Frontiers in translational systemic sclerosis research: A focus on the unmet 'cutaneous' clinical needs (Viewpoint)

Abstract

This viewpoint considers four cutaneous unmet clinical needs of patients with systemic sclerosis (SSc), namely the rapidly progressive skin thickening (scleroderma) which occurs early on in diffuse cutaneous disease; digital (finger and toe) ulcers; calcinosis; and cutaneous telangiectases. All four problems cause pain, disability and/or disfigurement, all impact on quality of life, and for each, we require effective treatments. For each unmet need, we give a brief description of the clinical problem (including clinical burden), pathophysiology and current treatment, followed by a personal viewpoint of the key questions which research must address. For the painful, debilitating skin thickening of early diffuse cutaneous SSc, studies are required to decide whether corticosteroids are effective and safe (current opinion is divided) and whether phototherapy approaches have a role. Also, we need to develop and validate reliable outcome measures for clinical trials of promising new therapies: these could be composite indices, novel non-invasive imaging methods and patient-reported outcome measures, possibly in combination as they provide complementary information. For digital ulcers, again we require validated outcome measures for clinical trials. We also need to explore local (including topical) treatments, which are free from systemic adverse effects, and preventative strategies for high-risk patients. For calcinosis, we need to better understand pathophysiology, to validate outcome measures and to develop topical treatments. For telangiectases, we need to "use" these highly accessible lesions to help unravel the vascular pathophysiology of SSc and explore their different properties as potential biomarkers.