SYSTEMIC SCLEROSIS: A Vascular Perspective
Section snippets
Definition
SSc is a generalized disorder of the interstitial connective tissues and vasculature with distinct abnormalities of three systems, immune and autoimmune, vascular and microvascular, and mesenchymal extracellular matrix (ECM), that lead to exuberant fibrosis. The principal target organs for vascular insufficiency and fibrosis are the skin, lungs, gastrointestinal tract, heart, and kidneys. The process can vary from aggressive and fulminating to indolent and chronic. The rate of involvement of
Raynaud's Phenomenon (RP)
As mentioned earlier, the prevalence of RP varies by as much as six-fold depending on the population surveyed, from a low of 5% to a high of 30%. Multiple factors have been proposed to explain these differences. In a US study7, 24, 28 consisting of whites and blacks, the prevalence varied from 5% to 10% and a disproportionately high prevalence noted in black men was adequately accounted for by the high proportion of heavy manual labor carried out by the study subjects. Thus occupation must be
The Physiologic Lesion
The markedly attenuated microvascular bed in SSc can be studied physiologically as well as morphologically. Exaggerated vasospasm and dramatically reduced microvascular volumes have been well documented by such notables as Sir Thomas Lewis, Grant and Bland, Coffman and Cohen, Nilsson and Lassen, Downey and Cannon, Burch et al, Maricq et al, Jablonska et al, Rowell et al, Norton et al, and most recently by Cooke et al. Cooke et al have recently demonstrated, using Doppler techniques, that
VASCULAR MANAGEMENT AND THERAPY
This article is not intended to be exhaustive in a clinical or therapeutic context. Probably the most significant change in the life of an SSc patient has been the introduction and use of ACE inhibitors to prevent renal failure, hypertension, and the direct proliferative and vasculotoxic effects of angiotensin II on blood-vessel wall cells. These may be the only class of drugs in which definite prolongation of life in SSc is well documented and generally agreed upon. They are especially helpful
SUMMARY
The horizon is bright for SSc in a vascular context. Surrogate markers can now be routinely used in the management of the active patient; new cytokines, such as VEGF, can be studied along with the known abnormalities of the cytokine cascade (TGFβ1, PDGF) for a more integrated understanding of the vascular pathogenesis of SSc (Fig. 6); and combination therapies can be applied before vascular insufficiency leads to vital organ failure. Thus, despite reimbursement and research funding constraints,
ACKNOWLEDGMENTS
The author thanks Beth Gladden and her staff for the preparation of this article.
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2018, Medical HypothesesCitation Excerpt :This suggests dermal sheath thickening and perifollicular fibrosis may be causative rather than associative to hair thinning, but by which mechanisms? The earliest signs of fibrosis in scleroderma patients appear in the areas of severest vascular perturbation [29]. Liver fibrosis pathogenesis models demonstrate that excessive extracellular matrix synthesis and deposition lead to hepatic microvascular and nutritive degradation [30] – potentiating that decreased oxygen and nutrient supply are consequences of fibrosis progression.
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Address reprint requests to E. Carwile LeRoy, MD, Department of Microbiology and Immunology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425
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From the Medical University of South Carolina, Charleston, South Carolina