Systemic glucocorticoid therapy for SLE

Glucocorticoids (GCs) are among the most prescribed drug treatments for systemic lupus erythematosus (SLE) and are 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 GCs have remained irreplaceable in the management of SLE. However, there are parallel dose-dependent effects of GCs on immune and metabolic pathways, which are essential to the role of GC physiologic concentrations but result in considerable harm at pharmacologic concentrations. Recent evidence suggests these harmful effects include not only well-described cushingoid effects but effects inextricably linked to the effects of active disease itself on long-term SLE organ damage outcomes. Recommendations for the use of GC in SLE include the use of 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. A deeper understanding of the mechanisms of action of GCs 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 benefit and harm of GC use will remain a core skill of the lupus physician.