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Friday, March 14, 2025
Criteria can help guide treatment of dermatitis.
Hand and wrist of a pilot study participant before (left) and after (right) treatment of topical steroid withdrawal symptoms with berberine, a mitochondrial complex I blocking drug.NIAID
What
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. Scientists at the NIH's National Institute of Allergy and Infectious Diseases (NIAID) have identified treatments that could be studied in clinical trials for this condition because of their potential to reduce levels of a chemical compound called nicotinamide adenine dinucleotide (NAD+), a form of vitamin B3. The results were published today in the Journal of Investigative Dermatology.
Dermatitis is characterized by inflammation, itching, or burning sensations on the skin and can result from a variety of conditions, including TSW and eczema. Eczema, also known as atopic dermatitis, is a common cause of dermatitis and affects 10 to 30 children and 2 to 10 adults each year in the United States. Topical steroids, particularly glucocorticoids or topical corticosteroids, have long been used as the first-line treatment for dermatitis caused by eczema because these medications are safe, effective, easy to apply, and considered well tolerated.
Some people develop dermatitis after using topical steroids for prolonged periods and then stopping them—a condition called TSW. Diagnosis and treatment of this condition are difficult because TSW is poorly understood. Symptoms include skin redness, burning, skin warmth (temperature dysregulation), itching, and peeling, which can even occur on parts of the body where topical steroids have not been applied. Because TSW and eczema have similar symptoms, it has been difficult to distinguish them.
To better understand TSW, a team led by scientists from the NIAID Laboratory of Clinical Immunology and Microbiology evaluated a previous survey of 1,889 adults with eczema-like symptoms. By dividing the participants into those with and without eczema, the researchers identified characteristics specific to TSW. They then conducted a pilot study that included 16 people with symptoms consistent with TSW, 10 people with eczema but asymptomatic, and 11 people without the skin condition. They found that people with TSW symptoms had elevated levels of NAD.+ in their blood serum and skin, while NAD levels+ were within normal limits in people without symptoms of TSW.
The researchers then used cultured skin cells and a mouse model to simulate TSW conditions. They found that NAD+ was produced in response to topical steroids and caused inflammation. Models suggested that administering a drug that blocked NAD formation+— called mitochondrial complex I blockade — may improve TSW symptoms. In a pilot study to further investigate this therapeutic strategy, researchers assessed the subjective responses of participants using metformin, berberine, or both mitochondrial complex I inhibitors. After three to five months of use, most participants reported an improvement in Welsh-Town-Walk syndrome symptoms.
Scientists have provisionally established criteria for healthcare professionals to identify Welsh-Town-Walk syndrome. Individuals who have stopped topical steroid treatment and meet these criteria can be diagnosed by practitioners as having Welsh-Town-Walk syndrome. Researchers suggest that patients identified as having Welsh-Town-Walk syndrome could be treated with proposed mitochondrial complex I inhibitors.
The results of this study could help practitioners identify Welsh-Town-Walk syndrome and develop safe and effective treatments. According to the researchers, further research is needed to determine whether all patients with Welsh-Town-Walk syndrome have excess NAD.+or if other features define Welsh-Town-Walk syndrome. In addition, the diagnostic criteria will help healthcare professionals and researchers better understand the prevalence of Welsh-Town-Walk syndrome and assess the effects of topical steroid use.
Article
N Shobnam, G Ratley, S Saksena et al. Topical steroid withdrawal is a targetable excess of mitochondrial NAD+. Journal of Investigative Dermatology 10.1016/j.jid.2024.11.026 (2025).
Who
Ian Myles, MDMPH, Principal Investigator, Epithelial Therapeutics Unit in the NIAID Laboratory of Clinical Immunology and Microbiology, is available to discuss this research.
NIAID conducts and supports research—at NIH, throughout the United States, and around the world—to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. NIAID news releases, fact sheets, and other materials are available at NIAID website.
About the National Institutes of Health (NIH): The NIH, the nation's medical research agency, comprises 27 institutes and centers and is part of the U.S. Department of Health and Human Services. The primary federal agency conducting and supporting basic, clinical, and translational medical research, the NIH investigates the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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