DISEASE COURSE AND PROGNOSIS.

Although once considered a relatively benign disease, RA is now known to result in considerable disability and a higher than expected mortality rate. Approximately 20% of patients will improve spontaneously or even achieve remission, especially in the 1st year of disease; however, chronic disease progression and functional deterioration occur in the majority. Long-term studies have shown RA patients to have 6 times the probability of severe limitations in activity, 4 times as many restricted activity days, and 10 times the work disability rate as the general population, and approximately 50% are forced to stop working within 10 years of diagnosis. A higher mortality rate also correlates with the degree of disability and results from infections, systemic manifestations, and gastrointestinal bleeding or perforation. The economic impact on the health care system is also substantial.

THERAPEUTIC MANAGEMENT.

Objectives of management include (1) relief of pain and stiffness, (2) reduction of inflammation, (3) minimization of undesirable drug side effects, (4) preservation of muscle strength and joint function, and (5) maintenance of as normal a lifestyle as possible. The basic initial program that achieves these objectives for the great majority of patients consists of (1) adequate rest, (2) adequate anti-inflammatory therapy, and (3) physical measures to maintain joint function. An additional objective, (6) to attempt to modify the disease course with early, aggressive drug therapies, has recently been advocated because of prognosis studies and the findings that rheumatoid pannus invades and irreversibly damages articular cartilage within 1 to 2 years of disease onset. Identification of patients at highest risk for a poor outcome may be possible by detecting high serum levels of rheumatoid

factor and by DNA typing of HLA-DRB1 alleles; however, this approach is currently unproven. Moreover, it is unclear that the current armamentarium of disease-modifying drugs can achieve this goal.

Any confusion arising from the complementary requirements of rest and exercise should be promptly dispelled. Bed rest tends to decrease the general systemic inflammatory response, and most patients soon learn that their midafternoon fatigue is significantly reduced by a period of rest. During acute attacks, longer rest periods and perhaps even remaining in bed for the duration of the attack may be required to treat the inflammation.

At the same time, full range of joint motion should be maintained, which can usually be accomplished by the patient through graded exercise programs. However, during acute attacks, passive range-of-motion exercises by a physical therapist or instructed layperson may be indicated. Physical overexertion increases synovitis and inflammation in joints affected by RA, but this limitation does not contradict the usefulness of appropriate exercise. Exercise, as well as heat treatments such as showers, baths, warm pools, paraffin baths, or hot packs, should be used to loosen the joints and relieve stiffness. Exercise following the heat treatment maintains the motion of affected joints and prevents muscle atrophy.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS.

Anti-inflammatory therapy is crucial to the basic program. Salicylates are inexpensive, generally well tolerated, and demonstrably effective in controlling RA inflammation. The patient needs to understand that a larger dose is required than would be used for analgesia alone. A constant blood level of 20 to 30 mg/dL is needed, which for most patients requires between 3 and 6 g of aspirin per day. All patients should be monitored for toxic levels by blood tests and should be alerted to report deafness, ringing in the ears, or gastrointestinal intolerance. With the availability of buffered and coated aspirin, a suitable salicylate preparation can be found for almost any patient.

Many other non-steroidal anti-inflammatory drugs (NSAIDs) that are effective against pain, fever, and inflammation in RA are available. These cyclooxygenase (COX)-1 and -2 inhibitors include ibuprofen, ketoprofen, flurbiprofen, oraprozin, naproxen, nabumetone, tolmetin, indomethacin, sulindac, piroxicam, diclofenac, diflunisal, and etodolac. Most of these drugs may be beneficial in RA but do not modify disease progression. Clinical experience suggests an occasional need to change from one to another of these drugs to minimize side effects and to give maximal symptomatic benefit to individual patients. Non-acetylated salicylates (sodium or choline) may be useful at times in patients intolerant of other NSAIDs or those with aspirin (and NSAID) hypersensitivity.