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Background: Osteonecrosis is common in systemic lupus erythematosus (SLE) and often disabling. The role of glucocorticoids in its development is well known.Objective: To explore other possible risk factors for osteonecrosis in SLE.Methods: A nested matched case-control study undertaken in the context of a large, longitudinal, multiethnic lupus cohort (LUMINA), currently formed of 571 SLE patients meeting American College of Rheumatology criteria. All those developing symptomatic osteonecrosis after the diagnosis of SLE were considered cases. Two controls matched for age, disease duration, ethnicity, and centre were selected for each case. Cases and controls were compared by univariable analyses using selected variables. Variables with p<0.10 and those thought clinically relevant were entered into conditional logistic regression models including either the average dose or the highest dose of glucocorticoids, with osteonecrosis as the dependent variable.Results: 32 cases were identified and 59 matched controls selected (in five cases only one control could be found). By univariable analyses, both groups were largely comparable for socioeconomic-demographic, clinical, and laboratory variables. Cases were less exposed to hydroxychloroquine (as assessed by the percentage of exposure time) (p = 0.026), used higher doses of glucocorticoids (average and highest doses) (p = 0.011 and 0.001, respectively), and received cytotoxic drugs more often (p = 0.015). In the multivariable analyses only cytotoxic drug use (both models) and the highest dose of glucocorticoids remained associated with the occurrence of osteonecrosis.Conclusions: Cytotoxic drug use is a risk factor for the development of symptomatic osteonecrosis in SLE patients, along with glucocorticoids. No definite protective factors were identified. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and >or=1 year follow-up were studied in two groups: jSLE (diagnosed at

Objectives: To determine the factors predictive of new or worsening proteinuria in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE)., Methods: Five hundred and twenty-nine SLE patients from a multiethnic US cohort [LUpus in MInorities: NAture versus Nurture (LUMINA)] were evaluated for new or worsening proteinuria using the categories of the Systemic Lupus Activity Measure-Revised: (1), normal; (2), trace or 1+ proteinuria on the dipstick; (3), 2-3+ proteinuria and (4), > or =4+ proteinuria. A rise in urinary protein was considered a positive event visit. Basic demographic and socioeconomic variables were assessed at baseline (T0). Clinical and immunological variables including disease features, activity, duration, comorbidities (such as hypertension and diabetes), medications and autoantibodies were assessed at the visit preceding a positive event visit. Selected HLA-DR and HLA-DQ alleles, and FCGR receptor polymorphisms were assessed. Data were analysed using logistic regression analyses and generalized estimating equations., Results: There were 243 patients (59.1% of 93 Texan Hispanics, 37.0% of 100 Puerto Rican Hispanics, 58.0% of 181 African Americans and 29.7% of 155 Caucasians) with new or worsening proteinuria, and 364 positive events in 2801 visits. Younger age [Odds ratio (OR) = 1.013, 95% confidence limits (CL) = 1.001-1.024, P < 0.0334], anti-dsDNA (OR = 1.554, CL = 1.149-2.100, P < 0.0042), and HLA-DRB1*1503 (OR = 1.746, 95% CL = 1.573-2.2673, P < 0.0103) were found to independently predict the occurrence of new or worsening proteinuria., Conclusion: The factors predictive of new or worsening proteinuria include traditional factors associated with lupus nephritis, such as age and anti-dsDNA, as well as HLA-DRB1*1503, which has not been previously described in association with lupus nephritis, new or worsening proteinuria.

The objective of this study was to determine the factors predictive of time to the occurrence of pulmonary damage in systemic lupus erythematosus (SLE). Six-hundred and twenty-six SLE patients from a multiethnic (Hispanics, African Americans and Caucasians) longitudinal study of outcome were studied. Pulmonary damage was defined as per the Systemic Lupus International Collaborating Clinics Damage Index. Socioeconomic-demographic, clinical, genetic, serological features, pharmacologic treatments, behavioural, psychological and disease activity [as per the Systemic Lupus Activity Measure-Revised (SLAM-R)] were examined. Factors associated with time to the occurrence of pulmonary damage were examined by Cox proportional hazards regressions. A Kaplan-Meier survival curve was also examined. Forty-six (7.3%) patients had pulmonary damage after a mean (SD) total disease duration of 5.3 (3.6) years. Among those patients, 25 had pulmonary fibrosis, 12 pulmonary hypertension, eight pleural fibrosis, four pulmonary infarction and four shrinking lung syndrome. Seven patients had more than one type of lung damage. Cumulative rates of pulmonary damage at five and 10 years were 7.6% and 11.6%, respectively. In the multivariable analyses, age (HR = 1.033, 95% CI 1.006-1.060; P = 0.0170), pneumonitis (HR = 2.307, 95% CI 1.123-4.739; P = 0.0229) and anti-RNP antibodies (HR = 2.344, 95% CI 1.190-4.618; P = 0.0138) were associated with a shorter time to the occurrence of pulmonary damage while photosensitivity (HR = 0.388, 95% CI 0.184-0.818; P = 0.0128) and oral ulcers (HR = 0.466, 95% CI 0.230-0.942; P = 0.0335) with a longer time. Pulmonary damage is relatively common in SLE. Age, pneumonitis and anti-RNP antibodies were associated with a shorter time to the development of permanent lung disease.

Objective: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome., Methods: SLE patients, age >or=16 yrs, disease duration

Renal involvement in systemic lupus erythematosus (SLE) is more frequent in minorities. We examined whether genetic or socioeconomic status (SES) explain these disparities in a large multiethnic (Hispanics from Texas and Puerto Rico, African Americans and Caucasians) SLE cohort. Renal involvement was defined as WHO Class II-V and/or proteinuria (> 0.5 g/24 h or 3+) attributable to SLE and/or abnormal urinary sediment, proteinuria 2+, elevated serum creatinine/ decreased creatinine clearance twice, 6 months apart present any time over the course of the disease. Ancestry informative markers (AIMS) were used to define the admixture proportions in each patient and group. Logistic regression models were examined to determine the percentage variance (R2) in renal involvement related to ethnicity that is explained by socio-economic status (SES) and admixture (adjusting for age, gender and disease duration, basic model). Four-hundred and fifty-nine (out of 575) patients were included; renal involvement occurred in 44.6% Texas Hispanics, 11.3% Puerto Rico Hispanics, 45.8% African Americans, 18.3% Caucasians. SES accounted for 14.5% of the variance due to ethnicity (after adjusting for basic model variables), admixture 36.8% and both, 12.2%; 45.9% of the variance remained unexplained. Alternative models for decreased glomerula filtration rate and end-stage renal disease were comparable in the distribution of the explanatory variables. Our data indicate that genetic factors appear to be more important than SES in explaining the ethnic disparities in the occurrence of renal involvement.

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.

Objectives: To determine if a polymorphic GTn repeat in the intron of the C-reactive protein (CRP) gene associates with occurrence of vascular arterial events in systemic lupus erythematosus (SLE)., Methods: We performed a nested case-control study on the LUMINA cohort of 546 Hispanic, African-American and Caucasian SLE patients. Twenty-five patients who developed vascular arterial events (i.e. myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene or significant tissue loss and/or arterial peripheral thrombosis) after enrolment were selected as cases and 32 ethnically matched patients with no previous vascular arterial events served as controls. Their CRP gene GTn polymorphism and plasma CRP was determined., Results: Patients with vascular events had more severe SLE and were more likely to have plasma CRP in the highest quintile of measured values. The overall distribution of GTn alleles for patients with vascular events had a greater number of the GT20 variant compared with controls [26.0% of alleles (13/50) vs 15.6% (10/64)]. This greater number of GT20 in patients with vascular events was observed for African-Americans [29.2% (7/24) vs 21.0% (8/38)] and Hispanics [33.0% (4/12) vs 0% (0/16)] but not for Caucasians [14.3% (2/14) vs 20.0% (2/10)]. For African-Americans and Hispanics combined (45 patients), the frequency of GT20 in those with vascular events (30.6%, 11/36) was significantly higher than in those without them (14.8%, 8/54) (P<0.05, one-tailed test for difference in proportions). When patients were categorized according to the number of GT20 alleles they carried (thus GT20/GT20, GT20/GTx or GTx/GTx, where x is any allele other than GT20), for both African-Americans and Hispanics the likelihood of vascular arterial events increased in proportion with the GT20 dose, and all GT20-homozygous patients developed vascular arterial events., Conclusions: The CRP GT20 variant is more likely to occur in African-American and Hispanic SLE patients than in Caucasian ones, and SLE patients carrying the GT20 allele are more likely to develop vascular arterial events.

Objective: To examine the predictors of damage in a multiethnic cohort of systemic lupus erythematosus (SLE) patients with a specific focus on damage at baseline., Patients and Methods: SLE patients from a multiethnic US (Hispanic, African-American and Caucasian) cohort (LUMINA: Lupus in Minority populations, Nature versus nurture) were included if they had > or =6 months of follow-up in the cohort. Damage was measured with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). The dependent variable was the change in SDI score between study visits. Predictors were from the preceding visit. Variables known to affect damage accrual in SLE were included in the analyses., Results: Three hundred and fifty-two patients (82 Hispanics, 153 African-Americans and 117 Caucasians) representing 1795 patient visits were included. Previous damage was found to be a significant predictor of subsequent damage accrual (P < 0.0001). Other variables predictive of subsequent damage accrual were disease activity (P < 0.0001), older age (P = 0.041) and use of corticosteroids (P = 0.0048)., Conclusions: Once damage occurs in SLE, further damage is expected to occur. This is more likely to be the case if disease activity persists. These data have clinical implications for the management of SLE patients.