Should all digital ulcers be included in future clinical trials of systemic sclerosis-related digital vasculopathy?

Digital ulcers (DU) are a common manifestation of systemic sclerosis (SSc) and occur at a variety of locations including the fingertips and over the extensor aspects of the hands. However, most recent clinical trials have included only fingertip DUs as these are believed to be ischaemic in aetiology, and therefore likely to benefit from treatment with vasoactive drug therapies. There is an emerging evidence base to suggest that all DUs in SSc could share an ischaemic component which is potentially responsive to vascular therapy. Our hypothesis is that is that DUs occurring at sites other than the fingertips, in particular, those overlying the extensor aspect of the hands, may also have a potentially reversible ischaemic component. We review the evidence under the headings: 'microvascular imaging', 'structural microvascular' and, 'functional vascular disease', 'macrovascular involvement' and 'vascular associates'. Based upon the current evidence, we would encourage the expert SSc community to reconsider the rationale for including only fingertip DUs in future SSc clinical trials, and suggest an agenda for future research.