Early on, small joints such as the hands, wrists, ankles, and feet are involved. As the disease progresses, larger joints also are affected. Virtually, any joint can be involved.
How does the damage occur in RA? What happens is that various white blood cells including polymorphonuclear leukocytes, macrophages, and specific lymphocytes called T cells and B cells become hyperactive and cause inflammation.
This leads to the production of chemical messengers, called cytokines. Cytokines cause damage by attracting more inflammatory cells to the area, causing more cytokines to be produced. Cytokines promote the release of destructive enzymes that destroy cartilage and other tissues.
Since rheumatoid arthritis is a systemic illness it can lead to damage involving the brain and peripheral nervous system, skin, lungs, heart, and eyes.
Further, treatment with many of the medicines used in rheumatoid arthritis can lead to side-effects that affect the gastrointestinal system, the lungs, heart, and bones.
Synovial inflammation causes joint pain, stiffness, swelling, warmth, and redness. As inflammation progresses, the synovium becomes swollen and takes on a life of its own.
At this stage it is called pannus and invades and destroys cartilage, bone, tendons, and ligaments resulting in joint deformity and loss of mobility.
The most common symptoms are morning stiffness, joint pain and swelling, nodules under the skin in about 20% of patients, and fatigue.
The course of RA is variable but progressive if untreated.
Rheumatoid arthritis is an acquired autoimmune disease with a genetic predisposition. About 70% of patients have the genetic markers, HLA-DR4 or HLA-DR1.
Rheumatoid factors, which are antibodies to IgG, occur in 60-80% of adult RA patients. The level of rheumatoid factor in the blood seems to correlate with prognosis.
The three abnormal factors that seem to be associated with the development of RA are an environmental trigger (the exact trigger is still unknown), genetic predisposition, and a hyper normal immune response.
RA affects about 1-2% of the population (2 million people) with a female to male ratio of about 3:1. Mortality in patients with RA is increased compared with the general population. Life expectancy is reduced about 7 years in men and 4 years in women.
Causes of death include infection, malignancies, and vascular disease. There is some evidence that atherosclerosis (hardening of the arteries) is accelerated and that certain cancers such as multiple myeloma and lymphoma occur more often.
The economic impact is staggering! Direct costs are $14 billion per year in the United States. After 5 years of disease, 27% of people are disabled. After 10 years between 40 to 60% of people are disabled.
The most important part of evaluating the patient is the history and physical examination. Helpful diagnostic laboratory tests include the rheumatoid factor, erythrocyte sedimentation test (ESR), and C-reactive protein (CRP).
Imaging procedures such as magnetic resonance imaging and ultrasound are helpful. Diagnostic x-rays are of limited use.
The goals of management include: aggressive and early treatment, reduction of signs and symptoms, prevention of deformities, maintenance of joint function, and possibly... cure. While this last option is still not quite achievable, it is becoming more of a possibility.
In addition to medications, treatment of RA includes diet, exercise, joint protection, occasionally joint surgery.
The approach to RA treatment has changed dramatically in the last 5 years.
Current treatment options involving medications include:
Non steroidal anti inflammatory drugs. These help to reduce pain and improve function. They do not have an effect on the underlying disease.
Corticosteroids suppress inflammation but also have no effect on the underlying disease. Used long term they may have undesirable side effects.
Disease-modifying anti-rheumatic drugs (DMARDS) such as methotrexate, sulfasalazine (Azulfidine), leflunomide (Arava), hydroxychloroquine (Plaquenil), and cyclosporine (Sandimmune) are employed.
And most recently, biologic therapies such as etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), abatacept (Orencia), and rituximab (Rituxan)have helped tremendously.
Waiting in the wings are other drugs such as tociluzimab (Actemra), certolizumab pegol (Cimzia), golimumab, and various oral drugs called the kinase inhibitors. The outlook for RA treatment is rosy.
And new medicines are on the horizon.
For a more complete discussion of treatment, see the pages on treatment.