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Resumen Objetivo Elaborar recomendaciones para la prevencion de infeccion en pacientes adultos con enfermedades reumaticas autoinmunes sistemicas (ERAS). Metodos Un panel de expertos, seleccionados con base en su curriculum y experiencia, identifico preguntas clinicas de investigacion relevantes para el objetivo del documento. Se realizaron revisiones sistematicas de la evidencia, que se graduo de acuerdo con los criterios del Scottish Intercollegiate Guidelines Network. Tras ello, se formularon las recomendaciones. Resultados Se seleccionaron cinco preguntas, referentes a la prevencion de infeccion por Pneumocystis jirovecii con trimetoprim-sulfametoxazol, medidas profilacticas contra el virus de la hepatitis B, vacunacion contra el virus del papiloma humano, vacunacion contra el Streptococcus pneumoniae y vacunacion contra el virus de la gripe. Se formularon un total de 18 recomendaciones, estructuradas por pregunta, con base en la evidencia encontrada para las diferentes ERAS y/o consenso de expertos. Conclusiones Existe suficiente evidencia sobre la seguridad y eficacia de las vacunaciones y otras medidas profilacticas frente a los microrganismos revisados en este documento como para ser recomendadas especificamente en pacientes con ERAS.

Objectives Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients. Methods The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis. Results CEC was downregulated in SLE patients [8.1 (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile–related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014]. Conclusion CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.

The appearance in the field of oncology of therapeutic molecules in the form of monoclonal antibodies, whose objective is to stimulate the patient's own immune system to be responsible for destroying cancer cells, has revolutionized the treatment of many cancers in recent years. This type of therapy, called immunotherapy, is also characterized by presenting side effects in the form of autoimmune diseases that we are still beginning to understand. From the point of view of the immune-mediated rheumatological side effects, we can find musculoskeletal manifestations, mechanical, inflammatory or systemic autoimmune diseases. The therapeutic approach to these side effects remains uncertain due to the absence of clinical trials and validated recommendations. The multidisciplinary management is crucial to successfully treat such cases. In the following manuscript, we will describe our case reports of rheumatologic immune-related adverse events in a university hospital.

espanolLa aparicion en el campo de la oncologia de moleculas terapeuticas en forma de anticuerpos monoclonales, cuyo objetivo consiste en estimular el propio sistema inmune del paciente para que sea este el encargado de destruir las celulas cancerigenas, ha revolucionado el tratamiento de diversos canceres en los ultimos anos. Este tipo de terapia, denominada inmunoterapia, se caracteriza ademas por presentar efectos secundarios en forma de enfermedades autoinmunes que todavia estamos empezando a conocer. Desde el punto de vista de los efectos secundarios inmunomediados reumatologicos, podemos encontrar manifestaciones musculoesqueleticas mecanicas, inflamatorias o enfermedad autoinmune sistemica. El manejo terapeutico de estos efectos secundarios se mantiene variable debido a la ausencia de ensayos clinicos y de recomendaciones validadas, siendo el manejo multidisciplinar fundamental para tratar con exito dichos casos. En este articulo presentamos nuestra serie de casos clinicos de pacientes en tratamiento con inmunoterapia y efectos secundarios inmunomediados reumatologicos en un hospital universitario. EnglishThe appearance in the field of oncology of therapeutic molecules in the form of monoclonal antibodies, whose objective is to stimulate the patient's own immune system to be responsible for destroying cancer cells, has revolutionized the treatment of many cancers in recent years. This type of therapy, called immunotherapy, is also characterized by presenting side effects in the form of autoimmune diseases that we are still beginning to understand. From the point of view of the immune-mediated rheumatological side effects, we can find musculoskeletal manifestations, mechanical, inflammatory or systemic autoimmune diseases. The therapeutic approach to these side effects remains uncertain due to the absence of clinical trials and validated recommendations. The multidisciplinary management is crucial to successfully treat such cases. In the following manuscript, we will describe our case reports of rheumatologic immune-related adverse events in a university hospital.

Objectives To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). Methods Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. Results Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. Conclusions There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Objective SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. Methods We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. Results From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. Conclusion Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

Objective: Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. Lipid profiles and CEC appear to be altered in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) due to disease activity and inflammation. CEC has been linked to cardiovascular events in the general population and to subclinical atherosclerosis in SLE and RA patients. The aim of this study was to establish whether CEC varies between patients with SLE and those with RA. Methods: The study encompassed 460 individuals (195 SLE patients and 265 patients with RA). CEC (using an in vitro assay) and concentrations of lipoprotein serum were assessed in both populations. A multivariable regression analysis was performed to study whether CEC differs between SLE patients and RA patients. Results: Comparison of lipid patterns revealed that patients with RA have lower HDL cholesterol and higher apolipoprotein B serum levels than SLE patients. CEC was downregulated in SLE patients compared to patients with RA (β -12 [95% confidence interval -13, -10], P < 0.001). It occurred independently of traditional cardiovascular risk factors, statin use, disease-related data, and other variations in the lipid profile related to the diseases. Conclusion: Patients with RA have a more proatherogenic lipid pattern compared to those with SLE. However, CEC seems to be more damaged in SLE patients than in RA patients. Sin financiación 5.178 JCR (2021) Q2, 12/34 Rheumatology 1.566 SJR (2021) Q1, 7/61 Rheumatology No data IDR 2021 UEC

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE. Methods: We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia. Results: Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient ?73 [95% confidence interval (CI) ?91 to ?54] ng/ml, p???0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient ?30 (95% CI ?54 to ?6) ng/ml, p?=?0.015]. Conclusion: PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels. The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: this work was supported by a grant to IF-A from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional - FEDER - (Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083). The research of MAG-G is supported by the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS program (RD12/0009 and RD16/0012).

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role. Invariant natural killer T cells, which are triggered specifically by lipid antigens, may protect against progression of subclinical atherosclerosis. However, currently our recommendation is that clinicians should focus on optimal management of standard CVD risk factors such as smoking, blood pressure and lipid levels. Fatigue is one of the most common and most limiting symptoms suffered by patients with SLE. The cause of fatigue is multifactorial and disease activity does not explain this symptom. Consequently, therapies directed towards reducing inflammation and disease activity do not reliably reduce fatigue and new approaches are needed. Currently, we recommend asking about sleep pattern, optimising pain relief and excluding other causes of fatigue such as anaemia and metabolic disturbances. For the subgroup of patients whose disease activity is not fully controlled by standard treatment regimes, a range of different biologic agents have been proposed and subjected to clinical trials. Many of these trials have given disappointing results, though belimumab, which targets B lymphocytes, did meet its primary endpoint. New biologics targeting B cells, T cells or cytokines (especially interferon) are still going through trials raising the hope that novel therapies for patients with refractory SLE may be available soon.

Resumen La terapia biologica ha cambiado el curso de las enfermedades reumaticas inflamatorias. La seguridad de la misma esta mas que documentada en diferentes estudios nacionales e internacionales. La baja frecuencia de las manifestaciones neurologicas dificulta en muchas ocasiones el establecer una relacion causal clara entre el tratamiento biologico y la clinica neurologica propiamente dicha. Los sintomas y signos neurologicos que pueden aparecer son multiples, y en ocasiones simulan enfermedades neurologicas desmielinizantes y/o neurodegenerativas. El conocimiento y el reporte de los mismos es fundamental para realizar un manejo exhaustivo de la terapia biologica en nuestros pacientes.

Biological therapy has changed the course of inflammatory rheumatic diseases. The safety is well documented in national and international studies. Neurological manifestations are uncommon and it is difficult to establish a clear causal relationship. The neurological signs and symptoms that may appear are multiple and sometimes mimic demyelinating neurological diseases and/or neurodegenerative diseases. Knowledge and disclosure of these cases is essential for a comprehensive management of biological therapy in our patients.

Patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have an increased premature prevalence of atherosclerosis. We aimed to determine whether there are differences in the prevalence of classic cardiovascular risk factors between SLE and RA. We also analysed the effect of traditional cardiovascular risk factors on the development of subclinical atherosclerosis in both conditions and if some disease-characteristic features are associated with these traditional cardiovascular risk factors.This was a cross-sectional study encompassing 602 individuals, 276 SLE and 326 RA patients. Subclinical atherosclerosis (presence of carotid plaques and carotid intima-media thickness [cIMT]) was determined by carotid ultrasonography. A multivariable regression analysis was performed to evaluate whether classic cardiovascular-related risk factors differentially influence subclinical carotid atherosclerosis in SLE compared to RA patients.Age (interaction factor [if] p=0.000), hypertension (if p=0.034), and diabetes (if p=0.037) had a higher effect on cIMT in RA than in SLE subjects. However, these traditional cardiovascular factors did not yield different effects on the presence of carotid plaques in RA and SLE when the univariate interaction was analysed. In addition, no differences were found in the influence of hypertension, diabetes, dyslipidaemia or current smoking on cIMT or carotid plaque after adjusting for demographics, the presence of other traditional cardiovascular factors, and disease-related data. Moreover, the additive effect of several cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between the two diseases.The influence of traditional cardiovascular risk factors on cIMT and carotid plaque is similar in RA and SLE.

Background Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients are associated with an increased and premature prevalence of atherosclerosis. This has been characteristically attributed to the inflammation present in both diseases Objectives To analyze the differences in the role of traditional cardiovascular risk factors in the subclinical atherosclerosis between the two diseases. Methods Cross-sectional study encompassing 602 subjects, 276 SLE and 326 RA patients. Carotid plaques were assessed by ultrasonography. A multivariable regression analysis was performed to evaluate if classic cardiovascular-related risk factors influence differentially on subclinical carotid atherosclerosis in SLE compared to RA patients. Results Traditional cardiovascular risk factors were found to be prevalent in RA and SLE patients. Age (interaction factor p=0.000), hypertension (interaction factor p=0.034), and diabetes (interaction factor p=0.037) were found to have a higher effect on cIMT in RA patients compared to SLE subjects. No differences between RA and SLE were discovered in the effect of traditional cardiovascular factors over the presence of carotid plaque when univariate interaction was performed. After final adjustment for demographics, the presence of others traditional cardiovascular factors, and disease related data, no differences were found in the influence of hypertension, diabetes, dyslipidemia or current smoking over cIMT or the presence of carotid plaque. Moreover, the effect of the addition of various cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between both diseases. Conclusion The influence of traditional cardiovascular risk factors (hypertension, diabetes, dyslipemia and smoking) over cIMT and carotid plaque is equal in RA and SLE. No interaction was found between traditional cardiovascular risk factors and disease related data in the effect of the former on subclinical atherosclerosis. Disclosure of Interests Hiurma Sanchez-Perez: None declared, Juan Carlos Quevedo-Abeledo: None declared, Inigo Rua-Figueroa: None declared, Beatriz Tejera-Segura: None declared, Vanessa Hernandez-Hernandez: None declared, Antonia de Vera-Gonzalez: None declared, Alejandra Delgado-Gonzalez: None declared, Raquel Lopez-Mejias: None declared, Soledad Ojeda Grant/research support from: AMGEN, Speakers bureau: AMGEN, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ivan Ferraz-Amaro: None declared

The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 [median % change 32 (3–141), p=0.021]. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.

Fatigue remains a debilitating feature of systemic lupus erythematosus (SLE). Although in some cases this may be the result of intercurrent fibromyalgia, mood disorder or untreated metabolic syndrome, in many cases the cause is unclear. The aim of this study was to investigate the relationship between fatigue and red cell distribution width (RDW), a measure of variability in erythrocyte size and volume.A total of 225 patients were recruited from three clinics in England and Australia. Patients completed the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score or 12-item Short Form survey (SF-12) to measure fatigue, which was compared with RDW and haemoglobin. In a subgroup of 72 patients, markers of disease activity were also assessed for correlation with fatigue using univariate and multivariate analysis with fatigue as the dependent variable.In all three groups, significant correlations between fatigue and RDW were observed (p0.001; p=0.02; p0.001 respectively) and this was preserved in multivariate analysis. There was no correlation between fatigue and haemoglobin in two groups (with the correlation between RDW and fatigue remaining significant in non-anaemic patients in the third group). In subgroup analysis, fatigue was not associated with any measures of disease activity.We report a reproducible, statistically significant association between RDW and fatigue levels in a diverse population of patients with SLE. The findings of this study raise the possibility of a potential novel biological basis for fatigue in those in whom there is a lack of an alternate explanation.

In recent years, the prevalence of rheumatic diseases has increased. The virtual consultation of rheumatology could help to avoid unnecessary visits and attend those who need an early visit. The virtual consultation is associated with telemedicine and telecommunication. The objective of this study is to describe the characteristics of all virtual consultations performed in the Rheumatology Service during a one year period. More than a 50% were resolved without giving the patients an appointment. With virtual consultation we have achieved: 1) a closer contact with primary care, 2) rapid resolution of doubts about rheumatic disease in patients, 3) improvement of training in rheumatic disorders and 4) prioritizing those patients requiring early assessment by a rheumatologist.

Objective.Composite scores of cardiovascular (CV) risk factors underestimate the CV risk in patients with systemic lupus erythematosus (SLE). Carotid artery ultrasound (US) was found useful in identifying high CV–risk patients with inflammatory arthritis. We assessed the effect of carotid US assessments on the CV risk stratification of patients with SLE.Methods.This cross-sectional study included 276 patients with SLE. These indices were measured: lipid profile, Systematic COronary Risk Evaluation (SCORE) risk calculation, and disease activity (SLE Disease Activity Index), severity (Katz), and damage [Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index]. Carotid plaques were assessed by US. A multivariable regression analysis, adjusted for classic CV-related factors, was performed to evaluate how risk reclassification was influenced by disease characteristics in patients with SLE.Results.Thirty-six percent of patients had carotid plaques. However, only 6% of them fulfilled the definitions for high or very high risk according to the SCORE risk charts. Following carotid US assessment, 32% of the patients were reclassified as very high risk. Disease duration (OR 1.04, 95% CI 1.00–1.07, p = 0.025) and a SLICC > 0 (OR 2.48 95% CI 1.15–5.34, p = 0.020) were independently associated with a higher risk of reclassification. A predictive model for reclassification included age (cutoff 52 yrs, sensitivity 60%, specificity 86%), disease duration (cutoff 24 yrs, sensitivity 40%, specificity 82%), presence of hypertension, SLICC > 0, waist circumference (cutoff 102 cm, sensitivity 48%, specificity 84%), and C3 (cutoff 127 mg/dl, sensitivity 52%, specificity 92%) and triglyceride (cutoff 140 mg/dl, sensitivity 68%, specificity 79%) serum levels.Conclusion.Reclassification into a very high–risk category is frequent after carotid US assessments in patients with SLE. This is independently influenced by disease damage.

Objective.In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA).Methods.This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion.Results.HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2= 0.845 vs r2= 0.928, p = 0.001) and β coefficients (−0.74, 95% CI −0.77 to −0.70 vs −1.09, 95% CI −1.17 to −1.02, ng/ml, p < 0.001) were different in RA.Conclusion.The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

The chemokine molecule CXCL5 (C-X-C motif chemokine ligand 5, also known as epithelial neutrophil activating peptide 78 -ENA78-) constitutes a link between obesity, inflammation and insulin resistance (IR) in the general population. CXCL5 has also been found to play a role in rheumatoid arthritis (RA) pathogenesis. Since chronic inflammation promotes IR and impairs pancreatic beta cell function in RA patients, we assessed the role of CXCL5 in the development of IR in RA.Cross-sectional study that encompassed 141 non-diabetic patients with RA. IR assessed by homeostatic model assessment (HOMA2), insulin and C-peptide serum levels and lipid profile, and CXCL5 serum levels were studied. Regression analysis was performed to evaluate how CXCL5 was related to IR, disease activity, and disease characteristics in RA patients.HOMA2-IR indexes showed high values for both IR and beta cell production (%B), and low insulin sensitivity (%S) in patients with RA. C reactive protein (beta coef. 0.2 [95%CI -1.5-1.9], p=0.80) and disease activity through DAS28 (beta coef. 13 [95%CI -14-41], p=0.34) revealed no relation with CXCL5. Other disease characteristics, such as disease duration, serological status, or use of methotrexate or anti-TNF alpha therapies, were not associated with CXCL5 serum levels. While glucocorticoids were related to insulin, C-peptide serum levels, and HOMA2-IR and HOMA2-%B-C peptide, the use of prednisone was not associated with CXCL5 serum levels. Insulin and C peptide serum levels and IR indexes showed strong correlations among each other, but not with CXCL5 (insulin r2=-0.034, p=0.69; C peptide r2=-0.050, p=0.56).CXCL5 is not related to IR in RA patients. Therefore, the mechanisms leading to IR in patients with RA may be different from those in the general population.

Purpose To develop a predictive risk score that assesses the probability of severe infection in SLE patients and to test it in an independent cohort. Methods The SLE severe infection score (SLESIS) was developed using data from the RELESSER (Spanish Society of Rheumatology Lupus Registry) cohort of 3658 SLE patients using a Cox regression model for repeated events (Andersen-Gill) The results were expressed as hazard ratio (HR) of developing one serious infection/1000 patient-years for patients with the risk factor compared to those without that factor. SLESIS for an individual patient is the sum of the HR values of all factors present at that time. SLESIS was validated using retrospective data from the UCLH (University College London Hospital) cohort including 699 SLE patients. Results The risk factors included in SCORE and their HR calculated from RELESSER data are shown in table 1. From 699 SLE UCLH patients, 98 (14%) developed serious infection. We compared these patients with 111 SLE controls who never suffered serious infection. The characteristics of the SLE infection and SLE non-infection groups are summarised in table 2. Median SLESIS at diagnosis in patients with infection was 4.27 (IQR 3.18) which was significantly higher than in the control group (Median 2.55, IQR 3.79) (z=3.341; p=0.0008). Median SLESIS just before infection was 5.3 (IQR 3.68) which was significantly higher compared to SLESIS at diagnosis (z=−5.733; p≤0.001) in those patients or SLESIS measured at the same time post-diagnosis in the non-infected group (Median 3.73 RI 3.7) (z=−4.765, p≤0.001). By Receiver Operator Characteristic analysis, we defined three possible cut-offs to distinguish patients with and without infection. For SLESIS just before infection, the area under the ROC curve was 0.75 (CI: 0.66 to 0.84) and the three selected cut offs (3.67, 3.79, 4.24) reached a sensitivity of 90% and specificity of 50%. Conclusion We have developed a score for predicting risk of serious infection in SLE and validated it in an independent cohort. Given the potential mortality from such infections, SLESIS could be clinically useful though the moderate sensitivity and specificity necessitate caution and further prospective studies.

Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications.

Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications.

Amylin, which is co-secreted with insulin, plays a role in glycemic regulation and is impaired in type 2 diabetes. In the present study we assess, for the first time, the implication of amylin in the development of insulin resistance (IR) in rheumatoid arthritis (RA).This was a cross-sectional study involving 361 non-diabetic individuals, 151 patients with RA and 210 sex-matched controls. Insulin, C-peptide, amylin, lipoprotein serum concentrations, and IR indexes by homeostatic model assessment (HOMA2) were evaluated in patients and controls. A multivariable analysis, adjusted for IR-related factors, was performed to determine the differences between patients and controls vis-à-vis amylin and how it is related to IR in RA.Insulin, C-peptide and HOMA2-IR indexes were higher in RA patients than in controls. Amylin serum levels were found to be upregulated in RA patients compared to controls (1.36 ± 0.81 vs. 1.79 ± 1.51 ng/ml, p=0.011), although this difference was lost after adjusting for covariates (p=0.46). While amylin positively correlated with the presence of rheumatoid factor (beta coef. 0.90 [95%CI -0.23-1.56], p=0.009) and SDAI (beta coef 0.01 [95%CI 0.00-0.03], p=0.034), no significant association with other disease activity scores, glucocorticoid intake, methotrexate use or TNF-alpha inhibitors was found.IR in RA does not appear to be mediated by amylin. This would imply that the mechanisms associated with IR in RA patients differ from those at work in type 2 diabetes.

Background Rheumatoid arthritis (RA) patients have higher levels of resistance to the action of insulin (IR) compared to healthy subjects.The “Incretin effect” consists in a greater release of insulin by the pancreas when there is a gastrointestinal glucose stimulation, compared to an intravenous stimulation. It is known that this effect is altered in patients with IR. Objectives To determine if the incretins-insulin axis is altered in patients with RA and if this correlates to IR in patients with RA, as well as if it is explainable by certain features of the disease. Methods Cross-sectional study that includes 361 non-diabetic individuals, 151 patients with RA and 210 controls. Serum levels of insulin, C-peptide, Amylin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP) and dipeptidyl peptidase 4 (DPP-4) were analyzed in patients and controls. Indexes of resistance and sensitivity to insulin activity were determined by HOMA2. A “meal test” consisting on the intake of 500 kcal was performed to a subset of 10 patients and 10 controls, in order to determine the postprandial curves of glucose, insulin, C-peptide, GLP-1 and GIP. Differences between patients and controls as well as the relationship of selected characteristics of the disease with the baseline and postprandial levels of incretins were analyzed using multivariate regression. During the meal test, areas under the curve (AUC), maximum concentrations and the minutes of response were compared between patients and controls. This study was approved by the Clinical Trial Committee of the University Hospital of the Canary Islands. Results Patients with RA showed, at baseline and after multivariate adjustment, higher levels of insulin (9.8±6.5 vs 13.0±13.4 U/ml, p=0.05), C-peptide (1.53±0.77 vs. 3.37±2.94 ng/ml, p=0.00), GLP-1 (0.49±1.28 vs. 0.71±0.22, p=0.00) and GIP (0.37±0.40 vs. 1.78±0.51, p=0.00). Similarly, IR indexes such as HOMA2-IR and HOMA2%B, built with insulin or Cpeptide, were higher in patients with RA compared to controls. Patients with RA, showed significantly lower levels of DPP-4 (811±459 vs. 696±301 ng/ml,p=0.02) after multivariate analysis. Amylin levels did not differ between patients and controls. Both C-reactive protein (beta coefficient 0.54,95% CI 0.16–0.96, p=0.013) and Erythrocyte Sedimentation Rate (beta coef. 0.01,0.00–0.01, p=0.033) showed a positive relationship with HOMA2%B and GIP levels, respectively. The presence of anti-cyclic citrullinated peptide antibody (beta coef. 157 CI 58–256, p=0.002) and the levels of disease activity measured by DAS28 (beta coef. 46,CI 6–87, p=0.026) and CDAI (beta coef 1.27 (0.28–2.26), p=0.012) showed a positive relationship with the levels of DPP-4. Patients with RA showed Pearson correlation coefficient of incretines, DPP-4 with insulin, C peptide and IR lower compared to control group. After the meal test patients with RA exhibited an AUC of glucose and GIP greater than controls and a slower C-Peptide response time (75 vs. 30 minutes, p=0.029). Conclusions Incretins-insulin axis is altered in patients with RA compared to controls. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is associated with a higher cardiovascular risk (CVR), at least doubled when compared with the general population, as well as an increased prevalence of atherosclerosis,which occurs prematurely and independently of traditional CVR factors. The presence of atheromatous plaques documented with carotid ultrasound (US) examination implies a change in the patient9s CVR category to “very high risk”,according to the “European Guidelines on cardiovascular disease prevention in clinical practice, 2016”. General guidelines do not take into account the specific increase in CVR risk that it9s present in patients with autoimmune diseases. Objectives To examine if the use of carotid US leads to a more accurate CVR classification in SLE patients, and in that way to a better CVR management. Methods Cross-sectional study that emcompassed 102 SLE patients currently being followed in our Rheumatology Department. Demographic variables, the presence of CVR factors and previous/current CV events, disease duration and drug use were analysed; lipid profile was assessed using blood tests, as well as carotid intima media thickness and the presence of carotid plaques using US scan. The current CVR status was calculated using the SCORE classification (low risk 10%). Results 95% of our patients were women,mean age was 51.6+/- years,median disease duration was 16 years (IQR 9–28). 35.29% of patients presented with at least one CVR factor before the SLE diagnosis,and 61.76% at the time of the research (19.60% current smokers, 39.21% high blood pressure (HBP),33.33% dyslipidemia, 7.84% type II diabetes. A CV event was diagnosed in 11.76% of our patients throughout their SLE disease. According to the SCORE classification,55 of them had a low CVR (53.92%),26 moderate CVR (25.49%),6 high CVR (5.88%) and 15 of them very highCVR (14.70%). Carotid plaques were found in 28 patients (27.45%): 23 of them had never had a CV event (22.54%),21.42% of them were current smokers,64.28% had HBP,53.57% dyslipidemia and 17.86% type II diabetes. After adjustment of the SCORE classification with the presence of carotid plaques,16.36% of patients from the “low CVR” category would be re-classified has having “very high CVR”, as well as 30.76% from the “moderate CVR” category and 50% from the “high CVR” category. Of note,8 patients within the “very high CVR” category also presented carotid plaques. Out of this patients with atheroma plaque,13 were not using statins,and in 2 of them it would have been mandatory in order to achieve the LDL Conclusions More than half of our SLE patients presented with at least 1 CVR factor. Around 15% of patients were categorised as “very high CVR” according to the SCORE classification.The presence of carotid plaque was found in 27.45% of our patients,and 82% of them hadn9t suffered any CV event. The use of carotid US examination allowed us to re-classify 20 patients (19.60%)in the “very high risk” category according to the SCORE classification. The need for a change in CVR management (ie., change in statin regime)was demonstrated in 4 of this 20 “re-classified” patients. Disclosure of Interest None declared

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA. This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry).

Resumen Fundamento y objetivo El sindrome de Lofgren se caracteriza por adenopatias hiliares, eritema nudoso y artritis. Es una variante benigna de sarcoidosis, frecuente en la region mediterranea. El objetivo de este estudio fue describir las caracteristicas clinicas, el tratamiento y la evolucion de una serie de pacientes diagnosticados de sindrome de Lofgren. Pacientes y metodo Estudio retrospectivo (1984-2013) en 2 hospitales universitarios con un area total de referencia de 1.015.000 habitantes. Resultados Se diagnosticaron 80 pacientes, 29 varones y 51 mujeres, con una media de edad de 42,3 anos. Cuarenta y ocho pacientes (60%) presentaron la triada clasica de la enfermedad: adenopatias hiliares, artritis y eritema nudoso; 18 (22%), adenopatias hiliares y artritis; y 13 (16%), adenopatias hiliares y eritema nudoso. Todos presentaron alteraciones en el estudio del torax y se clasificaron dentro del estadio i - ii . Se realizaron 39 biopsias, siendo caracteristicas de sarcoidosis 28 (35%). El tratamiento realizado consistio en antiinflamatorios no esteroideos (54 pacientes, 67%) y glucocorticoides (33 pacientes, 41%). Catorce pacientes (17%) presentaron recaida de la enfermedad. Conclusiones El sindrome de Lofgren es una forma benigna de sarcoidosis con un patron clinico caracteristico. En pocas ocasiones requiere confirmacion histologica, y tiene un buen pronostico.

Resumen La artritis septica de la articulacion acromioclavicular (ACV) es una entidad poco frecuente que se presenta en pacientes inmunosuprimidos o con discontinuidad de las barreras de defensa. En la literatura unicamente se han descrito 15 casos hasta la fecha. El diagnostico se basa en la presencia de clinica compatible junto al aislamiento del germen en la articulacion o en los hemocultivos. Las tecnicas de imagen (resonancia magnetica, ecografia o gammagrafia) pueden ser utiles en la localizacion del proceso. El tratamiento antibiotico es el mismo que en la artritis septica de otra localizacion y Staphylococcus aureus es tambien el microorganismo aislado con mas frecuencia. Se describen las caracteristicas clinicas, el tratamiento y la evolucion de los pacientes diagnosticados de artritis septica de la articulacion ACV en un servicio de Reumatologia, mediante estudio retrospectivo de revision de historias clinicas de los pacientes atendidos por artritis septica en dicha unidad (101 pacientes) en el periodo de 1989-2012. Seis enfermos (6%) tuvieron infeccion en la articulacion ACV con confirmacion microbiologica.

a b s t r a c t Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that occurs in immunosuppressed patients or those with discontinuity of defense barriers. There are only 15 cases described in the literature. The diagnosis is based on clinical features and the isolation of a microorganism in synovial fluid or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or scintigraphy) may be useful. Antibiotic treatment is the same as in septic arthritis in other locations. Staphylococcus aureus is the microorganism most frequently isolated. Our objective was to describe the clinical features, treatment and outcome of patients diagnosed with septic arthritis of the acromioclavicular joint at a Rheumatology Department. We developed a study with a retrospective design (1989–2012). The medical records of patients with septic arthritis were reviewed (101 patients). Those involving the acromioclavicular joint were selected (6 patients; 6%).

Objective Damage in patients with systemic lupus erythematosus is irreversible change in organs due to disease activity, concomitant disease or medication side-effects. It is measured using the Systemic Lupus International Collaborative Clinics Damage Index (SDI) and is associated with increased mortality. Previous reports have suggested associations between damage accrual and various ethnic, disease and treatment factors, but there is a dearth of long-term follow-up data from large multi-ethnic cohorts. We describe a study of damage and mortality in 300 patients from London, UK followed for up to 40 years. Methods We carried out retrospective analysis of medical records and SDI scores of 300 patients followed for up to 40 years (median 13.3 years). Characteristics of the groups who did and did not develop damage and those who died or survived to the end of follow-up were compared using univariable and multivariable analysis. Kaplan-Meier analysis was used to analyse factors affecting mortality and accrual of damage. Results Damage developed in 231/300 (77%) of patients. There was a linear accrual of damage over 40 years follow-up. Factors associated with damage were African/Caribbean ethnicity, renal and cerebral involvement, early use of high-dose corticosteroids or immunosuppressants, anti-RNP and antiphospholipid antibodies. Damage was strongly associated with mortality. Of 87 patients who died, 93% had damage compared with 70% of survivors (P < 0.001). Conclusion Development of damage is strongly associated with increased mortality. We identified groups at increased risk of developing damage, including those treated with high-dose steroids and immunosuppressants within the first two years.

ObjectiveSevere infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Our primary objective was to use data from a large Spanish cohort to develop a risk score for severe infection in SLE, the SLE Severe Infection Score (SLESIS) and to validate SLESIS in a separate cohort of 699 British patients.Design and settingRetrospective longitudinal study in a specialist tertiary care clinic in London, UK.ParticipantsPatients fulfilling international classification criteria for SLE (n=209). This included 98 patients who had suffered severe infections (defined as infection leading to hospitalisation and/or death) and 111 randomly selected patients who had never suffered severe infections.OutcomesWe retrospectively calculated SLESIS at diagnosis for all 209 patients. For the infection cases we also calculated SLESIS just prior to infection and compared it to SLESIS in 98 controls matched for disease duration. We carried out receiver operator characteristic (ROC) analysis to quantify predictive value of SLESIS for severe infection.ResultsMedian SLESIS (IQR) at diagnosis was higher in the infection group than in the control group (4.27 (3.18) vs 2.55 (3.79), p=0.0008). Median SLESIS prior to infection was higher than at diagnosis (6.64 vs 4.27, pConclusionsWe validated the association of SLESIS with severe infection in an independent cohort. Calculation of SLESIS at each clinic visit may help in management of infection risk in patients with SLE. Prospective studies are needed to confirm these findings.

Background Lipid profiles appear to be altered in rheumatoid arthritis (RA) patients because of disease activity and inflammation. Cholesterol efflux capacity (CEC), which is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages, has been linked not only to cardiovascular events in the general population but also to being impaired in patients with RA. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in patients with RA. Methods We conducted a cross-sectional study that encompassed 401 individuals, including 178 patients with RA and 223 sex-matched control subjects. CEC, using an in vitro assay, lipoprotein serum concentrations, and standard lipid profile, was assessed in patients and control subjects. Carotid intima-media thickness (CIMT) and carotid plaques were assessed in patients with RA. A multivariable analysis was performed to evaluate the relationship of CEC with RA-related data, lipid profile, and subclinical carotid atherosclerosis. Results Mean (SD) CEC was not significantly different between patients with RA (18.9 ± 9.0%) and control subjects (16.9 ± 10.4%) (p = 0.11). Patients with RA with low (β coefficient −5.2 [−10.0 to 0.3]%, p = 0.039) and moderate disease activity (β coefficient −4.6 [−8.5 to 0.7]%, p = 0.020) were associated with lower levels of CEC than patients in remission. Although no association with CIMT was found, higher CEC was independently associated with a lower risk for the presence of carotid plaque in patients with RA (odds ratio 0.94 [95% CI 0.89–0.98], p = 0.015). Conclusions CEC is independently associated with carotid plaque in patients with RA.

Insulin resistance (IR) plays a role in the increased cardiovascular risk of systemic lupus erythematosus (SLE) patients. This study aimed to determine the potential association of IR with disease activity, drug exposure and subclinical atherosclerosis in patients with SLE.This cross-sectional study encompassed 87 non-diabetic SLE patients and 82 sex-matched controls. Insulin and C-peptide serum levels, IR indexes by homeostatic model assessment (HOMA2) (both insulin-based: HOMA2-IR, and with C-peptide: HOMA2-IR-C-peptide) and lipid profiles were assessed in patients and controls. Activity (SLEDAI), severity (Katz) and damage (SLICC) index scores, as well as carotid intima-media thickness (cIMT) and carotid plaques, were determined in SLE patients. A multivariable regression analysis, adjusted for classic IR related factors, was performed to evaluate the differences in IR indexes between patients and controls and how IR is associated with disease-related characteristics, including carotid ultrasound results, in SLE patients.SLE patients had higher C-peptide serum levels (2.61±1.51 vs. 1.34±0.62 ng/ml, p=0.00) and elevated HOMA2-IRC-peptide index (1.90±1.12 vs. 0.97±0.45, p=0.00) than controls. These differences remained statistically significant after adjusting for classic cardiovascular risk factors and prednisone intake. Traditional IR-related factors, such as body mass index, waist circumference or hypertension, and prednisone intake were significantly associated with HOMA2-IR and HOMA2-IRC-peptide in SLE patients. SLICC damage index was independently associated with HOMA2-IR-C-peptide. The presence of carotid plaques and cIMT values were associated with IR indexes in SLE patients only in the univariate analysis.C-peptide serum levels are independently up-regulated in SLE patients. Although classic IR factors and prednisone are associated with IR, SLE damage over time also contributes to IR in an independent way.

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA, The present work was financed by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI12/00060 and PI15/00525) and RETICS Programs RD12/0009 from “Instituto Carlos III de Salud” (Health Ministry, Spain) and in part by grants from the European IMI BTCure Program. RL-M and BU are financed by RETICS (RD12/0009/0013). FG is supported by a Sara Borrell postdoctoral fellowship (CD15/00095).

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients.Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis.After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors.PCSK9 is down-regulated in patients with RA.

Resumen El sindrome de Vogt-Koyanagi-Harada (VKH), tambien conocido como sindrome uveomeningeo, es una panuveitis granulomatosa bilateral y difusa que cursa con desprendimiento de retina seroso y que puede acompanarse de afectacion del sistema nervioso central, alteraciones dermatologicas y auditivas. Su nombre deriva de los autores que la describieron por primera vez. Afecta a adultos de ambos generos, entre los 20 y 50 anos de edad, y presenta una prevalencia aumentada en razas negras. Este sindrome inflamatorio probablemente sea el resultado de un mecanismo autoinmune, influenciado por factores geneticos. La evolucion de la enfermedad se divide en 4 estadios clinicos: prodromico, uveitico agudo, de convalecencia y cronico recurrente. El diagnostico es fundamentalmente clinico, mediante los criterios establecidos por la Sociedad Americana de Uveitis (AUS) publicados en el ano 2001. Es necesario realizar diagnostico diferencial con la oftalmia simpatica, el linfoma primario de celulas B, la escleritis posterior y el sindrome de efusion uveal. El tratamiento precoz y mantenido es la base de una buena evolucion.

Resumen Osteofito es el nombre de la excrecencia osea formada en la enfermedad degenerativa, o artrosis, de la columna vertebral (espondilosis deformante). El origen es la osificacion de las fibras de Sharpey. Se visualiza en la radiologia simple como una excrecencia triangular que nace unos milimetros por encima del borde del cuerpo vertebral, extendiendose entre una vertebra y la siguiente con una trayectoria inicialmente horizontal y luego vertical. Al extenso crecimiento oseo en la cara anterolateral de la columna vertebral, asociada a la hiperostosis esqueletica idiopatica difusa, se le llama osificacion ondulante. La causa es una osificacion del ligamento vertebral longitudinal anterior, del disco intervertebral y del tejido paraverterbal. Se han descrito 2 tipos de sindesmofitos; el tipico y el atipico. El sindesmofito tipico es el propio de la espondilitis anquilosante y las enfermedades inflamatorias intestinales. Se debe a la osificacion de las fibras externas del anillo fibroso del disco intervertebral. Esta excrecencia osea es fina y vertical, y se extiende entre un cuerpo vertebral y el siguiente. Sin embargo, el sindesmofito atipico es el que encontramos en la psoriasis y el sindrome de Reiter. Este se caracteriza por su apariencia radiografica gruesa, separada del borde del cuerpo verterbal, pudiendo ser unilateral o asimetrica, y se debe a la osificacion de los tejidos paravertebrales.

OBJECTIVES: To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). RESULTS: RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. CONCLUSIONS: In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA., This study was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748 and PI12/00060) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. RLM is a recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013).