For more than 50 years, glucocorticosteroids have been important agents in treating diseases characterized by inflammation and exaggerated immune responses. The pioneering work of Hench and colleagues in rheumatoid arthritis showed the possible potency of these agents in such pathologic states.
Although substantial advances have been made in understanding the mechanisms by which glucocorticosteroids exert beneficial effects, considerable gaps in knowledge remain. Despite extensive data regarding the in vitro and in vivo activities of these drugs, it is probable that glucocorticosteroids have different beneficial activities in different diseases.
[...] For inflammatory and immunologically related disorders, it is incumbent on the treating physician to determine that glucocorticosteroids are the appropriate form of treatment and that other nonglucocorticosteroid approaches are unlikely to be equally beneficial. When glucocorticosteroid treatment becomes desirable, if not mandatory, efforts must focus on minimizing glucocorticosteroid side effects, while maintaining therapeutic efficacy. Generally, these goals can be attained at least partially by using short-acting glucocorticosteroid medications at the lowest possible dose and the greatest dosing interval for the shortest period of time. [...]
[...] Failures may occur if the attempt to begin tapering is premature because the disease is still active, if the dose is reduced too rapidly, if the decrements in dose are too large, if not enough prednisone is administered on the day, or if glucocorticosteroid "withdrawal" symptoms (e.g., myalgias, arthralgias, fever) are confused with a recrudescence of the disease. In some instances, tapering can be facilitated by using glucocorticosteroid-sparing drugs that help control the primary disease as glucocorticosteroids are reduced. Nonsteroidal anti-inflammatory agents, cytotoxic drugs (e.g., methotrexate, azathioprine, and cyclophosphamide), and other agents may permit tapering to alternate-day glucocorticosteroid regimens. [...]
[...] More recent work has suggested that the amount of supplemental glucocorticosteroids required during surgery can be estimated by ascertaining the "amount" of stress (minor, moderate, or severe) anticipated in the perioperative period, with an upward adjustment of daily hydrocortisone (25 mg for minor stress; 50 to 75 mg for moderate stress to 150 mg for major stress) for 3 days. Several protocols for tapering to an alternate-day regimen have been used. The single daily dose may be reduced in to 10-mg decrements to one half of the initial dose. [...]
[...] Current indications for pulse regimens have included recrudescence of disease despite long-term glucocorticosteroid therapy, a flare of disease activity in the setting of glucocorticosteroid side effects, the need to control disease until another modality (e.g., cytotoxic drug) becomes effective, and the onset of a rapidly progressive glucocorticosteroid-responsive syndrome. Conclusions Prolonged systemic glucocorticosteroid therapy is invariably associated with toxicity. In general, side effects depend on daily dose, dosing frequency, and duration of treatment and emphasize the need to treat with alternate-day regimens or the lowest daily dose possible for as briefly as feasible. [...]
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