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Pulmonary involvement in Sjogren syndrome (SS) could manifest as cystic lung disease (CLD). CLD in SS includes lymphocytic interstitial pneumonia (LIP) and pulmonary amyloidosis. Differential diagnosis usually requires surgical lung biopsy, whereas CT-guided percutaneous fine needle aspiration biopsy (CT-FNAB) has not yet explored. We describe the case of a 63-year-old never smoker Caucasian female with a SS diagnosis who displayed a newly detected diffuse CLD at high-resolution computed tomography, though totally asymptomatic. Given the favorable location of one big lesion at the superior left lobe, a CT-FNAB was proposed instead of a more invasive SLB. At histology examination a diagnosis of pulmonary nodular AL kappa amyloidosis in the context of SS was established. In conclusion, CT-FNAB might represent an alternative and less invasive diagnostic procedure than SLB in the differential diagnosis of CLD, even if further research is needed. Moreover, this case presents an unusual association between SS and pulmonary nodular AL kappa amyloidosis, with pulmonary nodules and cysts without systemic manifestations.

Objectives To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. Methods SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. Results We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P Conclusion ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

Objective To investigate the factors associated with discordance between patient and physician on the presence of a gout flare. Methods Patients’ self-reports of current gout flares were assessed with the question, ‘Are you having a gout flare today?’ which was then compared with a concurrent, blinded, physician’s assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups—patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed—were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis. Results Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0–10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]. Conclusion Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints.

Background Lung ultrasound is a bedside non-irradiating tool for assessment and monitoring of lung diseases. A lung ultrasound score based on visualized artefacts allows reliable quantification of lung aeration, and is useful to monitor mechanical ventilation setting, fluid resuscitation and antibiotic response in critical care. In the context of interstitial lung diseases associated to connective tissue disorders, lung ultrasound has been integrated to computed tomography for diagnosis and follow-up monitoring of chronic lung disease progression. Case presentation This case describes a severe acute exacerbation of interstitial lung disease associated to dermatomyositis–polymyositis requiring prolonged extra-corporeal life support. Lung ultrasound score was performed daily and allowed monitoring and guiding both the need of advanced imaging as computed tomography and immunosuppressive therapy. Conclusions This case suggests lung ultrasound may be a useful monitoring tool for the response to immunosuppressive therapy in acute severe rheumatic interstitial lung disease, where chest X-ray is poorly informative, and transportation is at high risk.

Objective.To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS).Methods.Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state.Results.Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively.Conclusion.Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

Zusammenfassung Einleitung Ziel dieser Datenerhebung war die Untersuchung der klinischen, demografischen und Komorbidität-assoziierten Daten der Gicht sowie der klinischen Praxis der hausärztlichen Gichtversorgung in Rheinland-Pfalz (RL-P). Methoden Gicht-spezifische Fragebögen wurden über die kassenärztliche Vereinigung an alle Hausarztpraxen in RL-P versendet. Die Fragebögen setzten sich aus Items zur Erfassung von Epidemiologie, Medikation und Komorbiditäten zusammen. Darüber hinaus wurden Fragen zur klinischen Manifestation der Gicht mit einem besonderen Fokus auf therapierefraktäre Fälle eingebunden. Schließlich wurden die Hausärzte angehalten, den aktuellen Versorgungsstatus anhand einer Ratingskala zu bewerten. Ergebnisse Daten von 4016 Gichtpatienten (Durchschnittsalter zur Zeit der Diagnose: 62,8 Jahre, IQR 55 – 67,8) wurden anonym erhoben. Der überwiegende Anteil der Patienten war männlich (75 %) mit Podagra als häufigste Manifestationsform der Gicht (85 %). Chronisch tophöse Verläufe wurden in 15 % (Median 10 %, IQR 2 – 20) der Fälle angegeben und eine axiale Beteiligung in 2,7 % (Median 0 %, IQR 0 – 2). Durchschnittlich 11,3 % der Fälle (median 10 %, IQR 2,3 – 20) wurden als schwer behandelbar („hard-to-treat gout“) definiert. Trotz alledem wurden Biologika nicht namentlich als verwendete Behandlungsform erwähnt. 32 % der Patienten erhielten die Gichtdiagnose von ihrem Hausarzt, während 68 % weitere Ärzte aufsuchen mussten. Eine definitive Diagnose konnte nach durchschnittlich 3,1 Monaten (Median 0,3, IQR 0,1 – 1) gestellt werden. Diskussion Zusammenfassend gibt es im Zeitalter der Biologika einen Bedarf zur Optimierung der Gichtversorgung. Wichtige Ziele sind die Verkürzung der Diagnosezeit und die Prävention chronischer Verläufe. Die Schaffung eines gesteigerten Bewusstseins für die Erkrankung Gicht und ihre Komorbiditäten, ein standardisierter Behandlungsplan und Patiententraining könnten wichtige Schritte in diese Richtung sein.

Eosinophilic granulomatosis with polyangiitis (EGPA), traditionally known as Churg–Strauss syndrome, is a form of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a group of...

We report the case of a 69-year-old woman, a never-smoker, with anti-melanoma differentiation-associated gene-5 (MDA5) antibody-positive amyopathic dermatomyositis (ADM) and autoimmune thrombocytop...

Background:Interstitial lung diseases (ILDs) represent a heterogeneous group of disorders with different treatment and prognosis. ILD may be the presenting or the dominant manifestation of a connective tissue disease (CTD). Multidisciplinary team (MDT) discussion is currently the diagnostic standard. However, there is no consensus on how MDT diagnosis is validated and on the core elements of discussion.Objectives:To explore the performance of a diagnostic algorithm for the differential diagnosis of ILD based on clinical, serological and radiological data, supporting clinician decision-making.Methods:In this retrospective study, analysis was performed on clinical, serological and radiological features at diagnosis and 1-year follow-up in 71 patients, including 41 with CTD-ILD and 30 with idiopathic interstitial pneumonias (IIPs). In order to identify robust hallmarks, we conducted the Receiver Operating Characteristic (ROC) curve analyses in logistic regression, to discriminate significantly different features between CTD-ILD and non-CTD-ILD groups.Results:Out of 71 patients 46% were women, with a mean age of 66±11 years. History of smoking (8.8% current and 39.8% former smokers), was more associated with IIPs. 54% of patients had dyspnea on exertion and 39% dry cough, both more frequently associated with IIPs (p = 0.016). Among radiological features, NSIP pattern was more frequent in CTD-ILD, while UIP was associated with IIP. Lung fibrosis extent was greater in IIP (p = 0.063), in which CT is generally performed in symptomatic patients at diagnosis and rarely for screening purpose. Baseline features with good performance (OR p-value ≤ 0.05) were eligible as potential candidate discriminators: age, sex, smoking habit, rheumatological signs and symptoms, autoantibodies, ILD patterns were selected, to build a multivariate model with high discrimination accuracy (AUC 0.971). The model has a sensitivity of 100% and specificity of 89.7%. The most relevant correlations between population features and CTD-ILD are presented in Table 1.Table 1.Correlation analysis of the most significant discriminative features.FeaturesOdds ratioP valueArea under ROC curveSex (female)3.290.019*0.643Age0.910.001*0.736Smoke0.120.738Respiratory symptoms (dyspnea and/or dry cough)0.260.016*0.644Rheumatological symptoms (any)28.80.839 • Raynaud’s phenomenon15.040.0110.654 • Cutaneous manifestations8.160.0530.593Autoantibodies (ANA, ENA, RF, ACPA, myositis-specific antibodies or aPL) positivity33.680.792Lung function test • Forced vital capacity (%FVC)0.970.1750.638 • Diffusing capacity of carbon monoxide (%DLCO)0.960.0720.665High-resolution computed tomography (HRCT) imaging • Honeycombing0.340.0680.593 • Emphysema0.140.005*0.647 • Extent of lung involvement (%)0.970.0630.668HRCT pattern • NSIP vs UIP30.033*0.625Abbreviations: ANA, antinuclear antibody; ENA, extractable nuclear antigen; RF, rheumatoid factor; ACPA, anti-citrullinated peptide antibody; aPL, antiphospholipid antibody; NSIP, nonspecific interstitial pneumonia; UIP, usual interstitial pneumonia.Conclusion:Our study shows that the most important variables in the differential diagnosis between CTD-ILD versus IIPs include, as expected, autoimmune features (rheumatological symptoms and serological data). Questionnaire tool containing these specific hallmarks may be relevant during MDT discussion, limiting the number of misdiagnosed CTD-ILDs and potentially avoiding further unnecessary investigations. However, only prospective cohort studies of early onset ILD are needed to fully validate the relative importance of clinical, serological, functional and radiological data.References:[1]Furini F. et al, The Role of the Multidisciplinary Evaluation of Interstitial Lung Diseases: Systematic Literature Review of the Current Evidence and Future Perspectives. Front Med (Lausanne). 2019; 6: 246.Disclosure of Interests:None declared

Objectives Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques. Results The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low–medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0–12 months), and high levels at T0–1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions. Conclusion Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients. Trial registration The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.

Objective To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions Our results support the association of the HLA complex with the susceptibility to ASSD.

Clinical Trial registry name and registration number: Zeus study, NCT02403115

Objectives Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques. Results LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months. Conclusions Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN. Trial registration The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).

Objectives Quantitative computed tomography (QCT) is a promising tool for objective assessment of interstitial lung disease (ILD) related to connective tissue diseases (CTD). However, its validity was never investigated. The aim of this study was to assess QCT feasibility, face, and content validity evaluation concerning CTD-ILD. Methods A rheumatologist and a chest radiologist conceived an online survey with nine statements: Two about general issue involving CTD-ILD, one for the face validity, three both for content validity and feasibility. Each statement had to be rated with a score from 0 to 100, respectively, (complete disagreement and agreement). We considered a statement supported by the experts if the median score was ≥75.0. Results A panel of 14 experts (11 from Europe, three from America) with a nine years median experience was enrolled. All the statements about feasibility, face and content validity were supported, except for QCT capability to recognize elementary lesions. Conclusions The panel of experts supported feasibility, face, and content validity of QCT assessment concerning CTD-ILD. This may stimulate a greater use in clinical practice and further studies to confirm its discriminative properties and its construct validity.

despite the absence of specific guidelines, the treatment with intravenous immunoglobulins (IvIg) is considered effective in patients with refractory idiopathic inflammatory myopathies (IIM). The aim of our study is to evaluate the effectiveness and the safety of IvIg and define the possible profile of IIM patients candidate to IvIg treatment.we performed a retrospective study of IIM pts. treated with IvIg (2 g/kg/month). We collected demographic, epidemiological, laboratory and clinical data. Additionally, to evaluate the toxicity, the adverse events occurred during the treatment were collected.123 patients with IIM were included in the study. The main indications for the prescription of IvIg were muscle (83.7% of patients) and esophageal involvement (45.5% of patients). IvIg were started mainly for refractory disease. At the end of treatment (mean duration 14 months), muscular necrosis enzymes decreased significantly and dysphagia VAS decreased significantly (p 0.001), while MMT value increased (104.6 ± 24.2 vs. 127.0 ± 22.2 p 0.001). Ninety-six pts. (78%) responded to IvIg. They had a shorter disease duration (p 0.001), higher creatine kinase levels (p 0.001), and higher prevalence of myalgias at the baseline (p = 0.023) compared to non-responders. The presence of Raynaud's phenomenon (p = 0.023-odds ratio 0.28 [0.11-0.72]) and skin involvement (p = 0.004, odds ratio 0.18 [0.06-0.55]), were associated to a worse response. Adverse events were mostly mild and transitory.Despite their high cost, IvIg confirmed their effectiveness in refractory IIM pts., particularly in muscular and esophageal manifestations. Specific clinical characteristics at the baseline may identify the patients with higher probability of response to the treatment.

Objective The aim of our study was to investigate clinical and histopathological findings in adult DM patients positive for anti-Mi2 (anti-Mi2+) antibodies compared with DM patients negative for anti-Mi2 (anti-Mi2–). Methods Clinical data of adult DM patients, who fulfilled EULAR/ACR 2017 classification criteria, were gathered from electronic medical records of three tertiary Rheumatology Units. Histopathological study was carried out on 12 anti-Mi2+ and 14 anti-Mi2– muscle biopsies performed for diagnostic purpose. Nine biopsies from immune mediated necrotizing myopathy (IMNM) patients were used as control group. Results Twenty-two anti-Mi2+ DM [90.9% female, mean age 56.5 (15.7) years] were compared with 69 anti-Mi2– DM patients [71% female, mean age 52.4 (17) years]. Anti-Mi2+ patients presented higher levels of serum muscle enzymes than anti-Mi2– patients [median (IQR) creatine-kinase fold increment: 16 (7–37)vs 3.5 (1–9.9), P 0.05]. In addition, the endomysial macrophage score was similar between anti-Mi2+ and IMNM patients [mean 1.2 (0.9) vs 1.3 (0.5), P >0.05], whereas lower macrophage infiltration was found in anti-Mi2– DM [mean 0.4 (0.5), Conclusions Anti-Mi2+ patients represent a specific DM subset with high muscle damage. Histological hallmarks were a higher prevalence of myofiber necrosis, endomysial involvement and macrophage infiltrates at muscle biopsy.

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

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, &ldquo, real life&rdquo, study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

This study aims to assess the peripheral blood cell count &ldquo, signature&rdquo, of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer&ndash, Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden&rsquo, s Index (&minus, 0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.

Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.

We thank Dr Santos-Moreno et al 1 for their interest in our paper2 and for sharing their experience on telemedicine use in patients with rheumatoid arthritis (RA). We agree on the fact that a preliminary consultation is necessary to assess the willingness of the patients to be evaluated by telemedicine and, possibly, to explain them how the platform works. However, given the different setting in which we applied telemedicine—a connective tissue diseases (CTDs) outpatient clinic—our approach was slightly different. In fact, unlike inflammatory arthritis, in which disease flares are in most cases symptomatic and impacting on patients’ quality of life and functionality, CTDs like systemic lupus erythematosus (SLE) or systemic sclerosis may give rise to more insidious manifestations. In our …

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to 28 April 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48–69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.

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

The diagnostic assessment of patients with Interstitial Lung Disease (ILD) can be challenging due to the large number of possible causes. Moreover, the diagnostic approach can be limited by the severity of the disease, which may not allow invasive exams. To overcome this issue, the referral centers for ILD organized Multidisciplinary Teams (MDTs), including physicians and experts in complementary discipline, to discuss the management of doubtful cases of ILD. MDT is currently considered the gold standard for ILD diagnosis, but it is not often simple to organize and, furthermore, rheumatologists are still not always included. In fact, even if rheumatologic conditions represent a common cause of ILD, they are sometimes difficult to recognize, considering the variegated clinical features and their association with all possible radiographic patterns of ILD. The first objective of this review is to describe the clinical, laboratory, and instrumental tests that can drive a diagnosis toward a possible rheumatic disease. The secondary objective is to propose a set of first-line tests to perform in all patients in order to recognize any possible rheumatic conditions underlying ILD.

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD, This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), cofunded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

OBJECTIVES To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjogren's syndrome (SS). DESIGN A pilot therapeutic study. SETTING ENT Clinics, Universities of Milan and Pavia. STUDY POPULATION We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B). OUTCOMES MEASURES The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire. RESULTS The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P

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.

Objective: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. Methods: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. Results: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23–10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68–8.17]), and serum urate level (OR 1.31 [95% CI 1.06–1.62]). Conclusion: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. (Less)

Background: Clinical evolution and optimal management of IPAF are still undefined and need prospective assessment. Objectives: to define the characteristics and evolution of IPAF patients in a multidisciplinary setting. Methods: IPAF pts referring to multidisciplinary Rheumatology/Pneumology outpatient clinic. We excluded patients with diagnosis of Anti-synthetase Sd. Data were retrospectively collected. Results: we analyzed the first 25 pts (19 F, 76%, 6 M, 24%), with a median onset age of 67 years (IQR, 59-74) and follow-up of 32 months (IQR 22-69). ANA test was positive in 23 (92%) cases (cytoplasmic+ in 17:68%). Anti-ENA screen was + in 9: 36% pts. One pt was + for anti-PM-Scl, one for for anti-Mi2 and one for anti-Ku Ab. Pts had mainly a NSIP pattern (19, 76%, cases; with concomitant OP, in 3). Three patients had UIP-like and 3 OP pattern. The majority of patients (15, 60%) satysfied only the morphological and serological domains. Clinical domains satisfied were: arthritis (4) Raynaud’s ph. (5) palmar teleangectasias (2) mechanic’s hands (1) and Hikers feet (1). Clinical spectrum time course was variable in 5 pts: 3 pts developed arthritis after ILD, and 2 developed ILD respectively after arthritis and inflammatory miopathy. Three pts were admitted in ICU for Rapidly Progressive (RP) ILD and 2 died. All pts received low dose steroids in combination mainly with Azathioprine, Mycophenolate, Cyclosporin, Hydroxychloroquine. 92% of patients were alive at FU. Conclusions: A multidisciplinary approach is useful in the diagnosis and the management of IPAF. RP-ILD was common, prognosis of IPAF was highly variable.

Introduction The effectiveness of CD20 targeting in connective tissue diseases (CTD) with lung involvement is controversial. This paper aims to review the current evidence about rituximab (RTX) use in CTD-related interstitial lung disease (ILD). Methods We performed a systematic review of papers published between January 2009 and May 2019. We included clinical trials, case/control studies and cohort studies. We excluded letters, case reports, case series, reviews, and full articles when not in English. The selected studies listed as primary or secondary outcome a variation in pulmonary function tests or in the scores used to radiologically stage lung involvement, in CTD-related ILD patients after RTX. Results Out of 1206 potentially eligible articles, 24 papers were selected: 3 retrospectively described cohorts of patients with different CTD, 14 dealt with systemic sclerosis (SSc)-related ILD, 5 with idiopathic inflammatory myopathies (IIMs)-related ILD, and 2 with Sjogren's Syndrome-related ILD. A direct comparison of the selected studies was hampered by their heterogeneity for outcomes, follow-up duration, the severity of lung involvement, and clinical features of study populations. However, an overall agreement existed concerning the effectiveness of RTX in the stabilization of lung disease, with some studies reporting an improvement of functional parameters from baseline. IIM-related ILD appeared more responsive than other CTD-related ILD to CD20 targeting. Conclusion RTX is a promising therapeutic tool in CTD-related ILD. This systematic review remarks the unmet need of multicenter prospective studies aiming to evaluate the effectiveness of RTX with adequate sample size and study design.

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.

Background The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) is a virtual Network that aims to improve and standardize the quality of care offered to rCTDs patients in Europe, empower patients, share knowledge and expertise, enhance research, support efficient use of resources. ERN ReCONNET covers 10 rCTDs: APS, UCTD, Idiopathic Inflammatory myopathies, IgG4, MCTD, Systemic sclerosis, Relapsing Polychondritis, SLE, Sjogren and EDS. Objectives Identification of unmet needs in diagnosis, monitoring and management of rCTDs after literature review of existing clinical practice guidelines (CPGs). Methods After the review of existing CPGs, the most relevant unmet needs, both for clinicians and patients, were identified by discussion among the members of the network. Results A considerable number of unmet needs were identified. In particular, the lack of shared classification criteria, of evidence-based CPGs, validated tools for the assessment of treatment response and disease activity/damage are the major unmet needs especially for the rarest rCTDs. Transversal topics for all rCTDs that need to be addressed are the scarcity of EU/international randomised controlled trials, the identification of patient-reported outcomes and non-adherence to treatment, quality of life indicators, the need to develop composite disease activity scores for all rCTDs and specific (inter)national web-based registries. Patients highlighted the need of a more holistic approach to rCTDs, demanding more attention to pain, fatigue and psychological aspects related to the diseases and the promotion of an early diagnosis. Conclusion The identification of rCTDs unmet needs provided a very useful picture on future actions to be undertaken in order to provide a better care to patients. Many activities are ongoing towards these goals in ERN ReCONNET. These will be possible as a result of a EU collaboration among rCTDs stakeholders, the main added value of ERN ReCONNET. Acknowledgement Thanks to all ERN ReCONNET Steering Committe, Healthcare Providers, ePAGs and Team for huge support. Disclosure of Interests Diana Marinello: None declared, Simone Ticciati: None declared, Rosaria Talarico: None declared, Tobias Alexander: None declared, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Lorenzo Cavagna: None declared, Lorenzo Beretta: None declared, Benjamin Chaigne: None declared, Alain Cornet Grant/research support from: No direct financial grants from Pharmaceutical companies, but some grants accrued LUPUS EUROPE does, in the form of Grants or payment for attending advisory boards or providing patient views, Speakers bureau: I have been involved in GSK panels to provide patient perspective. However, the minor service fee obtained accrued to LUPUS EUROPE ratyher than the company, Nathalie Costedoat-Chalumeau: None declared, Rebecca Fischer-Betz Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Charissa Hermine Frank: None declared, Ilaria Galetti: None declared, Jurgen Grunert: None declared, vera guimaraes: None declared, Luca Iaccarino: None declared, Maarten Limper Consultant for: GSK, Roche and Thermofisher, Speakers bureau: GSK and Roche, Fransiska Malfait: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, lisa matthews: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, alain meyer: None declared, Simona Rednic: None declared, Vasco Romao: None declared, Carlo Alberto Scire: None declared, Vanessa Smith: None declared, Alberto Sulli: None declared, Farah Tamirou: None declared, Anna Viola Taulaigo: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Ana Vieira: None declared, Maurizio Cutolo: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB

Background: Macrovascular involvement and cardiovascular (CV) risk have not been sufficiently studied in patients with mixed connective tissue disease (MCTD). In particular, the gold standard assessment method of aortic stiffness carotid-femoral pulse wave velocity (cfPWV) (1) has never been evaluated in patients with this disease. Objectives: Aims of the present study were to examine cfPWV in MCTD and to evaluate its associations with MCTD associated parameters and traditional CV risk factors. Methods: cfPWV measurements were performed in 43 MCTD patients and 107 healthy controls. The difference between cfPWV in the two groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Association of cfPWV with MCTD associated organ involvement, routine laboratory parameters and immunoserological markers was also evaluated. Finally, relationship of cfPWV with medications and traditional CV risk factors was examined. Results: Adjusted statistical analyses for confounding factors showed significantly higher cfPWV values in MCTD patients in comparison to controls (padj Conclusion: To our knowledge, this is the first study to show that patients with MCTD have significantly higher aortic stiffness and thus CV risk in comparison to controls. Except the disease itself, age and blood pressure were the main predictors of cfPWV. References [1] Bortel LM Van, Laurent S, Boutouyrie P, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. [2] J Hypertens2012; 30: 445–448. Disclosure of interests: Konstantinos Triantafyllias: None declared, Michele De Blasi : None declared, Freya Lutgendorf: None declared, Lorenzo Cavagna: None declared, Marco Stortz: None declared, Julia Weinmann-Menke : None declared, Stavros Konstantinides : None declared, Peter Galle : None declared, andreas Schwarting Grant/research support from: GSK, Pfizer, abbVie, Novartis, Roche, Speakers bureau: GSK, Novartis

Background: Dysphagia represents a frequent and disabling symptom in patients with Idiopathic Inflammatory Myopathies (IIMs) and it has been recently included in the new ACR/EULAR classification criteria for IIMs. Despite the clinical relevance, dysphagia assessment in IIMs is not currently standardized and evaluation tools are highly variable between different centers. Functional Endoscopic Evaluation of Swallowing (FESS) is an exam that allows, by using nasal endoscopy, the direct evaluation of anatomic structures and swallowing abilities in different swallowing phase. In fact, FESS could help the identification of different problems leading to dysphagia occurrence and to related dysphagia problems. Thanks to these characteristics, FESS for ENT specialists is the gold standard technique for evaluating swallowing functions. However, no studies so far have investigated the role of FESS in the assessment of IIMs and we are completely lacking a semeiotic description of FESS findings in these patients. Objectives: To provide the first semeiotic description of swallowing alterations evidenced by FEES in a cohort of IIMs patients. Methods: We retrospectively reviewed the FEES findings of IIMs patients performed at our hospital. Results: We enrolled 19 patients with a diagnosis of IIMs (10 patients were positive for a myositis specific antibody), of these 16 (84%) reported symptomatic dysphagia. We divided patients into 3 groups based on levels of peripheral muscle strength. Six patients (32%) had no clinical sign of active muscle disease (MRC scale 5, median CK 51 mU/ml, IQR 35-235), 5 patients (26%) had a mild reduction in muscle strength (MRC scale 4, median CK 76, IQR 54-220) and 8 patients (42%) showed a moderate-severe reduction in muscle strength (MRC scale ≤3, media CK 1440, IQR 628-6180). The 67% of patients without muscle disease activity showed an impairment in the oral phase of swallowing for solids and the 33% for fluids; 33% had a reduction in the activation of the pharyngeal phase of swallowing for both fluids and solids; only 17% of patients showed any sign of penetration, aspiration or pharyngeal residue for both solids and fluids. In the group of patients with moderate muscle activity, 80% of patients showed impairment in the oral phase of swallowing for solids and 40% for fluids; 60% had a reduction in the activation of the pharyngeal phase of swallowing for solids while 40% for fluids; 40% of patients showed signs of penetration, aspiration or pharyngeal residue for both solids and fluids. Finally, in the group of patients with severe muscle disease activity, 88% of patients showed an impairment in the oral phase of swallowing for solids and 50% for fluids; 63% had a reduction in the activation of the pharyngeal phase of swallowing for solids while 50% for fluids; 75% of patients showed signs of penetration, aspiration or pharyngeal residue for both solids and fluids. The 15% of all patients (3 cases, 1 from each group of muscle activity) showed a dysfunction in the upper esophageal sphincter. Of note, 3 patients (15%; 1 with moderate and 2 with severe muscle disease activity) required nutrition through nasogastric tube. Conclusion: We showed that FESS study identified swallowing dysfunctions in both the oral and pharyngeal phases of swallowing. Swallowing dysfunctions were more prevalent in patients with greater muscle involvement; however, alterations were not rare also in patients with no clinical signs of muscle activity and, in particular, in the few patients without reported symptoms of dysphagia. FEES appears as a useful tool for the evaluation of dysphagia in IIMs. Reference [1] Brady S, Otolaryngol Clin North Am. 2013Dec;46(6):1009-22 Disclosure of Interests: Emiliano Marasco: None declared, Giulia Bertino: None declared, Ludovico De Stefano: None declared, Lorenzo Volpiano: None declared, Pietro Canzi: None declared, Marco Benazzo: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Lorenzo Cavagna: None declared

Background Interstitial Pneumonia with Autoimmune feature (IPAF) is a recently defined disease that includes Interstitial Lung Disease (ILD) patients with features of autoimmunity, not satisfying any of the established classification criteria for connective tissue diseases (CTD). Even if IPAF pateints share clinical and serological findings with CTD, we are unaware about the clinical evolution of IPAF pateints. Objectives To define the characteristics and evolution of IPAF patients in a multidisciplinary setting. Methods We selected patients with a diagnosis of IPAF referring to a multidisciplinary Rheumatology/Pneumology/Radiology team at our hospital. We excluded from the analysis patients positive for antisynthetase antibodies, as diagnosed with antisynthetase syndrome. Data were retrospectively collected from our hospital medical records. Results We analyzed 25 patients (19 females, 76%, 6 males, 24%), with a median onset age of 67 years (interquartile range, IQR, 59-74) and a follow-up of 32 months (IQR 22-69). ANA test was positive in 23 (92%) cases (fig 1), whereas cytoplasmic positivity was observed in 17 (68%). Anti-ENA screen was positive in 9 patients (36%) (7 [28%] anti-Ro52 and 2 [8%] anti-RNP). One patient (4%) was positive for anti-PM-Scl, 1 (4%) for anti-Mi2 and 1 (4%) for anti-Ku antibodies. These 2 latter antibodies are not included in the serological domain of IPAF. Patients had mainly a Non Specific Interstitial Pneumonia (NSIP) pattern (19 [76%]; fibrosing in 7 [28%], and with concomitant organizing pneumonia (OP) in 3 [12%]). Three (12%) patients had Usual Interstitial Pneumonia-like and 3 (12%) an OP pattern. The majority of patients (15 [60%]) satisfied only the morphological and serological domains. Clinical domains satisfied were: arthritis (4 [16%]), Raynaud’s phenomenon (5 [20%]), palmar telangiectasias (2 [8%]), mechanic’s hands (1 [4%]) and hiker’s feet (1 [4%]). We observed other findings not included in IPAF criteria but suggestive for CTDs, both clinical (inflammatory myopathy 3 [12%]; dry eye1 [4%]; sclerodactyly 1 [4%]), and instrumental (scleroderma pattern at naifold capillaroscopy 1 [4%]; dilated esophagus at barium X-rays 2 [8%]). Clinical spectrum time course was variable in 5 (20%) cases: 3 (12%) patients developed arthritis after ILD, and 2 (8%) developed ILD respectively after arthritis and inflammatory myopathy onset. Three (12%) patients were admitted to the Intensive Care Unit for Rapidly Progressive (RP) ILD and 2 died (respectively 2 months and 54 months after ILD onset), whereas the alive patient had 2 ICU admission for RP-ILD. Five (20%) patients, including the only 1 dismissed from ICU, needed home O2 therapy. Ongoing and previous therapies are reported in figure 2. Conclusion We showed that the prognosis of IPAF is highly variable, with patients experiencing RP ILD, other slow progressive worsening of respiratory functions and other a substantially stable disease. Furthermore, we showed other findings, laboratory, clinical and instrumental, that could help clinicians in a better identification and stratification of IPAF patients. As a matter of fact, at present, IPAF appears as a generic term including very different conditions that can be further differentiated according to clinical and serological data. References [1] Fischer A, et al. Eur Respir J 2015 [2] Scire CA, et al. Resp Med 2017 [3] Sambataro G, et al. Eur Resp Rev2018 [4] Cavagna L, et al. Eur Resp Rev2018 Disclosure of Interests Emiliano Marasco: None declared, Federica Meloni: None declared, Giovanni Zanframundo: None declared, Adele Valentini: None declared, Valentina Morandi: None declared, Veronica Codullo: None declared, Lorenzo Volpiano: None declared, Claudia La Carruba: None declared, Francesca Motta: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Lorenzo Cavagna: None declared

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

© 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.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sj&ouml, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p &lt, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Objective To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies. Methods Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard. Results For all tested GUGC definitions, the simple definition of “self-report of gout or urate-lowering therapy use” had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%). Conclusion A simple definition of “self-report of gout or urate-lowering therapy use” has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered.

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

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:Antisynthetase syndrome (ASSD) is an heterogeneous disease characterized by the occurrence of anti-synthetase antibodies (ARS) and the classic triad of arthritis, myositis and Interstitial Lung Disease (ILD). Pulmonary involvment bears an increased risk of life threatening events, being the main cause of mortality in these patients. No significant differences in mortality have been noticed among the different ARS specificities. However the role of extractable nuclear antigen antibodies on mortality in these patients is still matter of debate.Objectives:To asses the effect of anti-RO antibodies on clinical characteristics and mortality in a large italian single-center cohort of ASSD patients.Methods:Cohort study of outcome, clinical and laboratory characteristics, at baseline and at last follow-up, of 55 ASSD patients progressively enrolled and followed-up at our out-patient clinic. Survival was estimated with Kaplan-Meier function and comparison between frequencies of clinical characteristics was studied with Chi-square test.Results:We identified 30 anti-Ro+ (M:F=1:4) and 25 anti-Ro- (M:F=1.5:1) ASSD patients. No difference in the age of onset was observed (p value=0.83). Classic triad prevalence and evolution was similar between the two groups with only significant difference of ILD prevalence at last follow up, higher in anti-Ro+ patients group (p value=0.01). Overall mortality was of 13 subjects (23%) during the follow-up period (median 53 months, IQR 16-114). Despite the significantly higher pulmonary involvment in the anti-Ro+ group no difference between mortality in anti-Ro positive and negative groups was observed. Adjusting mortality to include disease-related events only did not provide any additional difference (p value=0.5) (Table 1). Survival curves of the two groups were not different at any time point (Log-rank test, p value 0.98) (Figure 1).Table 1.Clinical and Demographic Characteristics of the cohortASSDRo+Ro-P valuePZ (M:F)30 (6:24)25 (14:10)/Age (years) at disease onset (median, IQR)56 (43-69)54 (46-68)0.83Disease duration (months) (median, IQR)55 (23-112)52 (13-130)0.681Arhtritis at onset (%)22 (73)17 (68)0.664Arhtritis at last follow-up (%)26 (86)18 (72)0.175Myositis at onset (%)12(40)15 (60)1Myositis at last follow-up (%)19 (63)21 (84)0.086ILD at onset (%)20 (66)12 (48)0.162ILD at last follow-up (%)30(100)20 (80)0.01Complete form at onset (%)8 (26)4 (16)0.34Complete form at last follow-up (%)17 (56)13 (52)0.729Raynaud phenomenon (%)7 (23)8 (32)0.472Mechanic’s hands (%)12 (40)12 (48)0.551Death (%)7 (25)6 (24)0.953Disease related death (%)3 (42)4 (66)0.506Figure 1.Kaplan-meier curve of anti-Ro+ and anti-Ro – ASSD patients.Conclusion:The clinical spectrum and the time course of ASSD is not significantly affected by the presence of anti-Ro antibodies, althuough ILD seems to be more associated to anti-Ro antibodies. Despite higher prevalence ofILD in Ro positive group no difference in mortality was observed in respect to anti-Ro negative patients.References:[1]Cavagna L. Medicine (Baltimore) 2015 Aug;94(32):e1144[2]Marie I. Semin Arthritis Rheum. 2012 Jun;41(6):890-9Disclosure of Interests:None declared

Background:Nailfold Videocapillaroscopy (NVC) is an essential tool for the assessment of Raynaud’s Phenomenon (RP) among the Scleroderma Spectrum Disorders (SSDs). Recently, NVC abnormalities have been associated with a diagnosis of Idiopathic Inflammatory Myopathies (IIMs), independently of the presence of RP (1). Moreover, both SSDs and IIMs are commonly associated with Interstitial Lung Disease (ILD), which is the main cause of mortality in these conditions.Objectives:To verify whether NVC may allow a better diagnostic classification in a cohort of patients with ILD followed by pulmonologists.Methods:361 patients affected by ILD were prospectively enrolled in a 30-months observational study. All these patients were clinically evaluated by rheumatologists and pulmonologists together and performed general blood tests, autoantibody research, chest High-Resolution Computed Tomography and NVC. The latter was considered positive in the presence of avascular areas or giant capillaries, and also the presence of Bushy Capillaries (BCs) was recorded.Results:NVC was positive in 17.7% of ILD patients, and a third of these patients did not present RP. Patients with NVC abnormalities had a diagnosis of definite Connective Tissue Disease in 78.1% of cases. NVC resulted decisive in 25% of patients with a final diagnosis of Systemic Sclerosis according to the ACR/EULAR 2013 criteria. The presence of BCs and/or NVC+ in ILD patients with normal serum levels of muscular enzymes was associated with amyopathic IIM (BCs= OR 3.9, 95CI 1.05-14.38, p=0.04; NVC+= OR 5, 95CI 1.29-19.3 p=0.02; BCs and/or NVC+= OR 5.41 95CI 1.24-23.48 p=0.02), regardless the presence of RP.Conclusion:NVC proved to be a valid tool in the correct assessment of ILD patients secondary to SSDs and amyopathic IIMs. Therefore, it could be considered in the diagnostic evaluation of patients affected by ILD, regardless of the presence of RP.References:[1]Sebastiani M et al. Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and possible clinical associations: results of a multicenter International Study.J Rheumatol2019; 46: 279-284Table 1.Comparison between ILD patients with and without NVC positivity..ItemsNVC+ patientsNVC- patientspNumber64297Mean Age (±SD)61.4±13.367.8±9.80.001Female%65.649.10.01RP%68.717.1HRCT patterns%NSIP51.536.80.02OP3.18n.s.UIP-like31.1544.8n.s.DIP1.53.4n.s.LIP1.50.4n.s.Indeterminate10.96.7n.s.Final Diagnosis%SSDs45.31IIMs256.4Other CTDs6.213.5n.s.IPAF10.919.5n.s.IPF7.827.90.0007Legend:DIP: Desquamative Interstitial Pneumonia; HRCT: High Resolution Computed Tomography; IIMs: Idiopathic Inflammatory Myopathies, Poly/dermatomyositis, antisynthetase syndrome; IPAF: Interstitial Pneumonia with Autoimmune Features; IPF: Idiopathic Pulmonary Fibrosis; LIP: Lymphocytic Interstitial Pneumonia; NSIP: Nonspecific Interstitial Pneumonia; OP: Organising Pneumonia; RP: Raynaud’s Phenomenon; SSDs: Scleroderma Spectrum Disorders, Systemic Sclerosis + Mixed Connective Tissue Disease; UIP: Usual Interstitial Pneumonia.Disclosure of Interests:Gianluca Sambataro: None declared, Domenico Sambataro: None declared, Francesca Pignataro: None declared, Nicoletta Del Papa: None declared, Michele Colaci: None declared, Lorenzo Malatino: None declared, Alessandro Libra: None declared, Fabio Pino: None declared, Sebastiano Emanuele Torrisi Speakers bureau: Boehringer Ingelheim; F. Hoffmann-La Roche Ltd., Stefano Palmucci Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Delphi International Srl, and F. Hoffmann-La Roche Ltd., Lorenzo Cavagna: None declared, Carlo Vanchieri Grant/research support from: F. Hoffmann-La Roche Ltd., Consultant of: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini

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

Background:Interstitial lung disease (ILD), is common in patients with idiopathic inflammatory myopathies (IIM) and strongly impact on patients’ morbidity and mortality. Patients with anti-aminoacyl-transfer RNA-synthetases (anti-ARS) antibodies are associated with an increased risk of ILD.Objectives:Defining the radiological characteristics of IIM patients, with special focus on serological groups, through qualitative, semiquantitative and quantitative analysis of lung CT.Methods:This was a prospective study conducted from 2016 to 2019. Ninety-eight IIM patients (35 men, 63 women) were included. Myositis specific autoantibodies (MSA) were assessed with Myositis Prophyle III (Euroimmune, Lubeck).Each patient had a baseline CT; the total score of Warrick (WS) was obtained at semiquantitative analysis. The radiological scores ILD% (interstitial lung disease %) and PVRS% (pulmonary vascular related structure) were the result of quantitative analysis in 61 patients (CALIPER). Pulmonary function tests (PFTs) included TLC%, FVC% and DLCO% (65 patients). The analysis was conducted in the whole group and divided in subgroups based on their MSA pattern: in particular anti-ARS (Group 1) and patients negative to MSA (Group 2) were analysed.Results:Positive correlations between ILD% and PVRS% (Rho=0.916; ρ=0.000), WS and ILD% (Rho=0.663; ρ=0.000) and WS and PVRS% (Rho=0.637; ρThe most relevant inverse correlations were found between ILD% and DLCO% (Rho=-0.590; ρ=0.001), PVRS% and DLCO% (Rho=-0.549; ρStatistically significant higher values of WS, ILD% and PVRS% were found in Group 1 (WS=15, ILD%=11 and PVRS%=3.5), compared to Group 2 (WS=2.5, ILD%=0.84 and PVRS%=2.2). NSIP pattern resulted dominant represented in the two groups (80% Group 1, 75% Group 2). No statistically significant differences of DLCO%, FVC% and TLCO% were found.Conclusion:The inverse correlations between the radiological scores and the functional data TLC% and DLCO% (ρDisclosure of Interests:None declared

Background:ASSD is characterized by antisynthetase antibodies (ARS) and the triad arthritis/myositis/Interstitial Lung Disease (ILD). ASSD and systemic sclerosis (SSc) may share features, like Raynaud’s phenomenon (RP), capillaroscopic alterations, and also some SSc specific autoantibodies.Objectives:To evaluate the characteristics of ASSD + for anticentromere antibodies (ACA).Methods:Retrospective analysis of clinical and laboratory characteristics of ACA + ASSD. Patients were identified in an established international cohort, randomly matched 1:1 for sex, age, disease duration and ARS positivity with a group of ACA - ASSD.Results:18 ACA + ASSD (15 females, 83%, 15 anti-Jo1, 2 anti-PL7, 1 anti-PL12 ARS) patients were identified. In comparison to ACA - group, no differences were observed in disease clinical presentation and evolution. Though, 9 ACA + patients (50%) satisfied the ACR/EULAR 2013 classification criteria for SSc and only 1 in ACA - group (p=0.007) (Table 1).An incomplete ASSD (lack of at least one triad finding) was observed in 15 patients in both ACA + and – group (p=1). Among these patients, 13 ACA + and 11 ACA – developed de-novo triad finding during disease course (p=0.651). In ACA + group, a de-novo arthritis was observed in 4 patients (vs 1, p=0.565), a de-novo myositis in 8 (vs 5, p=1), and a de-novo ILD in 7 (vs 10, p=1). The prevalence of complete forms was similar between ACA + and – group at both disease onset (3 vs 3, 17%, p=1) and last follow-up, (10 vs 11, 56% vs 61%, p=1). Of note, only 1 patient (6%) for each group died (p=1).Conclusion:The clinical spectrum time course of ACA+ and - ASSD is similar, even when ACA + patients could be classified as SSc. By considering the high prevalence of arthritis and myositis we observed, we suggest that ACA+ patients with arthritis and myositis, should be tested for ARS antibodies even when an ASSD is not clearly suspected.References:[1]Mirrakhimov AE. Curr Med Chem 2015;22:1963–75[2]Cavagna L. J Clin Med 2019;8:E2013[3]Sebastiani M. J Rheum 2019:46:279-84[4]van den Hoogen F. Ann Rheum Dis 2013;72:1747-55Table 1.Patients characteristics. IQR, interquartile range; ILD, interstitial Lung Disease; SSc, systemic sclerosisACA+ (18)ACA - (18)pAge (years) at disease onset (median, IQR)47 (37-63)47 (39-63)0.834Disease duration (months) (median, IQR)81 (62-169)77 (58-165)0.486anti Ro52antibody (%)12(67)11 (61)1Arthritis onset10 (56)13 (72)0.489Arthritis last follow-up (%)14 (78)14 (78%)1Myositis onset (%)7 (39)11 (61)0.318Myositis last follow-up (%)15 (83)16 (89)1ILD onset (%)9 (50)6 (33)0.5ILD last follow-up (%)16 (89)16 (89)1Complete form onset (%)3 (17)3 (17)1Complete form last follow-up (%)10 (56)11 (61)1Raynaud phenomenon (%)13 (72)9 (50)0.305Mechanic’s hands (%)6 (33)7 (38)1Teleangectasias (%)2 (11)0 (0)0.486Cutaneous sclerosis (%)510.177Acral ulcers (%)1 (6)0 (0)1Scleroderma pattern at NVC8 (44)7 (39)1Pulmonary arterial hypertension (%)3 (17)2 (11)12013 ACR/EULAR SSc classification criteria9 (50)1 (6)0.007Disclosure of Interests:Giovanni Zanframundo: None declared, Gianluca Sambataro: None declared, Veronica Codullo: None declared, Alessandro Biglia: None declared, Emanuele Bozzalla Cassione: None declared, Elena Bravi: None declared, 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, Marco Fornaro: None declared, Konstantinos Triantafyllias: None declared, Alberto Pesci: None declared, Paola Tomietto: None declared, Øyvind Molberg: None declared, Salvatore Scarpato: None declared, Reinhard Voll: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Carlomaurizio Montecucco: None declared, Lorenzo Cavagna: None declared

Background:Dermatomyositis (DM) shows a wide clinical spectrum that seems to be different based on the type of autoantibody status. Furthermore, less is known regarding to the histopathology of different serological subsets of DMObjectives:The aim of our study was to investigate clinical and histopathological hallmarks in adult DM patients positive for anti-Mi2 (Mi2+) antibody compared to DM patients negative for anti-Mi2 (Mi2-)Methods:All clinical data of adult DM patients admitted in three tertiary Rheumatology Units, who fulfilled EULAR/ACR 2017 classification criteria1, were included in this study. Overlap syndrome and antisynthetase syndrome were exclusion criterion. Serum samples were tested in the local reference laboratories using line immunoassays methods for Myositis specific and associated antibodies. Histopathological study was carried out from muscle biopsies performed for diagnostic purpose in outpatient clinic of Bari (Italy) University. Quantitative analysis was performed for myofiber and capillary features, whereas semi-quantitative analysis (score from 0 to 3) was performed for inflammatory cells infiltrate, both at endomysial and perimysial sitesResults:A total of 95 DM patients, followed for a median (IQR) follow-up of 28 (9-85) months, were analyzed. Of these, 23 (24.2%) patients (87% female, mean age at onset 55.4±16.2 years) were anti-Mi2+, while 72 (75.8%) patients were Mi2- (72.2% female, mean age at onset 55.2±17 years). All Mi2+ patients showed muscle involvement. Moreover, Mi2+ DM showed higher levels of serum creatine kinase (CK) at onset compared to Mi2- (CK (IQR): 2649 UI/l (1130-6000) vs 575 UI/l (164-1617), pConclusion:Mi2+ patients represent a specific DM subset with higher muscle damage, sarcoplasmic MAC deposits and endomysial macrophages infiltration as histological hallmarksReferences:[1]Ann Rheum Dis. 2017 Dec;76(12):1955-1964Disclosure of Interests:Marco Fornaro: None declared, Francesco Girolamo: None declared, Lorenzo Cavagna: None declared, Franco Franceschini: None declared, margherita giannini: None declared, Giovanni Zanframundo: None declared, Micaela Fredi: None declared, Marilin Tampoia: None declared, Angela Amati: None declared, Luigi Serlenga: None declared, Anna Lia: None declared, Liala Moschetti: None declared, Dario Dabbicco: None declared, Laura Coladonato: None declared, 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