Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD+

Journal of Investigative Dermatology

Clinical Summary

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What was studied

A multimodal pilot compared patients meeting a topical steroid withdrawal (TSW) profile (n=16) with atopic dermatitis (n=10) and healthy controls (n=11), using clinical criteria, skin metabolomics/transcriptomics, cellular and mouse models, and an open-label trial of complex I inhibitors (metformin, berberine).

Key findings

Skin omics in TSW implicated neuroinflammatory pathways tied to complex I–mediated oxidation of NAD+, complex I blockade mitigated glucocorticoid-induced metabolic effects in the implicated cell type, and an open-label trial of metformin/berberine was reported as “successful” (no quantitative outcomes provided).

Study limitations

Small pilot cohorts (TSW n=16; comparators n=10 and n=11), an open-label trial without controls and with unreported outcomes in the abstract, and a complex multimodal design that limits generalizability and causal inference.

Clinical implications

TSW appears mechanistically distinct from atopic dermatitis with a complex I/NAD+ signature; any use of metformin or berberine for TSW should be treated as investigational until controlled trials report outcomes.