Rheumatoid Arthritis

September 26, 2011

Rheumatoid arthritis (RA) is an autoimmune disease in which the joints are the primary target of progressive inflammation and destruction. This disease affects about 1% of the U.S. population and is nearly three times more common in women than men. It can occur at any age and tends to increase in frequency with age. However, it most commonly begins between ages 30 and 60. There is not one particular test that can easily establish the diagnosis of Rheumatoid arthritis. Rather, the diagnosis is based on a constellation of clinical, laboratory, and x-ray findings.

Despite extensive research, the cause of Rheumatoid arthritis is still not well understood. Autoimmune diseases occur when the immune system, the body’s natural defense mechanism against infection, mistakenly identifies “self” as a target to attack. Over the years, a number of bacteria and viruses have been suspected as possible triggers for the development of Rheumatoid arthritis, but none has been consistently identified. Familial studies and studies of twins suggest that genetic factors are important in developing Rheumatoid arthritis. Certain genetic markers, if present, not only suggest susceptibility, but may also indicate how severe the disease is likely to be. However, clustering in families is not common and genetic influences alone do not explain why a particular patient develops Rheumatoid arthritis. Cigarette smoking is the only environmental factor that has been shown to be associated with the development of Rheumatoid arthritis. In summary, Rheumatoid arthritis is a process which occurs in a genetically predisposed individual as a result of a yet unidentified trigger.

The primary target of inflammation in Rheumatoid arthritis is the joint. The interior of the joint is lined by a membrane called the synovium which secretes a lubricating fluid called synovial fluid. When the synovium becomes inflammed, as occurs in Rheumatoid arthritis, certain molecules and enzymes that can damage tissue are released. These mediators of inflammation can attack cartilage, ligaments, tendons, and bones. Unchecked, the damage from this inflammation can become permanent.

Most commonly, Rheumatoid arthritis develops over a period of several weeks as a gradually progressive joint inflammation. Most often, the same joints are affected on both sides of the body. Typically, the joints involved include, the small joints of the hands and feet, wrists, elbows, shoulders, knees, and ankles. In addition, the spine in the neck may be affected. Over time, this can lead to instability of the neck with potentially serious neurologic complications. Early in the disease, the disease may initially appear asymmetric, making the diagnosis less clear. Other possible diagnoses should always be considered, such as other types of arthritis, infection, or other rheumatic diseases such as lupus.

Early on, the joint symptoms are reversible and related to ongoing inflammation. Later in the course of the disease, irreversible joint damage may occur. Patients describe morning stiffness which is due to syn-ovial inflammation. Unlike degenerative arthritis (osteoarthritis) in which this stiffness is brief (minutes) in duration, the morning stiffness associated with Rheumatoid arthritis generally lasts 1 hour or more. Upon physical examination, joints which are more superficial and easily examined, such as the small joints of the hand or the knee, may show active signs of inflammation such as warmth, swelling, or redness. Over time, if this chronic inflammation continues untreated, the lining of the joints become scarred, cartilage is destroyed, and the bony surfaces of the joints become eroded, resulting in irreversible destructive damage. At this point, joint deformities become obvious and joint function is limited. Therefore, the goal of therapy is early identification of disease and aggressive treatment of the inflammatory process in order to prevent permanent joint damage.

Rheumatoid arthritis causes problems in other organ systems as well. Initially, some individuals experience fevers, weight loss, and fatigue. Up to 50% of patients with Rheumatoid arthritis may develop rheumatoid nodules, which are firm, soft accumulations of connective tissue typically located over pressure points such as the outer surface of the forearm or the Achilles tendon. Other patients develop a diffuse skin rash as part of their Rheumatoid arthritis. Rheumatoid arthritis can also involve the heart, lungs, and neurologic system. Inflammation of the lining of the lungs (pleurisy) or the heart (pericarditis) may occur. Fluid accumulation (effusions) may affect these organs as well. These findings vary from asymptomatic to severe, and may require increased immunosuppressive therapy or drainage of the fluid.
Neurologic manifestations in Rheumatoid arthritis may occur in several ways. First, arthritis which affects the cervical spine may lead to instability, pinched nerves, and problems with movement or sensation. These symptoms gradually get worse. Because of the possibility of cervical spine instability, care should be taken to avoid any unnecessary manipulation of the neck in a patient with Rheumatoid arthritis. Prior to elective surgery, an anesthesiologist should consult with a rheumatologist regarding intubation of a patient with possible cervical instability. Rheumatoid arthritis can also affect peripheral nerves. Nerves pass through compartments, which are also occupied by synovium and tendon sheaths. If these structures become inflammed, the nerves can be compressed. This causes symptoms which change with joint position or according to the degree of inflammation. Finally, the blood vessels supplying peripheral nerves may become inflamed. This causes neurologic symptoms that occur more abruptly and are not altered with a change in position.

The American College of Rheumatology has established criteria for the diagnosis of Rheumatoid arthritis based on clinical, laboratory, and x-ray changes. Clinical criteria include prolonged morning stiffness, arthritis of multiple joints in a symmetric pattern, and rheumatoid nodules. Laboratory tests and x-rays also help confirm the diagnosis of Rheumatoid arthritis. One particular blood test, the rheumatoid factor (RF), can be found in nearly 85% of patients with Rheumatoid arthritis. If present in high titers, it may predict more severe and unremitting disease as well as an increased risk for nonjoint manifestations of the disease. This lab test alone does not make the diagnosis of Rheumatoid arthritis and in fact may be negative early on in Rheumatoid arthritis. It is also important to realize that this test may be positive in healthy individuals or in those with other autoimmune, infectious, or cancerous conditions. Blood tests which can be followed as markers of inflammation include the erythrocyte sedimentation rate (ESR), C-reac-tive protein (CRP), and platelet count. Many individuals will also have anemia (low blood count) or low albumin (protein), which are frequently seen in patients with chronic diseases. Drainage of joint fluid may be performed to assess the degree of inflammation and to rule out infections. Rarely, a biopsy of joint synovium is performed to look for pathologic features that would support (or rule out) a diagnosis of Rheumatoid arthritis.

X-rays are performed periodically throughout the course of the disease. Early changes may reveal soft tissue swelling and thinning of the bones near the joints. As the disease advances, x-rays show bony erosions, joint space narrowing, and progressive joint destruction. One of the primary goals of therapy is to delay and prevent such destructive changes. Repeated x-rays are often done to monitor response to treatment. Checking hand or foot x-rays over the course of the disease helps the rheuma-tologist to judge whether the current therapy is working.

Treatment of Rheumatoid arthritis addresses a number of important goals. From the patient’s perspective, perhaps the most important goals are improvement of joint pain and swelling and preservation of joint function. These goals are important to the physician as well, but the physician is also trying to prevent further joint damage, reduce long-term disease-related illness and death, and carefully monitor for harmful side effects of medication. In general, there are two main classes of drugs for the treatment of Rheumatoid arthritis. One group of medications focuses on controlling symptoms by decreasing pain and inflammation. The other type of medication focuses on preventing further disease progression and improving long-term outcomes.

The first category of medications includes non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxy-genase-2 (Cox-2) inhibitors, and corticosteroids. These medications are effective in the treatment of inflammation and pain but do not prevent further disease progression. It is not recommended that any of these medications be used as the only therapy for the long-term treatment of Rheumatoid arthritis.

The mainstay of therapy for long-term treatment of Rheumatoid arthritis are the disease-modifying antirheumatic drugs (DMARDs). These medications vary in their mechanisms of action but in general alter the immune system by reducing its abnormal response as well as blocking pathways involved in the inflammatory process. The choice of a DMARD depends on a number of considerations. Clearly, the degree of disease activity and severity is important. Whether the patient has other diseases or certain lifestyle behaviors (such as alcohol consumption and increased risk of liver toxicty with certain drugs) is important as well. Finally, the patient’s willingness to comply with drug monitoring and drug dosing plays a role. In general, all of the DMARD class of medications increase the risk of developing infections because they suppress the immune system. A careful evaluation of the risks and benefits of each medication should be discussed and weighed against the risks of untreated disease.

In conclusion, Rheumatoid arthritis is a disease process primarily affecting the joints but potentially involving other organ systems as well. It is diagnosed by a combination of clinical, laboratory, and radiographic findings. Treatment is individualized to each patient with the primary objectives of reducing of inflammation and preserving joint function.
See Also: Arthritis, Autoimmune disorders

Suggested Reading

  • Klippel, J. H. (Ed.). (2001). Primer on the rheumatic diseases (12th ed.). Atlanta, GA: Arthritis Foundation.
  • Ruddy, S., Harris, E. D., & Sledge, C. B. (Eds.). (2001). Kelley’s textbook of rheumatology (6th ed.). Philadelphia: W.B. Saunders.

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