A Johns Hopkins Medicine study involving a dozen people with the inflammatory skin disease hidradenitis suppurativa (HS), which mostly affects skin folds, is believed to be the first to provide evidence that hormone-disrupting chemicals commonly found in ultra-processed food and single-use water bottles may contribute to the development of or worsen the condition in some people.
The new findings about the disorder build on previous reports about the role of endocrine-disrupting chemicals, a common environmental contaminant known to mimic, block or alter the body’s hormones, in human health. Researchers believe their findings suggest that reducing exposure could ease HS symptom severity and provide a new avenue of relief for a disease with limited FDA-approved treatment options that include biologic therapy and surgery.
Funded by the National Institutes of Health, the full report on the study was published in Nature Communications on Nov. 28 and includes insights into the molecular mechanisms that are involved in the disease.
Found in 2% to 3% of the U.S. population and predominantly diagnosed in African American women, hidradenitis suppurativa is thought to occur when hair follicles at areas of skin friction, such as the thighs, become inflamed and develop into abscesses, causing chronic skin infections, pain, tissue damage and scars.
While most diagnosed HS cases are considered sporadic and arise due to an interplay of environmental and genetic factors, roughly 1%–5% of patients have a single inherited mutation that causes the condition. Though the causes differ, outcomes and treatment responses are similar, suggesting that all cases share overlapping biological mechanisms.
To find underlying disease pathways linking inherited and sporadic HS, the researchers compared skin samples from 12 patients with HS — who were ages 22–67 and of African American, Asian American, Hispanic American and white heritage — to samples from eight patients without HS. They discovered that the levels of nicastrin (NCSTN), a commonly mutated gene in HS, were reduced in all participants. Specifically, they noted NCSTN levels were low in skin fibroblasts, a known immune regulator and cell type necessary for the maintenance of connective tissues.
Based on their observations and the known association between nicastrin mutations and inflammatory skin diseases, the researchers hypothesized NCSTN loss primes fibroblasts to react intensely to pro-inflammatory biological signals, such as TNF-alpha — a known contributor to HS, psoriasis and other inflammatory skin diseases. This results in the uncontrolled overproduction of inflammatory molecules.
“Until recently, keratinocytes (skin cells found in the outermost layer of skin) were the main focus of HS research,” says Kaitlin Williams, the study’s lead author and an M.D./Ph.D. candidate in the Garza Laboratory at the Johns Hopkins University School of Medicine. “But, we were able to show that intentionally stopping NCSTN expression in non-HS fibroblasts is enough to create a reactive, pro-inflammation environment. This suggests fibroblasts may be as important as keratinocytes in the inflammatory part of this disease.”
Connecting these findings to a known association between hidradenitis suppurativa and the consumption of ultra-processed foods, the researchers tested to see if the levels of plastic-associated endocrine disruptors (p-EDs) called bisphenols (e.g., BPA, BPB, BPS) and phthalates (e.g., DEHP, MEHP, MEP) were elevated in patients with HS and, if they were, how p-EDs possibly contributed to HS.
Using an imaging technique to detect the presence and location of specific chemicals in samples, researchers were able to observe elevated levels of p-ED metabolites (molecules made by the body as it breaks down p-Eds) in the skin of HS patients versus the non-HS control group.
The researchers then created a cocktail of eight common bisphenols and phthalates and applied them to normal fibroblasts. They discovered the p-ED cocktail lowered NCSTN levels proportionally to the concentration applied, recreating observations seen in HS samples from earlier in the study. Overall, the findings further implicate a possible role for p-EDs in some cases of HS.
The researchers say they hope to explore why p-EDs remain trapped in the skin at higher levels in people with HS, and whether intentionally increasing the expression of NCSTN could improve HS symptoms.
Reference:
Williams, K.L., Badiei, B., Reilly, J. et al. Plastic associated endocrine disruptors reduce Nicastrin protein and potentiate inflammation in hidradenitis suppurativa skin disease. Nat Commun 16, 10755 (2025). https://doi.org/10.1038/s41467-025-65789-7
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