Rheumatoid Arthritis

Rheumatoid arthritis (often called RA) is a chronic (long-standing) disease that damages the joints of the body. The damage is caused by inflammation, a normal response by the body’s immune system to “assaults” such as infections, wounds, and foreign objects.   

• The inflammation in the joints causes pain, stiffness, and swelling as well as many other symptoms.
  
  
• The inflammation often affects other organs and systems of the body.
  
  
• If the inflammation is not slowed or stopped, it can damage the affected joints and other tissues.

RA should not be confused with other forms of arthritis, such as osteoarthritis or arthritis associated with infections. RA is an autoimmune disease. This means that the body’s immune system mistakenly attacks the tissues it is supposed to protect.

• The immune system produces specialized cells and chemicals, which are released into the bloodstream and begin to attack body tissues.
  
  
• This response causes abnormal growth and inflammation in the synovium, the membrane that lines the joint. This process is called synovitis and is the hallmark of an inflammatory arthritis such as RA.
  
  
• As the synovitis expands inside and outside of the joint, it can damage the bone and cartilage of the joint and the surrounding tissues, such as ligaments, tendons, nerves, and blood vessels.
  
  

RA most often affects the smaller joints, such as those of the hands and/or feet, wrists, elbows, knees, and/or ankles. The symptoms often lead to significant discomfort and disability.

• Many people with RA have difficulty carrying out normal activities of daily living, such as standing, walking, dressing, washing, using the toilet, preparing food, and carrying out household chores.
  
  
• The symptoms of RA interfere with work for many people. As many as half of those with RA are no longer able to work 10-20 years after their condition is diagnosed.
  
  
• On average, life expectancy is somewhat shorter for people with RA than for the general population. This does not mean that everyone with RA has a shortened life span. RA itself is not a fatal disease. However, RA can be associated with many complications and treatment-related side effects that can contribute to premature death.

Although RA most often affects the joints, it is a disease of the entire body. It can affect many organs and body systems besides the joints. This is what is meant by systematic disease. 

• Musculoskeletal structures: Damage to muscles surrounding joints may cause atrophy (shrinking and weakening). This is most common in the hands. Atrophy also may result from not using a muscle, usually because of pain or swelling. Damage to bones and tendons can cause deformities, especially of the hands and feet. Osteoporosis and carpal tunnel syndrome are other common complications of RA.
  
  
• Skin: Many people with RA form small nodules on or near the joint that are visible under the skin. These “rheumatoid nodules” are most noticeable under the skin on the bony areas that stick out when a joint is flexed. Dark purplish areas on the skin (purpura) are caused by bleeding into the skin from blood vessels damaged by RA. This damage to the blood vessels is called vasculitis, and these vasculitic lesions also may cause skin ulcers.
  
  
• Heart: Collection of fluid around the heart from inflammation is not uncommon in RA. This usually causes only mild symptoms, if any, but it can be very severe. RA-related inflammation can affect the heart muscle, the heart valves, or the blood vessels of the heart (coronary arteries).
  
  
• Lungs: RA effects on the lungs may take several forms. Fluid may collect around one or both lungs, or tissues may become stiff or overgrown. Any of these effects can have a negative effect on breathing.
  
  
• Digestive tract: The digestive tract is usually not affected directly by RA. Dry mouth, related to Sjögren syndrome, is the most common symptom of gastrointestinal involvement. Digestive complications are much more likely to be caused by medications used to treat the condition, such as gastritis (stomach inflammation) or stomach ulcer associated with NSAID therapy. Any part of the digestive tract may become inflamed if the patient develops vasculitis, but this is uncommon. If the liver is involved (10%), it may become enlarged and cause discomfort in the abdomen.
  
  
• Kidneys: The kidneys usually are not affected directly by RA. Kidney problems in RA are much more likely to be caused by medications used to treat the condition. 
  
  
• Blood vessels: Vasculitic lesions can occur in any organ but are most common in the skin, where they appear as purpura or skin ulcers.
  
  
• Blood: Anemia or “low blood” is a common complication of RA. Anemia means that you have an abnormally low number of red blood cells and that these cells are low in hemoglobin, the substance that carries oxygen through the body. (Anemia has many different causes and is by no means unique to RA.)
  
  
• Nervous system: The deformity and damage to joints in RA often leads to entrapment of nerves. Carpal tunnel syndrome is one example of this. Entrapment can damage nerves and may lead to serious consequences.
  
  
• Eyes: The eyes commonly become dry and/or inflamed in RA. This is called Sjögren syndrome. The severity of this condition depends on which parts of the eye are affected.
  
  

Like many autoimmune diseases, RA typically waxes and wanes. Most people with RA experience periods in which their symptoms worsen (flares or active disease) separated by periods in which the symptoms improve. With successful treatment, symptoms may even go away completely (remission, or inactive disease).

About 2.1 million people in the United States are believed to have RA.

• About 1.5 million of these are women. Women are 2-3 times more likely to develop RA than men.
  
  
• RA affects all ages, races, and social and ethnic groups.
  
  
• It is most likely to strike people aged 35-50 years, but it can occur in children, teenagers, and elderly people. (A similar disease affecting young people is known as juvenile rheumatoid arthritis.)
  
  
• Worldwide, about 1% of people are believed to have RA, but the rate varies among different groups of people. For example, RA affects about 5-6% of some Native American groups, while the rate is very low in some Caribbean peoples of African descent.
  
  
• The rate is about 2-3% in people who have a close relative with RA, such as a parent, brother or sister, or child.

Although there is no cure for RA, the disease can be controlled in most people. Early, aggressive therapy to stop or slow down inflammation in the joints can prevent or reduce symptoms, prevent or reduce joint destruction and deformity, and prevent or lessen disability and other complications.

The cause of rheumatoid arthritis is not known. Many factors are involved in the abnormal activity of the immune system that characterizes RA. These factors include genetics (heredity), hormones (explaining why the disease is more common in women than men), and possibly infection by a bacterium or virus.

Although rheumatoid arthritis can have many different symptoms, joints are always affected. RA almost always affects the joints of the hands (such as the knuckle joints), wrists, elbows, knees, ankles, and/or feet. The larger joints, such as the shoulders, hips, and jaw may be affected. The vertebrae of the neck are sometimes involved in people who have had the disease for many years. Usually at least 2 or 3 different joints are involved on both sides of the body, often in a symmetrical (mirror image) pattern. The usual joint symptoms include the following:

• Stiffness: The joint does not move as well as it once did. Its “range of motion” (the extent to which the appendage of the joint, such as the arm, leg, or finger, can move in different directions) may be reduced. Typically, stiffness is most noticeable in the morning and improves later in the day.
  
  
• Inflammation: Redness, tenderness, and warmth are the hallmarks of inflammation.
  
  
• Swelling: The area around the affected joint is swollen and puffy.
  
  
• Nodules: These are hard bumps that appear on or near the joint. They often are found near the elbows. They are most noticeable on the part of the joint that juts out when the joint is flexed.
  
  
• Pain: Pain in RA has several sources. Pain can come from inflammation or swelling of the joint and surrounding tissues or from working the joint too hard. The intensity of the pain varies by the individual.

These symptoms may keep you from being able to carry out your normal activities. General symptoms include the following:

• Malaise (“blah” feeling)
  
  
• Fever
  
  
• Fatigue
  
  
• Loss of appetite
  
  
• Weight loss
  
  
• Myalgias (muscle aches)
  
  
• Weakness or loss of energy

The symptoms usually come on very gradually, although in a small number of people they come on very suddenly. In some cases, the general symptoms come before the joint symptoms, and you may think you have the flu or a similar illness.

The following suggest that RA is in remission:

• Morning stiffness lasting less than 15 minutes
  
  
• No fatigue
  
  
• No joint pain
  
  
• No joint tenderness or pain with motion
  
  
• No soft tissue swelling

Joint pain or stiffness or swelling around a joint that lasts more than 2 weeks warrants a visit to your health care provider.

|Questions to Ask the Doctor|

If you experience symptoms that you think may be caused by arthritis, talk to your doctor. Your doctor can talk to you about your treatment options.

On hearing your symptoms, your health care provider will suspect that you have rheumatoid arthritis or another type of arthritis or rheumatic disease. The diagnosis doesn’t end there, though. It is very important to know exactly which type of arthritis you have, because the treatment and outlook for each type may differ.

Your health care provider will conduct a thorough interview and physical examination to try to pinpoint the cause of the symptoms. You will be asked about your symptoms, about other medical problems now and in the past, about your family’s medical problems, about the medications you take, and about your habits and lifestyle.

There is no single test that can confirm the diagnosis of RA. Your health care provider will use the results of your interview and physical examination, lab tests, and imaging studies such as x-rays to determine whether you have RA. At any time in the process of making the diagnosis or treating the condition, your primary care provider may refer you to a rheumatologist (a specialist in diagnosing and treating rheumatic diseases such as RA).

Lab tests: Your health care provider may run any of the following tests:

• Complete blood count: This test measures how many of each type of blood cell are in your blood. This will show anemia as well as other irregularities that could indicate RA.
  
  
• Markers of inflammation: These include measures such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Levels of both of these are usually high in RA and may be good indicators of the extent of disease activity at any given time.
  
  
• Other blood tests: levels of electrolytes (such as calcium, magnesium, and potassium) and proteins may be tested. Kidney and liver functions also may be checked.
  
  
• Immunologic tests: levels of rheumatoid factor (RF), antinuclear antibodies (ANA), and possibly other antibodies (anti-RA33, anti-CCP) may be checked. The majority of people have a positive RF result during the disease’s active periods. A positive ANA result indicates an unusually active immune system. About 40% of people with RA have a positive ANA result. In the first few months of onset of RA, these immunologic tests may be negative, and, in some patients, they are always negative.

Synovial fluid analysis: The synovium produces fluid that helps lubricate and protect joints. Like blood, this fluid may be abnormal in RA. It may reveal characteristic signs of inflammation that point to RA, such as white blood cells. A sample of this fluid is withdrawn from a joint (usually the knee) through a needle in a procedure called arthrocentesis, or joint aspiration. The fluid is examined and analyzed for signs of inflammation.

Imaging studies: X-rays and sometimes other imaging studies often are used to detect damage to the joints.

• X-rays: X-rays may be taken of sites where symptoms or signs occur. Early in RA, the x-ray may be normal or show only soft tissue swelling, but damage can still be occurring. Over time, the usual finding is erosion of the bony part of the joint. These changes are distinguishable from changes seen with other types of arthritis such as osteoarthritis.
  
  
• MRI: MRI may allow earlier detection of bone erosion than x-rays.
  
  
• Ultrasound: Ultrasound uses high-frequency sound waves to take “pictures” of structures inside the body. It can be used to examine and to detect abnormal collections of fluid (effusions, which cause swelling) in the soft tissues around joints that are not easily accessible (such as hip joints or shoulder joints in obese patients).
  
  
• Bone scanning: In this test, a special picture of the entire skeleton is taken after a harmless radioactive isotope is injected into a vein. Diseased or damaged bone takes up the radioisotope in a different way than healthy bone and gives a characteristic picture. This technique may be used to detect inflammatory changes in bone.
  
  
• Densitometry: This scan detects changes in the thickness of bone that may indicate osteoporosis.
  
  
• Arthroscopy: A small “scope,” a long narrow tube with a light and a camera on the end, is used to examine the inside of the joint. The scope is inserted through a small incision in the skin. The camera transmits pictures to a video monitor, allowing the doctor to detect signs of RA or other joint disease. This test is not always necessary.

Classification

The American College of Rheumatology has developed a system for classifying RA. This system helps medical professionals determine the severity of your RA.

Stage I

• No damage seen on x-rays, although there may be signs of bone thinning

Stage II

• On x-ray, evidence of bone thinning around a joint with or without slight bone damage
  
  
• Slight cartilage damage possible
  
  
• Joint mobility may be limited; no joint deformities observed
  
  
• Atrophy of adjacent muscle
  
  
• Abnormalities of soft tissue around joint possible

Stage III

• On x-ray, evidence of cartilage and bone damage and bone thinning around the joint
  
  
• Joint deformity without permanent stiffening or fixation of the joint
  
  
• Extensive muscle atrophy
  
  
• Abnormalities of soft tissue around joint possible

Stage IV

• On x-ray, evidence of cartilage and bone damage and osteoporosis around joint
  
  
• Joint deformity with permanent stiffening or fixation of the joint (ankylosis)
  
  
• Extensive muscle atrophy
  
  
• Abnormalities of soft tissue around joint possible

Rheumatologists also classify the functional status of persons with RA, as follows:

• Class I - Completely able to perform usual activities of daily living
  
  
• Class II - Able to perform usual self-care and work activities but limited in activities outside of work (such as playing sports, household chores)
  
  
• Class III - Able to perform usual self-care activities but limited in work and other activities
  
  
• Class IV - Limited in ability to perform usual self-care, work, and other activities

Despite significant advances in treatment over the past decades, rheumatoid arthritis continues to be an incurable disease. Treatment of RA has 2 components: (1) reducing inflammation and preventing joint damage and disability and (2) relieving symptoms, especially pain. Although achieving the first goal may accomplish the second, many people need separate treatment for symptoms at some point in the disease.

|Self-Care at Home|

If you have joint pain or stiffness, you may think it is just a normal part of getting older and that there is nothing you can do. Nothing could be further from the truth. You have several options for medical treatment and even more to help prevent further joint damage and symptoms. You should discuss these measures with your health care provider to find ways to make them work for you.

• First of all, don’t delay diagnosis or treatment. Having a correct diagnosis allows your health care provider to form a treatment plan. Delaying treatment increases your risk that the arthritis will get worse and that you will develop serious complications.
  
  
• Learn everything you can about your condition. Ask your health care provider if you have questions. If you want to learn more, ask him or her to direct you to reliable sources of information. Some Internet resources are listed later in this article.
  
  
• Become an active participant in your care. Know the pros and cons of all of your treatment options, and work with your health care provider to decide on the best options for you. Understand your treatment plan and what benefits and side effects you can expect. If you don’t understand, ask.
  
  
• Learn about your symptoms. If you have RA, you probably have both general discomfort (aches and stiffness) and pain in specific joints. Learn to tell the difference. Pain in a specific joint often results from overuse. Pain in a joint that lasts more than 1 hour after an activity probably means that that activity was too stressful and should be avoided.

Increase your physical activity.

• Exercise is a very important part of a complete treatment plan for RA.
  
  
• You may think that exercise is bad for arthritic joints, but research overwhelmingly shows that exercise in RA helps reduce pain and fatigue, increases your range of motion (flexibility) and strength, and keeps you feeling better overall.
  
  
• Three types of exercise are helpful: range of motion exercise, strengthening exercise, and endurance (“cardio” or aerobic) exercise. Water aerobics are an excellent choice because they increase range of motion and endurance while keeping weight off the joints of your lower body.
  
  
• Talk to your health care provider about how to start an exercise program and what types of exercises to do. He or she may refer you to a physical therapist or exercise specialist.

Protect your joints.

• At least once a day, move each joint through its full range of motion. Do not overdo or move the joint in any way that causes pain. This helps keep freedom of motion in your joints
  
  
• Avoid situations that are likely to strain your joints. Remember that your joints are more susceptible to damage when they are swollen and painful. Avoid stressing the joint at such times.
  
  
• Learn proper “body mechanics.” This means learning to use and move your body in ways that reduce the stress on your joints. This is especially true for your hands, since you want to protect their flexibility. Ask your health care provider or physical therapist for suggestions on how to avoid joint strain.
  
  
• Be creative in thinking up new ways to carry out tasks and activities.
  
  
• Use the strongest joint available for the job. Avoid using your fingers, for example, if your wrist can do the job.
  
  
• Take advantage of assistive devices to carry out activities that have become difficult. These simple devices can work very well to reduce stress on certain joints. Talk to your health care provider or physical and/or occupational therapist about this.

Alternate periods of rest and activity through the day. This is called pacing.

• General rest is an important part of RA treatment, but avoid keeping your joints in the same position for too long a time. Get up and move; use your hands.
  
  
• Holding the joint still for long periods just promotes stiffness. Keep the joints moving to keep them flexible.
  
  
• If you must sit for long periods, say at work or while traveling, take a short break every hour: stand up, walk around, stretch, and flex your joints.
  
  
• Rest before you become tired or sore.

Take part in activities you enjoy every day.

• This can improve your outlook and help you put your arthritis in perspective.
  
  
• Some enjoyable activities are even helpful for your joints, such as walking, swimming, and light gardening.

Take steps toward a healthier lifestyle.

• Losing weight not only helps you look better, it helps you—and your joints—feel better. Reducing weight helps take stress off joints and reduces pain. A healthy weight also can help you prevent other serious medical conditions such as heart disease and diabetes.
  
  
• Eat a varied diet with plenty of fruits and vegetables, lean proteins, and low-fat dairy products. Make sure you are getting enough vitamin C and calcium. Ask your health care provider if you think you are not getting sufficient vitamins and minerals.
  
  
• Quit smoking. Not only will you feel better, but also you will be reducing your risk of complications of RA. You will also be reducing your risk of lung cancer, emphysema, and other breathing problems.

Get the most out of your treatment.

• Take your medications as directed by your health care provider. If you think a medication is not working or is causing side effects, talk to your health care provider before stopping the medication. Some medications take weeks or even months to reach their full benefit. In a few cases, stopping a medication suddenly can even be dangerous.
  
  
• Help yourself. If you feel tired and achy, a warm bath before bed can help you relax and feel better. Massages feel good and may help increase your energy and flexibility. Apply an ice pack or cold compress to a joint to reduce pain and swelling. (Keep a reusable ice pack in your freezer or try a bag of frozen vegetables!)

|Medical Treatment|

RA is a progressive inflammatory disease. This means that unless the inflammation is stopped or slowed, the condition will continue to get worse in most people. Although RA does occasionally go into remission without treatment, this is rare. Starting treatment soon after diagnosis of RA is strongly recommended. The best medical care for RA combines medication and nondrug approaches.

Nondrug approaches include the following:

• Physical therapy helps preserve and improve range of motion, increase muscle strength, and reduce pain.



• Hydrotherapy involves exercising or relaxing in warm water. Being in water reduces the weight on your joints. The warmth relaxes your muscles and helps relieve pain.



• Relaxation therapy teaches techniques for releasing muscle tension, which helps relieve pain.



• Both heat and cold treatments can relieve pain and reduce inflammation. Some people’s pain responds better to heat and other’s to cold. Heat can be applied by ultrasound, microwaves, warm wax, or moist compresses. Most of these are done in the medical office, although moist compresses can be applied at home. Cold can be applied with ice packs at home.



• Occupational therapy teaches you ways to use your body efficiently to reduce stress on your joints. It also can help you learn to decrease tension on the joints through the use of specially designed splints. Your occupational therapist can help you develop strategies for coping with daily life by adapting to your environment and using different assistive devices.



• Prosorba column: This is not a drug but a medical device. It filters antibodies linked to RA out of the blood. This procedure is available only in some medical centers and generally is used only for very severe RA.



• In some cases, reconstructive surgery and/or joint replacement operations provide the best outcome.

Drug approaches include a variety of medications used alone or in combinations.

• RA was traditionally treated with a stepwise approach starting with nonsteroidal anti-inflammatory drugs (NSAIDs) and progressing through more potent drugs such as glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologic response modifiers.



• DMARDs were avoided early in the disease because of their potentially serious side effects and because they did not often bring on remission. DMARDs were usually reserved for people who showed signs of joint damage.



• Over time, however, this strategy was recognized as being faulty, because people treated early with DMARDs have better long-term outcomes, with greater preservation of function, less work disability, and a smaller risk of premature death.



• The goal of drug treatment is to induce remission or at least eliminate evidence of disease activity.



• Early use of DMARDs not only controls inflammation better than less potent drugs but also helps prevent joint damage. Newer DMARDs work better than the older ones in long-term prevention of joint damage.



• The current approach, therefore, is to treat RA aggressively with DMARDs soon after diagnosis. Treating RA early, within 3-12 months after symptoms begin, is the best way to stop or slow progression of the disease and bring about remission.



• Ongoing (long-term) treatment with combinations of medications may offer the best control of RA for the majority of people.



• Combinations of these agents do not usually have more severe adverse effects than one agent alone.

Disease-modifying antirheumatic drugs (DMARDs)

• This is the single most important type of drug treatment in RA. This is not one type of drug, but several different types whose main similarity is that they all help people with RA.



• DMARDs can slow or stop the progression of RA and thus joint destruction and disability.



• Successful DMARD therapy may eliminate the need for other anti-inflammatory or analgesic (pain-relieving) medications.



• These drugs do not work for everyone with RA, but they give substantial relief to many.



• DMARDs may not reach their full effect for 2-3 months. It is important to keep taking the medication for at least that long before deciding it is not working. Until the full action of your DMARD takes effect, your health care provider may prescribe anti-inflammatory or analgesic medications as “bridging therapy” to reduce pain and swelling.



• DMARDs may be given alone or in combination with other types of drugs.



• These drugs have been shown to improve signs and symptoms (as well as quality of life) in most people with RA.

Biologic response modifiers

• These agents are carefully designed to block the actions of substances naturally produced by the immune system, such as tumor necrosis factor or interleukin-1. These substances are involved in the abnormal immune reaction associated with RA. Therefore, blocking their action can slow down the underlying autoimmune reaction and thus relieve symptoms and improve your overall condition.



• There are several different forms of these agents, and in some people, RA will get better with one form and not another.



• These agents slow down RA in a significant proportion of people with RA (40-70%, depending on the form) and can lead to remission. They do not cure the disease, as symptoms often return if the drug is stopped.



• These agents are often used in combination with one or more DMARDs in order to more fully suppress joint inflammation and improve function.



• These agents are expensive and the long-term effects are still under study. For these reasons, these drugs often are not the first choice of treatment in RA.



• Although it may take as long as 3 months to see whether a biologic agent is working in a specific individual, many people start to feel better within a few weeks.



• You cannot take these agents if you have an infection (especially tuberculosis), cancer now or in the recent past, or certain types of nervous system disorders.



• These agents improve signs and symptoms and quality of life in many people with RA.

Glucocorticoids

• Glucocorticoids (“steroids”) are potent anti-inflammatory drugs. They reduce symptoms, and they may stop or slow joint damage.



• These drugs can be given as pills by mouth, by intramuscular injection, or in some cases, they can be injected directly into a joint.



• These agents have many side effects. They can be safely given only for short periods—a few weeks or months--in most people and so are commonly used to bridge the gap while waiting for a DMARD to reach full effect.



• These agents are not for everyone. Your health care provider will decide whether glucocorticoids are right for you on the basis of your overall medical condition.



• Typically, these drugs are started at a relatively low, safe dose. Occasionally a high dose is given at first to have an immediate effect, and the dose is reduced gradually (“tapered”) over a few weeks or months.



• It is very important not to stop taking a glucocorticoid abruptly, as this can be dangerous. If you are having severe side effects, talk to your health care provider before stopping the drug.

Nonsteroidal anti-inflammatory drugs

• Nonsteroidal anti-inflammatory agents, or NSAIDs, reduce swelling and pain in RA. They do not slow joint damage, however, and therefore are not considered adequate treatment on their own. Like glucocorticoids, they often are used as a “bridge” to successful DMARD therapy.



• Several dozen NSAIDs are available. They can be classified into different groups of compounds. Commonly used NSAIDs include ibuprofen, naproxen, ketoprofen, piroxicam, and diclofenac.



• The most common and potentially serious adverse effects of NSAIDs occur in the digestive tract: stomach upset, belly pain, and bleeding.



• Rare side effects include serious skin reactions. NSAIDs may increase risk of heart attack and stroke.



• A newer generation of these drugs is called the COX-2 inhibitors, such as celecoxib (Celebrex). These drugs are more expensive although much less likely to cause digestive system effects.

Analgesics

• Acetaminophen/paracetamol, tramadol, codeine, opioids, and a variety of other analgesic medications can be employed to reduce pain.



• These agents do not affect swelling or joint destruction.

|Medications|

DMARDs: This group includes a wide variety of agents that work in many different ways. What they all have in common is that they interfere in the immune processes that promote inflammation in RA. They can actually stop or slow the progression of RA. They can also suppress the ability of the immune system to fight infections. Anyone taking one of these drugs must be very vigilant to watch for early signs of infection, such as fever, cough, or sore throat. Early treatment of infections can prevent more serious problems.

• Methotrexate (Rheumatrex, Folex PFS): We do not know exactly how this drug works in treatment of inflammatory reactions. It relieves symptoms of inflammation such as pain, swelling, and stiffness. People taking methotrexate have to have regular blood tests to measure whether the drug is having any adverse effects on the liver, kidneys, or blood cells. This drug is not suitable for some people with liver problems.

• Sulfasalazine (Azulfidine): This drug decreases inflammatory responses by an effect similar to that of aspirin or NSAIDs. People taking sulfasalazine must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.

• Leflunomide (Arava): This drug interferes with cells of the immune system and reduces inflammation. It reduces symptoms and may even slow progression of RA. People taking leflunomide must have regular blood tests to measure whether the drug is having any adverse effects on the liver or blood cells. This agent is not suitable for some people with liver or kidney problems.  

• Gold salts (aurothiomalate, auranofin [Ridaura]): These compounds contain very tiny amounts of the metal gold. We do not know why they stop inflammation. Apparently, the gold infiltrates into immune cells and interferes with their activities. People taking gold must have regular blood and urine tests to measure whether the drug is having any adverse effects on blood cells and the kidney.

• D-penicillamine: This agent combines with metals in the bloodstream and cells and removes them from the body. This suppresses certain actions of the immune system that promote RA. People taking D-penicillamine must have regular blood and urine tests to measure whether the drug is having any adverse effects on blood cells and the kidney.

• Hydroxychloroquine (Plaquenil): This drug was first used against the tropical parasite malaria. It inhibits certain cells that are necessary for the immune response that causes RA. People taking hydroxychloroquine must have eye examinations at least yearly to determine whether the drug is having any adverse effects on the retina.

• Azathioprine (Imuran): This drug stops production of cells that are part of the immune response associated with RA. Unfortunately, it also stops production of some other types of cells and thus can have serious side effects. It strongly suppresses the entire immune system and thus leaves the person vulnerable to infections and other problems. It is used only in severe cases of RA that have not gotten better with other DMARDs. People taking azathioprine must have regular blood tests to measure wither the drug is having any adverse effects on blood cells. 

• Cyclosporin A (Neoral): This drug was developed for use in people undergoing organ transplantation or bone marrow transplantation. These people must have their immune system suppressed to prevent rejection of the transplant. Cyclosporin blocks an important immune cell and interferes with the immune response in several other ways. People taking cyclosporin A must have regular blood tests and blood pressure checks to measure whether the drug is having any adverse effects on blood cells and blood pressure.

Biologic response modifiers: These agents act like substances produced normally in the body and block other natural substances that are part of the immune response. They block the process that leads to inflammation and damage to joints.

• Etanercept (Enbrel): This agent blocks the action of tumor necrosis factor, which in turn decreases inflammatory and immune responses. It is given by subcutaneous injection twice weekly. People taking etanercept must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.

• Infliximab (Remicade): This antibody blocks the action of tumor necrosis factor. It is often used in combination with methotrexate in people whose RA does not respond to methotrexate alone. It is given by intravenous infusion every 6-8 weeks. People taking infliximab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.

• Adalimumab (Humira): This is another blocker of tumor necrosis factor. It reduces inflammation and slows or stops worsening of joint damage in fairly severe RA. It is given by subcutaneous injection every 2 weeks. People taking adalimumab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.

• Anakinra (Kineret): This agent blocks the action of interleukin-1, which is partly responsible for the inflammation of RA. This in turn blocks inflammation and pain in RA. This agent usually is reserved for people whose RA has not improved with DMARDs. It is given by subcutaneous injection daily. People taking anakinra must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.

Glucocorticoids: These very potent agents block inflammation and other immune responses. They are often called steroids. They all work in the same way; they differ only in their potency and in the form in which they are given. Steroids may be given as pills, intravenously, or as injections into muscle or directly into a joint. In high doses, they can cause many serious side effects and thus are given only for the shortest possible periods and under strictly controlled circumstances. These drugs should never be stopped abruptly.

• Prednisone (Deltasone, Meticorten, Orasone)

• Betamethasone (Celestone)

Nonsteroidal anti-inflammatory drugs (NSAIDs): These drugs reduce swelling and pain but do not stop joint damage and alone are not sufficient to treat RA. These drugs work by blocking an enzyme called cyclo-oxygenase (COX) that promotes inflammation. There are at least 2 forms of the enzyme, COX-1 and COX-2. Some people with a history of stomach ulcers or liver problems should not take these drugs. This group includes aspirin, although aspirin is rarely used in RA because it is not as safe as other agents.

• COX-2 inhibitors: These agents block only the COX-2 enzyme, and often are referred to as "selective" NSAIDs. They have fewer side effects than the other NSAIDs while still reducing inflammation. Only celecoxib (Celebrex) currently remains on the US market.
  • Alert: On September 30, 2004, Merck & Co, Inc, announced a voluntary withdrawal of the COX-2 inhibitor rofecoxib (Vioxx) from the US and worldwide market because of its association with an increased rate of cardiovascular events (including heart attacks and strokes) compared to that of placebo. A major US Food and Drug Administration (FDA) study of rofecoxib found an apparent 3-fold increase in the risk of sudden cardiac death or heart attack among patients who had taken higher doses of the drug compared to the risk of patients who had not recently received similar medication. The report showed that even patients taking the standard starting dose of 12.5 mg or 25 mg of rofecoxib had a 50% greater chance of heart attack or sudden cardiac death than patients on any dose of celecoxib (Celebrex). The large-scale study was conducted after analyzing the medical records of 1.4 million people insured by Kaiser Permanente in Oakland, Calif, between 1999-2001. Note: The study has inherent limitations in that it is observational, rather than randomized and controlled.

  • Alert: On April 7, 2005, valdecoxib (Bextra, by Pfizer, Inc) was voluntarily withdrawn from the US market, pending further discussion with the FDA. The association of valdecoxib with potentially life-threatening risks, including myocardial infarction, stroke, and serious skin reactions, initiated an investigation to determine whether the benefits of the drug outweighed the risks. The serious skin reactions are most likely to occur in the first 2 weeks of treatment, but they can occur any time during therapy. Valdecoxib should be discontinued at the first sign of rash, mouth sores, and/or allergic reactions (eg, swelling, itching, shortness of breath). Other COX-2 inhibitors and traditional NSAIDs (eg, naproxen [Aleve, Naprosyn], ibuprofen [Motrin]) also have a risk for these rare, serious skin reactions, but the reported rate of the reaction appears to be greater for valdecoxib. New data regarding risks in individuals who take valdecoxib following heart bypass surgery showed an increased risk of heart attack, stroke, deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clots in the lungs).
  
  
• Nonselective NSAIDs: These drugs block both COX-1 and COX-2. They include ibuprofen (Motrin, Advil, etc.), ketoprofen (Oruvail), naproxen (Naprosyn), piroxicam (Feldene), and diclofenac (Voltaren, Cataflam).

Analgesics: These agents reduce pain but do not affect swelling or joint destruction.

• Acetaminophen (Tylenol, Feverall, Tempra): This drug is often used by people who cannot take NSAIDs because of hypersensitivity, ulcers, liver problems, or interactions with other drugs.

• Tramadol (Ultram)

• Opioids: These drugs may be used to treat moderately severe to severe pain that is not relieved by other analgesics.

|Surgery|

Some people with RA need several operations over time. Examples include removal of damaged synovium (synovectomy), tendon repairs, and replacement of badly damaged joints, especially the knees or hips.

Some people with RA have involvement of the vertebrae of the neck (cervical spine). This has the potential for compressing the spinal cord and causing serious consequences in the nervous system. These people occasionally need to undergo surgical fusion of the surgical spine. 

|Other Therapy|

No herb, “natural product,” or nutritional supplement has been shown definitively to be helpful in RA. Studies are underway to test some herbal products thought to be helpful in RA, but we do not know enough about them to recommend them.
 
A variety of complementary approaches may be effective in relieving pain. These include acupuncture and massage.

|Follow-up|

Regardless of whether a specialist or your primary care provider is treating you for rheumatoid arthritis, he or she should see you regularly to monitor your condition, your response to treatment, and side effects and other problems related to your RA or your treatment. The best way to monitor your condition is to see if you have any disability (loss of function) and, if so, how much.
 
The frequency of these visits depends on the activity of your rheumatoid arthritis. If your treatment is working well and your condition is stable, the visits can be less frequent than if your RA is getting worse, you are developing complications, or you are having severe side effects of treatment. Each person’s situation must be decided individually.

|Prevention|

There is no known way to prevent RA, although progression of the disease usually can be stopped or slowed by early, aggressive treatment.

|Outlook|

As a rule, the severity of RA waxes and wanes. Periods of active inflammation and tissue damage marked by worsening of symptoms (flares) are interspersed with periods of little or no activity, in which symptoms get better or go away altogether (remission). The duration of these cycles varies widely among individuals.

Outcomes are also highly variable. Some people have a relatively mild condition, with little disability or loss of function. Others at the opposite end of the spectrum experience severe disability due to pain and loss of function. Disease that remains persistently active for more than a year is likely to lead to joint deformities and disability. Approximately 40% of people have some degree of disability 10 years after their diagnosis. For most, RA is a chronic progressive illness, but about 5-10% of people experience remission without treatment. This is uncommon, however, after the first 3-6 months.

RA is not fatal, but complications of the disease shorten life span by a few years in some individuals. Although generally RA cannot be cured, the disease gradually becomes less aggressive and symptoms may even improve. However, any damage to joints and ligaments and any deformities that have occurred are permanent. RA can affect parts of the body other than the joints.

The early use of DMARDs and biologic response modifiers in RA has resulted in patients experiencing more profound relief of symptoms and less joint damage and less disability over time.

Common complications of RA include the following:

• Peripheral neuropathy and carpal tunnel syndrome: This condition results from damage to nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
  
  
• Anemia: This is a low level of hemoglobin, a protein in the blood that carries essential oxygen to cells and tissues. Symptoms include weakness, low energy, pallor, and shortness of breath.
  
  
• Scleritis: This is an inflammation of the blood vessels in the eye that can damage the eyes and impair vision.
  
  
• Infections: People with RA have a higher risk for infections. This is due partly to the abnormal immune system in RA and partly to the use of immune-suppressing medications for treatment.
  
  
• Digestive tract problems: Many people experience stomach and intestinal distress. Again, this is more often a side effect of medications used to treat RA.
  
  
• Osteoporosis: Osteoporosis is more common in women with RA than in women in general. The hip is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are older than 60 years.
  
  
• Lung disease: Certain conditions involving inflammation of the lungs seem to be more common in people with RA than in the general population. However, a definite link between cigarette smoking and RA may at least partly account for this finding. Cigarette smoking, in any case, may increase the severity of the disease.
  
  
• Heart disease: RA can affect the blood vessels and may increase the risk for coronary heart disease.
  
  
• Sjögren syndrome: This is another autoimmune rheumatic disease, like RA. It causes extreme dryness of certain body tissues, especially the eyes and mouth. Dryness of the eyes is most common in people with RA.
  
  
• Felty syndrome: This condition combines enlargement of the spleen with impairment of the immune system (low white blood cell count), leading to recurrent bacterial infections. This syndrome sometimes responds to DMARD therapy.
  
  
• Lymphoma and other cancers: The risk for lymphoma, a cancer of the lymph nodes, is higher than normal in people with RA. This is thought to be a result of abnormalities in the immune system. Other cancers that may be more common in people with RA include prostate and lung cancers.
  
  
• Macrophage activation syndrome: This is a life-threatening complication of RA and requires immediate treatment. Symptoms include persistent fever, weakness, drowsiness, and lethargy.

Overall, the rate of premature death is higher in people with RA than in the general population. The most common causes of premature death in people with RA are infection, vasculitis, and poor nutrition.

|Support Groups and Counseling|

Living with the effects of RA can be difficult. Sometimes you will feel frustrated, perhaps even angry or resentful. Sometimes it helps to have someone to talk to.
 
This is the purpose of support groups. Support groups consist of people in the same situation you are in. They come together to help each other and to help themselves. Support groups provide reassurance, motivation, and inspiration. They help you see that your situation is not unique, and that gives you power. They also provide practical tips on coping with your disease.
 
Support groups meet in person, on the telephone, or on the Internet. To find a support group that works for you, ask your health care provider or contact the following organizations or look on the Internet. If you do not have access to the Internet, go to the public library.

• Arthritis Foundation – (800) 283-7800

Arthritis Foundation
PO Box 7669
Atlanta, GA 30357-0669
(800) 283-7800
 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMD)
Information Clearinghouse
National Institutes of Health
1 AMS Circle
Bethesda, MD 20892-3675
(301) 495-4484 or toll free (877) 226-4267
 
American College of Rheumatology/Association of Rheumatology Health Professionals
1800 Century Place, Suite 250
Atlanta, GA 30345-4300
(404) 633-3777

|Web Links|

American College of Rheumatology/Association of Rheumatology Health Professionals
 
Arthritis Foundation
 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

RA, autoimmune disease, carpal tunnel syndrome, connective tissue disease, joint disease, joint stiffness, joint swelling, systematic disease, immune disorder, inflammation, inflammatory disorder, osteoporosis, rheumatic disease, rheumatoid nodules, synovitis, synovium, vasculitic nodules, vasculitis, juvenile rheumatoid arthritis, JRA, rheumatoid arthritis

Author: Howard R Smith, MD, Chief of Rheumatology; and Director of the Pain Management Center, Department of Internal Medicine, Division of Rheumatology, Huron Hospital, Cleveland Clinic Health Systems; Adjunct Professor of Medicine, Case Western Reserve University.

Coauthor(s): Josef S Smolen, MD, Chairman, Department of Rheumatology, Professor of Internal Medicine, Vienna General Hospital, University of Vienna; Chairman, Department of Medicine-Center for Rheumatic Diseases, Lainz Hospital, Vienna.

Editors: Kristine M Lohr, MD, Associate Chief, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology, University of Tennessee School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, ; Arthur Weinstein, MD, Professor of Medicine, Georgetown University; Associate Chairman, Department of Medicine, Director, Section of Rheumatology, Washington Hospital Center.