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Objective To analyse a cohort of pregnant patients with systemic lupus erythematosus and compare the outcomes of both the disease and pregnancy with the results of previous studies conducted in the same geographical area. Patients and methods Retrospective cohort study of 37 women with systemic lupus erythematosus (64 pregnancies) followed in a multidisciplinary unit. Comparative study with similar Spanish studies identified after literature search. Results Our cohort was characterized by an older age and by the presence of non-Caucasian patients. Although we found no clinical differences, from the serological point of view our cohort presented a higher frequency of antiphospholipid antibodies. Patients included in this study were treated more frequently with antimalarials and low-dose aspirin. Systemic lupus erythematosus flare frequency was very similar between the different studies, and we did not identify clear predictors for them. Although the rate of live births was similar among studies, the obstetric outcome of our series was better with a very low rate of preeclampsia, preterm birth and low birth weight newborn. The only predictor of adverse obstetric event was age. Conclusions Although changes in the therapeutic attitude and planning of pregnancy in recent years have not had a direct impact on the rate of systemic lupus erythematosus flares during pregnancy, they have meant an improvement in the obstetric results. The introduction of new variables independent of the disease such as age at conception, socio-cultural origin, or the availability of multidisciplinary units should be considered in the results of future studies.

The natural history of antiphospholipid antibodies (aPL) carriers is not well-established. The objectives of the present study were (a) to study the probability of developing clinical criteria of antiphospholipid syndrome (APS), (b) to identify potential risk factors for developing thrombosis and/or obstetric complications, (c) to study the association between the antibody profile and development of APS, and (d) to determine the efficacy of primary prophylaxis. We retrospectively analyzed 138 subjects with positive aPL who did not fulfill clinical criteria for APS. The mean follow-up time was 138 ± 63.0 months. Thirteen patients (9.4%) developed thrombosis after an average period of 73.0 ± 48.0 months. Independent risk factors for thrombosis were smoking, hypertension, thrombocytopenia, and triple aPL positivity. Low-dose acetyl salicylic acid did not prevent thrombotic events. A total of 28 obstetric complications were detected in 92 pregnancies. During the follow-up, only two women developed obstetric APS. Prophylactic treatment in pregnant women was associated with a better outcome in the prevention of early abortions. The thrombosis rate in patients with positive aPL who do not meet diagnostic criteria for APS is 0.82/100 patients-year. Smoking, hypertension, thrombocytopenia, and the aPL profile are independent risk factors for the development of thrombosis in aPL carriers. Although the incidence of obstetric complications in this population is high (31.6%), only a few of them meet APS criteria. In these women, prophylactic treatment might be effective in preventing early abortions.

ObjectivesThe Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA.MethodsThis was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact.ResultsMean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P ConclusionWe demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA.

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78 p = 0.001), obesity (HR 0.53, 95% CI 0.30-0.93 p = 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93 p = 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99 p = 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34 p = 0.011 and HR 2.53, 95% CI 1.61-3.96 p < 0.001).Conclusions: SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4?±?13.7 versus 48.9?±?24.4 ng/ml; p?=?0.0002) and ß-crosslaps (0.21?±?0.17 versus 0.34?±?0.22 ng/ml, p?=?0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects.

OBJECTIVES: (a) To determine serum 25-OH vitamin D (vitD) levels in primary antiphospholipid syndrome (APS) and to compare them with patients with positive antiphospholipid serology who do not meet clinical criteria for APS, and with healthy controls. (b) To analyze the association of vitD levels with both the clinical manifestations and the immunological profile of patients with primary APS. (c) To perform a meta-analysis evaluating potential differences in serum vitD levels between APS and controls as well as the frequency of vitD deficiency in APS patients. METHODS: Retrospective study including 74 patients with primary APS, 54 with positive antiphospholipid (aPL) serology not meeting clinical criteria for APS, and 215 healthy controls. We considered 30 and 10ng/ml as the thresholds for vitD insufficiency and deficiency, respectively. Meta-analysis included four case-control studies (325 primary APS patients and 507 controls) and was conducted by fitting random effects models and checked for heterogeneity. RESULTS: Median serum vitD levels were similar in the three groups: 21ng/ml in primary APS, 25ng/ml in the aPL-positive group, and 21ng/ml in controls (p = 0.115). However, we found differences in the PTH levels, being 40.4 ± 24.9pg/ml in APS, 34.1 ± 18.2pg/ml in aPL serology, and 23.4 ±12.6pg/ml in healthy controls (p < 0.001). Regarding vitD deficiency, we found significant differences across the groups: 16.2% in APS, 11.1% in patients with positive serology, and 3.7% in controls (p = 0.001). There was a trend for the presence of thrombotic events in patients with vitD deficiency (38.9% vs 19.1%, p = 0.071). The meta-analysis confirmed that the combined mean difference in serum vitD levels between APS and controls was -3.605 (p < 0.001) and that APS patients had an increased frequency of vitD deficiency, with an OR = 3.06 (95% CI: 2.12-4.43, p < 0.001). CONCLUSIONS: APS patients show higher frequency of vitD deficiency than the healthy individuals. The meta-analysis study, including three cohorts and ours, suggests that APS patients have significantly lower serum vitD levels and higher frequency of vitD deficiency than controls.

Objectives Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and one of the leading causes of death. Our aim was to analyze the association between emergency room visits due to this disease and meteorological variables and atmospheric contaminant levels in Santander, depending on the origin and trajectory of air masses. Methods Data from emergency room visits at Hospital Marques de Valdecilla were collected on a daily basis during an 8-year period. Data on concentrations of the main atmospheric pollutants and meteorological variables were also recorded. Retrotrajectories leading to Santander at a height of 1500 m above sea level were then calculated. Finally, a correlation model was produced to evaluate the effect of the contaminants on emergency visits due to COPD. Results There is a direct association between PM10 levels and the number of visits to the emergency room due to COPD. For every 10 μg/m3 increase in pollutant levels, emergency visits increase by3.34% (P=.00005), and this effect is enhanced in individuals over 74 years of age. This effect is heightened when PM10 levels depend on air masses from the South and when air recirculation occurs. There is no association between other pollutants and the number of visits to the emergency room. Conclusions Exposure to high levels of PM10 causes exacerbations in COPD patients. By studying the atmospheric circulation pattern, we can predict whether PM10 levels will be inappropriately high, and we can also obtain information about the particle components.

Resumen Objetivos La enfermedad pulmonar obstructiva cronica es una enfermedad de alta prevalencia y una de las principales causas de muerte a nivel mundial. El presente trabajo analiza la relacion de esta enfermedad con las variables meteorologicas y los niveles de contaminantes atmosfericos en Santander, atendiendo al origen y trayectoria de las masas de aire. Metodos Se recogieron datos diarios de visitas a urgencias en el Hospital Marques de Valdecilla de un periodo de 8 anos, asi como la concentracion de los principales contaminantes atmosfericos y de las variables meteorologicas. Posteriormente se calcularon las retrotrayectorias con destino en Santander, a una altura de 1.500 m sobre el nivel del terreno. Finalmente, se elaboro un modelo de correlacion para evaluar el efecto de los contaminantes sobre las urgencias por EPOC. Resultados Existe una asociacion directa entre los niveles de PM10 y las urgencias por EPOC. Por cada 10 μg/m 3 de aumento del contaminante, las urgencias incrementan un 3,34% (p = 0,00005), y el efecto se intensifica en las personas mayores de 74 anos. Cuando los niveles de PM10 son dependientes de masas de aire procedentes del Sur, asi como ante situaciones de recirculacion, el efecto es mayor. Con el resto de contaminantes la relacion con las urgencias no es estadisticamente significativa. Conclusiones La exposicion a PM10 provoca descompensaciones en los pacientes con EPOC. Atendiendo al patron de circulacion atmosferica se puede estimar si los niveles de PM10 van a ser elevados, y tambien se obtiene informacion sobre los componentes de las particulas.

Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by tremor at rest, bradykinesia, rigidity, and loss of postural reflexes. Patients can also exhibit a plethora of non-motor symptoms, such as autonomic dysfunction, sleep disturbances, and neuropsychiatric comorbidities. In the last years, a growing body of evidence has revealed that PD patients have relevant abnormalities in bone health. A substantial number of studies have shown that PD is associated with an increased risk of fractures, with low bone mineral density and with decreased vitamin D levels in serum. Osteoporosis in PD may be understood as a multifactorial process triggered by several causes, such as immobility or low sunlight exposure. However, several lines of evidence suggest that the presence of PD is associated with osteoporosis, fractures, and vitamin D abnormalities since the early stages of the disease and even before the onset of the motor symptoms. In the clinical setting, it must be kept in mind that fractures in PD patients may have deleterious consequences and even increase their functional impairment. In this regard, the availability of treatment guidelines based on clinical trials is an unmet need. This review summarizes the available studies from the last 26 years that have assessed bone health in PD regarding four major issues: (1) risk and specific features of fractures, (2) bone mineral density, (3) the vitamin D status, and (4) treatment options. In addition to the available literature, we endeavor to provide with insights into future developments in this area.

Resumen Introduccion El sindrome antifosfolipido (SAF) es un trastorno inmunitario adquirido, definido por la presencia de trombosis (arterial y/o venosa) y/o morbilidad del embarazo junto con la presencia de anticuerpos antifosfolipidicos (aFL) positivos. Existe una relacion clara entre los aFL y algunas manifestaciones no incluidas en los criterios clinicos, entre ellas, las hematologicas. Objetivos a) estudiar la probabilidad de desarrollar SAF clinico en pacientes con aFL positivos y trombocitopenia; b) identificar posibles factores de riesgo para trombosis, y c) estudiar la asociacion entre trombocitopenia y aFL. Metodos Estudio retrospectivo de 138 pacientes con aFL positivos sin cumplir criterios clinicos de SAF. Se definio trombocitopenia como una cifra de plaquetas ≤ 100.000/μl. Se excluyeron los pacientes con otras causas de trombocitopenia. Resultados Diecisiete de los 138 (12%) pacientes incluidos en el estudio presentaban trombocitopenia. La cifra media de plaquetas fue de 60.000/μl. El riesgo para desarrollar trombocitopenia fue mayor en los pacientes fumadores (OR 2,8; p = 0,044), en aquellos con anticoagulante lupico (OR 13,5; p Conclusiones En nuestra serie, la incidencia de trombocitopenia es del 12%. Los pacientes con aFL positivos que desarrollan trombocitopenia tienen un riesgo potencial de desarrollar trombosis. El tabaco podria ser un factor de riesgo para trombocitopenia. La carga de autoanticuerpos es un factor de riesgo para el desarrollo de trombocitopenia.

The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic.a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL.A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/μl. Patients with other causes of thrombocytopenia were excluded.Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/μl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P.001) and those with higher burden of aPL (OR 50.8; P.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis.In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia.

Introduction Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Materials and methods Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. Results We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p Conclusions SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

Background Spondylodiscitis have a large spectrum of clinical manifestations. The early diagnosis and treatment of this condition are essential to give the patient the best chance of a good outcome. Objectives To analyze the clinical characteristics, most frequent diagnostic methods and different treatments used in spondylodiscitis (SD) in our sanitary area. Methods Descriptive and retrospective study of patients with the diagnose of infectious SD (clinical or microbiological) from 2000 to 2018. In each case we studied the presence of underlying diseases, an episode of infection in the previous 6 months, way of presentation, location, diagnostic methods, treatment and evolution, comparing among different etiologies. Results 66 patients were diagnosed of spondylodiscitis. 44 men (24-90 years: mean 71.7). 62 were pyogenic, 3 tuberculous (TBC) SD, and 1 candida. The patients with TBC were younger (mean age: 45.3; p The most frequent presentation symptoms were: lumbar pain (90%), fever (53%) and neurological deficit (19%). Leucocytosis was present in only a third of the SD, observing an increase of ESR and CRP in the pyogen etiology (p no significative for low number of patients in SD group caused by TBC) and lower levels of hemoglobin, cholesterol and albumin. Lumbar area was affected in the 75.7% of SD (77% in G+ and 50% in G-). In a 13.6% of patients, more than one intersomatic space was affected, being visible the presence of an abscess in 47/66 cases (71.2%). It was necessary surgical treatment in 10/47 (21.2%). 5 patients died due to pathology related to SD (7.5%), without any correlation with a risk factor and other 5 presented a relapse in the subsequent months. Conclusion - The bacterial SD are the predominant group, being DM the most frequent risk factor. - The incidence of SD due to TBC and fungi is scarce in our environment, being absent the Brucella etiology. - The G+ SD usually have a previous associated bacteriemia. - The majority of the patients had pain in the presentation, but only half of them had associated fever. - The most frequent location of SD was lumbar. - We established a 7.5% of mortality rate in our sanitary area. Disclosure of Interests Isla Morante Bolado: None declared, Montserrat Santos Gomez: None declared, Ignacio Villa-Blanco: None declared, Leyre Riancho Zarrabeitia: None declared, Elena Aurrecoechea: None declared, Teresa Ruiz Jimeno: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in SLE patients. Objectives Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results We included 3651 SLE patients and 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin antibodies, 27.3% showed positivity for anti b2glycoprotein I and 24% for lupus anticoagulant). Overall 2283 patients were classified as SLE no aPL, 528 as SLE-APS and 840 as SLE-aPL. Demographic data, clinical and laboratory features in the different groups are showed in Table 1. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than SLE-aPL and SLE no aPL patients (p 0.5 grs), urinary cell casts, seizures and psychosis (p≤0.001). Overall, SLE-APS patients showed a lower rate of cutaneous manifestations and higher rates of neuropsychiatric, cardiac, pulmonary, renal, joint and ophthalmological manifestations (Table 1). In accordance with a more severe clinical profile, higher frequency of anti-DNA antibodies and hypocomplementemia were observed in the SLE-APS group (p Conclusion SLE-APS patients show a more severe clinical profile with higher frequency of major organ involvement and more damage accrual than SLE-aPL and SLE no APL. Disclosure of Interests Leyre Riancho-Zarrabeitia Grant/research support from: Abbvie, Pfizer, UCB, MSD, GSK, Amgen, Roche travel grants, Victor Martinez Taboada: None declared, Inigo Rua-Figueroa: None declared, Fernando Sanchez-Alonso: None declared, Maria Galindo-Izquierdo: None declared, Juan Ovalles: None declared, Alejandro Olive Grant/research support from: ND, Consultant for: ND, Paid instructor for: ND, Speakers bureau: ND, Antonio Fernandez-Nebro: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Raul Menor Almagro: None declared, Eva Tomero Muriel: None declared, Esther Uriarte Isacelaya: None declared, Alina Boteanu: None declared, Mariano Andres: None declared, Mercedes Freire Gonzalez: None declared, Gregorio Santos Soler: None declared, Esther Ruiz Lucea: None declared, Monica Ibanez Barcelo: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Carles Galisteo: None declared, Victor Quevedo Vila: None declared, Enrique Raya: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Lorena Exposito: None declared, Jose A Hernandez Beriain: None declared, Loreto Horcada: None declared, Jose M Pego-Reigosa: None declared

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in SLE patients. Objectives To investigate the association between the different aPL and SLE manifestations as well as to elucidate the influence of the load of antibodies. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results Out of a total of 3651 SLE patients, 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin (aCL) antibodies, 27.3% for anti b2glycoprotein I (aB2GPI) and 24% for lupus anticoagulant (LA)). Regarding the load of antibodies, 20.6%, 12.1% and 4.8% were positive for one, two and three antibodies, respectively. The association between the different aPL, the number of positive antibodies and antiphospholipid syndrome related manifestations is showed in Table 1. Overall, all types of aPL were associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL display a higher risk to develop clinical APS. Regarding specific lupus manifestations, all aPL types showed a significant negative association with cutaneous manifestations. LA and aCL were associated with an increased risk of cardiac, respiratory and neuropsychiatric manifestations (p Conclusion There is a hierarchy for aPL and the risk of APS and lupus manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE patients. IgG isotypes and the load of aPL antibodies increase the risk for clinical APS and major lupus manifestations. Disclosure of Interests: Leyre Riancho-Zarrabeitia Grant/research support from: Abbvie, Pfizer, UCB, MSD, GSK, Amgen, Roche travel grants, Victor Martinez Taboada: None declared, Inigo Rua-Figueroa: None declared, Fernando Sanchez-Alonso: None declared, Maria Galindo-Izquierdo: None declared, Juan Ovalles: None declared, Alejandro Olive Grant/research support from: ND, Consultant for: ND, Paid instructor for: ND, Speakers bureau: ND, Antonio Fernandez-Nebro: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Raul Menor-Almagro: None declared, Eva Tomero Muriel: None declared, Esther Uriarte Isacelaya: None declared, Alina Boteanu: None declared, Mariano Andres: None declared, Mercedes Freire Gonzalez: None declared, Gregorio Santos Soler: None declared, Esther Ruiz Lucea: None declared, Monica Ibanez Barcelo: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000 USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Carles Galisteo: None declared, Victor Quevedo Vila: None declared, Enrique Raya: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Lorena Exposito: None declared, Jose A Hernandez Beriain: None declared, Loreto Horcada: None declared, Jose M Pego-Reigosa: None declared

Background Recurrent pregnancy losses are the most common obstetric manifestation of antiphospholipid syndrome (APS). Despite standard therapy with low dose aspirin (LDA) and low molecular weight heparin (LMWH), the rate of successful pregnancies is not greater than 70%. Corticosteroids have been suggested as a potential therapy in these patients. Our aim is to describe a cohort of patients with obstetric APS treated with low dose corticosteroids. Methods Retrospective study including 9 women diagnosed with primary APS. Clinical records were reviewed to obtain demographic and clinical data. Results Two women had a history of thrombosis, while the remaining 7 had merely obstetric manifestations. All had suffered from early pregnancy losses and 1 of them also had a history of fetal death. We studied 42 pregnancies in these women. The mean number of pregnancies was 4.67±0.71 per woman. Maternal age was 35.8±4.6 years. Overall there were 30 abortions (71.4%) and 1 fetal death (2.4%) Regarding treatments used during pregnancy, 25 (59.5%) pregnancies were on some treatment: LDA (25), LMWH (24), corticosteroids (13), and intravenous immunoglobulins (IVIG) (4). As expected, in all pregnancies treated with corticosteroids, these drugs were combined with LDA and LMWH. When analyzing the effect of therapies, we found a tendency to decrease pregnancy loss in pregnancies treated with LDA (64 vs 82.4%; p=0.3) and LMWH (62.5 vs 83.3%; p=0.18). Treatment with corticosteroids, significantly increased the rate of successful pregnancy (the rate of pregnancy loss was 38.5% in treated vs 86.2% in non treated pregnancies; p=0.003). The results of the global pregnancy analysis were confirmed by bivariate and multivariate GEE analysis. In the bivariate analysis, LDA tended to be protective (OR=0.38, CI 0.11–1.33; p=0.129) and LMWH and corticosteroids significantly protected against pregnancy loss (OR=0.34, CI 0.13–0.85; p=0.021; and OR=0.17, CI 0.06–0.51; p=0.002, respectively). After multivariate analysis, only corticosteroids remained inversely associated with pregnancy loss (OR=0.09, CI 0.012–0.683; p=0.020). However, the independent effects of LDA/LMWH could not be adequately tested because all patients on corticosteroids were also treated with LDA and LMWH. As adverse events, 2 cases of gestational diabetes and 1 of preeclampsia were observed. Conclusions The addition of corticosteroids to standard therapy with LDA and LMWH seems to be safe and effective for improving the pregnancy outcome in women with obstetric APS. Funding Source(s): This work was supported by a next-Val grant from IDIVAL (NVAL 17/19)

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus (SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results We included 3651 SLE patients and 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin antibodies, 27.3% showed positivity for anti b2glycoprotein I and 24% for lupus anticoagulant). Overall 2283 patients were classified as SLE no aPL, 528 as SLE-APS and 840 as SLE-aPL. Demographic data, clinical and laboratory features in the different groups are showed in table 1. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than SLE-aPL and SLE no aPL patients (p 0.5 grs), urinary cell casts, seizures and psychosis (p0.001). Overall, SLE-APS patients showed a lower rate of cutaneous manifestations and higher rates of neuropsychiatric, cardiac, pulmonary, renal, joint and ophthalmological manifestations (table 1). In accordance with a more severe clinical profile, higher frequency of anti-DNA antibodies and hypocomplementemia were observed in the SLE-APS group (p Conclusions SLE-APS patients show a more severe clinical profile with higher frequency of major organ involvement and more damage accrual than SLE-aPL and SLE no APL. Funding Source(s): None

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus (SLE) patients. Our aim is to investigate the association between the different aPL and SLE manifestations as well as to elucidate the influence of the load of antibodies. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results Out of a total of 3651 SLE patients, 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin (aCL) antibodies, 27.3% for anti b2glycoprotein I (aB2GPI) and 24% for lupus anticoagulant (LA)). Regarding the load of antibodies, 20.6%, 12.1% and 4.8% were positive for one, two and three antibodies, respectively. The association between the different aPL, the number of positive antibodies and antiphospholipid syndrome related manifestations is showed in table 1. Overall, all types of aPL were associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL display a higher risk to develop clinical APS. Regarding specific lupus manifestations, all aPL types showed a negative association with cutaneous manifestations, and was also significantly associated with the load of autoantibodies (p Conclusions The present study in a large SLE cohort confirm than there is a hierarchy for aPL and the risk of APS and lupus manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE patients. IgG isotypes and the load of aPL antibodies confer a higher risk for clinical APS and major lupus manifestations. Funding Source(s): None

Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.

Kawasaki disease (KD) is a vasculitis of unelucidated pathogenesis that usually occurs in paediatric patients. In this study we analyse the temporal pattern and geographical distribution of the disease in Spain, and its relationship with atmospheric circulation patterns. We performed a retrospective study in which we collected all hospital admissions due to KD in the country between 2005 and 2015 and explored their relationship with demographic and geographical characteristics. Moreover, we calculated daily surface atmospheric patterns over Spain to study the relationship between weather types (WT) and KD Admissions. The average admission rate for KD in the paediatric population was 3.90 per 100,000, with a male to female ratio of 1.56:1. The highest rate of admissions was found in the 0–4-year-old group, with an incidence of 11.7 cases per 100,000. Admissions followed an annual cyclic pattern with a peak of incidence in January (p = 0.022) and a nadir in September. There was an upwards trend in the number of KD admissions in male sex during the study period (p = 0.004). However, there were marked geographical differences in the incidence rate. Finally, the analysis of the relationship between the WT and the number of admissions by KD revealed no statistically significant association. KD admissions follow a peculiar seasonal and spatial distribution, that suggest the involvement of environmental factors in the disease; however, the absence of an association with WT should be interpreted with caution and regional studies should be done to explore this relationship.

Objectives To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. Methods Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. Results A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13−76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4−8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range—IQR) 0.5 (0−2) versus 0 (0−0) ( p = 0.003), vitritis 0 (0−1.25) versus 0 (0−0) ( p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) ( p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0−30)mg at the onset of the anti-TNF-α therapy to 0 (0−0)mg at 2 years ( p = 0.02). Significant reduction was also achieved in the immunosuppressive load. Conclusion Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Introduction and objective Spontaneous retroperitoneal hematoma (SRH) is a potentially fatal clinical entity requiring immediate recognition and intervention. Material and methods The clinical records of 18-year-old and older patients admitted to the University Hospital Marques de Valdecilla from 2003 to 2013 were reviewed. “Spontaneous” was defined as unrelated to trauma, invasive procedures or bleeding due to aortic aneurysm rupture. Results Thirty-four patients with SRH (44% were on anticoagulant drugs). One-third of cases had chronic renal insufficiency. Abdominal pain was the most common symptom both in anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in non-anticoagulated patients). About one half of the patients developed shock. A CT scan was the most commonly performed diagnostic test, followed by abdominal ultrasound. Most cases were managed conservatively (80%). More than half of the patients (66%) restarted anticoagulation therapy after the acute event with a mean delay of 19 days (range 2–90 days). None of them suffered a new bleeding episode. Conclusion Restarting the anticoagulation treatment after hematoma resolution seems to be a safe practice. There is an increasing frequency of SRH in non-anticoagulated patients.

Background: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC). Methods: Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC. We determined the frequencies of different B-cell subsets in peripheral blood naïve and memory compartments. In addition, we measured serum B cell-activating factor (BAFF) levels and circulating pro-inflammatory cytokines, such as IL-6, by commercial ELISA and CBA, respectively. Results: Patients with pAPS showed a lower percentage of immature and naïve B cells than patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage of non-switched memory B cells than patients with SLE (p = 0.001). No differences either in the percentage of switched memory cells or plasma cells were found among the different groups. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A significant increase in the serum BAFF levels was also observed in pAPS patients compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS (p = 0.011). Conclusions: Our characterization of peripheral blood B-cell phenotypes in pAPS demonstrates different frequencies of circulating B cells at different stages of differentiation. These differences in the naïve B-cell repertoire could explain the higher number and variety of autoantibodies in SLE patients in comparison to pAPS patients, especially in those with obstetric complications.

Background Vitamin D, due to its immunoregulatory properties, has been implicated in the pathogenesis of autoimmune diseases, such as antiphospholipid syndrome (APS). Objectives A) To determine vitamin D levels in patients with primary APS and to compare them with patients with positive antiphospholipid antibodies (aPL), not meeting clinical criteria for APS, and with healthy controls. B) To analyze the association of the vitamin D levels with both the clinical manifestations and the immunological profile of patients with primary APS. Methods We conducted a retrospective study including patients attended at the rheumatology clinic from a tertiary facility in Northern Spain. We included 74 patients with primary APS, 54 patients with positive aPL serology not meeting clinical criteria for APS and 326 healthy controls adjusted by the month of vitamin D analysis. We considered 30 ng/ml and 10 ng/ml as the thresholds for vitamin D insufficiency and deficiency, respectively. Results Median levels of vitamin D were similar in the three groups: 21 (range 5–69) in primary APS, 25 (4–50) in the aPL-positive group, and 21 (4–105) in controls. Overall, 53.9% of measurements were performed during the sunny season (April to September). Ten percent of patients with primary APS were males, versus 16% in the aPL serology group and 26% among healthy controls (p=0.007). Mean age was 46±15 in primary APS, 49±17 in the aPL-positive group and 53±10 in the control group (p Conclusions More than 80% of patients with primary APS have insufficient levels of vitamin D and 16% of them have very low levels of vitamin D. Primary APS patients show a higher frequency of vitamin D deficiency than healthy controls. Patients with vitamin D insufficiency have more commonly positivity for lupus anticoagulant. Disclosure of Interest None declared

Background Antiphospholipid syndrome (APS) is an autoinmune disease characterized by the presence of antiphospholipid antibodies (aPL) and at least one clinical event (thrombosis and /or pregnancy morbidities). The titers of aPL can fluctuate and eventually become negative. This negativization, particularly if persistent, may be associated with a lower frequency of clinical events. Objectives To describe the clinical and serological course of patients with thrombotic APS as well as the factors related with the aPL negativization Methods We performed a retrospective study including patients attended at the Rheumatology clinic from a tertiary hospital in Northern Spain. We included 94 patients with thrombotic APS according to Sidney criteria of 2006. They were classified according to the serological evolution as persistently negative aPL, transiently positive, and persistently positive aPL according to previously established criteria. Results After a mean follow-up of 145±56 months, 48.9% of patients presented a persistently negative serology, whereas in 12.8% it was transiently positive, and persistently positive in 38.3%. When analyzing potential factors related to the negativization (table 1), we found that patients with positive lupus anticoagulant tended to have a persistently negative serology during follow-up, but it did not reach statistical significance (OR 2.7; 95% CI 0.8–9.4; p=0.145). We found no association between traditional cardiovascular risk factors or previous treatments and the serological evolution. Conclusions After a mean follow-up of 12 years, 49% of thrombotic APS patients presented a persistently negative serology. We found no significant association between immunological, traditional cardiovascular risk factors or previous treatments and the persistently negative serology. Disclosure of Interest None declared

Resumen La apoplejia pituitaria (AP) es una enfermedad potencialmente mortal causada por infarto isquemico o hemorragia aguda de un adenoma hipofisario. Aunque normalmente hay paresia oculomotora, la oftalmoplejia completa es una forma rara de presentacion, mas aun si la funcion visual esta respetada. Un varon de 70 anos se presento con cefalea retroorbitaria y oftalmoplejia progresiva completa derecha con agudeza visual preservada. Una RMN revelo una masa hipofisaria con focos hiperintensos en T1 y realce tras la administracion de gadolinio que se extendia hacia ambos senos cavernosos. Los analisis demostraron una insuficiencia hipofisaria parcial. Se inicio tratamiento sustitutivo con corticoides antes de una reseccion transesfenoidal de la masa. El examen anatomopatologico era compatible con un adenoma hipofisario. Una semana tras la intervencion, quedaba una leve limitacion para la abduccion del ojo derecho. La AP deberia tenerse en cuenta en los pacientes con oftalmoplejia y cefalea retroorbitaria aguda. Es necesaria una aproximacion multidisciplinar para resolver la disfuncion hormonal y preservar la funcion visual.

Objectives To explore the clinical and serological course of fertile women with positive antiphospholipid (aPL), and the factors and therapeutic implications associated with aPL negativization. Methods Retrospective study including 105 women with a positive aPL serology between 1995 and 2013 attending the obstetric autoimmune pathology clinic of a tertiary facility. Patients were classified into the following 3 groups: patients with primary antiphospholipid syndrome (pAPS, 49), patients with a positive serology for aPL, not meeting clinical criteria (42), and patients with systemic lupus erythematosus and a positive aPL serology (14). They were also classified according to the serological aPL evolution: persistently negative aPL, transiently positive serology, and persistently positive serology according to established criteria. Results After a mean follow-up of 114.4 ± 37.2 months, 59% of patients had persistently negative antibodies, while 25.7% of patients presented persistently positive aPL serology. Multivariate analysis confirmed that smoking (OR = 4; 95% CI: 1.45?11.08; p = 0.008) was an independent risk factor for positive persistence. Persistent positivity as well as a higher antibody load was associated with higher risk for further pregnancy morbidity. In 29 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 the 40.95 months of follow-up. Conclusions A significant proportion of fertile women with aPL antibodies became negative during follow-up. Tobacco use and the number of positive antibodies are associated with persistently positive serology. Patients with persistently positive aPL serology suffer more obstetric complications. Treatment withdrawal might be safe in selected patients.

Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-αantagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA.

[Background]: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. [Methods]: In order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20-77 yr) with unexplained low ALP levels. [Results]: Nine had mild hyperphosphatemia and three had mild hypercalcemia. ALP levels were inversely correlated with serum calcium (r = - 0.38, p = 0.012), pyridoxal phosphate (PLP; r = - 0.51, p = 0.001) and urine phosphoethanolamine (PEA; r = - 0.49, p = 0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none had major health problems. Mutations in ALPL were found in 21 subjects (50%), including six novel mutations. All but one, were heterozygous mutations. Missense mutations were the most common (present in 18 subjects; 86%) and the majority were predicted to have a damaging effect on protein activity. The presence of a mutated allele was associated with tooth loss (48% versus 12%; p = 0.04), slightly lower levels of serum ALP (p = 0.002), higher levels of PLP (p < 0.0001) and PEA (p < 0.0001), as well as mildly increased serum phosphate (p = 0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. [Conclusion]: One-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinical manifestations are usually mild, in approximately 50% of the cases, enzyme activity is low enough to cause substrate accumulation and may predispose to defects in calcified tissues., This work was supported by an unrestricted grant from Alexion.

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. Areas covered: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Expert opinion: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis.

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients.Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent.Forty-one patients (26women/15 men) were recruited. They had a mean age of 34.414 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n=8), mild leukopenia (n=3), myopathy (n=1), and infections (n=5).ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations., Dr MAG-G received grants/research supports from Abbott, MSD, and Roche, and had consultation fees/participation in company sponsored speaker?s bureau from Abbott, Pfizer, Roche, Janssen, Lilly, Bristol-Meiers, and MSD.; Dr FO-S received grants/research supports from Abbvie.; This work was also partially supported by RETICS Programs, RD08/0075 (RIER), and RD12/0009/0013 from Instituto de Salud Carlos III (ISCIII) (Spain).

Background and objectives: Single-organ vasculitis has been reported to affect the skin, kidneys, central nervous system, peripheral nerves, genitourinary tract, calf muscles, aorta, coronary arteries, retina, or gastrointestinal tract. However, isolated pulmonary vasculitis is a very rare entity. Our aims were to describe a case of localized pulmonary vasculitis affecting medium-sized vessels and review the literature. Methods: A patient with localized pulmonary vasculitis affecting medium-sized vessels that presented as pulmonary arterial hypertension is described. A MEDLINE database search of cases with localized pulmonary vasculitis was also conducted. Results: A 30-year-old man presented with pulmonary hypertension due to isolated pulmonary mediumsized vessel vasculitis that was confirmed histologically. Initially he responded to corticosteroids and vasodilator treatment, but therapy eventually lost efficacy. Treatment with rituximab was not effective, and as the clinical situation worsened, lung transplant was performed. Isolated large pulmonary vessel disease, often related to Takayasu disease or giant cell arteritis, may present as pulmonary artery hypertension, thus mimicking chronic thromboembolic disease. Medium- and small-vessel pulmonary vasculitis usually develops in the context of a systemic disease. Some cases of isolated small-vessel vasculitis have been reported presenting as diffuse alveolar hemorrhage. In contrast, our case developed pulmonary artery hypertension secondary to medium-sized vessels vasculitis. To our knowledge, this is the first case of lung transplantation in isolated pulmonary vasculitis. Conclusions: Pulmonary isolated vasculitis is a rare cause of pulmonary hypertension but it must be taken into consideration after more common disorders are excluded.

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 Intima media thickness (IMT) and coronary artery calcification (CAC) quantification using multidetector computed tomography (MDCT) scanner are useful in detecting subclinical atherosclerosis and are good surrogate markers of cardiovascular morbidity and mortality in general population and in rheumatoid arthritis (RA) A good correlation between these methods has been reported in RA, being CAC a slightly more sensitive technique (1) Objectives Our aim is to determine the value of IMT that better predicts the presence of coronary atherosclerosis, using CAC as reference and assuming CAC value of 100 as the cut-off point indicating high cardiovascular risk. Methods We evaluated 127 RA patients without previous cardiovascular events. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real - time ( QIMT , Esaote , Maastricht , Holland ). According to data from non-rheumatic patients and also from RA patients, an IMT≥0.90 mm is a good predictor of high cardiovascular risk. To determine CAC score, a CT Imaging of coronary arteries using a 32-slice MDCT scanner (Lightspeed, Pro 32, GE Healthcare, USA) was performed. Results Patients with IMT below 0.90 mm had CAC values of 88±210 whereas patients with IMT≥0.90 mm had mean CAC values of 190± 272 (p=0.066). We found a positive correlation between IMT and CAC (correlation coefficient 0,303; p=0.001). The IMT cut-off value ≥0.90 mm had a sensitivity of 32% for detecting CAC ≥100. ROC curve analysis showed and area under the curve of 0.664. The IMT cut-off value of 0.80 mm had a sensitivity of 40% and a specificity of 71.3%. Lowering the IMT cut-off point to 0.70, we reached a sensitivity of 76% and a specificity of 51.5% for CAC ≥100 detection. The positive predictive value for the IMT cut-off point of 0.70 mm was 76% in our population, being the negative predictive value 49.5% Conclusions IMT values ≥0.70 mm predict coronary artery calcification score above 100 with a sensitivity of 76%. According to that, the IMT value considered as predictor of high cardiovascular risk would be 0.70 mm instead of 0.90 mm. References Corrales A et al. “Cardiovascular risk stratification in rheumatic diseases: carotid ultrasound is more sensitive than coronary artery calcification score to detect subclinical atherosclerosis in patients with rheumatoid arthritis” Ann Rheum Dis. 2013,72 1764–1770. Disclosure of Interest None declared

Background Carotid ultrasonography (CU) and coronary artery calcification score (CAC) evaluated by multidetector computed tomography (MDCT) scanner are useful in detecting subclinical atherosclerosis and are good surrogate markers of cardiovascular morbidity and mortality in general population and in rheumatoid arthritis (RA). In RA, a good correlation between both diagnostic methods has been demonstrated, being CU more sensitive for detecting subclinical atherosclerosis. Objectives Our aim is to determine the association between the presence of carotid plaque and CAC quantification, and, using the presence of carotid plaque as a reference, to determine the cut-off value of CAC score that better predicts subclinical carotid atherosclerosis. Methods We evaluated 127 RA patients without previous cardiovascular events. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real - time ( QIMT , Esaote , Maastricht , Holland ). Carotid plaque was defined according to the Manheim Conference Consensus criteria. To determine CAC score, a CT Imaging of coronary arteries using a 32-slice MDCT scanner (Lightspeed, Pro 32, GE Healthcare, USA) was performed. A CAC score ≥100 was considered as a surrogate marker of very high cardiovascular risk. Results Unilateral and bilateral carotid plaque frequency and the mean CAC score in the different groups are summarized in table 1. Patients without carotid plaques had a mean CAC value of 23 ±49 [range 0–250], being 50 ±116 [0–569] in patients with unilateral plaque and 192± 302 [0–1205] in patients with bilateral plaques, being these differences statistically significant (p A ROC curve comparing the presence of carotid plaque and CAC quantification was performed, being the area under the curve 0.692. When we used CAC score value score ≥1 as the cut-off value to predict high cardiovascular risk, the sensitivity and specificity for the presence of carotid plaques increased (69.3% and 64.1%, respectively). Positive predictive value for CAC ≥1 was 81.3% in our population, being 48.1% the negative predictive value. Regarding bilateral carotid plaques, the CAC score ≥100 had a sensitivity of 40%. ROC curve showed an area under the curve of 0.712. Using a CAC score value score ≥1 as the cut-off value to predict high cardiovascular risk, the sensitivity to determine the presence of carotid plaques increased to 76.4% but the specificity decreased to 54.2%. Conclusions A CAC score value score ≥1 is good predictors of carotid plaques, showing sensitivity close to 70%. Our data support the use of a CAC score value score ≥1 instead of a CAC score ≥100 as the cut-off value to predict high cardiovascular risk in patients with RA. Disclosure of Interest None declared

Background Chronic inflammation plays a central role in the development of atherosclerosis, being especially relevant in patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are more prone to suffer cardiovascular events than the general population. Objectives Our aim was to study the prevalence of subclinical atherosclerosis in patients with RA and SLE and determine the differences between these conditions. Methods We evaluated 99 SLE patients and 206 sex- and age-matched RA patients without previous history of cardiovascular events. Subclinical atherosclerosis was defined by the presence of carotid plaque according to Manheim Consensus Conference criteria and/or intima-media thickness ≥0.90 mm. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real - time ( QIMT , Esaote , Maastricht , Holland ). After the univariate analysis, multivariate regression models were fitted to adjust for potential confounders. Results The mean age was 52 ± 13 years in RA and 51±13years in SLE (p=0.77). Demographic data and traditional cardiovascular risk factors are summarized in table 1. Regarding carotid plaques, there were no statistically significant differences. The frequency of carotid plaques was 40.2% among patients with RA and 44.4% in SLE patients. Bilateral plaques were present in 26% patients with RA and in 21.2% of those with SLE. An IMT ≥0.90 mm was observed in 9.8% RA patients and in 6.3% of SLE patients (p= NS). After adjusting for traditional cardiovascular risk factors and disease duration, there were no differences in the frequency of carotid plaques (OR SLE vs RA 1.52; CI 0.88–2.62) or in the frequency of IMT ≥0.90 mm (OR 0.75; CI 0.27–2.07). Conclusions The frequency of subclinical atherosclerosis is similar in patients with SLE and RA after adjusting for traditional cardiovascular risk factors. 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 Carotid plaque (CP) detected by ultrasonography and carotid intima-media thickness (cIMT) are useful surrogate markers for subclinical atherosclerosis and good predictors of cardiovascular disease in the general population and rheumatoid arthritis (RA). Objectives Our aim was to determine if cIMT may predict the presence of carotid plaques. Methods We evaluated 670 RA patients from NW Spain without previous history cardiovascular events. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real-time (QIMT, Esaote, Maastricht, Holland). The cIMT was determined as the average of three measurements in each common carotid artery. The final cIMT was the largest average cIMT (left or right). Carotid plaque was defined according to the Manheim Consensus Conference criteria. Based on studies reported in non-rheumatic patients, a cIMT was considered as associated with high cardiovascular risk if it was ≥0.90 mm. Results Unilateral and bilateral carotid plaque frequency and cIMT values are summarized in table 1. cIMT values were 0.619±0.105 mm in patients without plaques and 0.774 ± 0.161 mm in those with plaques (p Using 0.90 mm as the cIMT cut-off value for high cardiovascular risk, the sensitivity to detect carotid plaques was 21.2% and the specificity 99%. A ROC curve comparing the presence of carotid plaque and cIMT was performed, being the area under the curve 0.795. The best cIMT cut-off point to determine the presence of plaques was considered as the one with the highest sensitivity and specificity. According to that, 0.670 mm was found to be the best cut-off point, being sensitivity and specificity for plaque detection 71.9% and 74% respectively. Positive predictive value for a cIMT ≥0.670 mm was 78.3% in our population, being 66.8% the negative predictive value. Regarding bilateral plaques, a cIMT cut-off value of 0.90 mm had sensitivity of 27.7% and specificity of 96.6%. The ROC curve showed that the best cut-off point for bilateral plaque detection was also 0.670 mm with sensitivity 79.1% and specificity 64.2%. Conclusions In Spanish RA patients cIMT ≥0.670 mm is a good predictor of carotid plaques. Our study suggests the possibility of considering a cIMT lower than 0.90 mm as a predictor of high cardiovascular risk in RA. 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

Objectives To assess the efficacy of Tocilizumab (TCZ) in refractory uveitis associated to juvenile idiopathic arthritis (JiA). Methods Multicenter study of uveitis related to JiA and refractory to at least a) one standard synthetic immunosuppressive drug and, b) 1 anti-TNFα drug. Results We studied 13 patients/24 eyes (2 men/11 women) with a mean age of 20.38±9 years (range 8-38). The most frequent ocular pattern was anterior uveitis (n=11), bilateral (n=11), and chronic (n=13). Besides corticosteroids and before TCZ onset, they had received methotrexate (n=11), cyclosporine A (n=5), mycophenolate (n=1) and leflunomide (n=1). The first biologic treatment was: adalimumab (ADA) (n=6) (40 mg/sc/2 weeks), infliximab (IFX) (n=3) (5 mg/kg/i.v./every 6-8 weeks) and etanercept (ETN) (n=4). Before TCZ onset they had been switched to a second biologic drug (n=11) (most of them due to inefficacy), a third (n=5), a fourth (n=3) and even a fifth biologic therapy (n=1). The median of the duration of uveitis before the onset of TCZ was 122 months [IQR 42-178]. TCZ was used at a conventional dose (8 mg/kg/4 weeks) in most cases and combined in all cases (MTX=7, LFN=4, CsA=1, MMF=1). Improvement from baseline to 1 year was observed in: a) Visual acuity: from 0.46±0.35 to 0.52±0.37 (p=0.007); b) Anterior chamber cells from a median [IQR] of 1 [0.5-2] to 0 [0-0] (p=0.001), c) vitritis from 0 [0-1] to 0 [0-0] (p=0.06) and d) Macular thickness from a mean of 277±127 to 234±32 microns (p=0.04), and this allowed to taper corticosteroids from a mean of prednisone of 15±14 mg/day to 6±5 mg/day. After a mean follow-up of 15.2±8.3 months, ocular remission was achieved in 9 of 13 patients. The most severe adverse events of TCZ were severe thrombocytopenia (1), pneumonia (1), viral conjunctivitis and bullous impetigo (1). Conclusions Tocilizumab seems to be effective in refractory uveitis related to JiA. Disclosure of Interest None declared

Background Patients with systemic lupus erythematosus (SLE) have an increased cardiovascular (CV) risk, probably due to accelerated atherosclerosis. Objectives To analyze the prevalence of subclinical CV disease in SLE using carotid ultrasonography. Methods We studied 36 SLE patients and 127 age and sex matched controls. Traditional CV risk factors were recorded according to a standardized protocol. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real-time (QIMT, Esaote, Maastricht, Holland) to determine carotid intima-media thickness (cIMT) and plaques, according to the Mannheim Carotid Intima-Media Thickness Consensus. Results No statistically significant differences in the frequency of smoking, hypertension, diabetes mellitus or personal and family history of CV events between patients and controls were found. However, the prevalence of dyslipidemia was increased in SLE (31% vs 16% in controls; p=0.056) and SLE patients had a higher body mass index (BMI) (27.1±5.4 vs 25.2±4.8, p=0.051). The cIMT was also significantly higher in SLE patients when compared to controls (0.644±0.122 vs 0.573±0.113 mm; p=0.001). This difference persisted after adjustment for BMI and dyslipidemia (p=0.009). Moreover, the prevalence of carotid plaques in SLE patients was also increased (42% vs 23% in controls; p=0.033). Conclusions Both cIMT and carotid plaque frequency are increased in SLE patients. The presence of carotid plaques identifies individuals at very high cardiovascular risk. Therefore, tight controls of dyslipidemia and other cardiovascular risk factors should be conducted in SLE patients. Disclosure of Interest None declared

Background Patients with Rheumatoid Arthritis (RA) have an increased risk of atherosclerosis and cardiovascular disease (CD) when compared with the general population. Objectives We assessed if the inflammatory burden, the disease activity as well as specific features of the disease correlate with the presence of subclinical atherosclerosis in patients with RA. Methods A cohort of patients with RA without cardiovascular events was studied in a tertiary University Hospital. Carotid ultrasonography was performed by a MyLab 70 scanner (Esaote; Genoa, Italy), equipped with 7–12 MHz linear transducer and the automated software guided technique radiofrequency – Quality Intima Media Thickness in real-time (QIMT, Esaote, Maastricht, Holland) to determine carotid intima-media thickness (cIMT) and plaques, according to the Mannheim Carotid Intima-Media Thickness Consensus. We analyzed disease duration (>2 years, 2-10, >10 years), rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA) status, and PCR and ESR. DAS28 and SDAI were calculated. Logistic regression analyses were performed. Results We assessed 592 patients with RA (456 women/136 men; mean age 59±13 years) without history of cardiovascular events. Among them, 55% and 47% of patients had RF+ and ACPA+ respectively (61% were RF+ and/or ACPA +). The prevalence of plaques was not increased in RF+ and/or ACPA+ patients: OR: 1.02 [0.73-1.43] or in those with erosions on plain radiograph: OR: 1.03 [0.74-1.45]. A significant correlation between the mean CRP values in the last 5 years prior to carotid ultrasound and the cIMT (p=0.012) or the presence of carotid plaques (p=0.006) was found. However, this significant correlation was not observed after adjustment for age and smoking. No correlation between carotid ultrasound and DAS28 and SDAI was found. Conclusions Our study does not support a correlation between subclinical atherosclerosis assessed by carotid ultrasound and disease duration or specific features of RA. Disclosure of Interest None declared