Skin Histology in Systemic Sclerosis: a Relevant Clinical Biomarker
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SCLERODERMA (J VARGA, SECTION EDITOR)
Skin Histology in Systemic Sclerosis: a Relevant Clinical Biomarker Kimberly Showalter 1
&
Jessica K. Gordon 1
Accepted: 15 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Summary 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. Keywords Histology . Scleroderma . Systemic sclerosis . Fibroblasts . Skin . Biomarker
Introduction Since the first histopathologic description of scleroderma skin was performed in 1861 [1, 2], skin biopsies have been used to confirm the diagnosis of systemic sclerosis (SSc; scleroderma) or to describe treatment response in the context of SSc clinical trials. Indeed, skin biopsies are commonly used in SSc treatment trials; yet, these are sometimes incorporated as a means for gene expression analysis rather than for histopathological evaluation. For those clinical trials that include exploratory histologic outcomes, assessments of collagen and myofibroblasts (alpha-smooth muscle actin (aSMA) immunohistochemistry) are commonly used, yet there is no standard approach at this point in time [3]. In this review, we discuss the literature describing the use of skin histology in scleroderma clinical care and clinical trials. In our opinion, histopathological assessment may be useful in describing clinical and This article is part of the Topical Collection on Scleroderma * Kimberly Showalter [email protected] 1
Department of Medicine, Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA
pharmacodynamic response in trials, and future research is needed to determine whether histopathologic features may also one day serve as a prognostic biomarker in SSc.
Skin Histology as a Diagnostic Biomarker A diagnostic biomarker is defined by the National Institutes of Health and U.S. Food and Drug Administration (Biomarkers, EndpointS, and other Tools (BEST)
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