Potential Treatments for TSW Identified in NIH Study

Image Credit: © DermNet

Recent research conducted by the National Institutes of Health (NIH) has identified topical steroid withdrawal (TSW) as a condition distinct from eczema, primarily caused by elevated levels of nicotinamide adenine dinucleotide (NAD+), a form of vitamin B3. This study, led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), highlights potential treatment options aimed at reducing NAD+ levels. The findings, published in the Journal of Investigative Dermatology, may pave the way for targeted clinical trials and improved diagnostic criteria for TSW.¹

“Researchers at the National Institutes of Health (NIH) have determined that dermatitis resulting from topical steroid withdrawal (TSW) is distinct from eczema and is caused by an excess of an essential chemical compound in the body," a release from NIH stated.

Background

Dermatitis, a broad term describing skin inflammation, can arise from various conditions, including eczema and TSW. Eczema, or atopic dermatitis, is a prevalent disorder affecting 10 to 30% of children and 2 to 10% of adults annually in the United States. Topical steroids, primarily glucocorticoids or topical corticosteroids, have been the first-line treatment for eczema due to their efficacy and general tolerability.²

However, long-term use of topical steroids followed by cessation can lead to TSW, a poorly understood condition characterized by skin redness, burning sensations, thermal dysregulation, itching, and peeling. These symptoms often overlap with eczema, making differential diagnosis challenging.

Methodology

To differentiate TSW from eczema, NIAID researchers analyzed data from a previous survey involving 1,889 adults reporting eczema-like symptoms. Participants were classified into self-reported TSW and non-TSW groups, enabling researchers to identify distinct features of TSW.

A subsequent pilot study included 16 individuals exhibiting symptoms consistent with TSW, 10 individuals with eczema without TSW symptoms, and 11 healthy controls. Analysis of blood serum and skin samples revealed that NAD+ levels were significantly elevated in individuals with TSW, whereas those with eczema or without skin disease exhibited normal NAD+ levels.

Further investigation using cultured skin cells and a mouse model demonstrated that NAD+ production was stimulated by topical steroid application, contributing to inflammatory responses. This finding suggested that blocking NAD+ formation could alleviate TSW symptoms.

Potential Treatments

Researchers explored the therapeutic potential of mitochondrial complex I-blocking drugs, including metformin and berberine, to counteract excessive NAD+ production. In a preliminary study assessing subjective responses among participants using these drugs for three to five months, "most participants reported improvement in TSW symptoms." These findings suggest that mitochondrial complex I inhibition could be a viable treatment strategy for TSW.

Diagnostic Criteria and Future Implications

Based on their findings, the researchers established provisional diagnostic criteria for healthcare providers to identify TSW. Patients who discontinue topical steroids and exhibit characteristic symptoms may be diagnosed with TSW. The study authors emphasize that further research is needed to determine whether all individuals with TSW experience NAD+ overproduction or if additional factors contribute to the condition.

"The results of this study may help practitioners identify TSW in patients and work towards developing safe and effective treatments," the researchers stated. Furthermore, defining diagnostic criteria will enhance the understanding of TSW prevalence and improve assessments of topical steroid effects.

Conclusion

The NIH study represents a significant advancement in distinguishing TSW from eczema and identifying potential treatments targeting NAD+ metabolism. While further clinical trials are necessary to validate these findings, this research provides a foundation for improved diagnosis and management of TSW. By addressing the underlying biochemical mechanisms, healthcare providers may be better equipped to support patients experiencing TSW, leading to enhanced therapeutic outcomes.

References

1. Topical steroid withdrawal diagnostic criteria defined by NIH researchers. News release. National Institutes of Health. Published March 14, 2025. Accessed March 18, 2025. https://www.nih.gov/news-events/news-releases/topical-steroid-withdrawal-diagnostic-criteria-defined-nih-researchers
2. Nemeth V, Syed HA, Evans J. Eczema. [Updated 2024 Mar 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538209/