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To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA).QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables.413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS.We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

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.

Objective Gout treatment is largely suboptimal in clinical practice. We aimed to assess the predictors of disease-activity at 12 months in a real-life setting. Methods Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre-cohort study. Only patients with clinical diagnosis of gout were eligible. Disease-activity was evaluated by the Patient Acceptable Symptom State (PASS) on a visual analogue scale (VAS, 0=unsatisfactory, 100=satisfactory) at 0 (T0) and 12 months (T12), and the composite score called Gout Activity Score (GAS) calculated on the number of arthritic attacks (flare count), serum uric acid (sUA), cumulative number of tophi, VAS (T12), PtGA (T12). Multivariate linear regression model was performed to assess predictors of gout disease-activity at T12 with PASS and GAS as outcomes. Results: 201 patients had gout (diagnosis on synovial fluid in 45%, tophi in 26%, mean sUA 7.4±1.9 mg/L, 85% with urate-lowering therapy (ULT) in progress/initiated at T0); mean age 63±13 years, 88% men, median (interquartile range) disease duration 2.9 years (0.7-9.4). Follow-up visits were performed in 113 (56%) patients at T12. Mean PASS observed at T0 and at T12 were 38±27 and 74±23, respectively, whereas GAS at T12 was 10±8. A significant association was observed between the presence of tophi and PASS at T12 (-15.3, 95% CI -25.5, -5.2; p=0.003) and GAS at T12 (+4.0, 95% CI 0.6,7.4; p=0.02), adjusted for age, sex, disease duration, sUA

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

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

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.

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p

Objective We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. Methods Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. Results Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67–86) and 98% (95%CI, 87–100), respectively; only clinical criteria yielded 70% (95%CI, 59–80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (

OBJECTIVES: We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. RESULTS: Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67–86) and 98% (95%CI, 87–100), respectively; only clinical criteria yielded 70% (95%CI, 59–80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (

Background and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

The study of idiopathic inflammatory myopathies (IIMs) is acquiring growing importance among systemic autoimmune diseases and every year several articles are published about this group of diseases. Despite this growing interest, the management of IIMs is still critical due to the relative rarity of the condition. The availability of up-to-date knowledge of the evidence on this subject is essential to correctly understand this condition and provide the best care for the patients. The purpose of this review is to provide an overview of the most relevant literature contributions published in the last year.

Introduction Neuropsychiatric (NP) manifestations occur mostly in the early phases of the systemic lupus erythematosus (SLE) course. Nonspecific alterations are evident in conventional brain magnetic resonance imaging (MRI), regardless of clinically overt NP symptoms. The main aims of this study were to assess the prevalence of MRI abnormalities in newly diagnosed SLE, and to evaluate the impact of MRI changes during follow-up (FU) and the clinical course of NP symptoms. Materials and methods Newly diagnosed SLE patients with a baseline brain MRI and with available repeated MRI during FU were retrospectively evaluated. White-matter lesions and atrophy were recorded, comparing NPSLE and non-NPSLE patients. Cox proportional hazard models were used to compare NP events during FU with MRI data. Results Forty-four patients were included, 22 with NP events attributed to SLE. The baseline MRI scan was abnormal in 21 patients (47.73%). New NP events occurred in 17 patients, and worsening was found in repeated MRIs in 12 (27.27%). A worsening of MRI was associated with higher occurrence of new NP events during FU (adjusted hazard ratio 3.946 (1.175–13.253)). Conclusion Baseline MRI is useful in patients with an early diagnosis of SLE, allowing comparison with subsequent scans. In our study, radiological worsening of repeated brain MRI was associated with new NP events.

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

Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included, HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.

Introduction Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

The idiopathic inflammatory myopathies (IIMs) are a rare group of immune, systemic diseases characterised by muscle inflammation and frequently by extramuscular involvement. IIMs are heterogeneous with generally a chronic or subacute onset, which vary from less severe to more serious manifestations, not always easy to diagnose and even less to manage. In the past year, many studies have been published in order to clarify disease pathogenesis and improve patient management and treatment.The purpose of this review article is to provide an overview of the new insights in pathogenesis, serological findings, clinical manifestations and treatment of IIMs, summarising the most relevant studies published over the last year.

Background: our preliminary data demonstrated that expression and activity of P2X7R was impaired in Systemic Lupus Erythematosus (SLE) and associated with a reduced production of IL-1β1. Serositis is a typical manifestation of SLE characterized by a marked inflammation, which has been suggested to be an “inflammasome driven” manifestation. Objectives: to investigate the role of 1513A>C (rs3751143) and 489C>T (rs208294) Single Nucleotide Polymorphisms (SNPs) which are differently associated with loss or gain of function, respectively, of P2X7R, a potent activator of the NLRP3 inflammasome and IL-1β release, in patients with SLE and with a history of serositis (SLE-S). Methods: DNA was extracted from whole blood and used for evaluation of 2 P2X7R SNPs (1513A>C and 489C>T). Considering the combined action of these two SNPs, the overall activity of P2X7R was divided, into three groups: GOF (gain of function), normal function (NF), and LOF (loss of function). In addition, peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and employed to evaluate P2X7R and NLRP3 expression by RT-PCR, assess P2X7R activity as Benzoyl ATP (BzATP)-induced intracellular Calcium ([Ca2+]i) increments and evaluate in vitro IL-1β following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. Results: 33 SLE patients (pts), 11 with (SLE-S) and 22 without serositis (SLE-NS) were enrolled. Mean age was 40.9±10.9 years and disease duration was 135.3± 108.6 months. No significant difference in disease activity and clinical characteristic was found between the two groups (table 1). Evaluating 1513A>C SNP, 20 pts were positive for A/A and 13 for A/C phenotype respectively, while in case of 489C>T SNP, 7 pts presented C/C, 12 C/T and 14 T/T phenotype with a comparable distribution between SLE-NS and SLE-S (table 1). After combination of different phenotypes, 9 pts presented normal function (NF), 22 gain of function (GOF) and 2 loss of function (LOF) with no significant difference between SLE-S and SLE-NS (table 1). P2X7R activity, (evaluated as IL-1 β production and [Ca2+]i increments,) and expression (evaluated with RT-PCR) were comparable between SLE-S and SLE-NS. No significant difference was found between expression and activity of P2X7R and NLRP3 and the two SNPs evaluated (table 2). Conclusion: our data indicate that the 1513A>C and 489C>T SNPs do not seem linked with reduced activity and expression of P2X7R that we previously observed in our cohort of lupus patients. Furthermore, no significant association was found between expression of these SNPs and development of serositis. References [1] P2X7 receptor in systemic lupus erythematosus (SLE). Exploring a novel pathogenetic pathway in lupus related serositis. F. Furini. Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A871 Disclosure of Interests: Federica Furini: None declared, Anna Lisa Giuliani: None declared, Mattia Erminio Parlati: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Di Virgilio: None declared, Alessandra Bortoluzzi: None declared

Background Extracellular ATP (eATP) is one of the most diffuse danger associated molecular patterns (DAMPs) released actively through specific mechanisms from intact cells, or passively from damaged or dying cells1. An implication for eATP has been found in SLE2. Among receptors for eATP, P2X7R is deeply involved in inflammatory and immune processes and its activation drives different intracellular pathways such as NLRP3-inflammasome activation, IL-1β maturation and release, IL-6 and TNF-α production, regulation of lymphocyte proliferation and cell apoptosis3. Previous studies pointed out a possible relationship between P2X7R signaling pathways and SLE pathogenesis4 5. A marked inflammatory condition characterize serositis, that are among the most common manifestations of SLE, and chloroquine is one of the main drugs employed. Objectives The aim of this study was to investigate P2X7R expression and activity in SLE. Methods 48 SLE patients, and 20 healthy control (HC) subjects were enrolled. Among SLE patients, 16 (SLE-S) presented, and 32 (SLE-NS) did not present history of serositis. All subjects gave written informed consent to peripheral venous blood withdrawal after approval by the local ethic committee. Plasma samples were used to measure IL-1β, IL-6 and TNF-α levels by ELISA. Mononuclear cells were isolated from blood samples by Ficoll gradient sedimentation and employed as follow: i) assessment of IL-1β, IL-6 and TNF-α release after stimulation with lipopolysaccharide (LPS) and/or Benzoyl ATP (BzATP); ii) evaluation of P2X7R mRNA expression by RT-PCR; iii) measurement of P2X7R activity as BzATP-induced increase of intracellular Ca2+ concentration using the Fura2/AM probe. Results In SLE patients respect to HC, plasma IL-1β levels were unmodified whereas IL-6 was higher, resulting significantly increased in SLE-S. Monocytes isolated from SLE patients released lower quantities of IL-1β after stimulation with BzATP, whereas the release of both IL-6 and TNF-α was significantly augmented in SLE-NS respect to both HC and SLE-S subjects after all types of stimulation. RT-PCR showed reduced P2X7R and augmented NLRP3 mRNA expression in SLE patients. Accordingly, P2X7R activity was significantly reduced in all SLE patients and did not appear to be influenced by a chloroquine pre-treatment. Conclusion In SLE patients, compared to HC subjects, we found reduced P2X7R mRNA expression, increased NLRP3 mRNA, as a possible compensating mechanism, and correspondingly, significantly lower BzATP-induced intracellular Ca2+ increase, without an apparent influence by chloroquine, one of the drugs most diffusely used for SLE treatment. The in vitro IL-1β release was reduced, whereas plasma IL-1β was unaltered, indicating an alternative source, other than monocytes, of this cytokine. Conversely, IL-6 and TNF-α levels were increased in vitro, and IL-6 was present in plasma at higher levels. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 and TNF-α as possible therapeutic targets. References [1] Giuliani, A.L. et al. Extracellular nucleotides and nucleosides as signalling molecules. Immunol Lett, doi:10.1016/j.imlet.2018.11.006 (2018). [2] Magna, M. & Pisetsky, D.S. The Role of Cell Death in the Pathogenesis of SLE: Is Pyroptosis the Missing Link? Scand J Immunol 82, 218-224, (2015). [3] Di Virgilio, F. et al. The P2X7 Receptor in Infection and Inflammation. Immunity 47, 15-31, (2017). [4] Di Virgilio, F. & Giuliani, A.L. Purinergic signalling in autoimmunity: A role for the P2X7R in systemic lupus erythematosus? Biomed J 39, 326-338, (2016). [5] Faliti, C.E. et al. P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus. J Exp Med, (2019). Disclosure of Interests Anna Lisa Giuliani: None declared, Federica Furini: None declared, Alessandra Bortoluzzi: None declared, Marcello Govoni: None declared, Francesco Di Virgilio Consultant for: FDV is a member of the Scientific Advisory Board of Biosceptre Ltd, a UK-based biotech Company involved in the development of P2X7R-targeted therapeutics.

Background: Myositis specific antibodies play a central role in the assessment of idiopathic inflammatory myopathies (IIMs) as their presence may indicate specific disease subsets/manifestations or cancer risk. At present, anti-MDA5 antibodies have been associated with the occurrence of rapidly progressive interstitial lung disease (RP-ILD), a life-threatening condition, generally refractory to treatment. Objectives: To describe the relationship between malignancy and anti-MDA5 antibodies in IIMs. Methods: Patients with anti-MDA5+ IIMs and a history of cancer were included in this study. Data were retrospectively collected. Because of the lack of RP-ILD shared definitions, we defined RP-ILD as an admission to the Intensive Care Unit (ICU) for IIMs related respiratory insufficiency. Results: In our cohort (n=133, 67% females) we identified 17 patients (13%) with a history of cancer (8 males [47%], 9 females [53%]; median age at IIMs onset 62 years [IQR 53-67], at cancer diagnosis 56 years [IQR 51-66]). All but 1 patient had solid tumours, 5 (29%) had breast cancer. In 9 patients (53%) cancer diagnosis ranged ± 3 years from IIMs onset; in 3 patients the delay exceeded 120 months. Three patients (18%) developed RP-ILD respectively 82, 66 and 0 months after the diagnosis of cancer. Four (24%) patients died respectively 0 (neoplasia), 0 (RP-ILD in ICU, diagnosis of cancer after an autopsy), 7 (neoplasia) and 66 (infection after RP-ILD in ICU) months after cancer diagnosis. The 13 surviving patients had a median rheumatological follow-up of 47 months (IQR 19-84) and an oncological follow-up of 57 months (IQR 10-130). Interestingly, in the overall cohort 66% of patients without cancer (76 out of 116) had less than 3 years of follow-up. Of the 22 RP-ILD patients without neoplasia 14 died, 11 during ICU admission. In the latter patients, we could not rule out an occult neoplasia due to the emergency of the situation. Only one patient, with a 18 month history of IIMs before ICU admission, underwent autopsy and was reported negative for cancer. Conclusion: This is the first study addressed to tackle the relationship between cancer and anti-MDA5+ IIMs. Although in some cases no clear relationship between IIMs and cancer can be proved because of the time gap, in others the timing of occurrence of cancer and IIMs was very close, suggesting a link between these manifestations. Finally, we emphasize the importance of an accurate neoplasm screening in anti-MDA5+ RP-ILD, because treatment refractoriness could suggest the paraneoplastic nature of the manifestation. References [1] Barsotti S, et al. Rheumatol Int 2014 [2] Lu X, et al. PLoS One 2014 Disclosure of Interests: Ludovico De Stefano: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ellen De Langhe: None declared, Jorg Distler: None declared, Johannes Knitza: None declared, Ilaria Cavazzana: None declared, alain meyer: None declared, Jorge Rojas-Serrano: None declared, eugenio arrigoni: None declared, Federica Furini: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, paola parrocchini: None declared, Giovanni Zanframundo: None declared, Jose Antonio P. da Silva: None declared, elisa pedrollo: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Lorenzo Cavagna: None declared

Introduction: P2X7R is an extracellular ATP-gated receptor involved in inflammatory and autoimmune processes mainly acting through NLPR3-inflammasome activation and IL-1β release, also implicated in lymphocyte proliferation and cellular apoptosis. Several observations from animal models and patients' studies highlight a possible link between P2X7R-NLRP3 axis and Systemic Lupus Erythematosus (SLE) pathogenesis. The P2X7R-inflammasome axis in addition to the direct production of IL-1β and IL-18, indirectly mediates the release of other cytokines implicated in the pathogenesis of SLE, such as IL-6. The aim of this study was to investigate the role of P2X7R and NLRP3-inflammasome in SLE. Methods: Forty-eight SLE patients, 16 with (SLE-S) and 32 without (SLE-NS) history of serositis, and 20 healthy control (HC) subjects were enrolled. Demographic, clinical, and therapeutic data were collected. IL-1β and IL-6 plasma levels were evaluated by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by Ficoll gradient sedimentation and employed as follows: (1) evaluation of P2X7R and NLRP3 expression by RT-PCR; (2) determination of P2X7R activity as Benzoyl ATP (BzATP)-induced [Ca2+]i increments using Fura-2-AM fluorescent probe; (3) isolation of monocytes/macrophages and assessment of in vitro IL-1β and IL-6 release following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. Results: Plasma IL-1β levels were unmodified in SLE respect to HC whereas IL-6 levels were higher in SLE than in HC, resulting significantly increased in SLE-S. Macrophages isolated from SLE patients released lower quantities of IL-1β after stimulation with BzATP, whereas IL-6 release was significantly augmented in SLE-NS respect to both HC and SLE-S after all types of stimulation. The [Ca2+]i increase following BzATP stimulation was significantly lower in PBMCs from SLE patients than in PBMCs from HC. RT-PCR showed significantly reduced P2X7R and significantly augmented NLRP3 expression in PBMCs from SLE patients. Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis.

Background:Fertility is thought to be not reduced in women affected by systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease as well as medication exposure might impair gonadal function.Objectives:The aim of this systematic review was to explore clinical, hormonal, serological, instrumental and management factors associated with fertility outcomes in women of childbearing age with SLE.Methods:This systematic review was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English, published from 1972 to 15th August 2020 in Pubmed, EMBASE, Scopus and Cochrane Library. Study selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. Risk of bias of the included studies was assessed by using the NIH risk-of-bias tool [1].Results:Of 788 abstracts, we included in the review 45 studies of which 1 systematic literature reviews, 16 cross-sectional studies, 15 cohort studies, 12 observational studies and 1 case-series study, with a total of 4656 patients. The mean age was 33.5 ± 5.4 years, while the mean disease duration was 97.4 ± 65.2 months. Figure 1 illustrates the quality of the included studies. Definitions of fertility/premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered. Most studies did not use a hormonally based definition of fertility. Clinical factors associated with the development of POF were older age at the time initiation of therapy and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and ovarian failure, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids seem to be associated with a lower risk of ovarian failure compared to CYC. 3 studies demonstrated that POF was more frequent in patients treated with CYC not receiving gonadotropin-releasing hormone analogues (GnRH) in comparison to those co-treated with GnRH. 11 studies evaluated the impact of damage and disease activity on ovarian reserve in patients with SLE with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors able to influence fertility outcomes; among others nor Anti-Müllerian Hormone, neither anti-corpus luteum antibodies were associated with POF.Conclusion:The role of disease activity on fertility in SLE patients is contradictory. Regarding management factors associated with fertility in SLE women of childbearing age, the strongest evidence is about the treatment with CYC and its cumulative dose. Hormonal and serological factors did not impact on fertility outcome but might be used as a surrogate of fertility, especially after treatment with disease-specific drugs.References:[1]Study Quality Assessment Tools NIH. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.[2]Andreoli L. et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017; 76: 476–485.Disclosure of Interests:None declared

Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999–2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD.

Background:anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some series, cancer. Historically, these associations have been detected with immunoprecipitation (IP), but in the last few years commercial lineblot (LB) assay have been released.Objectives:to analyze the clinical features associated to anti-NXP2 antibodies, including the onset of concomitant cancers, both with LB and homemade IPMethods:clinical and serological data from medical charts of 213 patients with a diagnosis of inflammatory miosidites without anti-NXP2 (NXP2-), followed-up by two third-level Centers, and 61 anti-NXP2+ patients from 10 Rheumatological centers were analyzed. Anti-myositis specific (MSA) and anti-myositis associated antibodies (MAA) were detected in single centers by LB (Euroimmun Autoimmune Inflammatory Myopathies 16 antigens). Anti-NXP2 was confirmed by protein and RNA IP, as previously described (1)Results:clinical diagnosis of anti-NXP2+ positive with LB were 42 DM, 11 PM, inclusion body myositis (IBM) 4, necrotizing myositis and overlap (OM) 1 each. Anti-NXP2+ showed a lower age at onset (pIP did not confirmed anti-NXP2 antibodies in 18 sera: in 4 cases at least one MSA/MAA was identified by IP; these 18 patients did not show differences when compared with 213 anti-NXP2-.Conclusion:Protein IP confirmed anti-NXP2 antibodies in 63% of LB+ sera. Double positive cases showed more typical DM features and rarely occurred in IIM not DM. Anti-NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize IIM patients.References:[1]Arthritis Res Ther 2012,30;14:R97Acknowledgments:Forum Italiano per la Ricerca Malattie Autoimmuni (FIRMA)Disclosure of Interests:Micaela Fredi: None declared, Ilaria Cavazzana: None declared, Angela Ceribelli: None declared, Maria Grazia Lazzaroni: None declared, Simone Barsotti: None declared, Maurizio Benucci: None declared, Lorenzo Cavagna: None declared, Ludovico De Stefano: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Giacomo Emmi: None declared, Marco Fornaro: None declared, Federica Furini: None declared, Roberto Gerli: None declared, Maria Grazia Giudizi: None declared, Marcello Govoni: None declared, Anna Ghirardello: None declared, Luca Iaccarino Speakers bureau: GSK, Pfizer, Janssen, Novartis, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Maria Infantino: None declared, Alessandro Mathieu: None declared, Emiliano Marasco: None declared, Paola Migliorini: None declared, Boaz Palterer: None declared, paola parronchi: None declared, Matteo Piga: None declared, Federico Pratesi: None declared, Antonella Radice: None declared, Carlo Selmi: None declared, Valeria Riccieri: None declared, Marilin Tampoia: None declared, Giovanni Zanframundo: None declared, Angela Tincani: None declared, Franco Franceschini: None declared

Background:Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.Objectives:For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.Methods:All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.Results:At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; pConclusion:The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.References:[1]Manfredi A, et al. Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device). BMC Pulm Med. 2019;19:111.[2]Bendstrup E, et al. Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. J Clin Med. 2019:8Disclosure of Interests:Marco Sebastiani: None declared, Caterina Vacchi: None declared, Giulia Cassone: None declared, Fabiola Atzeni: None declared, Martina Biggioggero: None declared, Antonio Carriero: None declared, Gian Luca Erre: None declared, Anna Laura Fedele: None declared, Federica Furini: None declared, Paola Tomietto: None declared, Vincenzo Venerito: None declared, Belén Atienza-Mateo: None declared, Giovanni Della Casa: None declared, Stefania Cerri: None declared, Gilda Sandri: None declared, Adalgisa Palermo: None declared, Elena Galli: None declared, Fabrizio Pancaldi: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Carlo Salvarani: None declared, Andreina Manfredi: None declared

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

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ, This article has been corrected since it first published. The authors would like to notify that title of the article has been changed to:Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines. RMD Open 2019;5:e000784corr1. doi:10.1136/rmdopen-2018-000784cor, Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients’ and clinicians’ unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union’s Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. iii) IVIG is a treatment of resistantDM that may be also used in other resistant-IIMs; iv) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients’ preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations., This publication was funded by the European Union’s Health Programme (2014-2020), Framework Partnership Agreement number: 739531 – ERN ReCONNET. The content of this publication represents the views of the authors only and it is their sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA) or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.

Background Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated. Aims To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). Methods In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Results Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern. Conclusions The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.

In the past years the peripheral nervous system (PNS) involvement in systemic lupus erythematosus (SLE) has received little attention despite its potential significant impact. The true prevalence of PNS in SLE reported in studies is variable and strongly influenced by American College of Rheumatology (ACR) case definition that includes seven PNS manifestations (acute inflammatory demyelinating polyradiculoneuropathy, autonomic disorder, mononeuropathy, myasthenia gravis, cranial neuropathy, plexopathy and polyneuropathy). Other peripheral manifestations, such as chronic inflammatory demyelinating polyradiculoneuropathy and small fibre neuropathy, not included in the ACR nomenclature, have not been well characterised in SLE. The aim of this review is to focus on epidemiology, pathogenesis, diagnosis and clinical features of all possible different expressions of PNS involvement in SLE, with the final objective to profile the patient's clinical characteristics.

Background Diffuse alveolar haemorrhage (DAH) is a rare and severe manifestation of ANCA-associated vasculitides (AAV). Objectives To identify predictors of survival in patients with AAV-DAH. Methods A retrospective study of 102 consecutive patients (50% females; mean age 59±17 years) from 27 Italian Centres diagnosed with AAV-DAH was planned. Cox regression unadjusted analyses were performed. Results Among AAV patients, 47% had Granulomatosis with Polyangiitis (GPA), 47% Microscopic Polyangiitis (MPA) and 6% Eosinophilic Granulomatosis with Polyangiitis (EGPA). At DAH onset, mean BVAS was 20±8 and most patients had renal involvement (RI). Admission to Intensive Care Unit was needed in 27% of patients, while ventilatory support (VS) was required in 46%. At least one cardiovascular risk factor (CVRF) was recorded in 48%. Over a median follow-up of 39 months (25%–75% IQR 66 months), 19/102 patients (18.6%) died (figure 1). All patients received high-dose glucocorticoids in association with Cyclophosphamide (CYC 78%, mean cumulative dose 8±7 g) or Rituximab (37%). Plasma exchange was performed in 46%. Infections occurred in 38%. Age>65 years (HR 3.05 [95% CI 1.18–7.9], p=0.04), CVRF ≥2 (HR 8.85 [95% CI [AG7] 2.34–33.50], p=0.01), BVAS (v.3) (HR 1.07 [95% CI 1.01–1.13], p=0.01) were associated with mortality, whereas FFS was not. The need for VS (HR 4.54 [95% CI 1.48–13.85], p=0.008) and infections (HR 3.98 [95% CI 1.48–10.69] were also associated with mortality. Conclusions Older age, VS, CVRF and infections affect the survival in AAV. There is a need for specific outcome measeures. Disclosure of Interest None declared

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterised by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). Despite Raynaud’s phenomenon (RP) is another typical feature of ASSD, nailfold videocapillaroscopy (NVC) assessment of these patients has been only sporadically described, without the elucidating data for clinicians. Objectives To describe NVC features of ASSD patients and to investigate possible correlations with clinical and serological features of the disease. Methods We retrospectively analysed NVC images of 190 ASSD patients (females/males 3.76, mean age 49.7±12.8 years, mean disease duration 51.2±71.4 months, 133 anti-Jo-1 and 57 non-anti-Jo-1 positive patients). For each patient, we examined number of capillaries, giant capillaries, micro-haemorrhages, avascular areas, ramified capillaries, and the presence of scleroderma (SSc) patterns. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results NVC abnormalities were observed in 62.1% of AASD patients compared with 29.3% of a group of 75 patients with primary Raynaud’s phenomenon (p Conclusions NVC abnormalities are commonly observed in ASSD, independently to the occurrence of RP. The presence of a SSc-like pattern should let to identify a more defined ASSD subtype and prospective studies could confirm the association with clinical and serological features of ASSD. Disclosure of Interest None declared

Osteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide, with a strong impact on individual and population health. OA is a clinically heterogeneous disease presenting with different clinical phenotypes recognising systemic and local risk factors. The pathogenesis is multifactorial including constitutive features of the joint, non-modifiable and modifiable risk factors. Epidemiological studies highlight the link between metabolic syndrome and OA and the effect of interplay between immunological and metabolic processes is getting increasing emphasis because of to the discovery that metabolic syndrome is implicated in OA pathogenesis and progression. In addition, recent findings suggest a potential role of dietary factors in susceptibility and progression of OA. In this review, we summarise the most robust evidence on epidemiology and classical risk factors OA, also exploring the most recent evidence on metabolic changes and Mediterranean diet for OA as a possible target to impact on the natural history of the disease.

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union's Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ' preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations. info:eu-repo/semantics/publishedVersion

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). As in inflammatory myopathies, nailfold videocapillaroscopy (NVC) alterations have been sporadically described also in ASSD patients, but no elucidating data are available. Objectives To investigate the possible specific NVC features of ASSD patients. Methods Within the framework of a multicenter study, we retrospectively analyzed NVC images of ASSD patients, after excluding patients with overlap syndrome with systemic sclerosis. Two operators in a blind manner re-evaluated all patients with at least one image per finger. For each patient, we examined number of capillaries (mean number of capillaries per mm in the distal row), enlarged and giant capillaries, micro-hemorrhages, avascular areas, ramified capillaries, and the presence of a scleroderma (SSc)-like pattern, according to Manfredi et al. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results The NVC of 54 ASSD patients were analyzed (males/females 1/6.8, mean age 55.79, CI95% 51.9–59.9 years, mean disease duration 59.4, CI95% 27.9–90.9 months). Raynaud9s phenomenon (RP) was recorded in 51.9% of patients, arthritis in 79.6%, myositis in 53.7%, and ILD in 92.6%. NVC alterations were observed in 53.7% of AASD patients. Nineteen patients (35.2%) showed a SSc-like pattern; the main features were disarrangement of hairpin and angiogenetic aspects (42.6%), avascular areas (38.9%), giant capillaries (27.6%), and microhemorrhages (20.4%). Finally, the mean number of capillaries was reduced (7.8±2/mm). No significant association was recorded between SSc-like pattern and the presence of arthritis, myositis, and ILD, nor with RP. Among other NVC features, angiogenesis was significantly associated to female gender (p=0.031), while microhemorrhages were inversely associated to the presence of arthritis (0.033). No association was observed between NVC features and autoantibodies profile. Of interest, in 58% of patients with ILD we observed at least a NVC alteration vs no patients without ILD (p=0.04). Finally, in patients with RP NVC alterations were recorded in 15/28 patients (53.6%) and a SSc-like pattern in 11/28 (39.3%), while only 57.9% of patients with SSc-like pattern had a clinically manifest Raynaud9s phenomenon. Conclusions Despite preliminary, the present is the first study concerning NVC in AASD patients. Regardless of the presence of Raynaud9s phenomenon, NVC alterations are frequently observed; in particular, a SSc-like pattern is recorded in more than 1/3 of patients. NVC should be performed in all ASSD patients at diagnosis regardless of the presence of RP in the patient history and during follow-up. ASSD should be always considered in the screening of RP. A prospective multicenter study has been planned to identify specific patterns and possible associations between NVC findings and clinical and serological features of ASSD. References Manfredi A, et al. 2015. Sebastiani M, et al. 2014. Disclosure of Interest None declared

Background The occurrence of osteoporosis (OP) and fragility fractures (FF) is a frequent comorbidity in patients with systemic lupus erythematosus (SLE), mainly due to the concomitant presence of many risks factors for secondary osteoporosis (drugs, gender, concomitant diseases). The use of corticosteroids (CS) increases the risk of osteoporosis induced by corticosteroid (GIOP) and FF [1]. Denosumab is monoclonal antibody that binds to RANKL, inhibiting osteoclast formation and activation, used for both male and women OP to prevent FFx [2,3]. Previous RCT [2] reported a numerically higher serious adverse events of infections in the denosumab users. In particular severe skin infections were significantly more frequent [4]. The possible increase in infection risk might be a concern in subjects treated with CS. The use of denosumab in SLE with GIOP patients is recently reported in 17 cases within a RCT [5]. Anyway, no data regarding the tolerability and disease activity during therapy were reported Objectives Our aim was to analyze the prevalence, the tolerability, and relevant changes in disease activity or damage in a cohort of SLE patients treated with denosumab Methods among all SLE patients currently followed in two referral Center we selected the ones that received at least one dose of denosumab. Clinical, serological manifestations, concomitant diseases and therapies were collected from clinical charts. Damage index (SDI), activity index (SLEDAI-2K) were calculated when denosumab was introduced (first cycle) and at the last evaluation (last cycle). For statistical analysis Chi-squared test or Fisher exact test was used Results Among 793 patients in our cohorts, 21 (2.6%) were treated with denosumab. Demographic data reported a female prevalence (19 cases,90%), mean age at onset of 38±12years, mean duration of disease of 28±10years and mean follow-up of 21±7.8years; most frequent manifestations were arthritis (90%), cutaneous (67%) and neurological (67%). All patients were still treated with CS (mean duration of 25±6.8 years) with a daily dose of 8.5±3.5mg/day. Other risk factors for OP were present in the majority of them: drugs (anticoagulants in 6pts, cyclosporin in 3 and antiepileptic in 2), chronic kidney disease (CKD) (4pts), hypovitaminosis D (15pts), anorexia, celiac disease and hemochromatosis (1pt, each). Indication for denosumab was OP with FFx in 17 cases: denosumab was used for a new FF during biphosphonates or after teriparatide. In the other 4 the indication was primary prevention with contraindications at the use of biphosphonates for concomitant severe CKD. Mean duration therapy was 4 cycles (range 1–8): data regarding disease activity, damage and adverse events are reported in table 1. No new FFx developed in any of the included patients at the last evaluation available. Conclusions In our cohorts denosumab is still used in few selected patients. However it could be considered as a valid option in GIOP patients because it was globally well tolerated and in our cohort it9s efficacy in the prevention of new fragility fractures was confirmed References Gudbjornsson, et al. Ann Rheum Dis 2002;61,32–36. Cummings SR et al. N Eng J Med 2009; 61:756–65. Austin M et al. J Bone Miner Res 2012;27:687–93. Watts NB, Osteoporos Int 2012;23:327–37. Mok CC, et al. Bone 2015;75:222–8. Disclosure of Interest None declared

To assess validity, responsiveness and interpretability of the UltraSound-CLinical ARthritis Activity (US-CLARA) index in patients with rheumatoid arthritis (RA).In this longitudinal study were involved RA patients starting treatment with abatacept. Subjects were followed along three visits in the first 6 months of therapy and underwent a comprehensive clinimetric evaluation. Validity was explored correlating the baseline scores and the cumulative inflammatory burden of the US-CLARA with the other composite indices applied. Sensitivity to change was assessed after 6 months of treatment in terms of internal and external responsiveness. Interpretability was defined in terms of determination of cutoffs against external criteria for remission (REM), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) of SDAI.One-hundred and thirty patients completed the study.moderate correlations were observed between US-CLARA and both DAS28-CRP and DAS28-ESR. Higher correlations were also found between US-CLARA and both SDAI and CDAI scores. Responsiveness: internal responsiveness was wide, with SRM and ES ranging from 0.91 to 1.51. US-CLARA responsiveness was similar to that of DAS28, SDAI, or CDAI. Similarly, the area under ROC curve (AUC-ROC) of US-CLARA gives identical results. The AUC of cumulative inflammatory burden, calculated during the 6-months follow-up of all combinations were highly correlated (p0.0001). Interpretability: cutoff values for REM, US-CLARA2.0; for LDA, 2.0 ≤US-CLARA3; for MDA, 3 ≤US-CLARA ≤4.8; for HDA, US-CLARA4.8.The US-CLARA is valid and sensitive tool to assess disease activity in RA.

The clinical spectrum and prognosis of systemic sclerosis (SSc) seem to vary among patients' populations recruited during different time periods. In order to verify this possible evolution we investigated the clinico-serological and survival rate in a large Italian SSc series (821 patients; 746 females, 75 males; mean age 53.7±13.9SD years) recruited between 2000 and 2011. The observed findings were compared with previous studies of the world literature.Compared to older Italian SSc series, the present patients' population showed a significantly increased prevalence of limited cutaneous SSc (from 72 to 87.5%; p ≤.0001) and serum anti-centromere antibodies (from 39 to 47,4%; p ≤.001), with a significant reduction of lung (from 81 to 63.7%; p ≤.0001), heart (from 35 to 20.5%; p ≤.0001), and renal involvement (from 10 to 3.8%; p ≤.0001), and skin ulcers (from 54 to 16.5%; p ≤.0001). Cumulative 10th-year survival showed a clear-cut increase (80.7%) compared to our previous series (69.2%). These findings were mirrored by the results of survival studies published during the last five decades, grouped according to the time periods of patients'' recruitment at the referral centers. A clear progression of 10th-year survival rates was detectable, from the 54% median survival of the oldest studies (1935-1974) to 74% and 83.5% of the more recent SSc series, 1976-1999 and after 1999, respectively. In conclusion, the favorable evolution of SSc pathomorphosis and prognosis during the last decades might be related to more diffuse physician/patient awareness of this harmful disease and availability of diagnostic tools, the consequent wider recruitment of patients in the early stages of the disease, as well as to the improved therapeutic strategies.

Objective. To evaluate the involvement of the bursa located next to the head of the 5th metatarsal bone in patients with psoriatic arthritis (PsA) in comparison with the other seronegative spondyloarthritis (SpA).Methods. All patients with PsA seen during a period of 24 months were enrolled. The control group included healthy subjects and patients with the other SpA. All subjects underwent clinical and ultrasound (US) examination of the lateral surface of the 5th metatarsal.Results. 150 PsA patients (88 M; 62 F), 172 SpA (107 M; 65 F), and 95 healthy controls (58 M; 37 F) were evaluated. Based on clinical and US evaluation, bursitis was diagnosed in 17/150 (11.3%) PsA patients but in none of the SpA (P<0.0001) and healthy (P=0.0002) controls. In detecting bursitis, US was more sensitive than clinical examination, although the difference did not reach statistical significance (P=0.09).Conclusion. The bursa of the 5th metatarsophalangeal joint appears to be involved in PsA more frequently than by chance. If confirmed by other studies, this finding could be considered as a distinctive clinical sign of PsA, useful for differential diagnosis with the other SpA. In asymptomatic patients, US proved to be more sensitive in the detection of bursitis.

Background A complex variety of musculoskeletal manifestations have been described in HIV patients, including conditions belonging to the wide spectrum of spondyloarthropathies (SpA). Enthesitis is a distinctive feature of SpA. Peripheral enthesitis is usually revealed by clinical findings but it may also be asymptomatic and detected only by imaging, such as conventional radiography, magnetic resonance or ultrasonography (US). Objectives The aim of the present study was to evaluate by US examination the prevalence of enthesitis in patients with HIV infection without rheumatic clinical symptoms in comparison with control healthy subjects. Methods 28 patients with aymptomatic HIV infection (22 M and 6 F; mean age:43 ± 8.6) were consecutively examined with US (Toshiba- Aplio XG- 12–18 MHz linear array transducer). All patients were recently diagnosed as HIV infected, didn9t take any HIV treatment and had no clinical signs or symptoms of joint or enthesis involvement. 25 healthy subjects, matched for sex, age and BMI were studied as controls. The following sites were examined bilaterally by US: common extensor tendon insertion on the lateral epicondyle of the humerus; quadriceps tendon insertion on the superior pole of the patella; patellar tendon insertion (patellar ligament origin and the patellar ligament insertion at the tibial tuberosity); Achilles tendon insertions on the calcaneus. The following abnormal findings were recorded: thickness, bony erosions, enthesophytes and bursitis. Local blood flow was examined using Power Doppler (PD) mode. US and PDUS were performed by an experienced operator and blinded to the clinical examination. Results 20/28 HIV patients (71.4%) presented almost one enthesis abnormality in comparison with 3/25 (12%) healthy controls (p 0.8 intra-class correlation variability). Conclusions US revealed a high frequency of subclinical enthesis abnormalities in asymptomatic HIV patients without rheumatic clinical signs and symptoms, highlighting the important role of US investigation and the strong association of HIV infection with rheumatic manifestations typical of SpA. References Iordache L et al. Autoimmune diseases in HIV-infected patients: 52 cases and literature review Autoimmun Rev. 2014 Aug;13(8) Reveille D et al Rheumatologic complications of HIV infection. Best Practice & Research Clinical Rheumatology 2006; 20 Balint PV et al Ultrasonography of entheseal insertions in lower limb in spondylarthropathy. Ann Rheum Dis 2002;61 Disclosure of Interest None declared

Background PM-Scl antibodies (abs) belong to the group of myositis-associated antibodies and typically determine a nucleolar or speckled pattern on immunofluorescence. These abs found in patients (pts) with Scleromyositis and, less frequently, in isolated forms of Systemic sclerosis (SSc), Polymyositis (PM) and Dermatomyositis (DM). In SSc pts PM-Scl +, pulmonary involvement seems less severe, while they show more frequent arthritis. Raynaud9s phenomenon (RP), digital ulcers (DU) and gastroesophageal involvement appear to be less frequently expressed. In myositis the association with esophageal and lung involvement is well known. Objectives To characterize demographic and clinical features of a single center series of PM-Scl positive patients. Methods Sera from 48 SSc and 60 idiopathic inflammatory myophaties (MII) attending local outpatient clinic, detected with EUROIMMUNE Myositis Profile 4 kit, were tested to search PM-ScL antibodies. Demographic, laboratory and clinical data (RP, arthritis, DU, muscular involvement, disphagia) were retrospectively retrieved from available clinical charts. The presence of interstitial lung disease (ILD), was evaluated by HRCT (measured by using score of Goh for the extension) and functional respiratory testing (FVC and DLCO). Severe ILD was defined by: Goh score of>20 and FVC and DLCO Results 23 Pts (18 F) resulted positive for PM-Scl. The mean age was 60.5±9.4 years and the mean disease duration was 145.9± 76.3 months. 1 patient had negative ANA, 1 showed ANA anticentromere and 1 dot pattern; the remaining 20 patients (86,9%) were ANA+ showing nucleolar pattern. By applying available formal classification criteria 5 (21.7%) pts were diagnosed as DM, 2 (8.7%) as DM amyopathic, 3 (13.05%) as overlap Scleromyositis, 3 (13.05%) as PM, 1 (4.4%) as cancer associated PM, 9 (39.1%) as SSc (2 diffuse, limited 6, intermediate 1). 13 (56.5%) pts had no evidence of cytopathic muscle involvement (defined as normal CPK, myoglobin and LDH). 5 pts (21.7%) presented a Goh score >20, 1 FVC 4 pts presented arthritis. 14 (60.8%) had RP, 6 (26%) DU, 8 (34.8%), dysphagia (see images 1). When compared with patients with SSc and MII negative for PM-Scl, MII PM-Scl + pts did not show significant greater risk of developing ILD (Goh>20)dysphagia or minor muscle involvement. SSc PM-Scl + pts seem to have a greater risk of developing arthritis and DU than their corresponding SSc PM-Scl negative pts (p 20) and dysphagia. Conclusions The role of PM-Scl as a risk factor for ILD in MII pts is not confirmed, but should be considered the positivity in the control group of Jo1, representing per se a major risk factor for this complication (image 2). For patients with SSc is confirmed the role of PM-Scl as a risk factor for arthritis and digital ulcers but not for ILD. References Long-term out come of patients with polymiositis/dermatomyositis and anti PM/Scl antibody. Marie et al. Journal of Dermatology 2010; 162(2): 337–44 Disclosure of Interest None declared

Background Articular involvement is reported to occur in up to 85% of patients with antisynthetase syndrome (ASSD) and it may be the only onset feature, although with frequencies and characteristics not still defined Objectives To determine in a large international cohort of anti Jo-1 positive ASSD the prevalence of isolated arthritis at disease onset. To describe the clinical, serological and radiological characteristics and evolution of these patients Methods We included all anti Jo-1 positive patients referring to participating centres and with an isolated arthritis at disease onset. The pattern of articular involvement, radiological and serological characteristics of patients were analysed. IgM-Rheumatoid factor (RF) was assessed by immunonephelometry; anti-cyclic citrullinated peptide antibodies (ACPA) by commercial second-generation ELISA kits; anti Jo-1 and anti-Ro positivity by commercially available ELISA kits Results An isolated arthritis was the first manifestation in 54 (41 females, 13 males) out of the 225 patients included (167 females, 58 males), with a prevalence of 24%. Main characteristics of arthritis and overal results has been completely reported in table 1. Conclusions We confirmed that an isolated polyarthritis is the first symptom of anti Jo-1 positive ASSD in up to a quarter of cases. Arthritis is mainly polyarticular and symmetrical, and the positivity for IgM RF or ACPA or both is not a rare finding, as well as the occurrence of marginal X-rays joint erosions. Anti-Ro positivity and RP occurrence may help clinician in the early identification of ASSD, even if the high rate of subsequent appearance of ILD and myositis clearly suggest that the screening for an underlying ASSD should be performed also in patients that may be undoubtedly diagnosed with RA. References Cavagna L, et al. Characterization of anti Jo-1 positive antisynthetase syndrome: results from an international multicentre study. Arthritis Rheum 2014;11:S550. Lefevre G, et al. Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients. Rheumatology (Oxford). 2014 Oct 27. pii:keu404. [Epub ahead of print] Disclosure of Interest None declared

Background The prevalence of neuroimaging abnormalities is not defined in newly-diagnosed Systemic Lupus Erythematosus (SLE), especially in those patients without overt neuropsychiatric (NP) symptoms; furthermore the clinical significance of these alterations is not clear at all. Objectives To assess the prevalence of brain abnormalities found by Magnetic Resonance Imaging (MRI) in a monocentric cohort of patients with early SLE onset (within 12 months from diagnosis) with (NP-SLE) or without NP manifestations (SLE) and to assess if early abnormal neuroimaging findings could have a predictive role for lesion load progression or the occurrence of subsequent NP events. Methods We selected SLE patients, less than 55 years, diagnosed according to the 1997 ACR criteria, who underwent brain MRI examinations within 12 months since diagnosis and then repeated it in the following 24-36 months. Brain MRI results were considered as absence or presence of white matter hyperintensities (scoring 0-3 if focal lesions were respectively none, 1, 2-4 or >5) and also as absence or presence of atrophy (scoring 0-3 if atrophy was absent, light, moderate or severe) according to a modified semiquantitative scoring system proposed by Petri et al. Then we evaluated the appearance of each new NP event along a median follow up period of 42 months. Results We retrospectively evaluated 752 patients referred consecutively at our clinic dedicated to SLE in a period of 20 years (between 1995 and 2014); 46 patients met the criteria for inclusion in the study. The mean age of the whole studied population was 34 years (14-55 yrs), 93.5% female. Of these patients, 28 had at least 1 NP event at time of diagnosis (61%). Overall an abnormal MRI was reported in 21 patients (46%), especially in those with NP involvement (18 NP-SLE and 3 SLE, p=0,0023). At baseline median atrophy score and WMHI score were 0,15 and 1,02 respectively. After the first NP event all patients either increased their immunosuppressive therapy (steroid and/or cyclophosphamyde bolus) or added aspirin low dose or anticoagulant drugs. At the time of the second MRI, a lesion load progression or worsening was seen in 26% (12): 29% (8) of NPSLE and 22% (4) of SLE pts (p>0,05); in all SLE patients the first MRI was negative. Total and median (1,2) WMHI score worsened during FU, median score for atrophy doubled (0,28). Almost all (92%) worsened MRI were associated with positivity of antiphospholipid antibodies. Comparing patients with unchanged MRI to those with worsened MRI a new NP event was recorded in 5 pts versus 6 pts (p=0,02), for a total of 11 new NP episodes. Conclusions Imaging abnormalities are present in a high percentage of SLE individuals at onset of disease (46%). A basal neuroimaging evaluation in young patients with newly diagnosed SLE is recommended especially because the evolution of the neuroradiological pictures seems to be independent of the previous history. Serial assessment is extremely useful to compare with any further imaging finding. Although a predictive value for abnormal neuroimaging in new appearance of NP event has yet to be demonstrated we found that MRI worsening could predict the occurrence of new NP event during follow up. Disclosure of Interest None declared

Background The term undifferentiated connective tissue diseases (UCTD) has been widely used to identify conditions not fulfilling classification criteria for a defined connective tissue diseases (CTD). Recently the introduction of new classification criteria for different CTD allowed to take a significant step forward for their early identification and for a more reliable diagnosis of UCTD. Objectives To analyze the clinical and serological characteristics of a large cohort of patients (pts) with UCTD and to evaluate: the incidence of Systemic Lupus Erythematosus (SLE) defined according two different “set” of classification criteria for lupus, ACR 1997 and SLICC 2012, in a time frame of 15 years (1999-2013); to analyse clinical and serological data comparing pts affected by stable UCTD to UCTD evolved to SLE. Methods A cohort of pts referred to our clinic dedicated to UCTD, who met the classification criteria proposed by Mosca et al. [1], were retrospectively analyzed. The pts with a median follow-up less than one year were excluded. Clinical and serological assessment was performed at the time of diagnosis (T0) and at 3 different time points indicated as T1 (time interval between the first and third year), T2 (between the third and fifth year) and T3 (from the fifth to the tenth year). The classification criteria for SLE, ACR 1997 and SLICC 2012, were applied to each patient at time T0, T1, T2 and T3. Results 329 pts were enrolled. An observation period up to T1 was recorded for the entire sample, up to T2 for 273 pts and 206 pts had completed the follow-up to T3. At T0 no pts met SLE/ACR criteria (according to inclusion criteria of study), whilst 44 pts met SLE/SLICC criteria: 41 females (F, 93.2%) and 3 males (M), mean age 40.1±14 years. Overall, at the end of the observation period, the SLE/SLICC criteria were cumulatively observed in 67 pts (20.4%), while 14 pts met the ACR criteria. In 12 pts both sets of criteria were satisfied. At the end of follow-up, 260 pts did not meet any set of classification criteria (UCTD stable, 79% of the whole population, 253 F and 7 M, mean age 53.6±15.5 years). During the follow-up the rate of progression to SLE was stable over the years, with a number of switch to SLE constant even after 5 years of diagnosis of UCTD. A peak rate of new cases was observed at T3 where five new cases of SLE/ACR (2.4%) and 7 cases of SLE/SLICC (3.4%) were recorded. The baseline clinical and serological characteristics of pts with stable UCTD were compared to pts evolved in SLE. Acute or subacute skin rash (p 0.02), serositis (p 0.03) and the presence of antiphospholipid antibodies (p 0.02) were the variables correlated with the progression to SLE/SLICC. Acute or subacute skin rash (p 0.001) and the presence of antiphospholipid antibodies (p 0.03) were the variables correlated with the evolution to SLE/ACR. Conclusions From our study in a cohort of UCTD pts the application of the new set of SLICC classification criteria for SLE, compared with the old ACR criteria, would not seem to have contributed significantly in terms of predictability of the evolution towards lupus, but certainly they expanded the number of pts classified as SLE at onset of the disease allowing a certain diagnosis in a greater number of pts who would otherwise be classified as UCTD. References Mosca M et al. Clin Exp Rheumatol 1999;17:615-620. Disclosure of Interest None declared

Background the overlap syndrome Systemic sclerosis-rheumatoid arthritis (SSc-RA) is characterized by the presence in the same patient of clinical and laboratory features that meet the classification criteria for both diseases. The current literature shows how that lung involvement is more frequent and severe in SSc-RA than in SSc alone [1]. Objectives to describe the frequency of clinically significant interstitial lung disease (ILD), determining the reduction of the forced vital capacity (FVC) or the alveolar-capillary diffusion of carbon monoxide (DLCO) in a group of 25 patients with SSc-RA compared to a control group of 570 patients with SSc alone. Methods data were retrieved from a database and from medical records of patients followed at the outpatient clinic dedicated to SSc of the Rheumatology Unit of S. Anna Hospital, Ferrara. All patients fulfilled the classification criteria for SSc (ACR 1980 and LeRoy 2001) and RA (1987). For both groups (SSc and SSc-RA) the following seroimmunologic data were assessed: anticentromere antibodies (ACA), anti topoisomerase 1 (Scl 70), rheumatoid factor (RF) and anti-citrulline (ACPA). Pulmonary involvement was assessed by high-resolution chest CT scan using the score of Warrick, and spirometry including DLCO. A cut-off of Warrick9s score able to detect patients with ILD has been identified by the application of a regression curve between the total score at HRCT and spirometry data (FVC and/or DLCO 10 able to alter lung function. Results in the SSc control group FR was available in 38% of cases and ACPA only in 8.9% RF and ACPA were available in all 25 SSc-RA patients. Positivity for both FR and ACCP was detected in 23 SSc-RA patients whilst 2 were seronegative. ILD was more frequent in SSc-RA group compared to SSc (76% VS 33%, p Conclusions an increased risk of ILD in SSc-RA compared to SSc was confirmed. In SSc-RA group, ACA seems to lose its role as a “protective” factor against the possible development of pulmonary fibrosis. If this information is confirmed, in SSc-RA patients, despite their ACA positivity, it could justify a more “tight” clinical-instrumental follow-up, to detect lung involvement early and to monitor its evolution. References Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity. Szucs G, Szekanecz Z, Zilahi E et al. Rheumatology (Oxford). 2007 Jun;46(6):989-93 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5137