Systemic Sclerosis

An Update

Uwe-Frithjof Haustein, MD, PhD

Disclosures

Lab Med. 2011;42(9):562-572. 

In This Article

Pathophysiology

The course and even the initial events in the pathogenesis of SSc are still poorly understood. The microvasculature (EC, platelets, capillaries) is 1 of the first affected systems, sometimes preceding the outbreak of the disease even by years (Raynaud's phenomenon). There is evidence that the disease may be immunologically triggered, again as an early event.[28] T lymphocytes in collaboration with monocytes, EC, platelets, and mast cells act as mediators and targets in the pathophysiological network. These cells express and release adhesion molecules, ILs, and growth factors that act on FBs. In addition, hypoxia causes oxidative stress in various organs. The excessive tissue fibrosis is due to an expansion of fibrogenic clones of tissue FBs and their transformation into myofibroblasts that behave relatively autonomously and over-express genes encoding ECM components.[29] Tyrosine kinases have been shown to regulate the release and activity of various cytokines and growth factors such as transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF). This leads to excessive deposition of collagen and other connective tissue matrix proteins in the skin and internal organs as well as in the walls of blood vessels.

As known from many other autoimmune diseases, the pathogenesis of SSc is partly based on genetic background and modulated by environmental factors.[30] The following sections will discuss the 3 main pathogenetic pathways. These include microvasculature abnormalities, abnormal immune response, and dysregulation of FB activity (Figure 1).

Figure 1.

Pathogenesis of SSc. The crosstalk of genetics with environmental influences involves a network between vascular alterations (EC), autoimmune aberrations (T cells, B cells, Auto-ab), and activation of FBS by adhesion molecules, cytokines, chemokines, and growth factors with the consequences of an excessive deposition of collagen and other ECM substances in the connective tissue (fibrosis).

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