Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc).

In the last few years, a number of studies have been published on a condition characterized by Raynaud's phenomenon (RP) associated with systemic sclerosis (SSc) marker autoantibodies and/or scleroderma-type capillaroscopic abnormalities and referred to as very early/early SSc. The present review is devoted to analyze pathophysiologic, clinical, and evolutive aspects of the condition that would induce to label it as Undifferentiated Connective Tissue Disease at risk for SSc and to split it into 3 subsets (i.e. RP associated to marker autoantibodies and scleroderma-type capillaroscopic abnormalities; RP associated to marker autoantibodies in the absence of scleroderma-type capillaroscopic abnormalities; and RP associated to scleroderma-type capillaroscopic abnormalities without any detectable marker autoantibody), which have been shown to carry different degrees of risk, but not the certainty, to develop overt SSc over time. This nosographic approach is instrumental to plan future studies devoted to investigate validated biomarkers heralding the development of major vascular disease manifestations as well as skin and/or organ fibrosis in patients at risk.