What Causes Scleroderma? PDF Print E-mail
Monday, 13 September 2010 16:52
Collagen is a group of naturally occurring proteins, found exclusively in animals and especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, constituting about 25% to 35% of the whole-body protein content. Beside connective tissue, collagen (in the form of elongated fibrils) is mostly found in fibrous tissues such as tendons and ligaments, and abundant in the cornea, cartilage, bones, blood vessels, the gut, and intervertebral discs.

The connective tissue is the material between the cells of the body that gives tissues form and strength. Fibrous in nature, it is produced by special cells called fibroblasts and made up of dozens of proteins, including collagen (a fibrous protein building block), proteoglycans (a group of proteins that maintain tissue stiffness), and glycoproteins (composed of a protein and a sugar).

Connective tissue also surrounds and supports many of the organs and structures within the body, including the skin, blood vessels, and nerves.

Similarly, many cells of the immune system are found in the connective tissue. In Scleroderma, autoimmunity leads to excessive production and accumulation of collagen in the skin and other connective tissues, causing hardening and scarring (fibrosis). Smaller blood vessels are also damaged, causing many of the complications associated with the disorder, including high blood pressure and the onset of Raynaud's.

Although doctors aren't sure what prompts this abnormal collagen production, the body's immune system plays a significant role. For reasons still unknown, the system turns against the body, attacking the cells (fibroblasts) that produce collagen. Collagen is usually produced in small amounts, but the attack prompts inflammation and the eventual overproduction of the collagen, which replaces normal tissue in the skin and other organs.

Some medical scientists, researchers, and experts assert that Scleroderma is caused by a number of inherited or genetic abnormalities or vulnerabilities, which were triggered by environmental factors, such as a virus, certain adhesive and coating materials, and organic solvents such as vinyl chloride or trichloroethylene. It should be noted however, that research is being conducted to verify these and similar connections.

According to Dr. Laura Hummers and Dr. Fred Wigley, several drugs are used that have in vitro (in the tissue culture) ability to reduce collagen production or to destabilize tissue collagen. The older medications in this category include colchicine, para-aminobenzoic acid (PABA), dimethyl sulfoxide, and D-penicillamine. Although there is evidence for and against the use of these agents, most experts are disappointed with them and believe that the benefit either does not exist or the drug is not potent enough to warrant its use.

The search for new drugs that alter the fibrotic reaction is probably one of the most active areas of Scleroderma research. Strategies include directly suppressing the fibroblast and its ability to make collagen, inhibiting the cytokines that activate the fibroblast, and the use of agents that might break down collagen faster and promote tissue remodeling.

For futher reading, we encourage you to visit some of the sources identified below. You can also login, to download Chapter 23 of Systemic Sclerosis, 2nd Edition written by Dr. Laura Hummers and Dr. Fred Wigley, in which the previous three paragraphs were taken, from the link provided below.

Sources:
  • A.D.A.M (2009), “Scleroderma”, viewed online at http://nyti.ms/cntoNm
  • Health Grades Inc. (2010), “Causes of Scleroderma”, Wrong Diagnosis; viewed online at http://bit.ly/avwwlq
  • John Hopkins Scleroderma Center (2010), “Scleroderma Treatment Options”, viewed online at http://bit.ly/bCHCbg
  • Mayo Foundation (2010), “Scleroderma”, viewed online at http://bit.ly/9CBlAF
  • Science Daily (2005), “New Clues Into Causes of Scleroderma”, viewed online at http://bit.ly/bXHefF
  • Trafton, A. (2010), “Exposing collagen's double life”, MIT News; viewed online at http://bit.ly/cIkfTc
  • Wellsphere (2010), “Autoimmunity leads to excessive production of collagen in scleroderma”, Wellsphere; viewed online at http://bit.ly/bFhwYn
  • Wikipedia (2010), “Collagen”, viewed online at http://bit.ly/aqzwsH

 
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