From the grey area of pre-systemic sclerosis to very early disease and irreversible tissue damage: the challenge of defining at-risk patients for future preventive trials in systemic sclerosis

: This viewpoint aims to explore whether precondition trials could be applied in systemic sclerosis (SSc)-the systemic autoimmune rheumatic disease (SARD) associated with the highest mortality and substantial morbidity. In contrast to type 1 diabetes and rheumatoid arthritis (RA), where predisease states have been more clearly defined, a consensus definition for pre-SSc is still lacking. A consensus framework for patients with signs and symptoms also common to other SARDs/connective tissue diseases, but that potentially identify a patient at a pre-SSc stage, needs to be collectively drafted. Such a framework would provide the basis for earlier recognition, risk stratification, and ultimately, timely intervention in pre-SSc. Considering the paradigm shift already achieved in type 1 diabetes and RA, a similar strategy targeting patients at risk of SSc could foster the development of innovative approaches to SSc management-preventing the onset of key SSc-related signs and symptoms, promoting long-term remission, and reducing SSc-related morbidity and mortality.