What Is Rheumatoid Arthritis?
Risk Factors
Why Your Sex Matters
Symptoms
Diagnosis
Treatment
Future Approaches to Rheumatoid Arthritis Treatment

What Is Rheumatoid Arthritis?
More than two million Americans—about 75 percent of them women—are affected by rheumatoid arthritis (RA), a chronic inflammation of the lining of the joints (synovium). Although it can occur at any age, women typically first notice symptoms between the ages of 30 and 50. RA is the most common rheumatic autoimmune disease and can lead to permanent joint damage, and can cause chronic pain, loss of function, and disability. RA can also be a systemic disease, affecting other parts of the body.

Risk Factors
RA appears to be caused by a combination of genetic vulnerability, environmental triggers, and hormonal influences. People with the genetic marker, a portion of DNA that is used to identify an individual disease or trait, known as HLA-DR4, appear to have an increased risk of developing RA and of having more severe disease. Some of the suspected environmental triggers include Epstein-Barr virus and bacteria including streptococci (which causes strep throat and rheumatic fever), salmonella (which causes food poisoning), Escherichia coli (E. coli, which causes urinary tract infections), Helicobacter pylori (which causes stomach ulcers),and Borrelia burgdorferi (which causes Lyme disease). Cigarette smoking is also linked to RA.

Why Your Sex Matters
While women are two to three times more likely to get RA than men, men tend  to be affected more severely. Studies show that women who have never had a child are twice as likely to develop RA as women who have. The disease often improves during pregnancy (when estrogen levels are high), but worsens after delivery (when estrogen levels drop). The peak age for RA appears to be after age 40, when estrogen levels are fluctuating or declining. Recent research suggests that if RA is diagnosed after menopause, it may progress at a faster rate. This has spurred research into the role that estrogen may play in RA; some scientists are studying whether oral contraceptives might be protective.

Women with RA may have reduced fertility, which can predate their diagnosis. Some drug treatments used for RA can also affect fertility. Menopausal symptoms in women with RA can be treated with low-dose estrogen, but hormone therapy needs to be individualized (as it does for any menopausal woman).

The risk of premature atherosclerosis (thickening of artery walls by cholesterol-laden plaques) and coronary artery disease is greater among women with RA. Some research indicates that women under age 50 with RA have three times the risk of death from heart attack and congestive heart failure as healthy women of the same age. Corticosteroids such asprednisone, one of the mainstays of RA therapy, can also increase cholesterol and the risk of diabetes, infections, and osteoporosis. Women taking corticosteroids may need bone-building drugs or cholesterol-lowering medications. In addition, RA has been linked to low bone density independent of corticosteroid therapy.

Symptoms 
The first symptoms of RA may include swelling, stiffness (often worse in the morning), and general aching of the joints. RA affects joints on both sides of the body, in contrast to osteoarthritis, a disease of wear and tear, that may strike joints in one area. The joints affected by RA also may be warm or red. Other common symptoms are fatigue, weakness, muscle pain, and depression.

In 50 percent of women, symptoms come on gradually and can wax and wane. As the disease progresses, inflamed cells in the joint release enzymes that can digest bone and cartilage, often causing the joint to lose its shape and alignment, and increasing pain and loss of movement. Early diagnosis and treatment are important in minimizing joint destruction, so it is essential to see a doctor if tell-tale symptoms persist for a number of weeks.

Around 20 percent of women with RA may develop raised, firm lumps just under the skin known as rheumatoid nodules. These nodules often occur in areas where there is repeated pressure on the skin, such as the elbows. Because RA can be systemic, these nodules may arise in the eyes, heart, or lungs.

Up to half of women with RA may develop inflammation in the lining of the lungs (pleurisy), making it painful to take a deep breath. Inflammation may also develop around the sac enclosing the heart (pericarditis); symptoms include chest pain, dry cough, and fever. Even blood vessels may become inflamed in RA; a sign of this vasculitis can be tiny broken blood vessels in the nail bed.

Diagnosis
Doctors may need to perform several tests to diagnose RA properly. The work-up will most likely include a complete medical history, physical exam, and lab tests and X-rays. During the physical exam, your doctor will look forevidence of joint swelling, tenderness, redness, misalignment, or loss of motion. Expect to describe your pain, including the times of day it is most and least severe. Blood tests include a test for an antibodycalled rheumatoid factor (RF); approximately 70 to 80 percent of people with RA have positive tests for rheumatoid factor (but it may not be detected early on in RA).

It is important to note that RF can be present in other conditions (including lupus and even infections), so testing positive is only one factor in making a diagnosis. Other blood tests look for evidence of inflammation, including an erythrocyte sedimentation rate (ESR or SEDrate), which measures the speed at which red blood cells fall to the bottom of a test tube, and C-reactive protein (CRP), which is elevated with systemic inflammation. A complete blood count may reveal anemia, alow red blood cell count, which often occurs in RA. X-rays are used to determine the degree of joint erosion, cartilage loss, and joint distortion.

Treatment 
Your doctor will prescribe treatments to attack RA on several fronts: to relieve pain and reduce inflammation, and to stop or slow joint damage. The choice of medications takes into account how severe your symptoms are and how far the disease has progressed. Nonsteroidal anti inflammatory drugs (NSAIDs) are commonly used to combat pain. These include aspirin and its chemical cousins, ibuprofen and naproxen, diclofenac, andindomethacin, and newer NSAIDs, called COX-2 inhibitors. However, COX-2 drugs carry an increased risk of heart attack and stroke and should not be used if you have or are at increased risk for cardiovascular disease. Recent studies show that all NSAIDs also carry slight cardiovascular risks and should not be used at high doses for prolonged periods.)

Corticosteroids such as prednisone are used to combat inflammation and modulate immune over-reactivity. Disease modifying antirheumatic drugs (DMARDs), including methotrexate and leflunomide, may be used to slow joint destruction. The newest DMARDs are “biologic” agents that inhibit the cytokines that promote inflammation and joint destruction.These include the TNF α blockers.

Joint replacement surgery is often needed for RA patients with severely damaged joints. Just about any joint in the body can now be replaced, and the surgery dramatically improves function and pain. Exercise and stress reduction are important for RA patients. Patients and their health care providers are turning increasingly to alternative and complementary therapies such as massage and acupuncture.

Future Approaches to Rheumatoid Arthritis Treatment
Researchers are looking at agents that block the processes by which arthritis begins. One strategy being tested is the use of cancer drugs, such asrituximab, to selectively destroy B cells, which contribute to the disease process of RA. Another biological drug being tested for RA, alefacept, targets specific T cells.

Stem cell transplantation is another novel therapy under study. Stem cells are primitive cells in the bone marrow that can multiply into specific blood cells. In this experimental treatment, a patient’s immune system is destroyed with high doses of chemotherapy drugs and then reconstituted with stem cells from the person’s own red blood cells (autologous stem cells).

Studies are also being done on new markers that could be used to diagnose RA earlier, before joint destruction has begun (or perhaps in women at high risk before the disease process is fully underway). One such experimental test looks for autoantibodies, called cycliccitrullinated peptides (CCP); one study found that 93 percent of those who tested positive for CCPs went on to develop RA after three years, but only 25 percent of those who tested negative developed RA.

Return to Autoimmunity Chapter Table of Contents
Continue to Next Section: Autoimmune Thyroid Disease

You can download the entire “Savvy Woman Patient” chapter on Autoimmunity as a PDF.