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Objectives To assess the clinical profile of patients with anti-polymyositis/Scl (PM/Scl) antibodies in a cohort of Spanish patients with systemic sclerosis. Methods From the Spanish Scleroderma Study Group database, we selected patients in whom PM/Scl antibodies had been tested. We compared demographic, clinical, laboratory, and survival data between patients with and without PM/Scl antibodies. Results Seventy-two of 947 patients (7.6%) tested positive for PM/Scl antibodies. Patients with PM/Scl antibodies presented initially with more puffy fingers and arthralgias but less Raynaud phenomenon. Regarding cumulative manifestations, myositis and arthritis were more prevalent in patients with PM/Scl antibodies, as well as pulmonary fibrosis. On the contrary, patients with PM/Scl antibodies had less pulmonary hypertension. No difference in terms of survival at 5 and 10 years was noticed between the 2 groups. Conclusions In Spanish systemic sclerosis patients, PM/Scl antibodies are associated with a distinct clinical profile. However, PM/Scl antibodies did not influence survival.

Biomarcadores; Disfunción endotelial; Células progenitoras Biomarcadors; Disfunció endotelial; Cèl·lules progenitores Biomarkers; Endothelial dysfunction; Progenitor cells Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b−) and activated (CD31+CD42b−CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH. This research was funded by grants PI12/00510, PI15/00582 and PI18/00960 from the Institute of Health Carlos III (ISCiii), Spain, co-funded by the European Union (ERDF/ESF); the Catalan Society of Respiratory Medicine (SOCAP); and the Fundación Contra la Hipertensión Pulmonar (FCHP). OTC is the former recipient of a Marie Curie Post-Doctoral Fellowship Award BIOTRACK-IDIBAPS, and the current recipient of a Miguel Servet contract from ISCiii (CP17/00114).

OBJECTIVES: Left ventricular diastolic dysfunction (LVDD) remains poorly studied in Systemic Sclerosis (SSc). To determine the prevalence and to define factors associated with LVDD and survival in a large cohort of patients with SSc. METHODS: An observational study was conducted with data from the multicentre Spanish Scleroderma Registry (RESCLE) to identify factors associated with LVDD and estimate survival. RESULTS: Out of 1517 patients, 319 (21.0%) had LVDD. The subset of sine scleroderma SSc was associated to LVDD (14.7% vs. 10.6%, p =0.048), whilst diffuse cutaneous SSc was more prevalent in non-LVDD (16.0 % vs. 21.2%, p =0.041). Multivariable analysis identified that LVDD was associated with older age at diagnosis of SSc (OR 1.05; 95% CI 1.04 to 1.06), longer time from diagnosis (OR 1.04; 95% CI 1.03 to 1.06), presence of telangiectasia (OR 1.42; 95% CI 1.08 to 1.88), treatment with calcium channel blockers (CCB) (OR 1.51; 95% CI 1.16 to 1.96), and inversely related to angiotensin-converting-enzyme inhibitors (ACEi) use (OR 0.59; 95% CI 0.44 to 0.80). SSc patients with LVDD had increased mortality (23.8 vs. 17.4%, p =0.010) and shortened survival from the first SSc symptom (p =0.040), even though it was not found to be an independent risk factor for death. CONCLUSIONS: LVDD is relatively common in SSc patients, and it is associated with worst prognosis, older age, longer time from diagnosis of SSc, presence of telangiectasia and vasodilator treatment.

Objective To analyse the prevalence, the clinical characteristics, the overall survival and the event-free survival (EFS) of SSc patients who express anti-U11/U12 RNP (RNPC-3) antibodies. Methods A total of 447 SSc patients from Barcelona (n = 286) and Milan (n = 161) were selected. All samples were tested using a particle-based multi-analyte technology. We compared anti-RNPC-3 positive and negative patients. Epidemiological, clinical features and survival were analysed. End-stage lung disease (ESLD) was defined if the patient developed forced vital capacity Results Nineteen of 447 (4.3%) patients had anti-RNPC-3 antibodies and interstitial lung disease (ILD) was more frequent (11, 57.9% vs 144, 33.6%, P =0.030) in individuals with anti-RNPC-3 antibodies. More patients reached ESLD in the positive group (7, 36.8% vs 74, 17.3%, P = 0.006), and a higher use of non-glucocorticoid immunosuppressive drugs was observed (11, 57.9% vs 130, 30.4%, P = 0.012). Anti-RNPC-3 positive patients had lower EFS, both in the total cohort (log-rank P =0.001), as well as in patients with ILD (log-rank P = 0.002). In multivariate Cox regression analysis, diffuse cutaneous subtype, age at onset, the presence of ILD or pulmonary arterial hypertension and the expression of anti-RNPC-3 positivity or anti-topo I were independently associated with worse EFS. Conclusion The presence of anti-RNPC-3 was associated with higher frequency of ILD and either ESLD or death. These data suggest anti-RNPC-3 is an independent poor prognosis antibody in SSc, especially if ILD is also present.

Introduction Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment. Methods We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not. Results Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [−0.1 (−4.8, 4.69), P = 0.988] or in SRC [0.7 (−2.2, 3.7), P = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s.d.) 7.6 (5.8) years vs 2.9 (5.3); P = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P Conclusion There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC.

System sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. In this study, we obtained DNA methylation and expression profiles of CD4+ T cells from 48 SSc patients and 16 healthy controls. Consequently, we identified 9112 and 3929 differentially methylated CpGs positions (DMPs) and differentially expressed genes (DEGs) respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing promoter capture Hi-C data, we confirmed that 212 CD4+ T cel specific pairs of DMP-DEG physically interact involving CTCF. Finally, utilizing SSc GWAS data, we identified four important SSc-associated susceptibility loci, TNIP1 (rs3792783), GSDMB (rs9303277), IL12RB1 (rs2305743) and CSK (rs1378942), that physically interact with DMP-DEG pairs cg17239269-ANXA6, cg19458020-CCR7, cg10808810-JUND and cg11062629-ULK3 respectively. Overall, our study reveals a solid link between genetic, epigenetic and transcriptional deregulation in CD4+ T cells of SSc patients, providing a novel integrated view of SSc pathogenic determinants.

Objective. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with anti-topoisomerase (ATA) whereas limited cutaneous (lcSSc) and sine scleroderma (ssSSc) are mainly associated with anti-centromere antibody (ACA). Serodiscordant patients were defined as lcSSc subjects with ATA, dcSSc with ACA, and ssSSc with ATA. The aim of the present study was to compare the clinical manifestations and prognosis between serodiscordant patients and their counterparts (those with lcSSc with ACA, dcSSc with ATA and ssSSc with ACA, respectively). Methods. From the Spanish Scleroderma Registry we selected those patients for whom skin involvement (dcSSc, lcSSc or ssSSc) was detailed at baseline and last visit and ACA and ATA had been determined. Demographic, clinical characteristics, and survival data were compared according to the antibody status. Results. The whole cohort comprised 901 patients and six mutually exclusive groups were defined: lcSScACA in 511 (57%) patients, lcSScATA group in 87 (10%), dcSScATA group in 172 (19%), dcSScACA group in 21 (2%), ssSScACA group in 92 (10%), and ssSScATA group in 18 (2%) patients, respectively. Interstitial lung disease (ILD) and severe ILD were more frequent in patients with dcSScATA than in those with dcSScACA. Conversely, the prevalence of isolated pulmonary hypertension (without ILD) was higher in those with dcSScACA (15% vs. 2%; p=0.018). No differences were found regarding survival when comparing serodiscordant patients with the seroconcordants patients. Conclusion. In our cohort, the prevalence of serodiscordant SSc patients was low. They differed from their counterparts in some clinical manifestations. The management of patients with SSc should be guided by both serology and cutaneous subtype.

Objective Lung transplantation (LT) has been proposed as a treatment for advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH) associated to systemic sclerosis (SSc) but few studies have been reported. The aim of this study was to describe the clinical features, complications and survival of a single-center cohort of patients with SSc that underwent LT and to compare their survival with a group of non-SSc transplanted patients. Methods Fifteen patients with SSc were transplanted between May 2005 and April 2015. Standard international criteria were used to determine eligibility for LT. The severity of gastroesophageal involvement was not considered as a major contraindication if symptoms were under control. Results Eight (53.3%) patients had diffuse cutaneous SSc. Eleven (73%) underwent bilateral LT. The main indication for LT was ILD, with or associated PH in 4 cases. Acute cellular rejection and infections were the most frequent complications. Functional lung tests tended to keep stable after transplantation. Median survival was 2.4 years (Q1–Q3: 0.7–3.7 years). We did not find differences in survival between patients transplanted with SSc versus those transplanted due to non-SSc ILD or PH. SSc complications were scarce with no patient developing PH after LT. Conclusions LT was an effective treatment for advanced ILD and/or PH associated to SSc in our study. Gastroesophageal reflux was not a limitation for LT in SSc in this study. Complications and survival did not differ from non-SSc patients undergoing LT.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Objectives According to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated. Methods The characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression. Results 1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria ( p = 0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1–47.2). Conclusions The classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment.

Emerging data have shown an increased risk of malignancy among patients diagnosed with systemic sclerosis (SSc) so identification of risk factors linking both disorders might have prognostic implications. The aim of this study was to assess the clinical and treatment-related risk factors for cancer in a single-center cohort of patients with SSc.Demographic, clinical, capillaroscopic, immunological and treatment-related data from 432 consecutive SSc patients were retrospectively analyzed. Variables that reached significant association in the univariate analysis were entered into a logistic regression in order to identify independent risk factors for cancer.Malignancy was diagnosed in 53 patients (12.2%). Fifty-eight neoplasms were identified, among which breast (n=15), lung (n=10) and hematologic (n=9) malignancies were the most prevalent. In 19 patients the diagnosis of both scleroderma and tumour was made in3years apart. Cancer significantly decreased the probability of survival (OR=2.61; 95%CI 1.46-4.69; p=0.001). No association with age, sex, smoking, cutaneous subset or RNA polymerase-III antibodies was found. However, risk of cancer was directly associated with the presence of anti-PM/Scl antibodies (OR=3.90; 95%CI 1.31-11.61; p=0.014), and inversely related to aspirin use (OR=0.33; 95%CI 0.12-0.90; p=0.031), which remained as independent risk factors for cancer on multivariate analysis.PM/Scl antibodies seem to be associated with a higher risk of cancer in scleroderma. In contrast, the use of aspirin is related to a lower risk of cancer in our series. More studies are needed to ascertain the role of anti PM/Scl antibodies and aspirin in the development of malignancy among patients with SSc.

Resumen Introduccion La enfermedad pulmonar intersticial (EPI) es una de las principales causas de muerte en los pacientes con esclerosis sistemica (ES). En este estudio se investigaron biomarcadores en el aire exhalado (AE) y en el condensado de aire exhalado (CAE) y se analizo su posible papel como factores pronostico de la EPI en pacientes con ES. Metodos Se analizo prospectivamente la fraccion exhalada de oxido nitrico (FeNO) y el monoxido de carbono exhalado (COe) en AE, y se determinaron los valores de pH, nitritos, nitratos e interleucina-6 en CAE, en 35 pacientes con ES. La tomografia computarizada de alta resolucion (TACAR) toracica mostro signos de EPI en 12 pacientes, no estando presentes en los 23 restantes. En el momento de la inclusion se determinaron los biomarcadores en el AE y en el CAE, y durante los 4 anos de seguimiento se efectuaron anualmente pruebas de funcion respiratoria. Resultados No se observaron diferencias entre grupos en los valores iniciales de los diferentes biomarcadores. En todos los pacientes examinados los valores disminuidos de pH en CAE se asociaron con una reduccion en la capacidad de difusion de monoxido de carbono (DLCO) durante el seguimiento. Valores disminuidos de FeNO se correlacionaron con una menor capacidad vital forzada (FVC) inicial y a los 4 anos, asi como con una reduccion de FVC y DLCO durante el seguimiento. En los pacientes con EPI los valores mas altos de COe se correlacionaron con FVC mas disminuidas al inicio. En el conjunto de la cohorte se identifico una menor supervivencia libre de progresion en los pacientes con un pH en CAE inferior a 7,88 y en los que presentaban un FeNO inferior a 10,75 ppb (Log Rank: p = 0,03 y p Conclusiones Los biomarcadores en el AE y en el CAE son utiles para detectar pacientes con una mayor probabilidad de presentar un deterioro de la funcion pulmonar durante el seguimiento de la enfermedad.

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15 years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points > 65 years-old), male gender (+1 point), lcSSc subset (−1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart (+1 point) and renal involvement (+2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p = .189), intermediate risk (26.5% vs. 25.5%, p = .911) and high risk (47.8% vs. 59%, p = .316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p = .530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.

The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p

Background Systemic Sclerosis (SSc) is an autoimmune desease that is characterized by progressive and severe fibrosis with cutaneous and visceral involvement, fibroproliferative vasculopathy and alterations of cellular and humoral immunity, very heterogenous from the clinical and immunological point of view. There are many types of antibodies related to the disease that are used in the diagnosis and characterization. Antibodies anti-Ku and anti-Ro52 have been found, although they are not specific to the disease, that could play an important role in the prognosis and clinical expression. Objectives To evaluate the clinical pattern and prognosis of SSc patients who carry antibodies Anti-Ku and Anti-Ro52. Methods A retrospective, multicentric study of SSc patients included in the Spanish Registry of Scleroderma (RESCLE). Clinical, demographic, prevalence, serological, and survival data were analyzed Results A total of 401 samples were analyzed for anti-Ku with 12 positive results (3%). For anti-R052, 1724 sampled were analyzed with 246 positive results (14%). It is observed, from the multivariant analysis, that patients with anti-Ro52 presented, in higher frequency, an association with Sicca syndrome (p Conclusion As opposed to finding SSc specific antinbodies such as anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA), the presence of anti-Ku or anti-Ro52 is not conclusive of any distinctive clinical profile. References [1] Mehra S., et al. Autoantibodies in systemic sclerosis. Autoinmunity Reviews 2013; 12:340-354. [2] Stern E., Denton C. The Pathogenesis of systemic Sclerosis. Rheum Dis Clin North Am 2015; 41(3):367-82. [3] Cavazzana I., et al. A subset of systemic sclerosis but not of systemic lupus erythematosus is defined by isolated anti-Ku autoantibodies. Clin Exp Rheumatology 2013; 31:118-21. [4] Iniesta N.; et al. Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis. Clin Exp Rheumatology 2017; 35(suppl. 106)S00-S00. Disclosure of Interests None declared

Objectives To describe the efficacy of intravenous immunoglobulin (IVIG) therapy in different organic conditions of Systemic Sclerosis (SSc). Methods Retrospective multicenter observational study that enrolled patients with SSc treated with IVIG. We collected epidemiological data, SSc complications, treatments and functional tests. Regarding IVIG treatment we recorded the reason to use, number of cycles, and the clinical efficacy at the end of the last IVIG cycle were collected at investigator’s discretion. For the comparison of variables, the Chi-square, Fisher’s F test and the T test was used. Results 41 patients (83% women) were recruited, with a mean age of 58 ± 18.2 years old. The age of diagnosis was 48 ± 8 years old. The diffuse cutaneous SSc was the most frequent in the sample (61%) and 24/41 had Overlap syndrome (49% myositis). Regarding the different SSc complications in treated patients the most frequent were digestive involvement, arthritis and interstitial lung disease (78%, 73%, and 63% respectively). 12% of patients developed cancer and 25% died during the follow-up. The most frequent indication IVIG was myositis (51%) followed by cutaneous (17%). The mean of cycles was 10. 37% of patients had previously undergone treatment with biological therapy, being RTX the most used therapy. 80% of patients had a history of use with corticosteroid therapy. When evaluating the degree of skin involvement (mRSS) patients showed a significant improvement of -2.89 ± 5.2(p Conclusion Our results suggest that IVIG can be useful for the management of some conditions in specific profiles of patients with SSc. Prospective studies and randomized clinical trials are necessary to establish the efficacy and safety of IVIG to treat the different conditions of SSc. Disclosure of Interests Jose Luis TANDAIPAN JAIME: None declared, Alfredo Guillen del Castillo : None declared, Carmen Pilar Simeon-Aznar: None declared, Patricia Carreira: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Jose M Pego-Reigosa: None declared, Rosario Garcia de Vicuna Grant/research support from: Abbvie, BMS, Lilly, MSD, Novartis, Roche, Consultant for: Biogen, BMS, Mylan, Pfizer, Sanofi and Sandoz, Speakers bureau: BMS, Pfizer, Lilly, Sandoz, Anna Pros: None declared, Carlos De la Puente Bujidos: None declared, Vera Ortiz-Santamaria Speakers bureau: GSK, Roche, Pfizer, MSD, Belen Atienza-Mateo: None declared, J Lluch Pons : None declared, Manuel Rubio-Rivas: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND

Background Scleroderma or systemic sclerosis (SSc) is a systemic, chronic autoimmune disease characterized by great clinical heterogeneity. In recent years, studies have proven that there is a relationship between SSc and neoplasia. SSc is associated with an increased risk of certain types of cancer, particularly lung, liver, hematological, non-melanoma skin and urothelial cancer. Despite this increasement, the relative risk of developing cancer is still low in these patients. In the literature, neoplasms have been described in 3-11% of patients with SSc. Objectives Our objective is to analyze the epidemiological, clinical and analytical characteristics previously described as possibly linked to the development of a cancer in patients with systemic sclerosis (SSc) in the Vall d’Hebron Hospital cohort. Methods We analyzed 583 patients in the Vall d’Hebron Hospital cohort of SSc. The inclusion criteria were age > 18 years and the diagnosis of SSc limited, diffuse and SSc sine scleroderma. The different variables were analyzed by univariate statistical analysis with SPSS v21. Results We included 521 patients with diagnosis from January 1985 to August 2016. 88.7% were women, with an average age of 53. 94 patients were diagnosed with neoplasia. The analyzed variables and their statistical significance and the types of cancer developed by our cohort patients are shown in Fig 1. Conclusion In the analyzed cohort, a slow pattern in capillaroscopy, positivity for Pm/Scl and the use of ARBs is associated with the development of neoplasia in patients with SSc. It has an inverse association the positivity of Scl70 (ATA I), the active pattern in capillaroscopy and the use of azathioprine and CCBs. In our cohort 94 patients with SSc have developed cancer. The most prevalent types of cancer were breast cancer, hematologic malignancies and lung cancer, as shown in the literature. References [1] Onishi A, Sugiyama D, Kumagai S, Morinobu A. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum 2013; 65: 1913–21. [2] Bernal-Bello D, de Tena JG, Guillen-del Castillo A, et al. Novel risk factors related to cancer in scleroderma. Autoimmun Rev 2017. Disclosure of Interests None declared

Background Systemic sclerosis (SSc) is a systemic autoimmune disease with extremely heterogeneous clinical features and unknown etiology, although numerous studies suggest a relationship with environmental and occupational factors. So far there is little information on whether toxic substances can play a relevant role in its phenotypic expression (1). Objectives To analyze in a cohort of patients with SSc the proportion of patients exposed to toxic and their correlation with epidemiologic, clinical and serological data. Methods A survey was conducted aimed at the knowledge of the working life of patients from six centers belonging to the Spanish Scleroderma Registry (RESCLE), categorizing them in six groups: no potential exposure to toxic substances, potential exposure to silica, to hydrocarbons, to organic solvents, to mixed toxics (silica and/or hydrocarbons and/or organic solvents) and to another toxics. In all patients 87 epidemiological, clinical and analytical variables included in the registry were analyzed, carrying out a comparative study between groups. Results 225 SSc patients were selected. Of these, 81 patients (36%) had worked in professions with potential risk of toxic exposure, 64 women out of the 227 included (28%) and 17 men out of the 28 included (60%). The toxic agent most frequently involved was silica in 29 patients (35.8%), followed by hydrocarbons in 21 (25.9%), mixture of toxic substances in 21 other patients (25.9%), organic solvents in 4 patients (4.9%) and other toxic in 6 cases (7.4%). Toxic exposure was associated with a lower risk of being female (OR 0.15, p Conclusion In our cohort of 225 patients with SSc, 60% of male patients and 28% of women worked in a profession with a potential risk of toxic exposure. In this preliminary study, important differences were observed in the probability of a different phenotypic expression of the SSc according to the history of occupational exposure to toxins. Studies with a larger number of patients are needed to establish these associations in a solid way. References [1] Marie I, et al. Environmental risk factors of systemic sclerosis. Semin Immunopathol. 2015Sep;37(5):463-73. Disclosure of Interests None declared

Background: Systemic sclerosis (SSc) is a systemic disease that may affect many organs; among them, cardiac involvement. The prevalence of cardiac involvement in SSc varies depending on the sensitivity of the methods used for its detection. Indirect evidence suggests that subclinical cardiac involvement may eventually occur in the vast majority of patients with SSc. Early detection and monitoring of myocardial involvement are integral to SSc management, as cardiovascular involvement is known to be a poor prognostic indicator when present Objectives: To describe myocardial perfusion abnormalities and potentially associated coronary arteries lesions using non-invasive imaging techniques in a group of patients with SSc and suggestive symptoms of myocardial involvement (symptomatic) in comparison with a control group of patients with SSc without cardiac symptoms Methods: A retrospective observational study was performed including a total of 61 patients diagnosed with SSc, 52 symptomatic, with dyspnea and/or chest pain (57.98 ± 12.3 years, 45 women) and 9 asymptomatic controls (50.2±15.21 years, 8 women). All patients underwent a post-stress (treadmill or pharmacological) myocardic perfusion gated-SPECT, a cold-induced stress SPECT, that were compared to a rest SPECT (to assess ischemia and/or necrosis), as well as a cardiac CT-angiography (to asses significant coronary arteries lesions, considering stenosis of more than 50%) Results: Twenty-one out of the 52 symptomatic patients (50%) showed myocardial perfusion defects in the stress-rest SPECT: 13 (25%) showed ischemia, 13 (25%) fibrosis/necrosis, and 5 (9.6%) ischemia and necrosis. In the cold-induced SPECT, 17 patients (32.7%) had myocardial perfusion abnormalities: 10 (19.2%) showed ischemia, 13 (25%) fibrosis/necrosis and 6 (11.5%) ischemia and necrosis. In the other hand, of the 9 asymptomatic patients only 1 (11%) had ischemia and necrosis in the stress-rest SPECT, being only positive for necrosis in the cold-induced SPECT images. In the cardiac CT-angiography, 7/52 patients (13.4%) showed significant coronary lesions, 4 (57.2%) of them with perfusion defects in the SPECT images, and 3 (42.8%) without significant perfusion alterations Of the 9 asymptomatic patients, 1 (11%) had significant coronary lesions, being the same patient who presented perfusion defects in myocardial SPECT images Conclusion: The gated-SPECT is a sensitive tool for detecting myocardial perfusion alterations, normally with no associated significant coronary lesions, suggesting microvascular abnormalities. In this cohort, myocardial perfusion abnormalities were detected in 50% of symptomatic patients, whereas in only 11% of non-symptomatic patients References [1] Fernandez-Codina A, Simeon-Aznar CP2, Pinal-Fernandez I, Rodriguez-Palomares J, Pizzi MN, Hidalgo CE, Guillen-Del Castillo A, Prado-Galbarro FJ, Sarria-Santamera A, Fonollosa-Pla V, Vilardell-Tarres M. Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival. Rheumatol Int. 2017 Jan;37(1):75-84. doi: 10.1007/s00296-015-3382-2. Epub 2015 Oct 25. [2] Rangarajan V, Matiasz R, Freed BH. Cardiac complications of systemic sclerosis and management: recent progress. Curr Opin Rheumatol. 2017 Nov;29(6):574-584. doi: 10.1097/BOR. Disclosure of Interests: None declared

Background The prevalence of myopathy in systemic sclerosis (SSc) or scleroderma patients varies from 5% to 81% depending on the diagnostic criteria used to define the muscle involvement. The histopathological characteristics found in these patients and their correlation with the clinical features and autoantibody profile has not been fully characterized. Objectives To characterize the muscle involvement and histopathology findings in patients with SSc. Methods This retrospective cross-sectional study included all patients from Scleroderma Cohort of Vall d’Hebron General and Hospital Clinic de Barcelona with muscle biopsies available for review performed at the Muscle Research Unit of Hospital Clinic de Barcelona from May 2004 to November 2018. Muscle biopsies were performed, for weakness or raised CK and/or aldolase. Histological sections were independently evaluated by two myopathology experts looking for inflammation in the endomisium, perimisium and perivascular areas. The presence of necrosis, regeneration, fibrosis, neurogenic atrophy, and fiber type grouping as well as perifascicular atrophy were also recorded. Based on the autoantibody profiles patients were classified into five groups, “Scl70”, “PM/Scl”, “centromere”, “U1-RNP”, and “nucleolar and centromer IFI ANA pattern without specificity for anti-Scl70 or anticentromer”. Demographic and clinical data were obtained by chart review. Results 42 subjects were included, 33 (78,6%) of them were women. Considering the immunological profile 12 had Scl70, 12 PM/Scl, 5 anticentromere, 2 U1RNP, and 11 had ANA pattern without specificity for anti-Scl70 or anticentromer. Most of patients (90.5%) were Caucasians, 2 (4.8%) were Hispanic, and 2 of other ethnic background. The mean age at the onset of SSc was 42.1 (SD 2.5) years and at the muscular symptoms 50.7 (SD 2.1) years, respectively. Twenty-two (52.4%) patients presented with high CK level (mean level of 1316 ± 353.8 U/L; normal value ≥200 U/L) whereas 38 (90.5%) exhibited high aldolase level (mean 19 ± 2.53 U/L, normal value Among the pathological features, 28 (66.7%) biopsies had fibrosis. Neurogenic atrophy was detected in 4 (9.5%) and fiber type grouping was present in 9 (21.4%) muscle biopsies. In near half of the muscle biopsies (45.2%) inflammatory infiltrate was present. Compared to other patients, those positive for PM/Scl had more perivascular (75%), endomysial (50%) and perimisial inflammation (75%) and perifascicular atrophy (42%) (all p Conclusion In our cohort of SSc patients with muscle involvement, two main histopathological patterns were found, fibrosis and inflammation. Almost half patients presented with elevated aldolase with normal CK levels. The muscle disease heterogeneity suggests that a variety of pathologic mechanisms play a role in the scleroderma associated myopathy but those patients with histopathological inflammatory features deserve to be treated with immunosuppressive therapy. References [1] Arthritis Care Res (Hoboken). 2015; 67: 1416-25 [2] Ther Adv Musculoskelet Dis. 2017; 9: 3–10. [3] Arthritis Res Ther. 2014; 16: R111. Disclosure of Interests None declared

Background Carotid Doppler-ultrasound is useful for the detection of subclinical atheromatosis(1), and also for the evaluation of hemodynamic characteristics of carotid arteries(2). Objectives The aim of this study is to evaluate the hemodynamic parameters of carotid arteries and its relation with vascular related Systemic Sclerosis (SSc) complications and subclinical atheromatosis. Methods 157 patients with SSc of the cohort of Vall d’Hebron Hospital were included according to the ACR/EULAR 2013 criteria and LeRoy classification. The left and right common carotid arteries (CCA), bulb and internal carotid arteries (ICA) were scanned using Doppler ultrasound for the detection of plaques and for the measurement of the Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Pulsatility Index (PI), Resistance Index (RI) and Systole/Diastole ratio (S/D), using the software incorporated in GE Healthcare’s Vivid I equipment. Results 157 patients were included, 132 women (84.1%), the mean age was 56 years old (range 20-83) and the mean of years of disease evolution was 19 years (range 3-57). 64.2% were SSc limited subset, 20.9% SSc diffuse subset, 9.5% SSc sine scleroderma and 4.7% early SSc subset. 49.3% had digital ulcers, 41.9% had interstitial lung disease and 14.2% had pulmonary hypertension. There were no statistically significant differences in hemodynamic parameters in relation to Raynaud’s phenomenon, digital ulcers or pulmonary hypertension. Seventy-five patients (47.7%) had carotid plaques. Patients with plaques had lower CCA PSV (66.8cm/s vs 76.7cm/s, p Ratio ICA PSV/CCA PSV was calculated, without showing significant differences in the presence of plaques or vascular manifestations of the SSc. The PSV greater than 120m/s, as an isolated measure, did not show statistically significant differences related to the presence of plaques. The PSV greater than 150 showed statistically significant differences (p Conclusion In our study we have not found relation between carotid hemodynamic parameters and microvascular related SSc complications such as Raynaud’s phenomenon, the presence of digital ulcers or pulmonary hypertension. Patients with SSc and atheromatous disease have a characteristic carotid hemodynamic profile consisting in lower PSV and EDV, and higher PI and RI, both at CCA and at ICA. The presence of increased PI and RI in patients with plaques, could suggest a primary damage of the vascular wall in patients with SSc. More studies are needed to determine if these data are the cause or a consequence of the presence of plaques. In our study the PSV greater than 150 cm/s isolated shows a high specificity for the presence of plaques. References [1] Sanz Perez I. et al. Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts, quantification of coronary calcium and carotid ultrasonography. Autoimmun Rev. 2018;17(9):900–5. [2] Staub D. et al. Prediction of cardiovascular morbidity and mortality: Comparison of the internal carotid artery resistive index with the common carotid artery intima-media thickness. Stroke. 2006;37(3):800–5. Disclosure of Interests None declared

Background Scleroderma Renal Crisis (SRC) is a serious complication of Systemic Sclerosis (SSc). Nowadays, it seems that there is a reduction in its prevalence and mortality1. Objectives To evaluate the characteristics of patients with SRC in a large cohort of SSc pacients. To investigate predictors of SRC, and epidemiologic differences over time. Methods 1933 patients were collected in ongoing registry of Spanish SSc pacients – RESCLE. We did descriptive study and epidemiologic analysis. Results Out of 1933 SSc, 43 (2.2%) developed SRC. Univariate analysis showed significant differences of SRC vs. non-SRC cases: SSc subtypes: diffuse cutaneous SSc (dcSSc), 72% vs. 19%; limited cutaneous SSc (lcSSc), 26% vs. 61%. Demographics: Female gender, 77% vs. 89%; time from SSc onset to SSc diagnosis, 3.0±8.0 vs. 6.6±9.5 years; arterial hypertension (HT), 56% vs. 32%. 1st manifestation: Raynaud’s phenomenon (RP), 68% vs. 82%. Clinical manifestations: RP, 88% vs. 96%; digital ulcers, 70% vs. 38%; arthritis, 45% vs. 20%; myositis, 30% vs. 13%; joint contractures, 45% vs. 18%; intestinal involvement, 24% vs. 11%; malabsorption, 24% vs. 7%; interstitial lung disease 58% vs. 41%; pulmonary HT, 56% vs. 29%; pericardial effusion, 28% vs. 7.4%; pericarditis, 24% vs. 8.3%; ischemic cardiopathy, 31% vs. 12%; diastolic dysfunction, 67% vs. 34%. Capillaroscopy: active pattern 77% vs. 33%. Immunological data: anti-Topoisomerase I, 39% vs. 20%; anti-centromere, 15% vs. 49%; anti-RNApol III, 45% vs. 11%. Prognosis: Overall mortality, 56% vs. 18%; SSc-related mortality, 83% vs. 49%. Survival at 5, 10, 20, and 30 years was 73% vs. 96%, 56% vs. 92%, 28% vs. 80%, and 28% vs. 67%, respectively. Treatment: ACEI use, 35% vs. 14%, corticoid use, 51% vs. 25%. Multivariate analysis: dsSSc subtype, RR 22.68 (5.81-88.51) p Conclusion In RESCLE cohort, SRC predominated in dcSSc patients, and it was associated to intestinal malabsorption, and an active pattern by capillaroscopy. SRC showed a very poor prognosis. Finally, we evidenced a decreasing prevalence of SRC over time in our cohort. Reference [1] Turk M, et al. The Frequency of Scleroderma Renal Crisis over Time: A Metaanalysis. J Rheumatol 2016; 43: 1350. Disclosure of Interests None declared

Objective.Monotherapy is an option as first-line therapy for pulmonary arterial hypertension (PAH). However, combination therapy is a beneficial alternative. Our objective was to evaluate the efficacy of monotherapy versus combination therapy in patients with systemic sclerosis (SSc)–associated PAH.Methods.All patients with SSc-associated PAH from the Spanish Scleroderma Registry (RESCLE) were reviewed. Patients were split into 3 groups: monotherapy versus sequential combination versus upfront combination therapy. The primary endpoint was death from any cause at 1, 3, and 5 years from PAH diagnosis.Results.Seventy-six patients (4.2%) out of 1817 had SSc-related PAH. Thirty-four patients (45%) were receiving monotherapy [endothelin receptor antagonist (n = 22; 29%) or phosphodiesterase-5 inhibitors (n = 12; 16%)], 25 (33%) sequential combination, and 17 (22%) upfront combination therapy. A lower forced vital capacity/DLCO in the sequential combination group was reported (2.9 ± 1.1 vs 1.8 ± 0.4 vs 2.3 ± 0.8; p = 0.085) and also a higher mean pulmonary arterial pressure in combination groups (37.2 ± 8.7 mmHg vs 40.8 ± 8.8 vs 46 ± 15.9; p = 0.026) at baseline. Treatment regimen (p = 0.017) and functional class (p = 0.007) were found to be independent predictors of mortality. Sequential combination therapy was found to be an independent protective factor (HR 0.11, 95% CI 0.03–0.51; p = 0.004), while upfront combination therapy showed a trend (HR 0.68, 95% CI 0.23–1.97; p = 0.476). Survival from PAH diagnosis among monotherapy, sequential, and upfront combination groups was 78% versus 95.8% versus 94.1% at 1 year, 40.7% versus 81.5% versus 51.8% at 3 years, and 31.6% versus 56.5% versus 34.5% at 5 years (p = 0.007), respectively. Side effects were not significantly different among groups.Conclusion.Combination sequential therapy improved survival in our cohort.

Primary biliary cirrhosis (PBC) is associated to any systemic autoimmune disease (SAD), in particular systemic sclerosis (SSc). To investigate the prevalence of SAD in a cohort of patients with PBC, specifically the prevalence of SSc and its clinical subtypes, and determining the clinical and biological profile of patients with associated PBC and SSc.Observational study of 62 patients with PBC following a protocol that included an anamnesis and physical examination to detect the presence of SAD as well as a nailfold capillaroscopy and an immunological study with specific SSc autoantibodies. A comparative analysis was conducted between patients with isolated PBC and patients with PBC and an associated SAD.SAD was associated to PBC in 22 patients (35,4%), and SSc was the most frequent illness, identified in 13 cases (21%). Five patients (8%) without previous diagnosis of SAD fulfilled pre-scleroderma criteria, according to LeRoy and Medsger criteria. The presence of anticentromere antibodies (54,5% vs. 5%, P.001) was the unique immunological determination identified more frequently in patients with PBC-SAD. The SSc suggestive capillary pattern was visualized in 11 patients (20,4%), mainly the slow pattern. No factors associated with greater morbi-mortality were identified in the PBC-SAD group.It does exist a subgroup of patients with PBC and clinical-biological features suggestive of an SAD, which advise a protocolized study to detect early the association to an SAD.

Resumen Introduccion y objetivos La cirrosis biliar primaria (CBP) se asocia a algunas enfermedades autoinmunes sistemicas (EAS), en particular a la esclerosis sistemica (ES. Determinar la prevalencia de EAS en una cohorte de pacientes con CBP, especificamente la ES y sus diferentes subtipos clinicos, y establecer el perfil clinico-biologico propio de estos pacientes. Metodos Estudio observacional de 62 pacientes con CBP, con un protocolo que incluia una anamnesis y exploracion fisica dirigidas a detectar una EAS, la realizacion de una capilaroscopia ungueal microscopica y un amplio estudio de autoinmunidad, incluido el perfil de anticuerpos especificos de ES. Se realizo un analisis comparativo entre el grupo de pacientes con CBP aislada y los pacientes con CBP y una EAS asociada. Resultados Se asocio una EAS en 22 pacientes (35,4%), y la ES fue la entidad mas frecuente (21%), del subtipo cutaneo limitado (11%). Cinco pacientes (8%) sin EAS previa cumplian criterios de preesclerodermia, segun los criterios de LeRoy y Medsger. Los anticuerpos anticentromero (54,5 vs. 5%, p Conclusiones Existe un subgrupo de pacientes con CBP con caracteristicas clinico-biologicas que sugieren la asociacion con una EAS, con elevada probabilidad, y que recomiendan el estudio protocolizado de estos pacientes con CBP para detectar de forma precoz EAS.

Background:Scleroderma renal crisis (SRC) prevalence is decreasing. However, no Systemic Sclerosis (SSc) patient’s registry has evaluated that decrease over time. No treatment have been able to prevent SRC development.Objectives:Primary objective: to identify SRC prevalence in 2 periods in the RESCLE(Registro deESCLErodermia) registry. Secondary objective: to idenfy which features could justify that change on SRC prevalence.Methods:Up to December 2018, 1937 SSc patients were included by 31 referral centers in RESCLE registry. SRC prevalence and incidence in diagnosed patients before and after 2003 was determined. Clinical characteristics of diagnosed patients in each period of time were analysed to identify differences between them.Results:Out of 1937 SSc, 43 (2.2%) developed SRC. Prevalence of SRC before and after 2003 was 3.5% and 1.08%. SRC Incidence: Graphic 1. Significant differences between Pre-2003 vs. Post-2003 SSc cohorts were found in univariate analysis: Table 1 and 2.Table. 1.Univariate analysisPre-2003(%)Post-2003(%)Demographic datalcSSc6359dcSSc2815ssSSc6.414Early SSc1.13.3Very early SSc1.99.6Age at SSc dx49.1(±15.2)y55.0(±15.6)yTime from SSc dx to SRC1.1(0.2-4.3)y0.6(0.1-1.5)yACR/EULAR 2013 criteria9986ComorbiditiesSmoked2037Arterial hypertension3529Diagnostic proceduresPAPs >40mmHg by Echocardiography3825Not-sclerodermal pattern at VCS8.919Lupus anticoagulant124.8Prognostic featuresOverall mortality2911ILD-related death101.6Conclusion:SRC Prevalence and Incidence has decreased. Prevalence is three-fold in diagnosed SSc cohort pre-2003 than in post-2003. The post-2003 cohort showed lesser prevalence of dcSSc subtype, earlier SSc diagnosis, less organic involvement and more intensive treatment than pre-2003 cohort. All these findings could explain the decline in the SRC prevalence.Figure:Table 2.Univariate analysisPre-2003 (%)Post-2003 (%)Clinical dataSkin sclerosis (as 1stsymptom)7.24.1Digital ulcers4931Telangiectasia6652Acroosteolysis124.6Calcinosis2914Joint contractures2813ILD4937Cardiac conduction alteration2027Left diastolic dysfunction4132Peripheral neuropathy136.1Sicca syndrome3724Treatment featuresCalcium channel blockers2340Specific vasodilators2.114Prostaglandin0.993.4Angiotensin system inhibitors5.116Corticosteroids1120Immunosuppressant315y: years old; lcSSc: limited cutaneous SSc; dcSSc: diffuse cutaneous SSc; ssSSc: sine scleroderma SSc; ILD: Interstitial lung disease; PAPs: systolic Pulmonary Arterial Pressure; VCS: Video-capillaroscopy; dx: diagnosisDisclosure of Interests:Xavier Pla Salas: None declared, Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Alfredo Guillén del Castillo: None declared, María Esther Sánchez García: None declared, Jorge Sánchez-Redondo: None declared, Eduardo L. Callejas-Moraga: None declared, Luis Sáez-Comet: None declared, Jose Antonio Vargas-Hitos: None declared, Jose Antonio Todolí Parra: None declared, Luis Trapiella Martínez: None declared, Ignasi Rodriguez-Pubto: None declared, Mayka Freire: None declared, Isaac Pons Martin del Campo: None declared, Vicent Fonollosa-Pla Consultant of: Actelion pharmaceuticals, GSK, MSD., Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

To evaluate the clinical features and survival of patients with positive anti-RNA polymerase III (anti-RNAP III) in a Spanish single centre.We analysed 221 patients with SSc according to LeRoy and Medsger criteria. Twenty-six patients with positivity for anti-RNAP III antibodies were compared with 195 negative patients. Epidemiological, clinical, immunological features and survival were analysed.In patients with anti-RNAP III positivity diffuse cutaneous SSc (dcSSc) subset was the most prevalent (20, 76.9% vs. 35, 17.9%, p0.001), with shorter diagnosis delay (4.11 ± 7.34 years vs. 6.77 ± 9.22 years, p = 0.005). Patients with anti-RNAP III antibodies had higher frequency of arterial hypertension (13, 50% vs. 55, 28.2%, p = 0.024), scleroderma renal crisis (SRC) (3, 11.5% vs. 3, 1.5%, p = 0.023), arthritis (9, 34.6% vs. 35, 17.9%, p = 0.046), tendon friction rubs (4, 15.4% vs. 1, 0.5%, p = 0.001) and contractures (5, 19.2% vs. 10, 5.1%, p = 0.02). There were no differences found in the presence of cancer or in global survival. In the multivariate survival analysis, severe interstitial lung disease (ILD) (HR: 8.61, 95%CI 3.40 - 21.81), pulmonary arterial hypertension (PAH) (HR: 4.05, 95%CI 1.42 - 11.61) and SRC (HR: 17.27, 95%CI 3.36 - 88.97) were the only factors associated with poor prognosis.In this cohort anti-RNAP III antibodies are related with dcSSc subset, shorter diagnostic delay and higher prevalence of musculoskeletal involvement, arterial hypertension and SRC. ILD, PAH and SRC were independent prognostic factors.

Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in the TMEM173 gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs.We aimed at detecting the reported three mutations of transmembrane protein 173 (TMEM173) exon 5 in 100 patients suffering from: systemic lupus erythematosus (SLE) (n = 22), primary antiphospholipid syndrome (PAPS) (n = 20), systemic sclerosis (SSc) (n = 20), dermatomyositis (DM) (n = 20), and vasculitis (n = 18). Samples from 19 healthy controls were also included. Sequence analyses were performed from the derived TMEM173 exon 5 PCR fragment amplified from DNA obtained from whole blood.Neither mutations nor single nucleotide polymorphisms (SNPs) in the exon 5 of the TMEM173 gene were detected. Just the rs7380272 SNP, located in the intronic region upstream exon 5, was detected in some patients and controls. The allele frequency of this SNP, though, was not statistically different between the patients groups and the control group.Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of the TMEM173 gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, as TMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway.

Cardiac involvement (CI) is a known complication of SSc associated with increased mortality. Our objective was to describe a cohort of patients with SSc and CI and to assess the differences between cutaneous subsets regarding their presentation and survival. Three hundred and ninety-three Spanish patients from a single center, diagnosed with SSc, were retrospectively studied for evidence of CI using noninvasive and invasive tests from 1976 to 2011. Clinical, epidemiological, immunological and therapeutic features of patients with CI were compared to those without it and within the different cutaneous subsets of SSc. CI was present in 173 (44 %) patients. Mitral regurgitation (67 %), conduction alterations (45 %) and left ventricle diastolic dysfunction (40 %) were the most common findings. Pericardial involvement and heart failure were more frequent in diffuse SSc (dcSSc) than in limited or sine scleroderma SSc. CI accounted for 20 % of deaths, and it was an independent mortality risk factor (HR 2.1, P = 0.02), but once CI was established, classical dcSSc mortality risk factors determined mortality. Patients with dcSSc developed CI faster than limited (HR 1.9, P = 0.003) or sine SSc patients (HR 2.5, P = 0.002), specially during the first year after SSc onset. We found statistically significant differences between the 3 SSc subsets in the presentation of pericardial involvement and heart failure. CI increased the mortality and appeared at a higher rate, especially during the first year after SSc onset. Screening for heart involvement should be performed at diagnosis and during follow-up.

Objective.To compare American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis (SSc) with previous American Rheumatology Association (ARA) criteria.Methods.This was a cross-sectional multicenter study comparing sensitivity of both criteria in the cutaneous subsets in the Spanish scleroderma registry (RESCLE) cohort.Results.In 1222 patients with SSc, the most prevalent items were Raynaud phenomenon (95%), skin thickening (91%), and abnormal capillaroscopy (89%). ARA criteria classified as SSc 63.5% of all patients, and 63%, 100%, 11.2%, and 0% in the limited, diffuse, sine, and pre-SSc subsets, respectively. ACR/EULAR criteria classified 87.5% of all patients and 98.5%, 100%, 41.8%, and 15.9% in the same subsets, respectively.Conclusion.ACR/EULAR criteria are more sensitive than ARA criteria, especially in limited, sine, and pre-SSc subsets.

Background Epidemiological data suggest that some viruses may be linked to the development of autoimmunity. Objectives The objective of this work was to determine the presence of HHV-8 viral DNA in whole blood from patients suffering from different systemic autoimmune diseases (SAD). We also aimed at testing the prevalence of patients showing antibodies against an HHV-8 orfK8.1 peptide. Study design Two hundred and eighty SAD patients and 50 healthy blood donor controls were included. Molecular analyses were performed by nested PCR from DNA obtained from whole blood and an enzyme immunoassay was developed in order to test for the presence of antibodies directed against a synthetic peptide derived from the HHV-8 orfK8.1 protein. Results Only 2 out of the 280 samples analyzed yielded the specific HHV-8 PCR product. Antibodies against orfK8.1 were detected in 2 SLE patients, 1 patient suffering from Sjogren's syndrome and 2 patients with vasculitis. Conclusions We conclude that HHV-8 is usually not present in blood neither from autoimmune patients nor from healthy controls. Furthermore, HHV-8 antibodies against the HHV-8 orfK8.1 peptide were rarely detected. It leads us to infer that HHV-8 is not involved on the development of these disorders. It does not rule out the possibility that other environmental and microbiological triggers may account for their etiopathogenesis.