Sex-Based Differences in Systemic Sclerosis Among Egyptian Patients: Insights from a Multicenter Observational Study in a Genetically Distinct North African Mediterranean Population

<b>Background:</b> Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease with variable clinical expression influenced by genetic, environmental, and sex-related factors. Understanding sex-based differences in disease phenotypes and severity can improve personalized management strategies, especially in underrepresented populations. This study aims to explore sex-based differences in disease phenotypes and severity in a population with a distinct genetic background. <b>Materials and Methods:</b> This cross-sectional study included 197 SSc patients (177 females and 20 males) enrolled from 5 tertiary care centres across Egypt. All participants met the 2013 ACR/EULAR classification criteria for SSc and the criteria proposed by LeRoy and Medsger. The demographic, clinical, and serological data were collected and defined according to the previously developed severity score and activity index. <b>Results:</b> This study highlights key sex-related differences in disease severity and management. Egyptian male patients exhibited more severe skin involvement and were more likely to receive more aggressive treatment regimens, including corticosteroids and phosphodiesterase inhibitors. Conversely, female patients demonstrated a higher frequency of moderate general systemic involvement and comparatively lower rates of pulmonary complications. <b>Conclusions:</b> Sex-related differences in Egyptian SSc patients appear limited, suggesting that population-specific genetic and environmental factors may play a more prominent role in disease expression than sex alone.