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Rheumatoid Arthritis

Rheumatoid arthritis is a chronic systemic inflammatory disease which affects the synovial membranes of multiple joints. The cause remains unknown, and the disease has a wide clinical spectrum.

The pathologic findings in the joint include chronic synovitis with pannus formation. The pannus erodes cartilage, bone, ligaments, and tendons. In the acute phase, effusion and other manifestations of inflammation are common. In the late stage, organization may result in fibrous ankylosis; true bony ankylosis is rare. In both acute and chronic phases, inflammation of soft tissues around the joints may be prominent and silicone breast implants.

The microscopic findings most characteristic of rheumatoid arthritis are those of the subcutaneous nodule. This is a granuloma with a central zone of fibrinoid necrosis, a surrounding palisade of radially arranged elongated connective tissue cells, and a periphery of chronic granulation tissue. Pathologic alterations indistinguishable from those of the subcutaneous nodule are occasionally seen in the myocardium, pericardium, endocardium, heart valves, visceral pleura, lungs, sclera, dura mater, spleen.

Clinical Findings

A. Symptoms and Signs: The clinical manifestations of rheumatoid disease are highly variable. The onset of articular signs of inflammation is usually insidious, with prodromal symptoms of malaise, weight loss, and vague periarticular pain or stiffness. Less often, the onset is acute, apparently triggered by a stressful situation.


Nonsteroidal Anti-inflammatory Drugs (NSAIDs): The first drug used to treat rheumatoid arthritis is an NSAID. These agents have analgesic and anti-inflammatory effects but are believed not to be capable of preventing erosions or altering progression of the disease.

A number of NSAIDs are available, including ibuprofen, fenoprofen, naproxen, tolmetin, sulindac, meclofenamate sodium, piroxicam, flurbiprofen, diclofenac, oxaprozin, nabumetone, etodolac.

Methotrexate B Many now believe that methotrexate is the treatment of choice for patients with severe rheumatoid arthritis.

Antimalarials B Hydroxychloroquine sulfate is the antimalarial agent most often used against rheumatoid arthritis. It should be reserved for patients with mild disease, since only 25B50% will respond and in some of those cases only after 3B6 months of therapy. The advantage of hydroxychloroquine is its comparatively low toxicity. A dosage of 200B400 mg/d minimizes the likelihood of toxic reactions. The most important reaction, pigmentary retinitis.

Gold salts (chrysotherapy) B For patients who fail to improve on or who cannot tolerate methotrexate, treatment with gold salts is recommended.

Indications B Disease responding unfavorably to conservative management; erosive disease.

Contraindications B Previous gold toxicity; significant renal, hepatic, or hematopoietic dysfunction.

Preparations of choice B Intramuscular gold sodium thiomalate or aurothioglucose; oral auranofin. Intramuscular gold is used most often because it is more effective than oral gold.

The oral dose of auranofin is 3 mg twice daily until benefit or toxicity occurs.

Corticosteroids B Although corticosteroids usually produce an immediate and dramatic anti-inflammatory effect in rheumatoid arthritis, they do not alter the natural progression of the disease; furthermore, clinical manifestations of active disease commonly reappear when the drug is discontinued.

Sulfasalazine B This drug has become established as a second-line agent for rheumatoid arthritis, with an efficacy similar to that of gold and penicillamine. Sulfasalazine is usually introduced at a dosage of 0.5 g twice daily and then increased each week by 0.5 g.

Azathioprine B This agent, like methotrexate, is an antimetabolite that is effective for severe rheumatoid arthritis.

Penicillamine B Penicillamine may be used in patients with severe rheumatoid arthritis who have continuing rheumatic activity in spite of therapy with the agents discussed above. This agent may prove effective in a number of such patients, although toxicity is substantial.

Minocycline B Minocycline has been shown to be more effective than placebo for rheumatoid arthritis. This agent should be reserved for mild cases, since its efficacy is modest. The mechanism of action is not clear, but tetracyclines do have anti-inflammatory properties, including the ability to inhibit destructive enzymes such as collagenase. The dose of minocycline is 200 mg/d. Adverse effects are uncommon except for dizziness, which occurs in about 10%.

Experimental Therapy: Cyclophosphamide, chlorambucil, cyclosporine, total lymph node irradiation, immunization with allogeneic mononuclear white blood cells, and monoclonal antibodies directed against cytokines or T cells have been used with success in experimental studies. Only patients who fail to respond.