Diagnosing and treating topical steroid withdrawal (TSW) is difficult because this condition is not well understood, but researchers at the National Institutes of Health (NIH) have established criteria that can be used by healthcare providers to identify TSW in people.
Specifically, protracted neuroinflammatory symptoms distinguish TSW from eczema. TSW symptoms include skin redness, burning sensations, thermal dysregulation, itching, and peeling, which can even occur on body parts where topical steroids were not applied. People who have stopped topical steroid treatment and meet the criteria may be diagnosed by practitioners as having TSW. Moreover, the researchers suggest that patients identified as having TSW could be treated using mitochondrial complex I-blocking drugs.
To better understand TSW, the researchers evaluated a previous survey that included 1,889 adults with symptoms similar to eczema. By dividing the participants into those with self-reported TSW and those without, the researchers identified characteristics unique to TSW. The researchers then conducted a pilot study that included 16 people with symptoms consistent with TSW, 10 people with eczema but no symptoms of TSW, and 11 people without skin disease.
They found that people with TSW symptoms had elevated levels of nicotinamide adenine dinucleotide (NAD+), a form of vitamin B3, in their blood serum and skin, while NAD+ levels were within a typical range in people without TSW symptoms.
The researchers subsequently used cultured skin cells and a mouse model to mimic TSW conditions. They found that NAD+ was produced in response to topical steroids and caused inflammation. The models suggested that administration of a drug that blocked the formation of NAD+—called a mitochondrial complex I blockade—would improve TSW symptoms.
In a pilot study to further assess this treatment strategy, the researchers evaluated subjective responses among study participants who used the mitochondrial complex I-blocking drugs metformin, berberine, or both. After three to five months of use, most participants reported improvement in TSW symptoms.
More research is needed to determine whether all patients with TSW have an excess of NAD+, or if there are other features that define TSW, the researchers conclude.
The findings are published in the Journal of Investigative Dermatology.
PHOTO CAPTION: Hand and wrist of a participant in the pilot study before (left) and after (right) treatment of topical steroid withdrawal symptoms with berberine, a mitochondrial complex I-blocking drug.
PHOTO CREDIT: The National Institute of Allergy and Infectious Diseases
