Rheumatoid arthritis symptoms and diagnosis

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

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 is a recognized factor that increases 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.
• 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.
• Vasculitis (inflammation of the blood vessels) may cause a wide variety of symptoms, depending upon where the inflamed blood vessels are located.

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

GENERAL MEASURES

Nonpharmacologic therapies include treatments other than medications and are the foundation of treatment for all people with rheumatoid arthritis. There are a wide variety of nonpharmacologic therapies available.

Education and counseling — Education and counseling can help you to better understand the nature of rheumatoid arthritis and cope with the challenges of this condition. You and your healthcare providers can work together to formulate a long-term treatment plan, define reasonable expectations, and evaluate both standard and alternative treatment options.

Nonpharmacologic measures such as biofeedback and cognitive behavioral therapy may help in controlling rheumatoid arthritis symptoms. These measures can reduce pain and disability and improve self-esteem. Programs on topics such as self-management skills, social support, biofeedback, and psychotherapy are offered by the Arthritis Foundation in the US (http://www.arthritis.org/local-offices/) and by similar organizations worldwide. These services are also offered by many hospitals and clinics. These programs have been shown to reduce pain, depression, and disability in people with arthritis and to allow them to gain some control over their illness.

Rest — Fatigue is a common symptom of rheumatoid arthritis. Inflamed joints should be rested, but physical fitness should be maintained as much as possible. Several studies have shown that physical fitness improved the quality of sleep, which in turn helped with fatigue. The advice of physical and occupational therapists should be sought for help with fitness programs, if joint pain or limited joint motion interferes with exercise activities.

Exercise — Pain and stiffness often prompt people with rheumatoid arthritis to become inactive. Unfortunately, inactivity can lead to a loss of joint motion, contractions, and a loss of muscle strength. Weakness, in turn, decreases joint stability and further increases fatigue.

Regular exercise can help prevent and reverse these effects [2]. Several different kinds of exercise can be beneficial, including range-of-motion exercises to preserve and restore joint motion, exercises to increase strength (isometric, isotonic, and isokinetic exercises), and exercises to increase endurance (walking, swimming, and cycling).

Exercise programs for people with rheumatoid arthritis should be designed by a physical therapist and tailored to the severity of your condition, your build, and your former activity level. A separate article discusses exercise and arthritis. (See "Patient information: Arthritis and exercise (Beyond the Basics)".)

Physical and occupational therapy — Physical and occupational therapy can relieve pain, reduce inflammation, and help preserve joint structure and function for patients with rheumatoid arthritis.

Specific types of therapy are used to address specific effects of rheumatoid arthritis:

• The application of heat or cold can relieve pain or stiffness.
• Ultrasound may reduce inflammation of the sheaths surrounding tendons (tenosynovitis).
• Passive and active exercises can improve and maintain range of motion of the joints.
• Rest and rest splinting can reduce joint pain and improve joint function.
• Finger splinting and other assistive devices can prevent deformities and improve hand function.
• Relaxation techniques can relieve secondary muscle spasm.

Physical therapy may also include a consultation with a podiatrist who can make foot orthotics (devices that ensure correct position of the foot) and supportive footwear. Occupational therapists also focus on helping people with rheumatoid arthritis to be able to continue to actively participate in work and recreational activity with special attention to maintaining good function of the hands and arms.

Nutrition and dietary therapy — People with active rheumatoid arthritis sometimes lose their appetite or are unable to eat an adequate amount of food. Dietary therapy helps to ensure that you eat an adequate amount of calories and nutrients. However, weight loss may be recommended for overweight and obese people to reduce stress on inflamed joints. (See "Patient information: Weight loss treatments (Beyond the Basics)".)

People with rheumatoid arthritis have a higher risk of developing coronary artery disease. High blood cholesterol is one risk factor for coronary disease that can respond to changes in diet. A nutritionist can recommend specific foods to eat or avoid to achieve a desirable cholesterol level. (See "Patient information: High cholesterol and lipids (hyperlipidemia) (Beyond the Basics)".)

Changes in diet have been investigated as treatments for rheumatoid arthritis. The addition of fish oils and some plant oils, such as borage seed oil, have modestly improved arthritis pain and joint swelling. However, there is no diet that can cure rheumatoid arthritis. No herbal or nutritional supplements, such as cartilage or collagen, can cure rheumatoid arthritis; these treatments can be dangerous and are not usually recommended. (See "Patient information: Complementary therapies for rheumatoid arthritis (Beyond the Basics)".)

Smoking and alcohol — Several different studies have shown that smoking is a risk factor for rheumatoid arthritis and that quitting smoking can improve disease. People who smoke need to quit completely. Assistance in quitting should be obtained, if needed. Moderate alcohol consumption is not harmful to rheumatoid arthritis, although it may increase the risk of liver damage from some drugs such as methotrexate. People should discuss the safety of alcohol use with their doctor, because recommendations depend on the medications a person is taking and on their other medical conditions. (See "Patient information: Quitting smoking (Beyond the Basics)".)

Measures to reduce bone loss — Rheumatoid arthritis causes bone loss, which can lead to osteoporosis. Bone loss is more likely in people who are inactive. The use of glucocorticoids, such as prednisone, further increases the risk of bone loss, especially in postmenopausal women. (See "Patient information: Bone density testing (Beyond the Basics)".)

Several measures can minimize the bone loss associated with steroid therapy [3]:

• Use the lowest possible dose of glucocorticoids for the shortest possible time, when possible, to minimize bone loss.
• Consume an adequate amount of calcium and vitamin D, either in the diet or by taking supplements. (See "Patient information: Calcium and vitamin D for bone health (Beyond the Basics)".)
• Use medications that can reduce bone loss, including that which is caused by glucocorticoids. (See "Patient information: Osteoporosis prevention and treatment (Beyond the Basics)".)

RHEUMATOID ARTHRITIS MEDICATIONS

Medications are the cornerstone of treatment for active rheumatoid arthritis. The goals of treatment with rheumatoid arthritis medications are to achieve remission and to prevent further damage of the joints and loss of function, without causing permanent or unacceptable side effects.

The type and intensity of rheumatoid arthritis treatment with medication depends upon individual factors and potential drug side effects. In most cases, the dose of a medication is increased until inflammation is suppressed or until drug side effects become unacceptable.

The challenge of using medications is to balance the side effects against the need to control inflammation. All patients with rheumatoid arthritis who use medications need regular medical care and blood tests to monitor for complications. If side effects occur, they can often be minimized or eliminated by reducing the dose or by switching to a different drug.

Several classes of drugs are used to treat rheumatoid arthritis: nonsteroidal antiinflammatory drugs (NSAIDs), disease modifying antirheumatic drugs (DMARDs) (which include both traditional DMARDs and biologic agents), glucocorticoids, and, if needed, pain medications.

Nonsteroidal antiinflammatory drugs — Nonsteroidal antiinflammatory drugs (NSAIDs) may be recommended to relieve pain and reduce minor inflammation. However, NSAIDs do not reduce the long-term damaging effects of rheumatoid arthritis on the joints.

NSAIDs must be taken continuously and at a specific dose to have an antiinflammatory effect. Even at the correct doses, NSAIDs must usually be taken for several weeks before their effectiveness is known. If the initial dose of NSAIDs does not improve symptoms, a clinician may recommend increasing the dose gradually or switching to another NSAID. You should not take two NSAIDs at the same time.

Many NSAIDS have significant side effects, including gastrointestinal bleeding, fluid retention, and an increased risk of heart disease. The risks need to be weighed carefully against the benefit when taking these drugs.

More detailed information about NSAIDs is available separately. (See "Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)".)

Disease-modifying antirheumatic drugs — Disease-modifying antirheumatic drugs (DMARDs) can substantially reduce the inflammation of rheumatoid arthritis, reduce or prevent joint damage, preserve joint structure and function, and enable a person to continue his or her daily activities. Although some DMARDs act slowly, they may allow you to take a lower dose of glucocorticoids to control pain and inflammation.

Drugs in this class include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. Detailed information about these medications is available in a separate topic review. 

An improvement in symptoms may require four to six weeks of treatment with methotrexate, one to two months of treatment with sulfasalazine, and two to three months of treatment with hydroxychloroquine. Even longer durations of treatment may be needed to derive the full benefits of these drugs. 

Biologic agents — Biologic agents, also known as biologics, are disease-modifying antirheumatic drugs (DMARDs) that were designed to prevent or reduce the inflammation that damages joints. Biologics target molecules on cells of the immune system, joints, and the products that are secreted in the joints, all of which can cause inflammation and joint destruction. There are several types of biologics, each of which targets a specific type of molecule involved in this process. (See "Overview of biologic agents in the rheumatic diseases".)

Biologics are often reserved for people who have not completely responded to DMARDs and for those who cannot tolerate DMARDs in doses large enough to control inflammation.

Biologics that bind tumor necrosis factor (TNF) include etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab. These are called anti-TNF agents or TNF inhibitors. There are additional biologics that target other molecules instead of TNF. These are usually used for people with arthritis that is not well-controlled with methotrexate and one of the anti-TNF agents.

Unlike DMARDs, which can take a month or more to begin working, biologics tend to work rapidly, within two weeks for some medications and within four to six weeks for others. Biologics may be used alone or in combination with other DMARDs (eg, methotrexate), NSAIDs,and/or glucocorticoids (steroids).

All biologic agents must be injected. Some can be injected under the skin by the patient, a family member, or nurse. There are others that must be injected into a vein, which is typically done in a doctor's office or clinic; this takes between one and three hours to complete.

Side effects — Biologic agents interfere with the immune system's ability to fight infection and should not be used in people with serious infections.

Testing for tuberculosis (TB) is necessary before starting anti-TNF therapy. People who have evidence of prior TB infection should be treated because there is an increased risk of developing active TB while receiving anti-TNF therapy. 

Anti-TNF agents are not recommended for people who have lymphoma or who have been treated for lymphoma in the past; people with rheumatoid arthritis, especially those with severe disease, have an increased risk of lymphoma regardless of what treatment is used. Anti-TNF agents have been associated with a further increase in the risk of lymphoma in some studies but not others; more research is needed to define this risk.

Steroids (glucocorticoids) — Glucocorticoids, also called steroids, have strong antiinflammatory effects. Drugs in this class include prednisone and prednisolone. Glucocorticoids may be taken by mouth, injected into a vein, or injected directly into a joint. Glucocorticoids quickly improve symptoms of rheumatoid arthritis such as pain and stiffness and also decrease joint swelling and tenderness.

Glucocorticoids are generally used to treat rheumatoid arthritis that severely limits a person's ability to function normally. For such people, glucocorticoid treatment may help control symptoms and preserve function until other slower-acting drugs with greater ability to prevent joint damage begin to work. They may also be used to treat flares of disease, while a person is receiving other treatments.

Side effects — Steroids have many possible side effects, including weight gain, worsening diabetes, promotion of cataracts in the eyes, thinning of bones (osteopenia and osteoporosis), and an increased risk of infection. Thus, when steroids are used, the goal is to use the lowest possible dose for the shortest period of time.

Pain relievers — Pain relievers relieve pain, but they have no effect on inflammation. Drugs in this class include acetaminophen, tramadol, and capsaicin cream or ointment. Use of narcotics like codeine, oxycodone, and hydrocodone is generally discouraged because they also have no effect on inflammation and because of the long-term nature of rheumatoid arthritis and the risk of dependence and addiction.

However, people with a badly damaged joint who cannot undergo joint replacement surgery may benefit from use of a long-acting narcotic under the supervision of a rheumatologist or pain specialist.

Treatment of flares — Flares are temporary exacerbations of rheumatoid arthritis that can occur in addition to the ongoing inflammation. In people who are already taking methotrexate or oral steroids, flares can often be controlled by increasing the doses of these drugs. Alternatively, flares can be controlled by steroids that are given by injection. Rest is often helpful during flares; hospitalization is rarely necessary.

Which rheumatoid arthritis treatment will I get? — The type of drugs that your doctor recommends will depend on how severe your arthritis is and how well you respond to the medications. If you have early, mild arthritis, your treatment may be different from someone who has more severe arthritis or whose arthritis persists despite initial treatment efforts. In general, nearly all patients with rheumatoid arthritis will receive a disease modifying antirheumatic drug (DMARD) as part of their treatment program. A different DMARD, whether one of the traditional DMARDs or a biologic agent, will be used either instead of or in addition to the initial drug, if the treatment used is judged to be inadequate. 

SURGERY

A person with end-stage rheumatoid arthritis has little or no evidence of ongoing inflammation but often has significant joint damage with deformity and loss of joint function. End-stage rheumatoid arthritis treatment includes therapies that reduce pain and slow or prevent additional changes in joint structure and function.

Patients with end-stage rheumatoid arthritis may have pain due to joint damage rather than inflammation. In this case, surgery may be recommended to replace a damaged joint