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Cardiovascular disease is one of the main causes of death in patients with systemic lupus erythematosus (SLE). On the other hand, sclerostin is a reliable and early biomarker of vascular calcification. This study aimed to estimate the association between sclerostin and two markers of cardiovascular risk, carotid atherosclerotic plaque (CP) and carotid-femoral pulse wave velocity (PWV), in women with SLE. The presence of CP (determined by carotid artery ultrasound) and PWV were measured in 68 women with SLE and preserved renal function. None of the participants had a history of cardiovascular disease. Serum levels of sclerostin were determined using the ELISA method. Other factors associated with increased cardiovascular risk were also measured. The association between sclerostin, CP and PWV was assessed using Receiver Operating Characteristic (ROC) curves and multivariate regression models. The area under the ROC curve was 0.785 (95% confidence interval [CI] 0.662–0.871) for CP and 0.834 (95% CI 0.729–0.916) for dichotomized PWV. After adjusting for other cardiovascular risk factors, it was found that a 10-units increase in sclerostin values was associated with a 44% increase in the odds of CP (95% CI 1–105), but no adjusted association was observed between sclerostin and PWV. Predictive models included age (for both outcomes), hypertension, Framingham risk score and C-reactive protein (for PWV), but not sclerostin. Sclerostin is associated with the presence of CP in women with SLE. Further research should confirm its possible role as a biomarker of cardiovascular risk in these patients.

Systemic Lupus Erythematosus (SLE) is closely related to cardiovascular morbidity and mortality. We aimed to examine the association of ideal cardiovascular health (ICH) with arterial stiffness, inflammation, and physical fitness in women with SLE.This cross-sectional study included 76 women with SLE (age 43.4±13.8 years old). Ideal levels of 7 health metrics (smoking, body mass index, physical activity, healthy diet, blood pressure, cholesterol, and glucose) were used to define the ICH score (ranging from 0 to 7 ideal metrics) and the ICH status ( defined as presenting ≥4 ideal metrics). Arterial stiffness was measured through pulse wave velocity (PWV) and inflammation through serum high sensitivity C-reactive protein (hs-CRP). Cardiorespiratory fitness (CRF) was measured by 6-min walk test (6MWT), and Siconolfi step test and muscular strength by handgrip strength and 30-s chair stand, and range of motion (ROM) by the back-scratch test.Higher ICH score was associated with lower PWV (β = -0.122, p = 0.002), lower hs-CRP (β = -0.234, p = 0.056), higher CRF [6MWT (β = 0.263, p = 0.041); Siconolfi step test (β = 0.330, p 0.001)], higher ROM (β = 0.278, p = 0.013) and higher relative handgrip strength (β = 0.248, p = 0.024). Women with ICH status presented lower PWV (mean difference 0.40 m/s, 95% CI 0.17 to 0.63, p = 0.001), and higher CRF [assessed by 6MWT (mean difference 43.9 m, 95% CI 5.0 to 82.7, p = 0.028)], than women with non-ICH status. Sensitivity analyses using ICH score ranging 0-14 and considering ICH status with ≥5 metrics revealed consistent results.ICH is associated with lower arterial stiffness, lower inflammation, and higher fitness in women with SLE. Although these results extend current knowledge about the potential role of ICH for primordial prevention of CVD in SLE, they are yet to be confirmed in future prospective research .

This work was funded by the Consejerı́a de Salud, Junta de Andalucı́a (grant numbers: PI-0525-2016 and PIER-0223-2019). BG-C was supported by the Spanish Ministry of Education (FPU15/00002). AS-M was supported by the Spanish Ministry of Science, Innovation and Universities (ref. RTI2018–093302- A-I00). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., Aims: Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE. Methods: A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry. Results: Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P, Consejerı́a de Salud, Junta de Andalucı́a (grant numbers: PI-0525-2016 and PIER-0223-2019), Spanish Ministry of Education (FPU15/00002), Spanish Ministry of Science, Innovation and Universities (ref. RTI2018–093302- A-I00)

Objective The objective of this study was to determine the safety of tattoos in patients with systemic lupus erythematosus (SLE). Methods Patients ( N = 147; ≤55 years; 92% women) were asked if they had tattoos. The characteristics of the tattoos and the immediate complications were investigated and compared with those of a matched control group. We examined retrospectively after the tattoo was completed whether there had been flare-ups or increased organ damage (Systemic Lupus International Collaborating Clinics/American Collage of Rheumatology Damage Index (SDI)). Finally, we compared the SLE-related characteristics of patients with and without tattoos. Results Twenty-eight patients (19%, 26 women, median (interquartile range) age 33 (25–42) years, 65 tattoos in total) had ≥1 tattoo. At the time the tattoo was done the median (interquartile range) SLEDAI and SDI were 2 (0–2) and 0 (0–1), respectively. The characteristics of the tattoos were similar to those of controls. No patients experienced acute complications. After a median follow-up of 17 (12–20) months (3 (2–4) visits/year) four patients had five mild-to-moderate flare-ups. The median time between the tattoo and the flare-up was 9 (6–14) months. No increase in SDI was observed. The SLE-related characteristics of patients with and without tattoos were similar. Conclusion Tattoos seem to be safe in SLE patients with inactive or low active disease.

Abnormal heart rate variability (HRV) has been observed in patients with systemic lupus erythematosus (SLE). In a combined cross-sectional and interventional study approach, we investigated the association of HRV with inflammation and oxidative stress markers, patient-reported outcomes, and the effect of 12 weeks of aerobic exercise in HRV. Fifty-five women with SLE (mean age 43.5 ± 14.0 years) were assigned to either aerobic exercise (n = 26) or usual care (n = 29) in a non-randomized trial. HRV was assessed using a heart rate monitor during 10 min, inflammatory and oxidative stress markers were obtained, psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey) were also assessed. Low frequency to high frequency power (LFHF) ratio was associated with physical fatigue (p = 0.019). Sample entropy was inversely associated with high-sensitivity C-reactive protein (p = 0.014) and myeloperoxidase (p = 0.007). There were no significant between-group differences in the changes in HRV derived parameters after the exercise intervention. High-sensitivity C-reactive protein and myeloperoxidase were negatively related to sample entropy and physical fatigue was positively related to LFHF ratio. However, an exercise intervention of 12 weeks of aerobic training did not produce any changes in HRV derived parameters in women with SLE in comparison to a control group., Fundacion para la Investigacion Biosanitaria de Andalucia Oriental PI-0525-2016 PIER-0223-2019, Spanish Ministry of Universities FPU18/01107

To evaluate the effects of aerobic exercise on patient-reported outcomes (PROs) in women with systemic lupus erythematosus (SLE), and whether changes in cardiorespiratory fitness (CRF) mediate the changes in PROs. A total of 58 women with SLE were assigned to either an exercise group (EG; n = 26) or a control group (CG; n = 32) in this non-randomized clinical trial. The EG comprised 12 weeks of aerobic exercise (2 sessions/week) between 40%-75% of the individual’s heart rate reserve. At baseline, and at week 12, CRF (Bruce test) and PROs were assessed including psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey). In comparison to the CG, the EG showed a significant reduction in general fatigue (mean difference (MD) −2.86 units; 95%CI −5.70 to −0.01; p = 0.049), physical fatigue (MD −4.33 units; 95%CI −7.02 to −1.65; p = 0.002) and a non-significant reduction of reduced motivation (MD − 1.29 units; 95%CI −2.60 to 0.03; p = 0.055). There were no significant between-group differences in the changes in psychological stress, sleep quality, depressive symptoms, quality of life, or other fatigue dimensions (all p > 0.05). Changes in CRF mediated the effects of the exercise intervention on general fatigue by 53.8%. The results suggest that 12 weeks of progressive aerobic exercise might improve relevant dimensions of fatigue in women with SLE, despite the absence of effects on other PROs. Improvements in CRF seem to mediate the effect of exercise on general fatigue.Implications for rehabilitationAerobic exercise could be safely introduced in rehabilitation programs for inactive patients with SLE with mild disease activity.Including physical activity recommendations as part of rehabilitation could improve relevant aspects of fatigue in women with SLE.When rehabilitation aims at reducing fatigue, cardiorespiratory fitness improvements derived from physical activity might enhance benefits. Aerobic exercise could be safely introduced in rehabilitation programs for inactive patients with SLE with mild disease activity. Including physical activity recommendations as part of rehabilitation could improve relevant aspects of fatigue in women with SLE. When rehabilitation aims at reducing fatigue, cardiorespiratory fitness improvements derived from physical activity might enhance benefits.

Background and objective Non-adherence to treatment is usually a clinical problem in patients with systemic lupus erythematosus (SLE). Increasing the knowledge of predictors of treatment adherence can be meaningful in the clinical setting. The main objective of the present study was to analyze the influence of sociodemographic, clinical and psychological variables on the degree of treatment adherence in a sample of Spanish women with SLE. Patients and method This is an observational–transversal study. All participants were evaluated for the degree of treatment adherence, their clinical status, psychopathological manifestations, the level of perceived stress and self-efficacy. The sample was divided into two groups (adherent vs non-adherent). The factors associated with a lack of adherence in this sample were analyzed by means of logistic regression. Results This study comprises 72 women with SLE (average age = 36.72 ± 12.2 years). Almost 64% of patients with SLE were non-adherent to treatment. The results showed that a low educational level, being unemployed, living with a partner and alcohol abuse were associated with low treatment adherence. There were significant mean differences between groups in psychopathological subscales of somatization, obsession–compulsion and general psychopathological indices. There were also mean differences between groups for the level of perceived stress. The use of non-steroidal anti-inflammatory drugs, suffering arthrosis and scoring higher in dimensions of psychopathology were significant predictors of treatment adherence, explaining between 35% and 47% of its variability. Conclusions Including the clinical and psychopathological manifestations as important aspects in the clinical reasoning of health professionals could improve the adherence to treatment of patients with SLE.

Aim Sleep problems are a common complaint in systemic lupus erythematosus (SLE) patients. We analyzed sleep quality with subjective and objective measures in a sample with SLE and its possible relationships with the main manifestations of the disease. Methods Twenty-one women with SLE and 20 healthy women participated in the study. All participants were evaluated with actigraphy for a week and they completed self-report instruments of sleep quality, quality of life, fatigue, anxiety, depression and perceived stress. Comparison analyses between the two groups were done using Chi-square and Student's t-tests. The association between sleep quality and the remaining variables was explored using Pearson correlation coefficients. Results SLE patients had higher fragmentation index in the actigraphic analysis and a perception of poorer sleep quality, more fatigue, anxiety and depression than the control group. Bivariate analyses showed that the perception of more sleep disturbance and daytime dysfunction was associated with a lower health-related quality of life, more fatigue, emotional discomfort and more perceived stress. Also, the fragmentation index in the actigraphy was significantly related to the perception of poorer quality of sleep. Conclusion SLE women had a poorer sleep quality (objective and subjective). These alterations could play a modulatory role in clinical and psychological manifestations of the disease and affect the quality of life in this population. More research is needed to clarify these relations and to determine the potential benefits of interventions directed to improve sleep in the clinical managing of the patients with SLE.

Objectives: This study analyzed sleep quality in fibromyalgia (FM) and systemic lupus erythematosus (SLE) and explored its relationship with other clinical and psychological manifestations.Methods:...

Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine the association of different components of physical fitness with body composition in women with SLE with mild disease activity. Materials and Methods: This cross-sectional study included 77 women with SLE (43.2 &plusmn, 13.8 years old) and clinical stability during the previous 6 months. Body composition (including body mass index (BMI), fat mass index (FMI), waist circumference, waist-to-height ratio and waist-to-hip ratio) was assessed using a stadiometer, an anthropometric tape, and a bioimpedance device. Physical fitness included cardiorespiratory fitness (Siconolfi step test and 6 min walk test), muscular strength (handgrip strength test as upper body measure and 30 s chair stand as lower body measure), and flexibility (back-scratch test). Participants with a fitness level equal or above the median of the study sample were categorized as &ldquo, fit&rdquo, and those below the median were categorized as &ldquo, unfit&rdquo, Linear regression assessed the association of physical fitness with body composition parameters. Results: Cardiorespiratory fitness and upper body muscular strength were negatively associated with BMI, FMI, waist circumference, and waist-to-height ratio (all, p &lt, 0.05). Lower body muscular strength and flexibility were negatively related to FMI, waist circumference, waist-to-height ratio, and waist-to-hip ratio (all, p &lt, 0.05). These relationships were still significant after controlling for age, disease duration, accrual damage, and SLE activity. Overall, fit patients presented significantly lower values in all body composition parameters compared to unfit patients (all, p &lt, 0.05). Conclusions: The main findings of the present study suggest that physical fitness is inversely associated with body composition in women with SLE. Given the cross-sectional nature of this study, future clinical trials should study the causal pathways underlying these relationships.

This study aimed to examine the association of relative handgrip strength (rHGS) with cardiometabolic disease risk factors in women with systemic lupus erythematosus (SLE). Methods: Seventy-seven women with SLE (mean age 43.2, SD 13.8) and clinical stability during the previous six months were included. Handgrip strength was assessed with a digital dynamometer and rHGS was defined as absolute handgrip strength (aHGS) divided by body mass index (BMI). We measured blood pressure, markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]), arterial stiffness (pulse wave velocity [PWV]), and renal function. A clustered cardiometabolic risk index (z-score) was computed. Results: Pearson0 s bivariate correlations revealed that higher rHGS was associated with lower systolic blood pressure (SBP), triglycerides, hs-CRP, PWV, and lower clustered cardiometabolic risk (rrange = from −0.43 to −0.23; all p < 0.05). Multivariable linear regression analyses adjusted for age, disease activity (SLEDAI), and accrual damage (SDI) confirmed these results (all p < 0.05) except for triglycerides. Conclusions: The findings suggest that higher rHGS is significantly associated with lower cardiometabolic risk in women with SLE., Consejería de Salud, Junta de Andalucía (grant numbers: PI-0525-2016 and PIER-0223-2019), Spanish Ministry of Education (FPU15/00002), Spanish Ministry of Science, Innovation and Universities (FPU18/01107), Gerty Cory pre-doctoral program for deficit areas at the University of Almería

To the Editor: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis affecting the small- and medium-sized arteries. It is characterized by bronchial asthma often accompanied by pulmonary infiltrates, chronic sinusitis, nasal polyps, and peripheral blood eosinophilia, and occasionally followed by a multisystem vasculitic phase involving several organs. Neurological involvement occurs in 51%–86%, usually affecting the peripheral nerves. Conversely, the central nervous system (CNS) is seldom affected (< 10%). In these cases, cerebral ischemic infarction (∼80%) and diffuse encephalopathy (∼10%) have been by far the findings most frequently reported. Published data on EGPA with CNS hemorrhage are limited to anecdotal case reports1–10,11–20,21,22,23,24,25,26. We described a case of EGPA presenting with intracerebral hemorrhage (ICH) and did a comprehensive review of the literature. Ethics board approval was not required in accordance with the policy of our hospital. A 48-year-old man was admitted because of malaise, intermittent low-grade fever, and mild weight loss in … Address correspondence to Dr. J.M. Sabio, Servicio de Medicina Interna, 9th planta Hospital Universitario Virgen de las Nieves, Avda. Fuerzas Armadas No. 2, 18012 Granada, Spain. E-mail: jomasabio{at}gmail.com

Objectives To examine the association of objectively measured physical activity (PA) intensity levels and sedentary time with arterial stiffness in women with systemic lupus erythematosus (SLE) with mild disease activity and to analyze whether participants meeting the international PA guidelines have lower arterial stiffness than those not meeting the PA guidelines. Methods The study comprised 47 women with SLE (average age 41.2 [standard deviation 13.9]) years, with clinical and treatment stability during the 6 months prior to the study. PA intensity levels and sedentary time were objectively measured with triaxial accelerometry. Arterial stiffness was assessed through pulse wave velocity, evaluated by Mobil-O-Graph® 24h pulse wave analysis monitor. Results The average time in moderate to vigorous PA in bouts of 10 consecutive minutes was 135.1±151.8 minutes per week. There was no association of PA intensity levels and sedentary time with arterial stiffness, either in crude analyses or after adjusting for potential confounders. Participants who met the international PA guidelines did not show lower pulse wave velocity than those not meeting them (b = -0.169; 95% CI: -0.480 to 0.143; P = 0.280). Conclusions Our results suggest that PA intensity levels and sedentary time are not associated with arterial stiffness in patients with SLE. Further analyses revealed that patients with SLE meeting international PA guidelines did not present lower arterial stiffness than those not meeting the PA guidelines. Future prospective research is needed to better understand the association of PA and sedentary time with arterial stiffness in patients with SLE., This work was supported by Fundación para la Investigación Biosanitaria de Andalucia Oriental, Grant numbers: PI-0525-2016 (http:// www.fibao.es/; http://www.ibsgranada.es/) to JAVH. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Blood pressure (BP) physiologically declines more than 10% at night. Subjects who do not experience this drop are classified as non-dippers. They have a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non-dipper pattern have been associated in the general population. Patients with systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency, a non-dipper pattern and CVD. We aimed to evaluate a possible relationship between vitamin D deficiency and non-dipper pattern in patients with SLE.Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided into dippers and non-dippers. 25-hydroxyvitamin D (25(OH)D) levels were compared between both groups. A multivariate analysis was used to determine which variables were independently associated with non-dipper pattern.62% of patients were non-dippers. They had lower levels of 25(OH)D than dippers (19.4±8.9 vs. 25.9±10.1 ng/ml, p=0.005). Patients with lower 25(OH)D levels were more likely to be non-dippers (OR 3.7, 95%CI 1.2-11.4; p=0.025). The nocturnal decline of mean BP correlated with levels of 25(OH)D (r=0.227, p=0.047). Night-time systolic, diastolic and mean BP inversely correlated with the levels of 25(OH)D (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but only night- time systolic BP remained significant after adjustment for age and body mass index (r=-0.228, p=0.049). 25(OH)D levels and the use of mycophenolate were found to be independently associated with non-dipper pattern in SLE patients.Vitamin D deficiency may contribute to the development of a non-dipper pattern in patients with SLE.

Aim To determine if there are ethnic differences in the prevalence of antiphospholipid syndrome (APS), clinical presentation and autoantibody profile between Roma and Caucasian patients with systemic lupus erythematosus (SLE). Method A cross-sectional study was conducted including data from Roma and Caucasian SLE patients consecutively attending six hospitals in Spain. Socio-demographic characteristics, prevalence of APS, clinical and analytical features of SLE and APS were compared between ethnic groups. Results Data from 52 Roma and 98 Caucasian SLE patients were included. Roma SLE patients had a higher risk (odds ratio 2.56, 95% CI 1.02–6.39) and prevalence of APS (28.8% vs. 13.3%, P = 0.027). Furthermore, Roma SLE patients had a statistically significant higher prevalence of abortions (23.5% vs. 10.2%, P = 0.049). In relation to other APS diagnostic criteria, Roma SLE patients had a non-statistically significant higher prevalence of fetal deaths (14.3% vs. 5.1%, P = 0.106) and thrombotic events (21.1% vs. 12.2%, P = 0.160). In relation to SLE clinical features, Roma patients had a significantly higher prevalence of arthritis (75% vs. 57.1%, P = 0.034) and non-significant higher prevalence of serositis (44.2% vs. 29.6%, P = 0.104), discoid lesions (11.5% vs. 5.1%, P = 0.191), oral ulcers (46.1% vs. 34.7%, P = 0.218) and livedo reticularis (21.1% vs. 15.3%, P = 0.374). No statistically significant differences were found in the Systemic Lupus International Collaborating Clinics Damage Index or the autoimmune serological profile. Conclusion Prevalence and risk of APS were significantly higher in Roma SLE patients. Furthermore, Roma patients had a significantly higher prevalence of abortions and a non-significant higher prevalence of fetal deaths and thrombotic events.

To evaluate psychopathological status and stress level from a sample with SLE; compare mental functioning and stress levels between women with SLE and healthy women; determine whether disease duration, disease activity, cumulative organ damage and stress have an influence on psychopathological symptoms in SLE patients; and evaluate whether perception of stress is related to SLE severity.We conducted a cross-sectional study of 425 participants; 202 women with SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age-matched controls. The assessment included the clinical characteristics (disease duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive, comparative, univariate and multivariate analysis were performed.SLE patients showed psychopathological alterations in the somatisation, obsessive-compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported significantly higher scores on the psychopathological dimensions and perceived stress compared to healthy women, except for paranoid ideation. Disease duration, SLE activity, cumulative organ damage, and perceived stress were shown to be significant predictors of psychopathological manifestations, explaining a range, between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived stress was related to SLE activity, after controlling for psychopathological dimensions.The psychopathological manifestations in SLE appeared to be influenced by perceived stress, disease duration, disease activity and cumulative organ damage. In turn, perceived stress was associated with disease severity. This knowledge may contribute to a more comprehensive perspective of these manifestations in the SLE population in the clinical setting.

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47phox were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti–double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. This work was supported by grants from Comisión Interministerial de Ciencia y Tecnología (SAF2010-22066-C02-01, SAF2011-28150), Junta de Andalucía (Proyecto de excelencia, P12-CTS-2722), Ministerio de Ciencia e Innovación Campus de Excelencia Internacional (Programa GREIB), and Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (Red HERACLES RD06/0009, RIC RD12/0042/0011 and RD12/0042/0040), Spain. M.J. Zarzuelo is a holder of studentship from Spanish Ministry of Science and Education.

Objective.To compare the prevalence and disability of headache in patients with systemic lupus erythematosus (SLE) with the general population and to assess the role of chronic psychological stress (CPS) in headache development.Methods.One hundred seventy patients with SLE and 102 control subjects matched for age, sex, and level of education were included in this multicenter, cross-sectional study. CPS, headache-related disability, and chronic analgesic intake (CAI) were evaluated in all participants.Results.No statistical differences in the prevalence of headache between both groups were observed but headache disability was significantly higher in patients with SLE. In addition, a higher average score in the Cohen Perceived Stress Scale (CPSS) and a higher prevalence of patients with CAI were observed in patients with SLE. In multivariate analysis, CPSS score was positively (OR 1.09; 95% CI: 1.03–1.14; p = 0.001) and CAI negatively (OR 0.43; 95% CI: 0.19–0.99; p = 0.049) associated with headache in patients with SLE.Conclusion.Despite the prevalence of headache in patients with SLE and the general population being similar, headache-related disability may be higher in patients with SLE. Moreover, CPS might play a role in the pathogenesis of SLE headache, whereas CAI might have a protective effect against it.

ObjectivesTo study the association of different components of physical fitness [flexibility, muscle strength and cardiorespiratory fitness (CRF)] and a clustered fitness score with health-related quality of life (HRQoL) in women with systemic lupus erythematosus (SLE) and to analyze whether participants with high fitness level have better HRQoL.MethodsThis cross-sectional study included 70 women with SLE (aged 42.5; SD 13.9 years). The back-scratch test assessed flexibility, the 30-sec chair stand and handgrip strength tests assessed muscle strength, and the 6-min walk test (n = 49) assessed CRF. HRQoL was assessed through the 36-item Short-Form Health Survey (SF-36).ResultsFlexibility was positively associated with the physical function dimension and the physical component summary (PCS) (rpartial between 0.26 and 0.31; pConclusionsOur study suggests that muscle strength and CRF are positively associated with HRQoL, while flexibility showed contradictory results. These findings highlight the importance of maintaining adequate fitness levels in women with SLE.

Journal Article; INTRODUCTION AND OBJECTIVES The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. MATERIAL AND METHODS 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett's formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. RESULTS Clinical basal characteristics were similar in both groups. QTc interval was 415±21.4 milliseconds in all patients, and 407±19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. CONCLUSION QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events. Yes

To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis.We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P0.05), and sicca syndrome (37.5% vs 14.5%, P0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor.The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements.

Objectives: Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. Methods: A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex-gene interaction was further validated using parametric and non-parametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. Results: A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10 -8) A significant sex-gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. Conclusions: The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.

Objective.Hypertension (HT) is more prevalent in patients with systemic lupus erythematosus (SLE) than among the general population and it has been associated with atherosclerotic cardiovascular diseases in these patients. We examined the proportion of HT and factors associated with it in young and old women with SLE.Methods.Participants (112 women with SLE and 223 healthy age-matched women) were categorized as young (age ≤ 40 years) or old (age > 40 years). We compared cardiovascular and specific SLE-related variables and inflammatory markers in hypertensive and normotensive women with SLE for each age range. We also assessed the factors independently associated with HT in the entire cohort and in each age range by means of a multivariate regression analysis.Results.The prevalence of HT was higher in women with SLE than in controls (56% vs 29%; p < 0.001), and was proportionally higher in younger women with SLE (40% vs 11%; p < 0.001) than in older women with SLE (74% vs 47%; p = 0.001). After adjustment for potential confounders, HT was associated with renal involvement and higher nonobesity-related insulin levels in younger women with SLE. In older patients, HT was associated with age, renal involvement, and obesity. Finally, in the entire cohort, HT was associated with age, insulin, renal involvement, and the Systemic Lupus Erythematosus Disease Activity Index score.Conclusion.An association between HT and insulin has been identified in women with SLE, particularly younger ones. Factors associated with HT in women with SLE differed depending on their age. HT was more prevalent in women with SLE than in control subjects, being proportionally higher in young women with SLE.

The objective of this article was to evaluate whether serum uric acid (SUA) correlates with arterial stiffness and inflammation markers in a cohort of women with systemic lupus erythematosus (SLE) without overt atherosclerotic cardiovascular diseases, who attended a community hospital. One hundred and two women with SLE were assessed as part of this cross-sectional study. Carotid-femoral pulse wave velocity (PWV) was measured using an automatic device (Complior®). C-reactive protein (CRP), fibrinogen and homocysteine levels as well as other metabolic results were recorded. Duration and activity of SLE, damage accrual and treatments were recorded. SLE women were categorized as having or not having hyperuricaemia (HU) according to SUA levels (greater than or up to 6.2 mg/dl, respectively). A multiple linear regression analysis was used to determine the independent link between SUA levels and other variables. Women with SLE and HU (n = 15, 15%) had a worse cardiovascular risk profile that included ageing, hypertension, obesity, higher total cholesterol levels, renal failure and presence of metabolic syndrome. Also, the duration of SLE was increased and damage accrual was greater. In the unadjusted analysis, SUA levels correlated with PWV, CRP, fibrinogen and homocysteine. However, in a multivariate linear regression analysis, SUA levels independently correlated with the duration of SLE, creatinine, total cholesterol and homocysteine levels but did not correlate with PWV. In conclusion, SUA was associated with arterial stiffness, but not independently of age and homocysteine levels. Nevertheless, SUA might be an ancillary indicator of subclinical atherosclerosis in SLE women without clinically evident atherosclerotic cardiovascular disease. Lupus (2010) 19, 591—598.

Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE). Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% Cl 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.1,9 [95% Cl 1.50-3.22], P = 0.00007). Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population. (Less)

Objective.To compare 24-h ambulatory blood pressure (BP) monitoring (ABPM) values and patterns in women with systemic lupus erythematosus (SLE) with those of a matched control group and their relationship with the presence of subclinical atherosclerosis.Methods.ABPM was assessed in 70 women with SLE and in 65 sex- and age-matched controls without a history of clinic cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (PWV), which is a marker of subclinical atherosclerosis and a predictor of future CVD, was measured. Multivariate logistic analysis was used to determine which explanatory variables were independently associated with the non-dipper pattern and the presence of nocturnal hypertension (HTN) in women with SLE.Results.No differences in PWV were found between patients and controls [median 7.3, interquartile range (IQR) 6.5–8.1 m/s vs median 7.1, IQR 6.5–7.8 m/s, p = 0.474]. The frequency of nondipper pattern (p = 0.025) and nocturnal HTN (p = 0.004) was significantly higher in women with SLE than in controls. White-coat and masked HTN were present in 10% and 11% of patients and in 20% and 8% of controls, respectively (p > 0.05 in all cases). The concordance between office and ambulatory HTN in the SLE and control groups was modest (κ = 0.325 and κ = 0.451, respectively). PWV and chronic kidney disease, and PWV and the Systemic Lupus Erythematosus Disease Activity Index were found to be independently associated with nocturnal HTN and nondipper pattern, respectively.Conclusion.Women with SLE were more likely to have an altered nighttime BP pattern than controls. In women with SLE, nondipper pattern and nocturnal HTN were independently associated with increased subclinical atherosclerosis measured by PWV.

Learning point for clinicians Mucocutaneous leishmaniasis is an increasingly common opportunistic infection that should be considered during treatment with mycophenolate mofetil, especially when other immunosuppressant drugs (such as corticosteroids) or diseases (such as systemic lupus erythematosus) are present. Leishmaniasis is an infectious disease in which immunosupression is a well-known risk factor for its development. We report the first case of a patient with systemic lupus erythematosus (SLE) who was diagnosed of mucocutaneous leishmaniasis (ML) while taking mycophenolate mofetil (MMF) for lupus nephritis. A 51-year-old woman from the south of Spain with an 8-year history of SLE was diagnosed with diffuse proliferative glomerulonephritis 6 years after her SLE diagnosis, which was satisfactorily treated until complete remission was achieved with MMF (1 g b.i.d) and decreasing doses of prednisone (from 30 mg to 10 mg q.d). The …

The aim of this study was to evaluate the potential association of functional polymorphisms of macrophage migration inhibitory factor with systemic lupus erythematosus. Our study includes 711 systemic lupus erythematosus (SLE) patients and 755 healthy controls. We genotyped the migration inhibitory factor (MIF) -173G/C using a polymerase chain reaction (PCR) system with predeveloped TaqMan allelic discrimination assay and the MIF -794 CATTn microsatellite polymorphism using a PCR-fluorescent method. A statistically significant difference in the distribution of the MIF -173*C allele between SLE patients and controls (P=0.004, OR=1.34, 95% CI=1.05-1.27) was observed. In addition, the frequency of the MIF -173* C/C genotype was higher in SLE patient (P=0.002, OR 2.58, 95% CI 1.32-5.10). No differences in the distribution of CATTn were found. However, the haplotypes analyses showed that only the CATT7-MIF -173* C haplotype was associated with a higher susceptibility to SLE (P=0.001, OR 1.84, 95% CI 1.35-2.79). No association with clinical features was detected in any case. These results suggest that both, MIF -173*C allele and CATT7-MIF -173*C haplotype, confer susceptibility to SLE in our population. © 2006 Nature Publishing Group. All rights reserved.

We evaluated the influence of the hereditary make-up on the development of systemic lupus erythematosus (SLE) in two ethnic groups [Gypsy and white Caucasian Mediterranean (WCM) populations], living in the same geographic area. We compared 81 WCM and 25 Gypsy patients with SLE. The control group consisted of 185 healthy unrelated individuals, 105 WC and 80 Gypsies. In the Gypsy population, the onset of SLE occurred at earlier ages than in the other ethnic group (25.9 versus 32.0 years, P = 0.02), and showed lower SLEDAI peak values (4.9 versus 7.0, P = 0.016). The frequency of joint, kidney, gastrointestinal and eye involvement was significantly lower in Gypsy patients. In contrast, SLE-associated antiphospholipid syndrome, thrombosis and livedo reticularis were more frequent in Gypsies than in the majority ethnic group (WCM). In WCM patients, DRB1*1303- DQB1*0301 haplotype was associated with SLE ( P = 0.001, Pc= 0.038). We found SLE to be associated with DR5 ( P = 0.006, Pc= 0.05) in the Gypsy population as well as a protective effect of DPB1*0401 when DR5 was not present ( P = 0.008, Pc= 0.032). In conclusion, we found some clinical differences between WCM and Gypsy patients with SLE. Furthermore, HLA associations between HLA-DRB1-DQB1 and SLE were different for Gypsy people.

Objective The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. Patients and methods In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. Results Women with SLE tended to have lower 25(OH)D levels ( p = 0.078) and a higher frequency of 25(OH)D deficiency (defined as Conclusion Low 25(OH)D levels were found to be associated with increased IR in nondiabetic women with SLE independently of BMI. Low 25(OH)D levels, but not IR, could be associated with increased arterial stiffness in these patients.

To compare the presence of subclinical atherosclerosis measured by means of pulse wave velocity (PWV) in women with primary Sjögren's syndrome (SS) versus a healthy age- and sex-matched control group, and to identify factors independently associated with PWV in primary SS.Forty-four women with primary SS and 78 age-matched healthy women without overt cardiovascular (CV) diseases were assessed for traditional and nontraditional CV risk factors. PWV was also performed. A linear regression analysis was used to identify factors independently associated with PWV in primary SS.Women with primary SS had significantly higher PWV than controls (P = 0.030), and the frequency of increased PWV was significantly higher in this group (25% versus 8%; P = 0.013). The proportion of patients ages ≤50 years (ratio 4.6) with increased PWV was almost 2-fold higher than those ages50 years (ratio 2.4) with respect to controls. Positivity for anti-SSB was more frequent in patients with normal PWV than in those with increased PWV (61% versus 18%; P = 0.034). Women with primary SS and increased PWV had lower levels of 25-hydroxyvitamin D (25[OH]D; P = 0.047) than primary SS patients with normal PWV. In addition, 25(OH)D levels tended to correlate inversely with PWV in women with primary SS (P = 0.067), but not in controls (P = 0.97). In multivariate analysis, the Framingham Risk Score (FRS) and Sjögren's Syndrome Damage Index emerged as factors independently correlated with PWV.Women with primary SS had higher PWV than controls, but a similar FRS. The FRS and chronic damage were found to be independently associated with PWV.

Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant.

Homocysteine has been linked to atherosclerosis and hypertension (HT) in the general population. However, there is limited evidence regarding the effect of homocysteine on blood pressure and arterial stiffness in systemic lupus erythematosus (SLE). We examined whether homocysteine is associated with HT and arterial stiffness in women with SLE.In total, 99 women with SLE without a history of cardiovascular disease or diabetes mellitus and 101 matched controls were included in this cross-sectional study. Participants were analyzed for homocysteine levels, cardiovascular risk factors, and arterial stiffness assessed by means of carotid-femoral pulse wave velocity (PWV). Associations between homocysteine, systolic blood pressure (SBP), PWV, and HT were tested using univariate and multivariate analyses.Homocysteine levels (mean ± SD 12.3 ± 4.8 versus 9.3 ± 3.8 μmoles/liter), PWV (mean ± SD 7.54 ± 1.1 versus 7.10 ± 1.1 meters/second), SBP (mean ± SD 119 ± 13 versus 115 ± 12 mm Hg), and the prevalence of hyperhomocysteinemia (23% versus 7%) and HT (43% versus 12%) were significantly higher in women with SLE (P0.050 for all). In the univariate analysis, homocysteine correlated positively with SBP (P = 0.001) and PWV (P = 0.023) in women with SLE but not in controls. In the multiple linear regression analysis, SBP was independently associated with homocysteine and body mass index (BMI) in women with SLE. Similarly, in the multivariate logistic regression analysis, homocysteine levels (or hyperhomocysteinemia), BMI, and daily prednisone dose were independently associated with HT in women with SLE.Homocysteine was independently associated with SBP and HT in women with SLE, but not in controls. Elevated homocysteine levels could increase the risk of HT in SLE.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3′–5′ exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi–Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ~8370 patients with SLE and ~7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case–control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25–2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E−13, OR=5.2, 95% CI=3.18–8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.

To determine the “in-vitro” intrinsic cell radiosensitivity (RS) as a risk indicator of radiation-related side-effects in patients with systemic lupus erythematosus (SLE) compared with healthy subjects (control group). Moreover, we elucidated if clinical, therapeutic and biological parameters could affect the “in-vitro” intrinsic RS in patients with SLE. Intrinsic RS was determined by the quantification of the initial radiation-induced DNA double-strand breaks in peripheral lymphocytes, measured by pulsed-field gel electrophoresis from 52 patients with SLE and a control group consisting of 48 sex- and age-matched healthy subjects. No difference in intrinsic RS was found among both groups. However, SLE patients with anaemia, increased erythrocyte sedimentation rate and those with positive result for anti-La/SSB and anti-RNP antibodies showed significantly higher DNA double-strand breaks than those without them. In our study, patients with SLE did not have a higher intrinsic RS than healthy subjects. According to these results, and with the caution of being a limited laboratory study, the use of radiotherapy should not be avoided in patients with SLE when it is clinically needed.

The aim of this study was to determine the potential role of three IRF3 gene polymorphisms (rs2304204, rs7251 and rs2304207) with systemic lupus erythematosus (SLE). Our study population consisted of 610 patients with SLE and 730 healthy controls. All individual were of Spanish Caucasian origin. The IRF3 polymorphisms were genotyped using a PCR system with pre-developed TaqMan allelic discrimination assay. No statistically significant differences were found when allele and genotype distribution of rs2304204, rs7251 and rs2304207 polymorphisms were compared between patients with SLE and controls [overall P values: rs7251, P = 0.06; rs2304204, P = 0.26 and rs2304207, P = 0.36, by chi-squared test on a 3 × 2 contingency table. Overall allelic P values: rs7251, P = 0.8, OR (95%CI) = 1.03 (0.87–1.22); rs2304204, P = 0.2, OR (95%CI) = 1.12 (0.93–1.34) and rs2304207, P = 0.8, OR (95%CI) = 1.02 (0.82–1.26)]. In addition, no evidence of association with haplotypes and clinical features of SLE was found. Our data suggest that the IRF3 polymorphisms do not appear to play a major role in the susceptibility or severity of SLE in a Spanish population.

The aim of this study was to assess the possible association between the p53 suppressor gene codon 72 polymorphism and systemic lupus erythematosus (SLE). Our study population consisted of 513 SLE patients and 567 healthy controls. All the individuals were of Spanish Caucasian origin. Genotyping of the p53 codon 72 polymorphism was performed by allele-specific PCR. No statistically significant differences were observed between SLE patients and healthy controls when p53 codon 72 genotype and allele frequencies were compared. In addition, no evidence for association with clinical subfeatures of SLE was found. In conclusion, the p53 codon 72 polymorphism associated with SLE in a Korean population does not appear to play a major role in the susceptibility or severity of SLE in the Spanish population.

This article is available from: http://www.biomedcentral.com/1471-2350/7/48, [Background] Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1α, and MCP-1 for systemic lupus erythematosus., [Methods] The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1α, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay., [Results] No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1α, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found., [Conclusion] These results suggest that the tested functional variation of RANTES, IL-8, IL-1α, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population., This work was supported by grant SAF03-3460 from Plan Nacional de I+D+I, and in part by the Junta de Andalucía, grupo CTS-180. We thank Sasha Zhernakova for her excellent technical assistance.

The prevalence of primary aldosteronism (PA) has experienced an important increase, and many authors consider this condition as the main cause of secondary hypertension (HT).Retrospective study of a series of 54 patients having PA who were studied in our Unit between 1999 and 2003.The prevalence of PA was 5.1%. Out of 54 PA cases, 13 corresponded to aldosterone-producing adenomas (APA), 30 to bilateral adrenal hyperplasia (BAH), one was one case of nodular bilateral hyperplasia and another case was a nodular unilateral hyperplasia. In 9 cases, an etiologic diagnosis could not be done. APA were more frequent in women and BAH in men; with regard to sex, no significant differences were found. The blood pressure (BP) was significantly higher in patients with APA compared with BAH patients. In patients with APA, kalemia was significantly lower than in BAH patients. Adrenal CT scan identified 90% of APA, while scintigraphy detected 100% of BAH. Spironolactone therapy significantly decreased the BP in APA and BAH patients, although this fall was higher in patients with APA.The prevalence of PA was 5.1%. Although the tests used for the screening and diagnosis of PA are controversial, a PA ought to be investigated in all patients with refractory HT, independently of the existence of hypokalemia. Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable.

There are not studies about the utility of modified liberation doxazosin (MLD) in the combined treatment of the true resistant hypertension (TRH). The aim of this study was to determinate the effect of MLD on the blood pressure (BP), insulin resistance, and the catecholamine secretion in these patients.Twenty seven patients with TRH from our unit were studied above and after 12 weeks of treatment with MLD (8 mg/day). The following parameters, among others, were analysed: office BP, ambulatory BP (ABPM), rennin, aldosterone and insulin plasmatic levels, urinary catecholamines and the insulin sensitivity index.Two patients were excluded because of adverse sides. After the treatment period, 53.8% of patients experimented a decrease of office diastolic BP higher than 10 mmHg, and 44% of them presented a decrease of 24-hour diastolic BP higher than 5 mmHg (answer patients). Likewise, 38.5% and 24% of patients achieved an adequate office BP and ABPM control, respectively. Also, a significant decrease of insulin resistance and urinary catecholamines, and an increase of aldosterone in plasma were observed. The rest of parameters remained invariables.MLD could be useful in the TRH treatment, because this drug decreased significantly BP, insulin resistance and catecholamine secretion in these patients, with a good tolerance.

Background: Sialochemistry has been proposed as a simple and useful tool for the diagnosis of Sjogren syndrome (SS). Although many changes have been detected in several constituents of saliva from patients with SS, none are individually sensitive or specific enough for diagnosing SS. The aim of this study was to assess the value of the combined determination of β2-microglobulin (β2m) and gamma-glutamyl-transferase (GGT) activity in serum and saliva as a diagnostic instrument for differentiating primary and secondary [to systemic lupus erythematosus (SLE)] SS patients from normal subjects. Methods: Nineteen primary SS (pSS) patients, 15 patients with SS secondary to SLE, and 25 SLE patients without SS were studied. Thirty healthy subjects were included in the study as control group. Results: By means of a mathematical model, (a) 84.1%, (b) 85.7%, and (c) 87.0% of patients were correctly classified as SS or normal when (a) salivary β2m and GGT values, (b) serum β2m and salivary GGT values, and (c) salivary β2m and GGT along with serum β2m values, respectively, were considered. To differentiate between pSS and sSS by means of the mathematical model, the combination of serum β2m and salivary GGT values achieved that 81.8% of the patients were correctly classified. Conclusion: Since sialochemistry is an easy, safe and reliable test, the combined determination of β2m and GGT in saliva and serum was useful for differentiating SS patients from normal subjects, but not excessively good for differentiating pSS from sSS patients.

White coat hypertension (WCH) is a prevalent clinical situation which requires a therapeutic management different from persistent hypertension (PH). To distinguish between patients with WCH and uncertain hypertension from patients with PH, an ambulatory blood pressure monitoring (ABPM) is usually indicated, yet it is not available in primary care. Thereby, predictors of WCH on the basis of pre-test (pre-ABPM) clinical characteristics have been suggested. However, little is known about the predictors of PH. The aim of this study was to ascertain predictors of PH in patients referred from the primary care due to suspicion of WCH or uncertain hypertension.A 24-hours ABPM was performed in 230 consecutive patients referred from primary care because of suspicion of WCH or uncertain hypertension. WCH was defined as an increased office BP with a mean daytime BP, as measured by ABPM,135/85 mmHg. Uncertain hypertension was diagnosed when patients had had episodic (2 or more) office BP140 and/or 90 mmHg together with normal BP determinations. Patients with increased office BP with a mean daytime BP [by ABPM]3 135/85 mmHg were considered as having PH.In 178 patients, ABPM was successful. Eighty-six patients (48.3%) had PH and the remainder (92 patients; 51.7%) were considered as having WCH. In the PH group, there were more males (67.4% vs 43.5%; p0.001), patients were older (42.8 [11.8] years vs 35.7 [11.2] years), there were more smokers (39.5 vs 26.1%; p = 0.056), they consumed more alcohol (p = 0.001) and coffee (p0.001) and they had higher levels of hemoglobin (p = 0.001) and creatinine (p = 0.003) and lower levels of uric acid (p0.001) than the WCH group. Also they had an office BP and an ambulatory BP higher than WCH patients. A multivariate logistic regression analysis revealed that PH was significantly associated with a male gender (odds ratio [OR] = 3.26; confidence interval [CI]: 1.54-6.88; p = 0.001), office systolic BP145 mmHg (OR = 6.53; CI, 2.67-16.11; p0.001), age (35 years) (OR = 5.03; CI, 2.35-10.78; p0.001) and smoking (OR = 3.07; CI, 1.38-6.84; p = 0.005).Our findings indicate that in patients referred from primary care due to suspicion of WCH or uncertain hypertension, the prevalence of PH was 48.3%. PH was more frequent among men older than 35 years, smokers and those with an ambulatory systolic BP145 mmHg.

The etiological role of hair dye treatment (HDT), some of them such as permanent hair dyes containing aromatic amines, in the development of SLE has been previously ruled out. However, the possible influence of HDT use on the course and prognosis of lupus patients has been assessed only in one short-term study. Since HDT is very extensive among the population, the knowledge of this possible negative effect may be very important. Thus, the aim of this study was to assess the long-term influence of several HDTs on the course and clinical severity of patients with both systemic lupus erythematosus (SLE) and cutaneous lupus (CL). In this longitudinal case series study, 91 SLE patients and 22 CL patients were prospectively studied from October 1988 to May 2000. They were divided into three groups: (a) non-HDT users— patients who have never used HDT (n = 65); (b) P-HDT users—HDT permanent type users, alone or in combination with other types of HDT (n = 28); (c) non P-HDT—users of other treatments different from permanent tinting (bleach, lowlights, etc; n = 20). In each patient we determined: (1) number of flares/year in SLE patients and worsening of cutaneous lesions for CL; (2) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index; (3) predominant damaged organs/systems according to the HDT use and type of HDT; and (4) subjective impression about the disease evolution in relation to HDT use. No significant differences were found with respect to flares/year and SLICC/ACR damage index between the study groups. Non-HDT group presented more renal involvement and serositis than both HDT-user groups. No patient related the HDT use to the worsening of his disease. Therefore, in this study no evidence of an association between the long-term use of several types of HDT and the clinical activity and course of SLE and CL was found.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which increased apoptosis and decreased apoptotic cells removal has been described as most relevant in the pathogenesis. Long-chain acyl-coenzyme A synthetases (ACSLs) have been involved in the immunological dysfunction of mouse models of lupus-like autoimmunity and apoptosis in different in vitro cell systems. The aim of this work was to assess among the ACSL isoforms the involvement of ACSL2, ACSL4 and ACSL5 in SLE pathogenesis. Findings With this end, we determined the ACSL2, ACSL4 and ACSL5 transcript levels in peripheral blood mononuclear cells (PBMCs) of 45 SLE patients and 49 healthy controls by quantitative real time-PCR (q-PCR). We found that patients with SLE had higher ACSL5 transcript levels than healthy controls [median (range), healthy controls = 16.5 (12.3–18.0) vs. SLE = 26.5 (17.8–41.7), P = 3.9×10 E-5] but no differences were found for ACSL2 and ACSL4. In in vitro experiments, ACSL5 mRNA expression was greatly increased when inducing apoptosis in Jurkat T cells and PBMCs by Phorbol-Myristate-Acetate plus Ionomycin (PMA+Io). On the other hand, short interference RNA (siRNA)-mediated silencing of ACSL5 decreased induced apoptosis in Jurkat T cells up to the control levels as well as decreased mRNA expression of FAS, FASLG and TNF. Conclusions These findings indicate that ACSL5 may play a role in the apoptosis that takes place in SLE. Our results point to ACSL5 as a potential novel functional marker of pathogenesis and a possible therapeutic target in SLE., Financial support for the study was provided by the Ministerio de Ciencia e Innovación-Fondos Feder (PN-SAF2009-11491) and Junta de Andalucía (P07-CVI-02551) to A. Alcina and Fondo de Investigación Sanitaria (FIS PI081636, CP10/00526) to F. Matesanz. M. Fedetz and D. Ndagire are holders of a fellowship from Fundación Española de Esclerosis Múltiple (FEDEM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.