Fingertip skin sclerosis is associated with systemic sclerosis (SSc, scleroderma), which is a multi-organ disease characterized by thickening, sclerosis and atrophy of the skin. Based on the extent of skin sclerosis, SSc is divided into limited cutaneous SSc (lcSSc), representing skin sclerosis limited to the fingers and forearms, and diffuse cutaneous SSc (dcSSc), in which skin sclerosis spreads beyond the upper arm to the trunk (1, 2).
The early stages of skin lesions in SSc include abnormalities in the perivascular region and inflammation, characterized by accumulation of fibroblasts, smooth muscle cells, and inflammatory cells, such as lymphocytes and macrophages (3-7). Mediators produced by inflammatory cells induce the synthesis of matrix proteins from fibroblasts, resulting in collagen hyperplasia, skin thickening and fibrosis (8, 9). Several lines of evidence suggest the involvement of mast cells in SSc skin lesions. Activated mast cells are present around the small vessel endothelium and produce tryptase and chymase, specific serine proteases, and TNF, which can induce vascular abnormalities, fibroblast growth, and collagen synthesis, resulting in skin sclerosis (10).
Mast cells also play a pivotal role in various inflammatory processes by producing a multitude of cytokines and mediators. Studies using the forearm tissues of SSc patients suggested that mast cells are the major source of TGF-β, a cytokine implicated in fibrosis (11). However, the role of mast cells in skin fibrosis of SSc remains to be fully elucidated, especially in skin tissues of the distal extremities.
Raynaud's phenomenon, a clinical feature of SSc, involves finger vasospasm, with the development of skin sclerosis in distal extremities. The present study was designed to assess the skin tissues of distal extremities, with a special focus on mast cell accumulation in the tissue using NanoZoomer Digital Pathology, and the correlation of mast cell accumulation in fingers and forearms with the pathogenesis of SSc.