Systemic sclerosis: a prototypic multisystem fibrotic disorder
John Varga, David Abraham
John Varga, David Abraham
Published March 1, 2007
Citation Information: J Clin Invest. 2007;117(3):557-567. https://doi.org/10.1172/JCI31139.
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Review Series

Systemic sclerosis: a prototypic multisystem fibrotic disorder

Abstract

A unique feature of systemic sclerosis (SSc) that distinguishes it from other fibrotic disorders is that autoimmunity and vasculopathy characteristically precede fibrosis. Moreover, fibrosis in SSc is not restricted to a single organ, but rather affects many organs and accounts for much of the morbidity and mortality associated with this disease. Although immunomodulatory drugs have been used extensively in the treatment of SSc, no therapy to date has been able to reverse or slow the progression of tissue fibrosis or substantially modify the natural progression of the disease. In this Review, we highlight recent studies that shed light on the cellular and molecular mechanisms underlying the fibrotic process in SSc and that identify cellular processes and intra- and extracellular proteins as potential novel targets for therapy in this prototypic multisystemic fibrotic disease.

Authors

John Varga, David Abraham

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Figure 2

Skin inflammation and fibrosis in SSc.

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Skin inflammation and fibrosis in SSc. (A) In early diffuse cutaneous SS...
(A) In early diffuse cutaneous SSc, moderate fibrosis in the upper dermis and at the dermal-epidermal junction is accompanied by evidence of keratinocyte hypertrophy with a flattening of the epidermis, leading to loss of reticular structure and decreased length of rete pegs (fingerlike structures that project up from the dermis and down from the epidermis, increasing the area of contact between the layers of the skin). In addition, inflammatory infiltrates are found in the dermis and near the dermal-epidermal junction, predominantly around small blood vessels. (B) Early-stage diffuse disease showing profound dermal inflammation characterized by perivascular mononuclear cellular infiltrate composed of monocytes and activated lymphocytes, with perivascular fibrosis and loss of pericytes and vessel integrity. (C) In established fibrosis, collagen accumulation leads to dermal thickening and the deposition of dense and closely packed collagen fibers throughout the dermis, with the loss of the microvasculature and dermal structures and the dermis-subcutaneous adipose tissue interface. All images are stained with H&E and photographed using a Zeiss Axioscope confocal microscope under light field. Original magnification, ×100 (A and C); ×200 (B).