Skin Histology in Systemic Sclerosis: a Relevant Clinical Biomarker

Purpose of review: Systemic sclerosis (SSc) is a life-threatening autoimmune disease that causes debilitating skin fibrosis. The skin in SSc is easily accessible, and skin biopsies may provide rich biological data regarding underlying disease pathophysiology. Here, we review literature relevant to the potential for skin histology to serve as a diagnostic, pharmacokinetic/response, and predictive biomarker in SSc.

Recent findings: Multiple histologic parameters correlate with SSc severity, including alpha smooth muscle actin (aSMA), CD34, collagen density, thickness, and inflammatory cell infiltration. Recent clinical trials incorporate skin histology as exploratory outcome measurements; however, a standard approach is not yet established. The possibility that skin histology may be useful as a predictive biomarker was suggested by a recent study that identified genes related to skin aSMA and CD34 staining intensity that were increased at baseline among improvers versus nonimprovers. Current literature supports skin histology as a mechanism to measure treatment response, but future work is needed to define minimally meaningful changes in key SSc skin histologic features.