Lupus International Collaborating Clinics Damage Research Articles

Association of HLA-DQB1∗06 with susceptibility to systemic lupus erythematosus in Egyptians

Aim of the workThis study was conducted to compare the HLA-DQB1∗06 allele frequency among Egyptian SLE patients and controls. The association of that allele with clinical features and distinct autoantibody profiles in SLE patients was also assessed. Patients and methodsThis study included 48 consecutive Egyptian SLE patients and 49 age and sex matched unrelated healthy Egyptian subjects as a control group. All patients underwent full history taking, thorough clinical examination, SLE cumulative organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Routine laboratory investigations were done as well Genomic DNA amplification by polymerase chain reaction with sequence-specific primers technique (PCR-SSP) to detect HLA DQB1∗6. ResultsHLA-DQB1∗06 was significantly more frequent among the SLE patients. Our results showed HLA-DQB1∗06 to be associated with SLE (39.6% in patients and 8.2% in controls, OR=7.23; 95% CI=2.22–23.6; P=.00). We found no association with the clinical findings or antibodies found in our patients apart from a significant negative association with vasculitis. ConclusionThe current work suggests that DQB1∗06 allele is a susceptibility allele in Egyptian patients with SLE but is not related to the clinical presentation or laboratory tests of SLE. To our knowledge this is the first study of the frequency of DQB1∗06 alleles in Egyptian SLE patients.

Construct and criterion validity of the Euro Qol-5D in patients with systemic lupus erythematosus.

ObjectiveTo investigate the construct and criterion validity of the Euro Qol-5D (EQ-5D), which allows quality-adjusted life-years to be calculated, in patients with systemic lupus erythematosus (SLE).MethodsConsecutive SLE patients who had been followed at the Renji Hospital, School of Medicine, Shanghai Jiao Tong University were recruited. Cross-sectional correlations of the EQ-5D with equivalent domains in disease-specific health-related quality of life (HRQoL), LupusQol, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) measures, the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and patient characteristics were tested. Discriminant validity to assess the ability to distinguish between patients of different disease severity was assessed. There also were evaluations of ceiling and floor effects.Results240 patients were recruited in total. The EQ-5D correlated moderately to strongly with all domains of the LupusQoL (r: 0.44–0.7) apart from intimate relationships (r = 0.25) and body image (r = 0.18). There was moderate negative correlation between EQ-5D and clinical assessment of disease, SLEDAI (r = −0.589) and SDI (r = −0.509). When compared with equivalent domains on LupusQoL, there was good construct validity in EQ-5D (r: 0.631–0.812). EQ-5D could also discriminate patients with varied disease severity (according SLEDAI and SDI). There was no floor effect in EQ-5D but the ceiling effect remains strong (34%).ConclusionOur results provide sufficient evidence that the EQ-5D displays construct and criterion validity for use in SLE patients. Disease-specific measures of HRQoL used alongside may be a better choice.

AB0526 Pregnancy Outcomes in Women with Systemic Lupus Erythematosus from A Mexican Cohort

BackgroundSystemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder that disproportionally affects women, especially in their reproductive years. SLE is associated with considerable pregnancy-related morbidity, including fetal loss, preterm birth...

AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Systemic Lupus Erythematosus: Relationship with Disease Activity

BackgroundThe B lymphocyte stimulator signaling pathway by BAFF and its homologue APRIL has an important role in the selection, maturation and survival of B cells and plays a significant role...

Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.

Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

The Systemic Lupus International Collaborating Clinics (SLICC) damage index: A systematic literature review

ObjectivesWe performed a systematic literature review to determine factors that influence damage and damage progression in SLE patients and how damage relates to mortality in this population. MethodsA search of Medline, Embase and Web of Science was performed, with papers included if they met the requirements of containing keywords relating to SLE and damage assessment using the SDI, published between 1990 and October 2012. ResultsA total of 358 articles were identified, with 50 included in this review. From 17 studies reporting damage at more than 2 time points, damage progressed over time, but the rate of damage accrual reported was variable across studies. Demographic factors that influence the accrual of damage in several reports include male gender, older age, longer disease duration, Afro-Caribbean and Indo-Asian ethnicity. Patients with higher disease activity at a single time point or over time accrue greater damage. Certain organ system involvement also predicts damage accrual, in particular renal and neuropsychiatric involvement. Corticosteroids, cyclophosphamide and azathioprine all show an association with damage accrual, while hydroxychloroquine appears to have a “protective” effect. Four studies, which examined prognosis, all demonstrated that damage is a predictor of future mortality. ConclusionsDamage in SLE patients increases over time and predicts future mortality. Patients at risk of damage can be identified from demographics factors and the pattern of clinical involvement. Disease activity, corticosteroids and immunosuppressive therapy are also associated with future damage but further studies are needed to separate the mechanisms of these associations from the problem of residual confounding.

AB0391 Sleep disorders in systemic lupus erythematosus patients: a cross sectional study

BackgroundSleep disturbances are frequently observed in rheumatic diseases and significantly affect the quality of life of patients. The prevalence and characteristic of sleep disturbances in Systemic Lupus Erythematosus (SLE) are...

SAT0229 Depression in systemic lupus erythematosus, dependent or independent of severity of disease?

BackgroundDepression is one of the most commonly reported neuropsychiatric symptoms in systemic lupus erythematosus (SLE) patients. However, the prevalence of depression in relation to the general population and its relationship...

AB0725 The metabolic syndrome in women with systemic lupus erythematosus: Association with disease characteristics and atherosclerosis

BackgroundPatients with Systemic lupus erythematosus (SLE) have an increased risk for cardiovascular disease (CVD) and develop early atherosclerosis. A possible explanation could be the metabolic syndrome likely associated with a...

THU0330 Damage in juvenile-onset systemic lupus erythematosus

BackgroundChildren and adolescents with juvenile-onset systemic lupus erythematosus (jSLE) face considerable morbidity due to sequelae of disease activity, comorbidities and adverse effects of treatment. In order to improve the management...

The Early Protective Effect of Hydroxychloroquine on the Risk of Cumulative Damage in Patients with Systemic Lupus Erythematosus

To assess whether hydroxychloroquine (HCQ) prevents early damage in patients with systemic lupus erythematosus (SLE). We updated an existing systematic review of literature on clinical effects of HCQ in patients with SLE. We conducted a nested case-control study embedded in an inception cohort of patients with SLE. Systemic Lupus International Collaborating Clinics Damage Index (SDI) at 3 years was considered as our primary outcome. Patients with SDI > 0 at 3 years were considered cases and patients with SDI = 0 were controls. Cases and controls were first compared by univariate analysis. Then conditional logistic regression models adjusting for potential confounders were done to study the effect of HCQ on damage accrual. Included in the analysis were 481 patients who had 3 or more years of followup. Out of this cohort, we could match 151 cases with 151 controls. Univariate analysis identified age, the use of any immunosuppressive drugs, HCQ, and cumulative dose of steroids as significant covariates associated with damage accrual. In multivariate analysis, the use of HCQ remained significantly associated with less damage (OR 0.34, 95% CI 0.132-0.867), while age (OR 1.05, 95% CI 1.027-1.078) and a variable combining SLE activity and steroid dose (OR 1.73, 95% CI 1.306-2.295) were associated with damage at 3 years. We demonstrated that HCQ use was associated with less damage at 3 years after diagnosis of SLE when attention was given and adjustment done for disease activity and steroid dose, duration of disease, and calendar year of diagnosis.

Construct and Criterion Validity of the Short Form-6D Utility Measure in Patients with Systemic Lupus Erythematosus

Preference-based measures, such as the Short Form-6D (SF-6D), allow quality-adjusted life-years, used in cost-utility evaluations, to be calculated. We investigated the construct and criterion validity of the SF-6D in patients with systemic lupus erythematosus (SLE). Female patients with SLE were recruited from outpatient clinics at 2 timepoints, 5 years apart. Cross-sectional correlation of the SF-6D with domains of the disease-specific LupusQol health-related quality of life (HRQOL) measure, the Systemic Lupus International Collaborating Clinics Damage Index (SDI; for damage) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; for activity) measures, and patient characteristics was tested. The ability to discriminate between groups defined by smoking status, presence/absence of carotid plaque, depression, and fatigue was tested using the t-test. In total 181 patients were recruited at baseline. The SF-6D correlated moderately to strongly with all domains of the LupusQoL (0.6-0.8) apart from intimate relationships (0.42) and body image (0.34). Correlations of the SF-6D with the demographic and disease-specific measures at baseline were small for the SDI score (-0.23) and age (-0.19) and in the expected direction. The SF-6D did not correlate with disease activity (SLEDAI -0.08). The SF-6D could distinguish those who smoked, had carotid plaque, had depression, and reported fatigue from those who did not, with the largest effect size being for depression (0.75). The SF-6D displays construct and criterion validity for use in patients with SLE, but the low correlation with aspects of intimate relationships and body image represents a concern and reinforces the need to collect disease-specific measures of HRQOL alongside generic preference-based instruments.

Quality of life in patients with systemic lupus erythematosus (SLE) compared with related controls within a unique African American population

The patient's perspective of how their health affects their function is health-related quality of life (HRQOL). HRQOL is poorer in patients with systemic lupus erythematosus (SLE). Few HRQOL studies in SLE patients have focused on African Americans despite an increased disease burden compared with Caucasians. The African American Gullah population of South Carolina has a homogeneous genetic and environmental background and a high prevalence of multi-patient families with SLE. Demographics, medical history, and Short-Form 36 (SF-36) were measured within a cohort of Gullah SLE cases and related controls. Compared with related controls (n = 37), cases (n = 89) had a lower Physical Component Summary (PCS, 41.8 vs. 52.3, p < 0.01), but not Mental Component Summary (MCS, 55.0 vs. 56.0, p = 0.70). The difference in PCS was no longer significant upon adjustment for working status, disability, and medical conditions. None of the 11 SLE American College of Rheumatology criteria, disease duration, or Systemic Lupus International Collaborating Clinics Damage Index were associated with either PCS or MCS. Cases and controls had similar MCS scores. We hypothesize that this lack of effect of SLE on MCS may be due to disease-coping mechanisms interplaying with cultural factors unique to the Gullah.

Differences in Regional Brain Activation Patterns Assessed by Functional Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus Stratified by Disease Duration

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

Resistin Levels in Lupus and Associations with Disease-specific Measures, Insulin Resistance, and Coronary Calcification

To evaluate levels of resistin in female subjects with systemic lupus erythematosus (SLE) compared to age and race-matched controls and to determine the relationship between resistin and systemic inflammation, disease measures, and coronary artery calcification (CAC). Resistin levels were measured on stored samples from 159 women with SLE and 70 controls as an extension of a previous cross-sectional study. Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC. In a multivariable linear regression model, a diagnosis of SLE was significantly associated with higher resistin levels independent of age, race, renal function, body mass index (BMI), high-sensitivity CRP (hsCRP), hypertension, diabetes, and steroid use. In SLE, resistin levels correlated positively with Systemic Lupus International Collaborating Clinics Damage Index, glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate, homocysteine, and disease duration (all p < 0.03). Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI. Resistin levels were significantly elevated in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml, respectively; p = 0.04). In multivariate logistic regression, the association was not present after adjustment for age, race, and GFR. SLE was independently associated with higher resistin levels. Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI. SLE cases with CAC had higher resistin levels than cases without CAC; however, this relationship was dependent on other established risk factors.

Prevalence and risk factors of vertebral compression fractures in female SLE patients

IntroductionOur objective was to determine the frequency of and factors associated with prevalent vertebral compression fractures in female systemic lupus erythematosus (SLE) patients attending rheumatologists in western Sweden.MethodsIn this cross sectional study 150 women were included. They were examined with x-ray of thoracic and lumbar spine (Th4 to L4). A reduction of at least 20% of any vertebral height, assessed by Genant's semiquantitative method, was defined as a fracture. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA).ResultsMedian patient age was 47 years (20 to 82) and disease duration 11 years (1 to 41). Only 6 (4%) women had a history of clinical compressions whereas 43 (29%) had at least one radiological fracture each. The patients with at least one fracture at any site were characterized by older age (P < 0.001), being postmenopausal (P < 0.01), higher Systemic Lupus International Collaborative Clinics Damage Index (P < 0.05), lower BMD total hip and femoral neck (P < 0.05), more peripheral fractures (P < 0.01), medication with bisphosphonates (P <0.05) and calcium and vitamin D3 (P < 0.05). There were no significant differences regarding current or cumulative glucocorticosteroid dose between the groups. In logistic regression analyses high age remained as a risk factor of at least one vertebral fracture at any site whereas low BMD in total hip was associated with vertebral fracture in the lumbar spine.ConclusionsRadiological compression fractures are common but seldom diagnosed in SLE patients. High age and low BMD in total hip, but not in spine, was associated with vertebral fractures.

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX)

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.

Validation of the Spanish, Portuguese and French versions of the Lupus Damage Index questionnaire: data from North and South America, Spain and Portugal

We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.

Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort.

To assess whether hydroxychloroquine can delay renal damage development in lupus nephritis patients. Lupus nephritis patients (n = 256) from the LUpus in MInorities, NAture versus nurture study (n = 635), a multiethnic cohort of African Americans, Hispanics, and Caucasians, age > or =16 years with disease duration < or =5 years at baseline (T0) were studied. Renal damage was defined using the Systemic Lupus International Collaborating Clinics Damage Index (> or =1 of the following lasting at least 6 months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria > or =3.5 gm and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n = 53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potential confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or the World Health Organization (WHO) class glomerulonephritis were also derived. Sixty-three (31.0%) of the 203 patients included developed renal damage over a mean +/- SD disease duration of 5.2 +/- 3.5 years. The most frequent renal damage domain item was proteinuria. Patients who received hydroxychloroquine (79.3%) exhibited a lower frequency of WHO class IV glomerulonephritis, had lower disease activity, and received lower glucocorticoid doses than those who did not take hydroxychloroquine. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (hazard ratio [HR] 0.12, 95% confidence interval [95% CI] 0.02-0.97, P = 0.0464) and reduced (HR 0.29, 95% CI 0.13-0.68, P = 0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in those who did not take hydroxychloroquine and those classified as WHO class IV glomerulonephritis (P < 0.0001). After adjusting for possible confounding factors, the protective effect of hydroxychloroquine in retarding renal damage occurrence in systemic lupus erythematosus is still evident.

Evaluation of Risk Factors That Contribute to High Prevalence of Premature Atherosclerosis in Chinese Premenopausal Systemic Lupus Erythematosus Patients

To evaluate the prevalence of atherosclerosis in Chinese premenopausal women with systemic lupus erythematosus (SLE) and study possible associations between traditional and nontraditional risk factors with premature atherosclerosis. We evaluated 111 premenopausal women with SLE and 40 healthy controls without clinical cardiovascular disease. B-mode ultrasound was used to measure carotid plaque and intima-media wall thickness (IMT). The frequency of risk factors for atherosclerosis in patients and controls was compared, and the relationship between the patients' clinical characteristics and carotid plaque was examined. At the same time, we used B-mode ultrasound to measure flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery to assess for difference in endothelial function between SLE patients and controls. Carotid plaque was more frequent in patients with lupus (16 of 111 patients) than in control subjects (0 of 40 subjects) (P = 0.007). The mean IMT was significantly higher in patients than in controls. Compared with controls, SLE patients were found to have a significantly higher prevalence of hypertension (P = 0.001), hypercholesterolemia (P = 0.022), and hypertriglyceridemia (P < 0.001). As compared with patients without plaque, patients with plaque were significantly older, had longer disease duration, higher body mass index, raised blood pressure, shorter prothrombin time, raised C-reactive protein, higher Systemic Lupus International Collaborating Clinics damage index score, higher cumulative prednisone dose, used less hydroxychloroquine, had higher mean IMT, lower FMD, and NMD. In logistic regression analysis, older age, higher body mass index, and higher Systemic Lupus International Collaborating Clinics damage index score were independently related to the presence of plaque. Using multiple regression analysis, we found SLE (P = 0.003) to be significantly associated with impaired FMD. In our Chinese SLE group, patients presented a higher prevalence of carotid atherosclerosis plaque than healthy controls. SLE patients have significant endothelial dysfunction. We found that risk factors identified in other SLE populations were associated with atherosclerosis in our Chinese group.