Scientists Uncover Hidden Cause of Mysterious Post-Steroid Skin Condition

For thousands of people struggling with debilitating skin symptoms after stopping topical steroid treatments, a new study from the National Institutes of Health (NIH) offers both validation and hope. Researchers have not only identified a distinct biological mechanism behind “topical steroid withdrawal” (TSW), but have also found two readily available medications that may help treat it.

The findings, published this week in the Journal of Investigative Dermatology, represent the first major scientific investigation into a condition that has been controversial in dermatology circles despite affecting potentially thousands of patients.

“Some have labeled the patient concerns as ‘steroid phobia,’” the study notes, highlighting the historical dismissal many patients have faced. But this new research provides compelling evidence that TSW is indeed “a distinct, iatrogenic dermatopathy deserving of further investigation.”

Topical steroids—more accurately called glucocorticoids or topical corticosteroids—have long been the first-line treatment for eczema and other inflammatory skin conditions. While effective for most, some patients develop severe reactions after discontinuing these medications, especially following prolonged use.

What makes this research groundbreaking is how it connects these symptoms to a specific biological mechanism: an excess of nicotinamide adenine dinucleotide (NAD+), a form of vitamin B3 naturally present in the body. This overabundance appears to trigger the severe inflammation, burning sensations, and other symptoms characteristic of TSW.

Led by researchers in NIH’s National Institute of Allergy and Infectious Diseases (NIAID), the study combined patient surveys, biological samples, and laboratory experiments to establish diagnostic criteria that distinguish TSW from ordinary eczema. The team evaluated 16 people with symptoms consistent with TSW, comparing them to 10 people with eczema but no TSW symptoms, and 11 people without skin disease.

Their analysis revealed that people with TSW had significantly elevated levels of NAD+ in their blood serum and skin, while those without TSW symptoms had typical levels. This excess appears to be produced in response to topical steroids and causes inflammation.

For many patients, TSW symptoms can persist for years after discontinuing steroid use—nearly 25% of survey respondents reported symptoms lasting longer than three years. This prolonged suffering has led to online communities where patients share experiences and seek solutions.

The NIH team found that a key distinction between TSW and ordinary eczema is that TSW symptoms often appear on parts of the body where topical steroids were never applied. Patients typically experience full-body redness, burning sensations, temperature dysregulation, and substantial skin shedding.

Based on their finding that excess NAD+ drives these symptoms, the researchers tested medications that block mitochondrial complex I, which produces NAD+. Two drugs—metformin (commonly used for diabetes) and berberine (a plant compound used in traditional Chinese medicine)—showed particular promise.

In a small pilot study, most participants reported improvement in TSW symptoms after three to five months of using either medication. While not a cure, this represents the first evidence-based treatment approach for a condition that has largely been managed through avoidance of steroids and time.

“These results suggest that expanded clinical assessments are warranted,” the researchers noted, though they cautioned that “no patient reported complete resolution of symptoms.”

The study has also provided provisional diagnostic criteria that healthcare providers can use to identify TSW in patients. People who have stopped topical steroid treatment and meet specific symptom criteria may now be diagnosed with TSW rather than simply being told they’re experiencing a flare-up of their original skin condition.

Dr. Ian Myles, Principal Investigator in NIAID’s Laboratory of Clinical Immunology and Microbiology, led the research team. The findings represent a collaboration between NIAID scientists and patient advocacy groups like the International Topical Steroid Awareness Network, whose members participated in the research.

For Kelly Barta and Kathryn Tullos, co-authors on the study who have advocated for TSW recognition, the research validates what patients have been reporting for years. Their involvement highlights the growing trend of patient-researcher partnerships in addressing poorly understood medical conditions.

The research team suggests that caution may be warranted for topical steroid exposures longer than four consecutive months. They emphasize that identifying preventive strategies and predictive factors should remain paramount, given the potentially life-altering nature of TSW.

As with many preliminary studies, the researchers acknowledge limitations, including the small sample size and the need for prospective severity indices specific to TSW. Further research will be needed to understand why some people develop this condition while others use topical steroids without incident.

The findings also raise questions about current prescribing practices for topical steroids, which are among the most commonly used medications in dermatology. While the study doesn’t suggest avoiding these effective treatments altogether, it does highlight the need for monitoring long-term use.

For patients currently experiencing TSW symptoms, the study offers not just hope for treatment but the validation many have sought from the medical community. As one participant put it, the most significant relief comes from having their experience scientifically verified after years of being told their symptoms were psychological or a return of their original condition.

The research was funded by the Air Force Office of Scientific Research, the St. Jude Research Collaborative on the Biology and Biophysics of RNP granules, and the National Institutes of Health.