Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that most commonly causes inflammation and tissue damage in joints (arthritis) and tendon sheaths, together with anemia. It can also produce diffuse inflammation in the lungs, pericardium, pleura, and the sclera of the eye, and also nodular lesions, most common in subcutaneous tissue under the skin. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility. It is diagnosed chiefly on symptoms and signs, but also with blood tests (especially a test called rheumatoid factor) and X-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues.

Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur.

Joints:
The arthritis of rheumatoid arthritis is due to synovitis, which is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness prevents their use. With time, RA nearly always affects multiple joints (it is a polyarthritis). Most commonly, small joints of the hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity.

Skin:
The rheumatoid nodule, which is often subcutaneous, is the feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both.

Lungs (fibrosis), kidneys (amyloidosis), heart (atherosclerosis, MI, stroke, pericarditis) and blood vessels (vasculitis) are also involved.


Diagnosis


X-rays:
X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, these may not show any changes in the early stages of the disease, but more advanced cases demonstrate erosions and bone resorption.

Blood tests:
When RA is clinically suspected, immunological studies are required, such as testing for the presence of rheumatoid factor (RF, a specific antibody). A negative RF does not rule out RA; rather, the arthritis is called seronegative. This is the case in about 15% of patients.

Because of this low specificity, a new serological test has been developed, which tests for the presence of so called anti-citrullinated protein antibodies (ACPAs). Like RF, this test is positive in only a proportion (67%) of all RA cases, but is rarely positive if RA is not present, giving it a specificity of around 95%.


Diagnostic criteria
The American College of Rheumatology has defined (1987) the following criteria for the classification of rheumatoid arthritis:
• Morning stiffness of >1 hour most mornings for at least 6 weeks.
• Arthritis and soft-tissue swelling of >3 of 14 joints/joint groups, present for at least 6 weeks
• Arthritis of hand joints, present for at least 6 weeks
• Symmetric arthritis, present for at least 6 weeks
• Subcutaneous nodules in specific places
• Rheumatoid factor at a level above the 95th percentile
• Radiological changes suggestive of joint erosion

At least four criteria have to be met for classification as RA.

Pathophysiology
Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.

The key pieces of evidence relating to pathogenesis are:

1. A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cell-associated protein PTPN22.
2. A link with cigarette smoking that appears to be causal.
3. A dramatic response in many cases to blockade of the cytokine TNF (alpha).
4. A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes.
5. A more or less random pattern of whether and when predisposed individuals are affected.
6. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA).

These data suggest that the disease involves abnormal B cell - T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random) epidemiology suggests that the rate limiting step in genesis of disease in predisposed individuals may be an inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation.


Treatment

There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process.
The goal of treatment is two-fold:
1) Alleviating the current symptoms, and
2) Preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked.
Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone can also have an important benefit if added to a proper specific anti-rheumatic treatment.
Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics. Treatment also includes rest and physical activity.

This is a brief article on Rheumatoid Arthritis. Some of the specifics regarding treatment will be presented in future articles on those topics (DMARDS, Pathology, etc.)

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