2025-03-14 アメリカ国立衛生研究所 (NIH)
<関連情報>
- https://www.nih.gov/news-events/news-releases/topical-steroid-withdrawal-diagnostic-criteria-defined-nih-researchers
- https://www.sciencedirect.com/science/article/abs/pii/S0022202X25000144
ステロイド局所離脱はミトコンドリアNAD+の過剰を標的とする Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD+
Nadia Shobnam, Grace Ratley, Sarini Saksena, Manoj Yadav, Prem Prashant Chaudhary, Ashleigh A. Sun, Katherine N. Howe, Manasi Gadkari, Luis M. Franco, Sundar Ganesan, Katelyn J. McCann, Amy P. Hsu, Kishore Kanakabandi, Stacy Ricklefs, Justin Lack, Weiming Yu, Morgan Similuk, Magdalena A. Walkiewicz, Donna D. Gardner, Kelly Barta, Kathryn Tullos, Ian A. Myles
Journal of Investigative Dermatology Available onlin:e 14 March 2025
DOI:https://doi.org/10.1016/j.jid.2024.11.026
abstract
Topical steroid withdrawal (TSW) is a controversial diagnosis advocated by patients but often confused for atopic dermatitis. We conducted a multimodal pilot study of 16 patients fitting the TSW diagnostic profile, contrasting them against patients with atopic dermatitis (n = 10) and healthy controls (n = 11). Our clinical evaluations established objective diagnostic criteria that distinguish TSW from atopic dermatitis, metabolomics and transcriptomics of skin biopsies suggested that neuroinflammatory pathways are associated with complex I–mediated oxidation of NAD+, cellular and mouse models demonstrated that NAD+ metabolism was proinflammatory and glucocorticoid responsive, whereas functional assays demonstrated that the metabolic effects of glucocorticoids on the only cell type that aligns with the distribution and duration of TSW pathology could be mitigated by complex I blockade. These results informed a successful open-label trial using complex I–inhibiting interventions: metformin and berberine. Although this work represents a pilot study, to our knowledge, this work offers previously unreported mechanistic insights into TSW.
