RHEUMATOID ARTHRITIS OVERVIEW

Rheumatoid arthritis is a chronic inflammatory condition. Rheumatoid arthritis symptoms develop gradually and may include joint pain, stiffness, and swelling. The condition can affect many tissues throughout the body, but the joints are usually most severely affected. The cause of rheumatoid arthritis is unknown.

This article discusses the risk factors, symptoms, and evaluation of rheumatoid arthritis. A number of other articles about rheumatoid arthritis are also available. (See "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)" and "Patient information: Disease-modifying antirheumatic drugs (DMARDs) (Beyond the Basics)" and "Patient information: Rheumatoid arthritis and pregnancy (Beyond the Basics)" and "Patient information: Complementary therapies for rheumatoid arthritis (Beyond the Basics)".)

RHEUMATOID ARTHRITIS RISK FACTORS

The specific cause of rheumatoid arthritis is not known. Researchers suspect that two types of factors affect a person's risk: susceptibility factors and initiating factors.

Rheumatoid arthritis most likely occurs when a susceptible person is exposed to factors that start the inflammatory process. Approximately 1 in every 100 individuals has rheumatoid arthritis. (See "Epidemiology of, risk factors for, and possible causes of rheumatoid arthritis".)

Gender, heredity, and genes largely determine a person's risk of developing rheumatoid arthritis.

Gender — Gender appears to play a major role in a person's susceptibility to rheumatoid arthritis. Women are about three times more likely than men to develop rheumatoid arthritis.

Heredity — Rheumatoid arthritis is not an inherited disease. Genes do not cause rheumatoid arthritis; they merely affect the risk of its development.

Specific genes — People with specific variants of human leukocyte antigen (HLA) genes are more likely to develop rheumatoid arthritis than people with other gene variants.

Initiating factors — Many individuals who carry HLA genes never develop the condition. Indeed, when one identical twin has rheumatoid arthritis, the chance that the other will develop disease is only about 1 in 3. This suggests that additional factors must be necessary for a person to develop RA.

Infection — Researchers suspect that infection with bacteria or viruses may be one of the factors that initiate rheumatoid arthritis. However, at this time, there is no definite evidence linking infection to rheumatoid arthritis.

Cigarette smoking — Cigarette smoking may increase the risk of developing rheumatoid arthritis. There is also some evidence that cigarette smoking increases the likelihood that rheumatoid arthritis will be severe when it occurs.

Stress — Patients often report episodes of stress or trauma preceding the onset of their rheumatoid arthritis. Stressful “life events” (eg, divorce, accidents, grief, etc.) are more common in people with RA in the six months before their diagnosis compared with the general population.

RHEUMATOID ARTHRITIS SYMPTOMS

In most people, rheumatoid arthritis begins insidiously, and weeks or months may pass before the characteristic symptoms are bothersome enough to cause a person to seek medical care. Early symptoms may include fatigue, muscle pain, a low-grade fever, weight loss, and numbness and tingling in the hands. In some cases, these symptoms occur before joint pain or stiffness is noticeable. (See "Clinical features of rheumatoid arthritis".)

Occasionally, rheumatoid arthritis begins with symptoms related to inflammation of tissues other than the joints. For example, a person may experience chest pain or shortness of breath.

Pattern of joints affected — Rheumatoid arthritis usually affects the same joints on both sides of the body.

In the early stages, rheumatoid arthritis typically affects small joints, especially the joints at the base of the fingers, the joints in the middle of the fingers, and the joints at the base of the toes. It may also begin in a single, large joint, such as the knee or shoulder, or it may come and go and move from one joint to another.

As the condition progresses, most people have inflammation of the joints in the arms or legs, and between 20 and 50 percent of people have inflammation of the large central joints (eg, hips) and spine.

Joint symptoms — The joint symptoms of rheumatoid arthritis usually begin gradually and include pain, stiffness, redness, warmth to the touch, and joint swelling.

The joint stiffness is most bothersome in the morning and after sitting still for a period of time. The stiffness can persist for more than one hour.

• Hands — The joints of the hands are often the very first joints affected by rheumatoid arthritis. These joints are tender when squeezed, and the hand's grip strength is often reduced. Occasionally, rheumatoid arthritis may lead to visible redness and swelling of the entire hand.
  
  Between 1 and 5 percent of people with rheumatoid arthritis develop carpal tunnel syndrome because swelling compresses a nerve that runs through the wrist; this syndrome is characterized by weakness, tingling, and numbness of certain areas of the hand.
  
  Certain characteristic hand deformities can occur with long-standing rheumatoid arthritis. The fingers may develop characteristic, exaggerated profiles, called swan neck deformities (picture 1) and boutonniere deformities, and they may drift together in the direction of the small finger. The tendons on the back of the hand may become very prominent and tight, which is called the bow string sign.
• Wrist — The wrist is the most commonly affected joint of the arm in people with rheumatoid arthritis. In the early stages of rheumatoid arthritis, it may become difficult to bend the wrist backward.
• Elbow — Rheumatoid arthritis may cause inflammation of the elbow. Swelling of this joint may compress nerves that travel through the arm and may cause numbness or tingling in the fingers.
• Shoulder — The shoulder may be inflamed in the later stages of rheumatoid arthritis, causing pain and limited motion.
• Foot — The joints of the feet are often affected in the early stages of rheumatoid arthritis, especially the joints at the base of the toes. Tenderness at these joints may cause a person to stand and walk with his or her weight on the heels, with the toes bent upward. The top of the foot may be swollen and red, and, occasionally, the heel may be painful.
• Ankle — Rheumatoid arthritis may cause inflammation of the ankle. Inflammation of this joint may cause nerve damage, leading to numbness and tingling in the foot.
• Knee — Rheumatoid arthritis may cause swelling of the knee, difficulty bending the knee, excessive looseness of the ligaments that surround and support the knee, and damage of the ends of the bones that meet at the knee. Rheumatoid arthritis may also cause the formation of a Baker's cyst (a cyst filled with joint fluid and located in the hollow space at the back of the knee).
• Hips — The hips may become inflamed in the later stages of rheumatoid arthritis. Pain in the hips may make it difficult to walk.
• Cervical spine — Rheumatoid arthritis may cause inflammation of the cervical spine, which is the area between the shoulders and the base of the head. Inflammation of the cervical spine may cause a painful and stiff neck and a decreased ability to bend the neck and turn the head.
• Cricoarytenoid joint — In about 30 percent of people with rheumatoid arthritis, there is inflammation of a joint near the windpipe called the cricoarytenoid joint. Inflammation of this joint can cause hoarseness and difficulty breathing.

Other symptoms — Although joint problems are the most commonly known issues in rheumatoid arthritis, the condition can be associated with a variety of other problems.

Rheumatoid nodules — Rheumatoid nodules are painless lumps that appear beneath the skin. These nodules may move easily when touched, or they may be fixed to deeper tissues. They most often occur on the underside of the forearm and on the elbow, but they can also occur on other pressure points, including the back of the head, the base of the spine, the Achilles tendon, and the tendons of the hand.

Inflammatory conditions — Rheumatoid arthritis may produce a variety of other symptoms, depending on which tissues are inflamed.

• Inflammation of the tissue lining the chest cavity and surrounding the heart may cause chest pain and difficulty breathing. (See "Patient information: Pericarditis (Beyond the Basics)".)
• Inflammation of the lung that is not due to infection may cause shortness of breath and a dry cough.
• Abnormal nerve function may cause numbness, tingling, or weakness.
• Inflammation of the white part of the eye may cause pain or vision problems.
• Enlargement of the spleen may cause a fall in the number of white blood cells, which may lead to infections.
• Sjögren's syndrome causes dry eyes and dry mouth, which can lead to a gritty feeling or a sensation of irritating material in the eyes. Mouth dryness may make it difficult to chew or swallow without drinking something at the same time. Women may develop vaginal dryness due to Sjögren's syndrome, leading to pain with sexual intercourse. (See "Patient information: Sjögren’s syndrome (Beyond the Basics)".)
• Vasculitis (inflammation of the blood vessels) may cause a wide variety of symptoms, depending upon where the inflamed blood vessels are located. (See "Patient information: Vasculitis (Beyond the Basics)".)

RHEUMATOID ARTHRITIS DIAGNOSIS

There is no single test used to diagnose rheumatoid arthritis. Instead, the diagnosis is based upon many factors, including the characteristic signs and symptoms, the results of laboratory tests, and the results of x-rays. (See "Diagnosis and differential diagnosis of rheumatoid arthritis".)

A person with well-established rheumatoid arthritis typically has or has had at least several of the following:

• Morning stiffness that lasts at least one hour and that has been present for at least six weeks
• Swelling of three or more joints for at least six weeks
• Swelling of the wrist, hand, or finger joints for at least six weeks
• Swelling of the same joints on both sides of the body
• Changes in hand x-rays that are characteristic of rheumatoid arthritis
• Rheumatoid nodules of the skin
• Blood test positive for rheumatoid factor and/or anti-citrullinated peptide/protein antibodies

Not all of these features are present in people with early RA, and these problems may be present in some people with other rheumatic conditions.

In some cases, it may be necessary to monitor the condition over time before a diagnosis of rheumatoid arthritis can be made with certainty.

Laboratory tests — Laboratory tests help to confirm the presence of rheumatoid arthritis, to differentiate it from other conditions, and to predict the likely course of the condition and its response to treatment.

Rheumatoid factor (RF) — An antibody called rheumatoid factor is present in the blood of 70 to 80 percent of people with rheumatoid arthritis. However, rheumatoid factor is also found in people with other types of rheumatic disease and in a small number of healthy individuals.

Anti-citrullinated peptide/protein antibody test — Blood tests for antibodies to citrullinated peptides/proteins (ACPA) are more specific than rheumatoid factor for diagnosing rheumatoid arthritis. Anti-ACPA antibody tests may be positive very early in the course of disease. The test is positive in most patients with rheumatoid arthritis.

RHEUMATOID ARTHRITIS TREATMENT

A separate article discusses rheumatoid arthritis treatment. (See "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)".)

RHEUMATOID ARTHRITIS DISEASE COURSE

Rheumatoid arthritis often has a variable course: it can go into remission, follow a fluctuating course, or worsen steadily. In most people with rheumatoid arthritis, the severity of symptoms fluctuates for weeks or months. It is generally impossible to predict how the disease will affect a particular individual. (See "Disease outcome and functional capacity in rheumatoid arthritis".)

Treatment can drive the condition into remission, although remission is rare without treatment. In about 10 to 20 percent of people, rheumatoid arthritis progresses steadily despite treatment. Remission in pregnancy is common, although greater than 90 percent of women have a flare of arthritis symptoms within three months after childbirth. (See "Patient information: Rheumatoid arthritis and pregnancy (Beyond the Basics)".)

Long-term effects of rheumatoid arthritis — The inflammation of rheumatoid arthritis can potentially damage the bones, cartilage, and other structures of the joints. The joint damage typically worsens over time and is irreversible.

The risk of these problems and the risk of joint damage and disability can be reduced when early and effective disease-modifying treatments are used. Treatment is strongly recommended as soon a person is diagnosed with rheumatoid arthritis, even in those who have not yet developed x-ray changes. (See "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient information: Rheumatoid arthritis (The Basics)
Patient information: Rheumatoid arthritis and pregnancy (The Basics)
Patient information: Hand pain (The Basics)
Patient information: Ganglion cyst (The Basics)
Patient information: Pyoderma gangrenosum (The Basics)
Patient information: Antinuclear antibodies (The Basics)
Patient information: Interstitial lung disease (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient information: Rheumatoid arthritis treatment (Beyond the Basics)
Patient information: Disease-modifying antirheumatic drugs (DMARDs) (Beyond the Basics)
Patient information: Rheumatoid arthritis and pregnancy (Beyond the Basics)
Patient information: Complementary therapies for rheumatoid arthritis (Beyond the Basics)
Patient information: Pericarditis (Beyond the Basics)
Patient information: Sjögren’s syndrome (Beyond the Basics)
Patient information: Vasculitis (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Assessment of rheumatoid arthritis activity in clinical trials and clinical practice
Cervical subluxation in rheumatoid arthritis
Clinical features of rheumatoid arthritis
Polyarticular onset juvenile idiopathic arthritis: Clinical manifestations and diagnosis
Clinically useful biologic markers in the diagnosis and assessment of outcome in rheumatoid arthritis
Diagnosis and differential diagnosis of rheumatoid arthritis
Disease outcome and functional capacity in rheumatoid arthritis
Epidemiology of, risk factors for, and possible causes of rheumatoid arthritis
Evaluation and medical management of end-stage rheumatoid arthritis
General principles of management of rheumatoid arthritis in adults
Interstitial lung disease in rheumatoid arthritis
Leflunomide in the treatment of rheumatoid arthritis
Polyarticular onset juvenile idiopathic arthritis: Management
Miscellaneous novel therapies in rheumatoid arthritis
Ocular manifestations of rheumatoid arthritis
Overview of the systemic and nonarticular manifestations of rheumatoid arthritis
Randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit IL-1, IL-6, and RANKL
Rheumatoid arthritis and pregnancy
Rituximab and other B cell targeted therapies for rheumatoid arthritis
Sulfasalazine in the treatment of rheumatoid arthritis
T cell targeted therapies for rheumatoid arthritis
Total joint replacement for severe rheumatoid arthritis
Initial treatment of mildly active rheumatoid arthritis in adults
Initial treatment of moderately to severely active rheumatoid arthritis in adults
Treatment of rheumatoid arthritis resistant to initial DMARD therapy in adults
Use of glucocorticoids in the treatment of rheumatoid arthritis
Use of methotrexate in the treatment of rheumatoid arthritis

The following organizations also provide reliable health information.

• National Library of Medicine
  (www.nlm.nih.gov/medlineplus/arthritis.html, available in Spanish)
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
  (301) 496-8188
  (www.niams.nih.gov/Health_Info/Arthritis/default.asp)
• National Institute on Aging
  (www.nia.nih.gov/health/publication/arthritis-advice, available in Spanish)
• American College of Rheumatology
  (404) 633-3777
  (www.rheumatology.org)
• The Arthritis Foundation
  (800) 283-7800
  (www.arthritis.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Arthritis Forum
  (http://arthritis.about.com/forum)

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