Hidradenitis Suppurativa Tunnels: Unveiling a Unique Disease Entity
Open accessAbstract
Hidradenitis suppurativa tunnel structures lined with epithelium within the dermis are unique features of advanced disease stages that significantly impair patients' QOL. The presence of hidradenitis suppurativa tunnels is associated with a decreased likelihood of achieving a clinical response, even when receiving biological therapy. The cellular and molecular mechanisms underlying tunnel formation and pathology are only partially understood, which hampers the development of more effective targeted therapies. Tunnels create a unique microenvironment that drives a vicious cycle of hidradenitis suppurativa inflammation, with tunnel keratinocytes exhibiting an activated phenotype characterized by distinct gene expression signatures. In this review, we summarize the current literature and discuss aspects of the pathophysiology of tunnels, including the role of hair follicle epidermal stem cells in tunnel formation, potential role of fibroblast-mediated epithelial-mesenchymal transition, role of dermal papilla fibroblasts, and aberrant proinflammatory repair response contributing to the observed fibrosis and scarring. Finally, tunnel structures are characterized by unique microbial dysbiosis and an overabundance of Gram-negative anaerobes that are not targeted by current therapeutics. In addition to outlining the possible mechanisms of tunnel formation, we provide perspectives on the translation of current knowledge into more effective treatment approaches for patients with hidradenitis suppurativa tunnels.
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In moderate-to-severe hidradenitis suppurativa, treatment includes targeted biologic agents, notably TNF-α inhibition with adalimumab and IL-17A inhibition with secukinumab, while strategies against the IL-17/IL-23 pathway, IL-1 signaling, and IL-36 and innate immune signaling remain under investigation.
“In moderate-to-severe disease, treatment includes targeted biologic agents, notably TNF-α inhibition with adalimumab, and IL-17A inhibition with secukinumab, while additional therapeutic strategies directed against the IL-17/IL-23 pathway, IL-1 signaling, and IL-36 and innate immune signaling pathways remain under investigation [42,43].”
From The Cutaneous Immune Microenvironment in Selected Inflammatory Skin Diseases: Linking Histopathology, Mechanisms, and Targeted Therapy (2026) · cites this paper as [43]
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Experimental — accuracy not yet measuredIn mild hidradenitis suppurativa, treatment relies on topical and systemic anti-inflammatory and antimicrobial therapies, including topical clindamycin and oral tetracyclines or clindamycin-rifampicin, which reduce bacterial load and secondary immune activation.
“In mild disease, treatment relies on topical and systemic anti-inflammatory and antimicrobial therapies, including topical clindamycin and oral tetracyclines or combination regimens such as clindamycin–rifampicin, which help reduce bacterial load and secondary immune activation.”
From The Cutaneous Immune Microenvironment in Selected Inflammatory Skin Diseases: Linking Histopathology, Mechanisms, and Targeted Therapy (2026) · cites this paper as [43]
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References 163 · Cited by 10
- Authors
- Vecin, N., Balukoff, N. C., Yaghi, M., Gonzalez, T., Sawaya, A. P., Strbo, N., Tomic-Canic, M., Lev-Tov, H., & Pastar, I.
- Affiliations
- University of Miami (US)
- Corresponding author
- Pastar, Irena
- ORCID
- Venue
- JID Innovations
- Publisher
- Elsevier BV
- Published
- 2025-05
- Volume
- 5
- Issue
- 3
- Pages
- 100350
- ISSN
- 2667-0267 (ISSN-L)
- PMC
- PMC11872476
- OpenAlex
- W4406651072
- Cited by
- 10
- References
- 163
- Citations by year
- 2026: 9 · 2025: 1
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JID Innovations (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Dermatology Foundation
- Hidradenitis Suppurativa Foundation
- Association for Psychological Science
- Heising-Simons Foundation
- NIH (R01AR083385)
- Topics
- Health Sciences › Medicine › Dermatology › Hidradenitis Suppurativa and Treatments
- Health Sciences › Medicine › Epidemiology › Autoimmune and Inflammatory Disorders
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- hidradenitis suppurativa, tunnel structure, epithelial-mesenchymal transition, dysbiosis, Gram-negative anaerobic bacteria, inflammation, biological therapy response, quality of life, pathophysiology
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