Common endocrine-disrupting chemicals found in plastics and ultraprocessed foods (UPFs) may be unexpected culprits in the development of hidradenitis suppurativa (HS), according to a small study published online on November 28 in Nature Communications. In particular, the study identifies plastic-associated endocrine disruptors (p-EDs) as potential environmental contributors to HS.

The findings “suggest that p-ED exposure contributes to HS pathogenesis, highlighting the need to address environmental exposures in HS and other gamma secretase-related diseases,” the authors wrote.

‘Novel’ Exploration

HS, an inflammatory skin disorder, has two subtypes: the more common sporadic HS and the less common monogenic HS, affecting only 1%-5% of cases and linked to mutations in the gamma-secretase protein complex — particularly the Nicastrin (NCSTN) gene.

Outcomes and treatment responses are similar between the sporadic and the inherited versions, raising the question of whether these conditions may share overlapping biological mechanisms.

Additionally, HS “has become more common, and nobody knows why,” senior author Luis Garza, MD, PhD, professor of dermatology, Johns Hopkins School of Medicine, Baltimore, told Medscape Medical News. “We wondered if chemicals in plastics, like the plastics used in food packaging, could explain this increase. These chemicals are in ultraprocessed food, whose use has similarly increased.”

Non-Hispanic Black populations consume the most UPFs and also have the highest HS incidence compared with Hispanic populations, who consume the lowest quantities of UPFs — although both populations have similar rates of obesity, a known driver of HS, according to the authors. The association of HS with UPF consumption and endocrine disorders therefore suggested a “novel avenue of investigation,” Garza said.

The Role of Fibroblasts

The researchers compared skin samples from 12 patients with HS to those of 8 control individuals without HS.

They found that the levels of NCSTN were reduced in all participants with HS. In particular, dermal fibroblasts from HS lesions showed markedly lower levels of NCSTN, a feature previously associated only with monogenic HS. The loss was specific to fibroblasts, which are known to play an immunoregulatory role and are critical for maintaining connective tissues.

When the researchers did a meta-analysis of data from two single-cell RNA sequencing studies, they found that fibroblasts are “originators,” not merely “perpetuators” of immune signaling in HS, driving high levels of CXCL/CCL cytokines.

“Until recently, keratinocytes were the main focus of HS research,” lead author Kaitlin Williams, an MD/PhD candidate at the Garza Laboratory, Johns Hopkins University School of Medicine, said in a Johns Hopkins Medicine press release on the study results.

“But we were able to show that intentionally stopping NCSTN expression in non-HS fibroblasts is enough to create a reactive, pro-inflammation environment,” she continued. “This suggests fibroblasts may be as important as keratinocytes in the inflammatory part of the disease.

‘Eat Whole Foods’

The researchers took their investigation a step further by exploring whether the levels of bisphenols and phthalates, which are p-EDs, might be present in patients with HS, and might contribute to the condition.

To do so, they used mass spectrometry imaging and found markedly elevated levels of both p-ED metabolites in the skin of the patients with HS group vs the skin of those in the control group. When they applied a mix of eight common p-EDs to normal fibroblasts, they found these chemicals lowered NCSTN levels proportionally to the concentration applied, which echoed the earlier findings of lower NCSTN in HS skin samples.

The pattern of detected chemicals also mirrored the profile of p-EDs found in UPFs.

“In this study, we demonstrate through hypothesis-driven approaches a novel contributory mechanism to HS pathogenesis, likely working in parallel with other disease-promoting events in this multifactorial disease,” the authors wrote.

NCSTN protein expression is lower in dermal fibroblasts of patients with HS, leading to a series of inflammatory occurrences. The authors “link dietary factors, a known risk factor for HS, with these molecular discoveries.”

Future research will focus on why p-EDs concentrate at higher levels in the skin of patients with HS and whether intentionally increasing NCSTN expression could ameliorate HS symptoms.

On a practical level, the take-home messages of these findings are “simple,” Garza said. “Rinse your food before you eat it. You can wash whole foods before you cook them, like a piece of chicken and some broccoli, but you cannot wash a frozen pizza or a bag of chips before you eat them. So simply try to eat more food that you have washed, instead of food you cannot wash.”

‘A Big Step Forward’

Asked to comment on the study, Christopher Sayed, MD, associate professor of dermatology and director of the Hidradenitis Suppurativa Clinic, The University of North Carolina at Chapel Hill, said that although previous “correlative dietary studies have suggested that diet and exposure to ultraprocessed foods can influence HS development, this is a big step forward in understanding how diet and environmental factors may influence HS activity.”

Sayed, who was not involved with the study, suggested that patients seeking guidance about potential dietary triggers for HS “may benefit from avoidance of ultraprocessed food and plastic exposure in packaging, although more research is needed to understand the impact of such lifestyle changes.”

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases/the National Institutes of Health, the Johns Hopkins University School of Medicine Department of Dermatology’s Ina R. Drew and Howard J. Drew Innovation Fund, the Cutaneous Translational Research Program, the Sidney Kimmel Comprehensive Cancer Center’s Oncology Tissue and Imaging Services Core, and the Johns Hopkins University School of Medicine Daniel Nathans Scholar fund. Garza reported receiving grant support from Sun Pharma Advanced Research Company (SPARC) to research intellectual property owned by The Johns Hopkins University and royalty payments from SPARC under a licensing agreement with the group, which is not related to the study. The other authors’ disclosures are listed on the original paper. Sayed reported being a speaker, investigator, and consultant for several pharmaceutical companies, but none are relevant to his remarks. 

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).