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Background: We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease., Methods: At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC., Results: Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant., Conclusions: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study., (Copyright 2006 Massachusetts Medical Society.)

Maintenance of blood flow involves the dynamic interactions between the endothelium, circulating cellular components, coagulation factors, and factors involved in fibrinolysis. Autoantibodies, inflammatory cytokines and other undefined triggers in a genetically predisposed person may lead to an imbalance in the equilibrium between the various hemostatic pathways resulting in potentially catastrophic thrombotic events. This article reviews the clinical manifestations and treatment of selected, potentially life-threatening thrombotic syndromes that may occur in association with autoimmune diseases. Special mention is made of thrombotic events associated with Behçet's syndrome.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ≤5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R ≥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. [ABSTRACT FROM AUTHOR]