Scleroderma

Definition

Scleroderma is a serious, progressive disease that affects the skin and connective tissue (including cartilage, bone, fat, and the tissue that supports the nerves and blood vessels throughout the body). Scleroderma is also frequently called systemic sclerosis.

Description

Connective tissue is found throughout the body. It is a fibrous tissue produced by special cells called fibroblasts. Many cells of the immune system exist within the connective tissue. Connective tissue supports all of the structures of the body, including the skin, the organs, and all of the body's blood vessels and nerves. Collagen is a type of protein fiber present in connective tissue.

In scleroderma, collagen is over produced and is defective. Collagen then accumulates throughout the body, causing the hardening (sclerosis), scarring (fibrosis), and the damage characteristic of scleroderma. Because collagen is found so widely throughout the body, the effects of scleroderma are almost always widespread.

Scleroderma occurs in all races of people all over the world. Patients are most often diagnosed between the ages of 30-50 years old. Women are three to four times more likely to suffer from the disorder. Young Afro-American women and Choctaw Native Americans have particularly high rates of the disease. Although some cases of scleroderma clearly run in families, most cases of scleroderma occur without any known family tendency for the disease.

Causes & symptoms

The cause of scleroderma remains puzzling. Although the accumulation of collagen appears to be a hallmark of the disease, doctors do not know why this happens. Some theories suggest that damage to blood vessels may occur prior to fibrosis. When blood vessels are damaged, the tissues of the body receive an inadequate amount of oxygen (a condition called ischemia). Some researchers believe that tissue ischemia and damage then causes the immune system to over react, creating an autoimmune disorder. The immune system is designed to produce cells that fight foreign invaders like bacteria, viruses, and fungi. In this theory of scleroderma, the immune system gears up to fight an invader, but no invader is actually present. Cells of the immune system, called antibodies, recognize the body's own tissues as foreign. The immune system cells turn against the already damaged blood vessels and then the vessels' supporting tissues. These immune cells are designed to deliver potent chemicals in order to kill foreign invaders. Some of these cells dump these chemicals on the body's own tissues instead, causing inflammation, swelling, damage, and scarring.

Most cases of scleroderma occur with no recognizable initiating event. Some cases, however, have been traced to poisonous (toxic) exposures. For example, coal miners and gold miners (both of whom have a lot of exposure to silica dust) have higher than normal rates of scleroderma. Other types of chemicals that have been associated with scleroderma include polyvinyl chloride, benzine, toluene, and epoxy resins. In 1981, 20,000 people in Spain were stricken with a syndrome similar to scleroderma when a toxic substance accidentally contaminated cooking oil. Some claims of a scleroderma-like illness have been made by women with silicone breast implants.

About 95% of all patients with scleroderma have a condition called Raynaud's phenomenon as their first symptom. In Raynaud's disease, the blood vessels of the fingers and/or toes (the digits) react abnormally to cold. The vessels clamp down, preventing blood flow to the end of the digit and, eventually, to the entire digit. The affected digit turns white, then blue, then red when it begins to get blood. Numbness, tingling, and pain are associated with this entire process. Over time, oxygen deprivation to these tissues may result in open, irritated pits (ulcers) in the surface of the skin. These ulcers can lead to tissue death (gangrene) and loss of the digit. These extreme symptoms of Raynaud's disease rarely occur, except when Raynaud's is associated with other conditions like scleroderma. When Raynaud's disease leads to scleroderma, the next symptoms are usually seen within two years of the first sign of Raynaud's.

Involvement of the skin leads to swelling underneath the skin of the hands, feet, legs, arms, and face. This is followed by thickening and tightening of the skin, which becomes taut and shiny. When this tightening is severe, it may cause deformity. For example, skin tightening on the hands may cause the fingers to become permanently curled (flexed), with no ability to straighten them. Structures within the skin are damaged (including those producing hair, oil, and sweat), and skin becomes dry and scaly. Ulcers may form, with the danger of infection. Calcium deposits often appear under the skin (calcinosis).

As the skin grows tight on the face, the mouth and nose become smaller. The small mouth may interfere with eating and caring for the teeth. Blood vessels under the skin may become enlarged and obvious through the skin, appearing as purplish marks (telangiectasis).

Muscle weakness, joint pain and stiffness, and carpal tunnel syndrome are common. Carpal tunnel syndrome involves scarring in the wrist, which puts pressure on the median nerve running through that area. This causes numbness, tingling, and weakness of some of the fingers.

The tube leading from the mouth to the stomach (the esophagus) becomes stiff and scarred. Patients may experience difficulty swallowing food. The acidic contents of the stomach may be allowed to flow backwards into the esophagus (esophageal reflux), causing severe symptoms of heartburn. Inflammation of the esophagus may occur (esophagitis).

The intestine becomes sluggish in processing food, causing bloating and pain. Foods are improperly processed, resulting in diarrhea, weight loss, and anemia. Telangiectasis developing in the stomach or intestine may cause rupture and bleeding.

The lungs are affected in about 66% of all patients with scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to tightening of the tissue around the chest, inflammation of the air sacs of the lung (alveolitis), increased chance of pneumonia, and an increased risk of cancer. All of these have made lung disease the most likely cause of death in scleroderma.

The lining around the heart (pericardium) may become inflamed (pericarditis). The heart may have an increasing amount of difficulty pumping blood effectively (heart failure). Irregular heart rhythms and enlargement of the heart also occur in scleroderma.

Kidney disease is a common complication. Damage to blood vessels of the kidneys is often responsible for a huge spike in blood pressure, called malignant hypertension. The blood pressure may be so high that the patient suffers from swelling of the brain, with an extreme headache, damage to the retinas of the eyes, seizures, and failure of the heart to pump blood into the body's circulatory system. The kidneys may also stop filtering blood appropriately, leading to kidney failure. Treatments for high blood pressure and these kidney complications have greatly improved. Prior to these treatments, kidney problems were the most common cause of death for patients with scleroderma.

Other problems associated with scleroderma include painful dryness of the eyes and mouth, a low functioning thyroid gland (hypothyroidism), difficulty of male patients to achieve/sustain an erection of the penis, and enlargement and destruction of the liver.

Diagnosis

Diagnosis involves recognizing the relatively unique characteristics of scleroderma symptoms. However, some of these symptoms can accompany other connective tissue diseases. Some nonspecific laboratory tests that may indicate an inflammatory disorder (but not specifically scleroderma) include:

• Elevated results from a special red blood cell test (erythrocyte sedimentation rate)
• Decreased red blood cell count (anemia)
• Positive tests for certain antibodies (including rheumatoid factor, anti-Scl-70 antibodies, anticentromere antibodies, and antinuclear antibodies).

Other tests can be performed to evaluate the extent of the disease. These can include:

• A test that reveals information about the electrical system of the heart (an electrocardiogram)
• Lung function tests
• X-ray studies of the gastrointestinal tract
• Various blood tests to study kidney functions.

Treatment

There is no cure for scleroderma. A drug called D-penicillamine has been used to interfere with the defective collagen. It is believed to help decrease the degree of skin thickening and tightening, and to slow the progress of the disease in other organs. Steroid medications have been used to interfere with the inflammatory process in scleroderma. Other drugs have been studied that reduce the activity of the immune system (immunosuppressants), including azathioprine, colchicine, interferon, and 5-fluorouracil. Because they can have serious side effects, these medications are only used for the most severe cases of scleroderma.

The various complications of scleroderma are treated individually. Raynaud's disease requires that patients try to keep their hands and feet warm constantly, and avoid situations where they will be exposed to cold temperatures. Thick ointments and creams are used to treat dry skin. Exercise and massage may help joint involvement, and may help patients retain more movement despite skin tightening. Skin ulcers will need prompt attention and may require antibiotics. Patients with esophageal reflux will be advised to eat small meals more often. They should also avoid foods that may make the reflux worse, like spicy foods and caffeine-containing items like coffee, tea, and chocolate. Medications may be given to treat heartburn. Patients must be monitored for the development of high blood pressure, and promptly and aggressively treated with appropriate medications. When fluid accumulates due to heart failure, diuretic medications can be given to help get rid of the excess fluid.

Prognosis

The prognosis for patients with scleroderma varies. Some patients, in fact, have a very limited form of the disease and only their skin is affected. This is called morphea. These patients have a very good prognosis. Other patients with a cluster of symptoms called the CREST syndrome also have a relatively good prognosis. CREST stands for:

• C=Calcinosis
• R=Raynaud's disease
• E=Esophageal dysmotility (stiffness and malfunctioning of the esophagus)
• S=Sclerodactyly (thick, hard, rigid skin over the fingers)
• T=Telangiectasis.

In general, patients with very widespread skin involvement have the worse prognosis. This level of disease seems to be accompanied by involvement of other organs and the most severe complications. Although women are more commonly stricken with scleroderma, males more often die of the disease. The most common causes of death include heart, kidney, and lung diseases. About 65% of all patients survive 10 years or more following a diagnosis of scleroderma.

Prevention

There are no known ways to prevent scleroderma. People can try to decrease exposure to those substances associated with high rates of the disease. These include silica dust, polyvinyl chloride, benzine, toluene, epoxy resins, and silicone breast implants.

Key Terms

Autoimmune disorder

A disorder in which the body's immune cells mistake the body's own tissues as foreign invaders; the immune cells then work to destroy tissues in the body.

Collagen

A protein fiber that is an important component of connective tissue.

Connective tissue

A group of tissues responsible for support throughout the body; includes cartilage, bone, fat, tissue underlying skin, and tissues that support organs, blood vessels, and nerves throughout the body.

Fibrosis

The abnormal development of fibrous tissue; scarring.

Inflammation

The body's response to tissue damage; includes hotness, swelling, redness, and pain in the affected part.

Sclerosis

Hardening.

Further Reading

For Your Information

Books

• Aaseng, Nathan. Autoimmune Diseases. New York: F. Watts, 1995.
• Gilliland, Bruce C. "Systemic Sclerosis (Scleroderma)." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

  Periodicals

• Legerton, C.W. III, et al. "Systemic Sclerosis: Clinical Management of Its Major Complications." Rheumatic Disease Clinics of North America, 17 (221)(1998).
• Ostezan, Laura B., and Jeffrey P. Callen. "Cutaneous Manifestations of Selected Rheumatologic Diseases." American Family Physician, 53 (5)(April 1996): 1625+.

  Organizations

• American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404) 633-3777. http://www.rheumatology.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.