Mandar Apte

Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case–control study within LUMINA, a multiethnic US cohort (LUMINA LVII)

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 ≥1 year follow-up were studied in two groups: jSLE (diagnosed at ≤18 years); aSLE (diagnosed at 19–50 years; matched for gender and disease duration at enrolment). Sociodemographic data, SLE manifestations, disease activity, damage accrual, SLE-related hospitalizations or emergency room visits, drug utilization, mortality and psychosocial characteristics and quality of life were compared. Data were analysed by univariable and multivariable analyses. Seventy-nine patients were studied (31 jSLE, 48 aSLE); 90% were women. Mean (SD) total disease duration was 6.8 (2.7) years in jSLE and 5.6 (3.3) years in aSLE (p = 0.077). Mean age at cohort entry was 18.4 (1.8) and 33.9 (9.2) years in jSLE and aSLE respectively. By univariable analysis, jSLE patients were more commonly of African-American descent, were more likely to have renal and neurological involvements, and to accrue renal damage; jSLE patients had lower levels of helplessness and scored higher in the physical component measure of the SF-36 than aSLE patients. Renal involvement [OR = 1.549, 95% CI (1.397–15.856)] and neurological involvement [OR = 1.642, 95% CI (1.689–15.786)] were independently associated with jSLE by multivariable analysis. There was a larger proportion of African-Americans within the jSLE group. After adjusting for ethnicity and follow-up time, jSLE patients experienced more renal and neurological manifestations, with more renal damage. There was a two-fold higher mortality rate in the jSLE group.

Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV)

Objective: To examine the predictors of time-to-seizure occurrence and their impact on damage accrual and mortality in LUMINA, a multiethnic (Hispanic, African American and Caucasian) cohort of patients with systemic lupus erythematosus. Methods: Seizures were defined as per the American College of Rheumatology (ARC) nomenclature and case definitions for neuropsychiatric lupus syndromes. Factors associated with time-to-seizure occurrence occurring at or after diagnosis (TD) of systemic lupus erythematosus were examined by univariable and multivariable Cox proportional hazard regression analyses. The impact of seizures on damage accrual and mortality was also examined by multivariable analyses after adjusting for variables known to affect these outcomes. Results: A total of 600 patients were included in these analyses. Of them, 40 (6.7%) developed seizures at or after TD; by multivariable analyses, disease activity and younger age were independent predictors of a shorter time-to-seizure occurrence (HR = 1.10 and 1.04; 95% CI 1.04 to 1.15 and 1.00 to 1.08, p = 0.0004 and 0.0304, respectively) whereas mucocutaneous involvement (HR = 0.34, 95% CI 0.16 to 0.41, p = 0.0039) and hydroxychloroquine use (HR = 0.35, 95% CI 0.15 to 0.80, p = 0.0131) were independent predictors of a longer time-to-seizure occurrence. Seizures were an independent contributor to damage accrual but not to mortality. Conclusions: Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual. Younger age and disease activity are independent predictors of a shorter time-to-seizure occurrence; antimalarials appear to have a protective role in seizure occurrence.

Systemic lupus erythematosus in a multiethnic US Cohort LUMINA XLVIII: factors predictive of pulmonary damage.

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. Lupus (2007) 16, 410—417.

The impact of increased body mass index on systemic lupus erythematosus: Data from LUMINA, a multiethnic cohort

Objective:The aim of this study was to examine the impact of an increased body mass index (BMI) on disease activity, damage accrual, fatigue, self-reported health-related quality of life (HRQOL), and fibromyalgia in patients with lupus using longitudinal data from LUMINA, a large multiethnic cohort. Methods:SLE patients (≥4 ACR revised criteria), ≤5 years disease duration at entry into the cohort (T0), of Hispanic (from Texas or from the Island of Puerto Rico), African American, or white ethnicity were included. BMI was ascertained at T0 or first recorded. The average scores from all visits for disease activity (SLAM-R), self-reported HRQOL (physical and mental component summary measures of the SF-36) and fatigue (Fatigue Severity Scale), the score at last visit for damage accrual (SLICC Damage Index), and fibromyalgia (ACR criteria), if present at any visit, were examined for their association with an increased BMI by univariable and multivariable analyses. Results:Three-hundred sixty-four patients were included; 28% were obese (BMI ≥30 kg/m2). An increased BMI was associated with older age, less social support, higher degree of helplessness, depression, more abnormal illness-related behaviors, poorer self-reported HRQOL, fatigue, and fibromyalgia, but not with disease activity or damage accrual by univariable analyses. In multivariable analyses, BMI was independently associated with fibromyalgia but not with disease activity, fatigue, or self-reported HRQOL. Conclusions:An increased BMI is independently associated with presence of fibromyalgia but not with disease activity, damage accrual, fatigue or self-reported quality of life in patients with SLE. Optimizing weight merits investigation to see if it can significantly impact this pervasive SLE-associated manifestation.

African–American and Hispanic ethnicities, renal involvement and obesity predispose to hypertension in systemic lupus erythematosus: results from LUMINA, a multiethnic cohort (LUMINAXLV)

Objective: To examine the predictors of the occurrence of hypertension in a large multiethnic US cohort. Patients and methods: There were 614 patients with systemic lupus erythematoses (SLE; ⩾4 American College of Rheumatology revised criteria) with ⩽5 years of disease duration at entry into the cohort (T0) and of Hispanic (Texan or Puerto Rican), African–American or Caucasian ethnicity. T0 variables were compared between patients who did and did not develop hypertension (blood pressure ⩾140/90 mm Hg on at least two occasions and/or the use of antihypertensive drugs) after T0. Significant and clinically relevant variables were then examined by a stepwise logistic regression model. Results: A total of 379 patients without hypertension at T0 were included (patients who developed hypertension prior to SLE diagnosis (n = 126) or before T0 (n = 109) were excluded). Predictors of hypertension were African–American and Texan–Hispanic ethnicities, renal involvement and a higher body mass index. Conclusions: Traditional cardiovascular risk factors, disease-related factors and ethnicity play a role in the occurrence of hypertension in patients with SLE. Controlling renal involvement and optimising body weight may prevent the occurrence of hypertension.

Predictors of premature gonadal failure in patients with systemic lupus erythematosus. Results from LUMINA, a multiethnic US cohort (LUMINA LVIII)

Objective: To examine the predictors of time to premature gonadal failure (PGF) in patients with systemic lupus erythematosus from LUMINA, a multiethnic US cohort. Methods: PGF was defined according to the SLICC Damage Index (SDI). Factors associated with time to PGF occurrence were examined by univariable and multivariable Cox proportional hazards regression analyses: three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3). Results: Thirty-seven of 316 women (11.7%) developed PGF (19 Texan–Hispanics, 14 African–Americans, four Caucasians and no Puerto Rican–Hispanics). By multivariable analyses, older age at T0 (hazards ratio (HR) = 1.10–1.14; 95% CI 1.02–1.05 to 1.19–1.23) and disease activity (Systemic Lupus Activity Measure-Revised) in all models (HR = 1.22–1.24; 95% CI 1.10–1.12 to 1.35–1.37), Texan–Hispanic ethnicity in models 2 and 3 (HR = 4.06–5.07; 95% CI 1.03–1.25 to 15.94–20.47) and cyclophosphamide use in models 1 and 3 (1–6 pulses) (HR = 4.01–4.65; 95% CI 1.55–1.68 to 9.56–13.94) were predictors of a shorter time to PGF. Conclusions: Disease activity and Texan–Hispanic ethnicity emerged as predictors of a shorter time to PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF.

Features Associated With, and the Impact of, Hemolytic Anemia in Patients With Systemic Lupus Erythematosus: LX, Results From a Multiethnic Cohort

OBJECTIVE To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. METHODS SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. RESULTS Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. CONCLUSION The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.