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Transcriptomic Signatures and Molecular Pathways in Hidradenitis Suppurativa-A Narrative Review.

Jasmine Spiteri¹, Dillon Mintoff^2,3, Laura Grech^1,4

¹Centre for Molecular Medicine & Biobanking, University of Malta, MSD 2080 Msida, Malta.

International Journal of Molecular Sciences

|August 28, 2025

Summary

Hidradenitis suppurativa (HS) involves immune dysregulation and epidermal barrier issues. Transcriptomic analysis reveals widespread inflammation and altered metabolic pathways, offering new therapeutic targets.

Keywords:

hidradenitis suppurativa pathomechanisms targeted treatment transcriptome

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Area of Science:

Dermatology
Immunology
Genomics

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting the pilosebaceous unit.
Recent research suggests immune, epidermal barrier, and metabolic dysregulation in HS pathogenesis.

Purpose of the Study:

To synthesize findings from transcriptomic studies on HS.
To identify key molecular pathways and potential therapeutic targets in HS.

Main Methods:

Review of 16 studies utilizing bulk and single-cell RNA sequencing.
Differential gene expression analysis and pathway enrichment analysis.

Main Results:

Significant upregulation of inflammatory cytokines/chemokines in lesional, perilesional, and non-lesional skin.
Downregulation of lipid metabolism, muscle contraction, and neuronal signaling pathways.
Enrichment of proinflammatory keratinocytes and immune cells (B cells, M1 macrophages, T cells) in HS lesions.

Conclusions:

Transcriptomic data highlights diffuse immune dysregulation and keratinocyte dysfunction in HS.
Identified therapeutic targets include the IL-1β-TH17 axis and B cell signaling.
Future research requires multi-omics integration and standardized phenotyping for biomarker discovery and personalized medicine.