High-sensitivity cardiac troponin I is a biomarker for increased arterial stiffness in systemic lupus erythematous women with normal kidney function.

Cardiovascular disease (CVD) is a main cause of death in patients with systemic lupus erythematous (SLE). Algorithms for cardiovascular risk stratification in general population underestimate the risk for CVD in SLE. Our study aimed to determine whether serum high-sensitivity cardiac troponin I (hs-cTnI) might help to identify SLE patients with subclinical atherosclerosis. Arterial stiffness was assessed measuring the carotid-femoral pulse wave velocity (PWV) in 68 SLE women with a normal or almost normal kidney function and in 71 controls of similar characteristics. None of the participants had a history of an overt CVD. Serum hs-cTnI level was measured using the chemiluminescence method. Factors associated with an increased PWV (iPWV) were identified and multivariate analysis was performed. When detectable, patients tended to have had higher hs-cTnI levels than controls [2.9 (2.3-4.0) vs 2.4 (2.2-4.1); p = 0.098] and were more likely to have detectable hs-cTnI [50% vs 28%, odds ratio (OR) 7.0; 95% confidence interval (CI) 0.008-0.013]. Also, patients with iPWV were more likely to have detectable hs-cTnI than those with normal PWV (OR 6.4; 95% CI 0.019-0.026). In the multivariate analysis, the age at SLE diagnosis (OR 1.24; 95% CI 1.04-1.48), systolic blood pressure (OR 1.28; 95% CI 1.10-1.48) and detectable hs-cTnI level (OR 2.04; 95% CI 1.18-3.50) were independently associated with an iPWV. The negative predictive value of having an iPWV with undetectable hs-cTnI levels was 88%. Hs-cTnI may be a useful biomarker for the identification of SLE patients with iPWV as a surrogated marker of subclinical atherosclerosis. Specifically targeted prospective studies are needed to confirm this hypothesis.

Characteristics and safety of tattoos in patients with systemic lupus erythematosus.

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.

Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

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.

A man with unilateral endophthalmitis: a case of disseminated nocardiosis.

We present the case of a patient with an infection by Nocardia which manifested itself with monocular endophthalmitis. Nocardia infection is not common and ocular involvement is one of the most uncommon presentations. In these cases it is very important to make an early diagnosis and intensive treatment to prevent the visual prognosis.

Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus.

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 < 10 ng/ml) than controls (p = 0.058). Patients from the lowest quartile of the 25(OH)D range had higher PWV (p = 0.043), fasting glucose (p = 0.035), insulinemia (p ≤ 0.001), HOMA-IR (p = 0.006), C4 (p = 0.012), as well as more frequent IR (p = 0.002) and metabolic syndrome (p = 0.052) than those in the upper quartile, and no differences were found in age, body mass index (BMI), blood pressure, lipid levels and renal function. In women with SLE, 25(OH)D inversely correlated with insulin (p = 0.006), HOMA-IR (p = 0.008) and C4 (p = 0.048) and tended to correlate with fibrinogen (p = 0.060) after adjustment for BMI, age, SLEDAI, prednisone dose, renal function, inflammation markers and seasonal variation, but not with PWV. In controls, 25(OH)D correlated only with homocysteine after the same adjustment, and the correlation with PWV tended to be significant after adjustment for BMI and age (r = -0.190, p = 0.10). 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.

Follow-up of patients with systemic lupus erythematosus: what is not found in the guidelines.

A series of measures in the management of patients with systemic lupus erythematosus (SLE) which usually are not found in the lupus guidelines are discussed. In the lupus patient who has been well-controlled in the long term, the dose of hydroxychloroquine should be progressively reduced, without decreasing more than approximately 600 mg per week. We recommend taking this drug in the morning in patients with insomnia, at night in those with dyspepsia and to separate the intake of the drug from the shower (and the water should be as cool as possible) in those patients with aquagenic pruritus. We do not use prednisone on alternate days and exceptionally divide the dose into ¾ before breakfast and » before dinner. Twenty to 30 min should be used per patient in every scheduled visit to assure a good clinical and human practice. We analyzed the follow-up of 112 consecutive patients from our systemic disease unit and found that 71.4% of them had symptoms that were unexplained by lupus and we only referred 8.9% of them to other specialists, probably because of our general training as internal medicine doctors. We suggest that knowing the views of SLE specialists might be of interest since, well-designed studies that would allow to progress in the understanding of this disease could be performed based on their experience.

Direct cost of management and treatment of active systemic lupus erythematosus and its flares in Spain: the LUCIE Study.

BACKGROUND AND OBJECTIVE: The cost of control and management of Systemic Lupus Erythematosus (SLE) in Spain is unknown. This study has aimed to describe the healthcare resources associated to control and treatment of LES and its flares and to estimate the associated direct costs. PATIENTS AND METHODS: This was a European, multicentric, retrospective study (2008-2010) carried out with the participation of 5 hospitals in Spain with experience in SLE. Adult SLE patients (ACR criteria), with positive auto-antibodies (ANA and/or anti-ds-DNA) and active disease were included. Patients were stratified into severe and non-severe SLE. Direct healthcare costs were estimated with resources used and their unit costs. RESULTS: Seventy-five out of 79 SLE patients were analyzed. Of these, 52% had severe disease, 91.9% were females and 90.7% were Caucasian. Mean (SD) age was 41.0 (14.5) years. Annual direct cost per patient related to SLE management was €5,968 (7,038) and €3,604 (5,159) for severe and non-severe patients, respectively (P=.002). Costs related to hospitalizations, pharmacological treatment, visits to specialists, and laboratory tests were higher for patients with severe disease. At least one flare during the observation period was present in 90.7% of patients. Severe flares were a significant predictor of increase in cost. CONCLUSIONS: The cost associated with SLE control and treatment is higher for severe SLE patients. Insufficient control of the disease activity results in an increase in flares. Its presence is related to an increase in costs, hospitalization being the major component.

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort.

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.

Quality-of-life predictor factors in patients with SLE and their modification after cognitive behavioural therapy.

OBJECTIVE: The aim of the study was to determine the clinical and psychological factors linked to health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE) and test the effectiveness of cognitive behavioural therapy in changing these factors. METHODS: We evaluated 34 patients with SLE over a period of 15 months. In order to study the variables related to items of QOL and the physical (PCS) and mental (MCS) component summaries of the SF-36, several multiple linear regression models were constructed. Patients were randomized and distributed into two similar groups; one of them received cognitive behavioural therapy and the other received the usual controlled care. The psychological aspects as well as the related-disease factors were evaluated four times during the study. RESULTS: Self-perceived stress (R² corrected: 0.314, t: -2.476, p < 0.021), vulnerability to stress (R² corrected: 0.448, T: -2.166, p < 0.04) and anxiety (R² corrected: 0.689, T: -7.294, p < 0.00) were predictor variables of MCS. The group of patients who received the therapy improved their level of physical role functioning, vitality, general health perceptions and mental health, compared with the group of patients who only received conventional care. CONCLUSION: QOL usually depends on multiple factors, some of which are stress and anxiety, which can be modified by a cognitive behavioural therapy, in order to obtain a significant improvement in the HRQOL, irrespective of the activity level of the disease. Frequent evaluations of the quality of life in patients with SLE and psychological treatment should also be considered.

Effects of low or medium-dose of prednisone on insulin resistance in patients with systemic lupus erythematosus.

OBJECTIVES: To determine the effect of low (< or =7.5 mg/day; LD-PRD group) or medium (>7.5 mg/day; MD-PRD group) doses of prednisone over the past 4 months on insulin levels and insulin resistance (IR) in SLE patients. METHODS: SLE patients were categorised in prednisone non-users (No PRD) (n=41), LD-PRD (n=71) and MD-PRD (n=16) users. We compared insulin levels, presence of increased IR using homeostasis model assessment (HOMA index), metabolic syndrome (MetS), and other clinical, metabolic and inflammatory parameters in the 3 groups. A Spearman's rho test was used to identify independent associations between daily prednisone dose, HOMA index and insulin levels and other parameters, after adjusting for confounders. RESULTS: No differences in increased IR, HOMA index and insulin between No PRD and LD-PRD were found. In contrast, the MD-PRD group was younger (p=0.001) and had higher insulin (p=0.015), higher HOMA index (p=0.019) and increased IR (OR 5.8, 95% CI (1.7-20), p=0.007) in comparison with the LD-PRD group. The HOMA index strongly correlated with body mass index (BMI) (rs=0.460, p<0.001) but not with clinical activity or inflammatory state after adjusting for confounders. Prednisone dose correlated with the HOMA index and insulin but not with inflammatory parameters (erythrocyte sedimentation rate p=0.075) after adjusting for confounder. CONCLUSIONS: Daily medium-dose prednisone use (>7.5 mg/d) but not low-dose (< or =7.5 mg/d) use increased insulin levels and IR in SLE, which may contribute to increased CV risk experienced by these patients.

Correlation of asymptomatic hyperuricaemia and serum uric acid levels with arterial stiffness in women with systemic lupus erythematosus without clinically evident atherosclerotic cardiovascular disease.

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.

In-vitro radiosensitivity in patients with systemic lupus erythematosus.

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.

Investigation of TLR5 and TLR7 as candidate genes for susceptibility to systemic lupus erythematosus.

OBJECTIVES: The aim of this study was to evaluate the relevance of genetic variants of TLR5 (rs5744168) and TLR7 (rs179008) gene in systemic lupus erythematosus (SLE) in a Spanish population. MATERIAL AND METHODS: Our study population consisted of 752 SLE patients and 1107 healthy controls. All individual were of Spanish Caucasian origin. The TLR5 and TLR7 polymorphisms were genotyped using a PCR system with pre-developed TaqMan allelic discrimination assay. RESULTS: No statistically significant differences were observed when the allele and genotype distribution of TLR5 rs5744168 and TLR7 rs179008 polymorphisms was compared between SLE patients and healthy controls. A significant increase frequency in the CC genotype of the TLR5 rs5744168 polymorphism among SLE patients without nephritis was found (93% vs. 87% in SLE patients with nephritis, p=0.03, OR=2.11 95%CI 0.93-3.51). However, this difference did not reach statistical significance in the allele frequencies (p=0.08). CONCLUSION: These results suggest that the tested variations of TLR5 and TLR7 genes do not confer a relevant role in the susceptibility or severity to SLE in the Spanish population.

No evidence for genetic association of interferon regulatory factor 3 in systemic lupus erythematosus.

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 x 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.

Metabolic syndrome in patients with systemic lupus erythematosus from Southern Spain.

The aim of this cross-sectional study was to establish the frequency, phenotype and characteristics of metabolic syndrome (MS), as defined by the Adult Treatment Panel III, in a cohort of patients with systemic lupus erythematosus (SLE) and its possible association with cardiovascular diseases (CVD). A total of 160 patients with SLE and 245 age, sex, educational level and ethnically matched controls were included. Association with cardiovascular risk factors, SLE features, treatment of SLE and history of CVD were assessed in patients with SLE and controls with and without MS. MS was non-significantly increased in patients with SLE (20%) compared with controls (13%; P = 0.083). It was more commonly observed in patients with SLE < or =40 years old (15.8%) than in controls of the same age group (4.2%; P < 0.001). The mean number of MS criteria was significantly higher among patients with SLE than in controls. The frequency of CVD was also 28-fold higher among patients with SLE (11.3%) than in controls (0.4%). SLE with MS presented higher levels of inflammatory markers than SLE without MS. In a multivariate analysis, educational level, serum triglycerides, HDL-cholesterol and C3 serum levels and hydroxychloroquine use were independently associated with MS.

Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus.

The aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin-23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.

Study of a functional polymorphism in the p53 gene in systemic lupus erythematosus: lack of replication 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.