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BackgroundAnti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is an entity of growing interest. However, data on epidemiology and clinical spectrum are still scarce and there is a need for the identification of its potential risk factors.ObjectivesTo characterize the demographic, genetic, clinical, and serological features of patients with anti-HMGCR IMNM in a region of northern Spain.MethodsStudy of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in Northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene.Results8 patients (5 women, 3 men) with a mean ± SD age of 64.9±7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had dyslipidemia and had been exposed to statins. Seven of the 8 of cases complained of myalgia. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 of them. None of the patients had extra-muscular involvement. No evidence of malignancy was found. All patients had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25-hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population.ConclusionIn northern Spain, the IMNM anti-HMGCR preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this diseaseTable 1.PatientAge/SexHLA DRB1*11rs4149056 genotypeMRC at the weakest muscle group*DysphagiaCK (IU/L) at diagnosisAnti-HMGCR titer (CU)Induction therapy*Maintenance therapyClinical improvement**CK (IU/L) at last follow-up visit156/MYesTT2No8963277.8GC. IVIG.MTXGC. IVIG. MTX. RTXMarked134269/FYesTT0Yes9271235.9GC iv bolus. IVIG.GC. MTX. RTX.Marked890364/FYesTT3No4000242.6IVIG.IVIG.RTXMarked1284479/MYesTT4No4977145.6GC. IVIG.GC. IVIG.Complete92562/FNoTT3No2116210.0GCGC.MTX.Marked236657/FYesTC4No2294259.3IGIVIGIVComplete235768/FYesTT3No3273236.0GC. IGIV. AZA.GC. AZAComplete249864/MYesTC4Yes11000179.0GC iv bolus. AZA.GC. AZAComplete161AZA: azathioprine; CK: creatinine kinase; CU: chemiluminescence units; F: female; GC: glucocorticoids; IVIG: intravenous immunoglobulins; M: male; MRC: medical research council scale; MTX: methotrexate; RTX: rituximab; ** Induction therapy initiated within 3 months of diagnosis. **Clinical improvement: no improvement (no improvement in MRC grade), mild improvement (improvement of MRC grade but still requiring assistance for activities of daily living), marked improvement (persistence of mild weakness without functional limitation), and complete improvement (return to baseline with no symptoms or signs of weakness).Disclosure of InterestsNone declared

Background:Joint damage is the pathological hallmark of rheumatoid arthritis (RA). To identify the genetic variation associated with a higher level of erosions has proven elusive.Objectives:The objective of the present study was to perform a genome-wide association study on joint damage in a cohort of RA patients of the Spanish population. Our aims were to provide independent validation of previously reported variants and to identify new candidate risk loci. A stratified analysis was performed based on positivity to ACPA status.Methods:A total of 1,135 patients diagnosed with RA using the ACR-EULAR criteria recruited by the IMID Consortium were genotyped using a 550,000 single-nucleotide polymorphism array. Additional SNPs were imputed using the 1KG genome data. Joint damage was performed using the S-score, a simplified radiographic erosion score that has a high correlation with the Sharp-van der Hejde score (1). Association testing of SNPs with joint damage was performed via linear regression with the addition of the years of evolution as covariate. The two main components of genetic variation were also added to adjust for potential population stratification. A total of 50 SNPs representing previously reported loci associated with joint damage were selected. Genetic association was also performed at the pathway level using Pascal.Results:45 out of 50 SNPs representing 31 previously reported loci for joint damage could be satisfactorily imputed. Association testing of the whole patient cohort replicated the association withIL2RAandTRAF1. Of relevance, after stratifying for anti-CCP five new loci were replicated:KIF5AandSOSTin ACPA-positive RA andCD40, DKK1andTNFin ACPA-negative RA.IL2RAwas only significant in the ACPA-positive group andTRAF1was not significant in either strata. GWAS on the ACPA-positive cohort and on the ACPA-negative group identified n=7 and n=18 loci with P-values < 1x10-5, respectively. From these, however, only 1 SNP showed nominal significant association in the other patient group. Based on this evidence, we performed a pathway-based analysis to understand the biological mechanisms underlying this difference. Pathway analysis showed 52 biological processes associated with joint damage in ACPA-negative RA and 32 pathways in the ACPA-positive group, with only two shared biological processes between the two groups. Fc Gamma receptor mediated phagocytosis was the topmost biological process associated with erosions specifically in ACPA-negative RA and Signalling by Fibroblast Growth Factor mutants was the top process specific for ACPA-positive patients.Conclusion:The results from our study provide suggestive evidence that the genetic basis for joint damage is different according to the presence of ACPA. Replication of the new candidate loci in an independent patient cohort is underway.References:[1]Lopez-Lasanta, M., Julià, A., Maymó, J., Fernández-Gutierrez, B., Ureña-Garnica, I., Blanco, F. J., ... & Tornero, J. (2015). Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis.Arthritis research & therapy,17(1), 242.Disclosure of Interests:Antonio Julià: None declared, Francisco Blanco: None declared, Benjamin Fernandez: None declared, Antonio Gonzalez: None declared, Juan D: None declared, Joan Maymó: None declared, Mercedes Alperi-López: None declared, Alejandro Olive: None declared, Héctor Corominas Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Victor Martinez Taboada: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Antonio Fernandez-Nebro: None declared, Alba Erra: None declared, Simon Sánchez Fernandez: None declared, Núria Palau: None declared, Maria Lopez Lasanta: None declared, Adrià Aterido: None declared, Jesús Tornero: None declared, Sara Marsal: None declared

Objectives:To investigate the prevalence, risk factors, and effects of primary renal disease on morbidity and mortality in patients with primary Sjögren’s syndrome (pSS).Methods:All patients in the SJÖGRENSER (registry of adult SSp patients of the Spanish Society of Rheumatology, cross-sectional phase) cohort were retrospectively investigated for the presence of clinically significant renal involvement directly related to pSS activity.Results:Of the 437 patients investigated, 39 (9%) presented overt renal involvement during follow-up. Severe renal disease necessitating kidney biopsy was relatively rare (23%).Renal involvement may complicate pSS at any time during the disease course and is associated with severe disease (indicated by higher scores of involvement, activity, and damage), systemic multiorgan involvement, and a higher frequency of lymphoma. Multivariate analysis showed that older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.07), higher European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index scores (OR 1.1, CI 1.03–1.18), serum anti-La/SSB positivity (OR 6.44, CI 1.36–30.37), and non-vasculitic cutaneous involvement (OR 8.64, 1.33–55.90) were independently associated with this complication.Chronic renal failure developed in 23 of 39 patients (59%); only 1 of them progressed to end-stage renal disease necessitating renal replacement therapy. Patients with renal disease showed higher Sjögren’s syndrome disease damage index scores (SSDDI), higher rates of hospitalization due to disease activity and higher rates of clinically relevant comorbidities.Conclusion:Renal involvement is an uncommon complication in pSS that was observed in 9% of patients. Although categorized as a non-negligible comorbidity, this condition shows a favorable prognosis.Disclosure of Interests:None declared

Background:The mortality in Systemic Lupus Erythematosus (SLE) varies largely across different countries most probably due to social, healthcare and ethnic differences.Objectives:To analyze the causes and identify predictive factors of mortality of SLE in Spain in the present century.Methods:We performed a cross-sectional and retrospective study analyzing data from the RELESSER cohort (Spanish Registry of Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). We included all patients diagnosed with SLE since the year 2000 and recorded sociodemographic, clinical and serological variables, comorbidities and treatments, as well as indicators of disease activity, damage and severity. The characteristics of the deceased patients were compared with those of the survivors, and variables with clinical significance or statistical significance were grouped into multivariate models to determine which ones were independently associated with the outcome of the disease.Results:A total of 2004 patients were included, 88.6% female, the mean age at diagnosis was 38.3 (± 15.3) years, with a mean delay in diagnosis of 28.9 (± 52.6) months. Up to 2.84% of the individuals had died. The leading cause of death was SLE activity (n=16), followed by infections (n=14), vascular events (n=7) and cancer (n=6). The mean age of death was 54.68 (± 20.13) years, and neither age, sex nor delay in diagnosis was independently associated with mortality. The presence of nephritis, depression, severe infections, organ damage (SLICC/ACR DI) or disease activity (SLEDAI), as well as the use of cyclophosphamide, rituximab or high doses of corticosteroids, were predictors of mortality in our cohort. Antimalarial treatment and skin manifestations were linked to improved survival.Conclusion:In the RELESSER cohort, clinical factors, co-morbidities, as well as therapeutic attitudes were associated with a significant increase in mortality in SLE. Interestingly, depression was independently associated to mortality. The activity of the disease and infections continue to be the main causes of death at the beginning of the 21st century amongst our patients.Disclosure of Interests:Clara Moriano: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Iñigo Rua-Figueroa: None declared, Elvira Diez Alvarez: None declared, Cristina Bermúdez: None declared, Francisco J López-Longo Grant/research support from: AbbVie and GSK, Speakers bureau: AbbVie, Actelion, Bristol Myers Squibb, GSK, MSD, Pfizer, Roche, and UCB Pharma, María Galindo-Izquierdo: None declared, Alejandro Olive: None declared, Eva Tomero Muriel: None declared, Antonio Fernandez-Nebro: None declared, Mercedes Freire González: None declared, Olaia Fernández- Berrizbeitia: None declared, Ana Pérez Gómez: None declared, Esther Uriarte Isacelaya: None declared, Carlos Marras Fernandez Cid: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, M. Rodíguez-Gómez: None declared, Paloma Vela-Casasempere: None declared, Alina Boteanu: None declared, J. Narváez: None declared, Victor Martinez Taboada: None declared, Blanca Hernández-Cruz Speakers bureau: Abbvie, Lilly, Sanofi, BMS, STADA, José Luis Andreu: None declared, José A Hernandez Beriain: None declared, Lorena Expósito: None declared, Raúl Menor-Almagro: None declared, Mónica Ibañez Barceló: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Carles Galisteo: None declared, Enrique Raya: None declared, Víctor Quevedo Vila: None declared, Tomas Vazquez Rodriguez: None declared, Jesus Ibañez: None declared, Jose M Pego-Reigosa: None declared

Objectives:Primary Sjögren´s Syndrome (pSS) is characterized by hyperactivity of the B cell, with the consequent production of autoantibodies. The presence of anti-Ro and anti-La has been associated with extraglandular manifestations and lymphoma development. The aim of this study is to evaluate the frequency of different serological profiles in patients of SJOGRENSER registry and to assess whether the combination of antibodies and serological markers are associated with the development of systemic disease and the systemic illness and/or the development of systemic disease and complications.Methods:SJOGRENSER is a transversal multicenter study with pSS patients (patients who meet 2002 pSS classification criteria); it is collected demographic, clinical, serological data and the activity index: ESSDAI and ESSPRI. It was established three serological profiles: 1. ANA/Ro+ with La/RF-; 2. ANA/Ro/La+ with RF-; 3. ANA/Ro/La/RF+. A descriptive analysis was done, with means and standard deviations, frequencies and proportions. Student t for quantitative variables and Chi2 for qualitative ones were performed to evaluate differences between groups, it was considered a p Results:Four hundred and thirty-seven patients were included, the most frequent serological patterns observed were: ANA/Ro/La/RF+ 221 patients (50.5%), ANA/Ro/La+ 61 patients (13.9%) and ANA/Ro+ 60 patients(13.7%). There were only two patients with ANA/La +. The ESSDAI score was significantly associated with the profile ANA/Ro/La/RF+ (6 vs 4, p=0.007) and the group with the ANA/Ro/La+ profile reached an ESSDAITable 1.Serological markers associated with the development of systemic diseaseInvolvementProfile 1ANA +Anti-Ro +Anti-La -RF –n=60N° (%)Profile 2ANA +Anti-Ro +Anti-La +RF –n= 61N° (%)Profile3ANA +Anti-Ro +Anti-La +RF +n= 221N°(%)pESSDAI index4460.007ESSDAI44 (73.3)48 (78.7)139 (63.2)0.043ESSPRI index6.15.35.00.007Constitutional syndrome5 (8.3)9 (14.8)51 (23.1)0.023Lymphadenopathy8 (13.3)9 (14.8)37 (16.7)0.790Glandular14 (23.3)16 (26.2)87 (39.4)0.024Articular49 (81.7)40 (65.6)187 (84.6)0.004Lung3 (5.0)4 (6.6)29 (13.2)0.100Kidney0 (0)5 (8.2)31 (14.1)0.006Peripheral nervous system5 (8.3)6 (9.8)18 (8.2)0.918Central nervous system4 (6.7)7 (11.5)13 (5.9)0.320Hematological24 (40.0)26 (42.6)147 (66.5)Biologic5 (8.3)4 (6.6)26 (11.8)0.428Lymphoma1 (1.7)2 (3.3)3 (1.4)0.598In contrast to the ESSPRI index was lower significantly associated with the profile ANA/Ro/La/RF+ and higher in the ANA/Ro+ (5 vs 6.1, p=0.007). The presence of antiLa and/or RF to the profile ANA/Ro+ rises the percentage of patients with constitutional syndrome, glandular, kidney and hematological affectation with statistically significant differences. The percentage of patients with articular involvement it was similar in the profiles ANA/Ro+ and ANA/Ro/La/RF +.The multinomial analysis showed that the profile ANA/Ro/La/RF+ was associated with higher ESSDAI values (OR=1.09 (1.01-1.17)). The hematological involvement was associated with the profiles ANA/Ro/La/FR+ (OR= 2.76 (1.46-5.22)). Higher scoring of ESSPRI was associated with the profile ANA/Ro+ (OR=0.79 (0.69-0.91)).Conclusion:The most frequent serological profile was ANA/Ro/La/RF+ and it was associated with higher ESSDAI score. The presence of antiLa and/or RF with an ANA/Ro+ increased the presence of systemic involvement. The ANA/Ro+ profile was associated with a higher level of ESSPRI.Disclosure of Interests:None declared

Objective To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Methods The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was assessed by stimulating PBMCs with specific ligands. Results A significantly increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite increased expression of TLR7, circulating monocytes from patients showed a significantly lower in vitro response to TLR7 agonists. No amino acid substitutions predicted to be functionally damaging were found in TLR7. A normal response to specific TLR7 agonists in patients in complete remission eliminated a genetic defect. TLR expression and function were also affected to some degree in other diseases characterised by a strong acute phase response. Conclusion These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.

Objective:To characterise the circulating cytokine profile and the cellular source of circulating cytokines in polymyalgia rheumatica (PMR).Methods:The study included 34 patients with active untreated PMR and 17 age-matched healthy controls (HC). Circulating cytokines were measured by cytometric bead array and ELISA. Intracellular cytokines were assessed in CD3+ and CD14+ cells by flow cytometry. Cytokines in cell culture supernatants were also determined after polyclonal stimulation of patients’ peripheral blood mononuclear cells.Results:Circulating levels of interleukin-6 (IL6) were significantly higher in subjects with active PMR than in HC. Corticosteroid (CS) treatment was followed by a decrease in the level of IL6. Intracellular cytokine staining showed that circulating monocytes did not produce higher amounts of proinflammatory cytokines in patients with PMR than in HC. There was a discordance between serum levels and cytokine-producing monocyte and T cells, and it was not possible to demonstrate a Th1 bias in the peripheral compartment.Conclusions:Active PMR is characterised by increased serum levels of IL6, but not of other proinflammatory cytokines, that are rapidly suppressed by CS treatment. As circulating monocytes do not show increased production of proinflammatory cytokines, IL6 may be mainly produced in the inflamed tissue. A study of the circulating cytokine profile and its cellular source may provide a clue to new therapeutic options.

Objective: Open label studies have suggested that tumour necrosis factor (TNF) antagonists led to sustained improvement and corticosteroid sparing effect in patients with giant cell arteritis (GCA). To confirm these observations, we conducted a randomised, double-blind, placebo controlled trial with etanercept in patients with biopsy-proven GCA with side effects secondary to corticosteroids. Methods: We randomly assigned patients with GCA to receive etanercept (n = 8) or placebo (n = 9) over 1 year together with corticosteroids that were reduced according to a predefined schedule. The primary outcome was the ability to withdraw the corticosteroid therapy and control the disease activity at 12 months. Results: Baseline characteristics were similar in the two groups, although patients in the etanercept group showed higher levels of basal glycaemia (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12 months, 50% of the patients in the etanercept group and 22.2% in the placebo group were able to control the disease without corticosteroid therapy (p value not significant). Patients in the etanercept group had a significant lower dose of accumulated prednisone during the first year of treatment (p = 0.03). There were no differences in the number and type of adverse events. Conclusion: The limited number of patients included in this study does not allow us to draw definitive conclusions. Etanercept therapy was well tolerated in this aged population. The therapeutic role of etanercept in patients with GCA should be evaluated in studies with a larger number of patients.

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness > 45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score >= 4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score >= 5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients >= 50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness > 45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.

Background Primary Sjogren syndrome (pSS) is a systemic autoimmune disease involving mainly the exocrine glandular system. Nevertheless, its clinical spectrum includes the development of multiple extra-glandular manifestations which will be determinant for the use of systemic therapy. Objectives The aim of our study was to describe the systemic therapy in a pSS cohort assisted in Spanish Rheumatology Departments and its association with the involvement of different organs. Methods This is a multicenter descriptive transversal study of pSS patients fulfilling European/American consensus criteria. Patients were included by randomization from thirty-three Rheumatology departments. Data were collected by reviewing clinical records and interviewing the patients. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates. Chi-square was used to establish the statistical associations, being considered a p Results Four hundred and thirty-seven patients were included. Ninety-five percent of them were women. The median age of the cohort was 58 years. Eighty-four percent of the patients have been treated (currently or previously) with non-steroidal anti-inflammatory drugs (NSAID), 49% had been treated with glucocorticoids (GC), 7% with boluses of GC, 51% with antimalarial, 13% with methotrexate (MTX), 10% with azathioprine (AZA), 4% with mycophenolate mofetil (MM) and 3% with cyclophosphamide (CF). NSAIDs were significantly used more frequently in patients with joint involvement. GC were significantly used more frequently in patients with joint, pulmonary, central and peripheral nervous system (CNS and PNS) involvement and cytopenia. GC boluses were used significantly more frequently in patients with musculoskeletal, pulmonary and nervous system involvement. Antimalarials were significantly used more frequently in patients with joint involvement. MTX was significantly used more frequently in patients with joint, CNS involvement and cytopenia. AZA was significantly used more frequently in patients with lung and CNS involvement and cytopenia. MM was significantly used more frequently in patients with renal, lung and PNS involvement, and cytopenia. CF was significantly used more frequently in patients with joint, pulmonary, CNS and PNS involvement. Conclusions Despite the absence of clinical controlled studies demonstrating efficacy and safety, systemic therapy use in SSp patients is very frequent. Its use is mainly associated with the presence of musculoskeletal, neurological, pulmonary and haematological manifestations. Disclosure of Interest None declared

Background Reliable data regarding the prevalence of specific medical comorbidities among patients with PrimarySjogren9s Syndrome (pSS) remain sparse and there are not comparative studies among patients with pSS and patients with Systemic Lupus Erythematosus (SLE). Objectives To compare the prevalence of the main comorbidities of two large cohorts of patients with pSS and SLE, with focus in cardiovascular (CV) diseases. Methods Cross-sectional multicenter study comparing cumulative prevalence of the most relevant comorbidities, with identical definition in both cohorts. Patients on follow-up from SJOGRENSER (Spanish Register of pSS) and RELESSER (Spanish Register of SLE), fulfilling AECG-2002 and ACR-97 classification criteria, were included. Binomial logistic regression analysis was carried out to explore potential differences, adjusting for age, sex and disease duration with further specific adjustments for each variable, including CV risk factors and treatments, when it was considered convenient. Results 437 pSS (95.2% female) and 2,960 SLE (89.5% female) patients were included. Mean age: 58.6 (p55-p75: 50.0–69.9) and 46.4years (22.4–41.6) respectively (p Patients with pSS were hospitalized by the disease activity lesser than SLE: 17% vs 53%, p The following comorbidities were less prevalent in pSS: Smoking [25.3% vs 48.2%, p Conclusions pSS patients have consistently less serious comorbidity burden compared with SLE patients, namely less CV diseases and less infections. In contrast, the risk of lymphoma exceeds that seen in SLE patients. The higher prevalence of CV events in SLE does not seem to be explained only by traditional CV risk factors, suggesting that SLE derived factors could be involved. Acknowledgement Systemic Autoimmune Diseases Group of Spanish Society of Rheumatology (EAS-SER) and SER Research Unit Disclosure of Interest None declared

Background Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of aPL and at least a clinical event defined as recurrent venous thrombosis, arterial thombosis or pregnancy morbidity. The titers of aPL usually fluctuate, they frequently decrease and eventually become negative during follow-up period, thus reducing the risk of thrombotic events. Objectives The aim of this study was to explore the clinical and serological course of fertile women with positive aPL, as well as the factors and the potential therapeutic implications associated with aPL negativization. Methods We conducted a retrospective study including women attending the obstetric autoimmune pathology clinic of a tertiary-facility serving a population in about 350,000 in Northern Spain. We included 105 women with a confirmed positive APL serology according to Sydney Criteria between October 1995 and December 2013. Patients were classified into 3 different groups: A) patients with primary APS (49), B) patients with a positive serology for APL, not meeting clinical criteria (42) and C) patients with systemic lupus erythematosus and a positive serology for APS (14). They were also classified, according to the serological APL evolution: patients with persistently negative aPL, transiently positive serology and persistently positive serology according to previously established criteria. Results After a mean follow up of 114,4±37,2 months, 59% patients had persistently negative antibodies, while 25,7% patients presented persistently positive aPL serology. After the multivariate analysis only the tobacco use (OR 3,5 p=0,013) was confirmed as an independent risk factor. The load of antibodies, specially the presence of triple positivity (OR: 2,4; IC: 0,16–2,36), was close to statistical significance (p=0,162). No other factors, including traditional cardiovascular risk factors, treatments or clinical manifestations reached statistical significance. Persistent positivity was associated with higher risk for further pregnancy morbidity (41 vs 52%; p=0,328). In 17 patients, with persistently negative serology who were asymptomatic, treatment with low dose aspirin was discontinued. No clinical events related to APS were reported after treatment withdrawal, during a 119,9 months follow-up period. Conclusions Our study suggests that among fertile women, antiphospholipid antibodies remain persistently positive only in one quarter of patients, being tobacco use an independent risk factors for its persistence. Among patients with persistently negative serology and with a low-risk profile discontinuation of antiplatelet therapy could be considered a safe choice. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease with heterogeneous clinical manifestations. Recent studies have suggested the existence of a genetic basis for the diverse SLE clinical phenotypes. Also, there is increasing evidence indicating that a substantial part of the genetic variation associated with complex diseases is explained by small-effect genes from common genetic pathways. Objectives The objective of the present study was to identify new genetic variation associated with SLE phenotypes using a genome-wide association study at the pathway level. Methods A total of 598,258 SNPs were genotyped in a discovery cohort of n=482 SLE patients of southern European ancestry using the Illumina platform Quad610. After quality control analysis, including ancestry estimation using principal-component analysis, genome-wide pathway analysis was performed. A total of 14 clinically relevant SLE phenotypes were tested for association with n>700 reference genetic pathways. Significantly associated pathways (corrected P-value in silico analysis on cell types of relevance in SLE pathogenesis. Results In the discovery stage, two genetic pathways were significantly associated with the presence of oral ulcers and antinuclear antibodies in SLE ( P FDR VEGF ) genetic pathway ( P =1.3e-2). Analyzing the transcriptional effect of the topical immunotherapies used for the treatment of oral ulcers in SLE, we found a significant differential expression of VEGF pathway genes ( P Conclusions In this work we have performed the first genome-wide association study for clinically relevant SLE phenotype using a pathway-based approach. With this new approach, we have identified and validated the association of VEGF genetic pathway with oral ulcers in SLE. These findings represent an important step towards the characterization of the genetic basis of phenotype heterogeneity in SLE. Disclosure of Interest None declared

Background Primary Sjogren9s syndrome (pSS) is a chronic systemic autoimmune disease that usually affects middle age women. It is characterized mainly by the involvement of the exocrine glands; However, patients with pSS presents a broad spectrum of systemic involvement and serologic characteristics. Objectives The aim of this study is to analyze clinical and serological differences in different age at diagnosis groups in a pSS Spanish cohort. Methods This is a multicenter transversal study of pSS patients whose fulfilled European-American consensus criteria from thirty-three Rheumatology Units. The patients were randomized into the following age groups: 65 years. Epidemiological, clinical and serological data were collected. All patients signed an informed consent, and the study was approved by the local ethics committees. Qualitative data were compared using the Chi-square tests. Quantitative variables were analyzed with a Kruskal-Wallis test. A value of p Results Four hundred and thirty-seven patients were included. The median age of the cohort was 58 years. Ninety-five percent of them were women.There were no statistically significant differences in the men and women percentage.The disease symptoms were initiated more frequently in 35–50 years group (38.5%).There were no statistically significant differences in the time to disease progression in the four age at diagnosis groups. No statistically significant differences were found in sicca syndrome among age groups. Ocular and oral symptoms were present in 95% of patients. The glandular involvement (46.7%), central nervous system (14.13%) and Raynaud9s phenomenon (29.3%) showed significantly more often in patients under 35 years. Genital involvement (54.5%) and asthenia (72.4%) showed significantly more often in the group of 35–50 years. The gastrointestinal involvement (20%) occurred significantly more frequently in the group of 50–65 years. Splenomegaly and cardiac involvement were less frequent manifestations in all four groups of patients ( 65 years (100% and 75% respectively). There were no significant differences in the ANA, anti-DNA, anti-Sm, anti-RNP, cryoglobulins and antiphospholipid antibodies values between groups. Conclusions Patients under 65 years old have an increased degree of systemic involvement. There are no differences in the presence of sicca syndrome. The FR is significantly more common in patients younger than 35-year-old, while the anti-Ro and anti-La antibodies tend to be it in more extreme age groups. Disclosure of Interest None declared

Background The prevalence of thrombosis in antiphospholipid syndrome (APS) and the factors vary depending on the population studied. Although aPL have a strong relationship with thrombosis and pregnancy morbidity, the value of each type of aPL as a marker to develop APS it is not fully clarified. Objectives To analyze the incidence of thrombosis in patients with positive aPL that do not meet clinical criteria for disease. To identify potential risk factors for thrombosis. To analyze the possible protective role of primary thromboprophylaxis. Methods Retrospective study of patients with positive aPL on at least 2 times, separated by a minimum of 12 weeks in medium or high titers without fulfilling clinical criteria for APS. The patients were selected from the database of the Department of Immunology of a tertiary hospital (1999- 2004). The presence of vascular event was confirmed through imaging tests. Cases of ischemic optic neuropathy (ION) were diagnosed by clinical and electrophysiological testing. Results After a mean follow-up of 146±60.3 months, of the 138 patients included in the study, 13 (9.4%) developed thrombosis. The mean time to thrombotic episode was 81.4±41.7 months. Several classic cardiovascular risk factors (CVRF) such as tobacco (61.5% in thrombosis group vs 23.2% in the group without thrombosis;p=0.003), hypertension (53.8% vs 15.3%;p=0.001) and dyslipidemia (DLP) (38.5% vs 5.6%;p=0.001) were more frequent in patients with thrombosis. These 3 classic CVRF were independent risk factors for thrombosis in the univariate analysis, with an OR of 6.5 (95%CI 2.0–21.3) for hypertension, 5.3 (95%CI 1.6–17.5) for tobacco and 10.5 (95%CI 2.7–40.8) for DLP. Regarding the different antibodies, only the lupus anticoagulant (LA) (p=0.062) and anticardiolipin antibodies (aCL) IgM (p=0.14) tended to be more frequent in patients with thrombosis. Positivity to the 3 types of antibodies (AL, aCL, AB2GPI) was associated with increased risk of thrombosis (OR 7 [95%CI 1.9–28.5]; p=0.004). Multivariate analysis showed as independent risk factors for thrombosis: smoking (OR 8.3 [95%CI 1.3–52.5]; p=0.024), hypertension (OR 15.9 [95%CI 1.8–138.7]; p=0.012), DLP (OR 16.9 [95%CI 1.4–108.3]; p=0.027) and IgM aCL (OR 18.7 [95%CI 12–277.7]; p=0.033). Of the 13 thrombotic events, 10 were arterial: 4 acute myocardial infarctions, 2 thrombosis of central retinal artery, 2 OIN 1 transient ischemic attack and 1 stroke. Three thrombosis occurred in venous territory as deep venous thrombosis of lower extremities, with secondary pulmonary thromboembolism in 2 patients. Regarding treatment, 102 patients received prophylaxis with ASA 100 mg, showing a tendency towards protection (OR 0.774 [95%CI 0.2–2.7]; p=0.686). Conclusions The incidence of thrombosis in patients with positive aPL that do not meet clinical criteria for the disease is about 10%. The tobacco, DLP, hypertension and IgM aCL are independent risk factors. Autoantibodies load increases the risk of thrombosis. The protective role of aspirin in this population seems limited and may raise primary thromboprophylaxis with oral anticoagulation in patients considered as high risk. Disclosure of Interest None declared

Background Primary Sjogren syndrome (pSS) is a chronic systemic autoimmune disease with a relevant impact in patients9 quality of life. Neurological manifestations of pSS could have an important impact on morbidity and mortality. Objectives The aim of our study was to evaluate central and peripheral neurological manifestations of a pSS cohort of patients assisted in Spanish Reumathology Departments. Methods This is a multicentre descriptive transversal study of pSS patients from thirty-three rheumatology departments. Patients fulfilling European/American consensus criteria were included after randomisation. By reviewing clinical records and interviewing the patients, we collected epidemiological, clinical, serologic, therapeutic, and disease activity indexes data. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates. Chi-square was used to establish the statistical associations, being considered a p Results Four hundred and thirty-seven patients were included. Ninety five percent of them were women. The median age of the cohort was 58 years. Thirty-four (7.8%) patients developed central nervous system (CNS) involvement. Interestingly, 15 patients developed CNS manifestations before the diagnosis of pSS. Fourteen patients referred headache, 11 patients some psychiatric disorder, 6 patients cerebral ischemic attack, 5 patients cognitive impairment, 5 patients multiple sclerosis, 3 patients cranial nerve involvement of central origin, 3 patients cerebral vasculitis, 2 patients optic neuritis, a patient aseptic meningitis and a patient myelopathy. ESSDAI index was significantly higher in patients with CNS involvement. Systemic treatments (glucocorticoids, bolus of glucocorticoids, azathioprine, methotrexate and cyclophosphamide) and biological treatments (anti-TNF, abatacept and tocilizumab) were used significantly more frequently in patients with CNS impairment. Thirty-nine (8.9%) patients developed peripheral nervous system (PNS) involvement, 14 of them, before the diagnosis of pSS. Thirteen patients had mixed polyneuropathy, 2 patients motor polyneuropathy, 8 patients sensitive polyneuropathy, 3 patients small fiber neuropathy, a patient developed mononeuritis multiplex and 8 patients focal mononeuropathy. Three patients had trigeminal sensory neuropathy, a patient III cranial neuropathy and 3 patients VII cranial neuropathy. SSDAI and ESSDAI indexes were significantly higher in patients with PNS involvement. Systemic therapies (glucocorticoids, bolus of glucocorticoids, methotrexate, mycophenolate mofetil and cyclophosphamide), biological treatments (rituximab) and intravenous immunoglobulins were used significantly more frequently in patients with PNS impairment. Conclusions More than 7% of pSS patients with pSS of our cohort developed nervous system manifestations. The CNS and PNS involvement led to a significantly higher disease activity, scored by formal activity indexes. The use of systemic and biological treatment was significantly higher in patients with nervous system involvement. Disclosure of Interest None declared

Background Antiphospholipid Syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis and/or pregnancy morbidity together with the presence of positive antiphospholipid antibodies (aPL) (anticardiolipin antibodies (aCL), anti -beta2 glycoprotein I (AB2GPI) and/or lupus anticoagulant (LA). There is a clear relationship between aPL and some events not included in the clinical criteria such us the hematologic manifestations. Among these, thrombocytopenia has been described in 20–50% of patients with APS. Although thrombocytopenia in APS is usually not serious, its impact on the clinical curse of the diseasesis unknown. Objectives a) To study the probability of developing clinical APS in patients with positive aPL and thrombocytopenia b) To identify potential risk factors for the development of APS. c) To study the association of thrombocytopenia with aPL autoantibodies. Methods Retrospective study of patients with positive aPL on at least 2 times, separated by a minimum of 12 weeks in medium or high titers without fulfilling clinical criteria for APS. The patients were selected from the database of the Department of Immunology of a tertiary hospital (1999–2004). Thrombocytopenia was defined as a platelet count ≤100000 platelets/L. We excluded patients with other causes of thrombocytopenia. Results 17 of 138 (12%) patients in the study had thrombocytopenia (mean platelet count 60,000/mm 3 ). Ten patients received oral glucocorticoids. Only 2 patients with 3 were treated with intravenous gammaglobulins. Smoking was more common in patients with thrombocytopenia (47.1% vs 24%; p=0.044). The risk for thrombocytopenia was almost 3 times higher in smokers (OR 2.8; 95%CI 1.0–8.0; p=0.044). We found no statistically significant relationship with the distribution of the different antibodies, except for AL (OR 13.5, 95%CI 3.8–47.6; p After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis (4 arterial: 1 anterior ischemic optic neuropathy, 1 transient ischemic attack, 1 stroke and 1 acute myocardial infarction, and 1 deep venous thrombosis of the lower limbs with secondary pulmonary embolism), fulfilling clinical criteria for APS. The mean time from the confirmation of the presence of aPL to the diagnosis of APS was 73±61.5 months. Patients with thrombocytopenia had higher number of thrombosis compared with patients with normal platelet count (29.4% vs 6.6%, OR 5.9; 95%CI 1.7–20.9; p=0.003). Conclusions a) In our series, the incidence of thrombocytopenia in patients with positive antiphospholipid antibodies that do not meet clinical criteria for APS is 12%. APL-positive patients who develop thrombocytopenia have a potential risk of developing APS in the future. b) Tobacco use could be a risk factor for the development of thrombocytopenia in this population. c) Autoantibodies load is a risk factor for the development of thrombocytopenia. Disclosure of Interest None declared

Background Primary Sjogren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocyte infiltration of the exocrine glands. Nevertheless, it can affect any organ and develop extra-glandular manifestations that even can precede the typical glandular manifestations and delay the diagnosis. Objectives The aim of our study was to evaluate the extra-glandular manifestations not included in disease activity indexes (Sjogren9s Syndrome Disease Activity Index and EULAR Sjogren9s Syndrome Disease Activity Index). Methods We conducted a multicenter descriptive transversal study of pSS patients fulfilling European/American criteria, from 33 Spanish rheumatology departments. Patients were selected by randomization. Every patient was interviewed for data collection and signed an informed consent. Data were also collected by reviewing medical records. Local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians and rates. Chi-square was used to establish the statistical associations. A p Results Four hundred and thirty-seven patients were included. Ninety-five percent of them were women. The median age of the cohort was 58 years. Nineteen percent of the patients referred involvement of the trachea or upper airway. Twenty-one percent of the patients developed Raynaud phenomenon. Twelve (2.7%) patients suffered cardiac impairment (6 pericarditis and 6 cardiac conduction disorders). Thirteen percent of the patients referred digestive involvement, being chronic atrophic gastritis the most frequent condition (21 patients), followed by esophageal motility alteration (12 patients), followed by lymphocytic colitis (3 patients). Seven percent of the patients developed hepatic involvement: primary biliary cirrhosis and autoimmune hepatitis were the most frequent (15 and 14 patients, respectively), followed by autoimmune cholangitis in 3 patients; 55 patients (13%) had anti-LKM antibodies, 15 patients anti-mitochondrial antibodies, and 5 patients anti-smooth muscle antibodies. Seven patients had pancreatic involvement. Seventy-eight patients (18%) had thyroid involvement: anti-thyroid peroxidase (anti-TPO) hypothyroidism was the most frequent (41 patients), followed by subclinical hypothyroidism in 23 patients, negative anti-TPO hypothyroidism in 12 patients, anti-TPO+ hyperthyroidism in one patient and anti-TPO- hyperthyroidism in one patient. Thyroid involvement was significantly more frequently in patients with anti-Ro+. Raynaud phenomenon was significantly more frequent in patients with anti-La antibodies. Digestive involvement was significantly more frequent in patients with low C3. Pancreatic involvement was significantly more frequent in patients with low C3 and C4. Hepatic and trachea involvement were significantly more frequent in patients with hypergammaglobulinemia. Conclusions Twenty percent of the patients with primary Sjogren syndrome developed extra-glandular manifestations not included in disease activity indexes. Serological characteristics may be helpful in identifying this subgroup of patients. Disclosure of Interest None declared

Background Nowadays there is a great variability in evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding, in part due to lack of knowledge. Objectives To develop recommendations on the evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding based on the best evidence and experience. Methods Recommendations were generated following nominal group methodology and Delphi technique. A panel of experts was established (12 rheumatologists). A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in the 1st panel meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinements. A national survey analyzing different aspects of this topic was undertaken separately. Then, a Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Results A total of 14 recommendations (see figure) were generated on the pre-conception period (oral and hormonal anticonception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High risk situations were included as lupus or antiphospholipid syndrome. A consensus >90% was reached in all but one recommendation. Conclusions These recommendations are intended to provide rheumatologists, patients, families and other stakeholders a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during fertility, pregnancy, post-partum and breastfeeding. Disclosure of Interest None declared

Background Primary Sjogren9s syndrome (pSS) is a chronic systemic autoimmune disease with a substantial impact on patient9s quality of life and associated comorbidities could worsen the prognosis and complicate the management of the disease. Objectives The aim of our study was to describe comorbidities in a Spanish cohort os pSS patients. Methods We took advantage of a multicenter descriptive transversal study of a cohort of pSS patients fulfilling European/American criteria. It is a randomised register of patients obtained from thirty three Reumathology clinics all over Spain. The presence of comorbidities was investigated in every patient. Previous informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). Results A total of 437 patients were included, 95% of them women, with a median age of 58 years. Dyslipidemia was the most common comorbidity, appearing in 33% of the cases, with hypertension in second place with a prevalence of 25%. Osteoporosis was present in 18% of patients. Furthermore, 37 patients had at least an osteoporotic fracture. Seventy four patients had never smoked. Diabetes was present in 6% of cases. Less than 7% of the patients had some kind of cardiovascular event: 4 patients ischemic heart disease, 14 patients peripheral arterial disease and 15 patients strokes. Among patients with peripheral arterial disease, only one patient showed positive anti phospholipid antibodies. Thirteen patients (3%) had heart failure. Sixty four patients (14%) had fibromyalgia. Five patients (1%) had celiac disease and 2 (0.46%), multiple sclerosis. Seven lymphomas were observed, four of them MALT type and two Hogdkin9s disease. Three patients developed multiple myeloma and two Waldenstrom9s macroglobulinemia. Twenty one cases of other malignancy were registered. Conclusions Primary Sjogren9s syndrome9s patients frequently present associated comorbidities, been dyslipidemia, arterial hypertension and osteoporosis the most prevalent. Lymphoma prevalence rate for this series is 1,6 percent. Disclosure of Interest None declared

Background Primary Sjogren syndrome (pSS) is a systemic autoimmune disease affecting primarily the exocrine glandular system that requires a multidisciplinary approach. Objectives The aim of our study was to describe the clinical and epidemiological features of a pSS9s cohort of patients visited in Spanish Reumathology Departments Methods This is a multicenter descriptive transversal study of pSS patients fulfilling European/American consensus criteria from thirty three Rheumatology departments. Patients were included by randomisati from an anonymized list provided by every department. Data were collected by reviewing clinical records and an interviewing the patients. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). Results Four hundred and thirtyseven patients were included. Ninety five percent of them were women, with a median age of 58. Eighteen percent of the patients had a familiar history of autoimmune disease, most commonly rheumatoid arthritis. Median age at the time of the first symptoms was 46 years and at pSS9s diagnosis was 50 years. Ocular symptoms (94%) were the most frequent complaint, followed by mouth dryness (94%), and ocular foreign body sensation (92%). Schirmer9s test was performed in 402 patients and was positive in 85% of the cases. Basal salivary flow test was performed in 133 patients, and 89% were positive. Rose Bengal staining test was performed in 144 patients and was positive in 81 percent of them. Salivary gland scintigraphy was performed in more than fifty percent of patients and 87% showed abnormal results. Salivary gland biopsy was obtained in 193 patients, fulfilling histological criteria in 69% of them. Anti-Ro/SS-A, in 93% of the cases, and anti-La/SS-B, in 67%, were found positive during follow up. Only 27% of the patients fulfilled the new 2012 SICCA-ACR classification criteria. Conclusions The clinical and demographical profile of pSS patients from Spanish rheumatology departments is similar to that previously described in other series. Diagnostic delay is substantial. A majority of patients showed ocular and oral symptoms. Schirmer test was the preferred diagnostic test used for dry eye evaluation. Only a small group of patients fulfilled the new 2012 ACR classification criteria. Disclosure of Interest None declared

Background There is strong evidence that Rheumatoid Arthritis (RA) patients expressing anti-cyclic citrullinated peptide antibodies (ACPA) have a differential genetic background compared to ACPA-negative RA patients. Objectives We performed a genome-wide association study (GWAS) on ACPA-positive RA patients to identify additional disease susceptibility genes. Methods A total of 924 ACPA-positive RA patients and 1,524 healthy controls were genotyped in 582,591 single-nucleotide polymorphisms (SNPs) in the discovery phase. The most significant SNPs were then analyzed in an independent cohort of 863 ACPA-positive patients and 1,152 healthy controls. Results In the discovery phase we found suggestive association ( P P SLC8A3 ) and the risk to develop ACPA-positive RA (OR (95%CI): 1.42 (1.25-1.6), combined P =3.19e-8). Conclusions This study identified a new locus associated with ACPA-positive RA. These results support the evidence that RA patients positive for ACPA have a specific genetic background. Disclosure of Interest None declared

Background Primary Sjogren syndrome (pSS) is a systemic autoimmune disease affecting primarily the exocrine glandular system. More than half of the patients with 10 or more years of follow up show extra-glandular manifestations, which will be determinant for the prognosis. Several validated methods are available in order to assess activity in pSS, including the Sjogren9s Syndrome Disease Activity Index (SSDAI) and the EULAR Sjogren9s Syndrome Disease Activity Index ESSDAI). Objectives The aim of our study was to evaluate disease activity in a representative cohort of patients followed in rheumatology departments. Methods We conducted a multicenter descriptive transversal study of a cohort of Spanish pSS patients fulfilling European/American criteria. It is a randomised register of patients obtained from 33 spanish rheumatology departments. We used SSDAI and ESSDAI in every patient. Informed consent was obtained and local ethics committees approved the study. Variables were analysed by descriptive statistical methods, using means, medians, and rates, with their deviations and interquartile ranges (p25-p75). Results A total of 437 patients were included. Median score for SSDAI was 1 (0-3, p25-p75) and for ESSDAI was 2 (0-4, p25-p75). More than 95% of patients did not show fever, night sweating or weight loss. Twenty percent of them manifested weakness. Less than 5% of patients suffered glandular inflammatory disease or lymphadenopathy. Thirty two percent referred joint pain with stiffness but only 3% had true sinovitis. Fourteen patients (3%) showed cutaneous involvement. Fourteen percent of patients developed pleural involvement. High resolution CT was performed in 89 patients and showed interstitial disease in less than 4% percent of them. Serum creatinine was elevated in 3% of the cases. Seven patients developed tubular acidosis and 2 patients glomerular involvement. Less than two percent of patients had central nervous system involvement and 3% had peripheral nervous system involvement. Twenty seven percent of patients developed some kind of cytopenia: anaemia 14%, lymphopenia 14%, neutropenia 7% and thrombocytopenia, 9%. Twenty three percent had monoclonal component and/or hypoclomplementemia and/or hypergammaglobulinemia and/or high Ig G levels. Four percent showed cryoglobulinemia and/or hypergammaglobulinemia and/or high Ig G levels and/or recent hypogammaglobulinemia or a recent IgG levels fall. Conclusions pSS patients show low scores at the systemic damage indexes. Most affected domains were haematological, biological and articular. Considering parenchymatous and pleural involvement, lung is the organ most frequently involved. Disclosure of Interest None declared

Background There are scanty data about infection in Systemic Lupus Erythematosus (SLE) patients from large multicenter cohorts. Objectives To describe the prevalence of severe infection (SInf), investigate associated factors and clinical meaning in a large SLE cohort from Spanish Rheumatology Society Lupus Registry (RELESSER). Methods Patients with Sinf were compared with patients without SInf in terms of severity, damage, comorbidities and demographic characteristics (bivariate analysis and Cox regression to survival until the first infection). Results A total of 3.658 SLE patients included, 90% female, median age 32.9 years (DQ 9.7), 93% Caucasian and 5% Hispanic (Amerindian,mestizo). Mean follow-up (months) was 120.2 (SD: ±87.6). A total of 705 (19.3%) of the patients suffered ≥1 SInf, with an overall of 1.227 SInf. The density of incidence was 29.2 (95%CI: 27.6 - 30.9) infections/ 1000 patients-year. The survival until second infection was lower than survival until first infection (log rank p Conclusions SInf remains a frequent and potentially fatal complication of SLE and/or immunosuppressive therapies, and it9s a marker of more severe disease. Respiratory bacterial infections are the most common SInf in SLE, but bloodstream infections are the most common mortal ones. A previous infectious event seems to increment the risk of a subsequent infection in SLE. SInf are more common in male and Hispanics and is associated age, tobacco use and other co-morbidities. Antimalarials use exerts a time-dependent protective effect Disclosure of Interest None declared