$Unique_ID{BRK04210} $Pretitle{} $Title{Scleroderma} $Subject{Scleroderma PSS Systemic Sclerosis Progressive Systemic Sclerosis Sclerosis, Familial Progressive Systemic Morphea Linear Scleroderma CREST Syndrome Mixed Connective Tissue Disease Lupus (Systemic Lupus Erythematosus) Polymyositis Dermatomyositis Raynaud's Disease and Phenomenon } $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1992, 1993 National Organization for Rare Disorders, Inc. 69: Scleroderma ** IMPORTANT ** It is possible that the main title of the article (Scleroderma) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms PSS Systemic Sclerosis Progressive Systemic Sclerosis Sclerosis, Familial Progressive Systemic Disorder Subdivisions: Morphea Linear Scleroderma CREST Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Mixed Connective Tissue Disease Lupus (Systemic Lupus Erythematosus) Polymyositis Dermatomyositis Raynaud's Disease and Phenomenon General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Scleroderma is a rare 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 effect certain parts of the body, and other types can effect the whole body and internal organs (systemic). 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. Telangiectasia, the appearance of small blood vessels near the surface of the skin, is unsightly but not debilitating. Patients with the CREST Syndrome are at increased risk of developing pulmonary hypertension. (For more information, choose "Raynaud" and "Pulmonary Hypertension" as your search term in the Rare Disease Database.) Causes The exact cause of Scleroderma is unknown. The immune system and vascular system, and connective tissue metabolism are known to play some part in the disease process. Affected Population Scleroderma is a rare disorder that affects approximately 50,000 to 100,000 people in the United States. The disease is 3 to 4 times more common in women than men. Scleroderma may occur at any age, but the symptoms most frequently begin in 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 get 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 also 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 patients the skin changes caused by Dermatomyositis are similar to those of Scleroderma. The skin may become dry, 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.) Therapies: Standard 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 dilate blood vessels. Vasodilators, including the drugs nifedipine (Procardia), reserpine (Serpasil), guanethidine (Ismelin), phenoxybenzamine (Dibenzyline), nicotinic acid, diltiazem, verapamil, and/or prazosin (Minipress) are prescribed. In rare cases of Scleroderma, calcinosis may require surgical intervention. For joint pain or arthritis, anti-inflammatory drugs are generally prescribed including aspirin, indomethadin (Indocin), and naproxen (Naprosyn). Some patients 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. When abnormalities of the heart occur (myocardial perfusions) 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. Acid reflux from the stomach into the esophagus may be partially controlled by dietary regulation. Patients 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 patients suffer from 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.) Therapies: Investigational Many possible causes of Scleroderma and other "sclerosis-like" connective tissue diseases are currently being investigated. These include a wide variety of chemical and environmental exposures (i.e., vinyl chloride, pentazocine, silicone, tricholorethylene, paraffin), as well as the use of adulterated L-tryptophan and appetite suppressants. There is some evidence that Scleroderma seems to cluster in certain geographic areas. Other studies have suggested that the tendency to develop Scleroderma and other sclerosis-like diseases runs in families. Scientists are studying the possible inheritance of a genetic trait that would predispose a person to this disorder. Some studies suggest the presence of an antibody that causes chromosomes to break (anticentromere antibody) in some people with CREST Syndrome. Other research suggests that a spontaneous genetic change (de novo) may cause a genetic predisposition to Scleroderma. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. It has been suggested that Scleroderma is actually a group of distinct disorders each of which has its own characteristic genetic or environmental predisposing risk factors. Several experimental treatments are currently being evaluated for use in treating people with Scleroderma. The orphan drug etretinate (Tigason) is now under study in the United States for the treatment of certain types of Scleroderma. The early steps of the production of excess collagen by cells may be blocked by Vitamin A components (retinoids) in etretinate. Excess collagen production is a primary abnormality of Scleroderma. It should be remembered that although this orphan drug is available experimentally in the United States, it is still under study and conclusive results are not yet available. The Arthritis Unit of Massachusetts General Hospital and the New England Deaconess Hospital are evaluating the effects of recombinant gamma-interferon in individuals with Scleroderma. More testing is necessary to determine the safety and effectiveness of this treatment. Interferon is a potential therapy for Scleroderma because of its inhibition of excessive synthesis of collagen, but side effects are common. The drug ketanserin, a serotonin antagonist, is being tested for treatment of the abnormal blood flow in the fingers caused by Raynaud's Phenomenon associated with Scleroderma. More research is needed before these types of drugs will be available for more general use. Cyclosporine (Sandimmune) may be of potential benefit for treating a number of skin diseases, including those seen in collagen vascular diseases. These include Pemphigus, Bullous Pemphigoid, Posterior Uveitis, Bechet's Disease, and collagen vascular disorders such as Scleroderma, severe Dermatomyositis, Sjogren's Syndrome, Mycosis Fungoides, and Alopecia Areata. Certain types of skin grafts have sometimes improved after cyclosporine treatment. However, cyclosporine is toxic and it reduces the function of the immune system; therefore, it is not ordinarily used to treat Scleroderma. Relapses can occur when the drug is stopped. More research is needed before cyclosporine can be recommended as a treatment for all but the most severe cases of Scleroderma. (For more information choose "Pemphigus," "Bechet," "Dermatomyositis," "Sjogren," "Mycosis Fungoides," and "Alopecia Areata" as your search term in the Rare Disease Database.) A treatment known as photochemotherapy is under investigation for people with Scleroderma. During this procedure, blood in removed from the body (as in dialysis) and certain blood cells (monocytes) are "washed" with a drug (8- methoxypsoralen). The blood is then exposed to ultraviolet light (type A). This process is known as photopheresis. It is hoped that this treatment might suppress collagen production and increase the levels of an enzyme that breaks down collagen (collagenase). More study is needed to determine the long-term safety and effectiveness of this treatment. Scleroderma has been treated experimentally with the local anesthetic and anti-inflammatory drug, dimethyl sulfoxide (DMSO), as part of the Arthritis research program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases. These investigational studies are being performed to determine the long-term effect of this drug on patients suffering from Scleroderma. Octreotide Acetate (Sandostatin), manufactured by Sandoz, is being studied as a treatment for the intestinal motility problems of people with Scleroderma. In a study of patients with Scleroderma and control patients, octreotide acetate was given to increase motility and relieve abdominal symptoms. More study is indicated to determine the long-term safety and effectiveness of this drug for Scleroderma. Clinical trials are underway to test the orphan drug chlorambucil as a treatment for Scleroderma. For more information, patients may have their physicians contact: Daniel Furtst, M.D. University of Iowa Iowa City, IA 52240 Scientists are studying a new orphan drug, Iloprost, for treatment of Raynaud's Phenomenon when it occurs along with Scleroderma. The drug is manufactured by Berlex Laboratories. More research is needed to determine the safety and effectiveness of this experimental treatment. Clinical trials are underway to study bronchoalveolar lavage in Interstitial Lung Disease that can be associated with Scleroderma. For more information, patients may have their physicians contact: Gary W. Hunninghake, M.D. Pulmonary Disease Division, C33, GH Dept. of Internal Medicine University of Iowa Hospitals and Clinics Iowa City, IA 52242 (319) 356-4187 Clinical trials are underway to study the safety and efficacy of Xomazyme COS. For more information, patients may have their physicians contact: Dr. Thomas D. Geppart University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75235 (214) 688-8351 This disease entry is based upon medical information available through April 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Scleroderma, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Scleroderma Society/Federation 1182 Teaneck Rd., Suite 104 Teaneck, NJ 107666 (201) 837-9826 Scleroderma Federation One Newbury St. Peabody, MA 01960 (508) 535-6600 Scleroderma Research Foundation Pueblo Medical Commons 2320 Bath St., Suite 307 Santa Barbara, CA 93105 (805) 563-9133 (800) 441-CURE United Scleroderma Foundation, Inc. P.O. Box 350 Watsonville, CA 94077-0350 (408) 728-2202 Scleroderma International Foundation 704 Gardner Center Road New Castle, PA 16101 The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1006. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1530-35. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 1321-1323. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 1515-1516. THE MANY FACES OF SCLERODERMA. J.D. Smiley; Am J Med Sci (Nov 1992; 304(5)). Pp. 319-33. TREATMENT OF SYSTEMIC SCLEROSIS. T.A. Medsger; Ann Rheum Dis (Nov 1991; 50(4)). Pp. 877-886. USE OF ANGIOTENSIN-CONVERTING-ENZYME INHIBITORS IN THE MANAGEMENT OF RENAL DISEASE. J.P. Asher; Clin Pharm (Jan 1991; 10(10)). Pp. 25-31. TREATMENT OF SYSTEMIC SCLEROSIS. V. Steen; Curr Opin Rheumatol (Dec 1991; 3(6)). Pp. 979-85. EPIDEMIOLOGY OF SCLERODERMA. A.J. Silman; Curr Opin Rheumatol (Dec 1991; 3(6)). Pp. 967-72. TREATMENT OF SYSTEMIC SCLEROSIS. F.M. Wigley; Curr Opin Rheumatol (Dec. 1992; 4(6)). Pp. 878-886. GENETIC AND ENVIRONMENTAL FACTORS IN SYSTEMIC SCLEROSIS. R.I. Fox; Curr Opin Rheumatol (Dec 1992 4(6)). Pp. 857-61. EXTRACORPOREAL PHOTOCHEMOTHERAPY INDUCES THE PRODUCTION OF TUMOR NECROSIS FACTOR-ALPHA BY MONOCYTES: IMPLICATIONS FOR THE TREATMENT OF CUTANEOUS T-CELL LYMPHOMAS AND SYSTEMIC SCLEROSIS. B.R. Vowels; J Invest Dermatol (May 1992; 98(5)). Pp. 686-692. TREATMENT OF AUTOIMMUNE DISEASE WITH EXTRACORPOREAL PHOTOCHEMOTHERAPY: PROGRESSIVE SYSTEMIC SCLEROSIS. A.H. Rook; Yale J Biol Med (Nov-Dec 1989; 62(6)). Pp. 639-645.