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Scleroderma

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Synonyms of Scleroderma

Disorder Subdivisions

General Discussion

Scleroderma is a rare autoimmune connective tissue disorder characterized by abnormal thickening of the skin. Connective tissue is composed of collagen, which supports and binds other body tissues. There are several types of scleroderma. Some types affect certain, specific parts of the body, while other types can affect the whole body and internal organs (systemic). Scleroderma is also known as progressive systemic sclerosis. The exact cause of scleroderma is unknown.

Symptoms

The early symptoms of scleroderma vary considerably. Distinctive abnormalities on the skin (cutaneous lesions) usually appear later in the course of the disease. Common symptoms of scleroderma may include painful joints (arthralgia), morning stiffness, fatigue, and/or weight loss. The intermittent loss (triggered by cold temperatures) of blood supply to the fingers, toes, nose, and/or ears (Raynaud's phenomenon) is an early and frequent complaint of people with scleroderma.

People with scleroderma have areas of skin that become hard and leathery (indurated). These areas of hardness are widespread and typically appear on both sides of the body. Eventually, tissue loss (atrophy) occurs and the skin becomes more highly colored (hyperpigmentation).

Morphea, or localized scleroderma, usually begins between the ages of 20 to 50 years as patches of yellowish or ivory-colored rigid, dry skin (inflammatory stage). These are followed by the appearance of firm, hard, oval-shaped plaques with ivory centers that are encircled by a violet ring. These spots generally appear on the trunk, face, and/or extremities. Many patients with localized morphea improve spontaneously (without treatment). Generalized morphea is more rare and serious, and involves the skin (dermis) but not the internal organs.

Linear scleroderma appears as a band-like thickening of skin on the arms or legs. This type of scleroderma is most likely to be on one side of the body (unilateral) but may be on both sides (bilateral). Linear scleroderma generally appears in young children and is characterized by the failure of one limb (i.e., arm or leg) to grow as rapidly as its counterpart. The band of thick skin may extend from the hip to the heel or from the shoulder to the hand. Deep tissue loss may occur along this band.

Systemic scleroderma includes a wide range of symptoms including inflammatory diseases of the muscles (i.e., polymyositis or dermatomyositis), swelling (edema) of the fingers and/or hands, microvascular abnormalities, lung disease (i.e., progressive interstitial fibrotic pulmonary disease), kidney dysfunction (i.e., rapidly progressive renal failure), cardiovascular problems (i.e., myocardial accelerated hypertension), gastrointestinal malfunction (i.e., lack of mobility of the esophagus and colon), and/or abnormalities of the immune system. (For more information, choose "Polymyositis" and "Dermatomyositis" as your search terms in the Rare Disease Database.)

CREST syndrome is an acronym for calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia. Calcinosis is the abnormal accumulation of calcium salts under the skin and in many other organs. Raynaud's phenomenon is a vascular disorder characterized by the intermittent loss of blood to various parts of the body, particularly the fingers, toes, nose, and/or ears. This typically occurs after exposure to cold and causes tingling sensations, numbness, and/or pain. Dysfunction of the lower esophagus results in heartburn (acid reflux into the throat and mouth) and possible scarring. The esophagus may eventually have areas that are narrowed (strictures), and swallowing may become difficult. The small intestine may also lose the ability to push food through to the large intestine (peristalsis), leading to malabsorption and increased bacterial growth in the small intestine. Sclerodactyly, a condition in which the skin becomes thin, shiny, and bright, results in decreased function of the fingers and toes. Affected individuals may also exhibit telangiectasia, meaning the appearance of small blood vessels near the surface of the skin. Individuals with CREST syndrome are at increased risk of developing pulmonary hypertension, a progressive disorder characterized by high blood pressure (hypertension) of the main artery of the lungs (pulmonary artery). (For more information, choose "Raynaud" and "Pulmonary Hypertension" as your search terms in the Rare Disease Database.)

Causes

The exact cause of scleroderma is unknown. The immune system and vascular system as well as connective tissue metabolism are known to play some role in the disease process. Researchers believe that several factors interact to produce scleroderma. These include abnormal immune activity, potential environmental triggers, and genetic makeup. Scleroderma is not thought to be passed on from parent to child, but it is believed that the presence of certain genes may make it more likely that a person will develop the disease (genetic predisposition).

Abnormal immune activity refers to when the body's natural defenses (antibodies) against invading or "foreign" organisms begin to attack the body's own tissue, often for unknown reasons (autoimmunity).

Some cases of scleroderma have been associated with silica dust, organic solvents, and L-tryptophan.

Affected Populations

The systemic form of scleroderma is thought to affect from 40,000 to 165,000 people in the United States. The disease is three to four times more common in females than in males. Scleroderma may occur at any age but the symptoms most frequently begin during midlife.

Related Disorders

Symptoms of the following disorders can be similar to those of scleroderma. Comparisons may be useful for a differential diagnosis:

Mixed connective tissue disease (MCTD) is a rare inflammatory disorder of the connective tissue. The symptoms of this disorder overlap with those of lupus (systemic lupus erythematosus), scleroderma, and polymyositis/dermatomyositis. Early symptoms may include a fever of unknown origin, painfully cold fingers in response to cold (Raynaud's phenomenon), swollen hands, fatigue, and/or non-deforming arthritis. Arthritis occurs in almost every case of mixed connective tissue disease, but rarely results in deformities similar to those seen in rheumatoid arthritis. People with mixed connective tissue disease commonly experience muscle pain and skin rashes. (For more information on this disorder, choose "Mixed Connective Tissue Disease" as your search term in the Rare Disease Database.)

Lupus (systemic lupus erythematosus or SLE) is a rare inflammatory connective tissue disease. The initial symptom of this disease is usually excessive fatigue. Most people with Lupus experience inflammation and swelling of the joints (arthritis), joint pain (arthralgia), and generalized muscle pain (myalgia). Skin rashes are common in people with lupus. About 50 percent of people with lupus exhibit a classic red "butterfly" rash across the bridge of the nose and cheeks. Other early symptoms may include fever, swollen glands, loss of appetite, weight loss, headaches, loss of hair, and swelling due to fluid retention. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)

Polymyositis is a rare inflammatory disorder characterized by the inflammation and degeneration of muscle and the supporting collagen connective tissue. The cause of this disorder is not known. The major early symptom of this disorder is muscle weakness, usually in the neck, trunk, and shoulders. Eventually, it may become difficult to rise from a sitting position, climb stairs, lift objects, and/or reach overhead. Occasionally, joint pain and tenderness also occur. Other symptoms may include inflammation of the lungs (interstitial pneumonitis), difficulty breathing, coughing, painfully cold fingers in response to cold (Raynaud's phenomenon), digestive problems, heart irregularities, and kidney failure. (For more information on this disorder, choose "Polymyositis" as your search term in the Rare Disease Database.)

Dermatomyositis is a rare inflammatory connective tissue disease. The cause is unknown. Dermatomyositis is identical to polymyositis but with the addition of a characteristic red skin rash. These red rashes generally occur before the muscle weakness occurs and usually appear on the face, knees, shoulders, and hands. In some affected individuals, the skin changes caused by dermatomyositis are similar to those associated with scleroderma. The skin may become dry and hard and have a brownish color. (For more information on this disorder, choose "Dermatomyositis" as your search term in the Rare Disease Database.)

Raynaud's disease is a rare disorder characterized by spasms of the blood vessels in the fingers, toes, nose, and ears (Raynaud's phenomenon) usually in response to cold. Raynaud's disease includes the symptoms of Raynaud's phenomenon along with other systemic disorders. The major symptom of this disorder is a dramatic stark white pallor of the affected fingers and toes when exposed to cold, although a blue or red color may also be present from time to time. Other symptoms in the affected fingers and toes vary in response to cold and may include a feeling of numbness, severe aching or pain, tingling or throbbing, a sensation of tightness, "pins and needles," and/or a profound loss of sensation. (For more information on this disorder, choose "Raynaud's" as your search term in the Rare Disease Database.)

Standard Therapies

Treatment of scleroderma is symptomatic and supportive. Medications used to control the hardening of the skin and internal organs (fibrosis) are D- penicillamine and cholchicine. Other skin care may include lubricating creams or antibiotic ointments for infected ulcerations.

Captopril and enalapril, angiotensin-converting enzyme inhibitors that inhibit the formation of angiotensin, are the drugs of choice for the treatment of kidney disease associated with scleroderma. Other vasodilators or beta-adrenergic blockers also have been used with some success. These agents are effective in controlling hypertension and can preserve kidney function.

If Raynaud's phenomenon occurs with scleroderma, drug therapy may help widen (dilate) blood vessels. Vasodilators, including the drugs nifedipine (Procardia), reserpine (Serpasil), guanethidine (Ismelin), phenoxybenzamine (Dibenzyline), nicotinic acid, diltiazem, verapamil, and/or prazosin (Minipress) may be prescribed.

In rare cases of scleroderma, abnormal accumulation of calcium salts under the skin and in other organs (calcinosis) may require surgical intervention. For joint pain or arthritis, anti-inflammatory drugs are generally prescribed including aspirin, indomethadin (Indocin), and naproxen (Naprosyn). Some individuals may require low doses of corticosteroid drugs to control these symptoms.

The management of symptoms of scleroderma related to pulmonary hypertension involves the use of supplemental oxygen.

The orphan drug Tracleer (bosentan) has been approved by the Food and Drug Administration (FDA) for treatment of pulmonary hypertension. Pulmonary hypertension occurs in some individuals with scleroderma. The drug improves the exercise ability of individuals with primary pulmonary hypertension allowing them to exert themselves physically without shortness of breath. Tracleer is manufactured by Actelion Pharmaceuticals US, Inc. of San Francisco, California.

Epoprostenol sodium (Flolan) was approved by the FDA in 2000 as a treatment for pulmonary hypertension in scleroderma. For information on Flolan, contact its manufacturer, GlaxoSmithKline.

When abnormalities of the heart (myocardial perfusions) occur as a result of scleroderma, the drugs nifedipine and dipyridamole may be administered. Nonsteroidal anti-inflammatory or corticosteroid drugs are typically used to treat the symptoms relating to the inflammation of the membranes of the heart (pericarditis).

When scleroderma causes the esophagus and/or gastrointestinal tract to become inflamed or ulcerated, the treatments of choice are drugs known as H2 blockers such as cimetidine or ranitidine; omeprazole may also be used. Metoclopramide has been beneficial in treating the symptoms associated with gastrointestinal dysmotility. Gastrointestinal dysmotility refers to problems with the muscular contractions of the stomach wall that are necessary to move or squeeze contents forward. Acid reflux from the stomach into the esophagus may be partially controlled by dietary regulation. Individuals are urged to avoid certain foods such as fats, spices, tea, coffee, and alcohol. Several small and frequent meals per day lighten the work of the gastrointestinal system. Sitting upright for at least 2 hours after eating aids the digestive process.

Good oral hygiene is important because gum disease is common in scleroderma. Some affected individuals may experience excessive dryness of the mouth and eyes. The combination of dry mouth and dry eyes is known as Sjogren's syndrome. (For more information, choose "Sjogren" as your search term in the Rare Disease Database.)

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

The Scleroderma Clinical Trials Consortium (SCTC) is a charitable non-profit organization dedicated to finding better treatment for scleroderma. Member institutions of the SCTC conduct clinical treatment trials of new (and sometimes old) medications that appear promising for the treatment of scleroderma. For information, visit:
http://www.sctc-online.org/aboutus.htm

A National Registry for Childhood Onset Scleroderma has been established to increase understanding of this disease and stimulate future research. The purpose is to identify and study specific antibodies that are often found in the blood of people affected by scleroderma. All aspects of participation, including a one-time-only blood sample, can be completed through the mail. For information, contact:

Jennifer Jablon
(800) 603-8960
http://www.sctc-online.org/studies/nrcos.htm
jablonj@msx.dept-med.pitt.edu

Organizations related to Scleroderma

References

TEXTBOOKS
Reeves WH, Richards HB. Scleroderma. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:33-34.

Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:431-33.

Berkow R, ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:380-82.

REVIEW ARTICLES
Leask A, Denton CP, Abraham DJ. Insights into the molecular mechanism of chronic fibrosis: the role of connective tissue growth factor in scleroderma. J Invest Dermatol. 2004;122:1-6.

Azad J, Dawn G, Shaffrali FC, et al. Does solitary morphea profunda progress. Clin Exp Dermatol. 2004;29:25-27.

Current Opin Rheumatol. 2003;15.748-790. Seven (7) Review Articles.

Acorn S, Joachim G, Wach JE. Scleroderma: living with unpredictability. AAOHN J. 2003;51:353-57.

Clin Exp Rheumatol. 2003;21 (3 Suppl 29):SS5-S46. Nine (9) Review Articles.

Scheinberg P. Stem-cell transplantation for autoimmune diseases. Cytotherapy. 2003;5:243-51.

Rheum Dis Clin North Am. 2003;29:211-408. Ten (10) Review Articles.

Joachim G, Acorn S. Life with a rare chronic disease: the scleroderma experience. J Adv Nurs. 2003;42:598-606.

Artlett CM. Microchimerism and scleroderma: an update. Curr Rhematol Rep. 2003;5:154-59.

Valentini G, Black C. Systemic sclerosis. Best Pract Res Clin Rheumatol. 2002;16:807-16.

Foeldvari I. Scleroderma in children. Curr Opin Rheumatol. 2002;14:699-703.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Scleroderma, Familial Progressive. Entry Number; 181750: Last Edit Date; 3/17/2004.

Scleroderma. MedlinePlus. Last Updated 29 April 2004.
http://www.nlm.nih.gov/medlineplus/scleroderma.html

The Scleroderma Foundation.
www.scleroderma.org

International Scleroderma Network.
www.sclero.org

Understanding scleroderma. Types, Symptoms, Diagnosis and Care. Scleroderma Research Foundation. ©2002.
http://www.srfcure.org/sclerod/index.html

About Scleroderma. The Scleroderma Society. nd.
http://www.sclerodermasociety.co.uk/

Current Studies. Scleroderma Clinical Trials Consortium. ©2004.
http://www.sctc-online.org/studies.htm

Report last updated: 2009/12/14 00:00:00 GMT+0