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Background:Prevalence of anti-neutrophil cytoplasmic antibody (ANCA) in patient with idiopathic pulmonary fibrosis (IPF) ranges from 1 to 35%, mainly anti-MPO. The presence of ANCA positivity seems to be a poorer prognostic factor in patient with IPF, and some of these patients will develop clinical vasculitis (7-23%).Unfortunately, the majority of the available studies on this topic are retrospective and the real natural history of the disease remains poorly understood.Objectives:Aim of the study was to investigate the clinical, serological and radiologic features of patients with interstitial lung disease (ILD) and positivity for anti-MPO, and to evaluate the survival of this population compared with IPF patients.Methods:We retrospectively analysed 30 patients with ILD and anti-MPO antibodies, without diagnosis of vasculitis, from 3 different rheumatology-pulmonology Italian Center.For each patient, clinical, radiologic and serological data were evaluated. Treatments were also collected, both immunosuppressants or antifibrotic agents.Finally, survival of ILD-MPO patients and of 90 unselected idiopathic pulmonary fibrosis (IPF) patients was compared.Results:Thirty patients were enrolled in the study (see table for the characteristics of the patients).Fibrosing pneumonia was described in 73.3% of patients (usual interstitial pneumonia [UIP] in 19 patients), and 10 patients (33.3%) received antifibrotic drugs, all with UIP pattern. Of interest, 7 patients were treated with immunosuppressants (azathioprine, cyclophosphamide, mycophenolate mofetil), independently by the ILD pattern and 21 (70%) low dosage of steroids.After a median period of 23.5 months (range 11-111), 7 patients developed an ANCA associated vasculitis, while other 3 developed other rheumatic diseases.Finally, when compared with IPF, ILD-MPO patients had a better survival (81.2%±0.9 vs 54.7±0.7 for ILD-MPO and IPF, respectively; p=0.045)Conclusion:ILD positive for anti-MPO antibodies are still a not definite condition. We need larger population to identify possible markers for the evolution in an ANCA associated vasculitis, to define the prognosis of disease and the better therapeutic approach.References: :[1]Mohammad AJ, et al. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017;44:1458-67Table.Serological, clinical and radiological features of anti-MPO + interstitial lung diseaseNumber30Males/female15/15Median age (years + IQR)68 (17)Median follow-up (months + IQR)39.5 (61)Smoke36.70%ILD pattern Usual interstitial pneumonia63.30% Nonspecific interstitial pneumonia16.70% Hipersensitivity pneumonia10% Other fibrosing pneumonia10%Median FVC (% + IQR)83 (23)Median DLCO (% + IQR)53 (28)Clinical features Raynaud’s phenomenon7.70% Sicca syndrome0 Arthralgias20% Arthritis3.40%Serology Antinuclear antibodies30.80% Anti-extractable nuclear antibodies (ENA)8% Anti-SSA4% Rheumatoid factor21.40%Therapy Immusuppressants23.30% Anti-fibrotic drugs33.30%Disclosure of Interests:None declared

Background:High Resolution Computed Tomography (HRCT) is the gold standard to evaluate Interstitial Lung Diseases (ILDs) extent and severity. Quantitative Computed Tomography (QCT) is a promising tool as it provides an operator-independent assessment of ILD extent. Even if there are emerging data on QCT in Systemic Sclerosis (SSc), its correlation with disease activity (DA) has not been yet studied.Objectives:To evaluate the correlation between QCT score and DA in an Italian cohort of SSc patients.Methods:A multicentric, observational study was conducted in three Italian rheumatological centers.Adult SSc patients classified according to the ACR/EULAR 2013 criteria [1] were assessed with pulmonary function tests, HRCT and for DA. CT images were analyzed quantitatively with the densitometric radiomic data obtained through a free open software – Mean lung attenuation (MLA), Standard Deviation (SD), Kurtosis, Skewness and Lung volume. DA assessment was conducted according to EUSTAR index [2]: a score ≥2.5 was considered indicative of high disease activity.Age below 18 and pregnancy were considered exclusion criteria. We used Student’s T test to evaluate the means of the parameters, Pearson’s r test for correlations, receiver operating characteristics curve to define the cutoff values of the significant details, and linear regression with collinearity test to define the role of the details. P value Results:Sixty patients were enrolled (male 8, female 52), with mean age 53.2 years (SD 15.6) and mean disease duration 5.3 years (SD 4.2). QCT indexes distribution was different in high DA vs low DA SSc patients. In particular mean lung attenuation (MLA, -834.7 vs -812.1, p =0.03), standard deviation (95.9 vs 102, p =0.03), skewness (2.2 vs 1.7, P =0.006) and kurtosis (5.5 vs 3.3, p =0.009) of the parenchymal lung and skewness (3.1 vs 2.8, p =0.03) of the whole lung were statistically different. DA correlates with MLA (r =0.28, p =0.003), standard deviation (r =0.21, p =0.02), skewness (r =-0.32, p =0.001) and kurtosis (r =-0.29, p =0.001) of the parenchymal lung and MLA (r =0.25, p =0.006), skewness (R =-0.27, p =0.003), kurtosis (r =-0.21, P =0.02) of the whole lung. The skewness of the parenchymal lung was the QCT index with the best performance in identifying high DA SSc patients (cutoff value ≤1.85; area under the curve 0.74, p =0.005; sensitivity 79.5%, specificity 68.7% accuracy 76.6%).Conclusion:To our knowledge, this is the first study which correlate the QCT score with DA in SSc patients. Our results suggest that QCT can identify SSc patients with high DA score. This could open a scenario of new applications as an operator-independent contribution in DA scores with a potential role in clinical practice. Further studies are needed to confirm the data and to better identify the most suitable parameters for the purpose.References:[1]Van den Hoogen F, et al. 2013 classification criteria for Systemic Sclerosis: and American college of rheumatology / European league against rheumatism collaborative initiative. Ann Rheum Dis 2013;72:1747-1755.[2]Valentini G, et al. The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index. Ann Rheum Dis 2017;76:270-276.Disclosure of Interests:None declared

Background:COVID-19 pandemic is a global emergency which may overlap on the clinical and radiological scenario of ILD in SSc. In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 superinfection from a progression of SSc-ILD.Objectives:The aim of our study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia.Methods:22 international readers were included and divided in the radiologist group (RAD) and non-radiologist group (nRAD). The RAD group included non-chest RAD and chest-RAD. A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study.Results:Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT parameters most frequently associated with SSc-ILD. The CT parameters most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p Conclusion:The CT differential diagnosis between COVID-19 Pneumonia and SSc-ILD is possible and may be fostered in practice by the use of a radiological score. In the case where an overlap of both diseases is suspected, the presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.References:[1]Orlandi M, Landini N, Bruni C, et al. Infection or autoimmunity? The clinical challenge of interstitial lung disease in systemic sclerosis during COVID 19 pandemic. J Rheumatol. 2020 Dec 1: jrheum.200832[2]Simpson S, Kay FU, Abbara S, et al. Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA [published online ahead of print, 2020 Apr 28]. J Thorac Imaging. 2020;10.1097/RTI.0000000000000524.[3]Cheng C, Li C, Zhao T, et al. COVID-19 with rheumatic diseases: a report of 5 cases. Clin Rheumatol. 2020;39(7):2025-2029.[4]Mariano RZ, Rio APTD, Reis F. Covid-19 overlapping with systemic sclerosis. Rev Soc Bras Med Trop. 2020 Sep 21;53:e20200450.Disclosure of Interests:None declared

Background:Lung involvement remains the main cause of morbidity and mortality in SSc. In 1 year clinical trials to assess lung involvement, FVC is usually evaluated and changes while the DLCO usually remains unchanged. In longer term observational studies, the DLCO often changes more than the FVC.Objectives:To examine, through a systematic literature review(SLR) and meta-analysis, whether DLCO%pred or FVC%pred (both to be designated solely as DLCO and FVC henceforth), responds more in assessing SSC interstitial lung disease in first year and longer term follow-up(FU).Methods:PubMed, EMBASE and COCHRANE databases were searched for english language articles on SSc published between 1960 and 31st October 2018. Any study that made reference to FVC and DLCO evaluation in SSc and reported their changes over the years was included. Reviewers double extracted articles to obtain agreement on>95% of pre-defined critical outcomes:DLCO and FVC at baseline,1 yr of FU and at the last assessment interstitial lung disease by HRCT of the lungs study design, duration of FU. Other variables included demographics. In all cases I^2 test for heterogeneity was used and a result from 75 to 100% was considered as high heterogeneity.A random effects meta-analysis was used. Differences in the degree of change in FVC and DLCO were tested with t-test without compensation for repeated analysis.Results:1870 articles were screened for eligibility and 21 were selected for the SLR and meta-analysis The analysis used 21 studies to evaluate changes of FVC and DCLO at 1 yr of FU. Only 5 studies were eligible to evaluate changes during longer FU (24.7 months(SD=20.4)). Heterogeneity was high at baseline and FU, (at 1 yr and >1 yr),both for the 21 studies at 1 yr (FVC:I^2 99.74%, 99.78%; DLCO: I^2=99.91%99.92%) and the 5 studies at > 1 year (FVC:I^2 92.86%;DLCO:I^2=99.54%), diminishing the confidence in the results. Table 1 gives the results of the random effects meta-analysis both for 21 and for the 5 studies evaluated. Regarding changes over 1 yr in the 21 studies, change of mean FVC was 2.7 (78.8vs81.5) while change in mean DLCO was 3.07(SE 8.20) (59.7vs 63.4). Considering the 5 studies during long term follow up, change in mean FVC was 2.0(7.36)(81.1vs83.1), and change in mean DLCO was -0.96 (16.95)(55.6vs54.7). Comparing the 1 yr changes in the 21 studies, change in mean FVC was 2.7(5.2)and change in mean DLCO was 3.07(8.2); difference in changes was not statistically significant (p=0.5791). During long term FU (24.7 months), change in mean FVC was 2.0(7.36)and change in mean DLCO was -0.96 (16.95); difference in changes was not statistically different (p=0.4698).Table 1.Results from Random Effect Meta-Analysis21 studies5 studiesFVC % predmean valueSEDLCO % pred mean valueSEFVC % predmean valueSEDLCO % pred mean valueSEBASELINE78.83.4359.75.5281.15.6855.611.591 YEAR FOLLOW UP81.53.8563.46.07---->1 YEAR FOLLOW UP----83.44.6854.712.37Conclusion:Our data are limited by great heterogeneity. Given this limitation, this SLR and meta-analysis indicates that there is no difference in the changes comparing FVC to DLCO at either 1 yr or during longer term follow-up. Corroboration of these results in prospective studies and in registries to make clear, comparable comparisons will be needed.Disclosure of Interests:Silvia Bellando Randone: None declared, Eleonora Cappellini: None declared, Letizia Nidiaci: None declared, Gemma Lepri: None declared, Maria Grazia Lazzaroni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gianluca Bagnato: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company)

Background:Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation and follow-up of the microvascular changes that mark the course of Systemic Sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, namely the cumulative Number of microhaEMOrrhages and microthromboses, is a good indicator of the steady state level and over time changes of disease activity (DA) in SSc (1-3).Objectives:To verify whether a high NEMO score, and then a high level of active microvascular derangement in the fingers may be predictive of the subsequent development of ischemic digital ulcers (IDUs).Methods:The NEMO score was assessed at baseline (T0) in 98 patients affected by SSc, according to the ACR-EULAR criteria. Out of them, 90 were females, 48 had the limited form and 50 the diffuse cutaneous variant of SSc. ACA and anti-Scl-70 antibodies were positive in 42 and 50 patients, respectively. The NVC pattern was early, active and late in 16, 42 and 40 patients, respectively.Afterwards, patients were closely followed up for 3 years, and the appearance of new IDUs was recorded in any time of the follow up.The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated, by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the development of IDUs.Results:During the follow up, 38 out of 98 patients developed one or more DUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (CI 11.0-21.5), and 4.5 (CI 4.0-6.0), respectively, pConclusion:NEMO score is not only a valid tool to assess the level of DA in the course of SSc, but this NVC parameter could also be used as a good predictor of the future development of IDUs in patients with this disease.References:[1]Sambataro et al. Arthritis Res Ther 2014;16:462-69[2]Andracco et al. Arthritis Res Ther 2017;19:133-41[3]Pignataro et al. Arthritis Res Ther. 2019;21(1):258Disclosure of Interests:Nicoletta Del Papa: None declared, Francesca Pignataro: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Gabriele Valentini Grant/research support from: BMS, MSD, NOVARTIS, LILLY, PFIZER, ABBVIE, CELGENE, Claudio Vitali: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

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:Systemic sclerosis (SSc) in a chronic autoimmune disease characterized by endothelial dysfunction and diffuse microangiopathy, leading to tissue ischemia and inducing fibrosis of skin and visceral organs. Furthermore, it was demonstrated the impairment of wall elasticity of large-medium vessels, such as aorta and its branches (1). SSc-related microangiopathy of vasa vasorum of the aortic wall could also be supposed. However no data on this hypothesis are available in literature.SSc microangiopathy may be easily studied at the nailfold by means of videocapillaroscopy. Indeed, capillaroscopic findings are representative of the microvascular damage caused by SSc troughout the body.Objectives:we aimed to investigate the presence of aortic root dilation, classical sign of aortic wall damage, in a cohort of SSc patients, and to correlate these findings with the capillaroscopic patterns (early, active, and late, according to Cutolo’s classification (2)).Methods:we recruited 125 SSc patients (M/F: 14/111, mean age 55+/-12.7 years, median disease duration 11 years) in 3 Rheumatology Centres in Sicily, Italy, from January to December 2019.Transthoracic echocardiogram with aortic root diameter measurement was carried out in all patients. Moreover, videocapillaroscopy with identification of early, active, or late SSc patterns was performed in the whole case series. Patients with early SSc pattern formed the subgroup 1, while those with the active or late patterns (both characterized by the reduction of capillary density) the subgroup 2.Results:we identified 8 (6.4%) SSc patients with aortic root dilation (diameter > 35 mm). Their age and their frequencies of cardiovascular risk factors were similar to the whole series. Moreover, videocapillaroscopy showed 62 (49.6%) early, 47 (37.6%) active, and 16 (12.8%) late SSc patterns.Aortic root dilation was observed in only one patient in the subgroup 1 (1/62, 1.6%), and in 7 cases of the subgroup 2 (7/63, 11.1%); p=0.03.Conclusion:in this multicentre study, we found that aortic root dilation is significantly associated with the reduction of capillary density at nailfold capillaroscopy (active or late SSc patterns). On the basis of these findings, we might argue that SSc-related microangiopathy of vasa vasorum could contribute to aortic wall damage, at least in a subset of SSc patients.References:[1]Bartoloni E, Pucci G, Cannarile F, Battista F, Alunno A, Giuliani M, Cafaro G, Gerli R, Schillaci G. Central hemodynamics and arterial stiffness in systemic sclerosis. Hypertension 2016; 68:1504-1511. 2.Cutolo M, Matucci-Cerinic M. Nailfold capillaroscopy and classification criteria for systemic sclerosis. Clin Exp Rheumatol 2007; 25:663-665.Disclosure of Interests:Michele Colaci: None declared, Ylenia Dal Bosco: None declared, Claudia Schinocca: None declared, Maria Letizia Aprile: None declared, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Ilenia De Andres: None declared, Alessandra Azzurra Russo: None declared, Gianluca Sambataro: None declared, Domenico Sambataro: None declared, Lorenzo Malatino: 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:systemic sclerosis (SSc) in a chronic autoimmune disease characterized by endothelial dysfunction, diffuse microangiopathy, and fibrosis of skin and visceral organs. Typical cardiac involvement may includes microvascular ischemia, contraction band necrosis, and patchy fibrosis, leading mainly to arrythmias and conduction defects, diastolic dysfunction, or right ventricular failure (secondary to pulmonary arterial hypertension) [1]. Valvular diseases are poorly described and generally not considered a typical sign of SSc [2-4].Objectives:we aimed to describe valvular alterations in a multicentre cohort of SSc patients.Methods:we consecutively recruited 118 SSc patients (M/F: 14/104, mean age 56.7±12.4 years, median disease duration 10 years, limited/diffuse skin subsets: 95/23, anti-centromere/anti-Scl70/others autoantibodies: 35/37/46) in 3 Rheumatology Centres in Sicily, Italy, from January to December 2019.Considering the cardiovascular risk factors, 40 (34%) patients were smokers, 7 (6%) diabetics, 12 (10%) showed hypercholesterolemia, 38 (32%) arterial hypertension, while none was obese. Transthoracic echocardiogram was carried out in all patients during their follow-up.Results:valvular abnormalities were as follow: mitral valve: insufficiency 85 (72%) cases - mild in 77/85, stenosis 2 (2%) - mild in 25/28, sclerosis/tickening 36 (30%), and calcification 9 (8%) patients; aortic valve: insufficiency 28 (24%), stenosis 4 (3%), sclerosis 29 (25%), and calcification 7 (6%) patients; tricuspid valve: insufficiency 91 (77%) cases, no cases of stenosis, sclerosis 5 (4%), and calcification 1 (1%) patients; pulmonary valve: insufficiency in 13 (11%) patients.As expected, tricuspid insufficiency (TI) was associated with pulmonary arterial hypertension (PAH) (moderate TI in 20% of patients with every TI and PAH vs. 4% of patients with TI without PAH, p=0.019).Aortic sclerosis (AS) was associated with the presence of arthritis (AS in 35% of patients with arthritis vs. 16% of patients without, p=0.029).No association was found with age, gender, disease duration, skin subset, autoantibodies, capillaroscopic patterns, presence of digital ulcers, lung, renal, or digestive involvements.Conclusion:in this multicentre SSc cohort study, we found that cardiac valve alterations are very common, even though generally not clinically relevant. The presence of PAH was associated with more severe TI. Finally, AS was associated with arthritis that could be considered sign of chronic inflammatory state, which is often linked with accelerated atherosclerosis and remodeling process of aortic valve [5].References:[1]Lambova S. Cardiac manifestations in systemic sclerosis. World J Cardiol 2014; 6:993-1005.[2]D’Angelo W, Fries JF, Masi AT, Shulman LE. Pathologic observations in systemic sclerosis (scleroderma).A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969; 46:428-440.[3]Kazzam E, Caidahl K, Hallgren R, et al. Mitral regurgitation and diastolic flow profile in systemic sclerosis. Int J Cardiol 1990; 29:357-363[4]Wranicz J, Zielińska M, Cygankiewicz I, et al. Early cardiovascular involvement in patients with systemic sclerosis (SSc). Med Sci Monit. 2002; 8:CR78-82.[5]Coté N, Mahmut A, Bosse Y, et al. Inflammation is associated with remodeling of calcific aortic valve disease. Inflammation 2013; 36:573-581.Disclosure of Interests:Michele Colaci: None declared, Claudia Schinocca: None declared, Ylenia Dal Bosco: None declared, Maria Letizia Aprile: None declared, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Ilenia De Andres: None declared, Alessandra Azzurra Russo: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Lorenzo Malatino: None declared

Background Autologous haematopoietic stem cell transplantation (AHSCT) has shown to be an effective therapeutic option to prolong survival of patients (pts) suffering from rapidly progressive diffuse cutaneous systemic sclerosis (rp-dcSSc). Objectives This study was aimed at retrospectively comparing the disease outcome of pts with rp-dcSSc treated with AHSCT to that of age-, and sex-matched group of clinically similar pts selected from our cohort and treated with conventional therapies. Methods Eighteen pts (5 M, 13F; median age 40, 20-62 yrs) that underwent AHSCT were compared to 36 age- and sex-matched pts (10 M, 26 F; median age 44, 19-62 yrs), all of them suffering from rp-dcSSc. At the starting evaluation point the two groups were also exactly comparable for disease-duration and clinical findings, in term of skin involvement (mRSS), DLCO as % of predicted value and disease activity (ESSG scoring system). AHSCT was performed by mobilisation with cyclophosphamide (CTX) and G-CSF, selection of CD34+ cells and conditioning regimen with CTX and rabbit ATG. Twenty-five pts in the control group received 6 monthly pulses of intravenous CTX (750mg/m 2 ), 11 received steroids, DMARDS (Methotrexate and Azathioprine) and vasoactive therapies (noCTX). The clinical course in AHSCT and control groups was evaluated from time 0 to 5 years by using Kaplan Meyer survival curves, computing the Hazard Ratio (HR) and Chi square distribution. Results Results of the survival curve analysis of different groups, expressed as HR (95%CI) are reported in the table. Conclusions This retrospective study confirms that AHSCT approach is more effective to induce a longer survival (p=0.0004), and shows that is also able to more rapidly reduce the mRss (p Disclosure of Interest None declared

Background Aromatase inhibitors (AI) are widely used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. The onset of musculoskeletal symptoms related to AI therapy limits the treatment compliance. Objectives To evaluate the incidence and the clinical presentation of musculoskeletal syndromes and the prevalence of autoantibodies during AI therapy. Methods We enrolled 49 consecutive postmenopausal patients with non-metastatic breast cancer treated with third generation AI for at least three months (AI+ group) and 10 postmenopausal controls with breast cancer in adjuvant therapy but not treated with AI (AI- group). The two groups were evaluated with a rheumatological examination (tender and swollen joint count, tender points, CDAI), with PRO-CLARA, FACIT-fatigue and HAQ questionnaires and ANA, ENA screen and ACPA dosage. ANA were assayed in indirect immunofluorescence on Hep-2 cells using as a cut-off a dilution of 1:80; ENA screen and ACPA were assayed with ELISA commercial kits. Results The mean ages were 62.6±9 years for AI+ group and 58±11.8 years for AI- group (p=0.2, U=140.5). In AI+ group, 27 (55%) patients exhibited at least one tender joint and 15 (30%) patients exhibited at least one swollen joint. In AI- group, two patients exhibited at least one tender joint and one patient exhibited at least one swollen joint. 22% of AI+ group patients and 20% of AI- group patients showed more than 11 tender points (TP). When patients with more than 11 TP positivity were excluded from the analysis, tender joint count was more higher in AI+ group (p=0.037). Differences between AI+ and AI- groups regarding PRO-CLARA, FACIT-fatigue, HAQ and CDAI were summarized in Tab. 1. In AI+ group, PRO-CLARA values correlates with FACIT-fatigue values (R=-0.59, p Conclusions In this preliminary study, we demonstrated a higher prevalence of arthralgia/arthritis in AI+ group than in AI- group. No significant difference in tender points count was detected between the two groups. In AI+ group, higher values of PRO-CLARA, HAQ and CDAI than those of AI- group were showed. A higher rate of ANA positivity was demonstrated in AI+ group. These results support the hypothesis of a possible role of an immune system dysregulation in the development of musculoskeletal syndromes during AI therapy. The expertise of a rheumatologist could help patients with estrogen receptor-positive breast cancer treated with AI to improve their quality of life and to ensure a greater compliance to AI therapy. References Lonning PE, et al. Endocr Relat Cancer. 2013 Jun 24;20(4):R183-201. Niravath P. Ann Oncol. 2013 Jun;24(6):1443-9. Shanmugam VK, et al. Breast Cancer Res Treat. 2012 Jan;131(2):699-708. Disclosure of Interest None declared

Background As in other autoimmune diseases, even in systemic sclerosis (SSc) the assessment of disease activity (DA) is essential to detect the window of opportunity for a successful treatment. The so far proposed composite indexes for DA assessment imply a long and expensive patient9s work up. Nailfold videocapillaroscopy (NVC) is commonly regarded as an instrument useful for SSc diagnosis and subsetting, and the presence of megacapillaries is considered the hallmark of an active disease. Objectives Since microvascular endothelial activation represents the key mechanism of the disease progression, the present study was specifically designed to evaluate whether the presence and number of micro-hemorrhages (MH) and micro-thrombosis (MT) in NVC could be considered potential predictors of DA in SSc. Methods The study population was constituted by 107 patients with SSc, 50 with the diffuse cutaneous (dc) and 57 with the limited cutaneous (lc) variants of the disease. European Scleroderma Study Group (ESSG) index (Valentini G, et al. Ann Rheum Dis 2001; 60:592-8)) was assumed as the gold standard for DA assessment, and patients having a score ≥3.5 classified as active. NVC was performed at the same time of DA evaluation. The sum of MH and MT detected by NVC examination in 2° to 5° fingers of both hands (named as NEMO score) was then obtained. Results The enrolled patients were predominantly females (97/107), had a mean age of 55.8 yrs. (range 18-84 yrs.) and mean disease duration of 6.1 yrs. (range 0-30 yrs.). According with the defined cut-off value of ESSG index, 32/107 patients were active (14 with dcSSc and 18 with lcSSc). NEMO values were significantly correlated with ESSG index scores (r=0.56, p 0.001), but not with patients9 age and disease duration. Considering the other components of ESSG index, NEMO score was significantly higher in patients having scleredema (p Conclusions The presence of MH and MT appears to be a good predictor for DA in patients with SSc, and enhances the role of NVC as a quick and easy technique to select the patients potentially candidate to be more aggressively treated. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3167