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Background Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients. Methods Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity. Results All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; p=0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025–0.968, p=0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252–1.028), p=0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth. Conclusions The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.

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.

Resumen Objetivo Analizar una cohorte de pacientes embarazadas con lupus eritematoso sistemico y comparar los desenlaces tanto de la enfermedad como del embarazo con los resultados de estudios previos realizados en la misma area geografica. Pacientes y metodos Estudio de cohortes retrospectivo de 37 mujeres con lupus eritematoso sistemico (64 embarazos) seguidas en una consulta multidisciplinar. Estudio comparativo con los estudios espanoles similares identificados tras revision bibliografica. Resultados Nuestra cohorte se caracterizo por una edad mas elevada y por la presencia de pacientes de origen no caucasico. Aunque no encontramos diferencias clinicas relevantes, serologicamente nuestra cohorte presento una mayor frecuencia de anticuerpos antifosfolipido. Las pacientes incluidas en este estudio fueron tratadas mas frecuentemente con antipaludicos y aspirina. La frecuencia de brotes fue muy similar entre los distintos estudios, y no identificamos predictores claros para los mismos. Aunque la tasa de nacidos vivos fue similar, el desenlace obstetrico de nuestra serie fue mejor, con una baja tasa de preeclampsia, parto pretermino y recien nacido de bajo peso. El unico predictor de acontecimiento obstetrico adverso fue la edad. Conclusiones Si bien los cambios en la actitud terapeutica y la planificacion del embarazo no han tenido un impacto directo sobre la tasa de reactivacion del lupus eritematoso sistemico durante el embarazo, si que han supuesto una mejoria en los resultados obstetricos. La introduccion de nuevas variables independientes de la enfermedad como la edad en la concepcion, la procedencia sociocultural, o la disponibilidad de unidades multidisciplinares deberan ser consideradas en los resultados de proximos estudios.

The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) is a tool proposed to quantify the risk for antiphospholipid antibody (aPL)-related clinical manifestations. However, aGAPSS has been validated mainly for thrombotic events and studies on APS-related obstetric manifestations are scarce. Furthermore, the majority of them included patients with positive aPL and different autoimmune diseases. Here, we assess the utility of aGAPSS to predict the response to treatment in aPL carriers without other autoimmune disorders. One-hundred and thirty-seven women with aPL ever pregnant were included. Sixty-five meet the APS classification criteria, 61 had APS-related obstetric manifestations, and 11 were asymptomatic carriers. The patients’ aGAPSS risk was grouped as low (N = 73), medium (6–11, N = 40), and high risk (≥ 12, N = 24). Since vascular risk factors included in the aGAPSS were infrequent in this population (

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.

Objetivo: Investigar la prevalencia de hipercalcemia en pacientes con artritis reumatoide (AR) y analizar las características clínicas y las causas de la hipercalcemia. Material y métodos: Estudio retrospectivo de revisión basado en casos que incluyó 500 pacientes con AR. Se identificaron los pacientes con niveles de calcio aumentados en al menos dos ocasiones. Resultados: La hipercalcemia estuvo presente en 24 de los 500 pacientes con AR (4,8%). La edad osciló entre 50 y 80 años, con una media de 68±10 años. La duración media de la enfermedad fue de 10±7 años. De los pacientes con hipercalcemia, 22 eran mujeres postmenopáusicas (92%) y solo dos eran hombres (8%). El hiperparatiroidismo se encontró en 9 pacientes de la serie; solo un paciente tenía una hipercalcemia maligna debido a un mieloma múltiple, y un caso fue consecuencia de una intoxicación por vitamina D. En un paciente la hipercalcemia parecía relacionada con el síndrome calcio-alcalino. En el resto de pacientes, la hipercalcemia fue idiopática (8/24) o el estudio fue incompleto (4/24). No se encontró una relación evidente entre la actividad de la enfermedad y la aparición de hipercalcemia. Conclusión: Al igual que sucede en la población general, el hiperparatiroidismo primario es la causa más común de hipercalcemia en pacientes con AR. En algunos pacientes no se identificaron otros trastornos causantes de hipercalcemia, lo que plantea la posibilidad de una relación causal entre la AR y la hipercalcemia. Objetive: To investigate the prevalence of hypercalcemia in patients with rheumatoid arthritis (RA) and analyze the clinical features and causes of hypercalcemia. Material and methods: Retrospective case?based review study that included 500 patients with RA. Patients with increased calcium levels on at least two occasions were identified. Results: Hypercalcemia was present in 24 of the 500 RA patients (4.8%). The age ranged between 50 and 80 years, with a mean of 68±10 years. The mean duration of the disease was 10±7 years. Of the patients with hypercalcemia, 22 were postmenopausal women (92%) and only two were men (8%). Hyperparathyroidism was found in 9 patients in the series; only one patient had malignant hypercalcemia due to multiple myeloma, and one case was a consequence of vitamin D intoxication. In one patient, hypercalcemia appeared to be related to calcium?alkali syndrome. In the remaining patients, hypercalcemia was idiopathic (8/24) or the study was incomplete (4/24). No obvious relationship was found between disease activity and the appearance of hypercalcemia. Conclusion: As in the general population, primary hyperparathyroidism is the most common cause of hypercalcemia in patients with RA. In some patients, no other disorders causing hypercalcemia were identified, raising the possibility of a causal relationship between RA and hypercalcemia.

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.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences. Funding: Supported by an investigator-initiated study (MD0075) funded by Kyowa-Kirin to J.A.R.

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.

Supplemental material, sj-pdf-1-lup-10.1177_0961203320950477 for Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality by Leyre Riancho-Zarrabeitia, Victor Martínez-Taboada, Iñigo Rúa-Figueroa, Fernando Alonso, María Galindo-Izquierdo, Juan Ovalles, Alejandro Olivé-Marqués, Antonio Fernández-Nebro, Jaime Calvo-Alén, Raúl Menor-Almagro, Eva Tomero-Muriel, Esther Uriarte-Isacelaya, Alina Botenau, Mariano Andres, Mercedes Freire-González, Gregorio Santos Soler, Esther Ruiz-Lucea, Mónica Ibáñez-Barceló, Iván Castellví, Carlos Galisteo, Víctor Quevedo Vila, Enrique Raya, Javier Narváez-García, Lorena Expósito, José A Hernández-Beriaín, Loreto Horcada, Elena Aurrecoechea and Jose M. Pego-Reigosa in Lupus

Supplemental material, sj-pdf-2-lup-10.1177_0961203320950477 for Antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) implies a more severe disease with more damage accrual and higher mortality by Leyre Riancho-Zarrabeitia, Victor Martínez-Taboada, Iñigo Rúa-Figueroa, Fernando Alonso, María Galindo-Izquierdo, Juan Ovalles, Alejandro Olivé-Marqués, Antonio Fernández-Nebro, Jaime Calvo-Alén, Raúl Menor-Almagro, Eva Tomero-Muriel, Esther Uriarte-Isacelaya, Alina Botenau, Mariano Andres, Mercedes Freire-González, Gregorio Santos Soler, Esther Ruiz-Lucea, Mónica Ibáñez-Barceló, Iván Castellví, Carlos Galisteo, Víctor Quevedo Vila, Enrique Raya, Javier Narváez-García, Lorena Expósito, José A Hernández-Beriaín, Loreto Horcada, Elena Aurrecoechea and Jose M. Pego-Reigosa in Lupus

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.

We report the case of a 15-year old girl who presented with a non-tender right upper eyelid swelling. Magnetic resonance confirmed the presence of an enlargement of the orbicular muscle with moderate contrast enhancement. Biopsy revealed the presence of necrotizing granulomatous vasculitis. Further studies ruled out systemic involvement. Thus, she was diagnosed with isolated granulomatosis with polyangiitis (GPA). Treatment with steroids and methotrexate was started. Due to the persistence of the lesion, rituximab (RTX) was added with excellent clinical and radiological response. This is, to the best of our knowledge, the first case of isolated orbital GPA treated with RTX in a pediatric patient.

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.

PURPOSE OF REVIEW: Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. RECENT FINDINGS: Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease. Acknowledgements: Supported by a grant from the Instituto de Salud Carlos III (PI 16/0915), which can be co-funded by the European Union (FEDER Funds).

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.