Rheumatoid Arthritis

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Rheumatoid arthritis primarily affects the synovium, the membrane that lines and lubricates a joint. It is the most common form of inflammatory arthritis.

Symptoms & Diagnosis

Curability

There is no cure for rheumatoid arthritis at present. Until the cause of RA is known, it will not be possible to eliminate the disease entirely. The goals of current treatment methods therefore are to relieve pain, reduce inflammation, stop or slow down joint damage and improve function and patient well-being.

Incidence

Anyone can get rheumatoid arthritis, including children and the elderly. However the disease usually begins in the young to middle adult years. Among people with RA, women outnumber men by 3-to-1. In the United States, approximately one percent of the population have rheumatoid arthritis. It occurs in all ethnic groups and in all parts of the world.

Initial symptoms

Initial symptoms of rheumatoid arthritis (RA) are generally pain and stiffness in the morning and few symptoms with activity.

The pain and swelling will usually progress on to obvious joint swelling and the level of stiffness in the morning increases. Other symptoms include fatigue and difficulty sleeping due to joint stiffness.

Symptoms

Rheumatoid arthritis can be distinguished from other forms of arthritis by the location and number of joints involved. The areas affected include the neck, shoulders, elbows, wrists and hands, especially the joints at the base and middle of the fingers, but not the joints at the end of the fingers. In the lower extremities, RA can affect the hips, knees, ankles and the joints at the base of the toes. RA tends to spare the low back. The joints affected tend to be involved in a symmetrical pattern. That is, if knuckles on the right hand are inflamed, it is likely that knuckles on the left hand will be inflamed as well. This symmetry is not found as often in most other types of arthritis.

Fatigue in RA is due to many factors. It can be due to the inflammation which produces chemicals called cytokines that commonly cause fatigue. People with RA might have a mild anemia that also might contribute to fatigue, and the sleep disturbance from night time pain may also be a factor. Finally, people with RA tend to decrease their exercise and thus lose stamina and strength and this might also play a role in their fatigue.

Progression

About one in 10 people with RA will have a single episode of disease activity (or joint inflammation) and a spontaneous long-lasting remission. However, in almost all people with RA, inflammation of the joints will persist for a long period of time. The way RA acts will vary from person to person. In some people, the disease will be mild with periods of activity (worsening joint inflammation) called "flares." In other cases, the disease will be continuously active and appear to get worse or progress over time.

Inflamed joints will be warm, swollen, tender, often red and painful or difficult to move. These physical signs of arthritis are due to inflammation of the lining of joints and tendons in a layer of tissue that is called synovium. The cells of the immune system within the synovium appear active and capable of causing tissue damage. If this inflammation persists or does not respond well to treatment, destruction of nearby cartilage bone tendons and ligaments can follow. This may lead to deformity and disability that can be permanent.  However, many patients with rheumatoid arthritis are able to get improved function and pain relief from surgical reconstruction of the damaged joints, such as total hip arthroplasty, total knee arthroplasty and total shoulder arthroplasty.

Over the last two decades, a much more aggressive approach to treating RA has been advocated. It was recognized that once the joints were damaged by the disease, the cartilage rarely returns to normal even if the RA later goes away. Treatment is now much earlier that it used to be. The goals of treatment are to relieve pain and inflammation, slow down or prevent destruction of joints and restore the use and function of areas that already have been damaged.

Rheumatoid nodules

About one-fifth of people with RA also develop rheumatoid nodules which are lumps of tissue that form under the skin often over bony areas. These occur most often around the elbow but can be found elsewhere on the body and even in internal organs. Occasionally, people with RA will develop inflammation of the membranes lining that surround the heart (pericarditis) and lung (pleuritis). RA can also cause an emphesema like condition called rheumatoid lung that can affect a person's ability to breath comfortably. People with RA often develop dry eyes and a dry mouth due to inflammation of tear glands and salivary glands (called sicca syndrome). Occasionally, a low white blood cell count may occur because of the rheumatoid arthritis. Rarely, people with RA develop vasculitis inflammation of blood vessels that can cause illness affecting the skin, nerves and other organs or tissues. All of the above conditions are rare with the exception of rheumatoid nodules. The nodules tend to occur in people with more serious forms of RA.

Causes

Rheumatoid arthritis is not inherited in the usual sense. That is, it is not passed directly from parents to children. A susceptibility or tendency to develop RA can be inherited, but other factors (currently under intense study) also are important. The gene that influences the likelihood or a tendency to have RA is one of the genes that controls the function of the immune system called the HLA-DR4 gene. However, not everyone who inherits this gene will develop the disease.

Many physicians and scientists believe that RA might be triggered by an infection, but there is presently no proof that this is fact. Rheumatoid arthritis is not contagious. It is possible that a germ to which everyone is exposed causes the body's immune system to react abnormally in individuals who are susceptible to rheumatoid arthritis.

In RA, the white blood cells of the immune system move from the bloodstream into the joint tissues. Joint fluid may increase and the white cells are found in the fluid as well. The white cells in the joint tissue and fluid produce many substances including antibodies and other molecules that lead to the joint damage and the sick feeling that occurs in people with rheumatoid arthritis.

Diagnosis

In diagnosing RA, a health care professional (physician, physician's assistant or nurse practioner) will take a complete patient history before performing a physical examination.

The care provider will look for certain features including the joints involved. Sometimes the physician will order laboratory tests and X-rays. Common joint patterns include involvement of many joints (large and small) and arthritis affecting the small joints of the hands and feet.

Blood tests can be useful to make a diagnosis of rheumatoid arthritis but are secondary to a history and physical examination. Abnormalities in blood tests common in RA can include anemia and the presence of the antibody called rheumatoid factor. Some people with rheumatoid arthritis do not have a positive rheumatoid factor, and indeed many individuals with a positive blood test for rheumatoid factor do not have RA. Although X-rays early in rheumatoid arthritis can be normal, the pattern of joint damage seen on X-rays of people with long term disease can help confirm the diagnosis. In some cases, it may not be easy for your health care provider to make the diagnosis with great certainty due to the lack of significant arthritis and other distinctive features of RA. It may take several months for enough features to appear to be certain of the diagnosis.

Treatment

The goals of current RA treatment methods are to relieve pain, reduce inflammation, stop or slow down joint damage and improve function and patient well-being.

There is no single standard treatment that applies to all people with RA. The disease may be very different from person to person. Instead a treatment program should be designed to best meet each person's needs, taking into account how severe the arthritis is, other medical problems and individual lifestyle and preferences. Often the use of two or more medications at a time, each serving a distinct purpose is necessary. Some of these medications affect the immune system, making careful monitoring a requirement for treatment.

Health care team

Treating rheumatoid arthritis usually involves a teamwork approach using health professionals from different disciplines to help an individual deal with the disease. Treatment most often is directed and coordinated by an arthritis specialist who is a physician with special training in arthritis and other diseases of the bones, muscles and joints. Treatment often can be given by a family physician or a physician specializing in internal medicine, but a consultation with an arthritis specialist is recommended. The arthritis specialist may continue to act as a consultant or, with the consent of the primary care provider, may assume primary responsibility for the medical treatment of the arthritis.

Other health professionals such as physical therapists, occupational therapists, nurses, psychologists, orthopedic surgeons and social workers often play other roles in implementing the treatment plan. Orthpoaedic surgeons can help patients return to function and decrease pain when medications fail. Hand surgeons and spine surgeons help patients whose rheumatoid arthritis has affected those areas; total hip arthroplasty, total knee arthroplasty and total shoulder arthroplasty also are frequently performaed in patients with rheumatoid arthritis if medications fail to relieve symptoms in those joints.

Diet

Some people with RA have discovered that particular foods will either aggravate or help their arthritis. However, physicians have done careful studies and currently do not find evidence or proof that change in the diet is important in either causing or curing rheumatoid arthritis. It is very important, however, to maintain a healthy diet that includes adequate protein and calcium.

During flares of arthritis, people lose their appetite and tend to lose weight. At these times, it is important to make sure to take in enough calories. When arthritis is less active or when people with RA are taking corticosteroids, it is important to avoid excessive weight gain. Alcohol intake should be very modest in people who are taking aspirin or NSAIDs, and people who take methotrexate should avoid alcohol completely. Other healthy practices, such as not smoking and getting regular medical checkups, also are very important for individuals with rheumatoid arthritis.

Exercise and therapy

People with RA need both rest and exercise, and this naturally is confusing for people with RA and their families.

It's important to realize that rheumatoid arthritis cannot be controlled by vigorous exercise alone and that fragile joints need special protection. But rest is good for a joint with active RA, and exercise is good for the surrounding muscles.

People with RA need to maintain a balance between rest and exercise. The course of the disease will fluctuate. There will be times when the joints are more warm, swollen and painful. There will be other times when the joints feel better and no longer are warm or swollen. During these times, you'll generally feel better and have less fatigue and morning stiffness. Exercise and activity need to be adjusted to suit these two different situations.

Rest

When the joints are warm and swollen, rest will help to settle the disease down. At times like this, it is necessary to rest more to do less unnecessary walking, participate in fewer activities, etc. Though reducing activity, you should still maintain joint mobility by doing range-of-motion exercises. These are light exercises done without any weights and designed to preserve the mobility in the painful joint. The joint should be taken through a full range of motion each day, paying special attention to the end of the motion where the mobility is lost. Ease the joint fully to the limit of range. Aquatic exercise usually can be continued at these times as the buoyancy of the water protects the joints from rapid or stressful movement.

Exercise

When the disease settles down and the joints become less warm and swollen, fatigue diminishes and morning stiffness reduces, you should expand your exercise program. Range-of-motion exercises should be continued on a daily basis to maintain or restore motion, but strengthening exercises also should be done. These exercises should be instructed by a therapist. The purpose is to rebuild the strength of muscles that have weakened during the acute phase of the disease. Strong muscles are important in providing support to joints and can be built with exercise. These strengthening exercises however have to be modified for people with damaged joints.

Evidence suggests that people with RA can become aerobically fit and that this may help improve stamina, reduce fatigue, reduce pain and even help depression if present! Aerobic exercise has not been shown to increase the joint inflammation when done properly. An aerobic program should be developed under the direction of a care provider and a physical therapist, especially for those people with more serious disease.

Occupational and physical therapy

Therapy treatments are helpful for most individuals with rheumatoid arthritis. Physical therapists can teach you how to exercise appropriately for your physical capabilities. They will give you valuable instruction on how best to use heat and cold treatments to reduce joint stiffness and swelling and make movement easier. At times, therapists may use special machines to apply deep heat or electrical stimulation to reduce pain or improve joint mobility.

Occupational therapists construct splints for the hand and wrist, and teach people how to best protect and use their joints when they are affected by arthritis. They also show people how to better cope with day-to-day tasks at work and at home, despite limitations that may be caused by RA. Sometimes this includes the use of practical tools and items that help individuals perform their day-to-day activities. It is important to remember that people with RA can and should be able to do most of the normal or usual things everyone else can, except that it takes them a little bit longer to do it.

Medications

It should be emphasized that all drugs have side effects, even over-the-counter medications. However, RA will produce its own problems such as joint destruction, if left untreated. Thus treatment decisions should be as informed as possible, weighing the benefits of treatment (relieving pain, preventing disability) against the risks and even the costs of using certain kinds of drugs.

Anti-inflammatories

Aspirin is still an important part of the treatment program for many people with RA. To be effective, it must be given in doses much higher than commonly used as an over-the-counter remedy for minor aches and pains. Compared to other similar nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin is less expensive and its blood level can be precisely measured. However, it can cause stomach problems in many people. Many providers recommend the use of enteric (coated) forms of aspirin. These are safer for the stomach, but they cost more.

NSAIDs (nonsteroidal anti-inflammatory drugs) are a large group of drugs that have mechanisms of action similar to that of aspirin. This group of drugs does not include corticosteroids (cortisone and other related substances). Like aspirin, these medications can relieve some of the signs of inflammation and some of the pain associated with rheumatoid arthritis. A side effect of these drugs can be bleeding from the stomach, although this does not occur as often as with plain aspirin. Sometimes people require additional medications to prevent the side effects of NSAIDs on the stomach. The various NSAIDs and aspirin, if taken in full doses, usually have the same levels of anti-inflammatory effect. However, different individuals may experience greater relief from one medication than another. Because aspirin has similar effects and side effects, one should not ordinarily take aspirin while taking a nonsteroidal anti-inflammatory drug. If you have any questions, it is best to check with your care provider.

Corticosteroids

The role of corticosteroids (cortisone prednisone and other similar substances) in rheumatoid arthritis is still debated by physicians. In the short run, cortisone can make people with RA feel dramatically better. However, if the drug is used over many months or years it may not continue to be as effective and side effects will begin to appear. These side effects are serious and can include easy bruising, thinning of the bones (osteoporosis), cataracts, weight gain, a round face, susceptibility to infections, diabetes and high blood pressure.

Corticosteroids can be given in the form of a pill, injected as a liquid into a joint directly or into a muscle. Much of the benefit and many of the side effects of this drug are directly related to the dose given. The therapeutic goal is always to find the lowest effective dose that will avoid as many of the side effects as possible. Most physicians agree that certain individuals with RA can take daily low doses of cortisone with minimal risk and important benefit. Usually, however, cortisone should not be relied upon as the main form of treatment for the majority of people with RA over the long-term course of the disease. For anyone who takes cortisone on a regular basis, careful attention should be directed to proper calcium, vitamin and hormone regulation; RA patients should always discuss these issues with their physician. Taking cortisone over prolonged periods has the effect of putting the body's own corticosteroid-making function at rest. Therefore, it will be necessary to supplement or increase the dose at times of high stress, such as surgery.

CAUTION: It is dangerous to suddenly stop or significantly change the amount of corticosteriods you are taking. Always consult your doctor before making changes in your dose of prednisone or other corticosteroid medication.

Gold

Injectable gold salts (Myochrysine Solganal) have been used in rheumatoid arthritis for more than 60 years. As experience was gained with this type of medication, physicians were able to establish doses that are both reasonably effective and acceptably safe. Some physicians have recently questioned the value of gold salts in rheumatoid arthritis. It is true that this type of medication does not work for all people with RA and that gold may lose its effectiveness over time in people who seem to benefit at first. Furthermore, it often takes three to six months to determine whether a person is getting benefits from gold salts. For this reason, people who begin gold injections must continue other medications, such as aspirin or NSAIDs. Despite certain drawbacks, most arthritis specialists still view gold salt injections as an important form of treatment for rheumatoid arthritis. Carefully done research studies over the past 35 years have shown that this form of treatment is effective and in some people gold treatment may slow down damage to cartilage and bone. A small group of people with RA experience dramatic and long-lasting improvement on gold. Gold injections are given weekly for six months or longer. In those people who have a good response, the medication usually can be tapered to once every three to four weeks. You, your physician and nurse will watch for side effects, such as rashes, protein in the urine and abnormal blood counts while you are receiving gold shots. Less frequent tests of blood and urine are required once injections are administered on a monthly basis.

Methotrexate

Since the mid-1980s, methotrexate (Rheumatrex) has become much more popular as a treatment for rheumatoid arthritis. It works more quickly than gold and maintains control of the disease in a larger proportion of people over periods of five years or longer. Methotrexate is given once a week as pills or as an injection. Unlike gold, it cannot be taken less frequently after the first six to 12 months but instead must be continued every week.

Methotrexate in much higher doses also is used to treat some forms of cancer, but it is not believed to cause cancer in the doses used to treat RA. Methotrexate is a drug that is felt to be reasonably safe in people without other major medical problems such as liver disease, kidney disease, lung problems or heart failure. Individuals taking methotrexate should drink little or no alcohol because methotrexate may produce liver damage in a small number of people. You may be advised to have a liver biopsy every three to five years while on methotrexate to verify that no damage has occurred, but the requirement for a liver biopsy has not been demonstrated with certainty. Your physician will frequently check your liver function and blood counts while you are taking methotrexate since the number of white blood cells can be lowered by this drug. Other side effects include an upset stomach and rarely, inflammation of the lungs.

In summary, methotrexate is an effective and important medication for the management of rheumatoid arthritis. However, individuals who are particularly vulnerable to its most serious side effects (people with kidney, lung or liver problems) may not be able to take this drug.

CAUTION: Methotrexate may cause birth defects. Women on methotrexate must go off their medication during pregnancy. Methotrexate should not be taken by people who have serious kidney or liver disease or who drink alcohol.

Other medications

Hydroxychloroquine (Plaquinil) and other antimalarials (drugs originally developed for treatment of malaria) have been used for many years to treat rheumatoid arthritis. Serious side effects are uncommon, but people on these medications must undergo regular eye examinations once or twice a year because of potential damage to the retina (even though this event is rare).

Sulfasalazine (Azulfidine) is a drug useful in the treatment of both rheumatoid arthritis and inflammatory diseases of the bowel. It is generally taken twice daily in a dose of 2 grams total per day. It also works more quickly than gold and it is felt by many rheumatologists to be somewhat less powerful than methotrexate. Side effects include rashes, upset stomach and lowered blood counts. Blood checks are done initially every month and less frequently after 3-6 months.

D-Penicillamine (Depend Cuprimine) is a slow-acting medication taken daily as one or more pill(s). It can cause side effects similar to those seen with gold and its use requires close supervision and careful monitoring. It is rarely used due to the availability of other effective and potentially less toxic medications.

Azathioprine (Imuran) is an immunosuppressive drug used in rheumatoid arthritis and other rheumatic diseases. It can help rheumatoid arthritis by suppressing over activity of the immune system but also can increase susceptibility to certain infections and lower blood counts.

Cyclophosphamide (Cytoxan) is a very powerful immunosuppressive drug. Because of its frequent and sometimes life threatening side effects, cyclophosphamide is only given to individuals with very severe arthritis unresponsive to other treatments or with serious complications outside the joint, such as vasculitis (blood vessel inflammation).

Analgesics (pain medications such as codeine, Darvon, etc.) are sometimes necessary in combination with other medications. Strong narcotic pain medications, if taken on a regular basis, often have undesirable side effects and can produce drug dependency. However, acetaminophen (Tylenol, Datril), an over-the-counter medicine often is useful for pain and generally does not interact with other medications.

New medications

In the last few years, several new and effective agents have been approved for the treatment of RA. Two of these are know as biologic agents since they are related to antibodies. Over the next few years, many more of these types of agents will be evaluated for treatment of RA and other inflammatory diseases.

Leflunomide (Arava) is a cousin to azathioprine. It is taken as a pill once a day and affects certain immune cells that cause inflammation. It has been shown to be as effective as methotrexate and sulfasalazine in the treatment of RA. Side effects can include elevation of liver tests, stomach upset and mild hair loss.

Etanercept (Enbrel) is one of the new biologic agents. It is a modified human antibody that "soaks up" a immune system chemical called TNF alpha. This TNF is responsible for much of the fatigue, swelling, osteoporosis and cartilage damage seen in RA. It is given by injection twice a week and works very quickly. Recent information shows that it can slow down the disease dramatically in some people. About 70-80% of people have initial benefit. Side effects have included small rashes at the spot where the etanercept is injected in some people. It is not recommended that this medication be given to people at risk for serious infection.

Infliximab (Remicaide) is another new biologic agent approved for use in RA. It is a combination of a human antibody and a small amount of an antibody from a mouse. It also attaches to and inactivated TNF alpha. It is given intravenously initially 3 times in six weeks, then every other month. Infliximab should also not be given to people at risk for serious infection. It is most effective when given with methotrexate.

Surgery

For individuals with rheumatoid arthritis and severe joint damage, surgery such as total joint replacement of the hips, knees or shoulders can mean the difference between being dependent on others and independent life at home or in the community. Such procedures are performed by orthopedic surgeons with special training in joint replacement. The damaged parts of the joints are replaced with metal or plastic components. These parts are attached to the bone with bone cement or by a careful tight fit of implants that allow the bone to form a biological bond. Some people with RA will benefit from replacement of other joints and from other types of surgery for hand and foot problems caused by the disease. People with early rheumatoid arthritis, however, should be placed on a program of medications and therapy before surgery is considered as a form of treatment.

Unproven remedies

It often is difficult to be patient when suffering from rheumatoid arthritis. People with rheumatoid arthritis might be tempted to try unproven treatments. A treatment that promises "a quick cure" or "miraculous relief" can sound wonderful. But remember these unproven treatments usually are expensive and will do nothing. The sensational successes advertised are usually illusions. They even may be harmful and often keep people from getting the medical care they really need. For example, magnet therapy has not been proven to work for rheumatoid arthritis. Discuss new treatments with a doctor and get his or her advice.

Strategies for coping

People with RA may find it difficult to cope. Because the disease may be unpredictable, is often characterized by chronic pain and can affect so many joints, emotional stress and depression may occur. While depression or other emotional problems do not cause rheumatoid arthritis, they can make it more difficult for a person to successfully cope with the disease.

It's important for people with RA and their families to learn all they can about the disease and to talk about it with each other, with their physicians and with other health professionals involved in their care. Counseling from mental health professionals on how to develop coping skills and social support mechanisms may be of help. Many people are helped by arthritis support groups.

In some people with RA, special medications may be needed to relieve depression. The knowledge that you are not alone and that others understand something about the challenges you are coping with can be your best emotional support.

Since rheumatoid arthritis often is long lasting, the improved treatments or even cures that may be found in the years ahead offer great hope for those who are now in early stages of the disease.

Above all, it's important not to give up in the fight against this disease. With the proper use of medications, good health practices, appropriate amounts of rest and exercise and the ability to cope with emotional stress, people with rheumatoid arthritis can make sure that everything is being done to control their illness. Most people with rheumatoid arthritis will lead productive, fulfilling lives despite their disease.

Climate

Rheumatoid arthritis occurs in all parts of the world, so climate cannot prevent or cure rheumatoid arthritis. Many people with RA do notice that abrupt changes in the weather or barometric pressure tend to aggravate symptoms of their arthritis. For most individuals, moving to a different climate does not make a big enough difference in their arthritis for this to be the only reason to make such a move.

Credits

Adapted from the pamphlet originally prepared for the Arthritis Foundation by David A. Fox, M.D. This material is protected by copyright.

Edited by Frederick Matsen III M.D., Seth S. Leopold M.D., and Gregory C. Gardner M.D.