Can disease specific measures for systemic lupus erythematosus predict patients health related quality of life?

Disease specific measures like systemic lupus erythematosus (SLE) Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics (SLICC) and Systemic Lupus Activity Measure (SLAM) are primarily based on physician assessment of disease severity along with blood tests pertinent to SLE. These are primarily used for research purposes and do not quantify the social impact of the disease or measure function and well being from the patients perspective. We wish to study the degree of correlation between the SLEDAI, SLICC and patient reported health related quality of life (HRQOL), to see if these measures can be used to gauge the disease impact from the patient's perspective. The aim of the study was, therefore, to assess the correlation between SLICC, SLEDAI and HRQOL in patients with systemic lupus erythematosus. We utilized the University of Chicago SLE database to obtain SLEDAI, SLICC and MOS SF-36 scores. A physician not directly involved in their care assessed SLEDAI, SLICC and SF-36 at the same visit. STATA-7SE software was used to obtain the two summary scores [physical component summary (PCS) and mental component summary (MCS)]. Multiple linear regression and correlation coefficients were obtained to assess the direction and relationship between HRQOL and these disease specific measures. On multivariate regression models, both SLICC and SLEDAI were predictive of the PCS scores (beta SLICC = - 1.036, P = 0.025, 95% CI - 1.9, -0.13: beta SLEDAI = - 0.322, P = 0.012, 95% CI -0.57, -0.07. R2= 0.14). Neither SLICC nor SLEDAI were predictive of MCS scores (beta SLICC =-0.015, P=0.97, 95% CI -1.03, 1.001: beta SLEDAI=-0.19, P=0.174, 95% CI -0.47, 0.08. R2 = 0.02). The correlation coefficients between SLEDAI and PCS, MCS were -0.29 and -0.15, respectively. The correlation coefficients between SLICC and PCS, MCS were -0.27 and -0.02, respectively. The conclusions are that SLEDAI and SLICC are poor indicators of HRQOL of patients with SLE.     

Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage

Cerebral single-photon emission computed tomography (SPECT) is a sensitive technique for the detection of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). The objective was to determine whether a relationship exists between cerebral hypoperfusion as detected by cerebral SPECT, cumulative tissue damage and the clinical activity of SLE. Cerebral technetium-99m-L,L-ethyl cysteinate dimer (99mTc-ECD) SPECT was performed in two groups of patients: 10 women with SLE (Group A) who had no previous history of major neuropsychiatric (NPS) manifestations and no minor NPS symptoms in the last six months, and 57 unselected women with SLE (Group B). In the same week that SPECT was performed, the SLE disease activity index (SLEDAI), SLICC/ACR damage index, native anti-DNA antibodies (ELISA) and erythrocyte sedimentation rate (ESR) were determined. In Group A, cerebral SPECT showed moderate or severe hypoperfusion (abnormal SPECT) in five patients without NPS symptoms, unrelated to age (mean 24.8 versus 27.8 years) or disease duration (mean 6.8 versus 9 years). Patients with significant cerebral hypoperfusion had greater clinical disease activity (mean SLEDAI 13.6 versus 7.6) (SLEDAI > 7 in 5/5 versus 1/5; Fisher: 0.023; OR: 33; 95% CI: 2.3-469.8) and ESR (mean 43.6 versus 9.8; P < 0.05). In Group B, the mean age of the 57 unselected women with SLE was 37 years (SD 6.3) and the mean duration of the disease was 9.7 years (SD 6.3). Cerebral SPECT revealed normal perfusion or mild hypoperfusion (normal SPECT) in 30 patients (52.6%), and moderate or severe hypoperfusion in 27 (47.4%). Hypoperfusion was unrelated to age, duration of SLE or concentrations of anti-DNA antibodies and C3 and C4 fractions. Patients with significant cerebral hypoperfusion had more active clinical disease (mean SLEDAI 13.92; SD 8.44 versus 4.56; SD 4.15) (Mann-Whitney, P < 0.005), more cumulative tissue damage (mean SLICC 2.66; SD 2.84 versus 1.03; SD 1.51) (Mann-Whitney, P = 0.035), and higher ESR values (mean 28.7; SD 22.5 versus 17.7; SD 13.3) (Mann-Whitney, P = 0.023) than patients with normal SPECT studies. Significant cerebral hypoperfusion was related both to NPS manifestations present at the time of the study (17 of 27, 63% versus 3 of 30, 10%) (OR: 15.3) and cumulative manifestations (19 of 27, 70.4% versus 8 of 30, 26.7%) (OR: 6.5), whether mild (OR: 5.5) or severe (OR: 8.2). In conclusion, cerebral hypoperfusion detected by SPECT in patients with SLE is related to clinical activity (SLEDAI), cumulative tissue damage (SLICC) and concomitant or previous NPS manifestations.     

Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus

Disease activity 6 months before pregnancy of patients with systemic lupus erythematosus (SLE) associated with adverse maternal and fetal outcomes is not well studied. The aim of the study was to identify predictors of adverse maternal and fetal outcomes in pregnant SLE patients, based on patients' background characteristics, clinical and laboratory data 6 months before pregnancy. Of 103 pregnancies, 55 pregnancies in 39 SLE patients were investigated. Clinical and laboratory data were recorded at regular intervals from 6 months before conception to 1 year after delivery. Primary outcomes included the predictors of combined adverse maternal and fetal outcomes. Potential explanatory variables included demographic, clinical and laboratory data 6 months before conception. Using logistic regression, history of nephritis (p?=?0.001, odds ratio [OR] 13.3, 95% confidence interval [CI] 2.7-65.1) and a high SLE Disease Activity Index (SLEDAI) score 6 months before pregnancy (p?=?0.015, OR 1.7, 95% CI 1.1-2.7) were associated with combined adverse maternal outcome, whereas flare during pregnancy (p?=?0.003, OR 29.3, 95% CI 3.1-273.1) predicted combined adverse fetal outcome. The area under the curve for SLEDAI score of combined maternal outcome was 0.73 (95% CI 0.58-0.87). The optimal cut-off point according to the receiver operating characteristic curve was 4, with a sensitivity of 64% and a specificity of 75%. In conclusion, a history of nephritis or a SLEDAI score of 4 or more in SLE patients 6 months before conception predicts adverse maternal outcomes, while disease flare during pregnancy predicts adverse fetal outcomes. Pregnancies should be delayed until the disease has been in remission for 6 months.     

Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms

Oxidative stress may play a role in the pathogenesis of systemic lupus erythematosus (SLE). We examined the hypothesis that oxidative stress was associated with indices of lupus disease activity and severity of symptoms. Urinary F2 isoprostane excretion, a validated marker of oxidative stress, was measured in 95 patients with SLE and 103 healthy controls. Outcome measures included SLEDAI and SLICC scores, the modified health assessment questionnaire, the fatigue severity scale (FSS), and visual analogue scales (VAS) for fatigue, pain and overall disease activity. F2 isoprostane excretion was compared in patients and controls, and its relationship with clinical variables in SLE examined. F2 isoprostane excretion did not differ significantly among patients with lupus (2.7 +/- 2.3 ng/mg Cr) and control subjects (2.2 +/- 1.4 ng/mg Cr) (P = 0.70). In patients with lupus, F2 isoprostane concentrations were independently associated with higher patient reported disease activity (VAS) (OR = 1.52, P = 0.01), fatigue (FSS, OR = 1.52, P = 0.03) and lower quality of life (OR = 0.73, P = 0.05), but not with objective markers or inflammation or disease activity. In conclusion, F2 isoprostane excretion is associated with patient-reported symptoms in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress may contribute to debilitating symptoms such as fatigue in SLE.     

Cigarette smoking and disease activity in systemic lupus erythematosus

OBJECTIVE: To investigate the effect of cigarette smoking on disease activity and cumulative organ damage in systemic lupus erythematosus (SLE). Methods. Extensive clinical and demographic variables, including current and previous cigarette smoking, were collected from 111 SLE patients using a detailed interview-administered questionnaire. Disease activity was estimated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Cumulative organ damage was measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR). Smoking status was correlated with disease activity and cumulative organ damage, while statistically adjusting for the individual effects of potentially confounding demographic and clinical variables using analysis of variance followed by Fisher's least significant difference method. Results. Current smokers demonstrated significantly higher (p < 0.001) SLEDAI scores (15.6 +/- 7.8) than ex-smokers (9.63 +/- 6.00), and never smokers (9.03 +/- 5.75). This association remained significant (p = 0.001) after adjusting for all covariates, including ethnicity, education level, income level, alcohol use, age of onset of SLE, current age, mean duration of SLE, marital status, and hydroxychloroquine therapy. Current smokers also demonstrated significantly (p = 0.003) higher scores for both the neurological and non-neurological components of SLEDAI. There was no significant difference in the SLICC/ACR scores across the various smoking groups, although there was a trend for more severe disease in current smokers. Conclusion. Cigarette smoking is associated with increased disease activity in SLE. These data further establish the association of SLE with cigarette smoking, and suggest that individuals with SLE should avoid all exposure to tobacco products.     

Lymphopenia is associated with neuropsychiatric manifestations and disease activity in paediatric systemic lupus erythematosus patients

OBJECTIVES: To investigate if lymphopenia is associated with clinical manifestations, disease activity and prognosis in systemic lupus erythematosus (SLE). METHODS: The charts of 186 paediatric patients with SLE diagnosed between 1985 and 2006 in a medical centre were retrospectively reviewed. Lymphocyte counts were recorded at the time of SLE diagnosis and SLE flares. Global disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Cumulative organ damage was assessed by the ACR/Systemic Lupus International Collaborating Clinics (SLICC) damage index. RESULTS: Lymphopenia (<1500/mm(3)) and marked lymphopenia (<500/mm(3)) was observed in 62.8 and 12.2% at the time of SLE diagnosis. At the time of SLE diagnosis, lymphopenia was significantly associated with oral ulcers, leucopenia, anti-dsDNA antibodies and C4 decrease. At the time of flares, lymphopenia was significantly associated with anti-dsDNA antibodies, methylprednisolone pulse therapy, disease activity and organ damage. Using multivariate logistic regression, marked lymphopenia was independently associated with neuropsychiatric manifestations [odds ratio (OR) 7.41, 95% confidence interval (CI) 1.99-27.0], and protective from LN (OR 0.13, 95% CI 0.03-0.53). CONCLUSIONS: Lymphopenia at SLE flares is associated with disease activity and organ damage. Marked lymphopenia is independently associated with neuropsychiatric manifestations.     

The prevalence of dyslipoproteinemia in Thai patients with systemic lupus erythematosus

Fasting blood samples taken from 93 pairs of outpatient systemic lupus erythematosus (SLE) women and matched controls were assessed for total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol. The demographic data, clinical manifestations, Mexican-SLE Disease Activity Index (MEX-SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and medication prescribed in the SLE patients were reviewed. A significant elevation of TG levels was observed in the SLE patients compared to controls (mean+/-SD 113.3+/-59.5 versus 77.7+/-45.7 mg/dL, P < 0.001). The HDL-c level was also significantly lower in SLE patients than controls (mean+/-SD 49.7+/-12.7 versus 65.0+/-14.8 mg/dL, P < 0.001). The percentage of samples with low HDL-c (<35 mg/dL) was higher in the SLE group (9.7%) than controls (0%; P = 0.002). The LDL-c and TC levels were comparable in both groups. The use of antimalarial drugs was negatively associated with TC (OR 0.22, 95%CI 0.08-0.61) and LDL-c levels (OR 0.27, 95%CI 0.09-0.80). The increased prevalence of dyslipoproteinemia in SLE patients in this report has confirmed the results of previous studies and emphasized the importance of controlling this modifiable cardiovascular risk factor by the combination of lifestyle modification and medical treatments.     

Damage accumulation in systemic lupus erythematosus and its relation to disease activity and mortality

OBJECTIVE: To describe damage accrual and the interconnections between disease activity measures, damage accrual, and death in a Nordic lupus cohort. METHODS: Longitudinal study in the population-based Tromso lupus cohort. Disease activity [SLE Disease Activity Index (SLEDAI)] and disease damage [by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI)] were recorded for each visit. Weighted average SLEDAI scores (WAS) were calculated to correct for variable observation times. Development of damage (SDI > 0), severe damage (SDI >or= 3), and death were used as separate endpoints. Univariate nonparametric analysis identified and hazard ratios (HR) by Cox regression techniques confirmed the independence of predictors for each outcome. RESULTS: Through 11.9 years of followup, 72 patients (46%) remained free of damage, 51 (32%) developed moderate damage, and 35 (22%) developed severe damage. SDI scores were higher in 37 nonsurvivors (23.4%; SDI 2.1) than in survivors (SDI 0.9; p < 0.05). Damage accrual was linear throughout the first decade of disease. The only independent predictor for SDI >/= 3 was a WAS score > 3 (hazard ratio 2.34; 95% CI 1.1-4.9). Age > 40 years at diagnosis (HR 5.6, 95% CI 2.4-12.7) and WAS > 3 (HR 2.4, 95% CI 1.2-4.9) were significant predictors for death. CONCLUSION: Damage accrual in SLE occurred in 54% of patients in a linear fashion over the first decade of disease. Global disease activity was the main determinant of damage accrual. Accrued damage was not an independent risk factor for death, which was predicted by age > 40 years and WAS > 3.     

Determinants of bone mass in systemic lupus erythematosus: a cross sectional study on premenopausal women.

OBJECTIVE: To evaluate bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE) and to assess the influence of disease related variables and use of corticosteroids. METHODS: Lumbar and femoral BMD were measured by dual x-ray absorptiometry (DXA) in 84 premenopausal patients with SLE (age 30.5+/-7.5 years). All patients were receiving corticosteroids at the time of the study. Variables evaluated were: disease duration, clinical pattern, disease activity (SLEDAI), cumulative damage index (SLICC/ACR), current and cumulative prednisone dose, duration of steroid treatment, and use of immunosuppressive agents. Osteoporosis was defined as a t score below 2.5 SD compared to a reference population of healthy women in at least one region of measurement. RESULTS: Vertebral and femoral BMD were significantly lower in patients with SLE than in age matched controls. Osteoporosis was detected in 22.6% of patients. No significant differences in BMD were detected between patients according to clinical pattern or activity index, whereas patients with damage index > 0 (n = 46) had a significantly lower BMD at both the lumbar (p = 0.008) and the femoral (p = 0.05) level. Compared with non-osteoporotic patients with SLE, women with osteoporosis had similar age, lower body mass index, significantly longer disease duration (p < 0.0001), higher cumulative steroid intake (p < 0.006), and higher SLICC/ACR score (p < 0.01). Stepwise logistic regression analysis showed that disease duration is independently associated with osteoporosis (OR 1.2 for each year of disease, 95% CI 1.07-1.33). Since disease duration and duration of steroid treatment were highly correlated, a new stepwise logistic model was run without disease duration, which revealed that prednisone was associated with an increased risk for osteoporosis (OR 1.16 for each year of treatment, 95% CI 1.05-1.29). CONCLUSION: Osteoporosis is a frequent feature in young patients with SLE. Disease duration is associated with an increased risk for osteoporosis, but the role of glucocorticoid treatment seems to be crucial. Steroid exposure was the only treatment related variable exerting an influence on the development of osteoporosis.     

Oestrogen receptor {alpha} gene polymorphisms in systemic lupus erythematosus

Objective: To analyse associations of two oestrogen receptor α (ORα) gene polymorphisms in 260 patients with SLE from northern Sweden. The two polymorphisms, PvuII T/C and the XbaI A/G, are located in the first intron of the ORα gene. Methods: All patients fulfilling at least four of the ACR criteria for SLE were consecutively recruited during one year. The SLEDAI score and SLICC damage index were recorded. 670 individuals from the same geographical area served as controls. DNA from the patients and controls was extracted and genotyped using the 5'' nuclease assay with an ABI PRISM 7900HT instrument. The genotype/phenotype relationships were calculated using SPSS. Results: The unusual PvuII C allele was associated with malar rash and the unusual XbaI G allele with photosensitivity (p = 0.001, OR = 2.53, 95% CI = 1.43 to 4.47 and p = 0.007, OR = 2.12, 95% CI = 1.22 to 3.66, respectively). The common XbaI AA genotype was associated with serositis (p = 0.013, OR = 1.92, 95% CI = 1.15 to 3.22). Based on the SLICC damage index associations of the common TT genotype and AA genotype with cognitive impairment were identified (p = 0.018, OR = 2.47, 95% CI = 1.17 to 5.25 and p = 0.018, OR = 2.75, 95% CI = 1.19 to 6.38 respectively). There was also an association of the XbaI AA genotype with the angina/coronary artery bypass variable (p = 0.042, OR = 2.58, 95% CI = 1.03 to 6.43). Of the variables describing disease severity and duration it was found that carriers of the unusual PvuII C allele showed a later onset of SLE (p = 0.02) and carriers of the unusual XbaI G allele a lower SLICC damage index. Conclusions: The unusual PvuII C and XbaI G alleles were associated with a milder form of SLE characterised by skin manifestations, later onset, and less organ damage.     

Serum levels of soluble Fas correlate with indices of organ damage in systemic lupus erythematosus

OBJECTIVE: To evaluate whether the levels of soluble form of the Fas apoptosis antigen (sCD95/sFas) varied from those of healthy control subjects in a group of patients with systemic lupus erythematosus (SLE). This was done to determine whether sFas has a role in either the disease activity or the organ damage in SLE. METHODS: Serum levels of sFas were measured over a period of 4 y (277 determinations) in 39 Arab patients with SLE and 22 age-, gender-, and race-matched healthy controls using double antibody ELISA. SLEDAI scores for disease activity and SLICC/ACR scores for cumulative organ damage were determined. Serum levels of acute phase reactants, complement, inflammatory cell counts, levels of autoantibodies, and kidney and liver function test results were obtained retrospectively from clinical records. RESULTS: sFas levels were significantly higher in patients with SLE (n = 39, 277 determinations) (0.60 ng/ml +/- 0.38) than in healthy controls (n = 22) (0.26 ng/ml +/- 0.11) (P < 0.00001). The levels of sFas correlated with SLICC/ACR (r = 0.36; P < 0.02), but not with SLEDAI. sFas correlated with renal and liver function tests measured by s-creatinine (r = 0.38; P < 0.0001), creatinine clearance (r = -0.30, P < 0.001), s-albumin (r = -0.28, P < 0.0001), and ALT (r = 0.35; P < 0.00001), but did not correlate with the levels of acute phase reactants. CONCLUSION: sFas is elevated in sera of SLE patient. Since sFas correlates with indices of organ damage but not with disease activity, it may be a marker of organ damage in SLE and may act to protect certain organs from further damage by inhibiting Fas-mediated apoptosis.     

Outcome of a national Israeli cohort of pediatric systemic lupus erythematosus

The aim of this study was to describe the clinical manifestations and outcomes of a national cohort of childhood systemic lupus erythematosus (cSLE). All cases of cSLE registered in the Israeli national registry of children with rheumatic diseases between 1987-2003 were examined for disease activity and damage by the SLE disease activity index (SLEDAI) and SLE collaborating clinics/American College of Rheumatology (SLICC/ACR) damage index. Demographic, clinical, laboratory and treatment factors were analysed for their effect on the outcome. One-hundred and two patients were identified, 81% females, with a mean age at diagnosis of 13.3 +/- 2.6 years. The mean SLEDAI score was 17.2 +/- 9.0 (range 2-60). Fifty four patients were followed for at least five years. The mean SLEDAI decreased to 7.6 +/- 6.3 (0-29) and the mean SLICC/ACR damage index was 0.7 +/- 1.6 (0-8). Five patients developed chronic renal failure. No patients died. No factors were found to be significantly associated with the outcome except the initial SLEDAI score. The five-year outcome of our national cSLE cohort was good; with relatively low activity and minimal damage in most patients. The initial SLEDAI predicted the development of late damage.     

Risk factors for amenorrhea in juvenile systemic lupus erythematosus (JSLE): a Brazilian multicentre cohort study

We evaluated the prevalence and clinical associations of amenorrhea in 298 female juvenile systemic lupus erythematosus (JSLE) patients (ACR criteria) followed in 12 Brazilian Paediatric Rheumatology centres. Amenorrhea was observed in 35 patients (11.7%) with a mean duration of 7.2 +/- 3.6 months. The hormones were performed in 32/35 patients and none of them had FSH and LH levels above and estradiol below the normal range according to pubertal changes. JSLE patients with amenorrhea were younger (15.04 +/- 2.5 versus 17.8 +/- 3.1 years; P = 0.001), and had a shorter period of time between menarche and current age (3.4 +/- 2.9 versus 6.7 +/- 5.4 years; P = 0.001). Interestingly, the frequency, cumulative dose, number of pulses and duration of intravenous cyclophosphamide treatment were alike in patients with and without amenorrhea (P > 0.05). In contrast, patients with amenorrhea had significantly higher SLEDAI (P = 0.01) and SLICC/ACR-DI (P = 0.024) scores compared to those without this condition. Independent risk factors identified by multivariate analysis were higher SLEDAI (OR = 1.059; CI = 1.004-1.116; P = 0.034) and SLICC/ACR-DI (OR = 2.125; IC = 1.373-3.291; P = 0.001) scores. Our data suggest that in spite of immunosuppressive therapy, JSLE patients have an adequate ovarian follicular reserve and amenorrhea is particularly associated with disease activity and damage.     

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 +/- 6.9 and 3.5 +/- 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis.     

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in patients with Systemic Lupus Erythematosus

Objective. To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. Methods. Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. Results. The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. Conclusion. Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.     

Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus

Despite the increased prevalence of cardiovascular disease in patients with systemic lupus erythematosus (SLE), little is known about the role of high sensitivity C-reactive protein (hsCRP) or whether ethnicity, gender, anthropometric measures and treatment can alter hsCRP levels. We evaluated the effects of treatment and demographic, anthropometric and socio-economic variables on hsCRP levels in SLE. High sensitivity C-reactive protein levels were measured using an immunoturbidimetric assay in 610 patients from the Hopkins Lupus Cohort, who were followed-up regularly. In stepwise multiple regression analyses, body mass index (BMI) [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.34-2.20, P < 0.001], African-American ethnicity (OR 1.97, 95% CI 1.22-3.19, P < 0.01), education (OR 0.60, 95% CI 0.42-0.86, P < 0.01), statin use (OR 0.38, 95% CI 0.18-0.82, P < 0.05), estrogen use (OR 3.65, 95% CI 1.19-11.22, P < 0.05), SLE Disease Activity Index score (OR 1.76, 95% CI 1.09-2.87, P < 0.05) and cumulative prednisone dose (OR 1.27, 95% CI 1.01-1.60, P < 0.05) were significant predictors of hsCRP levels. These findings suggest that hsCRP levels should be adjusted for BMI, ethnicity, education level, disease activity and medications when conducting cardiovascular risk assessment in patients with lupus.     

Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score < or =5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R > or =8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.     

Nephrotic-range proteinuria, the major risk factor for early atherosclerosis in juvenile-onset systemic lupus erythematosus

OBJECTIVE: To determine the presence of early carotid atherosclerosis and associated risk factors in patients with juvenile-onset systemic lupus erythematosus (SLE). METHODS: The carotid intima-media wall thickness (IMT) was measured by B-mode ultrasound in patients with SLE onset before the age of 16 years and in sex- and age-matched healthy control subjects. Risk factors for atherosclerosis were determined at the time of the ultrasound scan and included traditional cardiovascular and SLE-related risk factors. RESULTS: Twenty-six patients with juvenile-onset SLE and 26 healthy controls were studied. The mean (+/- SD) IMT of the SLE patients was significantly higher than that of the control group (0.57+/-0.05 mm and 0.54+/-0.03 mm, respectively; P = 0.006). The results of IMT measurement were not correlated with the patients' age, disease duration, SLE Disease Activity Index (SLEDAI) score, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (DI) score, laboratory indicators of lupus activity, or cumulative prednisone dose. Patients with nephrotic-range (NR) proteinuria (> or = 3.5 gm/24 hours; n = 6) had a significantly higher IMT than did those without (n = 20) (P = 0.02). Patients with NR proteinuria also had significantly higher SLEDAI scores, SLICC/ACR DI scores, and systolic and diastolic blood pressures, and significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and fibrinogen. No difference in any of the above variables, including the IMT, was observed when SLE patients without NR proteinuria were compared with healthy controls. CONCLUSION: These patients with juvenile-onset SLE had ultrasonographic evidence of premature atherosclerosis. The risk of early atherosclerosis may be higher in patients with NR proteinuria.     

Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage

OBJECTIVE: To determine the urinary levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with systemic lupus erythematosus (SLE) and to assess their relationship with clinical and laboratory features and the degree of activity and damage associated with the disease. METHODS: The study sample included 24 consecutive patients with SLE. 24-hour urine samples were collected for the determination of soluble VCAM-1 and ICAM-1 levels by ELISA. Disease activity was defined by the SLE Disease Active Index (SLEDAI) and disease outcome by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ ACR) damage index. RESULTS: The urinary soluble VCAM-1 level was significantly higher in patients with SLE compared to normal controls (32.35+/-34.27 vs. 4.66+/-3.8 ng/mg creatinine, p = 0.0005) and statistically significantly correlated with disease activity (SLEDAI), a low serum C3 level, decreased creatinine clearance and albuminuria, as well as with disease damage (SLICC/ACR damage index). In contrast, the urinary soluble ICAM-1 level was not significantly higher in the patients' group compared with the controls (4.5+/-5.19 vs. 2.72+/-2.31 ng/mg creatinine, p=0.2), but was statistically significantly correlated with hematuria and albuminuria. CONCLUSION: Our data suggest that the urinary level of soluble VCAM-1 significantly correlates with overall disease activity and damage scores, but not with nephritis in SLE.     

Toward electronic health recording: evaluation of electronic patient reported outcome measures (e-PROMs) system for remote monitoring of early systemic lupus patients

The study aimed to assess the value of evaluation of electronic patient reported outcome measures (e-PROMs) in the assessment and management of SLE disease activity flares, its association with adherence to therapy as well as organ damage. A randomized, controlled crossover study was carried out over a 24-month duration. One hundred forty-seven SLE patients meeting the revised American College of Rheumatology (ACR) criteria were enrolled. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess disease activity, whereas organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index. In the first 12 months, the patients were assessed every 3 months. At 12 months, the patients were randomized into a cohort of 73 patients who continued their care in the same style and 74 patients who completed an online e-PROMs questionnaire on monthly basis for another 12-month period. The data captured were then retrospectively analyzed at the end of the 24-month study period. At the end of the first year of the study, the mean SLEDAI and SDI scores were 8.72 (6.1) and 1.9 (2.2). At the end of the second year, the mean SLEDAI and SDI scores in the e-PROMs cohort were 3.1 (2.6) and 1.2 (1.3), whereas in the control group, the scores were 7.63 (6.7) and 1.8 (2.3), respectively (p < 0.01). Adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (OR 2.03, 95% CI 1.34 to 2.83, p < 0.001). Adherence to therapy was significantly (p < 0.1) higher in the e-PROMs group. e-PROMs was equivalent to PROMs paper format and has a potential disease-modifying effect as it facilitated close monitoring of disease activity with an option of management escalation whenever indicated.