vanessa Smith: None declared, Amber Vanhaecke: None declared, Miguel Guerra: None declared, Rossella De Angelis: None declared, Ellen Deschepper: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, Inventiva, CSF Behring, Consultant for: Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Bayer, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders, Ivan Foeldvari Consultant for: Chugai, Novartis, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Francesca Ingegnoli: None declared, Ulf Muller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Yves Piette: None declared, Valeria Riccieri: None declared, Barbara Ruaro: None declared, Alberto Sulli: None declared, Jacob M. van Laar Grant/research support from: Genentech, Consultant for: F. Hoffmann-La Roche, Ariane Herrick: None declared, Maurizio Cutolo: None declared

To assess the prevalence and factors associated with mild cognitive impairment (MCI) in patients suffering from psoriatic arthritis (PsA). A cross-sectional evaluation was conducted in consecutive PsA patients. Sociodemographic data and the clinimetric variables related to PsA and psoriasis were collected for each patient. MCI was assessed through the Montreal Cognitive Assessment (MoCA). The cognitive performance of PsA patients was compared to healthy subjects using one-way analysis of variance (ANOVA). The correlations among variables were studied by the Spearman rank correlation coefficient. A multivariate logistic regression analysis was carried out to establish the predictors of MCI. The study involved 96 PsA patients and 48 healthy subjects. MCI (defined as a MoCA score

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

Objective To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. Patients and methods Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. Results We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. Conclusion Belimumab is effective and safe when used in clinical practice setting.

Objectives To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS). Methods Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised. Results Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component. Conclusions Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed.

BACKGROUND The aim of this review is to investigate systematically the presence of the most extensively studied Synovial Fluid (SF) and/or serum markers in patients with Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Osteoarthritis (OA), and their associations and correlations with laboratory and clinical data, with a view to providing insights for future research. OBJECTIVE Papers were selected using the PRISMA flow-chart. Search of the electronic databases according to the above criteria found a total of 55 papers. Examination led to the exclusion of 39 papers. Finally, 16 studies met the inclusion criteria and are reviewed. As regards to interleukins we found: Higher TNF-α levels in patients with early RA and PsA than in those with osteoarthritis (p

Ultrasound (US) is a cost-effective, noninvasive, accessible imaging modality that clinicians use at the point of care to assess disease activity and therapeutic efficacy in different rheumatic conditions. However, its utility has been prevalently demonstrated in the field of chronic arthritides. Only in the last few years there was an interest to explore the potential of US beyond the musculoskeletal area. In this way, preliminary US data about the assessment of the different targets involved in systemic sclerosis such as joints, tendons, skin, vessels, and lung have been provided. The main purpose of this US review is to provide an overview of the potential role of US in the multi-target assessment of SSc and to discuss the current evidence supporting its relevance and applications in daily clinical practice.

Objective To determine the sensitivity, specificity, and accuracy of ultrasound (US) in the detection of cartilage calcification at knee level in patients with calcium pyrophosphate deposition disease (CPDD) and to assess the interobserver reliability. Methods Seventy-four CPDD patients and 83 controls with other chronic arthritis were included. All patients underwent a clinical examination, synovial fluid analysis, and radiographic assessment of the knee. US examinations were performed in order to detect hyperechoic spots within the hyaline cartilage layer and hyperechoic areas within the meniscal fibrocartilage. Twenty patients were assessed by 2 operators in order to calculate the interobserver reliability. Results A total of 314 knees in 157 patients (74 with CPDD, 19 with rheumatoid arthritis, 17 with spondyloarthritis, 32 with osteoarthritis, and 15 with gout) were assessed. In the 74 patients with CPDD, hyaline cartilage spots were detected by US in at least 1 knee in 44 patients (59.5%), whereas radiography detected hyaline cartilage spots in 34 patients (45.9%) (P < 0.001). Meniscal fibrocartilage calcifications were detected by US in 67 of the 74 CPDD patients (90.5%), whereas conventional radiography detected calcifications in 62 patients (83.7%) (P = 0.011). The criterion validity expressed as percentage of sensitivity, specificity, and accuracy of US in the detection of articular cartilage calcification was high. Both kappa values and overall agreement percentages showed moderate to excellent agreement. Conclusion US is an accurate and reliable imaging technique in the detection of articular cartilage calcification at knee level in patients with CPDD.

Objective.To test the learning curve of rheumatologists with different experience in videocapillaroscopy (VCP) attending an intensive training program focused on interpretation of the main capillary nailfold abnormalities, the scleroderma (systemic sclerosis, SSc) pattern, and the normal pattern, and to determine their interreader agreement with an experienced investigator.Methods.Five investigators (1 senior, 1 junior, and 3 beginners) participated in the exercise. The study was composed of 2 steps. First, an independent investigator selected representative VCP images of normal patterns and capillary abnormalities. The second step included the training program, which ran 4 hours per day for 7 days. The senior rheumatologist taught investigators to recognize and interpret the normal pattern, the capillary abnormalities, and the different types of SSc pattern. These abnormalities were considered: homogeneously enlarged capillaries, giant capillaries, irregularly enlarged capillaries, microhemorrhages, neoangiogenesis, avascular areas, and capillary density.Results.A total of 300 VCP images were read from all the investigators. Both κ values and overall agreement percentages of qualitative and quantitative assessments showed progressive improvement from poor to excellent from the beginning to the end of the exercise. The sensitivity and specificity of the participants in the assessment of SSc pattern at the last lecture session were high.Conclusion.Our pilot study suggests that after an intensive 1-week training program, novice investigators with little or no experience in VCP are able to interpret the main capillary abnormalities and SSc pattern and to achieve good interreader agreement rates.

Ultrasound is a rapidly evolving technique that is gaining an increasing success in the assessment of psoriatic arthritis. Most of the studies have been aimed at investigating its ability in the assessment of joints, tendons, and entheses in psoriatic arthritis patients. Less attention has been paid to demonstrate the potential of ultrasound in the evaluation of skin and nail. The aim of this pictorial essay was to show the main high-frequency grayscale and power Doppler ultrasound findings in patients with psoriatic arthritis at joint, tendon, enthesis, skin, and nail level.

To assess health-related quality of life (HRQL) in patients with primary Raynaud phenomenon (RP).The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) questionnaire and the EQ-5D questionnaire were administered to 81 patients with primary RP who had been referred to a rheumatological department. The scores were compared with data of control subjects.In the physical dimensions of the SF-36, the subjects who had RP had significantly lower scores (worse HRQL) than controls (47.6 +/- 9.8 vs. 52.2 +/- 9.3, P = 0.021). The physical component score (PCS) was correlated with age (P = 0.003) and the number of comorbidities (P = 0.004). The mental health component score (MCS) was significantly lower in RP subjects than in controls (41.9 +/- 9.4 vs. 46.1 +/- 10.7, P = 0.006). As regards anxiety/depression (of the EQ-5DA/D), considerably more RP patients (77.7%) reported at least some related problems as compared with controls (60.0%) (chi = 7.93; P = 0.005). Fifty-two RP patients (64.2%) and 178 controls (57.8%) described themselves as moderately anxious/depressed, whereas 11 RP patients (13.5%), and 7 controls (2.2%) reported extreme anxiety/depression (P0.0001).This study shows a reduction of the HRQL in patients with primary RP, compared with control subjects. The psychologic wellbeing represents the most involved area, whereas physical functioning and symptoms are significantly influenced by age and comorbidities. Moreover, these patients are more anxious/depressed (EQ-5DA/D). Longitudinal studies are needed to validate our findings, to explore the causal relationship between primary RP and emotional factors, and to possibly lead to encouraging behavioral therapies.