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Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Objective: To compare the accuracy of the Birmingham Vasculitis Activity Score (BVAS), version 3, and the Five Factor Score (FFS), version 1996 and version 2009, to assess survival in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Methods: A total of 550 patients with AAV (41.1% with granulomatosis with polyangiitis, 37.3% with microscopic polyangiitis, and 21.6% with eosinophilic granulomatosis with polyangiitis), diagnosed between 1990 and 2016, were analyzed. Receiver operating characteristic (ROC) curves and multivariable Cox analysis were used to assess the relationships between the outcome and the different scores. Results: Overall mortality was 33.1%. The mean ± SD BVAS at diagnosis was 17.96 ± 7.82 and was significantly higher in nonsurvivors than in survivors (mean ± SD 20.0 ± 8.14 versus 16.95 ± 7.47, respectively; P < 0.001). The mean ± SD 1996 FFS and 2009 FFS were 0.81 ± 0.94 and 1.47 ± 1.16, respectively, and were significantly higher in nonsurvivors than in survivors (mean ± SD 1996 FFS 1.17 ± 1.07 versus 0.63 ± 0.81 [P < 0.001] and 2009 FFS 2.13 ± 1.09 versus 1.15 ± 1.05 [P < 0.001], respectively). Mortality rates increased according to the different 1996 FFS and 2009 FFS categories. In multivariate analysis, BVAS, 1996 FFS, and 2009 FFS were significantly related to death (P = 0.007, P = 0.020, P < 0.001, respectively), but the stronger predictor was the 2009 FFS (hazard ratio 2.9 [95% confidence interval 2.4–3.6]). When the accuracy of BVAS, 1996 FFS, and 2009 FFS to predict survival was compared in the global cohort, ROC analysis yielded area under the curve values of 0.60, 0.65, and 0.74, respectively, indicating that 2009 FFS had the best performance. Similar results were obtained when comparing these scores in patients diagnosed before and after 2001 and when assessing the 1-year, 5-year, and long-term mortality. Correlation among BVAS and 1996 FFS was modest (r = 0.49; P < 0.001) but higher than between BVAS and the 2009 FFS (r = 0.28; P < 0.001). Conclusion: BVAS and FFS are useful to predict survival in AAV, but the 2009 FFS has the best prognostic accuracy at any point of the disease course.

Resume Contexte La maladie associee aux IgG4 (MAG-4) est une maladie auto-immune qui declenche une cascade inflammatoire aboutissant a une fibrose. Les criteres d’evaluation sont limites et les options therapeutiques insuffisamment explorees. Objectifs Evaluer la variation du score d’activite de la MAG-4 (IgG4-RI) dans une cohorte de patients atteints et explorer leurs traitements et resultats. Methodes Nous avons etudie le phenotype clinique, la gravite de la maladie et la reponse au traitement dans une etude longitudinale multicentrique ambispective menee dans 14 hopitaux en Espagne. Tous les patients remplissaient les criteres de diagnostic du consensus international de 2012 sur cette maladie. Resultats Soixante-huit patients ont ete inclus, d’âge moyen 53,4 ans, avec une predominance d’hommes. Les tissus les plus frequemment touches etaient le retroperitoine (33 %), des pseudotumeurs de l’orbite (28 %) et les sinus maxillaires et paranasaux (24 %). Le score IgG4-RI etait plus eleve lorsque plusieurs organes etaient atteints et avant traitement. Il diminuait apres le traitement, ce qui est conforme aux taux eleves de reponse au traitement. La plupart des patients ont ete traites par glucocorticoides (GC), chirurgie, azathioprine (AZA), mycophenolate mofetil (MMF) ou rituximab (RTX). La plupart des episodes d’activite de la MAG-4 ont ete pris en charge avec des GC seuls, des GC et une intervention chirurgicale ou des GC et de l’AZA. Les taux de reponse etaient eleves pour tous les traitements mais les rechutes et les poussees etaient frequentes. Conclusion Le score IgG4-RI, encore en developpement, est un indicateur prometteur dans la MAG-4. Les algorithmes de traitement ne sont pas clairement definis. Les GC et le RTX sont les traitements medicamenteux disponibles soutenus par le plus d’elements probants. Il est possible que les traitements de fond antirhumatismaux jouent un role dans la MAG-4, justifiant de nouvelles etudes prospectives.

To evaluate the clinical manifestations, long-term clinical outcome and longitudinal pulmonary function in a large cohort of Spanish patients with anti-Jo1 antibodies.We retrospectively analyzed the clinical data and lung function parameters of 148 anti-Jo1 patients recruited from a multicentre registry including 18 Spanish hospitals. A composite endpoint was defined, comprising death due to respiratory failure directly related to antisynthetase syndrome (ASS), the need for long-term oxygen therapy or lung transplantation.Median follow-up was 78.3 months. Clinical presentation patterns at onset are as follows: isolated interstitial lung disease (ILD) (32.4%), isolated myositis (26.9%), concomitant myositis and ILD (22.8%), and isolated polyarthritis (17.9%). Myositis with ILD was the most frequent final clinical phenotype (67.6%). In most ASS patients, ILD was a non-progressive disease, tending to stabilize with therapy. The endpoint was reached in a significantly larger number of ILD patients with dyspnea at onset than those with paucisymptomatic or asymptomatic forms (p = 0.01). A steady FVC decrease was the hallmark of patients with end-stage lung disease. Estimated survival rates were 87.7% and 75.4% at 5 and 10 years, respectively. Cancer (p = 0.02) and advanced age at ASS diagnosis (p0.0001) were related to poorer survival. Mortality was significantly higher than in the general Spanish population, with a standardised mortality ratio (95% CI) of 4.03 (2.79-5.64).Anti-Jo1 ASS is a heterogeneous syndrome. ILD in ASS under immunosuppressive therapy is mainly a non-progressive disease. Dyspnea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis.

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.

Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P

Objectives To characterise the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically-guided multivariate model. Methods The HLH Study Group of the Spanish Group of Autoimmune Diseases (GEAS) was formed in 2013 with the aim of collecting a large series of Spanish adult patients with HLH with substantial experience in the management of patients with systemic diseases. By October 2017, the database included 151 consecutive patients who fulfilled at least 5 of the 8 criteria proposed by the Histiocytosis Society in 2004. Results The cohort consisted of 151 patients (91 male, mean age 51.4 years). After a mean follow-up of 17 months, 80 (53%) patients died. With respect to the HLH-dependent variables, adenopathies (HR 0.63, p=0.040), low platelets (HR 3.39, p=0.008), leukopenia (HR 1.81, p=0.047), severe hyponatremia (HR 1.61, p=0.042), disseminated intravascular coagulation (HR 1.87, p=0.034), bacterial infection (HR 1.99, p=0.025), mixed microbiological infections (HR 3.42, p=0.008) and >1 infectious trigger (HR 2.95, p=0.003) were associated with death. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (p 1 (p=0.011) infections and glucocorticoid monotherapy (p=0.021). After adjusting for confounding variables, platelets 1 infectious trigger (HR 3.43) and mixed microbiological infection (HR 2.96) remained significant. Multivariate Cox proportional hazards regression analysis identified >1 infectious trigger (HR 2.60, 95% CI 1.16 to 5.84) as the only variable independently associated with death. Conclusions The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with >1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation and therapeutic management. Disclosure of Interest None declared

Objectives To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjogren syndrome (SjS). Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS. By January 2018, the database included 1535 consecutive patients fulfilling the 2002/2016 criteria. Life-threatening systemic disease was defined as an activity level scored as “High” in at least one ESSDAI domain. Results 209 (14%) were classified as presenting with a life-threatening systemic disease: 194 presented one ESSDAI domain classified as high, 14 two domains and only one presented three high activity domains. The high-ESSDAI domains included lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 22 (10%), cutaneous in 18 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%); the most frequent clinical presentations in each domain were, respectively, parotid lymphoma (n=41), focal neurological deficit (n=20), ganglionopathy (n=11), usual interstitial pneumonitis (n=9), renal failure (n=11), ulcerated cutaneous vasculitis (n=9), symmetric polyarthritis (m=17), severe thrombocytopenia (n=3) and severe myositis (n=3). With respect to therapeutic approach, 144 (69%) required glucocorticoids, 65 (31%) immunosuppressive agents and 42 (20%) biological therapies. During the follow-up, 36 (17%) patients died, mainly due to lymphoma (n=16), pulmonary fibrosis (n=5), end-stage renal failure (n=4), CNS progressive disease (n=3) and systemic vasculitis (n=3). Conclusions A 14% of patients with primary SjS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases. Disclosure of Interest None declared

Influence of epidemiology and ethnicity on systemic expression of primary Sjogren syndrome in 9974 patients

Background GCA is an inflamatory vasculitis affecting medium and large-sized arteries, that can result in arteritic anterior ischaemic optic neuropathy. C-reactive protein (CRP) level and erythocyte sedimentation rate (ESR) are usually elevated at GCA diagnosis, but inflammatory-marker negative disease does occur. Objectives To analyse the clinical and histological findings of patients with biopsy-proven GCA and negative inflammatory-markers at diagnosis. Methods multicenter-longitudinal retrospective study that included patients with biopsy-proven GCA recruited at 10 Hospitals from Spain (REVAS Study). Statistical analysis was performed using SPSS vs. 21. Results 418 patients: 290 (69.4%) females (ratio F/M: 2.3/1) were included. The mean age at diagnosis was 75.5±7 (53–92). The most frequent symptoms at diagnosis were recent onset headache (81%), toxic syndrome (47%) and rheumatic polymyalgia (44.5%). Jaw claudication, cranial hyperesthesia and amaurosis fugax were reported by 44.5%, 31.8% and 16.5% of patients, respectively. A total of 84 patients suffered permanent vision loss. Fourteen patients (3.3%) had normal ESR ( Conclusions typically patients with GCA present with elevated inflammatory-markers (ESR and CRP) at disease onset. However, a few percentages of patients (4%–5%) have normal ESR and CPR at diagnosis.1 In our series, 3.3% of patients had negative inflammatory-markers at diagnosis. These patients had fewer constitutional symptoms and more visual symptoms (amaurosis fugax and permanent visual loss) than patients with elevated ESR and/or CRP. Our result are similar to those published in the laiterature. Abnormal temporal arteries on physical examination may help to diagnosis Reference [1] Utility of Erithrocyte sedimentation rate and C-reactive protein for the diagnosis of Giant Cell arteritis. Semin Arthrithis Rheum2012;41:866–71 Disclosure of Interest None declared

Objectives To analyse whether thoracic involvement at diagnosis is associated with a specific clinical presentation of sarcoidosis. Methods The SARCOGEAS-SEMI is a nationwide registry of patients with sarcoidosis. Radiographic stages at diagnosis were classified as stage 0 (normal), stage I (only bilateral hilar lymphadenopathy -BHL-), stage II (BHL +pulmonary infiltrates), stage III (only infiltrates) and stage IV (fibrosis). Results The cohort consisted of 1245 patients (722 women, 523 men, mean age at diagnosis 47 years). Pulmonary imaging data at diagnosis was available in 1230 patients including 395 (32%) with stage I, 500 (40%) with stage II, 195 (16%) with stage III and 42 (3%) with stage IV. Patients with no thoracic involvement (stage 0) were more frequently women (73% vs 56%, p=0.002), older (52.1 vs 46.8 years, p=0.001) and had a higher frequency of skin (54% vs 34%, p Conclusions A specific clinical and epidemiological pattern of disease presentation was found in patients with no thoracic involvement and in those presenting with interstitial lung disease at diagnosis. Disclosure of Interest None declared

Objectives To take a “high-definition” picture of the main features of primary Sjogren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. Results By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. Conclusions International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. Disclosure of Interest None declared

Background GPA is a necrotizing granulomatous vasculitis associated with ANCA that usually involves ENT, lung and kidneys. ANCA are mostly directed against proteinase 3 (PR3), although in few cases are directed against myeloperoxidase (MPO) or negative. Objectives To analyse the phenotype, clinical course and outcome of patients with GPA according to ANCA positivity and specificity Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan 1995 and Jan 2016 in 21 Hospitals from Spain (REVAS-Study). We analysed the clinical characteristics, treatment and outcome, depending on the ANCA positivity and specificity. Statistical analysis was performed using SPSSvs.20 Results 221 patients with GPA were included:162 with PR3-ANCA, 36 with MPO-ANCA, and 23 with negative-ANCA. The mean-age at disease onset was higher in patients with MPO-ANCA (59.9□16.5 years) than in patients with PR3-ANCA (50.5□16.5) and negative ANCA (48□14.5), p=0.006. Compared to patients with PR3-ANCA, patients with MPO-ANCA presented a lower prevalence of toxic syndrome (42.9% vs. 55.6%, p=0.021), arthralgias (34.3% vs. 59.9%, p=0.008), arthritis (8.6% vs. 26.5%, p=0.026), pulmonary involvement (cavitated/infiltrated nodules, p=0.007 and p=0.05), and anaemia (57.1% vs. 77.8%, p=0.05). Renal disease was less severe in patients with MPO-ANCA (creatinine ≥1.58 mg/dL 14.3% vs. 30.4%,p=0.04). Subglottic stenosis and sensoryneural deafness were more frequent in patients with MPO-ANCA (20% vs. 6.8%, p=0.05% and 34.3% vs. 18%, p=0.03). The mean BVAS at baseline was lower in patients with MPO-ANCA (16.3□8.8) and negative ANCA (12.5□6.7) than in patients with PR3-ANCA (19.6□8.9), p=0.029. Patients with negative ANCA had less frequently toxic syndrome, fever, arthritis, subglottic stenosis, kidney disease, and peripheral neuropathy, and more frequently orbital masses. Disease relapses were less frequent in patients with MPO-ANCA than in patients with PR3-ANCA (37.1% vs. 48.8%, p=0.04), but more frequent than in patients with negative ANCA (20.8%), p=0.002. Patients with MPO-ANCA and negative ANCA received less frequently oral cyclophosphamide. No significant differences were found related to death in patients with MPO-ANCA and PR3-ANCA. Patients with negative ANCA had the lower mortality Conclusions A small percentage of patients with GPA present MPO-ANCA or negative ANCA. In our series, patients with MPO-ANCA were older at the disease onset, presented limited or less severe organic disease than patients with PR3-ANCA, lower percentage of relapses and lower requirement of aggressive therapies. Patients with negative ANCA had the best prognosis. Our findings are similar to those recently published,1 although our patients with MPO-ANCA were older. Classification of GPA patients considering ANCA specificity can improve the treatment stratification and reduce adverse events. Reference [1] Schirmer JH, et al. Myeloperoxidase-antineutrophil-cytoplasmic-antibody (ANCA) positive Granulomatosis with polyangiitis.A clinically distinct subset of ANCA-assocaited vasculitis. Arthritis Rheum2016;68:2953–63 Disclosure of Interest None declared

To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS).The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain.Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p0.001), lymphopenia (p0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p0.001) and cryoglobulins (p0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p0.001), immunosuppressants (p0.001), intravenous immunoglobulins (p=0.008) and rituximab (p0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved.13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.

Objectives To analyse the influence of geolocation on the clinical systemic presentation of primary Sjogren syndrome (SjS) at diagnosis. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. Centres were classified by continent, with an additional north-south sub-classification according to latitude (>or or or Results The highest baseline ESSDAI scores were reported from Southern vs Northern countries in Europe (7.2 vs 4.6, p Conclusions This study provides the first evidence for a strong influence of geolocation on the systemic phenotype of primary SjS at diagnosis. Geographical determinants should be considered as key variables when systemic disease is scored. Disclosure of Interest None declared

To describe the characteristics of patients with Behçet's disease (BD) who presented with venous thrombosis. In addition, we identified the factors associated with this venous involvement and those related with recurrent venous thrombosis.Up to January 2015, 544 BD patients from 20 Spanish hospitals had been included in the REGEB (REGistro de la Enfermedad de Behçet as Spanish nomenclature). We selected those patients who presented venous thrombosis. Descriptive analysis was performed and factors related with venous thrombosis were identified.Overall, 99 (18.2%) BD patients had vascular thrombosis, 91 (16.7%) of them (16.7%) involving venous vessels and 18 (19.7%) suffered from venous thrombotic relapse. Lower limbs were the most common location of deep venous thrombosis present in up to 60% of patients. In 12 (13.2%) patients, venous thrombosis affected two vascular territories simultaneously and in 6 (6.6%) the venous and arterial involvement coincided in time. Overall, at the diagnosis of venous thrombosis, 97.6% of patients presented concomitantly other clinical symptoms attributable to BD. In logistic regression multivariate analysis factors associated to venous thrombosis were male sex (Odds ratio [OR] 4.3, 95% confidence interval [CI] 2.5-7.7), erythema nodosum (OR 2.4, 95%CI 1.4-4.1), fever (OR 2.0, 95%CI 1.1-3.8), and central nervous system (CNS) involvement (OR 2.5, 95%CI 1.3-4.8). Considering relapses, CNS involvement was an independent risk factor according logistic regression. However, Cox multivariate analysis did not confirm this finding.We identified factors related with venous involvement in patients included in the REGEB cohort.

Background IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored. Objectives To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes. Methods We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis. Results Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common. Conclusions IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.

Background GPA is a necrotizing systemic vasculitis that usually involves ENT, lung and kidneys. Neurological manifestations appear in 25–50% of patients, usually involving peripheral nervous system. CNS involvement, has been reported in only 7–11% of cases Objectives to describe the clinical features and outcome of patients with GPA and CNS involvement in a large series of patients with AAV Methods multicenter retrospective-longitudinal study that encompassed patients diagnosed with AAV between Jan 1995 and Nov 2014 in 21 Centres from Spain (REVAS Study). Statistical anlysis was performed using SSPS vs20 package Results 455 patients (188 GPA, 167 MPA and 100 EGPA) were included. Mean age at diagnosis was 55.7±17.2y. ANCA were positive in 86.8% of cases (35.8% C-ANCA, 51% P-ANCA). Median time to diagnosis was 4 weeks (IQR 10). Median follow-up time was 80 months (IQR 105). Neurological involvement was documented in 156 (34.5%) patients, but only 33 (7.3%) presented CNS involvement at disease onset. From those patients, 20 (60.6%) had GPA. Mean age at diagnosis of patients with GPA and CNS involvement was 51.1±16.7y. ANCA were positive in all cases (15 C-ANCA-PR3, 5 P-ANCA-MPO). Headache was the main neurological symptom (60%) followed by sensory (45%) and motor impairment (35%). MRI and/or angio-CT scan were performed in all cases. Cerebral ischaemic lesions were observed in 10 patients, and granulomatous lesions in 9, including pachymeningitis (n=6), spinal cord pachymeningitis (n=2) and isolated granulomatous lesions (n=1). Lumbar puncture was performed in 8 (40%) patients and revealed CSF abnormalities in 70. Diagnosis was confirmed by meningeal biopsy (n=2), ENT biopsies (n=5) and renal biopsy (n=2) in patients with CNS granulomatous lesions, and by renal, pulmonary or peripheral nerve biopsy in patients with CNS ischemic lesions. Headache was predominant in patients with granulomatous lesions, while sensory and motor impairment were predominant in patients with ischemic lesions. Mean BVAS at disease onset was 29.2±9.7, significantly higher than in GPA total cohort (18.2±9.2). Renal involvement was more common in patients with ischaemic lesions than in those with granulomatous (80% vs. 40%, p Conclusions Patients with GPA and CNS involvement have more severe disease at presentation and more treatment-related side effects than patients without CNS involvement. Long-term neurological sequelae are more frequent in patients with ischaemic lesions and spinal cord pachymeningitis Disclosure of Interest None declared

Background GCA is the most common systemic vasculitis in elderly people. It is characterized by granulomatous involvement of the major branches of the aorta with predilection for the temporal arteries. Headache is the most frequent initial complaint, and permanent visual loss the most feared complication. Objectives to describe the initial manifestations and outcome of CGA in octogenarian patients, and to investigate if there are some differences compared to younger patients Methods demographic, clinical and histological features, treatment and outcome of all patients with biopsy-proven GCA recruited at 11 different Hospitals from Spain (REVAS Study) were analysed. Statistical analysis was performed using SPSS vs. 20 Results among the 418 patients included in the study, 180 (27.5%) were older than 80 y at disease onset (mean age 83.77±3.1, range 80–92y). Cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes) were more prevalent in octogenarian patients than in younger (73% vs. 50%, p=0.018). Headache was the most frequent initial complaint (78.5%), followed by polymyalgia rheumatica (49.6%), jaw claudication (48.7%) and toxic syndrome (43.5%). A total of 28 (24.35%) patients suffered permanent visual loss, due to anterior ischemic optic ischemic neuropathy (n=26) or central retina vein thrombosis (n=4). When compared with younger patients, neither headache, nor jaw claudication, nor scalp tenderness and polymyalgia, were more common in octogenarian patients. Only fever was less common in patients >80 y at diagnosis than in younger (27.7% vs. 72.3%, p=0.006), and permanent visual loss was most prevalent among octogenarian patients (24.3% vs. 15.7%, OR 1.73, 95CI 1.1–2.9, p=0.04). We found an inverse correlation between fever and permanent visual loss (p=0.001). Blindness was significantly correlated with jaw claudication (p=0.006) and amaurosis fugax (p=0.001). We did not found any significant correlation between blindness and vascular risk factors. Regarding to LAB, ESR was higher in octogenarian patients (p=0.006) as well as thrombocytosis >400.000 platelets/mm (p=0.026). No differences were found related to anaemia prevalence. Inflammatory infiltrate with lumen occlusion and giant cells were significantly more prevalent in temporal artery biopsies from patients with permanent bilateral visual loss (p=0.007 and p=0.01, respectively). No differences were found related to treatment. All patients received oral prednisone at tapering dosage, 85.9% calcium and vitamin D supplementation, and 60% bifosfonates. We did not found differences related to treatment-side effects (osteoporotic fracture, diabetes, infections) between octogenarian patients and the younger. Conclusions octogenarian patients with GCA have an increased risk of developing permanent visual compared to younger patients. The presence of jaw claudication and amaurosis fugax must prompt to initiate corticosteroid treatment quickly. No differences were found related to treatment side effects in octogenarian patients. Disclosure of Interest None declared

Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjogren Syndrome : Characterization Of Systemic Disease

Objectives To characterize the risk of solid and hematological cancer in a large, well-characterized cohort of patients with primary Sjogren syndrome (SjS). Methods The GEAS-SS multicenter registry is a network of Spanish reference centers with specific clinical experience in the management of SjS patients. By January 2016, we had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. Multivariate Cox proportional-hazards regression analysis allowed adjustment for age at diagnosis, gender and the statistically-significant baseline variables associated with cancer in the univariate analysis. The sex- and age-specific incidence rates (SIR) of cancer were estimated from 2012 Spanish mortality data modeling, using a set of age-, sex- and site-specific incidence:mortality ratios. Results After a mean follow-up of 91 months (9922.3 person-years), 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (34% of cancers, including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia (HR 1.06, p Conclusions One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with an enhanced risk of development of some types of non-hematological cancers (thyroid, oral cavity and stomach). Disclosure of Interest None declared

Objectives Baseline characterization of European patients diagnosed with primary Sjogren syndrome (SS) according to the 2002 AE criteria. Methods The Big Data Sjogren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS by merging international SS databases. International experts of the EULAR-SS Task Force were invited to participate. By January 2017, the database included 9302 consecutive patients recruited from 21 countries of the 5 continents. Results A total of 6586 (71%) patients were included from European countries. In comparison with non-European countries, European patients had a higher mean age (54 v 51yrs, p Conclusions European patients are diagnosed at older age, are more frequently men, and presented a lower frequency of anti-Ro/La antibodies and a higher frequency of immunological markers related to mixed cryoglobulinemia. Disclosure of Interest None declared

The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren’s syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39–88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet’s Ac1 and GI index (probability to concordance—e(K)—, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398–1.0), specificity of 0.89 (95% CI 0.518–0.997), and a positive probability reason of 9.00 (95% CI 7.1–11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81–1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome. © 2016 SIMI Sin financiación 2.453 JCR (2017) Q2, 41/154 Medicine, General and Internal UEM

ObjectivesTo analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.MethodsThe Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.ResultsWe included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).ConclusionsThis study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

Background AAV are still related to a high morbidity and mortality in spite of new available therapies. To recognize factors associated with a worse prognosis is essential to tailor the treatment Objectives To identify survival prognostic factors in a large cohort of patients with AAV from Spain and analyze changes in the new century Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan95 and Nov14 in 20 Hospitals from Spain (REVAS Study). Statistical analysis was done using SPSS vs21 Results 455 patients were included: 188 (41.3%) GPA, 167 (36.7%) MPA, 100 (22%) EGPA. Mean age at diagnosis was 55.7±17.2 y. ANCA were positive in 86.8% of cases:35.8% C-ANCA and 51% P-ANCA. Median time to diagnosis was 4 weeks (IQR 10). Median follow-up was 80 months (IQR 105). Renal, lung, neurological and cardiac involvement were present in 56.7, 54.7%, 34.5% and 12.7% of cases,respectively. Pulmonary-renal syndrome was observed in 17%, ENT in 44.8% and eye involvement in 13.4%. Mean BVAS at diagnosis was 17.7±7.7. All patients received oral glucocorticoids; 342 (75%) cyclophosphamide (50.3% oral), and 6.6% biological therapy. Dialysis was required in 16.4% of cases and plasma exchange in 7%. During follow-up, 22.2% of patients suffered leucopenia, 39% bacterial infections, 12.7% opportunistic infections and 5.3% neoplasms. One hundred thirty (28.6%) patients died: 74 (44.3%) with PAM, 42 (22.3%) with GPA and 14 (14%) with EGPA (p 65y (HR 4.6), cardiac (HR 3.9) and renal involvement (HR 2.0). ENT involvement was a protector factor (HR 0.4). Bacterial infections during follow-up were also independent predictor of poor prognosis (HR 2.0) Conclusions survival rate in AAV has significantly improved in the new century probably due to new treatment strategies, including less CF and biological therapy. Poor prognostic factors are age>65y, cardiac and renal involvement at diagnosis,and bacterial infections, while ENT involvement is protective. Disclosure of Interest None declared

Background visual loss is the most frequent ischemic complication and the main cause of permanent disability among patients with GCA. To identify factors related to this complication may help physicians to start an early treatment and assay new therapies Objectives To analyse clinical and histological findings related to visual loss in patients with GCA Methods demographic, clinical and histological features of patients with biopsy-proven GCA recruited at 10 Hospitals from Spain (REVAS Study) were analysed. Statistical analysis was performed using SPSS vs. 20 Results 418 patients were included: 290 (69.4%) females (ratio F/M: 2.3/1). The mean age at diagnosis was 75.5 ± 7 (53–92), 55% patients being older than 75y. The median diagnosis delay was 7 weeks (IQR 4–12). Cardiovascular risk factors were present in 45% of patients (hypertension in 48.8%, hypercholesterolemia in 26.6%, diabetes mellitus in 19.4%). The most frequent symptoms at CGA diagnosis were recent onset headache (81%), constitutional symptoms (47%) and polymyalgia rheumatic (44.5%). Jaw claudication, cranial hyperesthesia and amaurosis fugax were reported by 44.5%, 31.8% and 16.5%2 of patients, respectively. A total of 84 patients suffered vision loss (in 4 cases involving both eyes), due to anterior optic ischemic neuropathy (AION) in 78 (92.8%), and to central retinal artery occlusion in 6 (7.1%). CVA was recorded in 6.5% of cases. Anemia was present in 76.3% of patients. Mean ESR was 98±23.4. Patients with visual loss presented more frequently jaw claudication (71.6% vs 39.2%), cranial hyperesthesia (52.6% vs 28.7%) and amaurosis fugax (52.6% vs 8.6%), and less frequently low-grade fever (16.7% vs 43.1%) and toxic syndrome (37.2% vs 53.4%). Regarding to histological findings: patients with visual loss presented on TAB more intimal hyperplasia (70.5% vs 57.7%) and lumen occlusion >50% (53.8 vs 19.4%). No other differences were found. Univariated analysis showed than AION was significantly related to the presence of amaurosis fugax (OR 12.8, 95% CI 7.0–23.3, p Conclusions AION is the most frequent cause of vision loss in GCA. Jaw claudication, cranial hyperesthesia, amaurosis fugax, and age >75 older at diagnosis are significantly related to AION. A wider recognition of the disease would potentially reduce the prevalence of irreversible visual loss among GCA patients. Disclosure of Interest None declared

Background The Birmingham Vasculitis Activity Score (BVAS), and the Five Factor Score (FFS) at the time of diagnosis have been shown useful to asses prognosis in AAV (1,2), but few studies have been done comparing these tools to predict survival Objectives To compare the usefulness of BVAS vs 3, 1996 FFS and 2009 FFS at the time of diagnosis, to predict survival in a large cohort of patients with AAV from Spain Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan1995 and Nov13 in 20 Hospitals from Spain (REVAS Study). Patient survival was assessed by life-table analysis using the Kaplan-Meier method. Statistical analysis was done using SPSS vs21 Results 455 patients were included: 188 (41.3%) GPA, 167 (36.7%) MPA and 100 (22%) EGPA; 50.8% were men. Mean age at diagnosis was 55.7±17.2 y. ANCA were positive in 86.8% of cases: 35.8% C-ANCA and 51% P-ANCA. Median time to diagnosis was 4 weeks (IQR 10). Median follow-up time was 80 months (IQR 105) for global population. Renal involvement was present in 61.5% of cases, lung involvement in 54.7%, pulmonary-renal syndrome in 16.9%, neurological involvement in 34.5%, and cardiac involvement in 12.7%. ENT was observed in 44.8% of cases and eye involvement in 18.9%. Mean BVAS at diagnosis was 17.7±7.7; 1996FFS was ≤1 in 390 (85.8%) patients, and 2009FFS was ≤2 in 361 (79.4%). All patients received oral corticoids, 342 (75.1%) cyclophosphamide (49.7% IV and 50.3% oral), and 6.6% biological therapy. Dialysis was required in 16.4% of cases. During the follow-up, 39.1% of patients suffered bacterial infections, 9.2% sepsis,12.7% opportunistic infections and 5.3% neoplasms. One hundred thirty (28.6%) died:74 (44.3%) with PAM, 42 (22.3%) with GPA and 14 (14%) with EGPA (p Conclusions BVAS and FFS at diagnosis are signifivantly related to survival in AAV, but the stronger predictor of survival is the 2009 FFS. References Merkel P, Cuthbertson D, et al. Comparison of disease activity measures for ANCA-associated vasculitis. ARD 2009;68:103–6 Guillevin L, Seror R, et al. The Five-Factor Score Revisited Assessment of Prognoses of Systemic Necrotizing Vasculitides. Medicine 2011;90:19–27 Disclosure of Interest None declared

Objectives To analyse the influence of ethnicity on the clinical presentation at diagnosis in an international cohort of patients with primary Sjogren syndrome (pSS). Methods The Big Data Sjogren Project is a multicentre registry formed by international experts from the EULAR-SS Task Force. By January 2016, the database included 8315 consecutive patients fulfilling the 2002 AE criteria (20 countries, 5 continents). Ethnicity was classified according to FDA (White=W, Black/African American=B, Asian=A, Hispanic=H, Others=O). Results Ethnicity data was available in 7887 (95%) patients: 6177 W (78%), 1066 A (13%), 393 H (5%), 104 B (1%) and 147 O (2%). European patients were overwhelmingly white compared with Americans (96% vs 52%, p Conclusions White patients had the oldest age at diagnosis, Black/African Americans the highest frequency of men and the lowest mean age, Asians the highest frequency of women, the lowest frequency of sicca symptoms and the highest frequency of Ro/La and Hispanics the highest frequency of abnormal diagnostic tests. Ethnicity plays a capital role in the phenotypic expression at diagnosis of primary SS. Disclosure of Interest None declared

Objectives To analyse the diagnostic approach used in the largest international cohort of patients with primary Sjogren syndrome (pSS) Methods The Big Data Sjogren Project is a multicentre registry formed in 2014 by experts participating in the EULAR-SS Task Force. By January 2016, the database included 8315 consecutive patients fulfilling the 2002 criteria. The main features at diagnosis/recruitment (time of criteria fulfilment) were collected and analysed Results The cohort included 7753 (93%) women (mean age at diagnosis 53 years). Sicca symptoms were reported in more than 90% of patients at diagnosis (92% for dry eye and 92.5% for dry mouth). The diagnostic tests used included the determination of anti-Ro/La antibodies in 8250 (99%) patients, Schirmer test in 6205 (75%), salivary gland biopsy in 5988 (72%), salivary flows in 4941 (59%), corneal stainings in 3304 (40%), scintigraphy in 2578 (31%) and sialography in 873 (10%) patients. The mean number of diagnostic tests included in the 2002 AE criteria was 4.85 ± 1.44 (of a maximum of 8 different tests), and was higher in patients with negative ANA (5.18 vs 4.80 in ANA+, p Conclusions We found a heterogeneous diagnostic approach of pSS with respect to the number of 2002AE diagnostic tests carried out; the approach varied significantly according to geographic origin and baseline immunological profile Disclosure of Interest None declared

BACKGROUND: Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type. METHODS: Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m2 intravenously on Day 1 and fludarabine 25 mg/m2 intravenously on Days 1 through 5 (Days 1-3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m2 on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles. RESULTS: Twenty-two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0-273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression-free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic. CONCLUSIONS: Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first-line systemic treatment for patients with extranodal MALT lymphoma. Cancer 2009. © 2009 American Cancer Society.

Objectives To describe the main characteristics of patients with Behcet9s disease (BD) who presented with thrombosis included in the Spanish BD Registry Group (REGEB) and try to identify the prognostic factors associated with re-thrombosis in this cohort. Methods Up to December 2014, 541 BD patients from 20 Spanish hospitals had been included in the REGEB. We selected those patients who presented thrombotic manifestations. Descriptive analysis was performed and factors related with thrombosis recurrence were identified. This project was performed, on behalf of Systemic Autoimmune Diseases Group (GEAS) of the Spanish Society of Internal Medicine (SEMI). This registry started in 2009, with a multicenter, consecutive, and retrospective design. Results Among 541 BD patients, 85 (16%) had thrombosis. Sixty (70.6%) were men and the mean age of onset of the disease was 27.4 years (11) and median follow-up time was 160 months (range 0-418). Most patients (88.2%) were Caucasian. In 28 (32.9%) cases, HLA B51 was detected. In 36 (42.3%) patients, thrombosis was one of the presenting manifestation of BD and it concurred with other symptoms of BD in 71 (84%). Deep venous thrombosis in the legs (n=49) wasthe most frequent thrombosis followed by cerebral venous sinus thrombosis (n=10). Considering therapy, 68 (80%) patients received anticoagulation, 45 (52.9%) corticosteroids, 25 (29.4%) immunosuppressants and 2 (2.4%) infliximab. During follow-up, 18 (21%) patients presented a second episode of thrombosis and 5 (5.9%) a third. The median time between thrombosis was 26 months (range 1-260). Deep venous thrombosis in the legs was the most frequent (n=13), followed by inferior vena cava thrombosis (n=4), cerebral venous sinus thrombosis (n=3), stroke (n=2), and right ventricle thrombosis (n=1). Other concurrent symptoms of BD were seen in 87% of these events. Treatment at the moment of rethrombosis was anticoagulation in 5; corticosteroids in 9, and immunosuppressants in 5. Rethrombosis was treated with anticoagulants in 20 (87%) cases, corticosteroids in 11 (48%), immunosuppressants in 7 (30%) and adalimumab in one (1%) case. Univariate analysis showed significant association between rethrombosis and central nervous system (CNS) involvement, but it appears unrelated to other clinical signs, gender, use of immunosuppressants or anticoagulation at the moment of the thrombotic event. The Cox multivariate analysis confirmed the relation between rethrombosis and CNS involvement (p=0.26; HR 3.1 CI95% 1.1-8.4) Conclusions In the REGEB cohort, thrombosis was present in 16% of patients and re-thrombosis in 3.3%, respectively. Re-thrombosis was accompanied by other symptoms of disease activity in the majority of cases and were associated with CNS involvement. Prevalence of immunossupressant agents was no different in patients with rethrombosis. Of note, re-thrombosis occurred in one-fifth of patients receiving anticoagulation. Disclosure of Interest None declared

Background Antimitochondrial antibodies (AMA) are autoantibodies directed against proteins of the outer and inner mitochondrial membrane. M2 antibodies stand out because of their high sensitivity and specificity for the identification of primary biliary cirrhosis. Objectives To analyse the prevalence of AMA and M2 autoantibodies in a large cohort of Spanish patients with primary Sjogren syndrome (SS), and to correlate positive results with epidemiological, clinical and immunological expression of the disease. Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS. The cumulated ESSDAI index (2010 EULAR-SS disease activity index) was retrospectively calculated at diagnosis. AMA were detected by indirect immunofluorescence in triple rat tissue and M2 autoantibodies by ELISA against M2 proteins (PDC-E2, BCOADC-E2, OGDC-E2). Results AMA were tested consecutively in 733 patients with primary SS (688 women, mean age at diagnosis of 54.65 yrs), of whom 63 (9%) showed positive results. No significant differences were found in the main epidemiological, clinical and immunological features according to the presence or absence of AMA, except for a higher frequency of anti-Ro/SSA antibodies (83% vs 68%, p=0.015) and leucopenia (33% vs 21%, p=0.038) in AMA+ patients in comparison with those with negative AMA. M2 autoantibodies were tested in 210 patients, of whom 19 (9%) were positive. Comparison of the main epidemiological, clinical and immunological features according to the presence or absence of anti-M2 antibodies showed a higher frequency of anti-Ro/SSA antibodies (95% vs 74%, p=0.049), leucopenia (53% vs 19%, p=0.002), neutropenia (48% vs 22%, p=0.025), low C4 levels (26% vs 6%, p=0.008) and biological activity measured by the ESSDAI (84% vs 50%, p=0.007). We have the paired determination of AMA and anti-M2 in 23 patients with positive results: 12 have concordant positive results and 11 discordant (7 had negative AMA with positive M2, and 4 positive AMA with negative M2). The mean value of M2 autoantibodies in AMA+ patients was twice than in those with negative AMA, although the difference was not statistically significant (85.67 vs 41.51, p=0.126). Conclusions The study showed three key messages: i) the prevalence of AMA/M2 in primary SS was of 9%; ii) AMA/M2 correlated with the coexistence of Ro autoantibodies but not with systemic Sjogren; and iii) nearly half the patients showed discordant results between AMA and M2 positivities. We recommend the use of M2-ELISA to test for AMA in patients with primary SS. Disclosure of Interest None declared

Objectives To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjogren syndrome in daily practice, focusing on the adequacy of drug therapies for the level of systemic activity measured by the ESSDAI score. Methods By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for primary SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine and/or low dose of glucocorticoids (≤20 mg/d), high dose of glucocorticoids (>20 mg/d) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins and/or rituximab). Results The cohort consisted of 1120 patients, including 1048 (94%) females and 72 (6%) males, with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic Sjogren ever used during the follow-up were hydroxychloroquine (HCQ) in 282 (25%) patients, glucocorticoids in 475 (42%, used at doses >20 mg/d in 255 -23%>), immunosuppressive agents in 148 (13%), intravenous immunoglobulins (IVIG) in 25 (2%) and rituximab in 35 (3%) patients. The use of systemic therapies was more frequent in males (p=0.036) and was associated with the presence at diagnosis of anemia (p 20 mg of corticoids and 21/148 (14%) of those treated with immunosuppressive agents patients as inadequately treated, mainly associated with articular involvement of low/moderate activity. Conclusions The management of systemic Sjogren should be organ-specific, using low doses of corticoids in patients with moderate systemic activity, limiting the use of high doses of corticoids and second-line therapies to refractory or potentially-severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted. Disclosure of Interest None declared

Objectives To score systemic activity at diagnosis and correlate baseline activity classified according to the ESSDAI disease activity states with poor outcomes in a large cohort of patients with primary Sjogren syndrome (SS). Methods We include 1216 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of systemic activity were assessed at diagnosis as predictors of poor outcomes (lymphoma and death) using Cox proportional-hazards regression analysis adjusted for age at diagnosis. European systemic activity index (ESSDAI) scores were retrospectively calculated at diagnosis. Disease activity states (DAS) were defined according to the baseline ESSDAI score (low DAS for an ESSDAI Results After a mean follow-up of 114 months, 52 (4%) patients developed hematological neoplasia and 139 (11%) died. The most frequent systemic activity reported at the time of SS diagnosis included articular (37%), biological (35%), hematology (30%) and glandular (24%) involvements. At diagnosis, 138 (11%) patients showed a high DAS, 385 (32%) a moderate DAS, 422 (35%) a low DAS and 266 (22%) had no systemic activity (ESSDAI =0). No significant differences in the main baseline features were found according to the DAS except for the age at SS diagnosis, which was higher in patients with a high DAS (57 yrs vs 53 yrs for moderate DAS, 54 for low DAS and 56 for no activity, p=0.019). Patients who showed a high DAS at diagnosis of SS developed more frequently hematological neoplasia and had a poor survival in comparison with patients who showed no systemic activity (ESSDAI =0) (19% vs 2%, p Conclusions Categorization of baseline systemic activity using the ESSDAI disease activity states at diagnosis of primary Sjogren syndrome is useful to identify patients with a high risk of developing poor outcomes; patients who present at diagnosis with ESSDAI≥14 (high DAS) should be considered a high-risk population and should be followed more closely than those with no systemic activity. Disclosure of Interest None declared

Background AAV are still related to a high morbidity and mortality in spite of therapeutic advances.To identify factors present at diagnosis that are associated with a worse prognosis, it is essential to tailoring the treatment Objectives To describe the long-term survival rate and possible prognostic factors at presentation in a large cohort of patients with AAV from Spain, and compare BVAS a FFS prognostic scores Methods Multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan1995 and Dec 2013 in 20 Hospitals from Spain (REVAS Study). Statistical analysis was done using SPSS vs19. Results Four hundred and fifty patients (50.4% men) were included: 184 GPA,167 MPA and 99 EGPA. ANCA were positive in 86.4% of cases:36.2% C-ANCA, 50.2% P-ANCA. Mean age at diagnosis was 55.6±17.4 y. Mean time to diagnosis was 4 weeks (0-240). The most frequent symptoms at diagnosis were fever (53%),constitutional symptoms (51%), arthralgia (53%), hypertension (29%), purpura (20%) and hemoptisis (19%). Renal failure was present in 47% of cases, lung involvement in 45.3%, pulmonary-renal syndrome in 16%,and cardiac involvement in 11%. Sensory peripheral neuropathy was detected in 16% of cases,mononeuritis multiplex in 28% and CVA in 4.5%. ENT was observed in 35% and eye involvement in 20%. All patients received oral glucocorticoids. Cyclophosphamide was given to 286 patients (45.3%IV and 38% oral). Dialysis was required in 19% of cases and plasma exchange in 7%. During the follow-up 40% of patients suffered bacterial infections, 10% sepsis 14.6% opportunistic infections and 6% neoplasms. One hundred and twenty-nine (28.7%) died: 74 (44.3%) with MPA,41 (22.3%) with WG and 14 (14%) with CSS. Mean survival was 82.5 months (0-307). Mortality was significantly higher in MPA (p=0.00). Poor prognosis factors at diagnosis were renal failure (HR 1.6),cardiac failure (HR 3.3),bacterial infections (HR 1.8)and age at diagnosis >65y (HR 4.1).BVAS and FFS were significantly associated with outcome. Conclusions Among AAV, PAM is associated with the worse prognosis. Renal and cardiac failure, bacterial infections, and age at diagnosis >65y, are associated with a poor clinical outcome. Three of these factors are included in the revised version of FFS, supporting its usefulness as a prognostic score. References Flossmann O, Berden A, de Groot K et al. Long-term patient survival in ANCA-associated vasculitis. ARD 2011;70:488–94. Guillevin L, C,Seror R,et al.The Five-Factor Score Revisited Assessment of Prognoses of Systemic Necrotizing Vasculitides. Medicine 2011;90:19-27. Disclosure of Interest None declared

Background HScore is a numeric scoring system recently proposed by Fardet et al in 2014, designed to estimate the risk of having hemophagocytic syndrome (HS) in adults. Objectives The objective of this study is to analyze the potential use of the HScore as a prognostic factor in a large cohort of Spanish patients with adult HS. Methods In June 2013, the Study Group of Autoimmune Diseases (GEAS-SEMI) created the National Registry of Adult Patients with HS. Patients were diagnosed according to the fulfillment of the Histiocytosis Society criteria proposed in 1991 and updated in 2004. The HScore includes 9 clinical, laboratory and histopathological criteria, and the score may range from 0 to a maximum of 337 points. Results By January 2015, the REGHEM registry included 111 adult patients with HS, 65 (59%) men and 46 (41%) women, with a mean age at diagnosis of 49.16 years (range 12-85 years); nineteen patients (17%) were not born in Spain (58% from Latin America, 21% from Africa and 16% from Asia). Tissular hemophagocytosis was confirmed in 97/107 (87%) cases. The main underlying diseases diagnosed before HS were autoimmune/rheumatological diseases in 36 (33%) patients, chronic infections in 24 (22%) and neoplasia in 25 (23%) patients. The great majority of patients required ICU admission and death occurred in 59 (53%). The HScore was retrospectively calculated in 61 patients in whom all the criteria required could be applied: the mean HScore was 230,03 (range, 58-306). No significant differences for the mean HScore were found with respect to gender, age at diagnosis, underlying diseases, or severe internal organ involvement (pulmonary, renal or central nervous system). However, a higher mean HScore was found in foreign patients (257 vs 222, p=0.02), in patients with concomitant infections with confirmed microbiological isolation (243 vs 214, p=0.022) and in those who required vital support (248 vs 212, p=0.004). Patients who died showed a higher mean HScore in comparison with survivors (241 vs 217, p=0.05). Conclusions Hemophagocytic syndrome is a life-threatening multisystemic disease that often requires vital support in intensive care units. Despite this and the use of a complex therapeutic approach, half of the patients died. We found higher HScores in patients presenting with a complicated HS (concomitant infections, need for vital support and death). The use of the new HScore as prognostic factor may help to identify patients with a poor outcome. Disclosure of Interest None declared

Objectives To analyse the epidemiological, clinical and analytical features at diagnosis and the use of the European systemic activity index (ESSDAI) to predict the development of cancer in a large cohort of Spanish patients with primary Sjogren syndrome (SS). Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included thirteen Spanish reference centers with substantial experience in the management of SS patients. By January 2015, the database included 1216 consecutive patients fulfilling the 2002 classification criteria for primary SS. ESSDAI scores were retrospectively calculated at diagnosis. Disease activity states (DAS) were defined according to the baseline ESSDAI score (low DAS for an ESSDAI Results After a mean follow-up of 114 months, 84 (7%) patients developed solid cancer and 52 (4%) hematological neoplasia. The following baseline features at diagnosis were associated with the development of hematological neoplasia: male gender (19% vs 6%, p Conclusions Systemic and biological activity is closely related to the development of lymphoma in primary SS. Etiopathogenic factors such as B-cell hyperactivity and monoclonal, cryoglobulinemic-driven immunological responses have a dual effect, enhancing the risk of development of both systemic involvement and hematological neoplasia, but not the risk of solid neoplasia, whose development is independent of systemic Sjogren. Disclosure of Interest None declared

Background Haemophagocytic syndrome is an increasingly-recognised condition in adults, characterised by a wide range of aetiologies, symptoms and outcomes, but with a common aetiopathogenic pathway leading to organ damage: an excessive hyperinflammatory response. Objectives To analyze the main epidemiological, clinical features, analytical parameters, therapies and outcomes of patients with haemophagocytic syndrome. Methods In June 2013, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the national registry of patients with haemophagocytic syndrome. Patients fulfilled the diagnostic guidelines proposed by the Histiocyte Society in 1991 and updated in 2004. Results On December 31, 2013, a total of 50 patients with haemophagocytic syndrome were included in the GEAS-SEMI Registry, 31 (62%) men and 19 (38%) women, with a mean age at diagnosis of disease of 49.16 years (range 12-84 years); 18% were not born in Spain. The main signs and symptoms at presentation were fever in 46 (92%) patients, splenomegaly in 34 (68%), hepatomegaly in 27 (54%) and polyadenopathies in 25 (50%) patients.The main organs involved were the lungs in 23 (46%), the kidneys in 15 (30%) and the CNS in 8 (16%). The main analytical markers consisted of severe anemia (mean 7.56 g/L), thrombocytopenia (mean 55436.74/mm 3 ), hypertriglyceridemia (mean 432.89 mg/dL); raised transaminases were found in 40 (80%) patients, raised LDH in 36/48 (75%), and hyponatremia in 30/47 (64%). All patients showed high ferritin serum levels (mean 20392.84, range 413-190544 ng/mL). Tissular hemophagocytosis was confimed in bone marrow smear in 36 (72%) cases, bone marrow biopsy in 10 (20%), liver biopsy in 8 (16%) and other tissues in two. The main associated diseases were infections in 29 (48%) cases, autoimmune/rheumatological in 8 (16%) and hematological neoplasia in 12 (24%). Vital support was required in 28 (56%) patients. Therapies included corticosteroids in 40 patients, etoposide in 12, cyclosporin A in 12, methotrexate in 4, tacrolimus in 2, rituximab in 3, IVIG in 2 and chemotherapy in 5. Death occurred in 26 (52%) patients; the mortality rates according to the baseline disease was 8/12 (67%) in patients with hematological neoplasia, and 16/29 (55%) in those with infectious disease and 1/8 (12%) in those with autoimmune/rheumatic disease. Conclusions The rate of mortality of adult patients diagnosed with haemophagocytic syndrome exceeds 50% of cases, especially in patients with underlying hematological diseases. An early diagnosis is essential in order to initiate appropriate therapy and improve survival of patients with this challenging condition. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.6017

Objectives To analyse the association between the new 2010 EULAR-SS disease activity index (ESSDAI) and death in a large cohort of Spanish patients with primary Sjogren syndrome (pSS) Methods The GEAS-SS multicenter registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS. It includes 12 Spanish centers with experience in the management of SS. By November 2013, the database included 921 patients fulfilling the 2002 classification criteria for pSS. The cumulated ESSDAI index (2010 EULAR-SS disease activity index) was retrospectively calculated at diagnosis. Statistical values were expressed as the hazard ratio (HR) and 95% confidence interval (CI) for death. Results The cohort consisted of 921 patients, including 867 (94%) women with a mean age at diagnosis of 53.81±0.49 years (range, 14-88) and a disease evolution ranging from 6 to 360 months (mean,74.9±4). 882 (96%) patients presented xerostomia, 878 (95%) xerophtalmia, 805/863 (93%) had positive ocular tests, 598/676 (88%) altered parotid scintigraphy and 424/482 (88%) a salivary gland biopsy showing lymphocytic infiltrates grade 3 or 4. After a mean follow-up of 75 months, 83 (9%) patients died due to causes related to SS (n=27), infections (n=17), cardiovascular disease (n=20) and other causes (n=11); the cause of death was unknown in 8 patients. The active domains (score ≥1) associated with mortality were the constitutional (HR 2.66, CI 1.38-5.11), pulmonary (HR 2.13, CI 1.09-4.16) and biological (HR 3.01, CI 1.91-4.76), with the pulmonary and biological domains being independently associated with death. Specific analysis according to the cause of death showed that activity at the constitutional, lymphadenopathy, hematological and biological domains was a predictive factor of death related to pSS (HR of 6.27, 4.99, 2.59 and 7.88, respectively), while activity at the constitutional, cutaneous, pulmonary, renal neurological and hematological domains predicted mortality related to infection (HR of 4.23, 5.93, 5.93, 9.29, 4.46 and 3.7, respectively). No statistical associations were found between activity of the ESSDAI domains and mortality related to cardiovascular disease or other causes of death. Conclusions The degree of activity measured in the majority of domains of the new 2010 EULAR-SS disease activity index (ESSDAI) strongly correlated with mortality in a large cohort of Spanish patients with primary SS. Activity of constitutional and lymphadenopathy domains (closely related to lymphoma) correlated with death caused by the SS itself, while activity in the main extraglandular sites of involvement (in which high doses of corticosteroids and immunosuppressive agents are used) correlated principally with death caused by infection. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4342

Background Amaurosis is the most frequent ischemic complication and the main cause of permanent disability among patients with giant cell arteritis (GCA). Some premonitory symptoms of visual loss such as amaurosis fugax, diplopia and blurry vision have been described Objectives To determine associated clinical and histological findings in patients with GCA and visual loss due to anterior ischemic optic neuropathy (AION). Methods Demographic, clinical and histological features of patients with biopsy-proven GCA recruited at 6 different Hospitals from Spain were analyzed. Statistical analysis was performed using the SPSS vs. 17. Results There were 135 patients, 82 (60.7%) females and 53 (39.3) males, with a mean age of 74.9 ± 7 (58-89) at diagnosis. Cardiovascular risk factors were present in 45% of cases (hypertension in 40%, hypercholesterolemia in 20%, diabetes mellitus in 18.5%, and smoking habit in16.2%). The most frequent symptoms at CGA diagnosis were recent-onset headache (83%), jaw claudication (37%), cranial hyperesthesia 55 (40.7%) and constitutional symptoms (48.1%). Polymyalgia rheumatica was present in 50.4% of cases. Sixteen patients had lost vision due to AION, two of them involving both eyes. Sixty-two percent of patients complained of classical GCA cranial symptoms for an average of 7 weeks (range 2 days to 16 weeks). Seven (43.8%) patients had premonitory visual symptoms before visual loss. Six patients had an apparent isolated polymyalgia rheumatica for an average of 14 months (range 6 to 24 months). Mean ESR was 99 (28-163). 76.3 of patients had anemia. No significant relationship was found between visual loss development and cardiovascular risk factors. AION was significantly related to the presence of amaurosis fugax (p=0.002), jaw claudication (p=0.025) and temporal artery abnormalities on physical examination (p = 0.04). In addition, the presence of giant cells in temporal artery biopsy (p = 0.004), inflammatory infiltrate (p=.0.001) and elastic membrane disruption (p= 0.020), were significantly most frequent in patients with AION. Conclusions A high proportion of patients with permanent visual loss have a delayed diagnosis and treatment. A wider recognition of the disease would potentially reduce the prevalence of irreversible visual loss among GCA patients. References Font C et al. Clinical features in patients with permanent visula loss due to biopsy-proven giant celll arteritis. Br J Rheumatol 1997 Makkuni D. Is intimal hyperplasia a marker of neuro-opthalmic complications of giant cell arteritis?. Rheumatol 2008 Disclosure of Interest None Declared

Background Alveolar haemorrhage (AH) can be a mild or life-threatening manifestation of ANCA-associated vasculitides (AAV), but its prognostic impact and specific characteristics remain unclear. Objectives To determine the clinical features related to AH and the prognostic value of this manifestation in patients with AAV. Methods We analyzed the demographic, clinical and laboratory features of AH in a large series of patients with AAV from 18 different Hospitals of Spain, entered in the Spanish Registry of Systemic Vasculitides (REVAS) between January 1995 and June 2012. Statistical analysis was performed using the SPSS vs. 17. Results There were 343 patients with AAV (144 GPA, 131 MPA and 68 EGPA), with a mean age of 55.1 ± 17.8 yr (range: 17-91) at AAV diagnosis. ANCA were positive in 86.69% of cases (PR3-ANCA in 35.6% and MPO-ANCA in 51.3%). Mean follow-up was 78.6 ± 71.3 months. AH was present as an initial manifestation in 54 (15.7%) patients, 55.5% males and 44.5% females, mean age 57.4 ± 16.1 yr (range 21-84). Fifty-nine percent of patients had positive MPO-ANCA and 38.5% positive PR3-ANCA. Haemoptysis was present in 41 (77.8%) patients. The most frequent concomitant symptoms were fever (57.7%), constitutional symptoms (53.8%) and arthralgias (61%). Simultaneous renal failure (pulmo-renal syndrome) was present in 75% of patients and respiratory failure in 50%. Mechanical ventilation was required in 19.2% cases. Renal biopsy showed rapid crescentic glomerulonephritis in 52% patients. Lung biopsies found active vasculitis in 10 patients. Anemia was present in 96.2% of cases and severe renal failure (creatinine > 5.6 mg/dl) in 25%. Intravenous (iv) metilprednisolone was given to 80.8% of patients, iv cyclophosphamide (CF) to 61.5%, oral CF to 44.2%, azathioprine to 28.8%, methotrexate to 3.8%, mycophenolate to 9.6% and iv immunoglobulin to 7.7%. Plasma exchange was needed in 28.8%, and dialysis in 42.3%. During the follow-up, 48.1% of patients developed bacterial infections (42.3% pneumonia), 26.9% opportunistic infections, and 5.8% neoplasm. Five (9.3%) patients underwent kidney transplantation, and 14 (25.9%) died. AH was significantly related to the presence of haemoptysis (p 5.6 mg/dl, p Conclusions In our series AH was clearly related to MPA and positive MPO-ANCA, in contrast to other reported series (1). Minor or major haemoptysis was the principal event leading to AH diagnosis. AH alone was not predictive of a poor prognosis, although it was associated with high morbidity (mechanical ventilation, pneumonia). Concomitant AH and acute glomerulonephritis (pulmo-renal syndrome) was one of the most severe manifestations of AAV. References Kostianovsky A et al. Alveolar haemorrhage in ANCA-associated vasculitides: 80 patients’ features and prognostic factorsClin Exp Rheum 2012. Lee RW. Pulmonary renal vasculitis syndromes. Autoimmun Rev 2010; 9 :657-60. Disclosure of Interest None Declared