Systemic sclerosis (SSc), or scleroderma, is an autoimmune systemic disease with no cure and the highest case-specific mortality of all rheumatic diseases. SSc is 3-4 times more prevalent amongst Veterans, partially due to service-related exposures. Skin is by far the most commonly affected organ, and skin fibrosis, the hardening and tightening of the skin, is a hallmark feature of SSc. Although skin fibrosis is a key marker of overall disease severity and a significant cause of morbidity and impaired quality of life, tracking cutaneous SSc remains an important challenge. The clinical standard for assessing SSc severity, the modified Rodnan skin score, estimates the degree of skin thickening by pinching, but suffers high interobserver variability, inability to distinguish treatable active disease from damage, and insufficient sensitivity to change over time. The lack of reliable measures to track cutaneous disease activity can significantly delay treatment decisions due to missed opportunities for early intervention to positively alter the disease course. We propose to address this unmet need for cutaneous biomarkers of SSc with the Myoton, a user-friendly cellphone-sized device that we have pioneered as a reliable measure of skin sclerosis in graft-versus-host disease. The Myoton enables precise, reliable, and reproducible measure of mechanical attributes of the skin through rapid and simultaneous acquisition of five parameters. Our team has validated the Myoton against conventional clinical assessments, longitudinal therapeutic response, and in tissue models. Importantly, our existing standardized protocols enable novice Myoton users achieve high intra- and inter-observer reliability in clinical multicenter studies. In this proposal, we aim to validate skin mechanical parameters measured by the Myoton a practical cutaneous biomarker that is linked to the underlying pathology of SSc. We will enroll an observational cohort of 100 Veterans across the full spectrum of cutaneous SSc severity, and 100 matched healthy controls. Over the course of twelve months, we will acquire Myoton measurements, clinical assessments including the modified Rodnan skin score and standardized SSc-specific physician- and patient-reported outcome measures, high frequency ultrasound images, and skin biopsies. First, we will determine the associations between Myoton measurements and clinical phenotypes of cutaneous SSc. Second, we will determine the quantitative relationship between Myoton measurements and structural alterations, correlating to both skin thickness measured by high frequency ultrasound, and tissue pathology markers from histology. Finally, we will assess how changes in Myoton measurements over time reflect changes in cutaneous SSc severity. We will also evaluate the ability of early time point Myoton measurements to predict the one-year clinical progression. In summary, we will validate Myoton’s direct quantification of skin mechanics as a measure of cutane...