Systemic glucocorticoid therapy for SLE

Glucocorticoids are among the most prescribed drug treatments for systemic lupus erythematosus (SLE), used chronically in at least three-quarters of patients in most studies. No other class of medication combines lifesaving effects across such a broad range of immune and inflammatory pathways, along with a rapid onset of effect, and the ability to titrate dosing according to the clinical state. Thus, glucocorticoids have remained irreplaceable in the management of SLE. However, there are parallel dose-dependent effects of glucocorticoids on metabolic pathways, which are essential to the role of glucocorticoids at physiologic concentrations, but result in considerable harm at pharmacologic concentrations. Evidence suggests these harmful effects include not only well-described cushingoid effects, but also effects that compound the effects of active disease on long-term SLE organ damage. Recommendations for the use of glucocorticoids in SLE include using the lowest dose able to control disease activity in a given patient, but specific evidence-based guidelines on how to achieve this are mostly lacking. Deeper understanding of the mechanisms of action of glucocorticoids on the immune and metabolic systems underpin progress toward creating therapies that mimic the beneficial effects, but lack the harmful effects, of these drugs. Until such treatments are available, however, balancing the benefits and harm of glucocorticoid use will remain a core skill of the physician treating patients with lupus.