Scleroderma is a group of disorders that cause the skin and the fibers that provide support and framework for the body (called connective tissues) to harden and tighten. It typically starts with a few dry patches of skin on the face and hands. Over time, these patches of skin become thicker and harder, and more and more skin becomes affected. In some cases, the condition may also involve the internal organs and blood vessels.
Scleroderma is classified into two major categories: localized scleroderma and systemic scleroderma. Localized scleroderma only affects the skin. Often, localized conditions improve or go away on their own over time. However, the skin changes and damage that occurred when the disease was active are permanent.
Systemic scleroderma is a more serious type of scleroderma that affects the skin, deep tissues below the skin, blood vessels, and internal organs. When the internal organs become hard, they no longer function properly and death may occur. Systemic scleroderma may develop suddenly or it may start with the skin and progress gradually to the internal organs.
Scleroderma is a type of autoimmune disorder because it occurs when a patient's immune system does not function properly. Normally, the immune system helps fight against diseases and infections. In scleroderma patients, the immune system attacks the person's own cells. However, researchers have not discovered what causes this abnormal immune response.
Researchers also know that scleroderma is not a contagious illness.
For unknown reasons, scleroderma is more common in women than men. It is also more common in adults than children.
There is currently no cure for scleroderma. Patients who only have skin involvement have a better outlook, but they often suffer from low self-esteem and difficulty performing everyday tasks. The average life expectancy after systemic scleroderma is diagnosed is 12 years. This is because the condition usually worsens over time. Patients who have systemic scleroderma are most likely to die as a result of heart, kidney, lung, or gastrointestinal (digestive) complications.
General: Patients with all types of scleroderma have too much collagen in the body tissues, which causes tissues to become tight and hard. Collagen is a fibrous, or thread-like, protein that makes up connective tissues. Researchers believe that scleroderma is an autoimmune disorder because it appears that the body's immune system leads to an increase in collagen.
In healthy individuals, the immune system protects the body by fighting against diseases and infections. In scleroderma patients, the immune system attacks the person's own cells by mistake. This reaction causes swelling and the overproduction of collagen. However, researchers have not discovered what triggers this abnormal immune reaction.
Genetics: Some evidence suggests that a person's genetic makeup may make them more likely to develop scleroderma. This is because in some cases, the disease has been shown to run in families. However, most cases of scleroderma occur without any known family history of the disease.
Hormones: Some researchers believe that hormones may play a role in the development of scleroderma because women of all ages are more likely to develop scleroderma than men. Female predominance is most apparent during middle age. Research has shown that middle-aged women (ages 30-55) are seven to 12 times more likely to develop scleroderma than men. However, the role of estrogen or other female hormones in scleroderma has not been scientifically proven.
SIGNS AND SYMPTOMS
Morphea scleroderma: Morphea scleroderma causes reddish patches of skin to thicken into oval-shaped areas on the body. These patches become white in the middle with a purple border. Patients may develop one or several patches of thickened skin, which range in size from one-half inch to 12 inches wide. The patches typically occur on the chest, stomach, and back, but they may also develop on the legs, arms, and forehead. In general, skin patches caused by morphea scleroderma start to fade in about three to five years. However, individuals are typically left with darkened patches of skin, and in rare cases, muscle weakness.
Linear scleroderma: Linear scleroderma causes streaks of hardened skin to develop on the arms, legs, and/or forehead. In some cases, linear scleroderma may occur in combination with morphea scleroderma.
Systemic scleroderma (systemic sclerosis):
Diffuse cutaneous systemic sclerosis: Diffuse cutaneous systemic sclerosis usually develops suddenly. The skin on the fingers, hands, arms, legs, face, neck, and torso are most likely to become thick and hard. The skin may also be shiny and itchy. This form of scleroderma generally occurs in a symmetrical pattern. This means if one side of the body is affected, the other side will be affected in the same way. Other symptoms may include fatigue, decreased appetite, weight loss, and joint pain or swelling.
Diffuse cutaneous systemic sclerosis may also affect internal organs, such as the heart, lungs, kidneys, and digestive system. Symptoms of internal organ damage vary depending on the specific organ affected. For instance, if the lungs are affected, it may lead to difficulty breathing, shortness of breath, or chest tightness.
However, after three to five years, most patients with diffuse cutaneous systemic sclerosis enter a stable phase. During this stage, symptoms lessen. The skin may gradually start to soften. In some patients, the skin may start to appear normal again. In others, the skin may become thin, fragile, hairless, and without sweat glands. Once patients enter this stage, it is unlikely that new damage to internal organs will occur. However, internal damage that has already occurred is not reversible.
Limited cutaneous systemic sclerosis: Limited cutaneous systemic sclerosis usually develops gradually. It involves limited areas of the skin, including the fingers, hands, face, lower arms, and legs. In addition, patients often have all or some of the symptoms that some doctors call CREST, which stands for calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia.
Calcinosis occurs when there are calcium deposits in the connective tissues. These deposits usually occur in the hands, face, torso, and on the skin above the knees and elbows. These small deposits may break through the skin, causing painful wounds called ulcers.
Raynaud's phenomenon occurs when the small blood vessels in the hands and/or feet, and sometime the nose, ears, cheeks, or tongue, shrink in response to cold or anxiety. This reduces blood to flow to the affected parts of the body. As a result, the affected areas of the body may feel numb or turn white in color. Symptoms will start to go away once the patient is exposed to warm temperatures or reduces his/her level of stress. The affected body parts may then start to feel numb, prickly, or sting as they become warmed or as stress is reduced. As circulation improves, the affected skin may turn red, throb, or swell. Raynaud's phenomenon may lead to ulcers (open sores), scars, or gangrene. Patients with limited cutaneous systemic sclerosis often experience symptoms of Raynaud's phenomenon for years before the skin starts to thicken.
Esophageal dysfunction occurs when the tube that connects the throat and the stomach (called the esophagus) does not work properly. Normally, the muscles in the esophagus contract to allow food and drinks to enter the stomach. These muscles do not work properly in some patients with cutaneous systemic sclerosis. The muscles become damaged and are weaker than normal. As a result, patients may experience difficulty swallowing, chronic heartburn, and/or inflammation of the esophagus (called esophagitis).
Sclerodactyly occurs when the skin on the fingers or toes becomes thick and tight. Patients often have difficulty bending and straightening their fingers or toes. The skin may also appear darkened or shiny.
Telangiectasia occurs when the tiny blood vessels under the skin spontaneously become swollen. These inflamed blood vessels show up as tiny red spots, usually on the hands and face. This condition is painless, although it is visibly noticeable.
Sine scleroderma: Sine scleroderma may be similar to either limited or diffuse scleroderma because it involves one or more internal organs. However, the major difference is that sine scleroderma does not affect the skin. This form of scleroderma is extremely rare.
Some patients may develop symptoms that are similar or related to scleroderma. These patients may be diagnosed with undifferentiated connective tissue disease (UCTD) or overlap syndromes.
Undifferentiated connective tissue disease (UCTD): Undifferentiated connective tissue disease (UCTD) occurs when patients have some signs and symptoms of scleroderma but not enough to be diagnosed with a particular type of scleroderma. Over time, patients with UCTD may develop into a specific type of scleroderma, spontaneously improve, or stay the same.
Gastrointestinal complications: Patients with scleroderma often experience gastrointestinal damage. Scleroderma causes the muscular walls of the intestine to shrink. As a result, patients may be unable to properly absorb important vitamins and nutrients from their food. This may also lead to malnutrition and/or weight loss.
Scleroderma may also damage the lining of the esophagus, as well as the esophageal sphincter. This sphincter is important because it prevents stomach acid from entering the esophagus. When the sphincter is damaged, patients may experience heartburn when stomach acid enters the esophagus.
Lung complications: Scleroderma may cause lung tissue to become scarred, a condition called pulmonary fibrosis. As a result, the lungs do not function as efficiently as normal. Patients with pulmonary fibrosis may experience shortness of breath or difficulty breathing.
Some patients may also develop high blood pressure in the arteries that pump blood to the lungs. This life-threatening condition is called pulmonary hypertension.
Kidney dysfunction: If scleroderma involves the kidney, patients may develop high blood pressure, excessive amounts of protein in the urine, and a life-threatening condition called renal crisis. Renal crisis causes a sudden increase in blood pressure and kidney failure.
Heart complications: If scleroderma affects the heart, it may cause the heart tissue to become scarred. As a result, patients have an increased risk of developing irregular heartbeats, congestive heart failure, and inflammation of the sac that surrounds the heart (called pericarditis).
Self-esteem: The effects of scleroderma on the skin are noticeable. It may be difficult for some patients to accept changes in the skin, especially on the face. Properly managing scleroderma may help reduce or minimize the physical effects of the disease.
Quality of life: When the skin becomes tight and hard, it may make it difficult to perform everyday tasks. For instance, when the hands are involved, it may become difficult to bend and straighten the fingers. As a result, tasks that were once considered simple, such as brushing the teeth or buttoning a shirt, may become increasingly difficult. Patients who experience such difficulties should consider talking to an occupational therapist. These therapists may be able to recommend different ways to perform tasks or certain devices (e.g. Velcro© fasteners) to make daily activities easier.
General: During a physical examination, a healthcare provider will take a detailed medical history and check the skin for tight and hardened areas. The doctor will also examine the joints and tendons to look for inflammation and possible changes in connective tissue beneath the skin. In addition, the doctor will look for color changes in the hands and feet in response to coldness. If the hands or feet turn white in response to cold temperatures, this indicates Raynaud's phenomenon, which is often associated with scleroderma. If the patient's signs and symptoms indicate scleroderma, additional tests may be performed to confirm a diagnosis.
Blood tests: If scleroderma is suspected, a blood test is typically performed. A sample of the patient's blood will be analyzed for the presence of abnormal immune cells that are associated with scleroderma.
Tissue biopsy: A tissue biopsy may be performed to confirm a diagnosis. A small sample of the affected area of skin is removed and analyzed for abnormalities associated with scleroderma. Patients with scleroderma will have high levels of collagen in their tissues.
Computerized tomography: A computerized tomography (CT) scan may be performed to determine if there are calcium deposits in the joints. Calcium deposits are typically present in patients with limited cutaneous systemic sclerosis.
General: Treatment for scleroderma focuses on reducing the symptoms. Patients with scleroderma should visit their healthcare providers regularly to monitor their condition and help slow the progression of the disease.
Regular exercise: Patients with scleroderma should exercise regularly to maintain as much strength and flexibility as possible. There are many ways to exercise, including gardening, walking, sports activities, and dancing.
Patients should choose exercise programs that fit with their levels of strength and endurance. Exercise that causes extreme pain or discomfort may be harmful because it may lead to torn ligaments, pulled muscles, or sprained joints. Not everyone is able to handle intense types of exercise, such as tennis or running. According to the American Academy of Physicians, individuals who are pregnant or have bone disease or nerve injuries should participate in low-impact forms of exercise, such as walking or swimming. Individuals should talk with their healthcare providers before starting a new exercise plan.
Humidifiers: Patients with scleroderma may benefit from a humidifier, which increases the amount of moisture in the air. This helps prevent the skin from becoming dry.
Oil-based lotions: Oil-based creams and lotions may also help prevent the skin from becoming excessively dry. Creams should be applied frequently, especially after bathing or showering.
Changing eating habits: If scleroderma affects the gastrointestinal tract, patients may need to change their eating habits. Eating smaller, more frequent meals may reduce symptoms of heartburn. Avoiding late-night meals, spicy foods, fatty foods, alcohol, and caffeine may also help prevent digestive symptoms. Multivitamins may also be beneficial for patients who experience decreased nutrient absorption as a result of gastrointestinal damage. However, it is recommended that patients talk to their healthcare providers before taking dietary supplements.
Anti-inflammatories: Medications called nonsteroidal anti-inflammatory drugs (NSAIDs) are often taken to reduce joint pain and inflammation associated with scleroderma. Medications, such as ibuprofen (Motrin© or Advil©), are commonly used.
The frequency and severity of NSAID side effects vary. The most common side effects include nausea, vomiting, diarrhea, constipation, decreased appetite, rash, dizziness, headache, and drowsiness. The most serious side effects include kidney failure, liver failure, ulcers, heart-related problems, and prolonged bleeding after an injury or surgery. About 15% of patients who receive long-term NSAID treatment develop ulcers in the stomach or duodenum. Patients taking NSAIDs who have a history of gastrointestinal problems should consider taking a medication to protect the stomach, such as misoprostol (Cytotec©).
Disease-modifying antirheumatic drugs (DMARDs): Healthcare providers often prescribe disease-modifying antirheumatic drugs (DMARDs). These medications are called "disease-modifying" drugs because they slow the progression of scleroderma. These drugs may take weeks to months before they begin to take effect. Therefore, they are often used in combination with NSAIDs or corticosteroids. Commonly prescribed DMARDs include the gold compound auranofin (Ridaura©), hydroxychloroquine (Plaquenil©), sulfasalazine (Azulfidine©), and methotrexate (Rheumatrex©).
Immunosuppressants: Because scleroderma occurs when the immune system attacks the person's own body, patients often take medications called immunosuppressants. Immunosuppressants weaken the body's immune system, which helps reduce symptoms of scleroderma. Commonly prescribed immunosuppressants include leflunomide (Arava©), azathioprine (Imuran©), cyclosporine (Neoral© or Sandimmune©), and cyclophosphamide (Cytoxan©).
These medications may have serious side effects, including increased risk of infections, kidney problems, high blood pressure, and decreased levels of red blood cells. Other side effects may include increased hair growth, loss of appetite, vomiting, and upset stomach.
Calcium channel blockers: Severe cases of Raynaud's phenomenon may be treated with calcium channel blockers, such as nifedipine (Procardia©). These medications help open the small blood vessels and improve circulation.
Antihypertensives: Patients with pulmonary hypertension may benefit from antihypertensives such as prostacyclin (Iloprost©). These prescription-strength medications decrease the blood pressure in the arteries leading to the lungs.
Antacids: If scleroderma has caused esophageal damage and is causing heartburn, patients typically take antacids. These medications reduce the amount of stomach acid that is produced, and help reduce heartburn. Some over-the-counter H-2 receptor blockers, such as cimetidine (Tagamet HB©), famotidine (Pepcid AC©), nizatidine (Axid AR©), and ranitidine (Zantac 75©), may help provide quick relief of symptoms. Side effects of H-2 receptor blockers, which are uncommon, may include changes in bowel movements, dry mouth, dizziness, or drowsiness. Proton pump inhibitors, such as omeprazole (Prilosec OTC©), may also be taken short-term to help the esophagus heal. Patients should not take these medications long term unless they talk with their healthcare providers first.
Patients with persistent heartburn may require prescription-strength medications to manage symptoms and prevent esophageal damage. H-2 blockers, such as Axid©, Pepcid©, Tagamet©, and Zantac©, are commonly prescribed. Examples of prescription-strength proton pump inhibitors include esomeprazole (Nexium©), lansoprazole (Prevacid©), omeprazole (Prilosec©), pantoprazole (Protonix©), and rabeprazole (Aciphex©).
Unclear or conflicting scientific evidence:
Para-aminobenzoic acid (PABA): Potassium para-aminobenzoate (KPAB) has been proposed as a treatment for sclerodermatous skin changes. Clinical reviews have suggested the effectiveness of KPAB in the management of scleroderma, particularly with respect to skin changes, survival rate, and pulmonary function. However, clinical study on KPAB for management of sclerodermatous skin changes did not reveal any effect. The use of KPAB as a therapy in scleroderma remains controversial. Additional high quality clinical study is warranted.
Avoid oral use in children and pregnant or nursing women. Avoid with known hypersensitivity to PABA or its derivatives. Use cautiously in patients with renal disease. Abnormalities of liver function tests have been noted in patients taking PABA. Discontinue use if rash, nausea, or anorexia occurs. PABA should not be given concurrently with sulfonamides. Use cautiously in patients with bleeding disorders or taking anticoagulants. Use cautiously in patients with diabetes or hypoglycemia.
Fair negative scientific evidence:
DMSO (dimethyl sulfoxide): DMSO is naturally found in vegetables, fruits, grains, and animal products. It is also available as a dietary supplement. Research suggests that DMSO does not help treat scleroderma. Therefore, it is not recommended for this use.
Avoid if allergic DMSO. Use cautiously with urinary tract cancer, liver disorders, or kidney disorders. Avoid if pregnant or breastfeeding due to a lack of safety evidence.
Traditional or theoretical uses lacking sufficient evidence:
Acupuncture: Acupuncture is commonly used throughout the world. According to Chinese medicine theory, the human body contains a network of energy pathways through which vital energy, called "chi," circulates. These pathways contain specific points that function like gates, allowing chi to flow through the body. Needles are inserted into these points to regulate the flow of chi. Traditionally, acupuncture has been used to treat scleroderma. However, scientific studies are needed to determine if this treatment is safe and effective.
Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, medical conditions of unknown origin, or infections. Acupuncture should not be applied to the chest in patients with lung diseases or on any area that may rely on muscle tone to provide stability. Avoid use in infants, young children, or in patients with needle phobias. Use cautiously with bleeding disorders, neurological disorders, seizure disorders, or diabetes. Use cautiously in elderly or medically compromised patients. Use cautiously in patients who will drive or operate heavy machinery after acupuncture. Use cautiously if taking anticoagulants. Avoid if pregnant.
Avocado: Avocados are fruits that are a nutritious source of potassium. Although avocado has been suggested as a possible treatment for scleroderma, scientific studies are lacking in this area. Human studies are needed to determine if avocados are safe and effective for this condition.
Avoid if allergic or hypersensitive to avocado, banana, chestnut, or natural rubber latex. Avoid if taking monoamine oxidase inhibitors (MAOIs). Use cautiously if taking anticoagulants (blood thinners). Doses greater than those found in a normal diet are not recommended if pregnant or breastfeeding. Some types of avocado may be unsafe when breastfeeding.
Bromelain: Bromelain is an herb that contains a digestive enzyme that comes from the stem and the fruit of the pineapple plant. It has been proposed that bromelain may help treat symptoms of scleroderma. However, human studies have not evaluated the safety and efficacy of this therapy. Well-designed research is warranted in this area.
Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or other members of the Bromeliaceae family. Avoid with liver disease, kidney disease, or bleeding disorders. Use cautiously with bleeding disorders, stomach ulcers, high blood pressure, or acute genitourinary tract inflammation. Use cautiously before dental or surgical procedures or while driving or operating machinery. Use cautiously in children younger than two years of age. Avoid if pregnant or breastfeeding due to a lack of safety evidence.
Hydrotherapy: Hydrotherapy is broadly defined as the external application of water in any form or temperature for healing purposes. It may include immersion in a bath or body of water (such as the ocean or a pool), use of water jets, douches, application of wet towels to the skin, or water birth. Theoretically, hydrotherapy may help treat scleroderma. Well-designed studies are needed to determine if this therapy is safe and effective for scleroderma patients.
Avoid sudden or prolonged exposure to extreme temperatures in baths, wraps, saunas, or other forms of hydrotherapy, particularly with heart disease, lung disease, or if pregnant. Avoid with implanted medical devices (e.g. pacemakers, defibrillators, or liver infusion pumps). Vigorous use of water jets should be avoided with fractures, known blood clots, bleeding disorders, severe osteoporosis, open wounds, or during pregnancy. Use cautiously with Raynaud's disease, chilblains, acrocyanosis, erythrocyanosis, or impaired temperature sensitivity. Use cautiously if pregnant or breastfeeding. Hydrotherapy should not delay the time to diagnosis or treatment with more proven techniques or therapies, and it should not be used as the sole approach to illnesses. Patients with known illnesses should consult their physicians before starting hydrotherapy.
Niacin: Niacin (a component of vitamin B3) is a B-complex vitamin found in a many foods, including liver, poultry, fish, nuts, and dried beans. It is needed for the nervous system and gastrointestinal tract function. Although niacin has been suggested as a possible treatment for scleroderma, scientific evidence is lacking. Well-designed studies are needed to draw a firm conclusion in this area.
Avoid niacin or vitamin B3 if allergic to niacin or niacinamide. Use cautiously with peptic ulcer disease, diabetes mellitus, or gout. Avoid with liver disorders. Periodic monitoring of homocysteine levels may be warranted because niacin has been shown to increase homocysteine levels up to 55%. If pregnant or breastfeeding, niacin supplements should be only be taken under the supervision of a healthcare provider.
Organic food: In the United States, a product is considered "organic" if the food, the farm, handlers, and processors of that food all meet specific criteria from the U.S. Department of Agriculture (USDA). These criteria include that livestock receive no antibiotics or growth hormones and that produce is grown without most conventional pesticides, or synthetic or sewage sludge-based fertilizers. It has been suggested, but not scientifically proven, that organic food may help treat symptoms of scleroderma. In order to determine if organic food helps with this condition, well-designed scientific studies must be performed.
There is currently a lack of available safety information on organic food due to a lack of scientific research. Organic food is generally assumed to be at least as safe as conventional foods.
Physical therapy: The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injury. A variety of techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions. Although physical therapy has been used to treat scleroderma, studies have not been performed to determine the safety and efficacy of this treatment. Further research is warranted in this area.
Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, physical therapy may aggravate some pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature, although causality is unclear. Erectile dysfunction has also been reported. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Vitamin D: Vitamin D is found in many foods, including fish, eggs, fortified milk, and cod liver oil. The sun also helps the body produce vitamin D. Although vitamin D has been proposed as a possible treatment for scleroderma, scientific studies have not evaluated the safety or efficacy of this therapy.
Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses. Doses higher than recommended may cause toxic effects. Individuals with overactive thyroids, kidney disease, sarcoidosis, tuberculosis, or histoplasmosis have a higher risk of experiencing toxic effects. Vitamin D is generally considered safe for pregnant women. It may be necessary to give infants vitamin D supplements along with breast milk in order to prevent vitamin deficiencies.
Currently, there is no known method of prevention for scleroderma.
Patients who are diagnosed with scleroderma should visit their healthcare providers regularly to monitor their conditions. Properly managing the symptoms of the disease may help increase the patient's quality of life and help slow the progression of the disease.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
- American College of Rheumatology. www.rheumatology.org. Accessed April 28, 2009.
- Duraj V, Tafai A, Roshi E, et al. Esophageal damages in systemic scleroderma. Med Arh. 2007;61(1):47-8. View abstract
- Highland KB, Garin MC, Brown KK. The spectrum of scleroderma lung disease. Semin Respir Crit Care Med. 2007 Aug;28(4):418-29. View abstract
- Kane GC, Varga J, Conant EF, et al. Lung involvement in systemic sclerosis (scleroderma): relation to classification based on extent of skin involvement or autoantibody status. Respir Med. 1996 Apr;90(4):223-30. View abstract
- Lomeo RM, Cornella RJ, Schabel SI, et al. Progressive systemic sclerosis sine scleroderma presenting as pulmonary interstitial fibrosis. Am J Med. 1989 Nov;87(5):525-7. View abstract
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. www.niams.nih.gov. Accessed April 28, 2009.
- Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed April 28, 2009.
- Penn H, Howie AJ, Kingdon EJ, et al. Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM. 2007 Aug;100(8):485-94. Epub 2007 Jun 29. View abstract
- Scleroderma Foundation. www.scleroderma.org. Accessed April 28, 2009.
- Traub YM, Shapiro AP, Rodnan GP, et al. Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore). 1983 Nov;62(6):335-52. View abstract
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