What Is It?
Scleroderma is a chronic, autoimmune disease that can cause hardening and thickening of the skin and attack the heart, lungs, kidneys and gastrointestinal tract.
Women are three to four times more likely than men to be afflicted with scleroderma, a chronic, autoimmune disease that most often strikes women during middle age. It can cause hardening and thickening of the skin and attack the heart, lungs, kidneys and gastrointestinal tract.
The disease is caused by inflammation of small veins and arteries leading to overproduction of collagen in your body's connective tissue. Collagen is normally responsible for keeping your skin and organs supple, but when it is overproduced, it makes tissue thick and immobile.
Scleroderma literally means "hard skin," but the disease is most serious when it affects internal organs, hardening the tissues of the lungs, heart, kidneys, intestinal tract, muscles and joints. This stiffening can seriously harm the circulatory, digestive and respiratory systems. In some organs, the inflammation of blood vessels causes blockage of blood to the areas.
According to the Scleroderma Foundation, an estimated 300,000 people in the United States have the disease in one of its forms.
What causes scleroderma is unknown, but some early stage research suggests the involvement of both environmental and genetic factors. It appears likely that some people are genetically predisposed to scleroderma. And some research shows that certain environmental factors or combinations of factors--exposure to certain chemicals, for example--may play a role in triggering the disease. Though scleroderma affects members of all ethnic groups, researchers have found a high prevalence of the disease in Oklahoma Choctaw Native Americans. Additionally, African-American women seem to be more seriously affected when they get the disease. These facts reinforce the notion that there are chromosomal factors at work.
Researchers have discovered autoantibodies in scleroderma patients that are not seen in other autoimmune diseases. Learning how and why these antibodies form will lead to better understanding of the mechanisms that underlie this disorder.
Although scleroderma can run in families, in most cases it occurs in people who do not have a close relative with the disease. And scleroderma is not contagious.
Occupational exposure to silica dust (not silicone) has been linked to a scleroderma-like disease, particularly in men. Other substances linked to the development of scleroderma include paint thinners and certain chemotherapy drugs.
Scleroderma, like other autoimmune diseases, develops when the immune system turns its infection-fighting weapons including antibodies against the body's own healthy tissues. In scleroderma, the body produces specific autoantibodies. Blood tests for these antibodies are useful in defining the seriousness of the disease, although they are not present in all patients.
The disorder seems to be resistant to some drugs designed to suppress the immune system. However, new agents directed at newly recognized parts of the immune system are being tested. The disease is extremely complex and highly individualized. If you suspect you have scleroderma, you should seek a physician with experience diagnosing and treating the disease, since many physicians are not well versed in its intricacies.
Diagnosing scleroderma in its mildest forms can challenge even the most experienced physician, whereas the diagnosis is more straightforward if there is extensive skin thickening. Sometimes, the disease manifests itself in mild symptoms, but can also be life threatening. While symptoms and outcomes vary greatly, scleroderma is divided into two broad categories:
Localized scleroderma is the milder version, and the skin is usually the only organ affected. In one manifestation, called morphea, oval patches of inflamed and discolored skin may appear on the body. Many people with morphea will improve spontaneously over time. In localized scleroderma, a band or bands of skin may be thickened on the trunk or extremities. Usually affecting children under 18, localized scleroderma may be associated with loss or decreased growth of deep tissue or bone structure. When this type of scleroderma occurs on the face, it's called en coup de sabre, French for "a strike of the sword." While disfiguring, localized scleroderma isn't considered a serious threat to ability to function. Localized scleroderma almost never develops into the more serious systemic form of the disease.
Systemic sclerosis may affect blood vessels and connective tissue in various parts of your body (such as skin, the esophagus, gastrointestinal tract, lungs, kidneys, heart and other internal organs). It can also affect muscles and joints. This form of scleroderma may lead to disfigurement, serious disability, organ failure and early death.
Systemic sclerosis also comes in two forms:
* Limited systemic sclerosis. Skin thickening is confined to the fingers, hands and forearms, with or without skin tightening on the feet and lower legs. In limited sclerosis the course is usually much slower and less severe for many years, although severe lung involvement can occur.
Systemic-limited scleroderma is also sometimes referred to as CREST syndrome, which is characterized by:
** Calcinosis (accumulation of calcium deposits under the skin that may cause pain)
** Raynaud's phenomenon (characterized by a change in skin color of the fingers or toes due to cold)
** Esophageal dysfunction (caused by stiffening of the gastrointestinal tract muscles; gastroesophageal reflux, a form of indigestion, is a common result)
** Sclerodactyly (hardening of skin of the fingers or toes)
** Telangiectasias (tiny blood vessels near the surface of the skin that show through as round, red spots)
* Diffuse systemic sclerosis. Skin manifestations are more widespread, and internal organs--particularly the kidney, lungs and heart--may also be affected. This form of scleroderma can hinder the functions of your digestive system, create respiratory problems and cause kidney failure. If it goes untreated, systemic scleroderma may be fatal within a few years of onset.
Because scleroderma's symptoms vary in severity and type, it may be hard to get a definitive, positive diagnosis in the early stages of the disease. Consult a physician if you have any of the symptoms listed below, but remember that none of these necessarily mean you have scleroderma:
* pitted scars on the fingertips
* thickening or hardening of the skin (either in small patches or over larger portions of the face, hands and feet)
* finger ulcerations (sores)
* Raynaud's phenomenon; almost every scleroderma patients has this condition. Raynaud's can involve an abnormal sensitivity to cold in the extremities; a temporary change in hand and foot color to bluish or white or a change in sensation in the fingers and toes; pain; and occasionally ulcers of the fingertips or toes. Remember, however, that most patients with Raynaud's never progress to other symptoms of scleroderma.
* swelling and thickening of the skin on the hands and feet
* pain and stiffness of the joints
* joint contractures
* digestive system and gastrointestinal tract problems, especially heartburn, and problems with food getting stuck in the esophagus on the way to the stomach.
* dry mucus membranes
* kidney, heart and lung problems
* nonspecific symptoms such as extreme fatigue, generalized weakness, weight loss and vague aching of muscles, joints and bones
* shortness of breath with lung x-rays showing fibrosis
Another factor making diagnosis difficult is that many of these symptoms are common to other diseases, especially other connective-tissue diseases such as rheumatoid arthritis, lupus and polymyositis (muscle inflammation).
In addition to the symptoms and physical changes apparent on examination, your physician may look at blood tests measuring autoantibodies (such as the antinuclear antibody test), along with the nailfold capillary test. Based on the observation that small capillaries in the hands may be dilated or disappear early on in scleroderma patients, the test involves taking a microscopic look at skin under the fingernail, to see if capillaries look normal.
You may need to consult a number of physicians before receiving an accurate diagnosis. Remember that the results from one test alone cannot conclusively determine whether you have scleroderma. It may take a team of health care professionals to analyze various test results. They will probably also need to look at your complete medical history before making a definitive diagnosis.
As with many chronic illnesses such as high blood pressure, diabetes or asthma, there is no cure for scleroderma. However, there are effective treatments for many of the symptoms. Treatment will be determined by the type and severity of your particular symptoms. If you have been diagnosed with scleroderma, you may need to consult a team of health care professionals, including a rheumatologist and a dermatologist.
Some treatments may work on one patient and not another, and some may lose their effectiveness over time. What makes identifying successful treatments particularly difficult is that, in some patients, scleroderma can go into unexplained remission, which may give the impression that a particular course of treatment was effective even if it wasn't.
Your physician may refer you to a physical therapist, who can help you learn techniques to protect swollen and painful joints. This can involve learning different ways to perform such daily tasks as dressing, brushing your teeth and driving.
You and your physician need to be alert for any changes in your health; it's particularly essential to regularly monitor blood pressure, blood counts, urinalysis and kidney and lung function.
Various medications can be prescribed to reduce skin thickening and delay internal-organ involvement. Results are mixed. Be sure to discuss possible side effects with your physician. If you decide to start taking medications, you and your physician should monitor the effects carefully; some of these drugs can be toxic.
* Calcium channel blockers. These drugs increase blood flow by interrupting the normal flow of calcium into and out of the cells that make up the blood vessels and narrow arteries. They are prescribed to people with Raynaud's phenomenon to keep arteries from closing. Common side effects include low blood pressure, dizziness or lightheadedness, headache, nausea, leg swelling and irregular heartbeats.
* Angiotensin-converting enzyme (ACE) inhibitors. These drugs interfere with the body's chemical processes that constrict blood vessels, and they help alleviate the high blood pressure sometimes associated with scleroderma. Common side effects include dry persistent cough, rash and dizziness.
* Antiplatelet drugs. Antiplatelet therapy in the form of low-dose aspirin inhibits blood clotting.
* Glucocorticoids. These drugs may be used in low doses to relieve scleroderma-related pericarditis (inflammation of the membrane surrounding the heart) and myositis (inflammation of the muscles). The topical form may also be used on lesions of localized scleroderma.
* Immunosuppressants. A few immunosuppressant drugs, including the cancer drugs cyclophosphamide (Cytoxan) and methotrexate (Rheumatrex and Trexall), have been shown to be effective in treating the inflammatory stage of scleroderma in some people.
Nonsteroidal anti-inflammatory drugs (NSAIDs)--such as aspirin, ibuprofen and naproxen--may relieve some of your joint and tendon pain and swelling, as well as the chest pain that sometimes accompanies scleroderma. But NSAIDs can upset your stomach and aggravate the gastrointestinal (GI) symptoms of scleroderma. Plus, there is the potential for cardiovascular events and GI bleeding associated with the use of NSAIDS. It is important to ask your physician for safety information associated with pain relievers.
Lung fibrosis leading to pulmonary hypertension is one of the major complications of patients with scleroderma. For treatment of lung fibrosis, some success has been reported with the use of an immunosuppressive drug such as cyclophosphamide (Cytoxan), azathioprine (Azasan) or mycophenolate mofetil (CellCept). Treatment options for pulmonary hypertension associated with scleroderma include the endothelin receptor antagonist bosentan (Tracleer); the phosphodiesterase inhibitors sildenafil (Revatio), vardenafil (Levitra) or tadalafil (Adcicra); and various prostacyclin analogs, such as epoprostenol (Flolan), treprostinil (Remodulin) and iloprost (Ventavis). The medical community has concluded that corticosteroids should be used cautiously and only for people who have been carefully screened. For example, they may be used to manage people who also have muscle inflammation. If you are taking corticosteroids, you should monitor your blood pressure frequently and report any changes to your physician immediately.
With advanced lung fibrosis or pulmonary hypertension, the only options may be a single or double lung transplant, sometimes including a heart transplant if heart problems are severe or stem cell transplantation. Of course, pulmonary infections often require antibiotics.
If lifestyle and dietary changes aren't enough to avoid severe gastrointestinal symptoms and over-the-counter antacids don't work, you and your physician may want to consider H2 blockers such as ranitidine (Zantac), cimetidine (Tagamet) or famotidine (Pepcid AC), which reduce the amount of acid produced by the stomach. Proton pump inhibitors such as lansoprazole (Prevacid), omeprazole (Prilosec) and similar drugs are more powerful acid reducers and may be necessary.
Lifestyle changes can help mitigate the chronic heartburn (reflux) often associated with scleroderma. Preventive measures such as elevation of the head of the bed and frequent small meals can help. You should try to avoid eating late at night, and you may need to give up alcohol, coffee and tea, since they can increase heartburn.
If you have systemic sclerosis and develop heart and kidney complications, you may be treated much the same as any cardiac or renal patients. ACE (angiotensin-converting enzyme) inhibitors are used to treat kidney disease associated with scleroderma. ACE inhibitors are often used to treat high blood pressure, which occurs in scleroderma renal crises.
For skin thickening, treatments may include nitroglycerin ointment, phototherapy (light therapy), a form of vitamin D3 called calcipotriene (Dovonex), immunosuppressive drugs such as D-penicillamine and methotrexate (Rheumatrex, Trexall) or corticosteroids.
A scleroderma treatment plan almost always incorporates therapy for Raynaud's phenomenon, which afflicts about 90 percent of those with scleroderma. There are some basic lifestyle changes you can make to prevent or decrease the severity of the symptoms: You should dress warmly and limit outdoor activities in cold weather. If you live in the North, you may want to consider moving to a warmer climate. But remember, air conditioning can trigger attacks, so you may want to turn it off or wear a sweater when it's running. You may find that using insulated drinking glasses and wearing gloves to handle frozen or refrigerated food items will help.
This disorder is characterized by episodic attacks, called vasospastic attacks, that cause the blood vessels in the fingers and toes to constrict. During an attack, some of the same guidelines apply. The most important thing is to warm your hands and feet. In cold weather, go inside immediately. You may want to run warm water over your fingers and/or toes or soak them in warm water.
Since stress and emotional upset can trigger an attack, you may want to try to relax. If you are in a stressful situation, get out. In fact, you should learn to identify and avoid stressful situations. Many people with Raynaud's find that exercise helps reduce stress, but check with your physician before starting an exercise program.
In addition, if you smoke, stop. Not only is it bad for your overall health, the nicotine in cigarettes causes the skin temperature to drop, which may lead to an attack.
Several medications can relieve Raynaud's symptoms. Calcium channel blockers such as nifedipine (Procardia) and diltiazem (Cardizem), which relax blood vessels, may help. These drugs also can help heal skin ulcers on the fingertips or toes. As with any medication, there are some side effects, so discuss the benefits and potential dangers of any drug therapy with your physician.
You may consider using a nonspecific vasodilator (drug that relaxes blood vessels), such as nitroglycerin ointment. You would apply this directly to your fingers to help increase circulation. Other drugs used to treat Raynaud's include losartan potassium (Cozaar), doxazosin (Cardura), prazosin (Minipress) and pentoxifylline (Trental), a blood thinner.
A word of warning: these medications often have side effects that limit long-term use. Drugs used to treat Raynaud's phenomenon may affect a growing fetus. If you are pregnant or are trying to become pregnant, discuss your treatment options with your physician.
If you have been diagnosed with scleroderma, consult your physician before planning to have a baby. If you plan to become pregnant, you may need to adjust your medications and address specific risks with your doctor beforehand. Pregnancy in women with scleroderma is always considered high risk, and extra monitoring and precautions are necessary, both before and during the pregnancy. People with rapid onset or severe internal organ involvement may need to postpone pregnancy until the symptoms subside or until toxic treatments are finished. Some women with severe scleroderma may be advised to forego pregnancy or consider adoption or surrogate parenthood. Discuss your decision with your physician.
No one really knows enough about scleroderma to know whether there is a way to prevent the disease or delay its onset.
Occupational exposures to the silica dust (not silicone) found in mines and stonework settings have been linked to scleroderma. Solvents used in paint thinners and removers and certain chemotherapy drugs have also been implicated.
Although clear-cut guidance on prevention is lacking, there are measures you can take to prevent or lessen the symptoms if you have been diagnosed with scleroderma.
Dental care is essential. Some people with scleroderma develop excessive dryness of the mouth, which can lead to tooth decay. But oral hygiene may become difficult if your facial skin becomes tight. Visit your dentist often, and make sure he or she is aware of your condition. To combat dryness, try artificial saliva products. Excessively dry eyes also may cause discomfort. You can sometimes relieve dryness with lubricating drops and ointments.
Regular exercise or stretching can maintain joint flexibility and help keep your skin pliable. Other strategies include frequent massage of the skin and avoidance of detergent soaps, which dry the skin. Frequent use of bath oils and moisturizing lotions or ointments can help soften the skin, and a cold-water room humidifier can keep your skin moist.
Reducing stress is critical, and some experts suggest biofeedback training. It could help reduce pain and promote relaxation. You and your physician can decide whether this approach will work for you. Joining a scleroderma support group can also help with the emotional aspects of the disease, and you will be able to exchange information with others who have the same problems.
Facts to Know
1. Women are three to four times more likely than men to be afflicted with scleroderma. According to the Scleroderma Foundation, an estimated 300,000 people in the United States have the disease in one of its forms.
2. Scleroderma, which literally means "hard skin," is caused by an overproduction of collagen in your body's connective tissue. Collagen is normally responsible for keeping your skin and organs supple, but when it is overproduced, it makes tissue thick and immobile.
3. Occupational exposure to silica dust (not silicone), solvents used in paint thinners and removers and certain chemotherapy drugs have been linked to the disease.
4. Scleroderma is considered an autoimmune disease. Such diseases develop when the immune system turns its infection- fighting weapons--antibodies--against the body's own healthy tissues. In scleroderma, the body produces autoantibodies.
5. Localized scleroderma is one of the two major types of scleroderma. It is the milder version, in which the skin is generally the only organ affected. In one manifestation, called morphea, oval patches of inflamed and discolored skin may appear on the body. Many people with morphea will improve spontaneously over time.
6. Systemic sclerosis is the other major type of scleroderma. It is the more severe form. It can affect connective tissue in various parts of your body, such as skin, the esophagus, gastrointestinal tract, lungs, kidneys, heart and other internal organs. Systemic sclerosis can also affect blood vessels, muscles and joints.
7. Almost every scleroderma patients has Raynaud's phenomenon, which can involve an abnormal sensitivity to cold in the extremities, a temporary change in color and sensation in the fingers and toes, changes in skin color, pain and occasionally ulcers of the fingertips or toes.
8. Although scleroderma can run in families, in most cases, it occurs in people who do not have a relative with the disease. Scleroderma is also definitely not contagious.
9. Some of the major symptoms of scleroderma include thickening or hardening of the skin; finger sores; Raynaud's phenomenon; swelling of the hands and feet; joint pain and stiffness; joint contractures; digestive system and gastrointestinal tract problems; shortness of breath; and dryness of the skin and mucous membranes. Diagnosis involves determining which symptoms you have and may include blood tests for autoantibodies and the nailfold capillary test.
10. There is no cure for scleroderma, although research continues. If you have the disease, physicians can treat your symptoms and try to treat the underlying disease, using both medications and lifestyle changes.
Questions to Ask
Review the following Questions to Ask about scleroderma so you're prepared to discuss this important health issue with your health care professional.
1. Do my symptoms indicate scleroderma?
2. Can you rule out other disorders that might cause my symptoms?
3. What drugs are available to help me? What are their benefits and side effects? Will these drugs interact with any other medications I am taking?
4. What nonmedical strategies can we use to limit the progression of my scleroderma and relieve symptoms when they occur?
5. What should I do if medications don't seem to be working?
6. What precautions should I take to protect myself while exercising or being outdoors?
7. Can I benefit from dietary changes or losing weight?
8. What type of scleroderma do I have?
9. What can I do to be able to continue doing activities that are important to me?
10. Are there support groups or other programs for people with scleroderma?
1. What is scleroderma?
Scleroderma, which literally means "hard skin," is caused by an overproduction of collagen in your body's connective tissue. Collagen is normally responsible for keeping your skin and organs supple, but when it is overproduced, it makes tissue thick and immobile.
2. What's the difference between localized scleroderma and systemic sclerosis?
Localized scleroderma is the milder version, and the skin is generally the only organ affected. In one manifestation, called morphea, oval patches of inflamed and discolored skin may appear on the body. Systemic sclerosis may affect connective tissue in various parts of your body, such as skin, the esophagus, gastrointestinal tract, lungs, kidneys, heart and other internal organs. It can also affect blood vessels, muscles and joints. This form of scleroderma can lead to disfigurement, serious disability, organ failure and early death.
3. Do breast implants cause scleroderma?
There is no evidence that breast implants cause scleroderma.
4. What causes scleroderma?
Some people are born with a heightened genetic susceptibility, but other factors, including environmental ones, appear to play a part in development of the disease. Since women are three to four times more likely to contract scleroderma, gender obviously has a role. Scleroderma in men sometimes can be traced to particular environmental triggers: for example, exposure to silica dust and solvent mixtures.
5. Is there a proven cure for scleroderma?
No, although the disease may spontaneously improve as various treatments are being used. Symptoms often can be managed through lifestyle modifications and medications. Symptoms vary so widely from one individual to another, however, that treatment guidelines cannot be standardized. If you have scleroderma, talk to your physician about the best ways to treat your symptoms.
6. How can I tell if I have scleroderma?
Diagnosis is complicated, and you may need to consult more than one health care professional, for example a rheumatologist and dermatologist. Symptoms may include such nonspecific manifestations as extreme fatigue and pain in the joints, bones and muscles. Some of the more particular hallmarks of scleroderma include thickening or hardening of the skin; finger ulcerations (sores); Raynaud's phenomenon (abnormal sensitivity to cold and change in color in the extremities); digestive symptoms and gastrointestinal tract problems; shortness of breath; palpitations; and dry mucus membranes. A diagnosis will take into account presence of one or more of these symptoms, as well as blood tests for autoantibodies and perhaps a nailfold capillary test.
7. How can I prevent scleroderma?
There is no known way to prevent scleroderma.
8. Can I have a baby if I have scleroderma?
If you have been diagnosed with scleroderma, consult your physician before planning to have a baby. You may need to adjust your medications and address specific risks with your doctor beforehand. Many women with scleroderma have successfully had children, but it is always considered high risk and extra monitoring and precautions are necessary, both before and during the pregnancy. And women with rapid onset or severe internal organ involvement may need to postpone pregnancy until the symptoms subside or until toxic treatments are finished. Some women with severe scleroderma may be advised to forego pregnancy or consider adoption or surrogate parenthood. Discuss your decision with your physician.
9. Are medications available to treat scleroderma?
Drugs that tamp down the immune system may be prescribed, as well as low-dose aspirin, glucocorticoids, diuretics, nonsteroidal anti-inflammatory drugs for pain, topical antibiotics for finger sores, ACE inhibitors and calcium channel blockers to keep arteries clear and vasodilators for Raynaud's phenomenon. Be sure to ask your physician about side effects.
10. What is Raynaud's phenomenon?
Almost every scleroderma patient has this condition. Raynaud's can involve an abnormal sensitivity to cold in the extremities, a temporary change in color and sensation in the fingers and toes, changes in skin color, pain and occasionally ulcers of the fingertips or toes. If you have Raynaud's, there are some basic lifestyle changes you can make to prevent or decrease the severity of the symptoms, such as dressing warmly and limiting outdoor activities in cold weather.
Organizations and Support
For information and support on coping with Scleroderma, please see the recommended organizations, books and Spanish- language resources listed below.
American Academy of Dermatology
Address: P.O. Box 4014
Schaumburg, IL 60618
Hotline: 866-503-SKIN (7546)
Address: 300 Rosewood Drive, Suite 105
Danvers, MA 01923
Hotline: 1-800-722-HOPE (1-800-722-4673)
Scleroderma Research Foundation
Address: 220 Montgomery Street, Suite 1411
Santa Francisco, CA 94104
Hotline: 1-800-441-CURE (1-800-441-2873)
Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On with Your Life
by Rita Baron-Faust and Jill Buyon
Scleroderma Book: A Guide for Patients & Their Families
by Maureen D. Mayes M.D.
Medline Plus: Scleroderma
Address: US National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Address: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) / National Institutes of Health
1 AMS Circle
Bethesda, MD 20892
"Systemic scleroderma." The Cleveland Clinic. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/rheumatology/systemic-sclerosis/. Accessed May 2012.
"Pulmonary involvement." The Scleroderma Foundation. May 29, 2012. http://www.scleroderma.org/medical/pulmonary_articles/connolly_2002.shtm. Accessed May 2012.
"Erectile dysfunction drug could improve raynaud's symptoms associated with scleroderma." American College of Rheumatology Press Release. 2010. http://www.rheumatology.org/about/newsroom/2010/2010_erectile_dysfunction_drug_could_improve- raynuads_symptoms_associated_with_schleroderma.asp. Accessed July 2012.
"Scleroderma fact sheet." The Scleroderma Foundation and American College of Rheumatology. May 2008. http://www.rheumatology.org/public/factsheets/diseases_and_conditions/scleroderma.pdf. Accessed January 2010.
"Limited Scleroderma (CREST Syndrome)." The Mayo Clinic. June 2009. http://www.mayoclinic.com/health/crest- syndrome/DS00580. Accessed January 2010.
"Scleroderma." The Mayo Clinic. October 2008. http://www.mayoclinic.com/health/scleroderma/DS00362. Accessed January 2010.
"Scleroderma." The Mayo Clinic. October 2008. (NOTE: Different link from above) http://www.mayoclinic.com/print/scleroderma/DS00362/DSECTION=all&METHOD=print. Accessed January 2010.
"Scleroderma treatment options." Johns Hopkins Medicine. 2009. http://scleroderma.jhmi.edu/patients/treatment- options.html. Accessed January 2010.
Updated information from the International Scleroderma Network. January 2010. http://www.sclero.org/medical/treatments/mainstream/immunosuppressants.html. Accessed January 2010.
"Medication information." Scleroderma Foundation. Last updated November 16, 2007. http://www.scleroderma.org. Accessed November 2007.
"Occupational Exposure to Solvents and Gender-Related Risk of Systemic Sclerosis: a Metaanalysis of Case-Control Studies." The Journal of Rheumatology. January 2007. http://www.jrheum.com. Accessed November 2007.
"Medications for Scleroderma, Arthritis, Autoimmune and Rheumatic Diseases." The International Scleroderma Network. 2007. http://www.sclero.org. Accessed November 2007.
"Systemic sclerosis (scleroderma) and pregnancy." Uptodate. August 2007. http://patients.uptodate.com. Accessed November 2007.
"Types of scleroderma." MedifocusHealth. June 2007. http://www.medifocushealth.com. Accessed November 2007.
"What you need to know about scleroderma." The Cleveland Clinic. October 2006. http://www.clevelandclinic.org. Accessed November 2007.
"Overview of treatment and prognosis of scleroderma in adults." Uptodate.com. Updated September 2007. http://www.utdol.com. Accessed November 2007.
"Natural remedies for scleroderma." High Beam Encyclopedia. September 2006. http://www.encyclopedia.com. Accessed November 2007.
"Scleroderma Center." Johns Hopkins Medicine. 2007. http://scleroderma.jhmi.edu. Accessed November 2007.
Henness S, Wigley FM. http://www.ncbi.nlm.nih.gov. "Current drug therapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review." Curr Opin Rheumatol. 2007 Nov;19(6):611-618.
"Autoimmunity and pregnancy." The International Scleroderma Network. 2007. http://www.sclero.org. Accessed November 2007.
"FDA Issues Public Health Advisory on Vioxx as its Manufacturer Voluntarily Withdraws Its Product." U.S. Food and Drug Administration. http://www.fda.gov. Accessed October 1, 2004.
Scleroderma Research Foundation. http://www.srfcure.org. Accessed September 2003.
Clements, PJ, Furst, DE. Williams & Wilkins. 1996.
"Scleroderma." Arthritis Foundation. http://www.arthritis.org. Accessed August 2002.
Medsger, Thomas, Jr. "Chapter 74--Systemic Sclerosis (Scleroderma): Clinical Aspects." Arthritis and Allied Conditions. Baltimore. 13th ed. Ed. William Koopman. Williams & Wilkins. 1433-1462.
"Questions and Answers About Raynaud's Phenomenon." The National Institute of Arthritis and Musculoskeletal and Skin Diseases. May 2001. http://www.niams.nih.gov. Accessed August 2002.
"Raynaud's Phenomenon." Arthritis Foundation. http://www.arthritis.org. Accessed August 2002.
"Scleroderma" Arthritis Foundation. Brochure No: 835-5325. http://www.arthritis.org. Accessed August 2002.
"Handout on Health: Scleroderma" National Institute of Arthritis and Musculoskeletal Diseases. Published July 2001. http://www.niams.nih.gov. Accessed August 2002.
New Drops Offer Hope for Dry Eyes. Treatment Breaks the Cycle of Inflammation in Dry-Eye Disease. WebMD, April 12, 2000.
Scleroderma Fact Sheet. Scleroderma Foundation. http://www.scleroderma.org. Copyright 2002. Accessed September 2003.
"Scleroderma" EMedicine Journal. January 9, 2002, Vol. 3, No. 1. http://www.emedicine.com. Accessed August 2002.
Garabrant DH, et al. "Scleroderma and Solvent Exposure Among Women" Am J Epidemiol. 2003 March 15;157(6):493-500.