Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes

Abstract

Introduction There is a strong female preponderance reported in many connective tissue diseases and in almost all systemic sclerosis (SSc) case series. Methods We compared gender differences in SSc patients in a large single-center cohort, including demographic features, disease subtype, environmental exposures, disease-specific serum autoantibodies, organ system involvement (frequency and severity) and survival. Adjustment for cutaneous subset (diffuse cutaneous [dc] and limited cutaneous [lc]) was performed. Results We identified key characteristics which distinguished female from male SSc patients. Females were more frequently younger at disease onset with a longer disease duration at the time of their first visit. Females more often had lcSSc and, if an overlap syndrome was present, it was most often systemic lupus erythematosus. In contrast, males more frequently had dcSSc and overlap with myositis. Females more frequently had peripheral vascular involvement but in males it was more often severe. Males were more often cigarette smokers and more frequently had environmental exposures. Males more frequently had interstitial lung disease (ILD or pulmonary fibrosis) which was more severe. Females had a significantly increased frequency of anti-centromere antibody and males anti-topoisomerase I and anti-U3RNP antibody. Males had significantly reduced survival (73% at 5 years and 45% at 10 years after onset of SSc). The most frequent causes of death were ILD in males and pulmonary hypertension in females. Conclusions Gender differences may be important clues to understanding the natural history and pathogenesis of SSc.

Predictors of progression in systemic sclerosis patients with interstitial lung disease

“…Sex and ethnicity also appear to be important determinants of ILD development. Despite the strong female predominance reported in SSc (female to male ratio 4.7:1), men with SSc are more likely to develop ILD than women with SSc (relative risk 1.24; 95% confidence interval 1.01-1.52) [31,32]. A large multi-ethnic observational study conducted in the setting of a universal healthcare system found that in comparison to white patients of European descent, patients of Afro-Caribbean descent with SSc more frequently have ILD (31% versus 53%; p=0.007) [33].…”

The Prevalence of Autoimmune Disorders in Women: A Narrative Review

“…It causes an increased production of collagen with fibrosis, irregular immune system activation as well as vascular abnormalities. Systemic sclerosis, as with other autoimmune disorders, can be attributed to a defect in X inactivation that results in overexpression of many immune regulatory genes [24]. In an experiment conducted in the University of Pittsburgh regarding estrogen levels and systemic sclerosis, it was found that increased estrogen levels may cause skin thickening and organ fibrosis, hence why women are often diagnosed during childbearing age as estrogen levels increase substantially during pregnancy.…”

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases

“…Even though SSc is more prevalent in women, men with the disease showed remarkably higher circulating SCX levels. This result could be related to the poorer prognosis and higher severity of the disease in male SSc patients when compared to female SSc patients [49]. Contrary to SSc, patients with IPF are predominantly males; however, in this condition, SCX levels were similar in women and men.…”