Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug;145(8):1953-1968.e14.
doi: 10.1016/j.jid.2024.11.026. Epub 2025 Mar 14.

Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD

Nadia Shobnam  1 , Grace Ratley  1 , Sarini Saksena  1 , Manoj Yadav  1 , Prem Prashant Chaudhary  1 , Ashleigh A Sun  1 , Katherine N Howe  2 , Manasi Gadkari  3 , Luis M Franco  3 , Sundar Ganesan  4 , Katelyn J McCann  3 , Amy P Hsu  3 , Kishore Kanakabandi  5 , Stacy Ricklefs  5 , Justin Lack  6 , Weiming Yu  7 , Morgan Similuk  8 , Magdalena A Walkiewicz  8 , Donna D Gardner  9 , Kelly Barta  10 , Kathryn Tullos  10 , Ian A Myles  11
Affiliations

Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD

Nadia Shobnam et al. J Invest Dermatol. 2025 Aug.

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.

Keywords: Atopic dermatitis; Eczema; Glucocorticoids; Topical steroid withdrawal; Topical steroids.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

Allergy & Asthma Network has received funding from Sanofi, Regeneron, Genentech, Pfizer, and Novartis for unbranded disease awareness and education; such funding was not relevant to the presented research. Other authors have no conflicts of interest to report.

Update of

References

    1. Ahuja K, Lio P. Pediatric Topical Steroid Withdrawal Syndrome: What Is Known, What Is Unknown. Pediatr Dermatol 2024. - PMC - PubMed
    1. Anderson ED, Alishahedani ME, Myles IA. Epithelial-Mesenchymal Transition in Atopy: A Mini-Review. Front Allergy 2020;1. - PMC - PubMed
    1. Arendt-Nielsen L, Carstens E, Proctor G, Boucher Y, Clave P, Albin Nielsen K, et al. The Role of TRP Channels in Nicotinic Provoked Pain and Irritation from the Oral Cavity and Throat: Translating Animal Data to Humans. Nicotine Tob Res 2022;24(12):1849–60. - PMC - PubMed
    1. Arnold KA, Treister AD, Lio PA. Dupilumab in the management of topical corticosteroid withdrawal in atopic dermatitis: A retrospective case series. JAAD Case Rep 2018;4(9):860–2. - PMC - PubMed
    1. Auwera GVd, O’Connor B Genomics in the Cloud: Using Docker, GATK, and WDL in Terra. 1 ed: O’Reilly Media, 2020.

MeSH terms

LinkOut - more resources