Premature coronary artery disease in systemic lupus erythematosus in the absence of corticosteroid use.
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Adrenal Cortex Hormones↗
Biomedical subjects
M B Urowitz
Publications and source records attributed to M B Urowitz.
Prediction of short term mortality in systemic lupus erythematosus with time dependent measures of disease activity.
OBJECTIVE: To identify predictors of short term mortality in systemic lupus erythematosus (SLE) in terms of time dependent clinical indicators of disease activity from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). METHODS: We studied data collected on patients followed at the University of Toronto Lupus Clinic. Clinical and laboratory indicators of disease activity are recorded at each clinic visit and a SLEDAI summary score is calculated. Survival analyses were conducted in which the prognostic value of the time dependent indicators of disease activity was examined on 6-month mortality through a multivariate Cox regression model. Relative risks, confidence intervals, and significance levels were obtained for each indicator to reflect their clinical importance and statistical significance. RESULTS: The sample consisted of 806 patients followed for a median of 6.6 years; 702 (87%) were female, 671 (83%) were Caucasian, and the mean age at first clinic visit was 36 years. Seventy-two patients died within 6 months of their last clinic visit. In a univariate regression model, a categorical variable reflecting total SLEDAI score was highly prognostic for mortality (p < 0.001) and yielded increasing relative risks of 1.28 for SLEDAI 1-5 vs 0, 2.34 for SLEDAI 6-10 vs 0, 4.74 for SLEDAI 11-19 vs 0, and 14.11 for SLEDAI > 20 vs 0. In a separate multivariate Cox model examining the individual components of SLEDAI, presence of organic brain syndrome, retinal changes, cranial nerve involvement, proteinuria, pyuria, pleurisy, fever, thrombocytopenia, and leukopenia each significantly increased the risk of death, while new rash and anti-DNA antibodies conferred protective effects. CONCLUSION: This time dependent Cox regression analysis identified the extent to which SLE disease activity, revealed by SLEDAI, is prognostic for short term mortality. Further, important individual components were identified and their prognostic value for death was estimated.
Adult↗
Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus.
OBJECTIVE: To ascertain the relative effect of antimalarial (AM) agents on fasting lipid fractions in patients with systemic lupus erythematosus (SLE). METHODS: The study was cross sectional including all patients with SLE who were seen in our lupus clinic with fasting lipid profiles measured as part of evaluation from November 1995 to March 1999. RESULTS: A total of 123 patients with a mean age of 45.3 years and mean disease duration 13.4 years were studied; 73.2% were taking prednisone with a mean +/- SD dose of 10.9 +/- 9.2 mg/day, 48.0% were taking AM, and 30.8% were taking both. In the entire group, patients taking AM had a 12.5% lower total cholesterol (TC) (5.11 +/- 1.27 vs 5.84 +/- 1.23; p = 0.002), 22.1% lower very low density lipid-cholesterol (VLDL-C) (0.66 +/- 0.40 vs 0.85 +/- 0.39; p = 0.01), and 15.7% lower LDL-C (3.01 +/- 1.14 vs 3.58 +/- 1.10; p = 0.007). For patients taking prednisone, those taking concomitant AM (n = 38) had significantly lower TC (5.26 +/- 1.30 vs 5.99 +/- 1.29; p = 0.01), VLDL-C (0.65 +/- 0.39 vs 0.85 +/- 0.41; p = 0.02), and LDL-C (3.05 +/- 1.20 vs 3.69 +/- 1.09; p = 0.01) than those without AM (n = 48). For patients taking < or = 10 mg/day prednisone, TC (4.69 +/- 0.88 vs 5.74 +/- 1.20; p < 0.001), VLDL-C (0.61 +/- 0.37 vs 0.83 +/- 0.44; p = 0.05), and LDL-C (2.57 +/- 0.76 vs 3.49 +/- 1.04; p < 0.001) were still lower in patients with concomitant AM (n = 22) than those without AM (n = 36). CONCLUSION: TC, VLDL-C, and LDL-C levels were significantly lower in patients taking AM, including patients taking concomitant prednisone. Thus AM may have beneficial effects in SLE in addition to disease suppression.
Antimalarials↗
Evaluation of predictive factors for neurocognitive dysfunction in patients with inactive systemic lupus erythematosus.
OBJECTIVE: To determine predictive factors associated with the cognitive dysfunction in patients with inactive systemic lupus erythematosus (SLE). METHODS: Consecutive patients followed at the Lupus Clinic with inactive SLE (SLE Disease Activity Index, SLEDAI, = 0) underwent a battery of neuropsychological tests; Beck Depression Inventory and psychiatric assessment were also performed. Neurocognitive dysfunction was defined as 3 abnormal scores. Data were analyzed using chi-square tests, ANOVA tests, and logistic regression. RESULTS: Twenty-five of the 58 patients with SLE (43%) versus 9 of 47 healthy controls (19%) demonstrated neurocognitive dysfunction (p < 0.01). Neurocognitive dysfunction was not associated with depression or a psychiatric diagnosis, use of steroids, or previous or current evidence for fibromyalgia. SLEDAI > 10 at first presentation to the Lupus Clinic and previous vasculitis were associated with neurocognitive dysfunction, but previous central nervous system disease, renal disease, renal damage, or atherosclerotic complications were not. Neurophysiologic studies at the time of the assessment were not predictive of neurocognitive dysfunction. CONCLUSION: Patients with inactive SLE demonstrate neurocognitive dysfunction. This is associated with more disease activity at presentation, but is not associated with specific organ involvement or organ damage.
Adult↗
Single photon emission computed tomography dual isotope myocardial perfusion imaging in women with systemic lupus erythematosus. I. Prevalence and distribution of abnormalities.
OBJECTIVE: To determine the prevalence of myocardial perfusion abnormalities in women with systemic lupus erythematosus (SLE) using single photon emission computed tomography (SPECT) dual isotope myocardial perfusion imaging (DIMPI). METHODS: Consecutive female patients registered at the University of Toronto Lupus Clinic were offered DIMPI evaluation and all who accepted were studied. Patients underwent SPECT DIMPI using dipyridamole stress. Resting and stress images were acquired using thallium-201 (201TI) and technetium 99m-sestamibi (99mTc sestamibi), respectively. We recorded segmental perfusion abnormalities, severity and reversibility of any abnormality, and number of vessel territories involved. Ejection fraction was also measured. RESULTS: One hundred thirty patients were studied. Mean (SD) age and disease duration at study were 45.1 (11.1) years and 14.6 (9.4) years, respectively. Thirteen patients (10%) had a history of angina pectoris or myocardial infarction. Overall, 52 (40%) patients had an abnormality of myocardial perfusion, including 11 (85%) with a history of angina or myocardial infarction. In those with no history of coronary artery disease, 41 (35%) had an abnormality detected. The perfusion defect was reversible in 47 (90%). In 37 (71%) cases perfusion defects were seen in the region of a single vessel territory. Eighteen (13.8%) patients had an ejection fraction (EF) < 50%. CONCLUSION: Using SPECT DIMPI, 40% of all women with SLE and 35% of women with SLE with no history of coronary artery disease had abnormalities of myocardial perfusion, suggesting a high prevalence of early coronary artery disease. The early detection of disease will facilitate study of atherosclerotic risk factors; such women can also be targeted for a focused program of risk factor management.
Canada↗
Serial renal biopsy in systemic lupus erythematosus.
OBJECTIVE: To examine the role of sequential renal biopsies in patients with systemic lupus erythematosus (SLE), with regard to indications, morphologic change over time, and the clinical utility of repeat biopsies. METHODS: Patients with repeat renal biopsies were identified from the University of Toronto Lupus Clinic Database and their biopsies were reviewed blindly by a committee, using the WHO classification as well as activity and chronicity indices. Reasons for obtaining biopsy were documented, and therapeutic decisions following repeat biopsy were tabulated. RESULTS: Fifty-seven patients (49 F/9 M) had at least 2 renal biopsies between 1970 and 1994. The mean interval between biopsies was 4.2 years. The major reason for obtaining the first biopsy was disease diagnosis (32/57), while the majority of repeat biopsies were performed to discern the cause of increasing proteinuria (45/57). A comparison of the WHO classification of initial and repeat biopsies showed evolution to another class in 23 instances, but more commonly a change within a class was seen. A decrease in proliferative lesions (classes III and IV and subsets of V) was noted on repeat biopsies. The chronicity index increased significantly (p = 0.0001) and the activity index decreased (p = 0.064) between biopsies. Seventy-seven percent of patients had a change in treatment based on biopsy results. CONCLUSION: The major reason for repeat renal biopsy in patients with SLE was proteinuria. Renal morphology in patients with SLE can change with time, particularly in terms of chronicity and activity features. Repeat biopsies in patients with SLE appear to have clinical utility.
Adult↗
Prevalence of antibodies to beta2-glycoprotein I in systemic lupus erythematosus and their association with antiphospholipid antibody syndrome criteria: a single center study and literature review.
OBJECTIVE: To determine the prevalence of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in patients with systemic lupus erythematosus (SLE), and to assess their association with and predictive value for the clinical classification criteria of the antiphospholipid antibody syndrome (APS). METHODS: One hundred thirty-three consecutive patients with SLE were recruited from 2 lupus clinics in the University of Toronto. Serum and plasma samples were tested for IgG anticardiolipin antibodies (aCL), prolonged partial thromboplastin time (PTT), a panel of lupus anticoagulant (LAC) assays, and anti-beta2-GPI (IgG, IgM, IgA). Normal ranges for the assays were established using 129 healthy controls. A literature review from 1992 to 2000 was performed using beta2-GPI, SLE, APS, thrombosis, and recurrent pregnancy loss as key search words. RESULTS: The distribution of anti-beta2-GPI antibodies (of any isotype) in each group were as follows: all patients with SLE, 36.8%; SLE with clinical features of APS, 40.4%; SLE without clinical features of APS, 34.9%; and healthy controls, 3%. The positive predictive values of prolonged PTT, IgG aCL, and anti-beta2-GPI for at least one clinical feature of APS in SLE were 59.3, 50.0, and 38.8%, respectively. There were 27 patients with SLE who had antibodies to beta2-GPI but a normal PTT and negative aCL and LAC. Six (20.7%) of these had a history of thrombosis and/or recurrent pregnancy loss. Twelve studies (including ours) were identified in which patient groups were similar and the same antibody isotype was measured. No agreement was apparent after reviewing the literature regarding an association of anti-beta2-GPI IgG and clinical features of APS in patients with SLE. CONCLUSION: Antibodies to beta2-GPI were frequently seen (35%) in our SLE population. The prevalence of anti-beta2-GPI was similar in those with (19/47) and without (39/86) APS. Anti-beta2-GPI did, however, identify 6 patients with clinical features of APS who were negative for aCL and prolonged PTT. Our results indicate that anti-beta2-GPI may provide additional information for the diagnosis of APS in SLE, but do not supercede other established assays. However, when we attempted to place our results in the context of other reports, the literature review revealed that secondary diagnoses of patient groups and assay techniques are too variable among different investigators to allow useful comparison. Thus, no conclusions could be drawn regarding anti-beta3-GPI and clinical features of secondary APS in SLE.
Adolescent↗
Factors associated with refractory renal disease in patients with systemic lupus erythematosus: the role of patient nonadherence.
OBJECTIVE: To assess the prevalence and underlying reasons for the development of chronic renal insufficiency (CRI) in patients with systemic lupus erythematosus (SLE) seen over a 3-year period in our lupus clinic, in particular to determine the frequency and types of patient-dependent factors that were associated with nonadherence when it occurred. METHODS: We determined the frequency and types of patient-dependent factors that were associated with the development of CRI in patients with SLE. CRI was defined as a serum creatinine level > or = 200 mumol/l for at least 6 months. RESULTS: Of the 462 patients followed at the lupus clinic between 1995 and 1998, 17 patients developed CRI. Patient-related factors were deemed to be the major reason for the development of CRI in 5 of these. Three of the 5 patients were nonwhite, and the 2 patients who were white were new immigrants. All 5 patients were reluctant to take high-dose corticosteroids because of potential adverse effects. Financial problems contributed to nonadherence in 2 cases. Two patients refused to continue steroids and immunosuppressive therapy and chose to use "alternative" medications as their sole therapy. Of these 5 patients, 3 are now on long-term renal replacement therapy, 1 has died, and 1 patient continues to be followed with a serum creatinine level of 250 mumol/l. CONCLUSION: There is a need for an educational program based on patients' cultural background in order to enhance patients' understanding of the aims, risks, and benefits of therapy in SLE.
Anti-Inflammatory Agents↗
Factors associated with fatigue in patients with systemic lupus erythematosus.
OBJECTIVE: To examine the relation between fatigue, disease activity, damage, and quality of life measures in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients attending the University of Toronto Lupus Clinic were studied. Disease activity was assessed using the SLEDAI and SLAM-R and damage using the SLICC/ACR Damage index. Fatigue was measured by the Fatigue Severity Score (FSS) and health status by the SF-36 questionnaire. In all cases a tender point count was also performed. RESULTS: 81 patients were studied. Their mean (SD) age and disease duration were 43 (12.5) years and 12.7 (8.0) years respectively. The FSS did not correlate with the SLEDAI nor with the SLAM-R. There was no correlation with the SLICC damage index. Fatigue severity correlated with the tender point count (SCC r=0.46, p<0.001), and negatively with all domains of the SF36 (r values -0.50 to -0.82). Disease activity and damage accounted for only 4.8% and 4% respectively of the variance in fatigue severity reported by patients. CONCLUSION: In an outpatient population of SLE patients, fatigue severity correlates with poor health status and a higher tender point count. In patients with SLE, factors associated with quality of life and fibromyalgia seem to have a greater influence on the severity of reported fatigue than does the level of current disease activity.
Adult↗
Disease expression and class II HLA antigens in systemic lupus erythematosus.
The aim of this investigation was to examine the relationship between Class II HLA antigens and disease expression in systemic lupus erythematosus (SLE). HLA-DR and DQ antigen frequency was studied serologically in 217 SLE patients followed prospectively and compared to 320 healthy controls. The relationship between HLA antigens and the presence of disease manifestations, as well as death was investigated in 117 SLE patients enrolled within the first year of their disease. A univariate analysis confirmed the association between HLA-DR3 and SLE. HLA antigen DR1, DR6, DR7, DQw1 and DQw3 were decreased in patient group compared to the controls. A logistic regression model showed a significantly negative association with HLA-DR1, DR6 and DR7, and a positive association with HLA-DR3. The reduced frequency of HLA-DQw1 and DQw3 was maintained using a logistic procedure. Cox Proportional Hazards models revealed no association between HLA-Class II antigens and death. Logistic regression models revealed no associations between central nervous system (CNS) disease nor musculoskeletal manifestations with any of the DR antigens. There was a trend towards a lower frequency of HLA-DR6 in patients with renal involvement and lower prevalence of HLA-DR1 and HLA-DR7 in patients with vasculitis.
Adolescent↗
Evolving spectrum of mortality and morbidity in SLE.
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Female↗
The SLICC/ACR damage index: progress report and experience in the field.
The SLICC/ACR damage index for SLE was developed to assess accumulated damage since the onset of the disease. The damage includes non-reversible changes in organs and systems affected by the disease process itself, its therapy, or inter-current illness. This paper describes the development of the damage index, its validation and its use. It is recommended as an outcome measure for longitudinal studies of prognosis and response to new therapies, and as a stratification measure for clinical trials.
Health Status Indicators↗
Extrarenal disease activity in systemic lupus erythematosus is not suppressed by chronic renal insufficiency or renal replacement therapy.
OBJECTIVE: To assess whether chronic renal impairment (CRI) and/or renal replacement therapy (RRT) in systemic lupus erythematosus (SLE) are associated with reduced extrarenal SLE activity. METHODS: This was a retrospective cohort analysis of patients with SLE who are followed at the University of Toronto Lupus Clinic. Patients with SLE were studied in 2 stages; chronic renal insufficiency (defined as a serum creatinine > 200 mumol/1 for > 6 months) and following the institution of dialysis therapy. Controls consisted of the next 2 age and sex matched patients in the clinic with a history of lupus nephritis who had not developed renal insufficiency. We assessed the flare rate (an increase in nonrenal SLEDAI > or = 1.0) for patients and controls in the first 12 months of followup at the clinic in each stage. RESULTS: Twenty-one patients, 17 female and 4 male, were followed through 25 episodes of CRI or RRT as were 50 controls. In the CRI stage (n = 12), flares occurred in 8 (67%) within one year compared to 14 (58%) of 24 controls (p = NS). In the RRT stage (n = 13), flares occurred in 7 (54%) compared to 16 (62%) of 26 controls (p = NS). The magnitude as well as the characteristics of the flares did not differ between patients and controls in either stage. CONCLUSION: Patients with SLE who develop CRI, or who receive RRT, continue to display evidence of ongoing extrarenal disease activity. Such patients require careful longterm followup for management of their extrarenal disease.
Adult↗
Nasal-septal perforation in systemic lupus erythematosus--time for a closer look.
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Humans↗
Natural history of hypercholesterolemia in systemic lupus erythematosus.
OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.
Age of Onset↗
Contribution of traditional risk factors to coronary artery disease in patients with systemic lupus erythematosus.
OBJECTIVE: Several factors have been implicated in the high prevalence of premature coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We hypothesize that variables independent of traditional risk factors contribute significantly to the development of CAD in SLE. We investigated the relative contribution of traditional risk factors in SLE patients with CAD compared to non-SLE patients with premature CAD. METHODS: An age matched retrospective cohort analysis. The prevalence of traditional cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes, smoking, family history) in patients with SLE who developed CAD during the course of their illness was compared to a group of age matched non-SLE subjects with premature CAD. Sexes were analyzed separately using Fisher's exact test and unpaired t tests. RESULTS: Thirty-five patients with SLE (27 women, 8 men) with definite ischemic heart disease were identified along with 397 non-SLE subjects (83 women, 314 men). In women with SLE the mean number of CAD risk factors per cardiac event was 2.0 +/- 0.77 versus 2.90 +/- 1.19 for the comparison group (p = 0.0008). In men with SLE the mean number of CAD risk factors was 1.87 +/- 0.83 versus 2.73 +/- 0.99 in the comparison group (p = 0.016). CONCLUSION: SLE patients with a cardiac event have fewer traditional risk factors than non-SLE patients with premature CAD. Thus premature CAD in SLE cannot be attributed solely to an excess of traditional risk factors.
Adult↗
The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs.
OBJECTIVE: To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. METHODS: Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials; patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test, Fisher's exact test, and 2 way analysis of variance were used when appropriate. RESULTS: Initiation of antimalarials reduced the baseline total cholesterol by 4.1 % at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). CONCLUSION: Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia.
Antimalarials↗
Measures of disease activity and damage in SLE.
Criteria for the classification of systemic lupus erythematosus (SLE) are not sufficient to describe the degree of disease activity. Several instruments to assess disease activity have been developed. This chapter reviews the derivation, validation, and clinical application of current disease activity measures in SLE, as well as comparison among them. As patients with lupus survive longer, the sequelae of the disease activity and its therapy are becoming more common. The derivation and validation of the single, generally accepted SLICC/ACR damage index is also discussed.
Disease Progression↗