Patient information: Rheumatoid arthritis symptoms and diagnosis

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Patient information: Rheumatoid arthritis symptoms and diagnosis

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Last literature review version 16.3: October 2008 | This topic last updated: July 10, 2007 (More)


INTRODUCTION — Rheumatoid arthritis is a chronic inflammatory condition. The condition can affect many tissues throughout the body, but the joints are usually most severely affected. The specific cause of rheumatoid arthritis is unknown.

Rheumatoid arthritis symptoms develop gradually, and it is difficult to precisely date the beginning of the disease. Many people have symptoms that continue, some experience complete resolution, and other experience times when joint pain, stiffness, and swelling are worse and other times when symptoms are better. However, the onset, severity, and specific symptoms of this condition can vary greatly from person to person.

This topic review discusses the risk factors, signs and symptoms, and diagnostic process for rheumatoid arthritis. A number of other topics about rheumatoid arthritis are available separately. (See "Patient information: Rheumatoid arthritis treatment" and see "Patient information: Disease modifying antirheumatic drugs (DMARDs)" and see "Patient information: Rheumatoid arthritis and pregnancy" and see "Patient information: Complementary therapies for rheumatoid arthritis").

RISK FACTORS — The specific cause of rheumatoid arthritis is not known although 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.

Gender, heredity, and genes largely determine a person's susceptibility to 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. Furthermore, the risk of arthritis is increased in women who have never been pregnant and in women who have recently given birth.

Heredity — Rheumatoid arthritis is not an inherited disease. Genes do not cause the disease, they merely increase the risk of its development. The level of this risk has been studied by the analysis of identical twins, who have identical genes. The likelihood that both twins will have rheumatoid arthritis is between 12 and 30 percent. The risk of developing rheumatoid arthritis in non-identical twins and in first-degree relatives of affected people is lower, but still increased (between 1.5 and 4 percent) compared to the population in general (about 1 percent). These studies suggest that genes increase the risk of developing rheumatoid arthritis, but not to a degree that family members of people with RA require screening tests.

Specific genes — People with specific human leukocyte antigen (HLA) genes are more likely to develop rheumatoid arthritis than people without these genes. The presence or absence of particular HLA genes also appears to predict how severe rheumatoid arthritis will be and how well it will respond to treatment. Other, as yet unidentified genes probably also affect a person's risk.

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 initiates 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. The results of studies have not always agreed, but most studies suggest that cigarette smokers have an increased risk of rheumatoid arthritis. The risk appears to be related to the duration and intensity of smoking (eg, more than 6 to 9 cigarettes per day for at least 20 years in one study). 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. Stress is extremely difficult to measure but some studies do suggest that stressful "life events" (divorce, accidents, bereavement, etc) are more common in people with RA in the six months preceding the onset of disease compared to the general population.

Diet — There is no evidence that a particular diet causes rheumatoid arthritis, although a recent claim implicated red meat. Some researchers have claimed that food intolerance in a minority of patients can make the disease worse and that elimination of such foods can help symptoms. There is also evidence that polyunsaturated fats (found in fish oils and some vegetable oils) have a weak anti-inflammatory effect.

SYMPTOMS — The symptoms of early and established rheumatoid arthritis often differ. In addition, during any stage of this condition, the symptoms can vary widely from one person to another.

Initial signs and 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. Nonspecific and often confusing symptoms may predate the characteristic symptoms of rheumatoid arthritis by months or even years. These 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 in the absence of any joint symptoms.

Occasionally, rheumatoid arthritis begins with symptoms related to inflammation of tissues other than the joints. For example, a person may experience cardiac symptoms due to pericarditis (inflammation of the tissue surrounding the heart), respiratory symptoms due to pleural effusion (collection of fluid in the chest cavity), or widely varying symptoms due to vasculitis (inflammation of blood vessels) (see "Inflammatory conditions" below).

Pattern of joints affected — The number and type of joints affected by rheumatoid arthritis can vary widely. In contrast to some other types of arthritis, rheumatoid arthritis usually affects the same joints on both sides of the body.

In the early stages of the condition, the arthritis typically affects the small joints farthest from the center of the body, especially the joints at the base of the fingers (the metacarpophalangeal or MCP joints), the joints in the middle of the fingers (the proximal interphalangeal or PIP joints), and the joints at the base of the toes (the metatarsophalangeal or MTP joints).

However, the joint inflammation of early rheumatoid arthritis may follow many different patterns; for example, it may 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 extremities, and between 20 to 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 are characterized by pain and stiffness; they may also be red, warm to the touch, and visibly swollen. Changes in the shape and stability of the joint usually occur in the later stages of rheumatoid arthritis.

The joint stiffness of rheumatoid arthritis is most bothersome in the morning and after sitting still for a period of time. Although other inflammatory conditions can cause a similar stiffness, the stiffness of rheumatoid arthritis differs because it 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.

Rheumatoid arthritis may inflame the sheaths surrounding the tendons of the hand and lead to the formation of nodules, which may restrict movement of the fingers. In severe cases, inflammation and stretching of the tendons in the hand may cause them to rupture.

Certain characteristic hand deformities can occur with long-standing rheumatoid arthritis. The fingers may develop characteristic, exaggerated profiles, called swan neck deformities and boutonniere deformities, and may drift together in the direction of the small finger. This photograph depicts ulnar drift in a person with mixed connective tissue disease, although the appearance is similar in people with RA (show picture 1). The tendons on the back of the hand may become very prominent and taught, 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; in later stages, the bones of the wrist may slip out of their joints, causing the hand to bend toward the small finger. Inflammation and stretching of the wrist tendons may cause them to rupture.
Elbow — Rheumatoid arthritis may cause inflammation of the elbow. Swelling of this joint may compress nerves that travel through the arm and 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 metatarsophalangeal (MTP) joints (the joints at the base of the toes). Tenderness of the MTP 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. Over time, changes in the structure of the joints may lead to changes in the shape of the foot.
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.
In the later stages of rheumatoid arthritis, damage to the joints of the cervical spine can cause the joints to press on the spinal cord. Spinal cord compression can cause a variety of problems, including shooting pain in the arms, loss of coordination, and difficulty controlling bowel and bladder function.

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.

The presence of rheumatoid nodules can be very helpful in diagnosing rheumatoid arthritis. However, these nodules occur in only about 30 percent of people with rheumatoid arthritis, and are usually not present early in the course.

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

Pleuropericarditis (inflammation of the tissue lining the chest cavity and surrounding the heart) may cause chest pain and difficulty breathing. (See "Patient information: Pericarditis").
Interstitial pneumonitis (inflammation of the lung that is not due to infection) may cause shortness of breath and a dry cough.
Neuropathy (abnormal nerve function) may cause numbness, tingling, or weakness.
Scleritis (inflammation of the white part of the eye) may cause vision problems.
Splenomegaly (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: Sjogren's syndrome").
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").
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.

A person with rheumatoid arthritis must have at least four of the following criteria:

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, metacarpophalangeal (MCP), or proximal interphalangeal (PIP) 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
However, these criteria are most helpful in people with established rheumatoid arthritis, and not all of these criteria are present early in the course of RA. Furthermore, these problems may be present in some people with other rheumatic conditions.

Several other medical conditions have signs and symptoms similar to rheumatoid arthritis, including other inflammatory rheumatic diseases, fibromyalgia, and osteoarthritis, as well as arthritis caused by psoriasis, infection, and gout.

In most cases, the signs and symptoms and results of diagnostic tests help to differentiate between rheumatoid arthritis and another condition. However, in some cases, it may be necessary to monitor the condition over time before a diagnosis of rheumatoid arthritis can be made with certainty.

Medical history — During a medical history, a healthcare provider will ask about the presence, duration, and pattern of joint symptoms and any other symptoms. He or she will ask how these problems have impacted a person's daily activities. It is important to mention if other family members have a history of RA or another inflammatory arthritis.

Physical examination — During a physical examination, the joints will be examined to observe their range of motion, redness, warmth, and swelling. Swelling can be a sign of an effusion (a collection of excess fluid inside the joint) or synovitis (inflammation of the joint lining). The provider will also observe the muscles to see if there are signs of muscle loss.

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

Standard blood tests — In people with rheumatoid arthritis, standard blood tests may reveal anemia, an increased number of white blood cells or platelets, or abnormal liver function.

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.

Markers of inflammation — The erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) are nonspecific markers of inflammation. A high ESR and CRP suggest the presence of inflammation, but they do not indicate the cause of this inflammation. These markers are useful for distinguishing inflammatory arthritis, such as rheumatoid arthritis, from noninflammatory arthritis, such as osteoarthritis. (See "Patient information: Features and diagnosis of osteoarthritis").

Anti-cyclic citrullinated peptide antibody test — A blood test for antibodies to cyclic citrullinated peptides (anti-CCP) is more specific than rheumatoid factor for diagnosing rheumatoid arthritis. It may be positive very early in the course of disease. The test is positive in most patients with rheumatoid arthritis.

Antinuclear antibody (ANA) test — Between 30 and 40 percent of people with rheumatoid arthritis have autoantibodies (antibodies against the body's own tissue) called antinuclear antibodies (ANAs). However, many healthy people also have a positive ANA test. (See "Patient information: Antinuclear antibodies (ANA)").

Synovial fluid analysis — Small samples of synovial fluid (the fluid around the joint) can be withdrawn and analyzed. The joint fluid of people with RA usually contains inflammatory cells and substances.

X-rays — In people with RA, x-rays can show evidence of changes in the structure of cartilage and bone. These changes show the destruction and loss of bone or cartilage that occurs as RA progresses (show radiograph 1). Although x-rays are useful for monitoring the status of rheumatoid arthritis over time, they are usually not helpful for diagnosing rheumatoid arthritis in its early stages.

About 15 to 30 percent of people with rheumatoid arthritis will have changes on x-rays in the first year of this condition. However, after the first two years of rheumatoid arthritis, more than 90 percent of people have changes on x-rays. X-rays can also help to measure bone mineral density, which is often decreased in the later stages of rheumatoid arthritis.

Magnetic resonance imaging — Magnetic resonance imaging (MRI) scans are more sensitive than x-rays for detecting the bone damage caused by rheumatoid arthritis. Therefore, MRI scans may be more effective than x-rays for detecting the early changes of rheumatoid arthritis. MRI scans are also useful for assessing changes in the synovium (the joint lining) and for assessing compression of the cervical spinal cord.

However, the cost of MRI scanning is much greater than that of plain x-rays, so MRI is not widely used to diagnose or follow the course of rheumatoid arthritis.

TREATMENT — A separate topic review is available on the treatment of rheumatoid arthritis. (See "Patient information: Rheumatoid arthritis treatment").

DISEASE COURSE — Rheumatoid arthritis often has a variable course: it can go into remission, follow a fluctuating course, or progress steadily. In most people with rheumatoid arthritis, the severity of symptoms fluctuates for weeks or months and reflects the effects of treatment. The results of some diagnostic tests are helpful for predicting the course of the condition over time and for monitoring the effectiveness of treatment.

However, even the most powerful predictors are only accurate when applied to groups of people with rheumatoid arthritis, and it is generally impossible to predict how the disease will affect a particular individual.

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 within three months after childbirth. (See "Patient information: Rheumatoid arthritis and pregnancy").

Long-term effects of RA — The inflammation of active rheumatoid arthritis can potentially damage the bones, cartilage, and other structures of the joints. The joint damage is typically cumulative and irreversible. Severe disability, requiring daily assistance by others, occurs in a minority of patients. Impairment in function, such as inability to continue full-time employment, occurs in about half.

Compared with people who do not have RA, people with rheumatoid patients are at higher risk of the following:

Heart attacks and strokes at an earlier age
Developing certain forms of cancer of the lymph glands
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. Disease-modifying treatment is strongly recommended as soon a person is diagnosed with RA, even in those who have not yet developed x-ray changes. (See "Patient information: Rheumatoid arthritis treatment").

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.


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