Rheumatoid Arthritis.

This is a publication of the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases

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 the National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse, NIAMS, National Institutes of Health,

1 AMS Circle, Bethesda, Maryland 20892-3675, and on the NIAMS Web site at http://www.nih.gov/niams/healthinfo/.

Rheumatoid Arthritis

This booklet is for people who have rheumatoid arthritis, as well as for their family members, friends, and others who want to find out more about this disease. The booklet describes how rheumatoid arthritis develops, how it is diagnosed, and how it is treated, including what patients can do to help manage their disease. It also highlights current research efforts supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other components of the National Institutes of Health (NIH). If you have further questions after reading this booklet, you may wish to discuss them with your doctor.

Features Of Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. It has several special features that make it different from other kinds of arthritis. For example, rheumatoid arthritis generally occurs in a symmetrical pattern. This means that if one knee or hand is involved, the other one is also. The disease often affects the wrist joints and the finger joints closest to the hand. It can also affect other parts of the body besides the joints. In addition, people with the disease may have fatigue, occasional fever, and a general sense of not feeling well (malaise).

Another feature of rheumatoid arthritis is that it varies a lot from person to person. For some people, it lasts only a few months or a year or two and goes away without causing any noticeable damage. Other people have mild or moderate disease, with periods of worsening symptoms, called flares, and periods in which they feel better, called remissions. Still others have severe disease that is active most of the time, lasts for many years, and leads to serious joint damage and disability.

Although rheumatoid arthritis can have serious effects on a person's life and well-being, current treatment strategies--including pain relief and other medications, a balance between rest and exercise, and patient education and support programs--allow most people with the disease to lead active and productive lives. In recent years, research has led to a new understanding of rheumatoid arthritis and has increased the likelihood that, in time, researchers can find ways to greatly reduce the impact of this disease.

Features of Rheumatoid Arthritis

* Tender, warm, swollen joints.

* Symmetrical pattern. For example, if one knee is affected, the other one is also.

* Joint inflammation often affecting the wrist and finger joints closest to the hand; other affected joints can include those of the neck, shoulders, elbows, hips, knees, ankles, and feet.

* Fatigue, occasional fever, a general sense of not feeling well (malaise).

* Pain and stiffness lasting for more than 30 minutes in the morning or after a long rest.

* Symptoms that can last for many years.

* Symptoms in other parts of the body besides the joints.

* Variability of symptoms among people with the disease.

How Rheumatoid Arthritis Develops And Progresses

The Joints

A normal joint (the place where two bones meet) is surrounded by a joint capsule that protects and supports it (see illustration). Cartilage covers and cushions the ends of the two bones. The joint capsule is lined with a type of tissue called synovium, which produces synovial fluid. This clear fluid lubricates and nourishes the cartilage and bones inside the joint capsule.

In rheumatoid arthritis, the immune system, for unknown reasons, attacks a person's own cells inside the joint capsule. White blood cells that are part of the normal immune system travel to the synovium and cause a reaction. This reaction, or inflammation, is called synovitis, and it results in the warmth, redness, swelling, and pain that are typical symptoms of rheumatoid arthritis. During the inflammation process, the cells of the synovium grow and divide abnormally, making the normally thin synovium thick and resulting in a joint that is swollen and puffy to the touch (see illustration).

[ILLUSTRATION OMITTED]

As rheumatoid arthritis progresses, these abnormal synovial cells begin to invade and destroy the cartilage and bone within the joint. The surrounding muscles, ligaments, and tendons that support and stabilize the joint become weak and unable to work normally. All of these effects lead to the pain and deformities often seen in rheumatoid arthritis. Doctors studying rheumatoid arthritis now believe that damage to bones begins during the first year or two that a person has the disease. This is one reason early diagnosis and treatment are so important in the management of rheumatoid arthritis.

Other Parts of the Body

Some people also experience the effects of rheumatoid arthritis in places other than the joints. About one-quarter develop rheumatoid nodules. These are bumps under the skin that often form close to the joints. Many people with rheumatoid arthritis develop anemia, or a decrease in the normal number of red blood cells. Other effects, which occur less often, include neck pain and dry eyes and mouth. Very rarely, people may have inflammation of the blood vessels, the lining of the lungs, or the sac enclosing the heart.

Occurrence And Impact Of Rheumatoid Arthritis

Scientists estimate that about 2.1 million people, or 1 percent of the U.S. adult population, have rheumatoid arthritis. Interestingly, some recent studies have suggested that the overall number of new cases of rheumatoid arthritis may actually be going down. Scientists are now investigating why this may be happening.

Rheumatoid arthritis occurs in all races and ethnic groups. Although the disease often begins in middle age and occurs with increased frequency in older people, children and young adults also develop it. Like some other forms of arthritis, rheumatoid arthritis occurs much more frequently in women than in men. About two to three times as many women as men have the disease.

By all measures, the financial and social impact of all types of arthritis, including rheumatoid arthritis, is substantial, both for the Nation and for individuals. From an economic standpoint, the medical and surgical treatment for rheumatoid arthritis and the wages lost because of disability caused by the disease add up to millions of dollars. Daily joint pain is an inevitable consequence of the disease, and most patients also experience some degree of depression, anxiety, and feelings of helplessness. In some cases, rheumatoid arthritis can interfere with a person's ability to carry out normal daily activities, limit job opportunities, or disrupt the joys and responsibilities of family life. However, there are arthritis self-management programs that help people cope with the pain and other effects of the disease and help them lead independent and productive lives. These programs are described later in this booklet in the section Diagnosing and Treating Rheumatoid Arthritis.

Searching For The Cause Of Rheumatoid Arthritis

Rheumatoid arthritis is one of several "autoimmune" diseases ("auto" means self), so-called because a person's immune system attacks his or her own body tissues. Scientists still do not know exactly what causes this to happen, but research over the last few years has begun to unravel the factors involved.

Genetic (inherited) factors: Scientists have found that certain genes that play a role in the immune system are associated with a tendency to develop rheumatoid arthritis. At the same time, some people with rheumatoid arthritis do not have these particular genes, and other people have these genes but never develop the disease. This suggests that a person's genetic makeup is an important part of the story but not the whole answer. It is clear, however, that more than one gene is involved in determining whether a person develops rheumatoid arthritis and, if so, how severe the disease will become.

Environmental factors: Many scientists think that something must occur to trigger the disease process in people whose genetic makeup makes them susceptible to rheumatoid arthritis. An infectious agent such as a virus or bacterium appears likely, but the exact agent is not yet known. Note, however, that rheumatoid arthritis is not contagious: A person cannot "catch" it from someone else.

Other factors: Some scientists also think that a variety of hormonal factors may be involved. These hormones, or possibly deficiencies or changes in certain hormones, may promote the development of rheumatoid arthritis in a genetically susceptible person who has been exposed to a triggering agent from the environment.

Even though all the answers aren't known, one thing is certain: Rheumatoid arthritis develops as a result of an interaction of many factors. Much research is going on now to understand these factors and how they work together (see the Current Research section of this booklet).

Diagnosing And Treating Rheumatoid Arthritis

Diagnosing and treating rheumatoid arthritis is a team effort between the patient and several types of health care professionals. A person can go to his or her family doctor or internist or to a rheumatologist. A rheumatologist is a doctor who specializes in arthritis and other diseases of the joints, bones, and muscles. As treatment progresses, other professionals often help. These may include nurses, physical or occupational therapists, orthopedic surgeons, psychologists, and social workers.

Studies have shown that people who are well informed and participate actively in their own care experience less pain and make fewer visits to the doctor than do other people with rheumatoid arthritis.

Patient education and arthritis self-management programs, as well as support groups, help people to become better informed and to participate in their own care. An example of a self-management program is the arthritis self-help course offered by the Arthritis Foundation and developed at one of the NIAMS-supported Multipurpose Arthritis and Musculoskeletal Diseases Centers. Self-management programs teach about rheumatoid arthritis and its treatments, exercise and relaxation approaches, patient/health care provider communication, and problem solving. Research on these programs has shown that they have the following clear and long-lasting benefits:

* They help people understand the disease.

* They help people reduce their pain while remaining active.

* They help people cope physically, emotionally, and mentally.

* They help people feel greater control over their disease and help build a sense of confidence in the ability to function and lead a full, active, and independent life.

DIAGNOSIS

Rheumatoid arthritis can be difficult to diagnose in its early stages for several reasons. First, there is no single test for the disease. In addition, symptoms differ from person to person and can be more severe in some people than in others. Also, symptoms can be similar to those of other types of arthritis and joint conditions, and it may take some time for other conditions to be ruled out as possible diagnoses. Finally, the full range of symptoms develops over time, and only a few symptoms may be present in the early stages. As a result, doctors use a variety of tools to diagnose the disease and to rule out other conditions:

Medical history: This is the patient's description of symptoms and when and how they began. Good communication between patient and doctor is especially important here. For example, the patient's description of pain, stiffness, and joint function and how these change over time is critical to the doctor's initial assessment of the disease and his or her assessment of how the disease changes.

Physical examination: This includes the doctor's examination of the joints, skin, reflexes, and muscle strength.

Laboratory tests: One common test is for rheumatoid factor, an antibody that is eventually present in the blood of most rheumatoid arthritis patients. (An antibody is a special protein made by the immune system that normally helps fight foreign substances in the body.) Not all people with rheumatoid arthritis test positive for rheumatoid factor, however, especially early in the disease. And, some others who do test positive never develop the disease. Other common tests include one that indicates the presence of inflammation in the body (the erythrocyte sedimentation rate), a white blood cell count, and a blood test for anemia.

X rays: X rays are used to determine the degree of joint destruction. They are not useful in the early stages of rheumatoid arthritis before bone damage is evident, but they can be used later to monitor the progression of the disease.

TREATMENT

Doctors use a variety of approaches to treat rheumatoid arthritis. These are used in different combinations and at different times during the course of the disease and are chosen according to the patient's individual situation. No matter what treatment the doctor and patient choose, however, the goals are the same: relieve pain, reduce inflammation, slow down or stop joint damage, and improve the person's sense of well-being and ability to function.

Treatment is another key area for communication between patient and doctor. Talking to the doctor can help ensure that exercise and pain management programs are provided as needed and that drugs are prescribed appropriately. Talking can also help in making decisions about surgery.

Goals of Treatment

* Relieve pain

* Reduce inflammation

* Slow down or stop joint damage

* Slow down or stop joint damage

* Improve a person's sense of well-being and ability to function

Current Treatment Approaches

* Lifestyle

* Medications

* Surgery

* Routine monitoring and ongoing care

Lifestyle

This approach includes several activities that help improve a person's ability to function independently and maintain a positive outlook.

Rest and exercise: Both rest and exercise help in important ways. People with rheumatoid arthritis need a good balance between the two, with more rest when the disease is active and more exercise when it is not. Rest helps to reduce active joint inflammation and pain and to fight fatigue. The length of time needed for rest will vary from person to person, but in general, shorter rest breaks every now and then are more helpful than long times spent in bed.

Exercise is important for maintaining healthy and strong muscles, preserving joint mobility, and maintaining flexibility. Exercise can also help people sleep well, reduce pain, maintain a positive attitude, and lose weight. Exercise programs should be planned and carried out to take into account the person's physical abilities, limitations, and changing needs.

Care of joints: Some people find that using a splint for a short time around a painful joint reduces pain and swelling by supporting the joint and letting it rest. Splints are used mostly on wrists and hands, but also on ankles and feet. A doctor or a physical or occupational therapist can help a patient get a splint and ensure that it fits properly. Other ways to reduce stress on joints include self-help devices (for example, zipper pullers, long-handled shoe horns); devices to help with getting on and off chairs, toilet seats, and beds; and changes in the ways that a person carries out daily activities.

Stress reduction: People with rheumatoid arthritis face emotional challenges as well as physical ones. The emotions they feel because of the disease-fear, anger, frustration-combined with any pain and physical limitations can increase their stress level. Although there is no evidence that stress plays a role in causing rheumatoid arthritis, it can make living with the disease difficult at times. Stress may also affect the amount of pain a person feels. There are a number of successful techniques for coping with stress. Regular rest periods can help, as can relaxation, distraction, or visualization exercises. Exercise programs, participation in support groups, and good communication with the health care team are other ways to reduce stress.

Healthful diet: With the exception of several specific types of oils (mentioned in the Current Research section), there is no scientific evidence that any specific food or nutrient helps or harms most people with rheumatoid arthritis. However, an overall nutritious diet with enough-but not an excess of-calories, protein, and calcium is important. Some people may need to be careful about drinking alcoholic beverages because of the medications they take for rheumatoid arthritis. Those taking methotrexate may need to avoid alcohol altogether. Patients should ask their doctors for guidance on this issue.

Climate: Some people notice that their arthritis gets worse when there is a sudden change in the weather. However, there is no evidence that a specific climate can prevent or reduce the effects of rheumatoid arthritis. Moving to a new place with a different climate usually does not make a long-term difference in a person's rheumatoid arthritis.

Medications

Most people who have rheumatoid arthritis take medications. Some medications are used only for pain relief; others are used to reduce inflammation. Still others-often called disease-modifying antirheumatic drugs, or DMARDs-are used to try to slow the course of the disease. The person's general condition, the current and predicted severity of the illness, the length of time he or she will take the drug, and the drug's effectiveness and potential side effects are important considerations in prescribing drugs for rheumatoid arthritis. The table starting on page 20 shows currently used rheumatoid arthritis medications, along with their effects, side effects, and monitoring requirements.

Traditionally, rheumatoid arthritis therapy has involved an approach in which doctors prescribed aspirin or similar drugs, rest, and physical therapy first, and prescribed more powerful drugs later only if the disease became much worse. Recently, many doctors have changed their approach, especially for patients with severe, rapidly progressing rheumatoid arthritis. This change is based on the belief that early treatment with more powerful drugs, and the use of drug combinations in place of single drugs, may be more effective ways to halt the progression of the disease and reduce or prevent joint damage.

Surgery

Several types of surgery are available to patients with severe joint damage. These procedures can help reduce pain, improve the affected joint's function and appearance, and improve the patient's ability to perform daily activities. Surgery is not for everyone, however, and the decision should be made only after careful consideration by patient and doctor. Together they should discuss the patient's overall health and the effects of a surgical procedure, the condition of the joint or tendon that will be operated on, and the reason for and cost of the surgery. Surgical procedures include joint replacement, tendon reconstruction, and synovectomy.

Joint replacement: This is the most frequently performed surgery for rheumatoid arthritis, and it is done to relieve pain, improve or preserve joint function, and improve appearance. In making a decision about replacing a joint, people with rheumatoid arthritis should consider that some artificial joints function more like normal human joints than do others. Also, artificial joints are not always permanent and may eventually have to be replaced. This may be an issue for younger people.

Tendon reconstruction: Rheumatoid arthritis can damage and even rupture tendons, the tissues that attach muscle to bone. This surgery, which is used most frequently on the hands, reconstructs the damaged tendon by attaching an intact tendon to it. This procedure can help to restore some hand function, particularly if it is done early, before the tendon is completely ruptured.

Synovectomy: In this surgery, the doctor actually removes the inflamed synovial tissue. Synovectomy by itself is seldom performed now because not all of the tissue can be removed, and it eventually grows back. Synovectomy is done as part of reconstructive surgery, especially tendon reconstruction.

Routine Monitoring and Ongoing Care

Regular medical care is important to monitor the course of the disease, determine the effectiveness and any negative effects of medications, and change therapies as needed. Monitoring typically includes regular visits to the doctor. It may also include blood, urine, and other laboratory tests and x rays.

Osteoporosis prevention is one issue that patients may want to discuss with their doctors as part of their long-term, ongoing care. Osteoporosis is a condition in which bones lose calcium and become weakened and fragile. Many older women are at increased risk for osteoporosis, and their rheumatoid arthritis increases the risk further, particularly if they are taking corticosteroids such as prednisone. These patients may want to discuss with their doctors the potential benefits of calcium and vitamin D supplements, hormone replacement therapy, or other treatments for osteoporosis.

Alternative and Complementary Therapies

Special diets, vitamin supplements, and other alternative approaches have been suggested for the treatment of rheumatoid arthritis. Although many of these approaches may not be harmful in and of themselves, controlled scientific studies either have not been conducted or have found no definite benefit to these therapies. Some alternative or complementary approaches may help the patient cope or reduce some of the stress associated with living with a chronic illness. As with any therapy, patients should discuss the benefits and drawbacks with their doctors before beginning an alternative or new type of therapy. If the doctor feels the approach has value and will not be harmful, it can be incorporated into a patient's treatment plan. However, it is important not to neglect regular health care. The Arthritis Foundation publishes material on alternative therapies as well as established therapies, and patients may want to contact this organization for information. (See the For More Information section of this booklet.)

Medications Commonly Used To Treat Rheumatoid Arthritis

Medications             Uses/Effects          Side Effects

Aspirin and other       * Used to reduce      * Upset stomach
nonsteroidal            pain, swelling,
anti-inflammatory       and inflammation,     * Tendency to bruise
drugs (NSAIDs)          allowing patients     easily
                        to move more
Examples:               easily and carry      * Fluid retention
                        out normal            (NSAIDs other than
* Plain aspirin         activities            aspirin)
* Buffered aspirin      * Generally part      * Ulcers
                        of early and
* Ibuprofen             continuing            * Possible kidney and
(Advil,(*) Motrin IB)   therapy               liver damage (rare)
* Ketoprofen
(Orudis)
* Naproxen
(Naprosyn)
* Diclofenac
(Voltaren)
* Diflunisal
(Dolobid)
Disease-modifying       * Used to alter       Toxicity is an issue-
anti-rheumatic          the course of the     DMARDs can have
drugs (DMARDs)          disease and           serious side effects:
(also called            prevent joint and
slow-acting             cartilage             * Gold-skin rash,
antirheumatic drugs     destruction           mouth sores, upset
[SAARDs] or                                   stomach, kidney
second-line drugs)      * May produce         problems, low blood
                        significant           count
Examples:               improvement for
                        many patients         * Antimalarials-
* Gold, injectable or                         upset stomach, eye
oral (Myochrysine,      * Exactly how         problems (rare)
Ridaura)                they work still
                        unknown               * Penicillamine-skin
* Antimalarials,                              rashes, upset
such as                 * Generally take a    stomach, blood
hydroxychloroquine      few weeks or          abnormalities, kidney
(Plaquenil)             months to have        problems
                        an effect
* Penicillamine                               * Sulfasalazine-
(Cuprimine, Depen)      * Patients may        upset stomach
                        use several over
* Sulfasalazine         the course of the
(Azulfidine)            disease

Medications             Uses/Effects          Side Effects

Immuno-                 * Used to restrain    Toxicity is an issue-
suppressants            the overly active     immunosuppressants
(also considered        immune system,        can have serious side
DMARDs)                 which is key to       effects:
                        the disease
Examples:               process               * Methotrexate-
                                              upset stomach,
* Methotrexate          * Same concerns       potential liver
(Rheumatrex)            as with other         problems, low white
                        DMARDs:               blood cell count
* Azathioprine          potential toxicity
(Imuran)                and diminishing       * Azathioprine-
                        effectiveness         potential blood
* Cyclo-                over time             abnormalities, low
phosphamide                                   white blood cell
(Cytoxan)               * Methotrexate        count, possible
                        can result in         increased cancer risk
                        rapid
                        improvement;          * Cyclophosphamide-
                        appears to be         low white blood cell
                        very effective        count, other blood

                        * Azathioprine-       abnormalities,
                        first used in         increased cancer risk
                        higher doses
                        in cancer chemo-
                        therapy and
                        organ
                        transplantation;
                        used in patients
                        who have not
                        responded to
                        other drugs; used
                        in combination
                        therapy

                        * Cyclo-
                        phosphamide-
                        also used in
                        higher doses in
                        cancer
                        chemotherapy;
                        effective, but
                        used only in very
                        severe cases of
                        rheumatoid
                        arthritis because
                        of potential
                        toxicity

 Corticosteroids        * Used for their      * Osteoporosis
 (also known as         anti-inflammatory
 glucocorticoids)       and immuno-           * Mood changes
                        suppressive
 Examples:              effects               * Fragile skin, easy
                                               bruising
 * Prednisone           * Given either in
 (Deltasone,            pill form or as an    * Fluid retention
 Orasone)               injection into a
                        joint                 * Weight gain
 * Methylprednisolone
 (Medrol)               * Dramatic            * Muscle weakness
                        improvements in
                        very short time       * Onset or worsening
                                              of diabetes
                        * Potential for
                        serious side          * Cataracts
                        effects, especially
                        at high doses         * Increased risk of
                                              infection
                        * Often used early
                        while waiting for     * Hypertension (high
                        DMARDs to work        blood pressure)

                        * Also used for
                        severe flares and
                        when the disease
                        does not respond
                        to NSAIDs
                        and DMARDs

Medications             Monitoring

Aspirin and other       Patients should
nonsteroidal            have periodic blood
anti-inflammatory       tests.
drugs (NSAIDs)

Examples:

* Plain aspirin
* Buffered aspirin

* Ibuprofen
(Advil,(*) Motrin IB)
* Ketoprofen
(Orudis)
* Naproxen
(Naprosyn)
* Diclofenac
(Voltaren)
* Diflunisal
(Dolobid)

Disease-modifying       Patients should be
anti-rheumatic          monitored carefully
drugs (DMARDs)          for continued
(also called            effectiveness
slow-acting             of medication and
antirheumatic drugs     for side effects:
[SAARDs] or
second-line drugs)      * Gold-blood and
                        urine test monthly;
Examples:               more often in early
                        use of drug
* Gold, injectable or
oral (Myochrysine,      * Antimalarials-
Ridaura)                eye exam every 6
                        months
* Antimalarials,
such as                 * Penicillamine-
hydroxychloroquine      blood and urine test
(Plaquenil)             monthly; more often
                        in early use of drug
* Penicillamine
(Cuprimine, Depen)      * Sulfasalazine-
                        periodic blood and
* Sulfasalazine         urine tests
(Azulfidine)

Medications             Monitoring

Immuno-                 Patients should be
suppressants            monitored carefully
(also considered        for continued
DMARDs)                 effectiveness
                        of medication and
Examples:               for side effects:

* Methotrexate          * Methotrexate-
(Rheumatrex)            regular blood tests,
                        including liver
* Azathioprine          function test;
(Imuran)                baseline chest x ray

* Cyclo-                * Azathioprine-
phosphamide             regular blood and
(Cytoxan)               liver function tests

                        * Cyclophosphamide-
                        regular blood, urine,
                        and general medical
                        tests

Corticosteroids        Patients should be
(also known as         monitored carefully
glucocorticoids)       for continued
                       effectiveness of
Examples:              medication and for
                       side effects.
* Prednisone
(Deltasone,
Orasone)

* Methylprednisolone
(Medrol)

(*) Brand names included in this fact sheet 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.

Current Research

Over the last several decades, research has greatly increased our understanding of immunology, genetics, and cellular and molecular biology. This foundation in basic science is now showing results in several areas important to rheumatoid arthritis. Scientists are thinking about rheumatoid arthritis in exciting ways that were not possible even 10 years ago.

The National Institutes of Health funds a wide variety of medical research at its headquarters in Bethesda, Maryland, and at universities and medical centers across the United States. One of the NIH institutes, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, is a major supporter of research and research training in rheumatoid arthritis through grants to individual scientists, Specialized Centers of Research, and Multipurpose Arthritis and Musculoskeletal Diseases Centers.

Following are examples of current research directions in rheumatoid arthritis supported by the Federal Government through the NIAMS and other parts of the NIH.

Scientists are looking at basic abnormalities in the immune systems of people with rheumatoid arthritis and in some animal models of the disease to understand why and how the disease develops. Findings from these studies may lead to precise, targeted therapies that could stop the inflammatory process in its earliest stages. They may even lead to a vaccine that could prevent rheumatoid arthritis.

Researchers are studying genetic factors that predispose some people to developing rheumatoid arthritis, as well as factors connected with disease severity. Findings from these studies should increase our understanding of the disease and will help develop new therapies as well as guide treatment decisions. In a major effort aimed at identifying genes involved in rheumatoid arthritis, the NIH and the Arthritis Foundation have joined together to support the North American Rheumatoid Arthritis Consortium. This group of 12 research centers around the United States is collecting medical information and genetic material from 1,000 families in which two or more siblings have rheumatoid arthritis. It will serve as a national resource for genetic studies of this disease.

Scientists are also gaining insights into the genetic basis of rheumatoid arthritis by studying rats with autoimmune inflammatory arthritis that resembles human disease. NIAMS researchers have identified several genetic regions that affect arthritis susceptibility and severity in these animal models of the disease, and found some striking similarities between rats and humans. Identifying disease genes in rats should provide important new information that may yield clues to the causes of rheumatoid arthritis in humans.

Scientists are studying the complex relationships among the hormonal, nervous, and immune systems in rheumatoid arthritis. For example, they are exploring whether and how the normal changes in the levels of steroid hormones (such as estrogen and testosterone) during a person's lifetime may be related to the development, improvement, or flares of the disease. Scientists are also looking at how these systems interact with environmental and genetic factors. Results from these studies may suggest new treatment strategies.

Researchers are exploring why so many more women than men develop rheumatoid arthritis. In hopes of finding clues, they are studying female and male hormones and other elements that differ between women and men, such as possible differences in their immune responses.

To find clues to new treatments, researchers are examining why rheumatoid arthritis often improves during pregnancy. Results of one study suggest that the explanation may be related to differences in certain special proteins between a mother and her unborn child. These proteins help the immune system distinguish between the body's own cells and foreign cells. Such differences, the scientists speculate, may change the activity of the mother's immune system during pregnancy.

A growing body of evidence indicates that infectious agents, such as viruses and bacteria, may trigger rheumatoid arthritis in people who have an inherited predisposition to the disease. Investigators are trying to discover which infectious agents may be responsible. More broadly, they are also working to understand the basic mechanisms by which these agents might trigger the development of rheumatoid arthritis. Identifying the agents and understanding how they work could lead to new therapies.

Scientists are searching for new drugs or combinations of drugs that can reduce inflammation, can slow or stop the progression of rheumatoid arthritis, and also have few side effects. Studies in humans have shown that a number of compounds have such potential. For example, some studies are breaking new ground in the area of "biopharmaceuticals," or "biologics." These new drugs are based on compounds occurring naturally in the body, and are designed to target specific aspects of the inflammatory process.

Investigators have also shown that treatment of rheumatoid arthritis with minocycline, a drug in the tetracycline family, has a modest benefit. The effects of a related tetracycline called doxycycline are under investigation. Other studies have shown that the omega-3 fatty acids in certain fish or plant seed oils also may reduce rheumatoid arthritis inflammation. However, many people are not able to tolerate the large amounts of oil necessary for any benefit.

Investigators are examining many issues related to quality of life for rheumatoid arthritis patients and quality, cost, and effectiveness of health care services for these patients. Scientists have found that even a small improvement in a patient's sense of physical and mental well-being can have an impact on his or her quality of life and use of health care services. Results from studies like these will help health care providers design integrated treatment strategies that cover all of a patient's needs-emotional as well as physical.

Hope For The Future

Scientists are making rapid progress in understanding the complexities of rheumatoid arthritis-how and why it develops, why some people get it and others do not, why some people get it more severely than others. Results from research are having an impact today, enabling people with rheumatoid arthritis to remain active in life, family, and work far longer than was possible 20 years ago. There is also hope for tomorrow, as researchers continue to explore ways of stopping the disease process early, before it becomes destructive, or even preventing rheumatoid arthritis altogether.

For More Information

National Arthritis and Musculoskeletal and Skin Diseases
Information Clearinghouse
NIAMS/National Institutes of Health
1 AMS Circle
Bethesda, MD 20892-3675

The text of the booklet is also available 24 hours a day by fax. Using the phone on a fax machine, call NIAMS Fast Facts at [phone]. Listen to the instructions and dial 01301; the text will print to the fax machine.

The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse (NAMSIC) is a public service sponsored by the NIAMS that provides health information and information sources. The Clearinghouse provides information on rheumatoid arthritis, including a fact sheet on arthritis and exercise. Fact sheets, additional information, and research updates can also be found on the NIAMS Web site at http://www.nih.gov/niams/.

Arthritis Foundation
1330 West Peachtree Street
Atlanta, GA 30309
[phone]
[phone]

or your local chapter, listed in the telephone directory

Web address: http://www.arthritis.org

The Arthritis Foundation is the major voluntary organization 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 and treatment, nutrition, alternative therapies, and self-management strategies. Chapters nationwide offer exercise programs, classes, support groups, physician referral services, and free literature.

Acknowledgments

The NIAMS gratefully acknowledges the assistance of the following people in the preparation and review of this publication: John H. Klippel, M.D., NIAMS, NIH; Reva Lawrence, M.P.H., NIAMS, NIH; Amye L. Leong, San Pedro Peninsula, California; Michael D. Lockshin, M.D., Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York, New York; Kate Lorig, R.N., Dr. P.H., Stanford University, Stanford, California; J. Lee Nelson, M.D., Fred Hutchinson Cancer Research Center, Seattle, Washington; Stanley R. Pillemer, M.D., NIH; Paul H. Plotz, M.D., NIAMS, NIH; Paul G. Rochmis, M.D., Fairfax Virginia; and Ronald L. Wilder, M.D., Ph.D., NIAMS, NIH. Special thanks also go to Cheryl Yarboro, R.N., B.S.P.A., NIAMS, NIH, and to the patients who reviewed this publication and provided valuable input. This booklet was written by Anne Brown Rodgers of Cygnus Corporation.

About NIAMS and NAMSIC

The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse (NAMSIC) is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS, a part of the National Institutes of Health (NIH), leads the Federal medical research effort in arthritis and musculoskeletal and skin diseases. The NIAMS supports research and research training throughout the United States as well as on the NIH campus in Bethesda, Maryland, and disseminates health and research information. Additional information and research updates can be found on the NIAMS Web site at http://www.nih.gov/niams/