Rheumatoid arthritis

Alternative names
RA; Arthritis - rheumatoid

Definition
Rheumatoid arthritis is a chronic (long-term) inflammatory disease that primarily affects the joints and surrounding tissues, but can also affect other organ systems.

Causes, incidence, and risk factors

The cause of rheumatoid arthritis (RA) is unknown. However, RA involves an attack on the body by its own immune cells (auto-immune disease). Different cases may have different causes. Infectious, genetic, and hormonal factors may play a role.

The disease can occur at any age, but it begins most often between the ages of 25 and 55. The disease is more common in older people. Women are affected more often than men. Approximately 1-2% of the total population is affected. The course and the severity of the illness can vary considerably.

The onset of the disease is usually gradual, with fatigue, morning stiffness (lasting more than one hour), diffuse muscle aches, loss of appetite, and weakness. Eventually, Joint pain appears, with warmth, swelling, tenderness, and stiffness of the joint after inactivity.

RA usually affects joints on both sides of the body equally - wrists, fingers, knees, feet, and ankles are the most commonly affected.

When the synovium (the lining of the joint) becomes inflamed, it secretes more fluid and the joint becomes swollen. Later, the cartilage becomes rough and pitted. The underlying bone is eventually affected. Joint destruction may begin, often within 1-2 years after the appearance of the disease.

Deformities result from cartilage destruction, bone erosions, and tendon inflammation and rupture. A life-threatening joint complication can occur when the cervical spine becomes unstable as a result of RA.

Other features of the disease that do not involve the joints may occur. Rheumatoid nodules are painless, hard, round or oval masses that appear under the skin, usually on pressure points, such as the elbow or Achilles tendon. These are present in about 20% of cases and tend to reflect more severe disease.

On occasion, nodules appear in the eye where they sometimes cause inflammation. If they occur in the lungs, inflammation of the lining of the lung (pleurisy) may occur, causing Shortness of breath and fluid accumulation in the lung.

Anemia may occur due to failure of the bone marrow to produce enough new red cells to make up for the lost ones. Iron supplements will not usually help this condition because iron utilization in the body becomes impaired. Other blood abnormalities can also be found, for example, platelet counts that are either too high or too low.

Rheumatoid vasculitis (inflammation of the blood vessels) is a serious complication of RA and can be life-threatening. It can lead to skin ulcerations (and subsequent infections), bleeding stomach ulcers (which can lead to massive hemorrhage), and neuropathies (nerve problems causing pain, numbness or tingling).

Vasculitis may also affect the brain, nerves, and heart causing Strokes, sensory neuropathies (Numbness and tingling), Heart attacks, or heart failure.

Heart complications of RA commonly affect the outer lining of the heart. When inflamed, the condition is referred to as pericarditis. Inflammation of heart muscle, called myocarditis, can also develop. Both of these conditions can lead to Congestive heart failure characterized by Shortness of breath and fluid accumulation in the lung.

Eye complications include inflammation of various parts of the eye. These must be screened for in RA patients.

Symptoms

     
  • Fatigue  
  • General discomfort, uneasiness, or malaise  
  • Loss of appetite  
  • Low-grade fever  
  • Joint pain, joint stiffness, and joint swelling - often on both sides of the body  
  • Joint pain may include wrist pain, Knee pain, elbow pain, finger pain, toe pain, ankle pain, or neck pain  
  • Limited range of motion  
  • Morning stiffness lasting more than one hour  
  • Deformities of hands and feet  
  • Round, painless nodules under the skin  
  • Skin redness or inflammation  
  • Paleness  
  • Swollen glands  
  • Eye burning, itching, and discharge  
  • Numbness or tingling

Signs and tests

     
  • Joint X-ray  
  • Rheumatoid factor test is positive in about 75% of people with symptoms  
  • Erythrocyte sedimentation rate is elevated  
  • CBC may show low hematocrit (anemia) or abnormal platelet counts  
  • C-reactive protein may be a positive indication for patients with no detectable rheumatoid factor  
  • Synovial fluid analysis

Treatment
RA usually requires lifelong treatment, including various medications, physical therapy, education, and possibly surgery to relieve the symptoms of the disease.

MEDICATIONS

Early, aggressive treatment for RA can delay joint destruction. In addition to rest, strengthening exercises, and anti-inflammatory drugs, the current standard of care is to begin aggressive therapy with disease-modifying anti-rheumatic drugs (DMARDs) once the diagnosis is confirmed.

DMARDs include gold compounds, which can be injectible (Myochrysine and Solganal) or by mouth (auranofin/Ridaura). Methotrexate (Rheumatrex) is the most commonly used DMARD for rheumatoid arthritis with proven effectiveness.

Anti-inflammatory agents used to treat RA traditionally include aspirin and non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen (Motrin, Advil), fenoprofen, indomethacin, naproxen (Naprosyn), and others.

These are widely used medications that are effective in relieving pain and inflammation associated with RA. However, the side effects associated with frequent use of many of these medications include life-threatening gastrointestinal bleeding and kidney damage.

Similar drugs, called Cox-2 inhibitors, are now a mainstay of anti-inflammatory therapy because the risk of gastrointestinal bleeding is significantly lower. These include valdecoxib (Bextra) and celecoxib (Celebrex).

Antimalarial medications such as Hydroxychloroquine (Plaquenil) and Sulfasalazine (Azulfidine) are also beneficial, usually in conjunction with Methotrexate.

The benefits from these medications may take weeks or months to be apparent. Because they are associated with toxic side effects, frequent monitoring of blood tests while on these medications is imperative.

In the last few years, new and exciting medications have been introduced. Promising medications that are fast becoming first-line treatment, often in addition to methotrexate, are inhibitors of the inflammatory protein called tumor necrosis factor (TNF). These medications include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira).

Other relatively new medications include anakinra (Kineret), which blocks the inflammatory protein interleukin-1, and leflunomide (Arava), which inhibits the metabolism of nucleotides required for DNA synthesis in lymphocytes. Adalimumab, anakinra, and etanercept are injectable medications, whereas infliximab is given intravenously, and leflunomide is taken by mouth.

Other drugs that suppress the immune system, like azathioprine (Imuran) and cyclophosphamide (Cytoxan), are sometimes used in people who have failed other therapies. These medications, which are associated with toxic side effects, are usually reserved for severe cases of RA.

Corticosteroids have been used to reduce inflammation in RA for more than 40 years. However, because of potential long-term side effects, corticosteroid use is usually limited to short courses and low doses where possible. Side effects may include bruising, psychosis, thinning of the bones (Osteoporosis), cataracts, weight gain, susceptibility to infections, Diabetes, and High blood pressure. A number of medications can be administered with steroids to minimize Osteoporosis.

Consult a health care provider before long-term use of any medication, including over-the-counter medications.

SURGERY

Occasionally, surgery is performed for severely affected joints. The most successful surgeries are those on the knees and hips. Usually, the first surgical treatment is removal of the synovium (synovectomy).

A later alternative is total joint replacement with a joint prosthesis. Surgeries can relieve Joint pain, correct deformities, and modestly improve joint function. In extreme cases, total knee or hip replacement can mean the difference between being totally dependent on others and having an independent life at home.

LIFESTYLE CHANGES

Range-of-motion exercises and individualized exercise programs prescribed by a physical therapist can delay the loss of joint function.

Joint protection techniques, heat and cold treatments, and splints or orthotic devices to support and align joints may be very helpful.

Frequent rest periods between activities, as well as 8 to 10 hours of sleep per night, are recommended.

OTHER THERAPY

The Prosorba column is a device approved by the FDA in 1999 for the treatment of moderate to severe RA in adults with long-standing disease (who have not responded to DMARD’s). It works by removing inflammatory antibodies from the blood. The blood is removed through a small catheter and then passed through a column that binds the antibodies and removes them from the blood. The blood is then given back.

The procedure takes 2-3 hours, and must be done once a week for 12 weeks. Studies have reported that one third to one half of the people who receive this treatment may slow down, or even stop, the RA from worsening. Side effects include anemia, fatigue, fever, Low Blood pressure, and nausea. Some people have developed an infection from the catheter. Often there is a flare-up of Joint pain for several days after the treatment.

Sometimes therapists will use special machines to apply deep heat or electrical stimulation to reduce pain and improve joint mobility.

Occupational therapists can construct splints for your hand and wrist, and teach you how to best protect and use your 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 caused by RA.

MONITORING

Depending on the medications being taken, regular blood or urine tests should be done to monitor both progress and negative side effects.

Support Groups

For additional information and resources, see Arthritis support group.

Expectations (prognosis)

Frequently, the disease can be controlled with a combination of treatments. Treatment varies depending on the severity of the symptoms. Surgery may be needed, if medications fail.

The course of the disease varies between individuals. People with rheumatoid factor or subcutaneous nodules seem to have a more severe course of the disease. People who develop RA at younger ages also have a more rapidly progressive course.

Remission is most likely to occur in the first year. The probability decreases over time. By 10 to 15 years from diagnosis, about 20% of people have remission.

50-70% of patients remain capable of full-time employment. After 15-20 years, only 10% of patients are severely disabled, and unable to perform simple activities of daily living (washing, toileting, dressing, eating).

However, the average life expectancy may be shortened by 3 to 7 years with this disease, and patients with severe forms of RA may die 10-15 years earlier than expected.

As treatment for Rheumatoid Arthritis improves, severe disability and life-threatening complications appear to be decreasing, so these figures may be overly pessimistic.

Complications

Rheumatoid arthritis is not solely a disease of joint destruction. It can involve almost all organ systems. The treatments for RA have also yielded serious side effects, reducing the patient’s quality of life increasing the chance of death.

The complications of RA can include joint destruction, gastrointestinal bleeding, heart failure, pericarditis, pleuritis, lung disease, anemia, low or high platelets, eye disease, cervical (neck) spine instability, neuropathy, and vasculitis. Fortunately, better therapies appear to be reducing the occurrence of these severe complications.

Calling your health care provider

Call your health care provider if you think you have symptoms of rheumatoid arthritis.

Prevention

Rheumatoid arthritis has no known prevention. However, it is often possible to prevent further damage of the joints with proper early treatment.

Johns Hopkins patient information

Last revised: December 4, 2012
by Harutyun Medina, M.D.

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