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Pain is the main symptom of entheseal diseases (enthesopathies) despite a paucity of nerve endings in the enthesis itself. Eicosanoids, cytokines, and neuropeptides released during inflammatory and repeated non-physiological mechanical challenge not only stimulate or sensitize primary afferent neurons present in structures adjacent to the enthesis or but also trigger a "neuro-vascular invasion" that allows spreading of nerves and blood vessels into the enthesis. Nociceptive pseudo-unipolar neurons support this process by releasing neurotransmitters from peripheral endings that induce neovascularization and peripheral pain sensitization. This process may explain the frequently observed dissociation between subjective symptoms, i.e. pain and the structural findings in imaging in entheseal disease.

Objectives Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009. Material and methods Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020. Overall survival of SSc patients was described using the Kaplan–Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR). Results A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4% and 89.4%, respectively. The SMR was 0.96 (95% CI 0.81, 1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (P Conclusions In the past decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities and PAH with or without ILD represent the main poor prognostic factors.

BACKGROUND/OBJECTIVES: Several scoring systems have been specifically developed for risk stratification in COVID-19 patients. DESIGN: We compared, in a cohort of confirmed COVID-19 older patients, three specifically developed scores with a previously established early warning score. Main endpoint was all causes in-hospital death. SETTING: This is a single-center, retrospective observational study, conducted in the Emergency Department (ED) of an urban teaching hospital, referral center for COVID-19. PARTICIPANTS: We reviewed the clinical records of the confirmed COVID-19 patients aged 60 years or more consecutively admitted to our ED over a 6-week period (March 1st to April 15th, 2020). A total of 210 patients, aged between 60 and 98 years were included in the study cohort. MEASUREMENTS: International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol-Coronavirus Clinical Characterization Consortium (ISARIC-4C) score, COVID-GRAM Critical Illness Risk Score (COVID-GRAM), quick COVID-19 Severity Index (qCSI), National Early Warning Score (NEWS). RESULTS: Median age was 74 (67-82) and 133 (63.3%) were males. Globally, 42 patients (20.0%) deceased. All the score evaluated showed a fairly good predictive value with respect to in-hospital death. The ISARIC-4C score had the highest area under ROC curve (AUROC) 0.799 (0.738-0.851), followed by the COVID-GRAM 0.785 (0.723-0.838), NEWS 0.764 (0.700-0.819), and qCSI 0.749 (0.685-0.806). However, these differences were not statistical significant. CONCLUSION: Among the evaluated scores, the ISARIC-4C and the COVID-GRAM, calculated at ED admission, had the best performance, although the qCSI had similar efficacy by evaluating only three items. However, the NEWS, already widely validated in clinical practice, had a similar performance and could be appropriate for older patients with COVID-19.

Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu.One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A.Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p0.01).Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.

Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used.A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated.The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density.Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Background: Cardiovascular events (CVEs) are the first cause of death in patients with psoriatic arthritis (PsA). Depression is a recognized risk factor in cardiovascular events and is frequently associated with PsA. Flow-mediated dilatation (FMD) is a widely used method for assessing endothelial dysfunction, a parameter with strong prognostic implications for CVEs. The study aims to explore the relationship between FMD, depressive symptoms and serum cytokines in a cohort of patients with PsA.Patients and Methods: FMD was assessed in 50 consecutive PsA patients aged between 30 and 75 years without known cerebrovascular and coronary heart disease or diabetes. Depressive symptoms were reported using the related subscale of the Hospital Anxiety and Depression Scale (HDS). Disease features, activity indexes, and adjusted Framingham risk score (aFRS) were calculated. Serum level of IL-6, TNF-α, and IL-17A were also assessed.Results: In PsA patients (age 50.7 ± 10.2 years, male 42%, disease duration 5.9 ± 3.3 years, Disease Activity in PSoriatic Arthritis (DAPSA) score 14.0 ± 9.4) FMD inversely correlated with the severity of depressive symptoms according to HDS (ρ = −0.339, p = 0.016), age (ρ = −0.507, p = 0.001), aFRS (rs = −0.453, p < 0.001), duration of PsA (ρ = −0.507, p = 0.001), intensity of pain (ρ = −0.507, p = 0.001), and DAPSA (ρ = −0.507, p = 0.001). No statistically significant correlation was found between FMD or HDS and serum cytokines concentrations. HDS predicted FMD in a model adjusted for age, aFRS, PsA duration, and pain intensity (β = −0.271, p = 0.008), with depressive symptoms contributing directly to 6.4% of the variance.Conclusions: Depressive symptoms correlate with endothelial dysfunction with an exposure-response pattern in our cohort of PsA patients.

Background Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection. There are several reasons to hypothesize that the eye, and the retina in particular, could be a target of organ damage in SARS-CoV-2 infection. Methods This cohort observational study analyzes OCT angiography and structural OCT of 70 post-COVID-19 patients evaluated at 1-month hospital discharge and 22 healthy control subjects. Primary outcomes were macular vessel density (VD) and vessel perfusion (VP); structural OCT features were evaluated as secondary outcomes. In addition, patients and healthy volunteers were evaluated for best corrected visual acuity, slit lamp photograph, and fundus photo image. Results VD and VP in 3 × 3 and 6 × 6 mm scans for SCP and DCP showed no significant differences between the groups. Similarly, CMT and GCL did not reveal significant differences between post-COVID-19 and healthy patients. Nine patients (12.9%) featured retinal cotton wool spots and 10 patients had vitreous fibrillary degeneration. The prevalence of epiretinal membrane and macular hole was similar in the two groups. One case of extra papillary focal retinal hemorrhage was reported in the post-COVID-19 group. Conclusions Macula and perimacular vessel density and perfusion resulted unaltered in mild post-COVID-19 patients at 1-month hospital discharge, suggesting no or minimal retinal vascular involvement by SARS-CoV-2.

Background and aims The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P

Introduction The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p Conclusion Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (&kappa, = 0.475, p &lt, 0.001) and family history of SARD (&kappa, = 0.491, p &lt, 0.001) and fair for the identification of extrapulmonary symptoms (&kappa, = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (&kappa, = 0.436, p &lt, 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.

Background:Some infectious agents may act as inducers of autoimmune conditions1. Despite SARS-CoV-2 infection can induce autoimmune phenomena in infected people2, individual risk factors or underlining mechanisms leading to loss of immunological tolerance are still unknown.Objectives:To assess the rate of development of autoantibodies in convalescent SARS-CoV-2 patients and their relation on infection clinical course and disease parameters.Methods:One-hundred and nine convalescent SARS-CoV-2 patients were studied and underwent multidisciplinary assessment in a Day Hospital clinical setting. For each patient, demographic, clinical and immunological data were collected and, at study entry, autoimmune profile [antinuclear antibodies (ANAs), antibodies reacting with extractable nuclear antigens (anti-ENA), antineutrophil cytoplasmic antibodies (ANCAs), Lupus anticoagulant (LA), anticardiolipin antibodies (aCL) IgM and IgG, anti-β2 glycoprotein I (anti-β2GPI) IgM and IgG] was assessed by Fluorescent immunoassay. Moreover, IL-6 plasma levels were assessed by ELISA (ELLA).Results:After a median time from hospitalization for SARS-CoV-2 infection of 53.3 ± 0.9 days, 55(50.5%) SARS-CoV-2 convalescent patients showed the positivity (ABpos) of at least one autoantibody. In particular, 31(28.4%) were positive for LA, 11(10.1%) for IgM-RF, 8(7.3%) for ANA and 6(5.5.%) for IgG-aCL whilst less than 2% showed other autoantibody positivities (IgM-aCL, IgG-anti-β2GPI, ENA, ACPA, c-ANCA, Scl70 and RNP). Analyzing the patient-related characteristics associated with the development of autoimmunity, convalescent male patients were more likely characterized by the development of antiphospholipid antibodies (aPL) (37.3%) than female (16.7%; p=0.02). Considering the disease-related characteristics, convalescent SARS-CoV-2 patients who experienced severe pneumonia (i.e., oxygen support need) during hospitalization, more likely received IL-6R-inhibitor administration (47.3%) and developed more than one autoantibody (87.5%) (aPL + another AB) than convalescent SARS-CoV-2 patients who did not need oxygen support [(12.5%; p=0.02) (OR95%IC: 9.5(1.4-109.1)] or IL-6R-inihibitor (1.9%; pnegpatients (5.6 ± 1.5 pg/ml; p=0.07), mostly if considered autoantibodies other than aPL (15.4 ± 7.7 pg/ml)(p=0.01).Conclusion:Loss of self-tolerance is a common phenomenon in the medium-term follow-up of SARS-CoV-2 convalescent patients whose occurrence is dependent by a severe disease course and by an aberrant host inflammatory response. Long-term follow-up will reveal AB persistency and their clinical impact.References:[1]Barzilai O, et al. Current Opinion in Rheumatology 2007.[2]Zhou Y, et al. Clin Transl Sci. 2020.Disclosure of Interests:None declared

Importance Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design Observational clinical cohort study. Setting Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio Main outcomes and measures We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety. Key points Question SARS-CoV-2 infection remains a disease with many unknown aspects for which there are no therapies with proven efficacy. To date, it is recognized that COVID-19 disease may lead to the development of a cytokine storm for which drugs as IL-6R inhibitors may have beneficial effect. Findings In this observational clinical study, we reported the efficacy and safety of intravenous Sarilumab use in SARS-CoV-2 severe pneumonia with a global resolution rate of 83.0% (89.7% in medical wards and 64.3% in ICU) and an overall mortality rate of 5.7%. Meaning IL-6R-inhibition is an effective approach for severe SARS-CoV-2 pneumonia and intravenous Sarilumab is a promising treatment approach leading to an important clinical benefit and good safety in the short term.

BACKGROUND: A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID-19 assisted in the intensive care unit (ICU). However, VTE burden among non-ICU patients hospitalized for COVID-19 that receive guideline-recommended thromboprophylaxis is unknown. OBJECTIVES: To determine the incidence of VTE among non-ICU patients hospitalized for COVID-19 that receive pharmacological thromboprophylaxis. METHODS: We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non-ICU patients hospitalized for COVID-19, independent of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. RESULTS: The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6. Seventy-two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98-18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI -0.87-5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23-5.77). Significant differences between subjects with and without DVT were D-dimer > 3000 µg/L (P

SUMMARY Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is frequently associated with liver tests abnormalities. Aims To describe the evolution of liver involvement during SARS‐CoV‐2 infection and its effect on clinical course and mortality. Methods Data of 515 SARS‐CoV‐2 positive patients were collected at baseline and during follow‐up, last evaluation or death. Stratification based on need for hospitalization, severe disease and admission to intensive care unit (ICU) was performed. The association between liver tests abnormalities (baseline and peak values) and ICU admission or death was also explored. Results Liver tests abnormalities were found in 161 (31.3%) patients. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were increased in 20.4%, 19% and 13.6% of patients, respectively. Baseline liver tests abnormalities were associated with increased risk of ICU admission (OR 2.19 [95%CI 1.24‐3.89], p=0.007) but not with mortality (OR 0.84 [95%CI 0.49‐1.41], p=0.51). Conversely, ALP peak values were correlated with the risk of death (OR 1.007 [95%CI 1.002‐1.01], p=0.005) along with age, multiple comorbidities, acute respiratory distress syndrome (ARDS), ICU admission, and C‐reactive protein. Alterations of liver tests worsened within 15 days after hospitalization; however, in patients with the longest median follow‐up, the prevalence of liver tests alterations decreased over time, returning similar to that of baseline. Conclusions In SARS‐CoV‐2 positive patients without pre‐existing severe chronic liver disease, baseline liver tests abnormalities are associated with the risk of ICU admission and tend to normalize over time. ALP peak value seems to be predictive of a worse prognosis.

To study the long-term psychological effects of Covid-19 disease, we recruited 61 patients older than 60 years of age and administered the Kessler questionnaire K10 to assess psychological distress and classify them according to mental health risk groups. Patients' affective temperaments were assessed with the 39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A-39) and emotional dysregulation with the Difficulties in Emotion Regulation Scale (DERS). Patients were divided in two samples according to their scores on the K10, i.e., a high likelihood of psychological distress group (N = 18) and a low likelihood of psychological distress group (N = 43). The two groups differed on their gender composition, in that more women (N = 11) were in the former and more men in the latter (N = 29) (χ2 = 4.28; p = 0.039). The high likelihood of psychological distress group scored higher on the Cyclothymic (3.39 ± 3.45 vs. 0.93 ± 1.08, p < 0.001) and the Depressive (2.28 ± 2.82 vs. 0.65 ± 1.09, p = 0.01) affective temperaments of the TEMPS and on the lack of Impulse control (12.67 ± 4.04 vs. 9.63 ± 3.14, p = 0.003) and lack of Clarity (15.00 ± 5.56 vs. 9.85 ± 4.67, p = 0.004) scales of the DERS. Our results show that having had Covid-19 may be related with high likelihood for psychological distress in advanced-age people and this may in turn be associated with impaired emotional regulation and higher scores on depressive and cyclothymic temperaments.

Background:Pulmonary involvement is the main determinant of disease-related mortality in systemic sclerosis (SSc). The SENSCIS and INBUILD trials have documented the efficacy of the antifibrotic drug Nintedanib (NTN) in the treatment of SSc-related interstitial lung disease (SSc-ILD) and progressive forms of ILD other than Idiopathic Pulmonary Fibrosis1,2. The criteria for the use of this drug in patients with SSc-ILD in clinical practice are currently being defined.Objectives:To evaluate the proportion of patients eligible for NTN treatment based on the enrollment criteria fof the SENSCIS and INBUILD studies in a real-life cohort of SSc-ILD patients.Methods:We considered consecutive patients with ILD extension on CT ≥10% and disease duration ≤7 years with at least one visit in the period between September 2016 and December 2019. Data of the clinical visits were retrospectively evaluated. For each patient, we examined the visits during which a well-tolerated immunosuppressive therapy was modified because of progression of SSc-ILD and the most recent follow-up visit. Eligibility of patients for NTN was defined according to the inclusion criteria of the SENSCIS and INBUILD trials. Patients with more than 2 acral ulcers at the time of evaluation, history of digital amputation, pulmonary hypertension (functional class III-IV) and increased hemorrhagic or thrombotic risk were judged not eligible to NTN in trials.Results:A total of 177 visits regarding 78 patients were examined (females 80.8%, diffuse skin disease 51.3%, anti-Scl70 antibodies positivity 55.7%, age 54.8±16.0 years, disease duration 4.0±2.4 years). Considering the visits in which indication for a therapeutic change was given, 54 patients (54.5%) were eligible for NTN according to SENSCIS criteria and of these 31 (31.3%) also according to INBUILD criteria (Figure 1). In this group, 25 patients were treated with mycophenolate mofetil, 11 with azathioprine, 10 with cyclophosphamide, 7 with methotrexate and 8 with rituximab (2 in combination). At the latest available evaluation, 42 patients (62.8%) were eligible for NTN according to SENSCIS criteria and of these 12 (15.4%) also according to INBUILD criteria (Figure 1). In this group, 30 patients were in mycophenolate mofetil (6 in combination with biologic treatment), 5 in azathioprine, 1 in cyclophosphamide, 1 in methotrexate, 6 in rituximab, 2 in tocilizumab and 1 in pirfenidone. Overall, the factors limiting NTN start according to the trial enrollment criteria would have been: uncompromised (19.2%) or too low (6.4%) DLco values, too low FVC (3.4%), severe acral disease with ulcers (16.9%), severe pulmonary arterial hypertension (6.2%), increased thrombotic or haemorrhagic risk (6.2%). In the scenario of eligibility, skin progression was detectable in 43.4% of all visits.Conclusion:Treatment that can modify the progression of SSc-ILD are currently limited. Based on our retrospective analysis, the use of NTN in accordance with current clinical evidence could be considered in a significant percentage of patients with SSc-ILD.References:[1]Flaherty KR, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019.[2]Distler O, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019.Disclosure of Interests:None declared

Background:An increased incidence of cancer in patients with systemic sclerosis (SSc) is well-established1. Current knowledge about the onco-transforming power of immunosuppressive treatments in both non-rheumatological and rheumatological pathologies, suggests an increased incidence of hematological and solid neoplasms2. Evidences on the possible role of the immunosuppressants in the onset of cancer during SSc are lacking.Objectives:To evaluate the incidence of malignancies in SSc patients exposed to immunosuppressive therapy.Methods:The incidence of neoplasia in a cohort of 600 patients with SSc was evaluated retrospectively. Patients diagnosed with malignancy within 36 months from SSc onset were excluded from the analysis since suspected for paraneoplastic form. Patients exposed to methotrexate, cyclophosphamide, azathioprine and mycophenolate were confronted with a group comparable for age at onset, sex, disease variant, autoantibodies and exposure to other disease-specific therapies, using propensity score matching analysis. The considered follow-up was between the clinical onset and the diagnosis of cancer or the last available visit or the twenty-fifth year of illness.Results:The analysis was carried out on 526 patients observed for an average period of 12.1 ± 6.0 years (males 9.5%, age at onset 49.0 ± 15.3 years); 24.9% had diffuse cutaneous variant of the disease and 39.0% and 34.8% were respectively positive for anti-centromere and anti-Scl70 antibodies. During the follow-up, 19.0% of patients were exposed to cyclophosphamide, 15.3% to azathioprine, 14.4% to methotrexate and 11.6% to mycophenolate mofetil. Sixty-five cancer diagnoses were made after the 36th month from onset (incidence 1.02: 100 patients/year), comprising 16 mammary cancers, 12 cancers of the gastro-intestinal tract, 11 cancers of the head-neck area, 10 cancers of the lungs, 9 cases of skin-cancer, 5 haematological malignancies and 1 brain tumour. The incidence of cancers did not differ in relation to treatment with cyclophosphamide (X2 = 0.001, p = 0.961), azathioprine (X2 = 2.141, p = 0.143), mycophenolate mofetil (X2 = 0.001, p = 0.993) or methotrexate (X2 = 0.920, p = 0.337) (Figure 1).Conclusion:Our data are consistent with an increased incidence of neoplasms in the course of SSc, with a rate that appears almost doubled compared to the general Italian population with similar sex and age distribution (0.55: 100 patients/year; Italian Association of Tumor Registries data3). In our SSc cohort this risk is independent of exposure to immunosuppressive drugs commonly used for the treatment of scleroderma disease.References:[1]Akira O et al. Cancer Incidence in Systemic Sclerosis: Meta-Analysis of Population-Based Cohort Studies. Arthritis & Rheumatism. 2013[2]Zitvogel L et al. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006[3]Registri Tumori di popolazione in Italia: la Banca Dati AIRTUM (Associazione Italiana Registri Tumori). 2020Disclosure of Interests:None declared

Background:Systemic Sclerosis (SSc) is a chronic rheumatic disease characterized by an autoimmune disorder with vasculopathy that leads to an excess in collagen and other extracellular matrix proteins deposition. This process results in progressive fibrotic and vascular damage of skin and visceral organs. According to observational studies conducted in last decades, mean survival of SSc patients had improved with significant changes in causes of death.Objectives:To assess the 10-years survival in a large Italian multicentre cohort of SSc patients in the last decade compared to previous periods published since the 1980s, and to identify features that can justify any change.Methods:We retrospectively analysed all medical records of our longitudinal SSc cohorts, fulfilling 1980 ARA and/or 2013 EULAR/ACR Classification Criteria, with a median (IQR) follow-up of 91.5 (51-120) months from 4 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analysed. Survival rate was calculated with Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models were used to identify any predictor. Then, observed SSc survival was compared to those previously published and to that expected in the general population, calculated using official data published on the website United Nation World Population Prospects (www.macrotrends.net/countries/ITA/italy/death-rate).Results:Of 912 SSc patients (91.6% female; mean (SD) age at first non-Raynaud symptom (RS) 51 (15.4) years; median (IQR) disease duration from non-RS 24 (0-84.7) months) diffuse cutaneous involvement was defined in 182 (20%) patients. Anti-centromere and anti-topoisomerase-I were detected in 390 (42.8%) and 302 (33.1%) patients, respectively, while 220 (24.1%) presented antibodies for other extractible nuclear antigens. Prevalent non-Raynaud manifestations were interstitial lung disease detected in 459 (50.3%), digital ulcers in 395 (43.3%) and oesophagopathy in 371 (40.7%) patients, respectively, while other gastrointestinal manifestations were reported in 234 (25.7%) patients. Chronic renal failure was observed in 61 (6.7%) patients and pulmonary arterial hypertension (PAH) was confirmed at right heart catheterization in 38 (4.2%) patients. Three hundred twenty-two (35.3%) patients received immunosuppressant, 215 (23.5%) assumed an endothelin receptor antagonist and/or a 5-phosphodiesterase inhibitor, and 72 (7.9%) were treated with a biologic agent. The global 10-years survival was 89.4%; female gender (HR 0.33, CI95% 0.17-0.67), diffuse cutaneous involvement (HR 2.14, CI95% 1.17-3.91), presence of pulmonary hypertension (HR 2.61, CI95%1.31-5.16) and older age at non-RS (HR 1.1, CI95% 1.06-1.12) affected survival. Furthermore, as compared to previous Italian studies, our cohort showed a significant improvement in rate (see Figure 1).Conclusion:Survival in SSc patients has improved in last 5 decades but still reduced compared to that expected in general population above all 5 years after diagnosis. Early diagnosis, with reduced renal involvement, along with better screening and innovative therapeutic strategies may explain these achievements.Figure 1.Ten-years survival in SSc patients since 2009 (left); comparison of survival across different Italian SSc cohorts (box: current analysis) (right).References:[1]Giordano M, et al. The Journal of Rheumatology. 1986; 13:911-916.[2]Ferri C, et al. Medicine. 2002; 81:139-53.[3]Vettori S, et al. Reumatismo. 2010; 62(3):202-209.[4]Ferri C, et al. Autoimmun Rev. 2014; 13(10):1026-34.Disclosure of Interests:None declared

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

Background Depression is one of the most common comorbidities in patients with Psoriatic Arthritis (PsA) but risk factors for mood disorders in these patients are still largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been also associated with depressive symptoms in patients without systemic autoimmune diseases. Objectives The aim of this study is to determine risk factors for depressive symptoms and compare serum cytokines concentrations in subjects with and without depressive symptoms in a court of PsA patients. Methods Eighty consecutive patients with PsA were screened for depressive symptoms with depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). A validated cut-off of 8 was used to define patients with significative depressive mood. Patients with and without depressive symptoms were compared for the prevalence of general risk factors for depression, comorbidity, psoriatic disease age of onset, duration, activity and domains affected, treatment and serum levels of IL-6, TNF-α and IL-17A. Results Mean disease duration of skin disease and articular disease was 18.8 ± 15.3 years and 9.0 ± 11.1 years, respectively. All patients had a history of peripheral arthritis, 41.3% had dactylitis, 38.8% had enthesitis, 21.3% had spondylitis 82.5% had a psoriatic skin disease and 51.2% had psoriatic nail disease. According to DAPSA index, 20.0% were in remission, 50.0% in Low Disease Activity, 20.0% in Moderate Disease Activity and 10.0% in High Disease Activity. Thirty-five (43.8%) were in Minimal Disease Activity. Thirty-three patients (41.3%) had depressive symptoms according to HADS. Patients with and without depressive symptoms did not differ in terms of age, gender, comorbidity, general risk factors of depression, psoriatic disease age of onset, duration, domains affected, DAPSA activity, MDA achievement, PASI, HAQ, VAS pain, the intensity of treatment, serum TNF-α IL-17A and IL-23. Serum levels of IL-6 were higher in patients with depressive symptoms. (2.99±2.58 vs 1.54±1.60 pg/dl; p=0.006). A cut-off of 2.27 pg/ml of serum IL-6 had the best ability to predict a HADS≥8 according to higher Youden Index of the ROC curve (AUC 0.682±0.061; p=0.006). Multivariate logistic regression analysis revealed that serum IL-6≥2.27 pg/ml was a predictor of depressive symptoms even when adjusted for DAPSA, HAQ and PASI (OR 3,06; CI 1.14-8.20; p = 0.026). Conclusion Higher serum Il-6 is associated with depressive symptoms independently from articular and cutaneous disease activity and degree of disability. This association suggest a direct role of systemic inflammation in the modulation of mood in PsA patients. References [1] Husni ME, et al. The psychosocial burden of psoriatic arthritis. Semin Arthritis Rheum2017. [2] Ogata A, et al. Pathological Role of Interleukin-6 in Psoriatic Arthritis. Arthritis2012. [3] Hodes GE et al. Integrating Interleukin-6 into depression diagnosis and treatment. Neurobiol Stress 2016. [4] Zigmond AS et al. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983. Disclosure of Interests Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Dario Bruno: None declared, Giacomo Tanti: None declared, Giovanni Battista Canestrari: None declared, Maria Rosaria Magurano: None declared, Clara Di Mario: None declared, Barbara Tolusso: None declared, Giusy Peluso: 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

Background Multidisciplinary Team (MDT) meetings are the current “gold standard” in interstitial lung disease (ILD) diagnosis. Requisite participants are respiratory physicians, radiologists and pathologists. A rheumatologist physician is not routinary involved in MDT even if up to 20% of ILD are related to connective tissue disease, rheumatoid arthritis or systemic vasculitis. Objectives The aim of this study is to evaluate the prevalence and predictors of systemic rheumatological diseases in a cohort of patients with ILD, evaluated by a rheumatology specialist on the advice of MDT in a university hospital. Methods Thirty-two patients with ILD, evaluated at dedicated MDT were referred to a rheumatologist in 2018, usually for autoantibodies positivity or clinical history suspected for a rheumatological disorder. Rheumatologic evaluation included physical examination, routinary blood and urine tests, serum levels of C3 and C4, ANA, Rheumatoid Factor (RF), ANCAs, anti-Sm, anti-RNP, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-Jo1, anti-dsDNA and anti-CCP antibodies. Family history of autoimmune diseases, presence of rheumatologic red flags (Raynaud’s phenomenon, photosensitivity, inflammatory skin manifestations, sicca syndrome, recurrent fever, inflammatory arthralgias, paresthesias, oral or genital aphthosis, thrombosis and recurrent miscarriages), respiratory symptoms and pulmonary function test were also evaluated. When indicated, capillaroscopy, joint imaging and salivary gland biopsy were performed. Results Twenty-one patients (65.6%) were female. At the time of rheumatological evaluation, the patients had a mean age of 64.4±12.6 years with a mean period of 21.1±39.6 months since the first identification of ILD on a CT scan. Twenty-five (78.1%) and 18 (56.3%) patients respectively complained exertional dyspnea and cough, 6 patients (18.8%) were on oxygen therapy and 13 (40.6%) had a FVC Conclusion Single clinical or laboratory abnormalities are not strongly associated to a rheumatological diagnosis in patients with ILD, suggesting that only a comprehensive rheumatological evaluation allows correct classification of the disease associated with ILD and is mandatory to make or exclude a diagnosis. In this study, we evaluated only preselected patients by ILD-MDT, but the results indirectly suggest that direct participation of rheumatologist to MDT is advisable to increase accuracy and reduce delay in diagnosis and treatment. Disclosure of Interests: Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Lucrezia Verardi: None declared, Silvia Laura Bosello: 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

Background: Cardiovascular (CV) events are the leading cause of death in patients with psoriatic arthritis (PsA) but current cardiovascular risk prevention strategies in these subjects appear to be inadequate. The prevalence of depressive symptoms, even in the absence of a diagnosed depressive disorder, is greater in patients with PsA than in the general population. Objectives: The objective of the study is to evaluate the association between CV risk factors and depressive symptoms in a cohort of patients with PsA. Methods: We enrolled consecutive patients with PsA (CASPAR criteria) without a diagnosis of major depression or history of major CV events. The presence of significant depressive symptoms was defined by the Hospital Anxiety and Depression Scale (HADS) for scores ≥ 8. The subjects were characterized by disease phenotype, duration and activity (according to the DAPSA index) and immunosuppressive, antihypertensive, glucose-, urate- and lipid-lowering therapy. In order to assess the prevalence of traditional CV risk factors, patients were characterized by BMI, waist and hip circumference, blood pressure (BP), smoking habits, physical activity and familiarity for myocardial infarction, lipid, glucose and serum urate. The predicted risk of CV events was calculated by the Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) score and Systematic COronary Risk Evaluation (HeartSCORE) risk charts. Results: One-hundred patients with PsA were enrolled (males 47.0%, mean age 54.9±12.5 years, duration of illness 9.1±10.6 years) of which 20.6% were in remission, 43.3% in low disease activity, 28.8% in moderate disease activity and 10.3% in high disease activity according to DAPSA; 38% had significant depressive symptoms according to the HADS questionnaire. Patients without depressive symptoms had a higher mean age (57.8±12.3vs52.1±12.4 years, p=0.002) compared to patients with significant depressive symptoms but were comparable according to M:F ratio, duration and domains of psoriatic disease, PASI, DAPSA and immunosuppressive therapy. The presence of depressive symptoms was associated with a higher prevalence of obesity (34.2%vs9.7%, p=0.002) and “at risk” abdominal circumference (84.2%vs61.3%, p=0.015) and hip/waist ratio (81.6%vs50.0%, p=0.002). Moreover, these patients had more frequently a history of active or previous smoking (63.2%vs.40.3%, p=0.027) but did not differ according to lifestyle, BP, antihypertensive therapy or familiarity with myocardial infarction compared to patients without depressive symptoms. With regard to the metabolic profile, patients with and without depressive symptoms did not differ in terms of exposure to lipid- and glucose-lowering drugs and fasting glucose values. However, patients with depressive symptoms had increased atherogenic risk index more frequently (76.3%vs54.8%, p=0.046) and greater LDL/HDL ratio (2.6±1.2vs2.1±0.7, p=0.017) and serum triglycerides values (135.1±53.7 mg/dl vs 108.8±58.6 mg/dl, p=0.046). The estimated risk of cardiovascular events at 10 years for traditional risk factors was greater for patients with depressive symptoms (FRS 16.8±12.3vs10.4 ± 6.0, p=0.003; HeartSCORE 1.9±1.5vs1.1±1.0, p=0.011; ASCVD 11.7±8.8vs7.8±8.4, p=0.05). Conclusion: The presence of depressive symptoms is associated with a higher incidence of modifiable CV risk factors and a higher predicted risk of CV events in patients with PsA. Systematic research of depressive symptoms in patients with PsA could contribute to the correct assessment of CV risk, helping to implement more effective prevention strategies. Disclosure of Interests: Gerlando Natalello: None declared, Enrico De Lorenzis: None declared, Dario Bruno: None declared, Giacomo Tanti: None declared, Maria Rosaria Magurano: None declared, Barbara Tolusso: None declared, Giusy Peluso: 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

Background Interstitial lung d isease (ILD) is the leading cause of death in Systemic Sclerosis (SSc) but its pathogenesis is not fully understood. Esophageal disease is common in SSc and micro aspiration of both acid and non-acid gastroesophageal reflux could be involved in the pathogenesis of ILD. Esophagogastroduodenoscopy (EGD) is an essential tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc. Objectives The objective of the present study is to assess the role of EGD in predicting pulmonary functional deterioration in SSc patients. Methods One hundred and fifty patients with SSc and suspected esophageal involvement underwent EGD. Pulmonary function tests were performed at baseline and after a 36-months follow-up. Patients were characterized for disease phenotype, BMI, smoking exposure and medication history. A significant ILD progression was defined as a relative decline >= 10% of FVC or a concomitant decline >= 5% of FVC and >= 15% of DLCO. Results One hundred and thirty-six patients (90.5%) were female with a mean age of 55.6 ± 13.8 years and 12.1% were active smokers. Fifty patients (33.3%) had a diffuse cutaneous disease; 37.4% and 40.8% were positive for anti-centromere and anti-Scl70 antibodies respectively. The mean disease duration from the first non-Raynaud symptom was 5.9±6.7 years. Sixty-one patients (40.8%) showed EGD signs of reflux esophagitis. Among them, 31.3% had an erosive form (9.5% grade A, 15.6% grade B, 4.8% grade C and 1.4% grade D according to Los Angeles classification). At the baseline, 23.1% of the patients had a FVC Conclusion SSc patients with erosive esophagitis present a higher risk of progression of interstitial lung disease. This evidence supports a role of micro-aspiration of gastric contents in the development of inflammation and fibrosis of the airways. Disclosure of Interests Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Lucrezia Verardi: None declared, Umberto La Porta: None declared, Giovanni Battista Canestrari: None declared, Ludovica Berardini: None declared, Silvia Laura Bosello: 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

Objective Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. Methods We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. Results We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P, Highlights • We assessed and accurately described peripheral microvasculature in COVID-19 patients through nailfold videocapillaroscopy. • Capillary alterations at the nailfold bed suggest a broad COVID-related microvascular involvement. • Different alterations in acutely-ill and recovered patients resemble a transition from acute to post-acute injury.

Background:Gastrointestinal involvement(GI) is a common feature of systemic sclerosis(SSc) and can be highly disabling, representing a major cause of morbidity and reduced quality of life(QoL). The impact of dietary habits on GI symptoms, mood and QoL has not been extensively evaluated.Objectives:To evaluate the adherence to the Mediterranean Diet(MD) in an Italian multicenter cohort of SSc patients, and its impact on GI symptoms and other disease features, depression, anxiety and overall QoL.Methods:Consecutive SSc(ACR/EULAR2013) patients from 4 Italian cohorts were enrolled. Dietary habits and adherence to the MD were assessed using the 14-item MEDAS and QueMD questionnaires. Presence and severity of depressive/anxious symptoms and QoL were evaluated with the Hospital Anxiety and Depression Scale(HADS) and the SSc-HAQ(S-HAQ). GI symptoms were assessed with the Reflux Disease Questionnaire(RDQ) and the UCLA SCTC GI Tract 2.0 questionnaire(USG). Associations with patients’ lifestyle, disease characteristics, and nutritional status were explored.Results:265 patients (94.7% females; age 55.8±13.6years; disease duration 9.1±7.0years; diffuse SSc 31.8%; Scl70 + 35.8%;ulcers 23.4%;ILD 29.4%;BMI 23.7±4.4 Kg/m2; obese 11.3%,overweight 23.4%,underweight 4.9%) were enrolled.Overall MD adherence was moderate(7.5±1.9) according to MEDAS and it correlated with QueMD score(4.53±1.96)(R=.371,pGI symptoms were moderate/severe according to USG in 37(14.0%) patients(USG:0.41±0.40), and heartburn was the most common GI symptom(35.2%). The prevalence of significant anxiety and depression was 24.1% and 17.0%.An inverse correlation was found between MD adherence and mood disturbances at HADS(MEDAS; R=-0.181,p=0.04), work impairment(QueMD;R=-0.247,p=0.005) and reduced QoL, both for GI (constipation at USG: R=-0.133,p=0.032) and general S-HAQ items(bowel:R=-0.181,p=0.04;severity R=-0.202,p=0.01;Raynaud:R=-0.217,pConclusion:Unsatisfactory MD adherence is associated with a low mood, impaired QoL, work impairment, GI and vascular symptoms in Italian SSc patients. The promotion of a healthy lifestyle could positively impact on QoL and disease status of SSc patients.References:[1]Gnagnarella P, et a. NMCD 2018. DOI: 10.1016/j.numecd.2018.06.006[2]Jaeger VK et al. PLoS One, 2016.[3]Dinu M et al. Eur J Clin Nutr 2018. doi: 10.1038/ejcn.2017.58.[4]Khanna D, et al.Arthritis Rheum. 2009. doi: 10.1002/art.24730.Acknowledgments:GILSDisclosure of Interests:Giacomo De Luca Grant/research support from: SOBI, Speakers bureau: SOBI, Novartis, Pfizer, MSD, Celgene, Gerlando Natalello: None declared, Giuseppina Abignano: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Duygu Temiz Karadağ: None declared, Maria De Santis: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

Background:Cardiovascular complications are the leading cause of death in patients with psoriatic arthritis (PsA), but current strategies for reducing cardiovascular risk are still inadequate. Depression is a common comorbidity in PsA patients and it is recognized as an independent cardiovascular risk factor in the general population. Endothelial dysfunction, assessed as a reduction in brachial artery Flow Mediated Dilation (FMD), is a predictor of major cardiovascular events in high and low risk populations.Objectives:To investigate the relationship between endothelial function and depressive symptoms in a cohort of patients with PsA.Methods:Sixty consecutive patients with PsA, aged between 30 and 79 years, with no history of major cardiovascular events, were characterized for traditional cardiovascular risk factors and features of psoriatic disease. The risk of cardiovascular events according to traditional risk factors was calculated using the Framingham Risk Score (FRS) and the presence of depressive symptoms was defined through the Hospital Anxiety and Depression Scale (HDS) using the validated cut-off of 8. Endothelial function was assessed by FMD. Serum IL-6 was quantified by ELISA, IL-17 and TNF-α levels by Luminex method.Results:Patients had an average age of 52.1±11.0 years, 43.3% of them were male, 23.3% obese and 25.0% active smokers; 38.3%, 25.0% and 11.7% were treated for high blood pressure, dyslipidemia and diabetes mellitus, respectively. The 10-year risk of major cardiovascular events estimated by FRS was 10.4%. The mean duration of PsA was 9.4 years, 30.0% of patients were in minimal disease activity (MDA) and 61.7% and 46.7% were treated with conventional and biotechnological DMARDs, respectively. The mean HDS value was 6.9±3.2 and 43.4% of patients had significant depressive symptoms. The severity of depressive symptoms according to HDS correlated with disease activity according to DAPSA (r=0.449, p=0.001). The mean FMD was 7.8±3.8%, this value correlated inversely with age (r=-0.408,p2=0.23) and FRS normalized through logarithmic transformation (β=-0.32, p=0.009, R2=0.22).Conclusion:The degree of endothelial dysfunction quantified by FRS correlates with the severity of the depressive symptoms in patients with PsA, independently of the cardiovascular risk attributable to classical risk factors. The weak relationship between FRS and serum levels of IL-6, IL-17 and TNF-alpha suggests a role of factors independent of inflammation in the regulation of endothelial function in patients with PsA. Systematic research and treatment of depressive symptoms could contribute to a more complete stratification and a better management of cardiovascular risk in patients with PsA.Disclosure of Interests:Enrico De Lorenzis: None declared, Angela Di Giorgio: None declared, Gerlando Natalello: None declared, Antonio Nesci: None declared, Dario Bruno: None declared, Donatella Lucchetti: None declared, Giacomo Tanti: None declared, Clara Di Mario: None declared, Pietro Rubortone: None declared, Maria Rosaria Magurano: None declared, Barbara Tolusso: None declared, Angelo Santoliquido: None declared, Giusy Peluso: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer

Background:The staging of interstitial lung disease (ILD) is important to monitor disease progression and for prognostication. A disease severity scale of Systemic Sclerosis (SSc)-related lung disease has long been proposed (i.e. Medsger’s severity scale). This scale was mostly developed by discussion and consensus and stage thresholds were not computed by a data-driven approach. Hidden Markov models (HMM) are methods to estimate population quantities for chronic diseases with a staged interpretation which are diagnosed by markers measured at irregular intervals.Objectives:To build a SSc-ILD specific disease severity scale with prognostic relevance via HMM modeling.Methods:A total of 358 SSc patients at risk for or with ILD were enrolled in a discovery (207 cases, Milan1) and in a validation (151 cases, Milan2, Pavia and Rome) cohort. Patients were included if satisfied the following criteria: 1) Diagnosis of SSc according to the EULAR/ACR 2013 criteria, 2) absence of anticentromere antibodies, 3) dcSSc subset or 4) other subsets with either 4a) ILD-related antibodies (Scl70, PmScl, Ku) or 4b) evidence of ILD on HRCT, 5) disease duration < 5 years at the time of the first pulmonary function test (PFT). Serial PFTs were retrieved and the time up to the last available visit -if the patient alive-, or to death due to pulmonary complications, was recorded. HMM were used to estimate the threshold of a 3-stage model (SL3SI, Scleroderma Lung 3-Stage Index) based on PFT functional values (normal/mild, moderate, severe involvement) in the discovery cohort. Survival estimates of the SL3SI model were compared to Medsger’s severity classes estimates and their predictive capability evaluated via the explained residual variation (R2) of prediction errors (the higher the better). One-hundred random replicates were generated to simulate the prediction effort in patients with different disease duration and lung severity.Results:Patients characteristics are summarized in the Table. Fifteen-years survival estimates for Mesdger’s classes in the discovery set were: normal=0.88, mild=0.86, moderate=0.84 and severe=0.71. The SL3SI was defined by the following thresholds: normal/mild, FVC and DLco >=75%; moderate FVC or DLco 74-55%; severe, FVC or DLco 2values at 15 yrs for the SL3SI compared to Medsger’s classes, providing evidence for a better predictive capability of the former (discovery: 0.31 vs 0.25; validation: 0.28 vs 0.19).Conclusion:The SL3SI, a simplified 3-stage functional model of SSc-ILD, yields better survival estimates and long-term prognostic information than Medsger’s classes. Its reproducibility and ease of use make it a useful tool for the functional and prognostic evaluation of SSc patients at risk for or with ILD.Table:VariablesDiscovery (n=207)Replication (n=151)DcSSc62 (30%)98 (64%)Age at first PFR48.6±1249.1±14.4Disease duration at first PFR1.7±1.61.3±2.4FVC90.5±18.191.1±20.2DLco70.7±19.861.3±20.1ILD on HRCT179 (86%)125 (80%)Scl70157 (76%)153 (78%)SSA63 (30%)32 (21%)n of visits38571473Follow-up time, yrs11±5.610.6±5.7Deaths27 (13%)23 (15%)Disclosure of Interests:Alessandro Santaniello: None declared, Chiara Bellocchi: None declared, Luca Bettolini: None declared, Marcello Cassavia: None declared, Gaia Montanelli: None declared, Adriana Severino: None declared, Monica Caronni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Paolo Delvino: None declared, Claudio Tirelli: None declared, Lorenzo Cavagna: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Silvia Laura Bosello: None declared, Lorenzo Beretta Grant/research support from: Pfizer

Background Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc) but its pathogenesis and the risk factors of pulmonary function deterioration are not fully understood. Esophageal disease is high frequent in SSc and motor activity abnormalities with occult micro-aspiration of both acid and non-acid gastro oesophageal reflux has been implicated in the pathogenesis of ILD. DLCO reduction is considered the earliest sign of microaspiration-induced lung damage1. Cross-sectional studies have demonstrated an association of SSc-ILD and esophageal abnormalities on 24 hours intraesophageal pH-monitoring and esophageal manometry but prospective evaluation of lung deterioration is lacking2,3. Esophagogram was proposed as a useful tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc4. Objectives To assess the role of esophagogram in predicting pulmonary function test deterioration in SSc-patients. Methods We retrospectively evaluated 160 consecutive SSc patients who underwent esophagogram because of suspected upper gastro-intestinal involvement. All patients underwent baseline pulmonary function tests and global clinical evaluation. Eighty-five patients underwent a High Resolution CT within 3 months from esophagogram because of suspected lung involvement. One hundred twenty three patients underwent pulmonary function test every 6 months up to 24 months. Results Seventy five patients (46.9%) presented abnormalities of peristaltic waves, 50 patients (31.2%) showed structural changes (hypotonic oesophagus or dilatation) while indirect signs of cardial incontinence (patent cardia or gastro-esophageal reflux) were present in 36 patients (22.5%). A reduced peristaltic activity with a prolongation of transit time was associated to reduced DLCO (50.16%±19.80% vs 60.36±22.69%, p=0.002) and TLC (87.05%±20.43% vs 95.09±20.59%, p=0.017). An hypotonic oesophagus was reported in 25.2% of patients and it was associated to ILD on CT (72.0% vs 28.0%, p=0.033). Patients with hypotonic oesophagus presented a reduced FVC (84.63%±22.86% vs 102.93±21.40%, p Conclusions The esophagogram is wide available, well tolerated and inexpensive tool to assess upper gastro-intestinal tract involvement and its abnormalities are associated to SSc-ILD severity. Because of a faster deterioration of lung function is associated to esophagogram abnormalities, a complete gastro-intestinal evaluation in ILD-SSc patients is mandatory. References [1] Schachter LM, et al. Chest2003. [2] Christmann RB, et al. Semin Arthritis Rheum2010. [3] Marie I, et al. Arthritis Care Res2001. [4] Medsger TA, et al. Clin Exp Rheumatol2003. Disclosure of Interest None declared

Background Gastrointestinal (GI) symptoms are seen in majority of patients with Systemic Sclerosis (SSc) and are a common presenting feature of disease. Severe GI involvement may lead to malabsorption which represents a poor prognostic factor. Accordingly, a regular monitoring of gastrointestinal tract involvement and nutritional status appears crucial in SSc patients. Previous studies reported low values of bone mass density (BMD) in SSc patients1. While no specific relationship has emerged between the two conditions, it’s likely that disease related GI involvement may contribute to the alterations in BMD. Objectives To determine if GI-related clinical status was associated to low bone density in our cohort of SSc patients. Methods Two-hundred-ten unselected SSc patients have been enrolled. The 7-items UCLA SCTC GIT 2.0 questionnaire and Malnutrition Universal Screening Tool (MUST) were administered to each patient. A comprehensive medical history was collected. A blood panel for nutritional status was also performed. T-scores and Z-scores at lumbar spine, femoral neck, Ward’s and total hip measured by dual-energy X-ray absorptiometry (GE Lunar Prodigy) were measured. Results In our cohort, 86.7% of patients reported some GI symptoms. The mean UCLA GIT total score was 0.345±0.34 and 51 patients (24.3%) were at risk of malnutrition according to MUST (score ≥1). 53.7% patients had BMD values Patients with spine T-score Femoral neck T-score On the other hand, the comparison of patients with severe, moderate and mild symptoms according to UCLA GIT total score2 showed an association between progressively lower values of spine and total hip T-score and increasing severity of GI symptoms (ANOVA for spine T-score: p=0.015; for total hip T-score: p=0.048). Patients at risk of malnutrition (MUST score ≥1) presented significant lower T-score for all the considered sections (spine and hip) and significant lower total hip Z-score. Conclusions In our SSc cohort gastrointestinal symptoms were frequent and were associated with low BMD. Considering the heterogeneity of GI involvement, UCLA SCTC GIT 2.0 emerged as a useful and feasible tool to assess GI involvement and other associated comorbidities. In particular, SSc patients who report remarkable GI symptoms and are at risk of malnutrition according to MUST may benefit from a stricter control of BMD to promptly detect osteopenia and osteoporosis. References [1] Omair MA, et al. J Rheumatol. 2013 [2] Khanna D, et al. Curr Opin Rheumatol. 2013 Disclosure of Interest None declared

Background Psoriatic arthritis(PsA)is characterised by several comorbidities;among these obesity and overweight have a major impact on patients’ quality of life and on disease treatment. Obesity increases the risk of developing psoriatic arthritis in the general population compared to normal-weight subjects. Obesity increases the risk of developing arthritis in patients with psoriasis, especially for HLA B27 negative and late onset forms. Objectives Aim of the study was to evaluate the incidence of overweight and obesity in a cohort of PsA patients, the differences between disease phenotypes and therapeutic response between patients with normal weight and overweight/obesity. Methods In this retrospective observational study 332 PsA patients, afferent to our unit between 2010 and 2017, were assessed. At each visit data on disease characteristics, BMI, ongoing treatment, joint count and clinimetric indexes were collected. The baseline was defined as the onset of the disease in bio-naive patients or the start of the last bDMARD therapy for patients previously treated with cs or bDMARDS, while the last follow-up is considered the last visit at our unit Results The 332 patients had a mean age of 52.5±7.3 years;35% of the patients were normal weight, 39.5% were overweight and 25.5% obese. No differences were observed in terms of disease characteristics according to BMI cathegory at baseline and during follow-up, with comparable percentages of peripheral arthritis, enthesitis, dactylitis, axial arthritis or uveitis, as well as cutaneous psoriasis among the groups. At baseline, obese patients had more tender(4.4±5.2 vs 2.3±3.6 p=0.003)and swollen joints(mean value 2.3 vs 1 p=0.03)and higher activity indexes, as for DAS28(3.3±1.2 vs 2.7±1.2 p=0.002)and DAPSA(15.6±9.9 vs 11.5±9 p=0.004)compared to normal weight patients. The same difference was observed between normal-weight and overweight patients, with higher values of DAS28(3.04±1,4 vs 2,7±1.2,p=0.17)and DAPSA(13.6±11 vs 11.5±9, p=0.025)in overweight patients. No significant difference was observed in patients treated with NSAIDs, csDMARDs or bDMARDs according to BMI cathegory. In 190 patients followed according to the tight control strategy, with evaluations every 3 months, the disease activity indexes after two years of follow-up became similar in obese patients compared to normal weight patients. Among the normal-weight patients, 69.4% took csDMARDs,48.7% were treated with bDMARDs. 74.7% of obese patients took csDMARDs, while 36.1% took bDMARDs, with no statistically significant differences between the two groups(p=ns). In particular low-disease activity according to DAPSA was achieved in 76% of normal weight patients, compared with 68.9% of obese patients (p=ns), and also the percentage of patients reaching Minimal Disease Activity in the two groups was comparable (28.4% vs 22.7%, p=ns). Conclusions Clinical manifestations of psoriatic disease do not seem to differ according to BMI cathegory:however, at the first evaluation, obese patients appear to have more disease activity than non-obese patients. At the same treatment intensity, obese patients seem to achieve a percentage of remission comparable to normal weight patients, suggesting that the an intensive treatment strategy allows to obtain optimal results also in a more challenging group of patients. Disclosure of Interest None declared

Background Gastrointestinal involvement is recognized as a major cause of morbidity and mortality in Systemic Sclerosis (SSc) and its pathophysiology is still unclear. Few data on composition and function of gut microenvironment in SSc are reported in the literature but there is a growing body of evidences supporting the hypothesis of a relation between gut microbiota and the host immune system. Objectives The goal of this study was to characterize fecal microbiota in SSc patients compared to healthy subjects to investigate whether specific microbial species may be responsible of dysbiosis in SSc. Furthermore, we investigated the composition of microbiota in the different clinical subsets of SSc. Methods Faecal samples were obtained from 17 healthy controls and 39 SSc patients including subjects with different skin involvement (Diffuse and Limited) and disease duration. The BMI was normal and the mean age was similar both in SSc and controls groups. The composition of microbiota was determined through 16S rRNA pyrosequencing performed using the GS Titanium technology. Rarefaction was used to uniform abudance data. α-diversity was defined by the main indexes while β-diversity was determined according to Bray-Curtis and UniFrac, represented trough Principal Coordinate Analysis (PCoA) and compared using PERMANOVA test on distance matrices. Linear Discriminant Analysis Effect Size was used to identify taxa that showed differential expression between the groups. Results At genus level SSc patients showed a differential expression in 12 taxa compared to controls with higher levels of Ruminococcus, Streptococcus, Lactobacillus, Blautia, Coprococcus and Phascolarctobacterium and a depletion of Bacteroides, Butyciromonas, Odoribacter, Succinivibrio, Sutterella and Prevotella. The differences in microbiota composition between SSc patients and controls were supported also by PCoA of the values representing phylogenetic distance of microbial communities between specimens (p Conclusions Our analysis demonstrated an altered and distinct composition of gut microbiota in SSc patients compared to healthy controls. Furthermore, scleroderma patients show some differences in microbiota characteristics according to the extent of skin involvement, suggesting that microbiota may influence the severity of the disease. If validated and related to GI symptomathology and nutritional status our findings open up the opportunity of a rational intervention on microbiota to restore the gut equilibrium in SSc patients. Disclosure of Interest None declared