Healthcare (Commonwealth Union) – A study conducted by Johns Hopkins Medicine, which examined a small group of individuals with hidradenitis suppurativa (HS)—a chronic inflammatory skin condition that primarily affects areas where skin folds—appears to be the first to show evidence that hormone-disrupting chemicals, commonly present in ultra-processed foods and disposable plastic water bottles, may play a role in triggering or worsening the disease in some patients.
The latest findings go further on prior studies regarding endocrine-disrupting chemicals, environmental components known to make an impact with the hormones of the body by mimicking, blocking, or changing them. Scientists have pointed to the fact that lowering exposure to these chemicals could potentially bring down the serous nature of HS symptoms. This gives a new path for relief in a condition that at present has restricted FDA-approved treatment options, consisting of biologic therapies and surgical intervention.
With the backing of the National Institutes of Health, the full study appeared in November 28 in Nature Communications giving insights for the molecular mechanisms underlying HS.
Hidradenitis suppurativa affects roughly 2% to 3% of the U.S. population and is most frequently diagnosed in African American women. The condition is thought to come up when hair follicles in areas prone to friction—like the thighs—become inflamed and produce abscesses, that gives way to persistent skin infections, pain, tissue damage, along with scarring.
Although most cases of hidradenitis suppurativa (HS) are considered sporadic, arising from a combination of genetic and environmental influences, about 1%–5% of patients carry a single inherited mutation that directly causes the condition. Despite these differing origins, disease outcomes and responses to treatment are generally similar, indicating that both inherited and sporadic cases share overlapping biological processes.
To investigate the disease pathways linking inherited and sporadic HS, researchers analyzed skin samples from 12 HS patients, aged 22–67, representing African American, Asian American, Hispanic American, and white backgrounds, alongside samples from eight individuals without HS. They found that levels of nicastrin (NCSTN)—a gene frequently mutated in HS—were reduced across all participants. NCSTN was particularly reduced in skin fibroblasts, a key cell type playing a role in immune regulation as well as connective tissue maintenance.
Taking into account these results and the established link between nicastrin mutations and inflammatory skin disorders, the researchers made a suggestion that NCSTN deficiency sensitizes fibroblasts to pro-inflammatory signals like TNF-alpha, a molecule implicated in HS, psoriasis, and other inflammatory conditions. This heightened sensitivity triggers an increased formation of inflammatory molecules, that plays a role in disease development.
“Until recently, keratinocytes (skin cells found in the outermost layer of skin) were the main focus of HS research,” explained Kaitlin Williams, the lead author of the study 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.”
Building on earlier evidence linking hidradenitis suppurativa (HS) to diets high in ultra-processed foods, the team investigated whether patients with HS had heightened levels of plastic-related endocrine-disrupting chemicals (p-EDs) — specifically bisphenols (such as BPA, BPB, BPS) and phthalates (including DEHP, MEHP, MEP) — and how these substances might influence the disease.
Using a chemical-mapping imaging method, the researchers detected increased amounts of p-ED breakdown products (metabolites produced as the body processes these chemicals) in the skin of people with HS compared with those without the condition.
Next, the researchers mixed eight commonly encountered bisphenols and phthalates and exposed healthy fibroblasts to this blend. They found that the p-ED mixture reduced NCSTN levels in a dose-dependent manner, mirroring the changes previously observed in skin samples from HS patients. These results strengthen the case that p-EDs may contribute to HS in some individuals.
The team plans to investigate why p-EDs accumulate in the skin at higher concentrations in people with HS, and whether boosting NCSTN expression could help alleviate symptoms.
