Lips in health and in systemic sclerosis: relevant physiology, pathogenesis, existing therapeutic approaches and unmet needs.

Introduction: Systemic sclerosis (SSc), or scleroderma, is a chronic autoimmune disease marked by excessive collagen deposition and vasculopathy. Oro-facial manifestations of SSc, particularly involving the lips, are common including microcheilia, microstomia, and the classic "mask-like" face, all of which greatly affect patient quality of life. This review explores the lips in both health and SSc. We examine factors affecting lip health, methods of assessment, SSc-specific impacts, and discuss available therapeutic approaches. Methods: A comprehensive literature search was conducted via PubMed and Embase. All article types were considered from inception of the databases, and the search was last run on April 20, 2025. Results: The lips play a critical role in facial expression, communication, and appearance. Anatomy is complex and relevant to SSc pathogenesis. Relevant factors include gender differences, aging patterns, ethnicity, and lifestyle. The pathogenesis of lip involvement in SSc is multifactorial. In SSc, dermal fillers, autologous fat transfer, and platelet-rich plasma therapy have been shown to at least transiently volumize the lips and alleviate tightness. There is a lack of data on long-term benefits as well as standardized assessment tools for lip involvement in SSc. Conclusion: The impact of lip involvement in SSc presents significant unmet clinical needs. There is a critical need to benchmark natural lip variation due to ethnicity, aging, and gender to facilitate research. Future research agendas should focus on defining patient priorities, standardizing imaging techniques to assist in understanding pathogenesis and treatment response, and developing evidence based educational resources for patients and healthcare professionals.