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During a remission, they can disappear, or they can be mild. However, during a flare, they can be severe. Some people appear to have genetic factors that make it more likely. One theory is that bacteria or a virus triggers RA in people who have this genetic feature. In RA, the immune system's antibodies attack the synovium, which is the smooth lining of a joint. When this happens, pain and inflammation result. Inflammation causes the synovium to thicken. Eventually, if left untreated, it can invade and destroy cartilage — the connective tissue that cushions the ends of the bones.

The tendons and ligaments that hold the joint together can also weaken and stretch. The joint eventually loses its shape and configuration.

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

The damage can be severe. People who have obesity with RA also have a higher risk of diabetes and high blood pressure. The joint damage that occurs with RA can make it difficult to perform daily activities.

Innovations in Rheumatoid Arthritis Treatment - Brigham and Women's Hospital

RA can also be unpredictable. Often, a person does not know when a flare will happen. There is also a higher risk of developing the following conditions:. Carpal tunnel syndrome : This is a type of nerve damage that stems from compression and irritation of a nerve in the wrist. Symptoms include aching, numbness, and tingling in the fingers, thumb, and part of the hand.

Inflammation : This can affect the lungs, heart, blood vessels, eyes and other parts of the body. Tendon rupture : Inflammation in the tendons can lead to rupture, especially on the backs of the fingers. Cervical myelopathy : Dislocation of the joints in the neck or cervical spine can add pressure to the spinal cord.

Rheumatoid arthritis | Causes, symptoms, treatments

This can result in decreased mobility and pain on movement. As RA progresses, the risk of cervical myelopathy increases. Vasculitis : Inflammation of the blood vessels can cause them to weaken, thicken, narrow and scar. This can affect blood flow to tissues and organ function may be affected. Susceptibility to infections : There is a higher risk of developing colds, flu , pneumonia , and other diseases, especially if the person is taking immunosuppressant medications to manage RA.

People with RA should ensure their vaccinations, such as flu jabs, are up-to-date. In its early stages, it may be difficult for a doctor to diagnose RA as it can resemble other conditions. However, early diagnosis and treatment are essential to slow the progression of the disease. The CDC recommend diagnosis and an effective treatment strategy to begin within 6 months of the onset of symptoms.

A doctor will look at the person's clinical signs of inflammation and ask how long they have been there and how severe the symptoms are. They will also carry out a physical examination to check for any swelling, or functional limitations, or deformity. Erythrocyte sedimentation rate ESR or sed rate : This test assesses levels of inflammation in the body. It measures how fast red blood cells in a test tube separate from blood serum over a set period.

If the red blood cells settle quickly as sediment, inflammation levels are high. This test is not specific for RA and is a useful test for other inflammatory conditions or infections. A higher CRP level suggests that there is inflammation in the body. Anemia : Many people with RA also have anemia. Anemia happens when there are too few red blood cells in the blood. Red blood cells carry oxygen to the tissues and organs of the body. Rheumatoid factor : If an antibody known as rheumatoid factor is present in the blood, it can indicate that RA is present.

However, not everyone with RA tests positive for this factor. An X-ray or MRI of a joint can help a doctor identify what type of arthritis is present and monitor the progress of RA over time. If a person receives a diagnosis of RA, the doctor may refer them to a specialist known as a rheumatologist, who will advise on treatment options. Options include medications, physical therapy , occupational therapy, counseling, and surgery.

Examples include Advil, Motrin, and Aleve. Long-term use and high doses can lead to side effects, such as bruising, gastric ulcers, high blood pressure, and kidney and liver problems. Corticosteroids : These medications reduce pain and inflammation and may play a role in slowing down joint damage, but they cannot cure RA.

Relief is usually rapid, but the effect is variable. It can last a few weeks or months, depending on the severity of symptoms. Corticosteroids can help with acute symptoms or short-term flare-ups. Long-term use of corticosteroids can have serious side effects. These include cataracts , osteoporosis , glaucoma , diabetes mellitus, and obesity. DMARDs can slow the progression of the RA and prevent permanent damage to the joints and other tissues by interfering with the overactive immune system. It is most effective if a person uses it in the early stages, but it can take from 4 to 6 months to fully experience the benefits.

Examples include leflunomide Arava , methotrexate Rheumatrex, Trexall , sulfasalazine Azulfidine , minocycline Dynacin, Minocin , and hydroxychloroquine Plaquenil. Side effects can include liver damage and immune-related problems, such as bone marrow suppression, and a higher risk of severe lung infections.

Other types of immunosuppressants include cyclosporine Neoral, Sandimmune, Gengraf , azathioprine Imuran, Azasan , and cyclophosphamide Cytoxan. The human body produces tumor necrosis factor-alpha TNF-alpha , an inflammatory substance.

TNF-alpha inhibitors prevent inflammation. They can reduce pain, morning stiffness, and swollen or tender joints. People usually notice an improvement 2 weeks after starting treatment. Examples include Enbrel , infliximab Remicade and adalimumab Humira. An occupational therapist can help the individual learn new and effective ways of carrying out daily tasks.

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This can minimize stress to painful joints. For example, a person with painful fingers might learn to use a specially devised gripping and grabbing tool. When a flare-up occurs, the person should rest as much as possible. Over-exerting swollen and painful joints can make the symptoms worse. During times of remission, when symptoms are mild, the individual should exercise regularly to boost their general health and mobility and to strengthen the muscles around the joint.

Following a varied diet with plenty of fresh fruits and vegetable can help a person to feel better and maintain a healthy weight. Cold treatment can dull pain and reduce muscle spasms, but people with poor circulation or numbness should not use cold remedies. Finding ways to relieve mental stress may help control pain. Examples include meditation, guided imagery, deep breathing, and muscle relaxation. Some people with RA use the following, but there is little scientific evidence to confirm that they work:. RA is a painful and chronic condition that can cause joint damage and make it difficult for a person to carry out their daily tasks.

Anyone who experiences pain and swelling in two or more joints should see a doctor, as early treatment can reduce the risk of long-term problems. Article last reviewed by Tue 16 October Visit our Rheumatoid Arthritis category page for the latest news on this subject, or sign up to our newsletter to receive the latest updates on Rheumatoid Arthritis. All references are available in the References tab. Complications: Rheumatoid Arthritis. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved.

In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents.

Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities.

Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management. Rheumatoid arthritis RA is the most common inflammatory arthritis, with a lifetime prevalence of up to 1 percent worldwide. In a large U. Patients with inflammatory joint disease should be referred to a rheumatology subspecialist, especially if symptoms last more than six weeks.

In persons with RA, combination therapy with two or more disease-modifying antirheumatic drugs is more effective than monotherapy. However, more than one biologic agent should not be used at one time e. A guided exercise program can improve quality of life and muscle strength in patients with RA.


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Cardiovascular disease is the main cause of mortality in persons with RA; therefore, risk factors for coronary artery disease should be addressed in these patients. Like many autoimmune diseases, the etiology of RA is multifactorial. Genetic susceptibility is evident in familial clustering and monozygotic twin studies, with 50 percent of RA risk attributable to genetic factors. RA is characterized by inflammatory pathways that lead to proliferation of synovial cells in joints.

Subsequent pannus formation may lead to underlying cartilage destruction and bony erosions.

Why Your RA Went Into Remission, but Relapsed

Overproduction of proinflammatory cytokines, including tumor necrosis factor TNF and interleukin-6, drives the destructive process. Older age, a family history of the disease, and female sex are associated with increased risk of RA, although the sex differential is less prominent in older patients. Pregnancy often causes RA remission, likely because of immunologic tolerance. Patients with RA typically present with pain and stiffness in multiple joints.

The wrists, proximal interphalangeal joints, and metacarpophalangeal joints are most commonly involved. Morning stiffness lasting more than one hour suggests an inflammatory etiology. Boggy swelling due to synovitis may be visible Figure 1 , or subtle synovial thickening may be palpable on joint examination. Patients may also present with more indolent arthralgias before the onset of clinically apparent joint swelling. Systemic symptoms of fatigue, weight loss, and low-grade fever may occur with active disease.

Boggy swelling in proximal interphalangeal and metacarpophalangeal joints more prominent on patient's right hand in a patient with new-onset rheumatoid arthritis. Note that with joint swelling, the skin creases over the proximal interphalangeal joints become less apparent. The criteria do not include presence of rheumatoid nodules or radiographic erosive changes, both of which are less likely in early RA.

Symmetric arthritis is also not required in the criteria, allowing for early asymmetric presentation. One large joint. Two to 10 large joints. Four to 10 small joints with or without involvement of large joints. In addition, patients with erosive disease typical of RA with a history compatible with prior fulfillment of the criteria should be classified as having RA.

Patients with long-standing disease, including those whose disease is inactive with or without treatment , who, based on retrospectively available data, have previously fulfilled the criteria should be classified as having RA. If it is unclear about the relevant differential diagnoses to consider, an expert rheumatologist should be consulted. Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are excluded from assessment.

Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement. When rheumatoid factor information is only available as positive or negative, a positive result should be scored as low positive for rheumatoid factor. Ann Rheum Dis. In addition, Dutch researchers have developed and validated a clinical prediction rule for RA Table 2. Distribution of affected joints patients may receive points for more than one item.

Small joints of hands or feet. Upper extremities. Upper and lower extremities. Four to Number with RA. Number without RA. Likelihood ratio. Percentage with RA at one year. A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis. Arthritis Rheum. Autoimmune diseases such as RA are often characterized by the presence of autoantibodies. Rheumatoid factor is not specific for RA and may be present in patients with other diseases, such as hepatitis C, and in healthy older persons. Anti-citrullinated protein antibody is more specific for RA and may play a role in disease pathogenesis.

Baseline complete blood count with differential and assessment of renal and hepatic function are helpful because the results may influence treatment options e. Mild anemia of chronic disease occurs in 33 to 60 percent of all patients with RA, 20 although gastrointestinal blood loss should also be considered in patients taking corticosteroids or NSAIDs. Methotrexate is contraindicated in patients with hepatic disease, such as hepatitis C, and in patients with significant renal impairment. Hepatitis B reactivation can also occur with TNF inhibitor use.

Skin findings suggest systemic lupus erythematosus, systemic sclerosis, or psoriatic arthritis. Polymyalgia rheumatica should be considered in an older patient with symptoms primarily in the shoulder and hip, and the patient should be asked questions related to associated temporal arteritis.

Chest radiography is helpful to evaluate for sarcoidosis as an etiology of arthritis. Patients with inflammatory back symptoms, a history of inflammatory bowel disease, or inflammatory eye disease may have spondyloarthropathy. Persons with less than six weeks of symptoms may have a viral process, such as parvovirus.

Recurrent self-limited episodes of acute joint swelling suggest crystal arthropathy, and arthrocentesis should be performed to evaluate for monosodium urate monohydrate or calcium pyrophosphate dihydrate crystals. The presence of numerous myofascial trigger points and somatic symptoms may suggest fibromyalgia, which can coexist with RA. To help guide diagnosis and determine treatment strategy, patients with inflammatory arthritis should be promptly referred to a rheumatology subspecialist.

Medications for RA

After RA has been diagnosed and an initial evaluation performed, treatment should begin. Recent guidelines have addressed the management of RA, 21 , 22 but patient preference also plays an important role. There are special considerations for women of childbearing age because many medications have deleterious effects on pregnancy. Goals of therapy include minimizing joint pain and swelling, preventing deformity such as ulnar deviation and radiographic damage such as erosions , maintaining quality of life personal and work , and controlling extra-articular manifestations.

Methotrexate is recommended as the first-line treatment in patients with active RA, unless contraindicated or not tolerated.

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Sulfasalazine Azulfidine or hydroxychloroquine Plaquenil is recommended as monotherapy in patients with low disease activity or without poor prognostic features e. Leflunomide Arava. Hydroxychloroquine Plaquenil. Sulfasalazine Azulfidine. Minocycline Minocin. Drug-induced lupus erythematosus, Clostridium difficile colitis.

Gold sodium thiomalate. Penicillamine Cuprimine. Cyclosporine Sandimmune. Adalimumab Humira. Certolizumab pegol Cimzia. Etanercept Enbrel. Golimumab Simponi. Infliximab Remicade. Abatacept Orencia. Anakinra Kineret. Rituximab Rituxan. Infusion reaction, opportunistic infection, progressive multifocal leukoencephalopathy. Tocilizumab Actemra. Information from reference Combination therapy with two or more DMARDs is more effective than monotherapy; however, adverse effects may also be greater.

If TNF inhibitors are ineffective, additional biologic therapies can be considered. Simultaneous use of more than one biologic therapy e.

Drug therapy for RA may involve NSAIDs and oral, intramuscular, or intra-articular corticosteroids for controlling pain and inflammation. DMARDs are the preferred therapy. Dietary interventions, including vegetarian and Mediterranean diets, have been studied in the treatment of RA without convincing evidence of benefit. Results of randomized controlled trials support physical exercise to improve quality of life and muscle strength in patients with RA.

Remission is obtainable in 10 to 50 percent of patients with RA, depending on how remission is defined and the intensity of therapy. After the disease is controlled, medication dosages may be cautiously decreased to the minimum amount necessary. Patients will require frequent monitoring to ensure stable symptoms, and prompt increase in medication is recommended with disease flare-ups. Joint replacement is indicated when there is severe joint damage and unsatisfactory control of symptoms with medical management.

Long-term outcomes are good, with only 4 to 13 percent of large joint replacements requiring revision within 10 years. Although RA is considered a disease of the joints, it is also a systemic disease capable of involving multiple organ systems. Extra-articular manifestations of RA are included in Table 4. Present in 30 to 50 percent of persons with RA on autopsy, rarely leads to tamponade. May resemble bronchiolitis obliterans with organizing pneumonia, idiopathic pulmonary fibrosis, patient may also have pulmonary arterial hypertension.

Poor prognosis, increased mortality, rare but occurs with severe RA i. Information from references 1 , 2 , and Patients with RA have a twofold increased risk of lymphoma, which is thought to be caused by the underlying inflammatory process, and not a consequence of medical treatment. Biologic DMARDs, methotrexate, and leflunomide should not be initiated in patients with active herpes zoster, significant fungal infection, or bacterial infection requiring antibiotics. Affects up to 40 percent of patients with RA, can also be caused by corticosteroid use. Lung cancer. Skin cancer. Patients with RA live three to 12 years less than the general population.

The relatively new biologic therapies may reverse progression of atherosclerosis and extend life in those with RA. Data Sources: A PubMed search was completed in Clinical Queries using the key terms rheumatoid arthritis, extra-articular manifestations, and disease-modifying antirheumatic agents. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Search date: September 20, Already a member or subscriber? Log in. University School of Medicine. Address correspondence to Amy M.

Concord St. Reprints are not available from the author. Etiology and pathogenesis of rheumatoid arthritis. Kelley's Textbook of Rheumatology. Philadelphia, Pa. Bathon J, Tehlirian C. Rheumatoid arthritis clinical and laboratory manifestations. Primer on the Rheumatic Diseases. New York, NY: Springer; — Current risk factors for work disability associated with rheumatoid arthritis.