Abstract
Systemic sclerosis is an autoimmune disease of unknown origin characterized by excessive deposition of collagen and other connective tissue macromolecules in skin and multiple internal organs, severe alterations in the microvasculature, and humoral and cellular immunological abnormalities. Although the most apparent and almost universal clinical features of systemic sclerosis are related to the progressive thickening and fibrosis of the skin, some degree of involvement of multiple internal organs is uniformly present even when not clinically apparent. This chapter will examine the clinical aspects and pathogenesis of the disease and review some promising therapies that have been and are being developed that might modify the natural course of this serious and often lethal disorder.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Selected References
Arnett FC, Cho M, Chatterjee S, et al. Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts. Arthritis Rheum 2001;44(6):1359–1362.
Artlett CM, Smith JB, Jimenez SA. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 1998;338:1186–1191.
Cheema GS, Quismorio FP Jr. Interstitial lung disease in systemic sclerosis. Curr Opin Pulm Med 2001;7:283–290.
Cepeda EJ, Reveille JD. Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical indications and relevance. Curr Opin Rheumatol 2004;16:723–732.
Clark DA, Coker R. Transforming growth factor-beta (TGF-β). Int J Biochem Cell Biol 1998;30:293–298.
Coghlan JG, Mukerjee D. The heart and pulmonary vasculature in scleroderma: clinical features and pathobiology. Curr Opin Rheumatol 2001;13:495–499.
Derk CT, Jimenez SA. Systemic sclerosis: current views of its pathogen-esis. Autoimmun Rev 2003;2:181–191.
Derynck R, Zhang YE. Smad-dependent and smad-independent pathways in TGFβ family signalling. Nature 2003;425:577–584.
Dong C, Zhu S, Wang T, et al. Deficient Smad 7 expression: a putative molecular defect in scleroderma. Proc Natl Acad Sci USA 2002; 99:3908–3913.
Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical and serologic features and survival in 1,012 Italian patients. Medicine 2002;81:139–153.
Ghosh AK. Factors involved in the regulation of type I collagen gene expression: implication in fibrosis. Exp Biol Med (Maywood) 2002; 227(5):301–314.
Ihn H, Yamane K, Kubo M, et al. Blockade of endogenous transforming growth factor β signaling prevents up-regulated collagen synthesis in scleroderma fibroblasts: association with increased expression of transforming growth factor β receptors. Arthritis Rheum 2001;44:474–480.
Jimenez SA, Derk CT. Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med 2004;140:37–50.
Johnson RW, Tew MB, Arnett FC. The genetics of systemic sclerosis. Curr Rheumatol Rep 2002;4:99–107.
Lally EV, Jimenez SA, Kaplan SR. Progressive systemic sclerosis: mode of presentation, rapidly progressive disease course, and mortality based on an analysis of 91 patients. Semin Arthritis Rheum 1988;18:1–13.
LeRoy EC. Connective tissue synthesis by scleroderma skin fibroblasts in cell culture. J Exp Med 1972;135:1351,1352.
LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:202–205.
MacGregor AJ, Canavan R, Knight C, et al. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology 2001;40:453–459.
Moustakas A, Heldin C-H. Non-Smad TGF-β signals. J Cell Sci 2005; 118:3573–3584.
Nietert PJ, Silver RM. Systemic sclerosis: environmental and occupational risk factors. Curr Opin Rheumatol 2000;12:520–526.
Rose S, Young MA, Reynolds JC. Gastointestinal manifestations of scle-roderma. Gastroenterol Clin North Am 1998;27:563–594.
Rosenbloom J, Saitta B, Gaidarova S, et al. Inhibition of type I collagen gene expression in normal and systemic sclerosis fibroblasts by a specific inhibitor of geranylgeranyl transferase I. Arthritis Rheum 2000; 43:1624–1632.
Rubin LI, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896–903.
Shi-Wen X, Denton CP, Dashwood MR, et al. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. J Invest Dermatol 2001;116:417–425.
Steen VD. Scleroderma renal crisis. Rheum Dis Clin North Am 1996; 22:861–878.
Steen VD, Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 2000;43: 2437–2444.
Ten Dijke P, Hill CS. New insights into TGF-β-Smad signalling. Trends Biochem Sci 2004;29:265–273.
Varga J. Scleroderma and smads: dysfunctional smad family dynamics culminating in fibrosis. Arthritis Rheum 2002;46:1703–1713.
Whitman M, Raftery L. TGFβ signaling at the summit. Development 2005;132:4205–4210.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc.
About this chapter
Cite this chapter
Derk, C.T., Jimenez, S.A. (2006). Systemic Sclerosis. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_100
Download citation
DOI: https://doi.org/10.1007/978-1-59259-963-9_100
Publisher Name: Humana Press
Print ISBN: 978-1-58829-202-5
Online ISBN: 978-1-59259-963-9
eBook Packages: MedicineMedicine (R0)