Systemic scleroderma

The exact, underlying cause of systemic sclerosis is unknown. The cause appears to involve some injury to the cells that line blood vessels, resulting in excessive activation of dermal connective tissue cells, called fibroblasts. Fibroblasts normally produce collagen and other proteins. Build-up of collagen in the skin and other organs causes the signs and symptoms of the condition.

It is suspected that scleroderma may develop from a variety of factors, which may include:

• Abnormal immune or inflammatory activity
• Genetic susceptibility: while no specific genes are thought to cause scleroderma, certain variations in genes or combination of genes may increase a person's risk to be affected. These genes include several human leukocyte antigen (HLA) complex genes, and also non-HLA genes such as the TNFAIP3 ,CD247, IRF5, STAT4, _and PTPN22_ genes. However, while the risk of being affected by the disease is increased when a relative is affected, the condition is not passed directly from parents to children.
• Environmental triggers: suspected triggers may include infections; injury; drugs (e.g. vitamin K, cocaine, penicillamine, appetite suppressants and some chemotherapeutic agents); and chemicals (e.g. silica, organic solvents, pesticides, aliphatic hydrocarbons and epoxy resin).
• Hormones: because women develop scleroderma more often than men, researchers suspect that hormones may play a role, but the role of female hormones has not been proven.

Widespread scleroderma can also occur in association with other autoimmune diseases, including systemic lupus erythematosus and polymyositis.

It is thought that the disease is triggered from the exposure to the environmental factors in people who are genetically susceptible. In some people, genetic factors may be sufficiently strong to lead to the disease.

Because systemic scleroderma is not caused by a mutation in any one specific gene, clinical genetic testing to confirm a diagnosis or identify a "carrier" is not currently available. Even if someone is known to carry a version of a gene that may make them susceptible to the condition, it does not mean they will definitely develop the condition.

You can view a list of centers that may be involved in research projects on systemic scleroderma on Orphanet's Web site.

You can also view a list of clinical trials involving people with systemic scleroderma on ClinicalTrials.gov.

People interested in learning more about genes and genetic testing for systemic scleroderma should speak with a genetics professional.

Most cases of systemic scleroderma are not inherited, but instead, occur in people with no history of the condition in their family. However, several studies show that the risk of systemic scleroderma in first-degree relatives of people with the disease is increased and and a few cases of the condition have been reported to run in families, but there is no clear pattern of inheritance. Also, some people with systemic scleroderma have relatives with other autoimmune disorders.

.