Rheumatoid arthritis

Arthritis is inflammation of a joint, the place where moving bones meet. Rheumatoid arthritis is a painful, chronic inflammatory condition that can destroy joint tissue and, eventually, affect all body systems.


Anatomy
At the end of each bone is a tough, rubbery substance called cartilage. The cartilage protects the ends of the bones and also decreases friction.
The synovial membrane is a thin, protective layer of tissue that covers all joint surfaces except the cartilage. The synovial membrane secretes synovial fluid, which lubricates the joint surfaces.

Tissues that attach bone to bone and help stabilize the joints are called ligaments. Tendons attach bones to muscles.

Inflammation and pain can occur in any of these tissues.


Causes/associated factors
Rheumatoid arthritis affects about 2.1 million Americans. Although the exact cause of rheumatoid arthritis remains a mystery, it's known to be an autoimmune disorder (a condition in which the body's immune system fights against the body's own tissues).
Abnormal white blood cells produce inflammation and thickening of the synovial membrane in affected joints. The cells of this thickened membrane eventually weaken and destroy surrounding joint tissue. This causes pain, deformity and disability.

Certain genetic markers may contribute to the development of rheumatoid arthritis. Not everyone who has a genetic marker develops the disease, however.

It's possible that rheumatoid arthritis may be triggered by a certain type of virus or bacteria in people who are genetically predisposed to the disorder. Hormonal factors may also act as triggers.

The condition may appear anytime, but often begins during middle age. Rheumatoid arthritis is two to three times more likely to affect women, and it's more common in some Native American populations. People who have a family history of rheumatoid arthritis are also more likely to develop the condition.

The terms arthritis and rheumatism are often used interchangeably to describe pain or abnormalities in the joints. These symptoms may be part of a connective tissue or rheumatoid disease. A doctor who specializes in these conditions is called a rheumatologist.


Signs/symptoms
Symptoms of rheumatoid arthritis vary. Early symptoms often include:
joint pain
morning stiffness
fatigue
appetite loss
a general feeling of illness
mild fever
These symptoms are often followed by joint pain, swelling and warmth. Eventually, deformity and disability are likely.

Rheumatoid arthritis usually develops symmetrically in joints on both sides of the body, often affecting the hands or feet first. The wrists, elbows, shoulders, neck, ankles and knees are also commonly affected.

A cycle of recurrences (called flare-ups) and remissions (when symptoms are not as active) is common.

As the disease progresses there may be:

joint stiffness that continually worsens (especially in the morning and after more than 30 minutes of inactivity)
rheumatoid nodules (a collection of inflammatory cells) under the skin
anemia (a condition characterized by a low number of red blood cells or hemoglobin, a substance in the red blood cells that contains iron)

Diagnosis
The doctor will review your medical history and do a physical exam. There's no specific test to diagnose rheumatoid arthritis. However, as the disease progresses, X-rays or blood tests can detect the extent of cartilage and bone destruction or deformity.
Sometimes, a small amount of synovial fluid from the affected joint is examined.

For 75 to 80 percent of people who have rheumatoid arthritis, an abnormal protein called rheumatoid factor is detected in the blood. The amount of rheumatoid factor is related to the severity of the disease. Rheumatoid factor can also be found in the blood of some people who don't have rheumatoid arthritis.


Treatment
Early and aggressive treatment can help prevent disease progression and joint destruction. With treatment, most people with rheumatoid arthritis live active, productive lives. Your treatment plan will be designed to:
relieve pain
decrease inflammation
help you remain as active as possible
improve your joint function and overall well-being
prevent or minimize any further damage to the affected joints
Medication
Medication is often an important aspect of pain management. Before prescribing medication, your doctor will consider various factors, including:

the specifics of your condition
the presence of other medical conditions
how often the medications must be taken
how long the effects last
the cost
any personal preferences
Before taking any medication, make sure you understand the possible side effects. If you develop side effects, contact your doctor or seek medical attention immediately.

Remember not to mix over-the-counter and prescription arthritis medications.

Anti-inflammatory medications

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, are the most commonly used medications for joint pain and swelling. Valdecoxib (Bextra, for example) and Celecoxib (Celebrex, for example), also known as COX-2 inhibitors, are two newer prescription NSAIDs.
Because of recent safety concerns regarding the COX-2 inhibitors, the U.S. Food and Drug Administration (FDA) has advised doctors to evaluate alternatives to these medications. If your doctor determines that COX-2 inhibitors are appropriate for you, the FDA recommends using the lowest effective dose.

It's important to remember that NSAIDs don't alter the course of the disease or prevent joint destruction.

Benefits: These medications offer relief from pain and reduce the inflammation associated with rheumatoid arthritis.

Risks: The major side effects of NSAIDs are gastrointestinal problems such as upset stomach, damage to the stomach lining and gastrointestinal bleeding. Concern over a possible increased risk of heart attack or stroke in people taking COX-2 inhibitors is prompting more research about the risks of this class of NSAIDs.


Corticosteroids are more potent anti-inflammatory medications prescribed for short periods of time, often during intense flare-ups when your symptoms can't be controlled by other medications. Corticosteroids may also provide temporary relief until other forms of medication take effect.
Corticosteroids may be taken orally or injected directly into the affected joint, which may provide quicker relief.

Due to the possibility of serious side effects, corticosteroids are usually not prescribed for long periods of time. With long-term use, doctors may prescribe corticosteroids in low doses or for use every other day. Oral medication dosages must be tapered off if the medication is discontinued.

Benefits: Corticosteroids are strong medications that may be especially effective in relieving symptoms associated with inflammation or flare-ups. When injected directly into an affected joint, relief may be provided more quickly than with oral medication.

Risks: Corticosteroids can have significant side effects, most of which are dose- or duration-related. You may notice gastrointestinal disturbances such as peptic ulcers, nausea and vomiting. The medication may also affect your central nervous system in the form of insomnia, headaches and dizziness.

More serious side effects may include seizures or thromboembolism (the blocking of a blood vessel by a blood clot). Long-term use may cause osteoporosis, elevated blood sugar or diabetes. Sudden withdrawal can be fatal if you've taken orticosteroids for a prolonged period of time.

Disease-modifying medications
Disease-modifying antirheumatic drugs (DMARDs) slow the progression of rheumatoid arthritis. They're prescribed when the disease is active. Routine monitoring, including lab tests, is important to detect any side effects to these medications. Here are a few of the most common DMARDs:

Methotrexate (Rheumatrex, for example) suppresses the immune system. It's taken once a week either orally or by injection, and takes at least one month to take effect. Typically recommended for more serious cases, it's currently the most widely used and effective form of treating rheumatoid arthritis.
Benefits: It's generally well-tolerated.

Risks: Possible side effects of methotrexate include stomach irritation and inflammation of the lining of the mouth. Other side effects include damage to the liver or red blood cells. Thus, periodic blood testing is required. Methotrexate may also cause lung problems, a less common side effect.


Hydroxychloroquine (Plaquenil, for example) is an antimalarial drug that may be used in less severe cases of rheumatoid arthritis.
Benefits: It's usually well-tolerated.

Risks: Common side effects of hydroxychloroquine include headaches, appetite loss and abdominal pain. With prolonged use, follow-up eye exams are important. If retinal changes are detected, you may need to stop taking the medication.


Sulfasalazine (Azulfidine, for example) may also be prescribed in less severe cases, as long as you don't have a history of allergic reactions to sulfa medications. When taking this medication, it's important to drink plenty of fluids every day. Symptoms may not improve for several weeks or even months.
Benefits: Sulfasalazine has been established as a solid second-line treatment for rheumatoid arthritis. It's about as effective as Penicillamine and gold salts (described below).

Risks: Common side effects include headaches, nausea, vomiting, diarrhea, appetite loss, skin sensitivity to sun, and orange skin or urine. Ten to 25 percent of people taking sulfasalazine develop neutropenia (an abnormally small amount of neutrophil cells -- a type of white blood cell -- in the blood) and thrombocytopenia (a blood clotting disorder that causes excessive bleeding). You'll need to be monitored with complete blood cell counts for the first three months or more of treatment.


Gold salts (chrysotherapy) are given by injection or taken orally (by mouth). Although complete remissions are uncommon, about 60 percent of people who take gold salts find relief within three to six months. Gold salts are especially helpful for people who can't tolerate the drug methotrexate.
Benefits: Gold salts help relieve inflammation, especially for people who don't find relief with NSAIDs.

Risks: Diarrhea is a common side effect. Less frequent side effects include skin rashes, sores or white spots in the mouth, protein in the urine and a drop in white blood cells. Periodic blood and urine testing are important.


D-penicillamine (Penicillamine, for example) is about as effective as gold salts, but it's more toxic. It may also take awhile for symptoms to improve. This medication may be suggested for people who don't respond to or tolerate gold salts.
Benefits: D-penicillamine is believed to improve the protective function of the white blood cells against rheumatoid arthritis.

Risks: Rashes are the most common side effect of D-penicillamine. Because the bone marrow and kidneys may be affected, you'll need frequent lab monitoring of your blood and urine.


Azathioprine (Imuran, for example) also suppresses the immune system. It's used to treat severe, resistant rheumatoid arthritis. Improvement may not be noticed for six to eight weeks.
Benefits: This medication may be helpful when symptoms are severe and don't respond to other medications.

Risks: Because azathioprine suppresses the immune system, you'll be more prone to infection. Again, regular blood and liver function tests are important.


Leflunomide (Arava, for example) is a pyrimidine synthesis inhibitor, a new class of antirheumatic medication.
Benefits: Leflunomide may be as effective as methotrexate.

Risks: Leflunomide may cause diarrhea and abnormal liver function tests. Regular liver function tests are important.

Biologic response modifiers
Biologic response modifiers are a new class of medications that decrease joint inflammation by blocking the action of substances such as tumor necrosis factor (TNF) and interleukin (IL-1). They may be prescribed when symptoms don't respond to methotrexate or other types of therapy.

Etanercept (Enebrel, for example) is a TNF inhibitor given by injection twice a week.
Benefits: More than 60 percent of people taking etanercept show improvement. The drug appears to be tolerated well.

Risks: Minor irritation may occur at the injection site, and the medication may increase the risk of serious infections.


Infliximab (Remicade, for example) is a TNF inhibitor given intravenously. Repeat doses are given at two- to eight-week intervals.
Benefits: More than 60 percent of people taking infliximab show improvement.

Risks: Infliximab may cause anaphylaxis (a life-threatening allergic reaction). The drug may also cause the production of harmful antibodies (compounds that help neutralize or destroy foreign substances in the blood).


Adalimumab (Humira, for example) is a TNF inhibitor given by injection every other week.
Benefits: More than 50 percent of people taking adalimumab show improvement.

Risks: Adalimumab may cause minor irritation at the injection site, and the medication may increase the risk of serious infections, such as tuberculosis and sepsis (a blood infection).


Anakinra (Kineret, for example) is an IL-1 inhibitor given by daily injection for people age 18 or older who haven't responded to other DMARD therapies.
Benefits: Anakinra improves symptoms, joint changes and anemia in many people.

Risks: Anakinra may cause minor irritation at the injection site. The medication may increase the risk of infections.

Other medication therapies may include minocycline and cyclosporine. Combination therapy (the use of more than one class of medications) also shows promise in treating rheumatoid arthritis.

Nonmedication therapies


Prosorba column: Prosorba column is a blood-filtering device that removes harmful antibodies from the blood of people who have severe rheumatoid arthritis and have failed to respond to medication therapy or can't tolerate it. This specialized treatment is usually done in 12 weekly treatments.

Heat: Applying heat through warm baths or showers, warm compresses and the careful use of heat lamps can relax your muscles and alleviate pain and stiffness. Apply heat for no longer than 20 minutes at a time. Be careful not to burn your skin, especially if you're an older adult or have an impaired circulatory system.
Another note of caution: Don't use heat on any red, warm joint. Instead, notify your doctor. If you have diabetes or nerve damage to extremities, don't apply heat unless your doctor recommends it.


Rest and exercise: Research has shown the right balance of exercise and rest is beneficial to the joints and overall health. To reduce damage, protect and rest the affected joints -- especially during periods of inflammation. Maintain proper posture to help reduce the strain on your joints and spine, and discuss your daily activities with your doctor to find ways to decrease the strain on your joints. Crutches, canes or special braces for weight-bearing joints may help with walking, as well as reduce the pressure on your joints.
Take advantage of periods of disease inactivity to exercise more. Make sure any exercises are specifically approved by your doctor, however. When planning an appropriate exercise program for you, the doctor may enlist the help of a physical therapist. He or she can help you learn appropriate exercises, as well as encourage you to make exercise part of your daily routine.

With range-of-motion exercises, you'll move the affected joint through its entire range of motion without causing pain. The goal is to maintain flexibility, decrease pain and stiffness, and improve joint function. If the joint is inflamed, it can be moved through its range of motion without any effort on your part.

Muscle-strengthening exercises are used to strengthen specific muscle groups and stabilize weak joints. Conditioned muscles can offer support, help protect your joints and decrease pain.

Endurance exercises can help improve your overall fitness. Your doctor or physical therapist may recommend swimming, bicycling or other activities that would be easy on your joints. Avoid repetitive impact sports such as running, jogging or tennis. Also avoid exercising on hilly areas or hard surfaces.

Another note of caution: Avoid or reduce strengthening and endurance exercises during flare-ups or when you have severe pain. Avoid any specific exercises that increase your pain an hour or so later.


Orthotics: Your doctor may suggest orthotic devices for your shoes. These devices can help redistribute your weight and shift the mechanical force on your feet.

Weight reduction: Excess weight can add stress to your joints and further complicate rheumatoid arthritis. Logically, weight loss can play an important role in relieving symptoms and preventing joint dysfunction.
Surgery
If more conservative treatments aren't effective, surgery may be recommended for the joints in your feet, toes, ankles, knees, hips, hands, fingers, wrists or shoulders. Various surgical procedures may be available, including:

arthrodesis (bone fusion)
arthroplasty (joint rebuilding)
osteotomy (correction of deformities of the joints by cutting and resetting them)
resection (removal of a bone or part of a bone)
synovectomy (removal of the diseased synovium, the sack around the joint)
Discuss the benefits and risks of each type of surgery with your doctor. You may also want to consider getting a second opinion.

Benefits: Surgery usually offers pain relief and may improve the movement and function of your joints. Surgery may also offer cosmetic benefits, such as improvement in the appearance of deformed joints -- especially those in your hands.

Risks: Surgery may lead to complications if you have other health conditions, especially if you're overweight and the surgery involves a weight-bearing joint such as the hip or knee. Also, the younger you are, the more likely you are to need another surgery in the future because artificial joints tend to loosen over time.

Self-care measures
When you have rheumatoid arthritis, it's especially important to take good care of yourself. Consider these suggestions:

Learn about your medications, including how and when to take them, possible side effects and when to consult your doctor.

Eat healthfully and follow your exercise program to maintain a healthy weight.

Get plenty of rest.

If you find them helpful, use assistance devices for activities such as dressing, eating and bathing.

Avoid alcohol.

At work, modify your environment or workstation to decrease any strain or pain. Take breaks before your pain becomes difficult to manage.

Keep a diary of your responses to treatment and self-care measures to find out what works best for you.

Consider additional measures to control your pain, such as relaxation techniques, imagery or massage.

Develop and maintain a support network. Consider counseling and support groups.

Take an arthritis self-help course, such as the one offered by the Arthritis Foundation.

See your doctor for regular follow-up care or changes in treatment as needed.

If you become depressed, seek professional help.

Complications
Rheumatoid arthritis can affect many organs of the body. Complications of rheumatoid arthritis may include:
depression or anxiety
Sjögren's syndrome (a condition characterized by dryness of the eyes, mouth and other mucus membranes)
chronic eye inflammation, which can rarely lead to blindness if left untreated
skin ulcers
nerve entrapment or compression in affected joints, which can lead to numbness, weakness or loss of function in the affected extremity (such as carpal tunnel syndrome of the wrist)
hepatitis (inflammation of the liver)
lung or heart disease
osteoporosis (the loss of bone mass that leads to brittle bones)
disrupted growth in children

Pregnancy-specific information
Rheumatoid arthritis occasionally develops during pregnancy. About 75 percent of women who develop the condition during pregnancy improve, but then relapse within six months.
Rheumatoid arthritis isn't known to increase the risk of fetal abnormalities, but severe joint disease may affect your labor and delivery.

As with any medication, consult your doctor before taking a pain reliever or other medication during pregnancy. Because researchers haven't established the safety of NSAIDS during pregnancy, they're still considered a risk.


Senior-specific information
Although rheumatoid arthritis typically appears during middle age, it may also develop among older adults. You and your doctor may need to consider how other age-related illnesses may interact with rheumatoid arthritis. Your medication tolerance will depend on your overall health. Consult your doctor with any questions or concerns.

Prevention
Although there's no known way to prevent rheumatoid arthritis, early intervention can help reduce the frequency of flare-ups and prevent joint damage. Research continues on gene therapy and nutrition, such as the use of food or supplements containing fish oils and evening primrose oil. Oral contraceptives may also be associated with a lower risk of rheumatoid arthritis.