An in-depth report on the causes, diagnosis, and treatment of scleroderma.
Systemic sclerosis; Localized scleroderma
- Scleroderma is an uncommon, complex, autoimmune disease. The body's immune system attacks its own tissues. It affects the skin by causing hardened tissue or ulcers and may harm the internal organs.
- Doctors have made progress developing treatments to reduce symptoms, but there is no cure.
- There are two major forms of the disease. Systemic scleroderma is a serious condition, while localized scleroderma carries a good prognosis and normal lifespan. In children, localized scleroderma is three times more common than the systemic form of the disease.
- The cause and course of the disease is unclear, and more research is needed to assess treatment options.
Treatment involves a combination approach to treat the immune response, improve circulation, and stop the progression of skin symptoms. Several medications and therapies are in the very early phases of study for scleroderma. These agents show some promise, but additional study is needed to define their use:
- Bosentan is currently under study in the US for systemic scleroderma. It is already approved by the Food and Drug Administration (FDA) for the treatment of pulmonary hypertension. Two trials have demonstrated a reduction of new skin ulcers for certain scleroderma patients after taking Bosentan. The drug was approved in Europe in 2007 for the treatment of skin ulcers related to scleroderma.
- Early study results on a very small number of patients show some promise after non-myeloablative autologous haemopoietic stem-cell transplantation (HSCT) for those with severe disease. Longer follow up and further study is needed to learn if this treatment works and for which patients, as well as to evaluate its safety.
- Some biologic drugs -- such as rituximab (Rituxan) and Imatinib mesylate (Gleevac), used to treat certain cancers and illnesses that involve an overactive immune system -- may play a role in treating scleroderma. However, larger scale, randomized, multi-center studies are necessary to determine whether they are beneficial.
The Canadian Scleroderma Research Group (CSRG) convened an expert panel in the area of nutrition to develop new recommendations in the screening and management of nutritional disorders related to scleroderma. Recommendations cover areas of evaluation, referral, medications, and nutritional therapies.
The European League Against Rheumatism (EULAR), with experts from Europe, the United States, and Japan, has developed 14 evidence-based recommendations for the treatment of scleroderma.
The American College of Rheumatology has developed guidelines for improved diagnostic accuracy and consistency.
The name scleroderma comes from the Greek words skleros. which means hard, and derma. which means skin. The disease is categorized as a rheumatologic disorder because it affects the connective tissues in the body. It is rare, with an annual incidence of 18 - 20 new cases per million persons.
Scleroderma is marked by the following:
- Damage to the cells lining the walls of small arteries
- An abnormal build-up of tough scar-like tissue in the skin
Patients with scleroderma may develop either a localized or a systemic (body-wide) form of the disease.
Localized scleroderma usually affects only the skin on the hands and face. Its course is very slow, and it rarely, if ever, spreads throughout the body (becomes systemic) or causes serious complications. There are two main forms of localized scleroderma: morphea and linear scleroderma.
Morphea Scleroderma. In morphea scleroderma, patches of hard skin form and can last for years. Eventually, however, they may improve or even disappear. There is less than a 1% chance that this disorder will progress to systemic scleroderma.
Linear Scleroderma. Linear scleroderma causes bands of hard skin across the face or on a single arm or leg. Linear scleroderma may also involve muscle or bone. Rarely, if this type of scleroderma affects children or young adults, it may interfere with growth and cause severe deformities in the arms and legs.
Systemic scleroderma is also called systemic sclerosis. This form of the disease may affect the organs of the body, large areas of the skin, or both. This form of scleroderma has two main types: limited and diffuse scleroderma. Both forms are progressive, although most often the course of the disease in both types is slow.
Limited Scleroderma (also called CREST Syndrome). Limited scleroderma is a progressive disorder. It is classified as a systemic disease because its effects can be widespread throughout the body. It generally differs from diffuse scleroderma in the following ways:
- In most cases the internal organs are not affected.
- Patients with limited scleroderma have a less serious course, unless they develop pulmonary hypertension (a particular danger with the CREST syndrome). Pulmonary hypertension is high blood pressure in the lungs (see the Lung Complications section).
Limited scleroderma is commonly referred to by the acronym CREST, whose letters are the first initials of characteristics that are usually found in this syndrome:
- Calcinosis. With this condition, mineral crystal deposits form under the skin, usually around the joints. Skin ulcers filled with a thick white substance may form over the deposits.
- Raynaud's phenomenon. In this syndrome, the fingers of both hands are very sensitive to cold, and they remain cold and blue-colored after exposure to low temperatures. This occurs in nearly all cases of scleroderma, both limited and diffuse. It is caused by abnormal changes in small blood vessels. These changes cause the vessels to narrow, and blood flow is temporarily interrupted, usually in the fingers.
- Esophageal motility dysfunction. The esophagus carries food from the mouth to the stomach. In esophageal motility dysfunction, the muscles in the esophagus become scarred by scleroderma and do not contract normally. This can cause severe heartburn and other symptoms of gastroesophageal reflux disorder (GERD).
- Sclerodactylia (also called acrosclerosis). This is the stiffness and tightening of the skin of the fingers, a classic symptom of scleroderma. Bone loss may occur in the fingers and toes.
Telangiectasia. In this situation, widening of small blood vessels causes numerous flat red marks to form on the hands, face, and tongue.
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In general, people with limited scleroderma develop Raynaud's phenomenon long before they develop any of the other symptoms. One or more of the CREST conditions can also occur in other forms of scleroderma.
Diffuse Scleroderma. Diffuse scleroderma, the other type of systemic sclerosis, has the following characteristics:
- It can affect wide areas of the skin, connective tissue, and other organs.
- It can have a very slow course, but it also may start quickly and be accompanied by swelling of the whole hand. If it gets worse quickly early on, the condition can affect internal organs and become very severe -- even life threatening.
Diffuse scleroderma can overlap with other autoimmune diseases, including systemic lupus erythematosus and polymyositis. In such cases, the disorder is referred to as mixed connective disease.
Scleroderma is not common. It afflicts about 300,000 Americans, about a third of whom have the systemic form of the disease. The cause of scleroderma has not been determined, and there are few specific risk factors. The incidence tends to be higher in certain groups, however.
Age. Systemic scleroderma usually develops between the ages of 35 and 55. It is extremely rare in children. Localized scleroderma is more common in children than adults, but is extremely rare even in the young age group.
Gender. The prevalence of scleroderma is about four times higher in women than men, and it's higher during child-bearing years. This may reflect different causes of the disease in these two genders. (It should be noted that pregnancy itself is not a risk factor for scleroderma and that women in general are more susceptible to autoimmune diseases than men.)
Family History. A family history is the strongest risk factor for scleroderma, but even among family members, the risk is very low (less than 1%).
Genetics. Genetic factors appear to play a role in triggering the disease, but most cases are unlikely to be inherited. Preliminary research suggests that genes and gene to gene interactions play a role.
Ethnicity. Limited data on risk by ethnic group in the United States suggests that the risk from highest to lowest is the following: Choctaw Native Americans (highest), African-Americans, Hispanics, Caucasians, Japanese Americans.
African-Americans have a higher rate of diffuse scleroderma, lung involvement, and a worse prognosis than Caucasians. Other studies also found lower survival rates among Japanese Americans.
Genetic factors affect population groups differently. Studies are finding that ethnic groups differ in the number of specific scleroderma-related antibodies they produce. Caucasians, for instance, have a higher rate of anti-centromere antibodies, which are associated with limited disease, while African-American patients have higher rates of autoantibodies and genetic factors that are associated with a more severe condition. The condition is also more severe in Native Americans.
Symptoms and Complications
Raynaud's phenomenon is often the first sign of scleroderma. With this condition, small blood vessels constrict in the fingers, toes, ears, and sometimes even the nose.
Attacks of Raynaud's phenomenon can occur several times a day, and are often brought on or worsened by exposure to cold. Warmth relieves these attacks. In severe cases, attacks can develop regardless of the temperature. Severe cases may also cause open sores or damage to the skin and bones, if the circulation is cut off for too long.
Typically, the fingers go through three color changes:
- First, they become very pale.
- As the blood flow is cut off, they turn a bluish color, usually in the top two sections of the second and third fingers.
- Finally, when blood flow returns, the fingers become red.
Tingling and pain can occur in the affected regions.
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Raynaud's is very common and occurs in 3 - 5% of the general population. It's important to note that more than 80% of patients with Raynaud's phenomenon do not have scleroderma, lupus, rheumatoid arthritis, or other serious illnesses. Raynaud's is more likely to be a symptom of scleroderma or some other connective tissue disease if it develops after age 30, if it is severe, and if it is accompanied by other symptoms (such as skin changes and arthritis).
Course of Typical Skin Changes. The primary symptoms of scleroderma occur in the skin. They often take the following course:
- Typically, pitted scars appear first on the hands. The skin begins to thicken and harden on the hands, feet, and face. The fingers may swell. This condition is called sclerodactylia or acrosclerosis. Patients with diffuse scleroderma may have swelling of the whole hand before the skin significantly thickens.
- Thickened or hardened patches may also develop on other areas of the body. (Their appearance on the trunk and near the elbows or knees tends to be a sign of a more severe condition.)
- For the first 2 or 3 years, the skin continues to thicken and feel puffy.
- This process then stops, and can even get better. The skin may soften.
- As the disease progresses further, however, the skin loses its ability to stretch, and becomes shiny as it tightens across the underlying bone, particularly in the fingers, toes, and around the mouth.
Eventually, in severe cases, the fingers may lose the ability to move, and can be difficult to bend. The hands and feet may curl from the tightness of the skin. It may be difficult to open the mouth widely.