{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:28:25Z","timestamp":1786613305974,"version":"build-2736575974"},"reference-count":93,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Hidradenitis suppurativa (HS) is increasingly recognized as a disorder of intrinsic dysregulation at the intersection of genetic susceptibility, host\u2013microbial interactions, and hormonal signaling, with select environmental exposures acting as important secondary modifiers. This narrative review synthesizes mechanistic, clinical, and epidemiologic evidence on intrinsic and extrinsic contributors to HS pathogenesis. Genetic susceptibility for HS involves pathways regulating keratinocyte differentiation, epidermal stem cell function, and follicular architecture, including Notch signaling and transcriptional regulators such as SOX9 and KLF5. Microbiome alterations in both lesional and non-lesional skin suggest that early dysbiosis may contribute to follicular occlusion, epithelial disruption, and immune activation. Hormonal signaling, particularly androgen signaling, promotes follicular dysfunction and inflammation during periods of hormonal fluctuation, frequently aligning with the time of disease onset and flares. Environmental exposures vary considerably in the strength of supporting evidence: tobacco use and elevated body mass index have the most robust epidemiologic and mechanistic data, heat and humidity are increasingly recognized as disease activity modifiers, and evidence for air pollution and microplastics is growing. Collectively, these findings support a model in which HS arises from intrinsic follicular dysregulation shaped by genetic, microbial, and hormonal factors, with environmental exposures influencing but unlikely to independently initiate disease.<\/jats:p>","DOI":"10.3390\/jcm15166256","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"6256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic Dysregulation and Environmental Modifiers in Hidradenitis Suppurativa: Toward an Integrated Pathophysiologic Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Dorsa","family":"Moslehi","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lannika","family":"Johnson","sequence":"additional","affiliation":[{"name":"Miami Hidradenitis Suppurativa Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra P.","family":"Charrow","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Hidradenitis Suppurativa and Neutrophilic Dermatosis Program, Department of Dermatology, The Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Pastar","sequence":"additional","affiliation":[{"name":"Miami Hidradenitis Suppurativa Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0140-6736(24)02475-9","article-title":"Hidradenitis Suppurativa","volume":"405","author":"Sabat","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis Suppurativa","volume":"6","author":"Sabat","year":"2020","journal-title":"Nat. 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