Pathophysiological Mechanisms in Sclerosing Skin Diseases

Abstract

Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches.

Keywords: extracellular matrix; growth factor activation; nephrogenic systemic fibrosis; scleredema; scleromyxedema; stiff skin syndrome; systemic sclerosis.

Figure 1

Triggers, key cellular players and structural proteins involved in skin sclerosis. Activation of the innate as well as the adaptive immune system by diverse triggers is thought to lead to activation of different fibroblast progenitors and lineages. These then convert to the myofibroblast that plays a central role in producing excessive amounts of extracellular matrix and other protein components typically associated with certain subsets of sclerosing skin diseases.