Abstract
Corticosteroids are widely prescribed dermatological medications, with an estimated 13.8 million prescriptions annually in the United States. Growing awareness of their insidious adverse effects has prompted official safety warnings from Health Canada in 2022 and the United Kingdom’s Medicines and Healthcare products Regulatory Agency in 2021. This review provides a comprehensive analysis of the clinical spectrum of steroid-induced skin disease, ranging from local damage to systemic repercussions, and evaluates emerging data on steroid-sparing and potentially curative therapies. We examined large population-based studies, recent clinical trials, and mechanistic research published between 2020 and 2026. Key findings confirm that corticosteroid-associated cutaneous injury encompasses skin atrophy, topical steroid withdrawal syndrome (TSW), and systemic complications such as adrenal suppression, osteoporosis, and metabolic disturbances. Important mechanistic insights uncovered that NAD+ overproduction underlies the pathogenesis of TSW, while clinical trial evidence demonstrates that pimecrolimus can effectively reverse steroid-induced atrophy. Steroid-sparing therapeutic strategies have the potential to modify disease trajectories. The accumulated evidence mandates a fundamental shift in clinical practice: from sustained corticosteroid use toward early detection of steroid toxicity and timely implementation of steroid-sparing interventions. Targeted therapies designed to control excessive NAD+ production and repair atrophic skin now offer the promise of disease-modifying and curative treatments. The shift away from prolonged steroid use is now supported by robust mechanistic and clinical data, enabling a proactive approach. This strategy not only mitigates toxicity but also addresses the underlying pathophysiology, offering patients a path to lasting remission and improved outcomes