A recent pilot study has offered new insights into topical steroid withdrawal, a controversial diagnosis frequently mistaken for atopic dermatitis.
The study evaluated 16 patients with topical steroid withdrawal (TSW), 10 with atopic dermatitis (AD), and 11 healthy controls. Researchers identified objective diagnostic criteria that differentiate TSW from AD and proposed that TSW represents a distinct, iatrogenic dermatopathy that may benefit from targeted therapy.
Published in the Journal of Investigative Dermatology, researchers found that patients with TSW reported persistent or worsening symptoms despite continued topical corticosteroid (TCS) use. Approximately 25% experienced symptoms lasting longer than 3 years after discontinuing TCS. Predictive signs of TSW included reduced TCS efficacy, spreading rash despite treatment, and new-onset symptoms such as full-body erythema, flushing, temperature dysregulation, and anhidrosis.
“Patients described full-body redness, flushing, and anhidrosis occurring 4 to 6 weeks after discontinuation of TCS, which tended to spare the nose (‘headlamp sign’), palms, and soles, and often formed ‘red sleeves’ on the arms,” reported Nadia Shobnam of the National Institute of Allergy and Infectious Diseases.
Multiomics analysis revealed increased nicotinamide adenine dinucleotide (NAD⁺) oxidation in patients with TSW, associated with mitochondrial complex I overexpression. Open-label treatment with complex I inhibitors—metformin or berberine—resulted in subjective symptom improvement ranging from 5% to 80% over 3 to 5 months.
Serum metabolomics showed disruptions in the sphingolipid and urea cycle amino acid pathways compared with healthy controls. Microbiome analysis identified reduced bacterial diversity and increased Staphylococcus aureus burden; findings similar to those in AD.
The researchers proposed preliminary diagnostic criteria based on symptom prevalence: the presence of at least 1 major criterion and 3 minor criteria yielded over 90% sensitivity for identifying self-reported TSW. Major criteria included symptoms present in more than 80% of TSW cases and distinct from AD, while minor criteria were selected based on specificity.
Investigators concluded that TSW is a unique clinical entity that merits further investigation. They noted the importance of distinguishing TSW from AD and the potential therapeutic role of mitochondrial complex I inhibition.
Full disclosures can be found in the journal article.
