Vanesa Hernández-Hernández

Influence of disease activity on the physical activity of rheumatoid arthritis patients

OBJECTIVES The aims of this study were to study physical activity (PA) in patients with RA by accelerometry and to determine to what degree their mobility is affected by disease activity. METHODS A group of 50 RA patients, without lower limb clinical disease, and 50 age- and sex-matched healthy controls were included in this cross-sectional study. PA was assessed by accelerometry and with the International Physical Activity Questionnaire (IPAQ). We performed multiple regression analysis not only to compare PA between groups, but also to explore the relation between RA features, including disease activity and cardiovascular risk parameters, and PA. In a randomized group of 30 RA patients a test-retest study was carried out in order to determine the correlation between variations in disease activity and PA. RESULTS The number of minutes of moderate and vigorous activity per day, as evaluated by accelerometry, was significantly lower in RA patients than in healthy controls. In RA patients, accelerometry and IPAQ demonstrated concordance to a moderate degree [quadratic weighed kappa index 0.27 (0.06-0.48), P = 0.02]. HAQ negatively correlated with both IPAQ and accelerometry data. The 28-joint DAS using CRP (DAS28-CRP) was also inversely related with IPAQ. Framingham score and metabolic syndrome were inversely associated with PA in RA patients. Interestingly, variations in PA by accelerometry inversely correlated with changes in RA disease activity (r = -0.42, P = 0.02). CONCLUSION In RA patients, accelerometry is a reliable technique to evaluate PA. This study not only showed that RA patients spend less time doing moderate and vigorous PA than healthy controls, but also PA, as assessed by accelerometry, was sensitive to any changes in disease activity.

Mujer con artralgias y aumento de tamaño de miembros superiores

We present a 32-year-old woman with a history of hypothyroidism, on replacement therapy, menstruating and with no children. She had no family history of osteoarticular disease. She told us that she had been diagnosed with muscular dystrophy when she was four years old in her country of origin. She had no medical notes or history for this, stating that this diagnosis had been given because she had been late in starting to walk and that no muscular biopsy or specific study had been carried out. She was consulting due to mechanical arthralgia of lengthy evolution, with no joint swelling, no morning stiffness; the patient said her upper limbs had enlarged over the years and the diameter of her thighs and legs had also increased. Originally she had gone to our hospital’s Neurology Department, where analysis gave normal CPK, an electromyogram showed no evidence of myopathy and an MRI of the pelvic girdle did not reveal myositis; consequently, she was sent to our department for study. The examination highlighted the absence of synovitis, generally limited passive and active joint distances, normal muscular strength and an increase in the upper limb length. Her walk also drew attention with a certain oscillation of the pelvis, exaggerated lumbar lordosis and latero-lateral sway. The tendon reflexes were normal and there was no deformity in the toes or fingers. The simple radiological study carried out showed cortical thickening and sclerosis of the shafts of tubular bone. There was irregular and heterogeneous osteosclerosis, mottled areas of radiolucency with greater endosteal than periosteal involvement and narrowing of the spinal canals (Figure). The epiphyses were respected radiologically. Densitometry of femoral neck had a Z-score of +6.2.

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

BackgroundB cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors.MethodsExpression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines.ResultsB cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF.ConclusionsThese results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium.

A woman with joint pain and enlarge dupper limbs

Mujer de 32anos de edad con antecedentes personales de hipotiroidismo en tratamiento sustitutivo, menstruante y sin hijos. Referia no tener antecedentes familiares de enfermedad osteoarticular. Relataba haber sido diagnosticada, en su pais de origen, a la edad de 4anos de distrofia muscular. No se disponia de informes ni de historia previa en este sentido, refiriendo la paciente que dicho diagnostico se habia realizado por retraso en la adquisicion de la edad de deambulacion y que no se le habia realizado biopsia muscular ni aportaba ningun estudio especifico. Consultaba por artralgias mecanicas de largo tiempo de evolucion, sin tumefaccion articular, sin rigidez matinal y referia que desde hacia anos los miembros superiores habian aumentado de tamano y que el diametro de muslos y piernas tambien habian aumentado. Por todo esto habia acudido originalmente al Servicio de Neurologia de nuestro hospital, donde tras la realizacion de analitica con CPK normal, electromiograma sin datos de miopatia y estudio de resonancia magnetica de cintura pelviana sin datos de miositis, nos la remiten para estudio. A la exploracion destacaba ausencia de sinovitis, recorridos articulares pasivos y activos limitados de forma global, fuerza muscular normal y aumento de longitud de miembros superiores. Tambien llamaba la atencion una marcha con cierta oscilacion de la pelvis, lordosis lumbar exagerada y balanceo laterolateral. Los reflejos tendinosos eran normales y no habia deformidad en los dedos de los pies ni de las manos. El estudio radiologico simple realizado mostro engrosamiento cortical y esclerosis de las diafisis de los huesos tubulares con osteoesclerosis irregular y heterogenea con areas moteadas de radiolucencia con mayor afectacion endostica que periostica y estrechamiento de los canales medulares (fig. 1). Las epifisis estaban respetadas radiologicamente. Densitometria de cuello femoral Z-score +6,2DE.

THU0424 The Virtual Consultation of Rheumatology: Experiencie in A University Hospital

Background Rheumatic diseases, mostly chronic, are highly prevalent, with a big economic impact high. In Spain the prevalence of rheumatic diseases is similar to other chronic diseases such as hypertension and diabetes. This high prevalence has been the reason that in recent years major changes have occurred, leading rheumatologists to perform their daily work in addition to the hospital, at Specialist Care Centers (SCC) and Primary Care Centers as a consultant rheumatologist. We are currently implementing the virtual consultation (VC) as an alternative health care model. Objectives To describe our experience with the Rheumatology VC. Assess the advantages and disadvantages that VC implies. Methods Observational retrospective study to assess the Rheumatology VC conducted from April 1, 2013 until December 31, 2013, requested by 44 primary care physicians (PCP) corresponding to 3 health centers, with a reference population of 70,693 inhabitants. Results A total of 565 VC were performed on a 9-month period (April 2013-December 2013), with a maximum of 5 visits per day and with a commitment to answer within 24 hours. 53% of the VC were resolved without giving the patient an appointment, and represented questions related to the treatment or analytical data. 47% were given an appointment to be assessed in consultation: 67.5% were referred to SCC for suspected degenerative or soft tissue diseases, and 32.4% were referred to the hospital. Of the patients referred to the hospital, 52 (60.4%) had inflammatory and/or connective pathology, 21 (24.4%) soft tissue rheumatism that needed ultrasound testing and 13 (15.1%) pediatric rheumatologic diseases. The VC were answered within 24 hours, there was no waiting list. The benefits that we could appreciate with VC were: almost direct contact with PCP; to help improving the training of PCP in musculoskeletal diseases (eg, how to differentiate mechanical inflammatory pain, among others); to guide the PCP selecting the best additional tests to order before the patients attends the first consultation with the rheumatologist (eg, laboratory tests with CRP, ESR, radiographs, FR, ANA), according to the previous medical records of the patient, allowing the first consultation to be more efficient, and thus, diminish subsequent visits and the waiting list. On the other hand, the major limitation and disadvantage, is that rheumatologist are fundamentally clinical physicians and in this case we are not examining the patient, since we receive the clinical information from the PCP. Conclusions Our experience with the VC is positive. Despite the major limitation of taking decisions without the patient being present, we have achieved: 1) Almost immediate resolution of PCP doubts, 2) Contribute to improve the PCP training in medical pathology of the musculoskeletal system, 3) Avoid overloading care, 4) More efficient first visits 5) Early detection of inflammatory diseases that really need an specialized evaluation and/or early treatment. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3362

AB0316 Bone Mass, Osteoprotegerin and Vitamin D: Relation with Endothelial Dysfunction in Rheumatoid Arthritis Patients

Background In the general population,low bone mineral density (BMD)has been independently associated with cardiovascular disease. This relationship in patients with rheumatoid arthritis (RA) is not entirely understood. Objectives To study whether BMD, osteoprotegerin and vitamin D levels are associated with endothelial dysfunction in patients with RA. Methods 197 women (100 RA patients,97 controls) adjusted for age and comorbidity were recruited. BMD by dual energy X-ray absorptiometry (DEXA) of the hip, lumbar spine and total body;plasma levels of vitamin D and osteoprotegerin and arterial flow-mediated dilatation by brachial ultrasound were assessed,in both groups.Multivariate analysis and trend tests were performed to study the relationship between bone mass and endothelial dysfunction. Results RA patients showed lower lumbar bone mass values (β coef. gr/cm2 -64 [95%CI -122 to 6], p=0.03) and a decreased percentage of total body bone mass (β coef -0.3% [95%CI, 0.5 to 0.1],p=0.01) after adjustment for age and comorbidity. Although values tended to be lower in RA in other areas such as femoral neck, total hip, Wards triangle, or femoral shaft, these differences were not statistically significant. Osteoprotegerin levels were significantly higher in RA (log osteoprotegerin β coef -0.19 vs 0.62 ng/mL,p=0.00), while vitamin D levels tended to be lower (log vitamin D, 3.56 vs β coef. 3.66 ng/mL,p=0.19) but no statistical significance was reached.Patients exhibited lower flow mediated dilatation in comparison to controls (β coef. -5.5% [95%CI, 9.9 - 1.1],p=0.01). Vitamin D levels in controls, were positively related to the flow-mediated brachial dilatation after adjustment for age, percentage of total body bone mass and vascular comorbidity (β coef. 0.74% [95%CI -0.02-1.48], p=0.05). This relationship was not found in patients with RA. In our study, osteoprotegerin levels were not associated with endothelial dysfunction in both controls and patients.In healthy subjects, for each quartile decrease in brachial dilatation (after adjustment for age and other variables) we found inferior bone mass values in the femoral neck (β coef. T-score 0.68 [95%CI -0.00-1.35],p for linear trend =0.05), total hip (β coef. T-score 0.84 [95%CI -0.21-1.46],p=0.01 linear trend), femoral trochanter (β coef. T-score 0.78 [95% CI 0.13-1.42], p=0.02 for linear trend) and Wards triangle (β coef. T-score 0.62 [95% CI -0.05-1.28], p=0.06 for linear trend); this relationship was not found in lumbar spine and percentage of total body bone mass. When this analysis was performed in RA patients, the endothelial dysfunction values were not associated with bone mass. Conclusions In controls, BMD and vitamin D levels are associated with endothelial dysfunction.This association was not found in RA patients, suggesting that the relation of bone mass with endothelial damage may depend on the disease itself and not in relation with these parameters. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2039

SAT0467 Relationship of Body Composition and Abdominal Adiposity with Bone Mineral Density in Patients with Rheumatoid Arthritis

Background In general population,a high body mass index,is considered protective against osteoporosis.The relationship of body composition and abdominal adiposity with bone mineral density (BMD) in rheumatoid arthritis (RA) has not been explored. Objectives To study if body composition and abdominal adiposity are related to BMD in RA. Methods 197 women (100 RA, 97 controls) adjusted for age and comorbidity were recruited. We determine: body mass index, waist circumference, bone mass by DEXA of the hip, lumbar spine, total body; lean and fat mass according to specific rates and locations; sarcopenia patterns, levels of vitamin D and osteoprotegerin, as well as abdominal fat by MRI, in both groups. Multivariate analysis was performed to study the relationship between bone mass and patterns of body composition and with abdominal adiposity. Results RA patients showed lower levels of lumbar bone values (βcoef. gr/cm2 -64 [95% CI -122 to 6], p=0.03) and a lower percentage of total body bone mass (βcoef -0.3% [95% CI, 0.5 to 0.1], p=0.01) after adjustment for age and comorbidity. Although values tended to be lower in RA in other areas such as femoral neck, total hip, Wards triangle or femoral shaft, these differences were not statistically significant. Patients tended to have higher frequency of obesity as BMI>30 kg/m2 (43% vs. 31%, p=0.09), although the analysis of body compartments, fat and lean mass rates, as well as abdominal adiposity, showed no difference between patients and controls. Fat and lean masses were associated,in a positive way, with the levels of BMD at all sites in both groups (total hip β coef. Tscore 1.15 [95% CI 0.08- 0.24], p=0.00 in RA and β coef T score 0.16 [95% CI 0.07-0.24], p=0.00) in controls, after adjusting for age, comorbidity, and vitamin D levels and osteoprotegerin. The values of parietal abdominal adiposity showed a positive relationship with the values of total hip T score in both controls (0.04 T score β coef. [95% CI 0.01 to 0.07], p=0.01) and patients (0.05 T β coef. score [95% CI 0.02-0.07], p=0.00).This relationship was not found with the values of visceral abdominal adiposity. The presence of sarcopenia phenotype tended to be higher in patients (OR 2.95 [95% CI 0.93 to 9.29], p=0.06]. This sarcopenia was associated with lower BMD at the total hip (β coef. T score -1.90 [95% CI, 3.61-0.20], p=0.03) after adjustment for disease activity scores, age, ESR, CRP, rheumatoid factor and vitamin D and osteoprotegerin levels. In contrast, the presence of sarcopenia had no influence on bone mass in controls. Similarly, the combination of obesity and sarcopenia (sarcopenic obesity) showed no association with bone mass in either groups. Conclusions The protective role of fat and lean mass on BMD is preserved in patients. The pattern of sarcopenia, after adjusting for disease activity was associated with low bone mass in RA. This suggests an independent role of this sarcopenia on bone density in RA, but not in healthy subjects. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2041

THU0056 Impaired beta cell signaling is present in non diabetic rheumatoid arthritis patients

Objectives It has been suggested that resistance to insulin action is a feature that accompanies rheumatoid arthritis (RA), a disease where chronic inflammation predominates and classical triggers for insulin resistance (IR) like obesity and diabetes are absents. However, data regarding characterization of RA features associated with this insulin resistance (IR) are lacking. The aim of this study was to investigate how sensitivity to insulin and markers of beta cell dysfunction (proinsulin processing metabolites) are expressed in RA. Methods 101 non-diabetic RA patients and 99 non-diabetic sex and age-matched controls were included in this study. Insulin sensitivity function through homeostatic model assessment (HOMA2), and beta cell secretion through insulin, split and intact proinsulin, and C-peptide were assessed in both groups. We performed multiple regression analysis to compare IR between groups and to explore the relation between RA features and IR. Data were adjusted for glucocorticoids intake and for IR classical risk factors. Results RA patients compared to controls show higher HOMA-IR (logHOMA-IR, beta coefficient, 0.40 [95% CI 0.20-0.59], p=0.00). When this data was adjusted for glucocorticoids intake, non-on corticosteroid patients maintained a higher IR index (beta coef. 0.14 [95% CI 0.05-0.24], p=0.00). Current prednisone treatment was not associated with higher IR in the patients’ intragroup comparison (beta coef. 0.56 [1.13-1.19], p=0.22). Insulin processing signaling in RA patients showed impaired features via an elevated intact proinsulin levels (beta coef. 3.13 [0.81-5.44] pMol/L, p=0.03 for the comparison between patients and controls). Split proinsulin levels were also higher in RA patients (beta coef. 13.7 pmol/L [3.57-9.40], p=0.00) even adjusting for prednisone intake (beta coef. 2.66 pmol/L [95%CI 1.62-5.95] for non steroids RA patients when compared to controls). In multiple regression analysis, RA features (disease duration, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, disease activity through HAQ and DAS28 scores, and current non-biologic disease modifying antirheumatic drug), when adjusted for sex, age and body mass index, were not associated with IR or insulin propeptides. Conclusions Beta cell signaling is impaired in non-diabetic and non-corticoids RA patients. Disclosure of Interest None Declared