Rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disorder of autoimmune origin that principally attacks the joints, producing an inflammatory synovitis.

Synovitis is the inflammation of the synovial membrane, which is the connective tissue that line a joint. In rheumatoid arthritis, synovial tissues proliferate unchecked and result in stretching of tendons and ligaments and bony destruction with resultant deformities and disability.

The most common presentation of rheumatoid arthritis is insidious pain, swelling and stiffness of the wrist and the small joints of the hands and feet, although it may also affect the shoulders or the knees.

Rheumatoid arthritis is considered an autoimmune disease with the development of chronic inflammation as a result of defective self-tolerance, leading to tissue damage.

In addition to the joints, it may occasionally affect other parts of the body.

The causes of rheumatoid arthritis remain unknown.

Some proteins (markers) located on the surface of the cells, which may be inherited, seem to be related with the predisposition to suffer the disease.

The strongest known association genes are those related to the immune response, mainly the gene HLA-DRB1 located on chromosome 6 (6p21.32).

Rheumatoid arthritis affects 0.5 - 1% of the adult population worldwide.

It is approximately three times more common in women than men (female: male, 3:1).

Although rheumatoid arthritis may present at any age, the typical age of onset in women is in the childbearing years (20 to 40 years old) and in men in the sixth to eighth decade.

Smoking is described as a risk factor.

At onset, it characteristically affects small to medium joints (finger, toes and wrist joints). It presents with pain, stiffness, and swelling in multiple joints with a reduced range of motion.

Later, it may impact the knees, elbows, ankles, hip and shoulders.

As the disease progresses, joint laxity, subluxation, and cartilage degradation develop.

In late stages, joint fibrosis and soft tissue contractures may predominate.

Rheumatoid arthritis may be associated with systemic symptoms like:

• Fever
• Fatigue
• Anorexia or weight loss

The most common features for a diagnosis of rheumatoid arthritis are:

• Joint symptoms must be present for at least 6 weeks
• Prolonged morning stiffness
• Rheumatoid nodules (firm lumps under the skin)

After the initial evaluation a blood test and x-ray studies are necessary to confirm the diagnosis.

A blood test usually reveal:

• Elevated erythrocyte sedimentation rate (ESR)
• Elevated C-reactive protein (CRP)
• A positive rheumatoid factor (RF) test
• Presence of anti–cyclic citrullinated peptide (CCP) antibodies, that is the most specific lab finding

Radiographs of rheumatoid joints may demonstrate bony erosions. Early erosions typically occur at the margins of the joint.

The ultimate goal of the treatment is to improve joint mobility, reduce inflammation and relieve joint pain.

The most used drugs used to treat rheumatoid arthritis are:

• Aspirin and NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) to relieve joint pain, although they do not stop disease progression.
• Glucocorticoids, such as prednisone, to reduce inflammation and bone erosion. They usually have many side effects.
• Disease-modifying antirheumatic drugs (DMARDs) such as methotrex¬ate, hydroxychloroquine, leflunomide, sulfasalazine and gold salts. They slow disease progression by decreasing inflammatory mediators.
• Biologic agents reduce inflammation. The most used ones are anti-TNF agents (infliximab, adalimumab, certolizumab, etanercept, golimumab) and non anti-TNF agents (rituximab, anakinra, tocilizumab, abatacept).
• Immunosuppressants, such as azathioprine, cyclosporine, and cyclo¬phosphamide, are often reserved for more resistant cases.

A combination of several drugs previously mentioned are usually used in the treatment.

It is important to exercise regularly the joints to maintain range of motion and function.

Surgery is reserved for severe cases of functional incapacity. A synovectomy (a procedure where the synovial tissue surrounding a joint is removed) or the total replacement of the joint (hip or knee) are the most common.

In one third of all cases, there is an extra-articular manifestation. The most common ones are subcutaneous nodules but in a few cases, serious complications such as pleuritic and pericarditis can be seen.

Rheumatoid arthritis varies greatly in prognosis, ranging from mild disease with minimal joint injury to progressive polyarthritis and significant disability.

Although there is no cure for rheumatoid arthritis, the disease can be put into remission, particularly with early, aggressive management.