People with osteoarthritis often have joint pain and reduced motion. Unlike some other forms of arthritis, osteoarthritis affects only joints and not internal organs. Rheumatoid arthritis – the second most common form of arthritis – affects other parts of the body besides the joints. Osteoarthritis is the most common type of arthritis.

Who Gets Osteoarthritis?

Osteoarthritis occurs most often in older people. Younger people sometimes get osteoarthritis primarily from joint injuries.

What Causes Osteoarthritis?

The cause of osteoarthritis is unknown. Factors that might cause it include:

• Being overweight
• Getting older
• Joint injury
• Joints that are not properly formed
• A genetic defect in joint cartilage
• Stresses on the joints from certain jobs and playing sports.

How Is Osteoarthritis Diagnosed?

Osteoarthritis can occur in any joint. It occurs most often in the hands, knees, hips, and spine.

Warning signs of osteoarthritis are:

• Stiffness in a joint after getting out of bed or sitting for a long time
• Swelling or tenderness in one or more joints
• A crunching feeling or the sound of bone rubbing on bone.

No single test can diagnose osteoarthritis. Most doctors use several methods to diagnose the disease and rule out other problems:

• Medical history
• Physical exam
• X rays
• Other tests such as blood tests or exams of the fluid in the joints.

How Is Osteoarthritis Treated?

Doctors often combine treatments to fit a patient’s needs, lifestyle, and health. Osteoarthritis treatment has four main goals:

• Improve joint function
• Keep a healthy body weight
• Control pain
• Achieve a healthy lifestyle.

Osteoarthritis treatment plans can involve:

• Exercise
• Weight control
• Rest and joint care
• Nondrug pain relief techniques to control pain
• Medicines
• Complementary and alternative therapies
• Surgery.

How Can Self-Care and a “Good-Health Attitude” Help?

Three kinds of programs help people learn about osteoarthritis and self-care and improve their good-health attitude:

• Patient education programs
• Arthritis self-management programs
• Arthritis support groups.

These programs teach people about osteoarthritis and its treatments. They also have clear and long-lasting benefits. People in these programs learn to:

• Exercise and relax
• Talk with their doctor or other health care providers
• Solve problems.

People with osteoarthritis find that self-management programs help them:

• Understand the disease
• Reduce pain while staying active
• Cope with their body, mind, and emotions
• Have more control over the disease
• Live an active, independent life.

People with a good-health attitude:

• Focus on what they can do, not what they can’t do
• Focus on their strengths, not their weaknesses
• Break down activities into small tasks that are easy to manage
• Build fitness and healthy eating into their daily routines
• Develop ways to lower and manage stress
• Balance rest with activity
• Develop a support system of family, friends, and health care providers.

What Research Is Being Done on Osteoarthritis?

Osteoarthritis is not simply a disease of “wear and tear” that happens in joints as people get older. There is more to the disease than aging alone. Researchers are studying:

• Tools to detect osteoarthritis earlier
• Genes
• Tissue engineering
• A wide range of treatment strategies
• Osteoarthritis in animals
• Medicines to prevent joint damage
• Complementary and alternative therapies
• Vitamins and other supplements
• Injection of hyaluronic acid (a natural part of cartilage and joint fluid)
• Estrogen
• Biological and structural markers (biomarkers) for osteoarthritis.

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases - http://www.niams.nih.gov/Health_Info/Osteoarthritis/osteoarthritis_ff.asp

Current treatment with prednisone and the anti-cancer drug cyclophosphamide is effective, but has significant side effects and a high rate of disease recurrence. In a small number of patients with vasculitis, prednisone and methotrexate, another anti-cancer drug, have led to marked improvement, with fewer side effects than are seen with cyclophosphamide. This study will evaluate this drug combination in a larger patient population.

Patients 10 to 80 years of age with active Wegener’s granulomatosis, polyarteritis nodosa, Churg-Strauss vasculitis, or microscopic polyangiitis overlap may be eligible for this 2 1/2 to 3-year study. In addition, patients with glomerulonephritis (a type of kidney disease) and a positive blood test for C-ANCA (antibodies found in certain vasculitic kidney diseases) or inflammatory sinusitis or lung nodule or infiltrates in the absence of infection may also be enrolled.

Participants will take prednisone daily, by mouth, and low-dose methotrexate weekly, by mouth or by injection either under the skin, into a muscle or into a vein. Patients who significantly improve with treatment will gradually reduce, and eventually stop, the prednisone. If the remission lasts, methotrexate will also be reduced and stopped after 2 1/2 years. If active disease recurs, the original treatment program may be started again. Patients who never achieve complete remission with treatment but whose symptoms are well controlled and experience no serious side effects may choose to either continue low-dose methotrexate or stop therapy.

Patients will be hospitalized 4 to 6 times a year, about 2 to 8 days each time, depending on their disease severity and response to illness. In addition, they will have the following tests and procedures:

• Medical history and physical examination (upon admission to the study and then every 1 to 3 months).
• Blood tests for blood cell counts and for levels of enzymes that indicate liver damage (upon admission, then weekly, and finally, no less than monthly).
• Additional blood tests to measure blood chemistries and evaluate kidney function (upon admission and again when clinically indicated).
• Chest X-rays (upon admission and when clinically indicated).
• Computerized tomography (CT) and magnetic resonance imaging (as needed).
• Electrocardiogram (upon admission and then as clinically indicated).
• Lung function studies (upon admission and at least every 6 months or as clinically indicated).
• Ear, nose and throat evaluations (as clinically indicated).
• Liver biopsy, if blood tests to monitor liver function are persistently abnormal. This procedure is done in the hospital under sedation to induce relaxation and drowsiness. The skin over the liver (upper right abdomen) is numbed with a local anesthetic and a needle is passed rapidly in and out of the liver to collect a small tissue sample for microscopic examination.

• Sharp uric acid crystal deposits in joints, often in the big toe
• Deposits of uric acid (called tophi) that look like lumps under the skin
• Kidney stones from uric acid crystals in the kidneys.

For many people, the first attack of gout occurs in the big toe. Often, the attack wakes a person from sleep. The toe is very sore, red, warm, and swollen.

Gout can cause:

• Pain
• Swelling
• Redness
• Heat
• Stiffness in joints.

In addition to the big toe, gout can affect the:

• Insteps
• Ankles
• Heels
• Knees
• Wrists
• Fingers
• Elbows.

A gout attack can be brought on by stressful events, alcohol or drugs, or another illness. Early attacks usually get better within 3 to 10 days, even without treatment. The next attack may not occur for months or even years.

What Causes Gout?
How Is Gout Diagnosed?
How Is Gout Treated?
What Can People With Gout Do to Stay Healthy?
What Research Is Being Done on Gout?

What Causes Gout?

Gout is caused by the buildup of too much uric acid in the body. Uric acid comes from the breakdown of substances called purines. Purines are found in all of your body’s tissues. They are also in many foods, such as liver, dried beans and peas, and anchovies.

Normally, uric acid dissolves in the blood. It passes through the kidneys and out of the body in urine. But uric acid can build up in the blood when:

• The body increases the amount of uric acid it makes.
• The kidneys do not get rid of enough uric acid.
• A person eats too many foods high in purines.

When uric acid levels in the blood are high, it is called hyperuricemia. Most people with hyperuricemia do not develop gout. But if excess uric acid crystals form in the body, gout can develop.

You are more likely to have gout if you:

• Have family members with the disease
• Are a man
• Are overweight
• Drink too much alcohol
• Eat too many foods rich in purines
• Have an enzyme defect that makes it hard for the body to break down purines
• Are exposed to lead in the environment
• Have had an organ transplant
• Use some medicines such as diuretics, aspirin, cyclosporine, or levodopa
• Take the vitamin niacin.

How Is Gout Diagnosed?

Your doctor will ask about your symptoms, medical history, and family history of gout. Signs and symptoms of gout include:

• Hyperuricemia (high level of uric acid in the blood)
• Uric acid crystals in joint fluid
• More than one attack of acute arthritis
• Arthritis that develops in 1 day, producing a swollen, red, and warm joint
• Attack of arthritis in only one joint, usually the toe, ankle, or knee.

To confirm a diagnosis of gout, your doctor may draw a sample of fluid from an inflamed joint to look for crystals associated with gout.

How Is Gout Treated?

Doctors use medicines to treat an acute attack of gout, including:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids, such as prednisone
• Colchicine, which works best when taken within the first 12 hours of an acute attack.

Sometimes doctors prescribe NSAIDs or colchicine in small daily doses to prevent future attacks. There are also medicines that lower the level of uric acid in the blood.

What Can People With Gout Do to Stay Healthy?

Some things that you can do to stay healthy are:

• Take the medicines your doctor prescribes as directed.
• Tell your doctor about all the medicines and vitamins you take.
• Plan followup visits with your doctor.
• Maintain a healthy, balanced diet. Avoid foods that are high in purines, and drink plenty of water.
• Exercise regularly and maintain a healthy body weight. Ask your doctor about how to lose weight safely. Fast or extreme weight loss can increase uric acid levels in the blood.

What Research Is Being Done on Gout?

Scientists are studying:

• Which NSAIDs are the most effective treatments for gout
• Optimal dosages of medications for gout
• New medicines that safely lower uric acid in the blood and reduce symptoms
• New therapies that block a chemical called tumor necrosis factor
• Enzymes that break down purines in the body
• The role of foods and certain vitamins
• The role of genetics and environmental factors
• The interactions of cells involved in acute gout attacks.

Scientists are also studying the role of genetics and environmental factors in hyperuricemia and gout.

For More Information on Gout and Other Related Conditions:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information Clearinghouse
National Institutes of Health

1 AMS Circle
Bethesda,  MD 20892-3675
Phone: 301-495-4484
Toll Free: 877-22-NIAMS (226-4267)
TTY: 301–565–2966
Fax: 301-718-6366
Email: NIAMSinfo@mail.nih.gov
Website: http://www.niams.nih.gov

The information in this publication was summarized in easy-to-read format from information in a more detailed NIAMS publication. To order the Gout Q&A full-text version, please contact NIAMS using the contact information above. To view the complete text or to order online, visit http://www.niams.nih.gov.

For Your Information

This publication contains information about medications used to treat the health condition discussed here. When this publication was printed, we included the most up-to-date (accurate) information available. Occasionally, new information on medication is released.

For updates and for any questions about any medications you are taking, please contact the U.S. Food and Drug Administration at 1–888–INFO–FDA (1–888–463–6332, a toll-free call) or visit their Web site atwww.fda.gov.

U.S. Food and Drug Administration

Toll Free: 888-INFO-FDA (888-463-6332)
Website: http://www.fda.gov/

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases – http://www.niams.nih.gov/Health_Info/Gout/gout_ff.asp

What are the symptoms of Goodpasture’s syndrome?

Goodpasture’s syndrome can cause people to cough up blood or feel a burning sensation when urinating. But its first signs may be vague, such as fatigue, nausea, difficulty breathing, or paleness. These signs are followed by kidney involvement, represented first by small amounts of blood in the urine, protein in the urine, and other clinical and laboratory findings.

How is Goodpasture’s syndrome diagnosed?

To diagnose Goodpasture’s syndrome, doctors use a blood test, but a kidney or lung biopsy may be necessary to check for the presence of the harmful antibodies.

How is Goodpasture’s syndrome treated?

Goodpasture’s syndrome is treated with oral immunosuppressive drugs—cyclophosphamide and corticosteroids—to keep the immune system from making antibodies. Corticosteroid drugs may be given intravenously to control bleeding in the lungs. A process called plasmapheresis may be helpful and necessary to remove the harmful antibodies from the blood. In plasmapheresis, a patient’s blood is drawn, about 300 ml at a time, and placed in a centrifuge to separate the red and white blood cells from the plasma. The cells are then placed in a plasma substitute and returned to the body. This procedure is usually done in combination with immunosuppressive drug treatment.

Goodpasture’s syndrome may last only a few weeks or as long as 2 years. Bleeding in the lungs can be very serious and even fatal in some cases. But Goodpasture’s syndrome does not usually lead to permanent lung damage. Damage to the kidneys, however, may be long-lasting. If the kidneys fail, dialysis to remove waste products and extra fluid from the blood, or kidney transplantation, may become necessary.

For More Information

American Kidney Fund
6110 Executive Boulevard, Suite 1010
Rockville, MD 20852
Phone: 1–800–638–8299
Email: helpline@kidneyfund.org
Internet: www.kidneyfund.org

National Kidney Foundation, Inc.
30 East 33rd Street
New York, NY 10016
Phone: 1–800–622–9010 or 212–889–2210
Internet: www.kidney.org

You may also find additional information about this topic by visiting MedlinePlus at www.medlineplus.gov.

This publication may contain information about medications. When prepared, this publication included the most current information available. For updates or for questions about any medications, contact the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–888–463–6332) or visit www.fda.gov. Consult your doctor for more information.

National Kidney and Urologic Diseases Information Clearinghouse

3 Information Way
Bethesda, MD 20892–3580
Phone: 1–800–891–5390
TTY: 1–866–569–1162
Fax: 703–738–4929
Email: nkudic@info.niddk.nih.gov
Internet: www.kidney.niddk.nih.gov

The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health of the U.S. Department of Health and Human Services. Established in 1987, the Clearinghouse provides information about diseases of the kidneys and urologic system to people with kidney and urologic disorders and to their families, health care professionals, and the public. The NKUDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about kidney and urologic diseases.

This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.

NIH Publication No. 07–4558
April 2007

Source: National Kidney and Urologic Diseases Information Clearinghouse - http://kidney.niddk.nih.gov/kudiseases/pubs/goodpasture/

Illustration of Male Body

Joints are places where two bones meet, such as your elbow or knee. Over time, in some types of arthritis but not in all, the joints involved can become severely damaged.

There are different types of arthritis. In some diseases in which arthritis occurs, other organs, such as your eyes, your chest, or your skin, can also be affected. Some people may worry that arthritis means they won’t be able to work or take care of their children and their family. Others think that you just have to accept things like arthritis.

It’s true that arthritis can be painful. But there are things you can do to feel better. This booklet tells you some facts about arthritis and gives you some ideas about what to do, so you can keep doing many of the things you enjoy.

• What Are the Types of Arthritis?
• Do I Have Arthritis?
• What Can I Do?
• How Will the Doctor Help?
• How Should I Use Arthritis Medicine?
• What If I Still Hurt?
• You Can Feel Better!
• For More Help
• Acknowledgments

What Are the Types of Arthritis?

There are several types of arthritis. The two most common ones are osteoarthritis (AH-stee-oh-ar-THRY-tis) and rheumatoid (ROO-mah-toyd) arthritis.

Osteoarthritis is the most common form of arthritis. This condition usually comes with age and most often affects the fingers, knees, and hips. Sometimes osteoarthritis follows an injury to a joint. For example, a young person might hurt his knee badly playing soccer. Or someone might fall or be injured in a car accident. Then, years after the individual’s knee has apparently healed, he might get arthritis in his knee joint.

Rheumatoid arthritis happens when the body’s own defense system doesn’t work properly. It affects joints and bones (often of the hands and feet), and may also affect internal organs and systems. You may feel sick or tired, and you may have a fever.

Another common type of arthritis, gout, is caused by crystals that build up in the joints. It usually affects the big toe, but many other joints may be affected.

Arthritis is seen with many other conditions. These include:

• lupus (LOOP-us), in which the body’s defense system can harm the joints, the heart, the skin, the kidneys, and other organs
• an infection that gets into a joint and destroys the cushion between the bones.

Do I Have Arthritis?

Pain is the way your body tells you that something is wrong. Most types of arthritis cause pain in your joints. You might have trouble moving around. Some kinds of arthritis can affect different parts of your body. So, along with pain in your joints, you may:

• have a fever
• lose weight
• have trouble breathing
• get a rash or itch.

These symptoms may also be signs of other illnesses.

Gardening

What Can I Do?

Go see a doctor. Many people use herbs or medicines that you can buy without a prescription for pain. You should tell your doctor if you do. Only a doctor can tell if you have arthritis or a related condition and what to do about it. It’s important not to wait.

You’ll need to tell the doctor how you feel and where you hurt. The doctor will examine you and may take x rays (pictures) of your bones or joints. The x rays don’t hurt and aren’t dangerous. You may also have to give a little blood for tests that will help the doctor decide what kind of arthritis you may have.

Doctor and Patient

How Will the Doctor Help?

After the doctor knows what kind of arthritis you have, he or she will talk with you about the best way to treat it. The doctor may give you a prescription for medicine that will help with the pain, stiffness, and inflammation. Health insurance or public assistance may help you pay for the medicine, doctor visits, tests, and x rays.

How Should I Use Arthritis Medicine?

Before you leave the doctor’s office, make sure you ask about the best way to take the medicine the doctor prescribes. For example, you may need to take some medicines with milk, or you may need to eat something just before or after taking them, to make sure they don’t upset your stomach.

You should also ask how often to take the medicine or to put cream on the spots that bother you. Creams might make your skin and joints feel better. Sometimes, though, they can make your skin burn or break out in a rash. If this happens, call the doctor.

What If I Still Hurt?

Sometimes you might still have pain after using your medicine. Here are some things to try:

• Take a warm shower.
• Do some gentle stretching exercises.
• Use an ice pack on the sore area.
• Rest the sore joint.

If you still hurt after using your medicine correctly and doing one or more of these things, call your doctor. Another kind of medicine might work better for you. Some people can also benefit from surgery, such as joint replacement.

Mother and Child

You Can Feel Better!

Arthritis can damage your joints, internal organs, and skin. There are things you can do to keep the damage from getting worse. They might also make you feel better:

• Try to keep your weight down. Too much weight can make your knees and hips hurt.
• Exercise. Moving all of your joints will help you. The doctor or nurse can show you how to move more easily. Going for a walk every day will help, too.
• Take your medicines when and how you are supposed to. They can help reduce pain and stiffness.
• Try taking a warm shower in the morning.
• See your doctor regularly.
• Seek information that can help you.

Walking a dog

For More Help

For more information on arthritis and related conditions, contact any of the following organizations:

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  Information Clearinghouse
  National Institutes of Health

  1 AMS Circle
  Bethesda,  MD 20892-3675
  Phone: 301-495-4484
  Toll Free: 877-22-NIAMS (226-4267)
  TTY: 301–565–2966
  Fax: 301-718-6366
  Email: NIAMSinfo@mail.nih.gov
  Website: http://www.niams.nih.gov

  The NIAMS, a part of the National Institutes of Health (NIH), leads the Federal Government research effort in arthritis and musculoskeletal and skin diseases in the United States. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS.

• Arthritis Foundation

  P.O. Box 7669
  Atlanta,  GA 30357-0669
  Phone: 404-872-7100
  Toll Free: 800-283-7800
  Website: http://www.arthritis.org

  The Arthritis Foundation is the major voluntary organization devoted to supporting arthritis research and providing education and other services to people with arthritis. This foundation publishes free pamphlets on arthritis, as well as arthritis self-help books in English and Spanish.

• American Academy of Orthopaedic Surgeons (AAOS)

  6300 North River Road
  Rosemont,  IL 60018-4262
  Phone: 847-823-7186
  Toll Free: 800-824-BONE (2663)
  Fax: 847-823-8125
  Email: pemr@aaos.org
  Website: http://www.aaos.org

  The academy provides education and self-help services for orthopaedic surgeons (doctors) and other health providers. It supports improved patient care and informs the public about the science of orthopaedics (bone and joint health).

• American College of Rheumatology (ACR)

  1800 Century Place, Suite 250
  Atlanta,  GA 30345-4300
  Phone: 404-633-3777
  Fax: 404-633-1870
  Website: http://www.rheumatology.org

  This group provides referrals to doctors and health professionals who work on arthritis, rheumatic diseases, and related conditions. It also provides educational materials and guidelines.

Acknowledgments

The NIAMS thanks the following people and organizations for their contribution to this project:

Graciela S. Alarcón, M.D., M.P.H., University of Alabama at Birmingham;
Gwendolyn Davis, Activity Specialist, First Baptist Senior Center;
Virginia González, M.P.H., Stanford Patient Education Center, Stanford University School of Medicine, Palo Alto, CA;
John Klippel, M.D., Arthritis Foundation;
Carlos Lavernia, M.D., Miami, FL;
Cynthia Lindquist Mala, Ph.D., M.P.A., President, Cankdeska Cikana Community College;
Ted Mala, M.D., M.P.H., Lillian Perdomo, Executive Director of Multicultural Community Service;
Betty C. Proctor, Native Indian Sacred Earth Society;
Oscencio W. Tom, M.L.S., NLM, NIH;
the Arthritis Foundation;
the American Academy of Orthopaedic Surgeons;
and the American College of Rheumatology for help in preparing and reviewing this booklet.

Special thanks go to the patients with arthritis who reviewed this publication and provided valuable input.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at www.niams.nih.gov.

For Your Information

This publication contains information about medications used to treat the health condition discussed here. When this booklet was printed, we included the most up-to-date (accurate) information available. Occasionally, new information on medication is released.

For updates and for any questions about any medications you are taking, please contact the U.S. Food and Drug Administration at:

U.S. Food and Drug Administration

Toll Free: 888-INFO-FDA (888-463-6332)
Website: http://www.fda.gov/

This booklet is not copyrighted. You can make copies of it and give out as many as you want.

For more copies, contact

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information Clearinghouse
National Institutes of Health

1 AMS Circle
Bethesda,  MD 20892-3675
Phone: 301-495-4484
Toll Free: 877-22-NIAMS (226-4267)
TTY: 301–565–2966
Fax: 301-718-6366
Email: NIAMSinfo@mail.nih.gov
Website: http://www.niams.nih.gov

NIH Publication No. 07-7050

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases - http://www.niams.nih.gov/Health_Info/Arthritis/default.asp

The discovery of the two genes – ARTS1 and IL23R – brings the scientific community closer to fully understanding AS, says John D. Reveille, M.D., professor and director of the Division of Rheumatology and Clinical Immunogenetics at the University of Texas (UT) Medical School at Houston, who led the study with Matthew A. Brown, M.D., professor of immunogenetics at Australia’s University of Queensland.

In earlier studies of identical twins, Dr. Brown and his colleagues found that the cause of ankylosing spondylitis is more than 90 percent genetic. With the discovery of the newly identified genes, a large proportion of the genetic risk for AS has now been identified.

The IL23R gene, says Dr. Brown, plays a role in the immune system’s response to infection. ARTS1 is involved in processing infectious agents into “bite-size chunks” that can be seen – and fought – by the body’s immune system.

The recent discovery is based on work from the largest and most comprehensive genome-wide association scan conducted to date. In this part of the research project, investigators were searching for genetic information related to AS, as well as autoimmune thyroid disease/Graves’ Disease, breast cancer and multiple sclerosis.

“This discovery, to me, is the most important since 1973, when HLA-B27 was discovered,” says Reveille colleague Frank C. Arnett, M.D., professor of internal medicine and pathology and laboratory medicine at the UT Medical School. HLA-B27 is a powerful predisposing gene that increases the risk of getting AS by more than 100 times.

Dr. Arnett says the location of the genes and the fact they don’t coincide with those of autoimmune diseases, such as rheumatoid arthritis, lupus or juvenile diabetes, helps refute the long-held notion that AS is an autoimmune disease. “It is looking more like AS is not an autoimmune disease, but really an unusual response to infection. These genes working together probably impair the immune system’s ability to rid the body of some of these bacteria or their products.”

He also believes this discovery could eventually lead to ways to immunize people against AS. “I think these give us the genetic handles to identify the pathways that are involved in AS. Once you know the dysregulated pathway, you can find a drug to either strengthen or inhibit the pathway.”

In the meantime, Dr. Reveille says the two genes, along with HLA-B27, could also help physicians identify patients who are at the highest risk for developing AS. “For example, if you have a family member with AS, a simple blood test would be able to tell us if you are also at risk,” he says. “We could offer screenings for people with inflammatory back pain. In the past, [testing for the HLA-B27 gene] was all we had. Now we potentially have more tests.”

“This is a success story for genetics work,” says Dr. Reveille. “I think it will lead the way for other work to be done.”

AS is a chronic inflammatory arthritis characterized by joint stiffness, pain and extra bone growth that can result in partial or complete fusion of the spine. It typically strikes adolescent and young adult males. Currently there is no cure for the disease.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

###

Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nature Genetics 2007; 39 :1329-1337.

Ankylosing spondylitis is an inflammatory arthritis of the spine. It is characterized by joint stiffness, pain and extra bone growth that can result in partial or complete spinal fusion. Spine damage, as seen on x-ray, is one of the measurable features of AS that most greatly impacts quality of life and daily activities.

To reduce a field of 155 candidate variables that the research team thought might be predictors into a more promising subset for further study, Michael Ward, M.D., an investigator in the NIAMS Intramural Research Program, and his colleagues used a complex statistical technique called the random forest. This divides a sample population into subgroups based on random combinations of the candidate variables, and compares the resulting classification schemes — or “trees” — against real data, which reveals which variables, if any, truly have predictive value.

The results of the random forest approach revealed a number of highly ranked factors, both clinical and genetic, that seemed predictive of spine damage as seen on x-ray. Ward’s team then used a more conventional statistical approach, logistic regression, to determine the strength of the association between a predictor and spine damage severity. They found that the likelihood of having severe damage increased with age of disease onset, and men were twice as likely as women to be in the group. Current smokers were more than four times as likely to have severe damage as nonsmokers.

Of the genetic markers found in the AS patient population, many associated with immune system genes were predictive of disease severity. Of note, HLA-B27, which is a genetic marker strongly associated with susceptibility to AS, was not associated with disease severity. Interestingly, the random forest approach identified a genetic marker, DRB1*0801, that seems protective. Study participants with this marker were dramatically less likely to have the most severe spine damage.

Because changes to the spine progress slowly, over years, the study was limited to participants whose disease had been active for at least 20 years. It included more than 400 participants from the National Institutes of Health in Bethesda, Maryland, from Cedars-Sinai in Los Angeles, and from the University of Texas at Houston.

The researchers hope that giving people with AS a better understanding of their risk for severe spine damage will help them take advantage of the factors that can be controlled, such as not smoking and following their treatment plans.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

# # #

Ward MM, Hendrey MR, Malley JD, Learch TJ, Davis JC Jr, Reveille JD, Weisman MH. Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis. Arth & Rheum. 2009 July 15;61(7):859-66.

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases – http://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2009/ankylosing_predictors.asp

NIH Campus, Building 31, Room 4C32
Bethesda, Maryland

Co-chairs
Stephen I. Katz, M.D., Ph.D.
Susana Serrate-Sztein, M.D.

Introduction

For nearly 30 years, there has been a recognition that the number of physician scientists has been in decline. This trend has been observed in the rheumatic diseases field both in terms of a reduction in the number of researchers, and also in a decline in the number of rheumatologists in general. According to the American College of Rheumatology (ACR), 180 rheumatology fellows are trained per year, but this is not enough to sustain current programs.

The path that medical students take to become rheumatology researchers involves several stages. First, medical students who become interested in rheumatology research typically enter an internship/residency program to obtain the practical training necessary for becoming a certified physician. After approximately three years of residency training, these individuals would then enter a 2-5 year fellowship program in rheumatology research. Depending on the program and the trainee’s interests, his or her research may be entirely non-patient oriented or may consist of clinically-oriented, human subjects research. After completing specialty training, the fellow is then expected to obtain an independent position and establish his or her research program. It is clear that preventing trainees from dropping out of a research path and moving toward other career options requires addressing multiple challenges that arise at various points.

The purpose of this roundtable meeting was to discuss how to attract, train, and sustain a strong rheumatology research workforce. The participants represented major stakeholders in improving the academic rheumatology workforce: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Arthritis Foundation (AF), ACR, and ACR-Research and Education Foundation (ACR-REF), several leading academic rheumatologists, and two current rheumatology fellows. Specifically, participants were asked to address the needs and opportunities for developing future generations of physician scientists who will play a critical role in rheumatic diseases research.

Background

The NIAMS, AF, and ACR-REF offer a portfolio of funding mechanisms to support rheumatology trainees at various stages of their career. The NIAMS offers National Research Service Award Institutional Training Grants (T32) and Postdoctoral Individual National Research Service Awards (F32) which provide support around the beginning of the specialty training program. Note that the T32 is awarded to an institution to support multiple trainees of their choosing. In contrast, all other NIAMS training mechanisms are awarded to individuals. The Mentored Scientist Development Award (K01) and the Mentored Clinical Scientist Research Career Development Award (K08) are typically obtained later in the specialty training period, as is the Mentored Patient-Oriented Research Career Development Award (K23) which is sometimes also obtained after an independent position has been secured. The relatively new K99/R00 Pathway to Independence Award is meant to act as a bridge of support to an independent research position. Additional information on NIAMS training programs can be viewed at http://www.niams.nih.gov/Funding/Funding_Opportunities/activity_codes.asp.

The AF offers a Postdoctoral Fellowship Award that typically supports fellows at the beginning of their specialty training, and a Career Development Award to provide support just after an independent position is obtained. The ACR-REF Resident Research Preceptorship Award provides three months of support to introduce medical residents to research. The ACR-REF Physician Scientist Development Award and Clinical Investigator Fellowship offer support during the specialty training period. More information on these AF and ACR-REF awards can be found, respectively, at the following links: http://www.arthritis.org/information-for-researchers.php and http://www.rheumatology.org/ref/awards/index.asp.

Discussion

Defining the problem – insights from evaluations and anecdotal evidence

In discussing the obstacles that prevent trainees from becoming independent investigators, it is useful to break up the pathway into two major stages: the T32 (fellow)-to-K award transition and the K award-to-R (independent investigator) award transition. Both of these transitions present major challenges to trainees, but the nature of these obstacles tends to be different.

Several evaluations that have been conducted recently have provided important insights into the factors that must be addressed in order to increase the number of academic rheumatologists. In September 2007, an outside working group released an evaluation report focused on the effectiveness of the T32, F32, K01, and K08 funding mechanisms offered by NIAMS. A major outcome measure used to determine success of these programs was the ability of recipients to later obtain R01 funding. One caveat to this approach is that some independent investigators are funded through other mechanisms (e.g., other R grants, program project grants, non-NIH awards, etc.). Nevertheless, the evaluation has provided many insights into the status of training programs at the NIAMS. The full report can be viewed on the NIAMS Web site at http://www.niams.nih.gov/News_and_Events/Meetings_and_Events/Reports/2007/training_grant_eval_final_report.asp.

Results of the NIAMS training evaluation indicated that 17% of NIAMS T32 awardees go on to receive R01 funding, while much higher percentages of F32, K01, and K08 recipients (34%, 83%, and 55%, respectively) obtain R01 funding. The majority of NIAMS F32 recipients are Ph.D. fellows, while the majority of T32 recipients are M.D. fellows. While the T32 and F32 mechanisms are meant to target roughly the same career stage, anecdotal evidence suggests that for M.D. fellows, the T32 mechanism is used at an earlier stage than the F32. Therefore, because F32 and K awardees having M.D. degrees tend to be more senior than trainees appointed to T32s, it is perhaps not surprising that F32 and K recipients are more likely to reach successful research careers. It is difficult to predict early in the pathway which trainees will become successful. Thus, it may be necessary to support a relatively large number of fellows at this stage, even if only a small percentage go on to become independent researchers. Finally, the high rate of success of the K01 and K08 mechanisms, especially if one looks at success in terms of the percentage of recipients still involved in research, indicates that there is a robust rate of return for funds invested in these programs.

It is also important to consider that the T32 program has other indirect benefits to academic programs besides helping to produce investigators who obtain R01s. For example, clinical rheumatologists who don’t have significant research funding, but are still involved in research projects, are often trained via the T32 mechanism. Also, when an institution has a T32 program, it is more likely to provide fellows with training in performing clinical trials that is much more extensive than what is offered by involvement in industry-sponsored clinical trials.

The quality of mentoring has received attention as a potentially important factor determining whether a rheumatology trainee progresses to an independent research position. In recent years, several surveys of rheumatologists have illuminated the obstacles that trainees face when considering a career in research. In particular, an insightful study of rheumatology fellows is currently being prepared for publication by the ACR Committee on Research, Subcommittee of Young Investigators. Based on the survey results, fellows generally thought that the training programs they were enrolled in, and the quality of mentoring that they received, were very good. However, a potential caveat is that that the fellows may have only considered mentoring related to research and funding when answering the survey, rather than mentoring related to career issues more broadly such as how to successfully manage a research program and navigate personnel issues. Thus, the quality of mentoring that relates to career issues appears to still be an open question.

The effect of academic salaries on the decision to enter, or stay in, a career in rheumatology research is complex. The relatively low salaries earned during the fellowship years, particularly during the K-to-R transition, are thought to be an obstacle to continuing down the career path to independence. This is due to the fact that many fellows are burdened by large educational debt and are often beginning a stage in their lives where there is a perceived need for higher income (e.g., due to a growing family). The NIH Loan Repayment Program (LRP; see below) is targeted to this need. Similarly, the salary level later in the career path for independent investigators tends to be lower than that of private practice or industry. The extent to which this affects the decision to choose a career in academic rheumatology appears to differ according to the gender of the respondents. The salary level for more senior positions tended to be an obstacle for many male respondents, but was much less of an obstacle for females. Generally, those that were strongly interested in research were willing to tolerate the lower salaries.

Based on the ACR survey, the biggest obstacle for rheumatology fellows is the anxiety over obtaining research funding at the NIH. This is a major impediment at the T32-to-K transition. As fellows look ahead to the possibility of independent positions in rheumatology research, their views are affected by observing their mentors struggling to get NIH research funding. The effect that the funding environment has on their decision to pursue a rheumatology research career has been exacerbated by a number of factors that have recently come into play. These include the reduced state and/or institutional support for research, the fact that fellows are older now and in more of a hurry to start independent careers, and the institutional pressure on principal investigators to have two or more R01 grants to support their research. Another important issue is that industry and private practice are exerting a greater pull on the available pool of trainees than ever before. This is in part due to the higher salaries offered by industry and private practice, and the perception that careers in these fields offer more stability than in academia.

Possible solutions to career path obstacles

Although several mechanisms are available for rheumatology fellows from the NIAMS and other organizations, making the transition from an early training fellowship (e.g., T32) to a K award is challenging. While some solutions already exist, others could be implemented. The NIH LRP plays a very important role in lowering the opportunity cost of staying in academia. This 2-3 year award pays trainees up to $35,000 per year toward the relief of their qualified student loan debt. The success rate for the LRP is quite favorable (around 50%). However, this program needs to be better publicized as many residents and fellows are still not aware of it. The LRP is currently directed towards clinical researchers; however, the meeting participants suggested that the NIH may want to consider expanding it into basic research as well. For more information on the NIH LRP, please visit http://www.lrp.nih.gov/.

Another promising approach to reduce attrition during the T32-to-K phase is to enhance mentoring of trainees on career issues (e.g., understanding the NIH grants process, grant writing, project management, and enhancing the mentor-mentee relationship). There are some significant efforts in this arena already. For example, some NIH Institutes and Centers offer workshops that explain to junior scientists how the funding process works, how to improve the mentor-mentee relationship, and how to manage a research program. NIAMS staff members periodically give presentations at scientific conferences about career issues, focusing primarily on grant mechanisms and preparation. The ACR is organizing a new conference for junior rheumatology researchers to begin in 2008. Half of this conference will focus on presenting current research findings and the other half will be directed towards career issues and planning.

Another major obstacle to getting past the T32-to-K transition is the difficulty in obtaining the K award itself. The success rates for the NIAMS K08 and K23 awards over the past three years have averaged 34% and 40%, respectively. The ACR-REF plans to soon offer bridge funding, available for 1-2 years, for trainees who received a good, but not fundable, score on their applications for K08 and K23 awards. The purpose of this bridge funding is to ensure that qualified trainees have the highest likelihood of achieving success in obtaining future NIH awards. Thus, it allows them to continue to fund their fellowship while they prepare a resubmission of their K application.

To address challenges in the K-to-R01 transition, there are a number of possible approaches. There is a general feeling that the AF and ACR-REF can come together to find ways to move more fellows to independent positions. The AF is currently designing a program to supplement K awards. A major goal of this program is to address the relatively low salaries earned by trainees during their fellowship. However, in some cases, it may be more productive for some or all of the supplement to go to purchase of research supplies and equipment and/or to support research staff salaries. In this case, the supplement could enable the fellow to move his or her research further along and thus produce more of the preliminary data needed for future R01 applications. Potentially, the use of the supplemental funds could be determined on a case-by-case basis in order to have the greatest positive impact.

NIAMS Program Directors sometimes observe extremely qualified rheumatology fellows applying for K grants, when they would probably be competitive for an R01. A number of possible approaches to encourage these individuals to apply for R01 grants more quickly were discussed. Some participants in the discussion felt that academic institutions should try to be more flexible with the timing of tenure and promotion for fellows who have family responsibilities. More effort also needs to be put into getting the word out to junior investigators regarding the flexibility that already exists in this regard. In addition, all stakeholders should continue to consider whether it is more productive to place additional resources at the earlier part of the training pathway or at the late stages. Perhaps the earlier part of the pathway would be most productive due to the fact that institutions are generally more amenable to providing support to more senior trainees given that much has been invested in them by that stage already. Additional training surveys and evaluations could potentially shed light on this issue.

Summary of next steps

In the near future, the NIAMS, AF, ACR, and ACR-REF will be involved in various activities with the goal of increasing the number of rheumatology trainees that become successful independent investigators. The ACR is currently carrying out a large rheumatology workforce study and will introduce an action plan based on the results by the end of 2008. In addition, the ACR survey of fellows will soon be published. The ACR-REF will implement the bridge award that targets the T32-to-K transition. Likewise, the AF will implement their plan to offer a supplement to K awards, pending decisions on how the funds are to be used. The NIAMS will continue to assess policies that help facilitate the retention of junior investigators. To better inform these policy decisions, NIAMS plans to soon implement a mechanism for prospective data collection for recipients of training awards. Finally, NIAMS will continue to explore potential partnerships with organizations such as the AF and ACR, as appropriate.

Related Links

Description of NIAMS Research and Training Mechanisms

http://www.niams.nih.gov/Funding/Funding_Opportunities/activity_codes.asp

Evaluation of NIAMS T32, F32, K01, and K08 Mechanisms

http://www.niams.nih.gov/News_and_Events/Meetings_and_Events/Reports/2007/training_grant_eval_final_report.asp

Description of the NIH Loan Repayment Program

http://www.lrp.nih.gov/

Description of grants and awards offered by the AF

http://www.arthritis.org/information-for-researchers.php

Description of the ACR-REF grants and awards program

http://www.rheumatology.org/ref/awards/index.asp

Outside Participants

CROFFORD, Leslie, M.D.
Gloria W. Singletary Professor
Chief, Division of Rheumatology
Director, Center for the Advancement of Women’s Health
University of Kentucky

DAIKH, David, M.D., Ph.D.
Assistant Professor, Medicine
Chief, Division of Rheumatology
University of California at San Francisco

DAVIDSON, Anne, M.D.
Associate Professor
The Feinstein Institute for Medical Research
Northshore University Hospital

FITZGERALD, John, M.D., M.P.H., M.B.A.
Assistant Professor, Medicine
Department of Medicine/Rheumatology
University of California at Los Angeles

FOX, David, M.D.
Professor, Department of Internal Medicine
Chief, Division of Rheumatology
Director, Rheumatic Disease Core Center
University of Michigan

HARDIN, John, M.D.
Department of Medicine
Albert Einstein College of Medicine

HERNANDEZ, Milton, Ph.D.
Director, Office of Special Populations and Research Training
National Institute of Allergy and Infectious Diseases
National Institutes of Health

KARP, David R., M.D., Ph.D.
Associate Professor
Rheumatic Diseases Division
University of Texas Southwestern Medical Center

LANE, Nancy, M.D.
Director, Center for Healthy Aging
Vice Chair of Research, Department of Medicine
Professor of Medicine and Rheumatology
University of California at Davis

PARK, Christy, M.D.
Department of Medicine
University of Tennessee

ROSEN, Antony, M.D.
Mary Betty Stevens Professor of Medicine
Director, Division of Rheumatology
Johns Hopkins University

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases – http://www.niams.nih.gov/News_and_Events/Meetings_and_Events/Roundtables/2008/career_paths.asp

There are over 200 disorders that impact connective tissue. Some, like cellulitis, are the result of an infection. Injuries can cause connective tissue disorders, such as scars. Others, such as Ehlers-Danlos syndrome, Marfan syndrome, andosteogenesis imperfecta, are genetic. Still others, like scleroderma, have no known cause. Each disorder has its own symptoms and needs different treatment.

Source: MedlinePlus – http://www.nlm.nih.gov/medlineplus/connectivetissuedisorders.html

What Is Scleroderma?

Derived from the Greek words “sklerosis,” meaning hardness, and “derma,” meaning skin, scleroderma literally means hard skin. Although it is often referred to as if it were a single disease, scleroderma is really a symptom of a group of diseases that involve the abnormal growth of connective tissue, which supports the skin and internal organs. It is sometimes used, therefore, as an umbrella term for these disorders. In some forms of scleroderma, hard, tight skin is the extent of this abnormal process. In other forms, however, the problem goes much deeper, affecting blood vessels and internal organs, such as the heart, lungs, and kidneys.

Scleroderma is called both a rheumatic (roo-MA-tik) disease and a connective tissue disease. The term rheumatic disease refers to a group of conditions characterized by inflammation or pain in the muscles, joints, or fibrous tissue. A connective tissue disease is one that affects tissues such as skin, tendons, and cartilage.

In this booklet we’ll discuss the forms of scleroderma and the problems associated with each of them, as well as diagnosis and disease management. We’ll also take a look at what research is telling us about their possible causes and most effective treatments. And we will describe ways for people with scleroderma to live longer, healthier, and more productive lives.

• What Are the Different Types of Scleroderma?
• What Causes Scleroderma?
• Who Gets Scleroderma?
• How Is Scleroderma Diagnosed?
• What Other Conditions Can Look Like Scleroderma?
• How Is Scleroderma Treated?
• How Can Scleroderma Affect My Life?
• How Can I Play a Role in My Health Care?
• Is Research Close to Finding a Cure?
• More Questions? Count on More Answers
• For More Information
• Key Words

What Are the Different Types of Scleroderma?

The group of diseases we call scleroderma falls into two main classes: localized scleroderma and systemic sclerosis. (Localized diseases affect only certain parts of the body; systemic diseases can affect the whole body.) Both groups include subgroups. (See chart.) Although there are different ways these groups and subgroups may be broken down or referred to (and your doctor may use different terms from what you see here), the following is a common way of classifying these diseases:

Scleroderma Chart

Localized Scleroderma

Localized types of scleroderma are those limited to the skin and related tissues and, in some cases, the muscle below. Internal organs are not affected by localized scleroderma, and localized scleroderma can never progress to the systemic form of the disease. Often, localized conditions improve or go away on their own over time, but the skin changes and damage that occur when the disease is active can be permanent. For some people, localized scleroderma is serious and disabling.

There are two generally recognized types of localized scleroderma:

Morphea: Morphea (mor-FEE-ah) comes from a Greek word that means “form” or “structure.” The word refers to local patches of scleroderma. The first signs of the disease are reddish patches of skin that thicken into firm, oval-shaped areas. The center of each patch becomes ivory colored with violet borders. These patches sweat very little and have little hair growth. Patches appear most often on the chest, stomach, and back. Sometimes they appear on the face, arms, and legs.

Morphea can be either localized or generalized. Localized morphea limits itself to one or several patches, ranging in size from a half-inch to 12 inches in diameter. The condition sometimes appears on areas treated by radiation therapy. Some people have both morphea and linear scleroderma (described below). The disease is referred to as generalized morphea when the skin patches become very hard and dark and spread over larger areas of the body. Regardless of the type, morphea generally fades out in 3 to 5 years; however, people are often left with darkened skin patches and, in rare cases, muscle weakness.

Linear scleroderma: As suggested by its name, the disease is characterized by a single line or band of thickened or abnormally colored skin. Usually, the line runs down an arm or leg, but in some people it runs down the forehead. People sometimes use the French term en coup de sabre, or “sword stroke,” to describe this highly visible line.

Systemic Scleroderma (also known as Systemic Sclerosis)

This is the term for the form of the disease that not only includes the skin, but also involves the tissues beneath, the blood vessels, and the major organs. Systemic sclerosis is typically broken down into limited cutaneous scleroderma and diffuse cutaneous scleroderma. Some doctors break systemic sclerosis down into a third subset called systemic sclerosis sine (SEEN-ay, Latin for “without”) scleroderma. This means that patients have other manifestations of scleroderma but they do not have any overt skin thickening.

Limited cutaneous scleroderma: Limited cutaneous scleroderma typically comes on gradually and affects the skin only in certain areas: the fingers, hands, face, lower arms, and legs. Most people with limited disease have Raynaud’s phenomenon for years before skin thickening starts. Telangiectasia and calcinosis often follow. (See definitions below.) Gastrointestinal involvement occurs commonly, and some patients have severe lung problems, even though the skin thickening remains limited. People with limited disease often have all or some of the symptoms that some doctors call CREST, which stands for the following:

• Calcinosis (KAL-sin-OH-sis): the formation of calcium deposits in the connective tissues, which can be detected by x ray. These deposits are typically found on the fingers, hands, face, and trunk and on the skin above elbows and knees. When the deposits break through the skin, painful ulcers can result.
• Raynaud’s (ray-NOHZ) phenomenon: a condition in which the small blood vessels of the hands or feet contract in response to cold or anxiety. As the vessels contract, the hands or feet turn white and cold, then blue. As blood flow returns, they become red. Fingertip tissues may suffer damage, leading to ulcers, scars, or gangrene.
• Esophageal (eh-SOFF-uh-GEE-ul) dysfunction: impaired function of the esophagus (the tube connecting the throat and the stomach) that occurs when smooth muscles in the esophagus lose normal movement. In the upper and lower esophagus, the result can be swallowing difficulties. In the lower esophagus, the result can be chronic heartburn or inflammation.
• Sclerodactyly (SKLER-oh-DAK-till-ee): thick and tight skin on the fingers, resulting from deposits of excess collagen within skin layers. The condition makes it harder to bend or straighten the fingers. The skin may also appear shiny and darkened, with hair loss.
• Telangiectasia (tel-AN-jee-ek-TAY-zee-uhs): a condition caused by the swelling of tiny blood vessels, in which small red spots appear on the hands and face. Although not painful, these red spots can create cosmetic problems.

Diffuse cutaneous scleroderma: This condition typically comes on suddenly. Skin thickening begins in the hands and spreads quickly and over much of the body, affecting the hands, face, upper arms, upper legs, chest, and stomach in a symmetrical fashion (for example, if one arm or one side of the trunk is affected, the other is also affected). Some people may have more area of their skin affected than others. Internally, this condition can damage key organs such as the intestines, lungs, heart, and kidneys.

People with diffuse disease often are tired, lose appetite and weight, and have joint swelling or pain. Skin changes can cause the skin to swell, appear shiny, and feel tight and itchy.

The damage of diffuse scleroderma typically occurs over a few years. After the first 3 to 5 years, people with diffuse disease often enter a stable phase lasting for varying lengths of time. During this phase, symptoms subside: joint pain eases, fatigue lessens, and appetite returns. Progressive skin thickening and organ damage decrease.

Gradually, however, the skin may begin to soften, which tends to occur in reverse order of the thickening process: the last areas thickened are the first to begin softening. Some patients’ skin returns to a somewhat normal state, while other patients are left with thin, fragile skin without hair or sweat glands. Serious new damage to the heart, lungs, or kidneys is unlikely to occur, although patients are left with whatever damage they have in specific organs.

People with diffuse scleroderma face the most serious long-term outlook if they develop severe kidney, lung, digestive, or heart problems. Fortunately, less than one-third of patients with diffuse disease develop these severe problems. Early diagnosis and continual and careful monitoring are important.

What Causes Scleroderma?

Although scientists don’t know exactly what causes scleroderma, they are certain that people cannot catch it from or transmit it to others. Studies of twins suggest it is also not inherited. Scientists suspect that scleroderma comes from several factors that may include:

Abnormal immune or inflammatory activity: Like many other rheumatic disorders, scleroderma is believed to be an autoimmune disease. An autoimmune disease is one in which the immune system, for unknown reasons, turns against one’s own body.

In scleroderma, the immune system is thought to stimulate cells called fibroblasts so they produce too much collagen. The collagen forms thick connective tissue that builds up within the skin and internal organs and can interfere with their functioning. Blood vessels and joints can also be affected.

Genetic makeup: Although genes seem to put certain people at risk for scleroderma and play a role in its course, the disease is not passed from parent to child like some genetic diseases.

Environmental triggers: Research suggests that exposure to some environmental factors may trigger scleroderma-like disease (which is not actually scleroderma) in people who are genetically predisposed to it. Suspected triggers include viral infections, certain adhesive and coating materials, and organic solvents such as vinyl chloride or trichloroethylene. But no environmental agent has been shown to cause scleroderma. In the past, some people believed that silicone breast implants might have been a factor in developing connective tissue diseases such as scleroderma. But several studies have not shown evidence of a connection.

Hormones: By the middle to late childbearing years (age 30 to 55), women develop scleroderma 7 to 12 times more often than men. Because of female predominance at these and all ages, scientists suspect that hormonal differences between women and men play a part in the disease. However, the role of estrogen or other female hormones has not been proven.

Who Gets Scleroderma?

Although scleroderma is more common in women, the disease also occurs in men and children. It affects people of all races and ethnic groups. However, there are some patterns by disease type. For example:

• Localized forms of scleroderma are more common in people of European descent than in African Americans. Morphea usually appears between the ages of 20 and 40, and linear scleroderma usually occurs in children or teenagers.
• Systemic scleroderma, whether limited or diffuse, typically occurs in people from 30 to 50 years old. It affects more women of African American than European descent.

Because scleroderma can be hard to diagnose and it overlaps with or resembles other diseases, scientists can only estimate how many cases there actually are. Estimates for the number of people in the United States with systemic sclerosis range from 40,000 to 165,000. By contrast, a survey that included all scleroderma-related disorders, including Raynaud’s phenomenon, suggested a number between 250,000 and 992,500.

For some people, scleroderma (particularly the localized forms) is fairly mild and resolves with time. But for others, living with the disease and its effects day to day has a significant impact on their quality of life.

How Is Scleroderma Diagnosed?

Depending on your particular symptoms, a diagnosis of scleroderma may be made by a general internist, a dermatologist (a doctor who specializes in treating diseases of the skin, hair, and nails), an orthopaedist (a doctor who treats bone and joint disorders), a pulmonologist (a lung specialist), or a rheumatologist (a doctor specializing in treatment of musculoskeletal disorders and rheumatic diseases). A diagnosis of scleroderma is based largely on the medical history and findings from the physical exam. To make a diagnosis, your doctor will ask you a lot of questions about what has happened to you over time and about any symptoms you may be experiencing. Are you having a problem with heartburn or swallowing? Are you often tired or achy? Do your hands turn white in response to anxiety or cold temperatures?

Once your doctor has taken a thorough medical history, he or she will perform a physical exam. Finding one or more of the following factors can help the doctor diagnose a certain form of scleroderma:

• changed skin appearance and texture, including swollen fingers and hands and tight skin around the hands, face, mouth, or elsewhere
• calcium deposits developing under the skin
• changes in the tiny blood vessels (capillaries) at the base of the fingernails
• thickened skin patches.

Finally, your doctor may order lab tests to help confirm a suspected diagnosis. At least two proteins, called antibodies, are commonly found in the blood of people with scleroderma:

• Antitopoisomerase-1 or Anti-Scl-70 antibodies appear in the blood of up to 30 percent of people with diffuse systemic sclerosis.
• Anticentromere antibodies are found in the blood of as many as 50 percent of people with limited systemic sclerosis.

A number of other scleroderma-specific antibodies can occur in people with scleroderma, although less frequently. When present, however, they are helpful in clinical diagnosis and may give additional information as to the risks for specific organ problems.

Because not all people with scleroderma have these antibodies and because not all people with the antibodies have scleroderma, lab test results alone cannot confirm the diagnosis.

In some cases, your doctor may order a skin biopsy (the surgical removal of a small sample of skin for microscopic examination) to aid in or help confirm a diagnosis. However, skin biopsies also have their limitations: biopsy results cannot distinguish between localized and systemic disease, for example.

Diagnosing scleroderma is easiest when a person has typical symptoms and rapid skin thickening. In other cases, a diagnosis may take months, or even years, as the disease unfolds and reveals itself and as the doctor is able to rule out some other potential causes of the symptoms. In some cases, a diagnosis is never made, because the symptoms that prompted the visit to the doctor go away on their own.

Some patients have some symptoms related to scleroderma and may fit into one of the following groups:

• Undifferentiated connective tissue disease (UCTD): This is a term for patients who have some signs and symptoms of various related diseases, but not enough symptoms of any one disease to make a definitive diagnosis. In other words, their condition hasn’t “differentiated” into a particular connective tissue disease. In time, UCTD can go in one of three directions: it can change into a systemic disease such as systemic sclerosis, systemic lupus erythematosus, or rheumatoid arthritis; it can remain undifferentiated; or it can improve spontaneously.
• Overlap syndromes: This is a disease combination in which patients have symptoms and lab findings characteristic of two or more conditions.

What Other Conditions Can Look Like Scleroderma?

A number of other diseases have symptoms similar to those seen in scleroderma. Here are some of the most common scleroderma “look-alikes.”

Eosinophilic fasciitis (EF) (EE-oh-SIN-oh-FIL-ik fa-shi-EYE-tis): This disease involves the fascia (FA-shuh), the thin connective tissue around the muscles, particularly those of the forearms, arms, legs, and trunk. EF causes the muscles to become encased in collagen, the fibrous protein that makes up tissue such as the skin and tendons. Permanent shortening of the muscles and tendons, called contractures, may develop, sometimes causing disfigurement and problems with joint motion and function. EF may begin after hard physical exertion. The disease usually fades away after several years, but people sometimes have relapses. Although the upper layers of the skin are not thickened in EF, the thickened fascia may cause the skin to look somewhat like the tight, hard skin of scleroderma. A skin biopsy easily distinguishes between the two diseases.

Skin thickening on the fingers and hands: This also appears with diabetes, mycosis fungoides, amyloidosis, and adult celiac disease. It can also result from hand trauma.

Generalized scleroderma-like skin thickening: This may occur with scleromyxedema, graft-versus-host disease, porphyria cutanea tarda, and human adjuvant disease.

Internal organ damage: Similar to that seen in systemic sclerosis, this may instead be related to primary pulmonary hypertension, idiopathic pulmonary fibrosis, or collagenous colitis.

Raynaud’s phenomenon: This condition also appears with atherosclerosis or systemic lupus erythematosus or in the absence of underlying disease.

An explanation of most of these other diseases is beyond the scope of this booklet. What’s important to understand, however, is that diagnosing scleroderma isn’t always easy, and it may take time for you and your doctor to do this. While having a definite diagnosis may be helpful, you do not need to know the precise form of your disease to receive proper treatment.

How Is Scleroderma Treated?

Because scleroderma can affect many different organs and organ systems, you may have several different doctors involved in your care. Typically, care will be managed by a rheumatologist (a doctor specializing in treatment of musculoskeletal disorders and rheumatic diseases). Your rheumatologist may refer you to other specialists, depending on the specific problems you are having. For example, you may see a dermatologist for the treatment of skin symptoms, a nephrologist for kidney complications, a cardiologist for heart complications, a gastroenterologist for problems of the digestive tract, and a pulmonary specialist for lung involvement.

In addition to doctors, professionals such as nurse practitioners, physician assistants, physical or occupational therapists, psychologists, and social workers may play a role in your care. Dentists, orthodontists, and even speech therapists can treat oral complications that arise from thickening of tissues in and around the mouth and on the face.

Currently, there is no treatment that controls or stops the underlying problem – the overproduction of collagen – in all forms of scleroderma. Thus, treatment and management focus on relieving symptoms and limiting damage. Your treatment will depend on the particular problems you are having. Some treatments will be prescribed or given by your doctor. Others are things you can do on your own.

Here is a listing of the potential problems that can occur in systemic scleroderma and the medical and nonmedical treatments for them. These problems do not occur as a result or complication of localized scleroderma. This listing is not complete because different people experience different problems with scleroderma and not all treatments work equally well for all people. Work with your doctor to find the best treatment for your specific symptoms.

Raynaud’s phenomenon: More than 90 percent of people with scleroderma have this condition, in which the fingers and sometimes other extremities change color in response to cold temperature or anxiety. For many, Raynaud’s phenomenon precedes other manifestations of the disease. In other people, however, Raynaud’s phenomenon is unrelated to scleroderma, but may signal damage to the blood vessels supplying the hands arising from occupational injuries (from using jackhammers, for example), trauma, excessive smoking, circulatory problems, drug use, or exposure to toxic substances. For some people, cold fingers and toes are the extent of the problem and are little more than a nuisance. For others, the condition can worsen and lead to puffy fingers, finger ulcers, and other complications that require aggressive treatment.

If you have Raynaud’s phenomenon, the following measures may make you more comfortable and help prevent problems:

• Don’t smoke! Smoking narrows the blood vessels even more and makes Raynaud’s phenomenon worse.
• Dress warmly, with special attention to hands and feet. Dress in layers and try to stay indoors during cold weather.
• Use biofeedback, which governs various body processes that are not normally thought of as being under conscious control, and relaxation exercises.
• For severe cases, speak to your doctor about prescribing drugs called calcium channel blockers, such as nifedipine (Procardia*), which can open up small blood vessels and improve circulation. Other drugs are in development and may become available.
• If Raynaud’s phenomenon leads to skin sores or ulcers, increasing your dose of calcium channel blockers (under the direction of your doctor ONLY) may help. You can also protect skin ulcers from further injury or infection by applying nitroglycerine paste or antibiotic cream. Severe ulcerations on the fingertips can be treated with bioengineered skin.

Stiff, painful joints: In diffuse systemic sclerosis, hand joints can stiffen due to hardened skin around the joints or inflammation within them. Other joints can also become stiff and swollen.

• Stretching exercises under the direction of a physical or occupational therapist are extremely important to prevent loss of joint motion. These should be started as soon as scleroderma is diagnosed.
• Exercise regularly. Ask your doctor or physical therapist about an exercise plan that will help you increase and maintain range of motion in affected joints. Swimming can help maintain muscle strength, flexibility, and joint mobility.
• Use acetaminophen or an over-the-counter or prescription nonsteroidal anti-inflammatory drug, as recommended by your doctor, to help relieve joint or muscle pain. If pain is severe, speak to a rheumatologist about the possibility of prescription-strength drugs to ease pain and inflammation.
• Learn to do things in a new way. A physical or occupational therapist can help you learn to perform daily tasks, such as lifting and carrying objects or opening doors, in ways that will put less stress on tender joints.

Skin problems: When too much collagen builds up in the skin, it crowds out sweat and oil glands, causing the skin to become dry and stiff. If your skin is affected, try the following:

• Apply oil-based creams and lotions frequently, and always right after bathing.
• Apply sunscreen before you venture outdoors to protect against further damage from the sun’s rays.
• Use humidifiers to moisten the air in your home in colder winter climates. Clean humidifiers often to stop bacteria from growing in the water.
• Avoid very hot baths and showers, as hot water dries the skin.
• Avoid harsh soaps, household cleaners, and caustic chemicals, if at all possible. Otherwise, be sure to wear rubber gloves when you use such products.
• Exercise regularly. Exercise, especially swimming, stimulates blood circulation to affected areas.

Dry mouth and dental problems: Dental problems are common in people with scleroderma for a number of reasons. Tightening facial skin can make the mouth opening smaller and narrower, which makes it hard to care for teeth; dry mouth due to salivary gland damage speeds up tooth decay; and damage to connective tissues in the mouth can lead to loose teeth. You can avoid tooth and gum problems in several ways:

• Brush and floss your teeth regularly. If hand pain and stiffness make this difficult, consult your doctor or an occupational therapist about specially made toothbrush handles and devices to make flossing easier.
• Have regular dental checkups. Contact your dentist immediately if you experience mouth sores, mouth pain, or loose teeth.
• If decay is a problem, ask your dentist about fluoride rinses or prescription toothpastes that remineralize and harden tooth enamel.
• Consult a physical therapist about facial exercises to help keep your mouth and face more flexible.
• Keep your mouth moist by drinking plenty of water, sucking ice chips, using sugarless gum and hard candy, and avoiding mouthwashes with alcohol. If dry mouth still bothers you, ask your doctor about a saliva substitute – or prescription medications such as pilocarpine hydrochloride (Salagen) or cevimeline hydrochloride (Evoxac) – that can stimulate the flow of saliva.

Gastrointestinal (GI) problems: Systemic sclerosis can affect any part of the digestive system. As a result, you may experience problems such as heartburn, difficulty swallowing, early satiety (the feeling of being full after you’ve barely started eating), or intestinal complaints such as diarrhea, constipation, and gas. In cases where the intestines are damaged, your body may have difficulty absorbing nutrients from food. Although GI problems are diverse, here are some things that might help at least some of the problems you have:

• Eat small, frequent meals.
• To keep stomach contents from backing up into the esophagus, stand or sit for at least an hour (preferably 2 or 3 hours) after eating. When it is time to sleep, keep the head of your bed raised using blocks.
• Avoid late-night meals, spicy or fatty foods, alcohol, and caffeine, which can aggravate GI distress.
• Eat moist, soft foods, and chew them well. If you have difficulty swallowing or if your body doesn’t absorb nutrients properly, your doctor may prescribe a special diet.
• Ask your doctor about prescription medications for problems such as diarrhea, constipation, and heartburn. Some drugs called proton pump inhibitors are highly effective against heartburn. Oral antibiotics may stop bacterial overgrowth in the bowel, which can be a cause of diarrhea in some people with systemic sclerosis.

Lung damage: Virtually all people with systemic sclerosis have some loss of lung function. Some develop severe lung disease, which comes in two forms: pulmonary fibrosis (hardening or scarring of lung tissue because of excess collagen) and pulmonary hypertension (high blood pressure in the artery that carries blood from the heart to the lungs). Treatment for the two conditions is different:

• Pulmonary fibrosis may be treated with drugs that suppress the immune system, such as cyclophosphamide (Cytoxan) or azathioprine (Imuran), along with low doses of corticosteroids.
• Pulmonary hypertension may be treated with drugs that dilate the blood vessels, such as prostacyclin (Iloprost), or with newer medications that are prescribed specifically for treating pulmonary hypertension.

Regardless of your particular lung problem or its medical treatment, your role in the treatment process is essentially the same. To minimize lung complications, work closely with your medical team. Do the following:

• Watch for signs of lung disease, including fatigue, shortness of breath or difficulty breathing, and swollen feet. Report these symptoms to your doctor.
• Have your lungs closely checked, using standard lung-function tests, during the early stages of skin thickening. These tests, which can find problems at the earliest and most treatable stages, are needed because lung damage can occur even before you notice any symptoms.
• Get regular flu and pneumonia vaccines as recommended by your doctor. Contracting either illness could be dangerous for a person with lung disease.

Heart problems: Common among people with scleroderma, heart problems include scarring and weakening of the heart (cardiomyopathy), inflamed heart muscle (myocarditis), and abnormal heartbeat (arrhythmia). All of these problems can be treated. Treatment ranges from drugs to surgery and varies depending on the nature of the condition.

Kidney problems: Renal crisis occurs in about 10 percent of all patients with scleroderma, primarily those with early diffuse scleroderma. Renal crisis results in severe uncontrolled high blood pressure, which can quickly lead to kidney failure. It’s very important that you take measures to identify and treat the hypertension as soon as it occurs. These are things you can do:

• Check your blood pressure regularly. You should also check it if you have any new or different symptoms such as a headache or shortness of breath. If your blood pressure is higher than usual, call your doctor right away.
• If you have kidney problems, take your prescribed medications faithfully. In the past two decades, drugs known as ACE (angiotensin-converting enzyme) inhibitors, including captopril (Capoten), enalapril (Vasotec), and lisinopril, have made scleroderma-related kidney failure a less threatening problem than it used to be. But for these drugs to work, you must take them as soon as the hypertension is present.

Cosmetic problems: Even if scleroderma doesn’t cause any lasting physical disability, its effects on the skin’s appearance – particularly on the face – can take their toll on your self-esteem. Fortunately, there are procedures to correct some of the cosmetic problems scleroderma causes:

• The appearance of telangiectasias – small red spots on the hands and face caused by swelling of tiny blood vessels beneath the skin – may be reduced or even eliminated with the use of guided lasers.
• Facial changes of localized scleroderma – such as the en coup de sabre that may run down the forehead in people with linear scleroderma – may be corrected through cosmetic surgery. (However, such surgery is not appropriate for areas of the skin where the disease is active.)

* Brand names included in this booklet are provided as examples only, and their inclusion does not mean that these products are endorsed by the National Institutes of Health or any other Government agency. Also, if a particular brand name is not mentioned, this does not mean or imply that the product is unsatisfactory.

How Can Scleroderma Affect My Life?

Having a chronic disease can affect almost every aspect of your life, from family relationships to holding a job. For people with scleroderma, there may be other concerns about appearance or even the ability to dress, bathe, or handle the most basic daily tasks. Here are some areas in which scleroderma could intrude.

Appearance and self-esteem: Aside from the initial concerns about health and longevity, people with scleroderma quickly become concerned with how the disease will affect their appearance. Thick, hardened skin can be difficult to accept, particularly on the face. Systemic scleroderma may result in facial changes that eventually cause the opening to the mouth to become smaller and the upper lip to virtually disappear. Linear scleroderma may leave its mark on the forehead. Although these problems can’t always be prevented, their effects may be minimized with proper treatment. Also, special cosmetics – and in some cases plastic surgery – can help conceal scleroderma’s damage.

Caring for yourself: Tight, hard connective tissue in the hands can make it difficult to do what were once simple tasks, such as brushing your teeth and hair, pouring a cup of coffee, using a knife and fork, unlocking a door, or buttoning a jacket. If you have trouble using your hands, consult an occupational therapist, who can recommend new ways of doing things or devices to make tasks easier. Devices as simple as Velcro fasteners and built-up brush handles can help you be more independent.

Family relationships: Spouses, children, parents, and siblings may have trouble understanding why you don’t have the energy to keep house, drive to soccer practice, prepare meals, or hold a job the way you used to. If your condition isn’t that visible, they may even suggest you are just being lazy. On the other hand, they may be overly concerned and eager to help you, not allowing you to do the things you are able to do or giving up their own interests and activities to be with you. It’s important to learn as much about your form of the disease as you can and to share any information you have with your family. Involving them in counseling or a support group may also help them better understand the disease and how they can help you.

Sexual relations: Sexual relationships can be affected when systemic scleroderma enters the picture. For men, the disease’s effects on the blood vessels can lead to problems achieving an erection. For women, damage to the moisture-producing glands can cause vaginal dryness that makes intercourse painful. People of either sex may find they have difficulty moving the way they once did. They may be self-conscious about their appearance or afraid that their sexual partner will no longer find them attractive. With communication between partners, good medical care, and perhaps counseling, many of these changes can be overcome or at least worked around.

Pregnancy and childbearing: In the past, women with systemic scleroderma were often advised not to have children. But thanks to better medical treatments and a better understanding of the disease itself, that advice is changing. (Pregnancy, for example, is not likely to be a problem for women with localized scleroderma.) Although blood vessel involvement in the placenta may cause babies of women with systemic scleroderma to be born early, many women with the disease can have safe pregnancies and healthy babies if they follow some precautions.

One of the most important pieces of advice is to wait a few years after the disease starts before attempting a pregnancy. During the first 3 years, you are at the highest risk of developing severe problems of the heart, lungs, or kidneys that could be harmful to you and your unborn baby.

If you haven’t developed severe organ problems within 3 years of the disease’s onset, your chances of such problems are less and pregnancy would be safer. But it is important to have both your disease and your pregnancy monitored regularly. You’ll probably need to stay in close touch with both the doctor you typically see for your scleroderma and an obstetrician who is experienced in guiding high-risk pregnancies.

How Can I Play a Role in My Health Care?

Although your doctors direct your treatment, you are the one who must take your medicine regularly, follow your doctor’s advice, and report any problems promptly. In other words, the relationship between you and your doctors is a partnership, and you are the most important partner. Here’s what you can do to make the most of this important role.

• Get educated: Knowledge is your best defense against this disease. Learn as much as you can about scleroderma, both for your own benefit and to educate the people in your support network.
• Seek support: Recruit family members, friends, and coworkers to build a support network. This network will help you get through difficult times: when you are in pain; when you feel angry, sad, or afraid; or when you’re depressed. Also, look for a scleroderma support group in your community by calling a national scleroderma organization. (See “For More Information”.) If you can’t find a support group, you might want to consider organizing one.
• Assemble a health care team: You and your doctors will lead the team. Other members may include physical and occupational therapists, a psychologist or social worker, a dentist, and a pharmacist.
• Be patient: Understand that a final diagnosis can be difficult and may take a long time. Find a doctor with experience treating people with systemic and localized scleroderma. Then, even if you don’t yet have a specific diagnosis, you will get understanding and the right treatment for your symptoms.
• Speak up: When you have problems or notice changes in your condition, don’t feel too self-conscious to speak up during your appointment or even call your doctor or another member of your health care team. No problem is too small to ask about, and early treatment for any problem can make the disease more manageable.
• Don’t accept depression: Although it’s understandable that a person with a chronic illness such as scleroderma would become depressed, don’t accept depression as a normal consequence of your condition. If depression makes it hard for you to function well, don’t hesitate to ask your health care team for help. You may benefit from speaking with a psychologist or social worker or from using one of the effective medications on the market.
• Learn coping skills: Meditation, calming exercises, and relaxation techniques may help you cope with emotional difficulties and relieve pain and fatigue. Ask a member of your health care team to teach you these skills or to refer you to someone who can.
• Ask the experts: If you have problems doing daily activities, from brushing your hair and teeth to driving your car, consult an occupational or physical therapist. They have more helpful hints and devices than you can probably imagine. Social workers can often help resolve financial and insurance matters.

Is Research Close to Finding a Cure?

No one can say for sure when – or if – a cure will be found. But research is providing the next best thing: better ways to treat symptoms, prevent organ damage, and improve the quality of life for people with scleroderma. In the past two decades, multidisciplinary research has also provided new clues for understanding the disease, which is an important step toward prevention and cure.

Leading the way in funding for this research is the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH). Other sources of funding for scleroderma research include pharmaceutical companies and organizations such as the Scleroderma Foundation, the Scleroderma Research Foundation, and the Arthritis Foundation. Scientists at universities and medical centers throughout the United States conduct much of this research.

Studies of the immune system, genetics, cell biology, and molecular biology have helped reveal the causes of scleroderma, improve existing treatment, and create entirely new treatment approaches.

Some recent advances in the understanding or treatment of scleroderma include the following:

• A gene associated with scleroderma has been found in Oklahoma Choctaw Native Americans. Scientists believe that the gene, which codes for a protein called fibrillin-1, may put people at risk for the disease. Current studies are using new technology to look for other genes associated with the disease’s development and severity.
• The drug cyclophosphamide (Cytoxan) has been found effective in treating lung fibrosis. One recent study suggested that treating lung problems early with this immunosuppressive drug may help prevent further damage and increase chances of survival. Further research is assessing the impact of cyclophosphamide on quality of life in people with lung involvement.
• ACE inhibitors are used increasingly for scleroderma-related kidney problems. For the past two decades, ACE inhibitors have greatly reduced the risk of kidney failure in people with scleroderma. Now there is evidence that use of ACE inhibitors can actually heal the kidneys of people on dialysis for scleroderma-related kidney failure. As many as half the people who continue ACE inhibitors while on dialysis may be able to go off dialysis in 12 to 18 months.
• Several new and exciting drugs are now available to treat pulmonary hypertension. Previously, pulmonary hypertension was associated with a poor outcome, but medications such as prostacyclins, endothelin-receptor antagonists, and phosphodiesterase inhibitors – epoprostenol sodium (Flolan), bosentan (Tracleer), and sildenafil (Revatio) – have increased the quality of life and life expectancy for people with this dangerous form of lung damage.

Other studies are examining the following:

• The theory that scleroderma is a more aggressive disease associated with more internal organ damage and a worse prognosis in non-Caucasians. Researchers believe that although factors related to both genetics and socioeconomic status may play a role, autoantibodies may be the primary reason that African Americans have such severe disease. A current study is examining that theory. Researchers hope that by better understanding the factors involved in scleroderma, they can design interventions that would improve the course and outcome of the disease.
• The use of ultraviolet-B (UV-B) light to treat the skin manifestations of localized scleroderma. Exposure to UV light has been shown to reduce collagen (which is overproduced in people with scleroderma) in the skin by inducing enzymes that break down collagen and by inhibiting the production of new collagen.
• Changes in the tiny blood vessels of people with scleroderma. By studying these changes, scientists hope to find the cause of cold sensitivity in Raynaud’s phenomenon and a way to control the problem.
• Studies have shown that certain chemicals called cytokines, made from cells in the body, enhance the development of increased collagen. New agents that counteract these cytokines may be helpful in preventing skin thickening.
• Skin changes in laboratory mice in which a genetic defect prevents the breakdown of collagen, leading to thick skin and patchy hair loss. Scientists hope that by studying these mice they can answer many questions about skin changes in scleroderma. Scientists are also working to establish mouse models for other problems related to scleroderma. These models will make it easier to understand these problems and develop treatments for them.

Scleroderma research continues to advance as scientists and doctors learn more about how the disease develops and its underlying mechanisms. NIAMS funds a research center specializing in scleroderma at the University of Texas Health Science Center at Houston. Scientists there are conducting laboratory and clinical research on the disease with the goal of translating basic science findings quickly into improved treatment and patient care.

More Questions? Count on More Answers

Scleroderma poses a series of challenges for both patients and their health care teams. The good news is that scientists, doctors, and other health care professionals continue to find new ways to make earlier diagnoses and manage disease better. In addition, active patient support groups share with, care for, and educate each other. The impact of all of this activity is that people with scleroderma do much better and remain active far longer than they did 20 or 30 years ago. As for tomorrow, patients and the medical community will continue to push for longer, healthier, and more active lives for people with the diseases collectively known as scleroderma.

For More Information

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  Information Clearinghouse
  National Institutes of Health

  1 AMS Circle
  Bethesda,  MD 20892-3675
  Phone: 301-495-4484
  Toll Free: 877-22-NIAMS (226-4267)
  TTY: 301–565–2966
  Fax: 301-718-6366
  Email: NIAMSinfo@mail.nih.gov
  Website: http://www.niams.nih.gov

  NIAMS provides information about various forms of arthritis and other rheumatic diseases, as well as other bone, muscle, joint, and skin diseases. It distributes patient and professional education materials and refers people to other sources of information. Additional information and updates can be found on the NIAMS Web site.

• American Academy of Dermatology (AAD)

  P.O. Box 4014
  Schaumberg,  IL 60618-4014
  Phone: 847-330-0230
  Toll Free: 866-503-SKIN (7546)
  Fax: 847-240-1859
  Website: http://www.aad.org

  This national professional association for dermatologists publishes a pamphlet on skin conditions and provides referrals to doctors.

• American College of Rheumatology (ACR)

  1800 Century Place, Suite 250
  Atlanta,  GA 30345-4300
  Phone: 404-633-3777
  Fax: 404-633-1870
  Website: http://www.rheumatology.org

  The American College of Rheumatology is an organization of doctors and associated health professionals who specialize in arthritis and related diseases of the bones, joints, and muscles. The Association of Rheumatology Health Professionals, a division of ACR, aims to enhance the knowledge and skills of rheumatology health professionals and to promote their involvement in rheumatology research, education, and quality patient care. The association also works to advance and promote basic and continuing education in rheumatology for health professionals who provide care to people with rheumatic diseases.

• Scleroderma Foundation

  300 Rosewood Drive, Suite 105
  Danvers,  MA 01923
  Phone: 978-463-5843
  Toll Free: 800-722-HOPE (4673)
  Fax: 978-463-5809
  Email: sfinfo@scleroderma.org
  Website: http://www.scleroderma.org

  This voluntary organization publishes information and funds research on scleroderma. It also offers patient education seminars, support groups, doctor referrals, and information hotlines.

• Scleroderma Research Foundation

  220 Montgomery Street, Suite 1411
  San Francisco,  CA 94104
  Phone: 415-834-9444
  Toll Free: 800-441-CURE (2873)
  Fax: 415-834-9177
  Website: http://www.srfcure.org

  The foundation’s goal is to find a cure for scleroderma by funding and facilitating the most promising, highest quality research and by placing the disease and its need for a cure in the public eye. The foundation distributes patient handbooks and a twice-yearly, research-related newsletter.

• Arthritis Foundation

  P.O. Box 7669
  Atlanta,  GA 30357-0669
  Phone: 404-872-7100
  Toll Free: 800-283-7800
  Website: http://www.arthritis.org

  The Arthritis Foundation is devoted to supporting arthritis research and providing educational and other services to individuals with arthritis. The foundation publishes a free pamphlet on rheumatoid arthritis and a magazine for members on all types of arthritis. It also provides up-to-date information on research, treatment, nutrition, alternative therapies, and self-management strategies. Chapters nationwide offer exercise programs, classes, support groups, doctor referrals, and free literature. The foundation also has free information about lupus, scleroderma, and other autoimmune and rheumatic conditions on its Web site.

Key Words

Antibodies – special proteins produced by the body’s immune system. They recognize and help fight infectious agents, such as bacteria and other foreign substances that invade the body. The presence of certain antibodies in the blood can help to diagnose some diseases, including some forms of scleroderma.

Atherosclerosis – abnormal fatty deposits in the inner layers of large or medium-sized arteries, which can lead to hardening and narrowing of the arteries and blockages of the blood supply, especially to the heart.

Autoimmune disease – a disease in which the body’s immune system turns against and damages its own tissues.

Calcinosis – the formation of calcium deposits in the connective tissues, which can be detected by x ray. These deposits are typically found on the fingers, hands, face, and trunk and on the skin above elbows and knees. When the deposits break through the skin, painful ulcers can result.

Calcium channel blockers – medicines that lower blood pressure, relieve chest pain, and stabilize normal heart rhythms by inhibiting calcium movement into the heart muscles and smooth muscle cells. They are used to treat a variety of conditions and to prevent circulatory and kidney problems in scleroderma.

Collagen – a fabric-like material of fibrous threads that is a key component of the body’s connective tissues. In scleroderma, either too much collagen is produced or it is produced in the wrong places, causing stiff and inflamed skin, blood vessels, and internal organs.

Connective tissue – tissues such as skin, tendons, and cartilage that support and hold body parts together. The chief component of connective tissue is collagen.

CREST syndrome – an acronym for a collection of symptoms that occur to some degree in all people with systemic sclerosis. The symptoms are calcinosis, Raynaud’s phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Because of the predominance of CREST symptoms in people with limited systemic sclerosis, some people use the term CREST syndrome when referring to that form of the disease.

Eosinophilic fasciitis – a scleroderma-like disorder (often considered to be a localized form of scleroderma) featuring inflammation of the fascia (the thin, sheet-like connective tissues surrounding the muscles and other body structures) and an abnormally high number of a specific kind of white blood cells (eosinophils). The result of the inflammation may be fibrous buildup in the skin of arms and legs, contractures, and carpal tunnel syndrome.

Esophageal dysfunction – impaired function of the esophagus (the tube connecting the throat and the stomach) that occurs when smooth muscles in the esophagus lose normal movement. In the upper and lower esophagus, the result can be swallowing difficulties. In the lower esophagus, the result can be chronic heartburn or inflammation.

Fibroblast – a type of cell in connective tissue that secretes proteins, including collagen.

Fibrosis – a condition marked by increased fibrous tissue that develops between the cells of various organs or tissues. It is a common feature of scleroderma and some other diseases. Fibrosis causes hardening or stiffening of tissues in the skin, joints, and internal organs.

Graft-versus-host disease – a major complication of bone marrow transplantations and sometimes blood transfusions in which white blood cells called lymphocytes, which are found in the marrow or blood, attack tissues in the body into which they were transplanted.

Pulmonary fibrosis – hardening or scarring of lung tissue because of excess collagen. Pulmonary fibrosis occurs in a small percentage of people with systemic sclerosis.

Pulmonary hypertension – abnormally high blood pressure in the arteries supplying the lungs that may be caused by a number of factors, including damage from fibrosis.

Raynaud’s phenomenon – a condition in which the small blood vessels of the hands or feet contract in response to cold or anxiety. As the vessels contract, the hands or feet turn white and cold, then blue. As blood flow returns, they become red. Fingertip tissues may suffer damage, leading to ulcers, scars, or gangrene.

Rheumatic – an adjective used to describe a group of conditions characterized by inflammation or pain in the muscles, joints, and fibrous tissue. Rheumatic diseases or disorders can be related to autoimmunity or other causes.

Sclerodactyly – thick and tight skin on the fingers, resulting from deposits of excess collagen within skin layers. The condition makes it harder to bend or straighten the fingers. The skin may also appear shiny and darkened, with hair loss.

Systemic condition – a condition involving the body as a whole, as opposed to limited conditions that affect particular parts of the body.

Systemic lupus erythematosus – a systemic rheumatic disease that occurs predominantly in women and is characterized by autoimmune activity, a facial rash across the bridge of the nose and cheeks, Raynaud’s phenomenon, joint pain and swelling, fever, chest pain, hair loss, and other symptoms. Many of its symptoms overlap with those of scleroderma.

Telangiectasia – a condition caused by the swelling of tiny blood vessels, in which small red spots appear on the hands and face. Although not painful, these red spots can create cosmetic problems.

Acknowledgments

NIAMS gratefully acknowledges the assistance of Reva Lawrence, M.P.H., Barbara Mittleman, M.D., Alan Moshell, M.D., and Susana Serrate-Sztein, M.D., NIAMS, NIH; Stanley Pillemer, M.D., National Institute of Dental and Craniofacial Research, NIH; Philip Clements, M.D., University of California at Los Angeles; Vincent Falanga, M.D., Boston University; E. Carwile LeRoy, M.D., Medical University of South Carolina, Charleston; Morris Reichlin, M.D., Oklahoma Medical Research Foundation, Oklahoma City; Larry Solomon, M.D., Lutheran General Children’s Hospital, Park Ridge, IL; Virginia Steen, M.D., Georgetown University Medical Center, Washington, DC; Barbara White, M.D., University of Maryland at Baltimore; and the Scleroderma Foundation, Danvers, MA, in the preparation and review of this manuscript. Special thanks also go to the patients who reviewed this publication and provided valuable assistance. Mary Anne Dunkin was the primary author of this booklet.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. The NIAMS Information Clearinghouse is a public service sponsored by the Institute that provides health information and information sources. Additional information can be found on the NIAMS Web site at www.niams.nih.gov.

For Your Information

This publication contains information about medications used to treat the health condition discussed here. When this booklet was printed, we included the most up-to-date (accurate) information available. Occasionally, new information on medication is released.

For updates and for any questions about any medications you are taking, please contact the U.S. Food and Drug Administration at:

U.S. Food and Drug Administration

Toll Free: 888-INFO-FDA (888-463-6332)
Website: http://www.fda.gov/

For updates and questions about statistics, please contact the Centers for Disease Control and Prevention’s National Center for Health Statistics at:

Centers for Disease Control and Prevention’s National Center for Health Statistics

Toll Free: 800–232–4636
Website: http://www.cdc.gov/nchs

This booklet is not copyrighted. Readers are encouraged to duplicate and distribute as many copies as needed.

Additional copies of this booklet are available from:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information Clearinghouse
National Institutes of Health

1 AMS Circle
Bethesda,  MD 20892-3675
Phone: 301-495-4484
Toll Free: 877-22-NIAMS (226-4267)
TTY: 301–565–2966
Fax: 301-718-6366
Email: NIAMSinfo@mail.nih.gov
Website: http://www.niams.nih.gov

NIH Publication No. 06-4271

Source: National Institute of Arthritis and Musculoskeletal and Skin Disease – http://www.niams.nih.gov/Health_Info/Scleroderma/default.asp