Scleroderma (SD) is a rare autoimmune disease, which is divided into 2 categories: the localized SD and systemic SD. The localized SD mainly causes skin thickening of the fingers, whereas the systemic SD can further affect the blood vessels and internal organs. In this pilot study, the multispectral photoacoustic elastic tomography (PAET) imaging technique was used to recover the quantitative physiological and elastic properties of biological tissues for the diagnosis of SD. Three healthy subjects and 3 SD patients were recruited and clinically examined by a rheumatologist, and then their hand/fingers were scanned by both magnetic resonance imaging and our home-made photoacoustic imaging system. Physiological parameters including oxygen saturation (STO2), deoxy-hemoglobin (Hb) and oxy-hemoglobin (HbO(2)) concentrations and mechanical properties such as bulk elastic modulus images were reconstructed using the developed PAET reconstruction method. Our imaging results demonstrated that the physiological and elastic parameters exhibit striking differences between the SD and normal fingers, indicating that these biomarkers can serve as molecular signatures for early detection of SD. These quantitative physiological properties and bulk modulus may also pave a new path for improved understanding the pathological mechanism of SD.