Clinical and genetic factors predictive of mortality in early systemic sclerosis

Abstract

Objective. To investigate the clinical and genetic variables at initial presentation that predict survival in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort. Methods. GENISOS is a prospective, observational study of a multiethnic early systemic sclerosis (SSc) cohort. To date, a total of 250 patients have been enrolled. In addition to clinical and laboratory data, electrocardiograms (EKGs), chest radiographs, and pulmonary function tests have been obtained from each patient. A modified Rodnan skin thickness score, HLA class II genotyping, and a Medsger Damage Index also have been collected. We performed multivariable analyses utilizing the Cox regression following a purposeful model building strategy. Results. The study analyzed 122 white, 47 African American, and 71 Hispanic SSc patients with an average disease duration of 2.6 years at enrollment. At the time of analysis, 52 (20.8%) of the 250 patients had died. In the final multivariable model excluding HLA genes, 7 variables emerged as significant predictors of mortality: age >65 years at enrollment, forced vital capacity <50% predicted, clinically significant arrhythmia on EKG, absence of anticentromere antibodies, hypertension, chest radiograph suggestive of pulmonary fibrosis, and low body mass index (BMI). In separate modeling that included HLA genes, HLA alleles DRB1*0802 and DQA1*0501 were significant predictors of mortality in addition to the predictors mentioned above. Conclusion. A limited number of variables collected at presentation, including BMI, are able to predict mortality in patients with early SSc. In addition, some of the HLA genes associated with SSc susceptibility are useful for predicting SSc outcome.

Avaliação da capilaroscopia usando Endotelina-1 como um marcador de ativação endotelial na lesão microvascular e úlceras cutâneas

“…In our sample, the patients had a mean disease duration of 42 years, were predominantly female (92% of the sample) and the most prevalent form was the limited one -which affected 54% of all patients. The demographic pattern of the sample reflects a pattern that is typically found in this disease according to the literature 15,16 . The overlap form displayed higher levels of ET-1.…”

The Genetics of Scleroderma

“…The DRB1*1104 was found to be increased in patients with ATA. An additional epidemiologic study in the GENISOS (Genetics Versus Environment in Scleroderma Outcome Study) cohort found that HLA-DRB1*0802 and DQA1*0501 allotypes were independent predictors of mortality in addition to other factors (eg, body mass index, age >65 years, forced vital capacity 50% lower than predicted, presence of arrhythmia on electrocardiogram, pulmonary fibrosis, and absence of ACA) [10].…”

Translation and cross-cultural adaptation of the Scleroderma Health Assessment Questionnaire to Brazilian Portuguese

“…1 Systemic scleroderma is a heterogeneous disease ranging from a mild form characterized by lesser involvement of internal organs to a more severe type characterized by greater involvement of these organs and rapid progression, leading to disability and even death in some cases. 2 Systemic sclerosis affects women more than men, in proportions of 4:1. 3 The prevalence ranges from seven to 489 cases per million individuals.…”