Scleroderma
Scleroderma
Definition
Scleroderma is a 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). There are two major forms of the disorder. The type known as localized scleroderma mainly affects the skin. Systemic scleroderma, which is also called systemic sclerosis, affects the smaller blood vessels and internal organs of the body.
Description
Scleroderma is an autoimmune disorder, which means that the body's immune system turns against itself. In scleroderma, there is an overproduction of abnormal collagen (a type of protein fiber present in connective tissue). This collagen accumulates throughout the body, causing hardening (sclerosis), scarring (fibrosis), and other damage. The damage may affect the appearance of the skin, or it may involve only the internal organs. The symptoms and severity of scleroderma vary from person to person.
Scleroderma occurs in all races of people all over the world, but it affects about four females for every male. Among children, localized scleroderma is more common, and systemic sclerosis is comparatively rare. Most patients with systemic sclerosis are diagnosed between ages 30 and 50. In the United States, about 300,000 people have scleroderma. Young African-American women and Native Americans of the Choctaw tribe have especially high rates of the disease. In 2003, researchers reported that they had identified 12 different genetic markers associated with scleroderma in the Choctaw population.
Causes and symptoms
The cause of scleroderma is still a puzzle. Although the accumulation of collagen appears to be a hallmark of the disease, researchers do not know why it occurs. Some theories suggest that damage to blood vessels may cause the tissues of the body to receive an inadequate amount of oxygen—a condition called ischemia. Some researchers believe that the resulting damage causes the immune system to overreact, producing an autoimmune disorder. According to this theory of scleroderma, the immune system gears up to fight an invader, but no invader is actually present. Cells in the immune system called antibodies react to the body's own tissues as if they were foreign. The antibodies turn against the already damaged blood vessels and 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 have no recognizable triggering event. Some cases, however, have been traced to exposure to toxic (poisonous) substances. For example, coal miners and gold miners, who are exposed to high levels of silica dust, have above-average rates of scleroderma. Other chemicals associated with the disease include polyvinyl chloride, benzine, toluene, and epoxy resins. In 1981, 20,000 people in Spain were stricken with a syndrome similar to scleroderma when their cooking oil was accidentally contaminated. Certain medications, especially a drug used in cancer treatment called bleomycin (Blenoxane), may lead to scleroderma. Some claims of a scleroderma-like illness have been made by women with silicone breast implants, but a link has not been proven in numerous studies.
Symptoms of systemic scleroderma
A condition called Raynaud's phenomenon is the first symptom in about 95% of all patients with systemic scleroderma. In Raynaud's phenomenon, the blood vessels of the fingers and/or toes (the digits) react to cold in an abnormal way. The vessels clamp down, preventing blood flow to the tip of the digit. Eventually, the flow is cut off to the entire finger or toe. Over time, oxygen deprivation may result in open ulcers on the skin surface. These ulcers can lead to tissue death (gangrene ) and loss of the digit. When Raynaud's phenomenon is the first sign of scleroderma, the next symptoms usually appear within two years.
SKIN AND EXTREMITIES. Involvement of the skin leads to swelling underneath the skin of the hands, feet, legs, arms, and face. Swelling is followed by thickening and tightening of the skin, which becomes taut and shiny. Severe tightening may lead to abnormalities. For example, tightening of the skin on the hands may cause the fingers to become permanently curled (flexed). Structures within the skin are damaged (including those producing hair, oil, and sweat), and the skin becomes dry and scaly. Ulcers may form, with the danger of infection. Calcium deposits often appear under the skin.
In systemic scleroderma, the mouth and nose may become smaller as the skin on the face tightens. The small mouth may interfere with eating and dental hygiene. Blood vessels under the skin may become enlarged and show through the skin, appearing as purplish marks or red spots. This chronic dilation of the small blood vessels is called telangiectasis.
Muscle weakness, joint pain and stiffness, and carpal tunnel syndrome are common in scleroderma. Carpal tunnel syndrome involves scarring in the wrist, which puts pressure on the median nerve running through that area. Pressure on the nerve causes numbness, tingling, and weakness in some of the fingers.
DIGESTIVE TRACT. The tube leading from the mouth to the stomach (the esophagus) becomes stiff and scarred. Patients may have trouble swallowing food. The acid contents of the stomach may start to flow backward into the esophagus (esophageal reflux), causing a very uncomfortable condition known as heartburn. The esophagus may also become inflamed.
The intestine becomes sluggish in processing food, causing bloating and pain. Foods are not digested properly, resulting in diarrhea, weight loss, and anemia. Telangiectasis in the stomach or intestine may cause rupture and bleeding.
RESPIRATORY AND CIRCULATORY SYSTEMS. The lungs are affected in about 66% of all people with systemic scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to tightening of the tissue around the chest, inflammation of the air sacs in the lungs (alveolitis), increased risk of pneumonia, and an increased risk of cancer. For these reasons, lung disease is the most likely cause of death associated with scleroderma.
The lining around the heart (pericardium) may become inflamed. The heart may have greater difficulty pumping blood effectively (heart failure). Irregular heart rhythms and enlargement of the heart also occur in scleroderma.
Kidney disease is another common complication. Damage to blood vessels in the kidneys often causes a major rise in the person's blood pressure. The blood pressure may be so high that there is swelling of the brain, causing severe headaches, 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 and go into failure. Treatments for high blood pressure have greatly improved these kidney complications. Before these treatments were available, kidney problems were the most common cause of death for people with scleroderma.
Other problems associated with scleroderma include painful dryness of the eyes and mouth, enlargement and destruction of the liver, and a low-functioning thyroid gland.
Diagnosis
Diagnosis of scleroderma is complicated by the fact that some of its symptoms can accompany other connective-tissue diseases. The most important symptom is thickened or hardened skin on the fingers, hands, forearms, or face. This symptom is found in 98% of people with scleroderma. It can be detected in the course of a physical examination. The person's medical history may also contain important clues, such as exposure to toxic substances on the job. There are a number of nonspecific laboratory tests on blood samples that may indicate the presence of an inflammatory disorder (but not specifically scleroderma). The antinuclear antibody (ANA) test is positive in more than 95% of people with scleroderma.
Other tests can be performed to evaluate the extent of the disease. These include a test of the electrical system of the heart (an electrocardiogram), lung-function tests, and x-ray studies of the gastrointestinal tract. Various blood tests can be given to study kidney function.
Treatment
Mainstream treatments
As of early 2004 there is no cure for scleroderma. A drug called D-penicillamine has been used to interfere with the abnormal 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. Taking vitamin D and using ultraviolet light may be helpful for localized scleroderma. One group of British researchers reported in 2003 that long-wavelength ultraviolet A light is particularly effective in treating localized scleroderma. Corticosteroids have been used to treat joint pain, muscle cramps, and other symptoms of inflammation. Other drugs have been studied that reduce the activity of the immune system (immunosuppressants). Because these medications can have serious side effects, they are used in only the most severe cases of scleroderma.
The various complications of scleroderma are treated individually. Raynaud's phenomenon requires that people try to keep their hands and feet warm constantly. Nifedipine is a medication that is sometimes given to help control Raynaud's. Thick ointments and creams are used to treat dry skin. Exercise and massage may help joint involvement; they may also help people retain more movement despite skin tightening. An exercise regimen for stretching the mouth opening has been reported to be a helpful alternative to surgery in managing this condition. Skin ulcers need prompt attention and may require antibiotics. People with esophageal reflux will be advised to eat small amounts more often, rather than several large meals a day. They should also avoid spicy foods and items containing caffeine. Some patients with esophageal reflux have been successfully treated with surgery. Acid-reducing medications may be given for heartburn. People must be monitored for the development of high blood pressure. If found, they should be promptly treated with appropriate medications, usually ACE inhibitors or other vasodilators. When fluid accumulates due to heart failure, diuretics can be given to get rid of the excess fluid.
Patients with scleroderma may also benefit from some form of counseling or psychotherapy, as they are at increased risk of depression. One study found that 46% of the patients in its sample met the criteria for a depressive disorder.
Alternative treatments
One alternative therapy that some naturopaths have used in treating patients with scleroderma is superoxide dismutase (SOD), an antioxidant enzyme used in its injectable form. More research, however, needs to be done on the benefits of this treatment.
Prognosis
The prognosis for people with scleroderma varies. Some have a very limited form of the disease called morphea, which affects only the skin. These individuals have a very good prognosis. Other people have a subtype of systemic scleroderma called limited scleroderma. For them, the prognosis is relatively good. Limited scleroderma is characterized by limited involvement of the patient's skin and a cluster of five symptoms called the CREST syndrome. CREST stands for:
- C = Calcinosis
- R = Raynaud's disease (phenomenon)
- E = Esophageal dysmotility (stiffness and malfunctioning of the esophagus)
- S = Sclerodactyly (thick, hard, rigid skin over the fingers)
- T = Telangiectasias
In general, people with very widespread skin involvement have the worst prognosis. This level of disease is usually accompanied by involvement of other organs and the most severe complications. Although women are more commonly stricken with scleroderma, men more often die of the disease. The two factors that negatively affect survival are male sex and older age at diagnosis. The most common causes of death include heart, kidney, and lung diseases. About 65% of all patients survive 11 years or more following a diagnosis of scleroderma.
As of early 2004 there are no known ways to prevent scleroderma. People can try to decrease occupational exposure to high-risk substances.
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— The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
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.
Limited scleroderma— A subtype of systemic scleroderma with limited skin involvement. It is somestimes called the CREST form of scleroderma, after the initials of its five major symptoms.
Localized scleroderma— Thickening of the skin from overproduction of collagen.
Morphea— The most common form of localized scleroderma.
Raynaud phenomenon/Raynaud disease— A condition in which blood flow to the body's tissues is reduced by a malfunction of the nerves that regulate the constriction of blood vessels. When attacks of Raynaud's occur in the absence of other medical conditions, it is called Raynaud disease. When attacks occur as part of a disease (as in scleroderma), it is called Raynaud phenomenon.
Sclerosis— Hardening.
Systemic sclerosis— A rare disorder that causes thickening and scarring of multiple organ systems.
Telangiectasias— Very small arteriovenous malformations, or connections between the arteries and veins. The result is small red spots on the skin known as "spider veins."
Resources
BOOKS
Beers, Mark H., MD, and Robert Berkow, MD., editors. "Systemic Sclerosis." The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine, Part II: CAM Therapies for Specific Conditions: Scleroderma. New York: Simon and Schuster, 2002.
PERIODICALS
Dawe, R. S. "Ultraviolet A1 Phototherapy." British Journal of Dermatology 148 (April 2003): 626-637.
Hill, C. L., A. M. Nguyen, D. Roder, and P. Roberts-Thomson. "Risk of Cancer in Patients with Scleroderma: A Population Based Cohort Study." Annals of the Rheumatic Diseases 62 (August 2003): 728-731.
Matsuura, E., A. Ohta, F. Kanegae, et al. "Frequency and Analysis of Factors Closely Associated with the Development of Depressive Symptoms in Patients with Scleroderma." Journal of Rheumatology 30 (August 2003): 1782-1787.
Mayes, M. D., J. V. Lacey, Jr., J. Beebe-Dimmer, et al. "Prevalence, Incidence, Survival, and Disease Characteristics of Systemic Sclerosis in a Large US Population." Arthritis and Rheumatism 48 (August 2003): 2246-2255.
Pizzo, G., G. A. Scardina, and P. Messina. "Effects of a Nonsurgical Exercise Program on the Decreased Mouth Opening in Patients with Systemic Scleroderma." Clinical Oral Investigations 7 (September 2003): 175-178.
Zhou, X., F. K. Tan, N. Wang, et al. "Genome-Wide Association Study for Regions of Systemic Sclerosis Susceptibility in a Choctaw Indian Population with High Disease Prevalence." Arthritis and Rheumatism 48 (September 2003): 2585-2592.
ORGANIZATIONS
American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404) 633-3777. 〈http://www.rheumatology.org〉.
National Organization for Rare Disorders, Inc. (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813. (800) 999-6673 or (203) 744-0100. 〈http://www.rarediseases.org〉.
Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (978) 463-5843 or (800) 722-HOPE. Fax: (978) 463-5809. 〈http://www.scleroderma.org〉.
Scleroderma
Scleroderma
Definition
Scleroderma is a 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). There are two major forms of the disorder. The type known as localized scleroderma mainly affects the skin. Systemic scleroderma, which is also called systemic sclerosis, affects the smaller blood vessels and internal organs of the body.
Description
Scleroderma is an autoimmune disorder, which means that the body's immune system turns against itself. In scleroderma, there is an overproduction of abnormal collagen (a type of protein fiber present in connective tissue). This collagen accumulates throughout the body, causing hardening (sclerosis), scarring (fibrosis), and other damage. The damage may affect the appearance of the skin, or it may involve only the internal organs. The symptoms and severity of scleroderma vary from person to person.
Scleroderma occurs in all races of people all over the world, but it affects about four females for every male. Among children, localized scleroderma is more common, and systemic sclerosis is comparatively rare. Most patients with systemic sclerosis are diagnosed between ages 30 and 50. In the United States, about 300,000 people have scleroderma. Young African American women and Native Americans of the Choctaw tribe have especially high rates of the disease. In 2003, researchers reported that they had identified 12 different genetic markers associated with scleroderma in the Choctaw population.
Causes and symptoms
The cause of scleroderma is still a puzzle. Although the accumulation of collagen appears to be a hallmark of the disease, researchers do not know why it occurs. Some theories suggest that damage to blood vessels may cause the tissues of the body to receive an inadequate amount of oxygen—a condition called ischemia . Some researchers believe that the resulting damage causes the immune system to overreact, producing an autoimmune disorder. According to this theory of scleroderma, the immune system gears up to fight an invader, but no invader is actually present. Cells in the immune system called antibodies react to the body's own tissues as if they were foreign. The antibodies turn against the already damaged blood vessels and 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 have no recognizable triggering event. Some cases, however, have been traced to exposure to toxic (poisonous) substances. For example, coal miners and gold miners, who are exposed to high levels of silica dust, have above-average rates of scleroderma. Other chemicals associated with the disease include polyvinyl chloride, benzine, toluene, and epoxy resins. In 1981, 20,000 people in Spain were stricken with a syndrome similar to scleroderma when their cooking oil was accidentally contaminated. Certain medications, especially a drug used in cancer treatment called bleomycin (Blenoxane), may lead to scleroderma. Some claims of a scleroderma-like illness have been made by women with silicone breast implants , but a link has not been proven in numerous studies.
Symptoms of systemic scleroderma
A condition called Raynaud's phenomenon is the first symptom in about 95% of all patients with systemic scleroderma. In Raynaud's phenomenon, the blood vessels of the fingers and/or toes (the digits) react to cold in an abnormal way. The vessels clamp down, preventing blood flow to the tip of the digit. Eventually, the flow is cut off to the entire finger or toe. Over time, oxygen deprivation may result in open ulcers on the skin surface. These ulcers can lead to tissue death (gangrene ) and loss of the digit. When Raynaud's phenomenon is the first sign of scleroderma, the next symptoms usually appear within two years.
skin and extremities Involvement of the skin leads to swelling underneath the skin of the hands, feet, legs, arms, and face. Swelling is followed by thickening and tightening of the skin, which becomes taut and shiny. Severe tightening may lead to abnormalities. For example, tightening of the skin on the hands may cause the fingers to become permanently curled (flexed). Structures within the skin are damaged (including those producing hair, oil, and sweat), and the skin becomes dry and scaly. Ulcers may form, with the danger of infection. Calcium deposits often appear under the skin.
In systemic scleroderma, the mouth and nose may become smaller as the skin on the face tightens. The small mouth may interfere with eating and dental hygiene . Blood vessels under the skin may become enlarged and show through the skin, appearing as purplish marks or red spots. This chronic dilation of the small blood vessels is called telangiectasis.
Muscle weakness, joint pain and stiffness, and carpal tunnel syndrome are common in scleroderma. Carpal tunnel syndrome involves scarring in the wrist, which puts pressure on the median nerve running through that area. Pressure on the nerve causes numbness, tingling, and weakness in some of the fingers.
digestive tract The tube leading from the mouth to the stomach (the esophagus) becomes stiff and scarred. Patients may have trouble swallowing food. The acid contents of the stomach may start to flow backward into the esophagus (esophageal reflux), causing a very uncomfortable condition known as heartburn . The esophagus may also become inflamed.
The intestine becomes sluggish in processing food, causing bloating and pain. Foods are not digested properly, resulting in diarrhea , weight loss , and anemia . Telangiectasis in the stomach or intestine may cause rupture and bleeding.
respiratory and circulatory systems The lungs are affected in about 66% of all people with systemic scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to tightening of the tissue around the chest, inflammation of the air sacs in the lungs (alveolitis), increased risk of pneumonia , and an increased risk of cancer. For these reasons, lung disease is the most likely cause of death associated with scleroderma.
The lining around the heart (pericardium) may become inflamed. The heart may have greater difficulty pumping blood effectively (heart failure). Irregular heart rhythms and enlargement of the heart also occur in scleroderma.
Kidney disease is another common complication. Damage to blood vessels in the kidneys often causes a major rise in the person's blood pressure . The blood pressure may be so high that there is swelling of the brain, causing severe headaches , 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 and go into failure. Treatments for high blood pressure have greatly improved these kidney complications. Before these treatments were available, kidney problems were the most common cause of death for people with scleroderma.
Other problems associated with scleroderma include painful dryness of the eyes and mouth, enlargement and destruction of the liver, and a low-functioning thyroid gland.
Diagnosis
Diagnosis of scleroderma is complicated by the fact that some of its symptoms can accompany other connective-tissue diseases. The most important symptom is thickened or hardened skin on the fingers, hands, forearms, or face. This symptom is found in 98% of people with scleroderma. It can be detected in the course of a physical examination. The person's medical history may also contain important clues, such as exposure to toxic substances on the job. There are a number of nonspecific laboratory tests on blood samples that may indicate the presence of an inflammatory disorder (but not specifically scleroderma). The antinuclear antibody (ANA) test is positive in more than 95% of people with scleroderma.
Other tests can be performed to evaluate the extent of the disease. These include a test of the electrical system of the heart (an electrocardiogram), lung-function tests, and x-ray studies of the gastrointestinal tract. Various blood tests can be given to study kidney function.
Treatment
Mainstream treatments
As of early 2004 there is no cure for scleroderma. A drug called D-penicillamine has been used to interfere with the abnormal 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. Taking vitamin D and using ultraviolet light may be helpful for localized scleroderma. One group of British researchers reported in 2003 that long-wavelength ultraviolet A light is particularly effective in treating localized scleroderma. Corticosteroids have been used to treat joint pain, muscle cramps, and other symptoms of inflammation. Other drugs have been studied that reduce the activity of the immune system (immunosuppressants). Because these medications can have serious side effects, they are used in only the most severe cases of scleroderma.
The various complications of scleroderma are treated individually. Raynaud's phenomenon requires that people try to keep their hands and feet warm constantly. Nifedipine is a medication that is sometimes given to help control Raynaud's. Thick ointments and creams are used to treat dry skin . Exercise and massage may help joint involvement; they may also help people retain more movement despite skin tightening. An exercise regimen for stretching the mouth opening has been reported to be a helpful alternative to surgery in managing this condition. Skin ulcers need prompt attention and may require antibiotics . People with esophageal reflux will be advised to eat small amounts more often, rather than several large meals a day. They should also avoid spicy foods and items containing caffeine . Some patients with esophageal reflux have been successfully treated with surgery. Acid-reducing medications may be given for heartburn. People must be monitored for the development of high blood pressure. If found, they should be promptly treated with appropriate medications, usually ACE inhibitors or other vasodilators. When fluid accumulates due to heart failure, diuretics can be given to get rid of the excess fluid.
Patients with scleroderma may also benefit from some form of counseling or psychotherapy, as they are at increased risk of depression . One study found that 46% of the patients in its sample met the criteria for a depressive disorder.
Alternative treatments
One alternative therapy that some naturopaths have used in treating patients with scleroderma is superoxide dismutase (SOD), an antioxidant enzyme used in its injectable form. More research, however, needs to be done on the benefits of this treatment.
Prognosis
The prognosis for people with scleroderma varies. Some have a very limited form of the disease called morphea, which affects only the skin. These individuals have a very good prognosis. Other people have a subtype of systemic scleroderma called limited scleroderma. For them, the prognosis is relatively good. Limited scleroderma is characterized by limited involvement of the patient's skin and a cluster of five symptoms called the CREST syndrome. CREST stands for:
- C=Calcinosis
- R=Raynaud's disease (phenomenon)
- E=Esophageal dysmotility (stiffness and malfunctioning of the esophagus)
- S=Sclerodactyly (thick, hard, rigid skin over the fingers)
- T=Telangiectasias
In general, people with very widespread skin involvement have the worst prognosis. This level of disease is usually accompanied by involvement of other organs and the most severe complications. Although women are more commonly stricken with scleroderma, men more often die of the disease. The two factors that negatively affect survival are male sex and older age at diagnosis. The most common causes of death include heart, kidney, and lung diseases. About 65% of all patients survive 11 years or more following a diagnosis of scleroderma.
KEY TERMS
Collagen —The main supportive protein of cartilage, connective tissue, tendon, skin, and bone.
Connective tissue —A group of tissues responsible for support throughout the body.
Fibrosis —The abnormal development of fibrous tissue; scarring.
Limited scleroderma —A subtype of systemic scleroderma with limited skin involvement. It is somestimes called the CREST form of scleroderma, after the initials of its five major symptoms.
Localized scleroderma —Thickening of the skin from overproduction of collagen.
Morphea —The most common form of localized scleroderma.
Raynaud phenomenon/Raynaud disease —A condition in which blood flow to the body's tissues is reduced by a malfunction of the nerves that regulate the constriction of blood vessels.
Sclerosis —Hardening.
Systemic sclerosis —A rare disorder that causes thickening and scarring of multiple organ systems.
Telangiectasias —Very small arteriovenous malformations,
or connections between the arteries and veins. The result is small red spots on the skin known as “spider veins.”
There are no known ways to prevent scleroderma. People can try to decrease occupational exposure to high-risk substances.
Resources
books
Beers, Mark H., MD, and Robert Berkow, MD., editors. “Systemic Sclerosis.” The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Dr. Kenneth R. The Best Alternative Medicine, Part II: CAM Therapies for Specific Conditions: Scleroderma. New York: Simon and Schuster, 2002.
periodicals
Dawe, R. S. “Ultraviolet A1 Phototherapy.” British Journal of Dermatology 148 (April 2003): 626–637.
Hill, C. L., A. M. Nguyen, D. Roder, and P. Roberts Thomson. “Risk of Cancer in Patients with Scleroderma: A Population Based Cohort Study.” Annals of the Rheumatic Diseases 62 (August 2003): 728–731.
Matsuura, E., A. Ohta, F. Kanegae, et al. “Frequency and Analysis of Factors Closely Associated with the Development of Depressive Symptoms in Patients with Scleroderma.” Journal of Rheumatology 30 (August 2003): 1782–1787.
Mayes, M. D., J. V. Lacey, Jr., J. Beebe-Dimmer, et al. “Prevalence, Incidence, Survival, and Disease Characteristics of Systemic Sclerosis in a Large US Population.” Arthritis and Rheumatism 48 (August 2003):2246–2255.
Pizzo, G., G. A. Scardina, and P. Messina. “Effects of a Nonsurgical Exercise Program on the Decreased Mouth Opening in Patients with Systemic Scleroderma.” Clinical Oral Investigations 7 (September 2003):175–178.
Zhou, X., F. K. Tan, N. Wang, et al. “Genome-Wide Association Study for Regions of Systemic Sclerosis Susceptibility in a Choctaw Indian Population with High Disease Prevalence.” Arthritis and Rheumatism 48 (September 2003): 2585–2592.
organizations
American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404) 633-3777. http://www.rheumatology.org.
National Organization for Rare Disorders, Inc. (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813. (800) 999-6673 or (203) 744-0100. http://www.rarediseases.org.
Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (978) 463-5843 or (800) 722-HOPE. Fax:(978) 463-5809. http://www.scleroderma.org.
Rebecca J. Frey Ph.D.
Scleroderma
Scleroderma
Definition
Scleroderma is a 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). There are two major forms of the disorder. The type known as localized scleroderma mainly affects the skin. Systemic scleroderma, which is also called systemic sclerosis, affects the smaller blood vessels and internal organs of the body.
Description
Scleroderma is an autoimmune disorder, which means that the body's immune system turns against itself. In scleroderma, there is an overproduction of abnormal collagen (a type of protein fiber present in connective tissue). This collagen accumulates throughout the body, causing hardening (sclerosis), scarring (fibrosis), and other damage. The damage may affect the appearance of the skin, or it may involve only the internal organs. The symptoms and severity of scleroderma vary from person to person.
Genetic profile
The role of genetics in the transmission in scleroderma is unclear. Some cases clearly run in families, but most occur in people without any family history of the disease.
Demographics
Scleroderma occurs in all races of people all over the world, but it affects about four females for every male. Among children, localized scleroderma is more common, and systemic sclerosis is comparatively rare. Most patients with systemic sclerosis are diagnosed between ages 30 and 50. In the United States, about 300,000 people have scleroderma. Young African American women and Native Americans of the Choctaw tribe have especially high rates of the disease.
Signs and symptoms
The cause of scleroderma is still uncertain. Although the accumulation of collagen appears to be a hallmark of the disease, researchers do not know why it occurs. Some theories suggest that damage to blood vessels may cause the tissues of the body to receive an inadequate amount of oxygen–a condition called ischemia. Some researchers believe that the resulting damage causes the immune system to overreact, producing an autoimmune disorder. According to this theory of scleroderma, the immune system gears up to fight an invader, but no invader is actually present. Cells in the immune system, called antibodies, react to the body's own tissues as if they were foreign. The antibodies turn against the already damaged blood vessels and 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 have no recognizable triggering event. Some cases, however, have been traced to exposure to toxic (poisonous) substances. For example, coal miners and gold miners, who are exposed to high levels of silica dust, have above-average rates of scleroderma. Other chemicals associated with the disease include polyvinyl chloride, benzine, toluene, and epoxy resins. In 1981, 20,000 people in Spain were stricken with a syndrome similar to scleroderma when their cooking oil was accidentally contaminated. Certain medications, especially a drug used in cancer treatment called bleomycin (Blenoxane), may lead to scleroderma. Some claims of a scleroderma-like illness have been made by women with silicone breast implants, but a link has not been proven in numerous studies.
Symptoms of systemic scleroderma
A condition called Raynaud's phenomenon is the first symptom in about 95% of all patients with systemic scleroderma. In Raynaud's phenomenon, the blood vessels of the fingers and/or toes (the digits) react to cold in an abnormal way. The vessels clamp down, preventing blood flow to the tip of the digit. Eventually, the flow is cut off to the entire finger or toe. Over time, oxygen deprivation may result in open ulcers on the skin surface. These ulcers can lead to tissue death (gangrene) and loss of the digit. When Raynaud's phenomenon is the first sign of scleroderma, the next symptoms usually appear within two years.
SKIN AND EXTREMITIES Involvement of the skin leads to swelling underneath the skin of the hands, feet, legs, arms, and face. Swelling is followed by thickening and tightening of the skin, which becomes taut and shiny. Severe tightening may lead to abnormalities. For example, tightening of the skin on the hands may cause the fingers to become permanently curled (flexed). Structures within the skin are damaged (including those producing hair, oil, and sweat), and the skin becomes dry and scaly. Ulcers may form, with the danger of infection. Calcium deposits often appear under the skin.
In systemic scleroderma, the mouth and nose may become smaller as the skin on the face tightens. The small mouth may interfere with eating and dental hygiene. Blood vessels under the skin may become enlarged and show through the skin, appearing as purplish marks or red spots. This chronic dilation of the small blood vessels is called telangiectasis.
Muscle weakness, joint pain and stiffness, and carpal tunnel syndrome are common in scleroderma. Carpal tunnel syndrome involves scarring in the wrist, which puts pressure on the median nerve running through that area. Pressure on the nerve causes numbness, tingling, and weakness in some of the fingers.
DIGESTIVE TRACT The tube leading from the mouth to the stomach (the esophagus) becomes stiff and scarred. Patients may have trouble swallowing food. The acid contents of the stomach may start to flow backward into the esophagus (esophageal reflux), causing a very uncomfortable condition known as heartburn. The esophagus may also become inflamed.
The intestine becomes sluggish in processing food, causing bloating and pain. Foods are not digested properly, resulting in diarrhea, weight loss, and anemia. Telangiectasis in the stomach or intestine may cause rupture and bleeding.
RESPIRATORY AND CIRCULATORY SYSTEMS The lungs are affected in about 66% of all people with systemic scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to tightening of the tissue around the chest, inflammation of the air sacs in the lungs (alveolitis), increased risk of pneumonia, and an increased risk of cancer. For these reasons, lung disease is the most likely cause of death associated with scleroderma.
The lining around the heart (pericardium) may become inflamed. The heart may have greater difficulty pumping blood effectively (heart failure). Irregular heart rhythms and enlargement of the heart also occur in scleroderma.
Kidney disease is another common complication. Damage to blood vessels in the kidneys often causes a major rise in the person's blood pressure. The blood pressure may be so high that there is swelling of the brain, causing severe headaches, 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 and go into failure. Treatments for high blood pressure have greatly improved these kidney complications. Before these treatments were available, kidney problems were the most common cause of death for people with scleroderma.
Other problems associated with scleroderma include painful dryness of the eyes and mouth, enlargement and destruction of the liver, and a low-functioning thyroid gland.
Diagnosis
Diagnosis of scleroderma is complicated by the fact that some of its symptoms can accompany other connective-tissue diseases. The most important symptom is thickened or hardened skin on the fingers, hands, forearms, or face. This is found in 98% of people with scleroderma. It can be detected in the course of a physical examination. The person's medical history may also contain important clues, such as exposure to toxic substances on the job. There are a number of nonspecific laboratory tests on blood samples that may indicate the presence of an inflammatory disorder (but not specifically scleroderma). The antinuclear antibody (ANA) test is positive in more than 95% of people with scleroderma.
Other tests can be performed to evaluate the extent of the disease. These include a test of the electrical system of the heart (an electrocardiogram), lung-function tests, and x ray studies of the gastrointestinal tract. Various blood tests can be given to study kidney function.
Treatment and management
At this time there is no cure for scleroderma. A drug called D-penicillamine has been used to interfere with the abnormal 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. Taking vitamin D and using ultraviolet light may be helpful in treating localized scleroderma. Corticosteroids have been used to treat joint pain, muscle cramps, and other symptoms of inflammation. Other drugs have been studied that reduce
the activity of the immune system (immunosuppressants). Because these medications can have serious side effects, they are used in only the most severe cases of scleroderma.
The various complications of scleroderma are treated individually. Raynaud's phenomenon requires that people try to keep their hands and feet warm constantly. Nifedipine is a medication that is sometimes given to help control Raynaud's. Thick ointments and creams are used to treat dry skin. Exercise and massage may help joint involvement; they may also help people retain more movement despite skin tightening. Skin ulcers need prompt attention and may require antibiotics. People with esophageal reflux will be advised to eat small amounts more often, rather than several large meals a day. They should also avoid spicy foods and items containing caffeine. Some patients with esophageal reflux have been successfully treated with surgery. Acid-reducing medications may be given for heartburn. People must be monitored for the development of high blood pressure. If found, they should be promptly treated with appropriate medications, usually ACE inhibitors or other vasodilators. When fluid accumulates due to heart failure, diuretics can be given to get rid of the excess fluid.
Prognosis
The prognosis for people with scleroderma varies. Some have a very limited form of the disease called morphea, which affects only the skin. These individuals have a very good prognosis. Other people have a subtype of systemic scleroderma called limited scleroderma. For them, the prognosis is relatively good. Limited scleroderma is characterized by limited involvement of the patient's skin and a cluster of five symptoms called the CREST syndrome. CREST stands for:
- C=Calcinosis
- R=Raynaud's disease (phenomenon)
- E=Esophageal dysmotility (stiffness and malfunctioning of the esophagus)
- S=Sclerodactyly (thick, hard, rigid skin over the fingers)
- T=Telangiectasis
In general, people with very widespread skin involvement have the worst prognosis. This level of disease is usually accompanied by involvement of other organs and the most severe complications. Although women are more commonly stricken with scleroderma, men 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.
There are no known ways to prevent scleroderma. People can try to decrease occupational exposure to high-risk substances.
Resources
BOOKS
Aaseng, Nathan. Autoimmune Diseases. New York: F. Watts, 1995.
Gilliland, Bruce C. "Systemic Sclerosis (Scleroderma)." In Harrison's Principles of Internal Medicine, ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.
"Systemic Sclerosis." The Merck Manual of Diagnosis and Therapy, ed. Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 1999.
PERIODICALS
De Keyser, F., et al. "Occurrence of Scleroderma in Monozygotic Twins." Journal of Rheumatology 27 (September 2000): 2267-2269.
Englert, H., et al. "Familial Risk Estimation in Systemic Sclerosis." Australia and New Zealand Journal of Medicine 29 (February 1999): 36-41.
Legerton, C. W. III, et al. "Systemic Sclerosis: Clinical Management of Its Major Complications." Rheumatic Disease Clinics of North America, 17, no. 221 (1998).
Saito, S., et al. "Genetic and Immunologic Features Associated with Scleroderma-like Syndrome of TSK Mice. Current Rheumatology Reports 1 (October 1999): 34-37.
ORGANIZATIONS
American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404) 633-3777. <http://www.rheumatology.org>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (978) 463-5843 or (800) 722-HOPE. Fax: (978) 463-5809. <http://www.scleroderma.org.>.
Rebecca J. Frey, PhD