Causes:

Most likely this disease is caused by a number of inherited (genetic) abnormalities, which are triggered by environmental factors.

Inflammatory Response and Autoimmunity

The disease process leading to scleroderma appears to occur as an autoimmune response, in which an abnormal immune system attacks the body itself. In scleroderma, this response produces swelling (inflammation) and too much production of collagen. Collagen is the tough protein that helps build connective tissues such as tendons, bones, and ligaments. Collagen also helps scar tissue form. When normal tissue from skin, lungs, the esophagus, blood vessels, and other organs is replaced by this type of abnormal tissue, none of these body parts work as well, and many of the symptoms previously described occur.

Antigens are large molecules (usually proteins) on the surface of many cells -- both human cells, and cells of viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. When the immune system recognizes an antigen as being foreign (not part of the human body), it starts offensive and defensive actions against them by producing antibodies and other chemicals such as cytokines that destroy any cells in the area.

Much of this activity is directed by white blood cells known as T cells, which are subdivided into killer T cells and helper T cells (TH cells).

The actions of the helper T cells are of special interest in scleroderma. For some unknown reason, the T cells become overactive in scleroderma and mistake the body's own collagen for a foreign antigen. This triggers a series of immune responses to destroy the collagen. When the body creates antibodies against itself in this way, it is called an autoimmune response.

Fetal Cell Theory and Microchimerism

A process called microchimerism has been proposed as one cause of scleroderma. The theory arose from the fact that scleroderma occurs mostly in women, and its symptoms resemble those of graft-versus-host disease (GVHD). GVHD occurs in bone marrow transplant patients who have received cells from another person. It happens when the transplanted immune cells of the donor launch an attack against the patient's body.

Chimerism occurs when cells from two different individuals exist in the same body , such as cells from a fetus left in its mother's body after she gave birth. When there are low numbers of the cells of one body in another, the condition is referred to as microchimerism.

However, if microchimerism plays a role in scleroderma, it most likely does so only in a subset of patients.

Triggering the Immune Response

It is still not clear why the immune system responds abnormally in people with scleroderma. Some experts believe that environmental factors, such as a virus or a chemical, may trigger the response in individuals with a genetic vulnerability.

Chemicals. Occupational exposure to certain chemicals can cause blood vessel constriction and attacks of Raynaud's phenomenon. Despite the fact that women are at higher overall risk for scleroderma, among people who are exposed to solvents at work, men face a higher risk for the disease. However, no specific work-related factors have been proven to cause the disorder.

It is nearly impossible to determine whether specific chemicals may actually cause systemic scleroderma, primarily because few people develop the disease, even though many people are exposed to such chemicals. In addition, research has been unable to consistently repeat studies that have reported links with chemicals.

Studies have found, however, that certain industrial toxins are significantly associated with severe lung problems in people with scleroderma. The toxins most likely to be associated with severe disease include epoxy resins, white spirit, solvents, and silica mixed with welding fumes.

Radiation. Radiation therapy has been reported to cause local patches of scleroderma (morphea) or worsen preexisting scleroderma in patients. In some cases, scleroderma may occur years after radiation treatments.