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AFFECTING MORE THAN 2 million Americans, rheumatoid arthritis (RA) is a chronic, progressive, disabling autoimmune disease.1 Characterized by persistent inflammation of the synovium as well as inflammation of extra-articular sites, it's the most common type of inflammatory arthritis.2
Adults with RA are seven times more likely than those without it to suffer from moderate-to-severe disability.2 Untreated or undertreated, RA can lead to earlier death, disability, or complications from the medications used to treat the disease.2
This article takes a look at what RA is, how it's diagnosed and treated, and what you can do to help patients manage the disease.
RA usually affects adults between ages 30 and 70. Women are affected two to four times more frequently than men.2 The exact etiology of RA is unknown, but genetics may play a role; siblings of people with RA are two to four times more likely to develop RA than people in the general population.1,2 Other risk factors include viral illness and moderate-to-severe periodontal disease.3 RA is found in both nonsmokers and smokers with periodontal disease, but tends to be more severe in smokers.3
Primarily an inflammatory arthritis, RA can affect numerous joints (see Joints commonly affected by RA). Most commonly affected are the metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and metatarsophalangeal (MTP) joints. The ankles, wrists, and knees are also commonly affected.2
RA places patients at risk for other diseases, including infections. This increased risk can be due to the disease, disease treatments, or a combination. For example, the risk of acquiring tuberculosis increases six to nine times in patients with RA. A rare but often fatal infection, progressive multifocal leukoencephalopathy, has been associated with rituximab, a drug used to treat RA. Some medications used to treat RA may decrease the effectiveness of routine vaccinations, such as the influenza vaccine.4
Patients with RA also have a higher risk of cardiovascular disease (CVD), including myocardial infarction and stroke. Various factors may increase the risk, including the inflammatory component of the disease, genetics, and reduced exercise due to pain and mobility limitations. However, some medications used to treat RA, especially biologics and methotrexate, appear to reduce the risk.
Depression runs high in patients with RA, occurring twice as often in those with RA than in the general population. Prolonged or severe depression interferes with a patient's quality of life.5
Another possible complication is diabetes mellitus. Factors contributing to diabetes include long-term corticosteroid therapy to combat pain and inflammation, weight gain, and decreased physical activity.
Patients with RA are vulnerable to some types of cancer, especially lymphoma. This is thought to result from both the treatment and the disease. Lymphoma is two to five times more likely in patients with RA than in the general population.4
Ten years after the diagnosis, 30% to 60% of patients with RA are disabled, with the duration of the disease correlating to the degree of disability. Along with disability comes an increase in mortality. Patients with RA have one and a half to two times the mortality risk compared with the general population, usually from CVD or infection. In general, RA patients have a life expectancy 5 to 15 years less than people without the disease.1,2,4
Prognosis varies among individuals, but some indicators can lead to a poorer prognosis. These include functional limitation, presence of comorbid conditions such as CVD or diabetes, presence of associated syndromes such as Sjogren's syndrome, positive rheumatoid factor or anticyclic citrullinated peptide (anti-CCP) antibodies, or the presence of bony erosions on X-ray.6
Signs and symptoms of RA can be subtle or go into remission and reemerge, making the disease difficult to diagnose. Patients may report fatigue, malaise, and fever along with joint pain, stiffness, and edema. The two hallmarks of RA are morning stiffness in joints lasting an hour or more and symmetric edema of the small joints of the hands and feet. The American College of Rheumatology (ACR) has developed guidelines to help healthcare providers diagnose RA (see Diagnostic criteria for RA).2
During the physical exam, the healthcare provider will assess both the small joints of the hands and feet and the larger joints for edema and pain. The simple squeeze test, which is similar to a handshake, places pressure on the MCP or MTP joints of the hands or feet. A patient with edema will feel pain, an indication of early synovitis or swelling within the joint. Be cautious when shaking the hand of anyone who's complaining of joint swelling and pain in his or her hands and fingers.2 For information on how to perform the squeeze test, visit http://www.go-training.net/rheum/exam.
The healthcare provider will order radiographs and lab studies for the patient suspected of having RA. X-rays of the hands, fingers, wrists, ankles, feet, and toes help the healthcare provider evaluate joint health and find evidence of joint or bony erosion, which would indicate advanced disease.
Common lab tests include rheumatoid factor, anti-CCP, antinuclear antibody, and C-reactive protein (CRP). Anti-CCP is more specific than rheumatoid factor for RA but is found less often in patients with RA. A positive anti-CCP confirms the diagnosis of RA, but a patient who doesn't have a positive anti-CCP might have the disease. The other tests are less specific and often normal.2
The three main treatment goals for RA are to eliminate pain, prevent joint damage, and prevent loss of function. Complete remission may be possible if the disease is treated early and aggressively.1,7
Selection of a treatment plan is based on:
* disease activity
* severity of pain, edema, and function limitations
Function and pain are subjective measures, making these aspects difficult to quantify. Assessment scales can be used to assess disease activity and severity, and are often used to guide treatment, follow-up, and change in treatment regimens. Assessment scales have both a provider section and a patient assessment section.
For one of the more common scales, the ACR 20, the provider counts the number of edematous and tender joints and obtains a CRP value. The patient answers health assessment questions related to function and uses a visual analog scale to assess pain.1,6,7
The group of drugs used to treat RA is referred to as disease-modifying antirheumatic drugs (DMARDs), which are broken down into nonbiologics and biologics. DMARDs are used to interfere with the immune system. Nonbiologics are indirect and nonspecific; biologics interfere with a specific aspect of the immune system. The ultimate goal of DMARDs is to depress the overactive immune system, decreasing inflammation and progression of the disease process.4
Nonbiologics indirectly block the immune system through their individual drug actions; each drug acts differently because each is a different class of drug, such as a folic acid inhibitor or an antimalarial drug. On the other hand, biologics directly affect the immune system by interfering with a specific mediator of the immune system, such as tumor necrosis factor (TNF), interleukins, or lymphocytes.4
Either class of drug is appropriate as first-line treatment. The decision is based on the patient's disease severity, cost, patient preference, and ease of administration. Early treatment-within the first 3 months after diagnosis-is the goal to achieve remission.1,6,7
The major nonbiologic DMARD used is methotrexate. Other nonbiologics, which are given orally, include sulfasalazine, hydroxychloroquine, and leflunomide. In general, most nonbiologics are well tolerated, but they can affect liver and bone marrow functioning and depress the immune system.
First used as a chemotherapeutic agent in the late 1940s, methotrexate was approved to treat RA in 1972 and is still considered the gold standard. Because they may have impaired immune and liver function, patients with RA are screened for tuberculosis and hepatitis B and C before being prescribed methotrexate. Common adverse reactions include severe mouth ulcers, nausea, diarrhea, rash, alopecia, noncardiac chest pain, and fatigue. Potential toxic reactions include toxicity of the pulmonary, hepatic, and hematologic systems. To avoid complications, the patient must undergo lab tests (complete blood cell count and chemistry panel that includes liver function tests) every three months.1,6,7
Biologics are given subcutaneously or intravenously. This can interfere with patients' adherence to the treatment plan because they may need to make frequent office or clinic visits for therapy, or in some cases, learn to perform self-injections. Teach patients who perform self-injections to rotate injection sites to decrease keloids, abscesses, and other site reactions.1,6,7
Biologics include medications that block TNF-alpha, a mediator often responsible for inflammation. TNF inhibitors include adalimumab, certolizumab pegol, etanercept, golimumab, and infliimab. Other biologics interfere with interleukins (anakinra) and B- or T-cell lymphocytes (rituximab [B-cells] and abatacept [T-cells]).1,6,7
Because biologics interact directly with the immune system, adverse reactions include potentially fatal infections. The pathogens can be viral, bacterial, or fungal and cause such serious infections as hepatitis, tuberculosis, and sepsis. Rare adverse reactions include the development of lupus and multiple sclerosis.1,6,7
Patients who already have compromised immune systems (active or recurrent cancer, untreated infections, active or latent tuberculosis) aren't good candidates for these drugs. Patients on biologic therapy shouldn't receive live virus vaccines because they won't be able to mount a full immune response to the virus, leaving them at risk for developing the infection.1,6,7 In rare circumstances, patients taking biologics have developed heart failure. Use of biologics in a patient with heart failure could potentially worsen a preexisting illness.7
The pain of RA often leads to disability. Many of the medications used to treat RA, especially the nonbiologics, don't take full effect for 3 to 6 months. During those months, poorly managed pain can be disabling for the patient. Adjunctive medications, such as steroids and nonsteroidal anti-inflammatory drugs (NSAIDs), can help relieve pain.
The corticosteroid prednisone is often prescribed right after RA diagnosis to manage pain while the treatment regimen is being fine-tuned. Prednisone can relieve pain and inflammation in 24 to 48 hours. However, it can also mask the severity of the disease because of its anti-inflammatory properties. Weight gain, hypertension, dyslipidemia, cataracts, skin atrophy, and acne are common adverse reactions to prednisone. It should be prescribed for the smallest effective dose for the least amount of time.1,6,7
NSAIDs are often used for short-term control of pain and inflammation, but continual use is associated with a higher incidence of myocardial infarction, stroke, gastrointestinal bleeding, and renal disease, including renal failure.1,6,7
Providing detailed information about RA can help your patients get the most out of their treatment. Let them know the basics of the disease, including how it affects their everyday activities, possible complications, and treatment options.
Advise patients taking methotrexate to avoid alcohol, which can increase hepatic toxicity. Folic acid, often used to decrease the adverse reactions associated with methotrexate, can also interfere with the effectiveness of the drug. Remind them that methotrexate may decrease the immune system's response to vaccinations such as influenza and pneumonia. Because of the drug's potential for toxic effects, warn patients not to double up on missed doses.1,6,7
Tell patients to alert all their healthcare providers that they're taking methotrexate because numerous medications interact with the drug. Methotrexate is classified as pregnancy category X, which means it's known to cause birth defects. If appropriate, instruct women to use reliable contraception and to notify their healthcare provider immediately if they suspect they've become pregnant. Patients who are pregnant or trying to get pregnant should not take the drug.1
Lifestyle changes in diet and exercise are important for patients with RA. Advise them to eat a diet rich in grains, fruits, vegetables, and omega-3 fatty acids. Talk to them about maintaining a proper body weight and provide a list of the risk factors for dyslipidemia, hypertension, and diabetes. These diseases may develop as a complication of corticosteroid therapy or from a poor diet or inactivity related to pain. Excess body weight not only increases the risk of CVD but also adds stress to already painful joints. Encourage patients to exercise to keep joints flexible, maintain or improve balance and strength, and ward off depression.
Current research shows that gum disease can increase the development of TNF-alpha.3 Advise patients to brush and floss twice daily and to schedule biannual dental checkups and cleanings.
Encourage patients who smoke to stop and provide them with guidance on where to go for help. Encourage yearly influenza vaccinations.7
RA can be a devastating diagnosis and lead to a decreased life expectancy as well as disabling pain and loss of function. But with treatment, the disease can be managed and may go into remission. You play a major role in educating patients about RA, including treatment strategies and lifestyle changes that can help them prevent complications. With a good understanding of their disease, appropriate care, and follow-up, many RA patients lead fulfilling and productive lives.
According to ACR guidelines, the first four criteria must be present for at least 6 weeks:
* morning stiffness in joints for about 1 hour
* three or more joint areas demonstrating soft tissue swelling or fluid (wrist, PIP, MCP, elbow, knee, ankle, MTP)
* edema of wrist, MCP, or PIP joints
* symmetric arthritis
* positive rheumatoid factor (affects 95% of patients)
* subcutaneous rheumatoid nodules on joints, bony prominences, or extensor surfaces
* radiographic changes in hands or wrists.
1. Costenbader KH, Kountz DS. Treatment and management of early RA: a primary care primer. J Fam Pract. 2007;56(7 suppl):S1-S8. [Context Link]
2. Weinblatt ME, Kuritzky L. RAPID: Rheumatoid Arthritis. J Fam Pract. 2007;56(4 suppl):S1-S8. [Context Link]
3. Editor: Unhealthy gums linked to development of rheumatoid arthritis. Press Release: American College of Rheumatology. 2009. http://www.rheumatology.org/press/2009/2009_am_17.asp. [Context Link]
4. Bingham III CO, Miner MM. Treatment, management, and monitoring of established rheumatoid arthritis. J Fam Pract. 2007;56(10 suppl Rapid):S1-S7. [Context Link]
5. Sinclair VG, Wallston KA. Psychological vulnerability predicts increases in depressive symptoms in individuals with rheumatoid arthritis. Nurs Res. 2010;59(2):140-146. [Context Link]
6. Deodhar AA, Yamauchi PS, Ness S. Navigating an emerging crossroad: patient, provider and payer considerations in biologic therapies for immune-mediated diseases. Prime. 2008. [Context Link]
7. Saag KG, Teng GG, Patkar MN, et al. American College of Rheumatology 2008 recommendations for use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis & Rheumatism. 2008;59(6):762-784. [Context Link]
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