Notes

Eto na yung medical reference na nahanap ko mula sa libro na The Science and Practice of Pharmacy 21st EDITION

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disorder of unknown etiology. It is characterized by chronic, symmetric, and erosive destruction of the peripheral joints. The severity of the joint disease may fluctuate over time, but generally, joint destruction and deformity are the end results of this disease. There are also common manifestations of this disease affecting other body systems. For instance, subcutaneous nodules, pulmonary nodules and fibrosis, vasculitis, pericarditis, and episcleritis of the eye, are just some of the examples of extra-articular involvement.

Epidemiology—Approximately 3 million people in the US have RA. The onset is most common in the 3rd and 4th decades but may affect all age groups, including children. Women develop the disease more commonly than men do by a ratio of 2.5:1. The prevalence of disease increases with age for both males and females.

Etiology—The etiology is unknown. Histocompatibility typing has proven that a predisposition for the disease is inherited. Unknown environmental factors may play a role in the development of RA. Viruses and bacteria are suspected as possible causes, although to date there is no convincing evidence to support their etiologic role.

Pathophysiology—The disease is characterized by inflammation of the synovium. Infiltration by mononuclear leukocytes occurs along with edema, vascular congestion, and fibrin deposition. As a result of chronic inflammation, the synovium thickens, and forms large villi, which protrude into the joint space. This is referred to as pannus. The pannus erodes the underlying cartilage and bone. The inflammatory process and destruction of normal joint anatomy results in weakening of tendons, ligaments, and other supporting structures. This leads to instability and partial dislocation (subluxation) of the joint.

Rheumatoid nodules, characteristic of RA, are found most commonly in subcutaneous tissue over pressure points such as the extensor surface of the forearms. However, they also may be found in the lung, heart, or vocal cords. Microscopically, the nodules contain a central area of necrotic collagen surrounded by palisading cells and chronic inflammatory cells. Severe RA also may be complicated by vasculitis involving multiple organs.

Antibodies against immunoglobulin G (IgG) are found in the serum and synovial fluid of most patients with RA. The antibodies are of the IgM, IgG, and IgA classes of immunoglobulins and are called rheumatoid factors. Chronic antigenic stimulation is thought to induce production of these antibodies. The exact role of rheumatoid factor in the development of RA has not been demonstrated. However, immunologic mechanisms do appear to play a role in the pathogenesis of RA. Immune complexes of immunoglobulins, rheumatoid factor, and complement generate vasoactive and chemotactic substances in the joint. Lysosomal enzymes, which cause tissue injury, are released after phagocytic cells ingest the immune complexes. It is the release of these vasoactive substances and enzymes that are primarily responsible for the joint erosion and destruction that characterizes this disease.

Symptoms and Signs—The onset is usually insidious. Fatigue, weakness, joint stiffness, arthralgias, and myalgias may precede signs of joint inflammation. The joints gradually become tender, swollen, hot, and painful. Joint stiffness, particularly after a prolonged period of rest—"gelling," is a major complaint of patients with RA. Morning stiffness is a particular and almost universal complaint of patients with RA. In contrast to the rather brief (5-10 minutes) stiffness seen in patients with osteoarthritis, morning stiffness in RA is prolonged, sometimes lasting in excess of 1 hour.

Nearly all patients with RA will have synovitis of the wrist, metacarpophalangeal joints (MCP), and proximal interphalangeal joints (PIP) of the hands. Typically the distal interphalangeal joints (DIP) are spared. The cervical spine is frequently involved but interestingly, disease of the thoracic and lumbar spine is exceptionally rare. Other commonly affected joints are the shoulders, elbows, hips, knees, ankles, and metatarsophalangeal joints (MTP) of the feet.

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The hypertrophied synovium of involved joints may be palpated. Muscle weakness and atrophy often parallel the severity of the joint dis- ease. Range of motion, especially extension, becomes limited and can lead to flexion contractures. Swan-neck, boutonniere, and cock-up toes are terms used to describe the deformities of the hands and feet. Ulnar deviation of the fingers can occur.
Duration of morning stiffness, which usually is measured in hours, may be used to monitor disease activity. Other indicators include grip strength, time required to walk a certain distance, number and clinical assessment of joints involved, and radiographs demonstrating erosion of bone, loss of joint space, and soft-tissue swelling.
RA is a systemic disease involving multiple organ systems besides the joints. Rheumatoid nodules are found in 20% of RA patients. Less than 5% of the patients have vasculitis. However, the vasculitis may be severe and can result in peripheral neuropathy, nail-fold thrombi, digital gangrene, and leg ulcers. The most common ocular manifestation is keratoconjunctivitis sicca (Sjögren's syndrome); episcleritis also may oc- cur. In the lungs, interstitial fibrosis, rheumatoid nodules, and pleural effusions are seen. Inflammation of the pericardium may cause peri- carditis. Rarely this may result in cardiac tamponade. Rheumatoid nod- ules on the heart valves may lead to murmurs and nodules in the heart muscle that can cause electrical conduction disturbances.
Patients with severe arthritis may develop Felty's syndrome. Felty's syndrome was originally described as RA, splenomegaly, leukopenia, and leg ulcers. However, subsequent observations have shown that there is an additional association with lymphadenopathy and thrombo- cytopenia.
Mild to moderate anemia that is normochromic or hypochromic is found in patients with RA. The severity of the anemia parallels the activity of the disease. The defect is thought to be in iron utilization in hemoglobin synthesis (see anemia of chronic disease).
Other abnormal laboratory tests include a high erythrocyte sedimentation rate, which may be used to monitor disease activity. The latex aggregation test for IgM rheumatoid factor is positive in 70-80% of patients. Unfortunately, other diseases of chronic inflammation also are associated with a positive rheumatoid factor test, therefore, it is not specific to RA despite its name. Analysis of the synovial fluid, while not diagnostic, typically shows neutrophils (10,000-50,000/mm3) and elevated protein levels.

Diagnosis-The highly variable clinical course of RA makes prognosis difficult in individual patients. Spontaneous remissions and exacerbations are characteristic. Remissions occur most frequently in the early stages of the disease. Some patients may experience a complete re- mission with little or no joint deformity. Others have a chronically progressive course over many years with development of varying degrees of joint damage. A smaller group, 10-15%, has a relentless destructive course that results in severe deformities and crippling. The unpredictable course of RA also makes evaluation of therapy particularly difficult and contributes to the quackery seen in this field.
The diagnosis of RA is based on the clinical picture of symmetrical inflammatory arthritis usually involving small joints, characteristic radiograph changes, and a positive rheumatoid factor test. Other causes of inflammatory arthritis are Reiter's syndrome, psoriatic arthritis, and systemic lupus erythematosus. Arthritis associated with inflammatory bowel disease must be excluded. The arthritis associated with Lyme disease or hepatitis B may mimic RA. Degenerative joint disease may occur simultaneously.