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

Abstract

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory dermatosis of the pilosebaceous unit characterized by nodules, abscesses, and dermal tunnels. Recent transcriptomic studies have implicated dysregulation of innate and adaptive immune responses, epidermal barrier dysfunction, and systemic metabolic alterations. This review synthesizes findings from 16 studies investigating the HS transcriptome using bulk and single-cell RNA sequencing. Differential gene expression analyses revealed extensive upregulation of inflammatory cytokines and chemokines, particularly in lesional and perilesional skin. These changes were also mirrored in non-lesional skin, suggesting diffuse immune dysregulation beyond visibly affected areas. Downregulated pathways include those involved in lipid metabolism, muscle contraction, and neuronal signaling, potentially linking HS to obesity, metabolic syndrome, and neuropsychiatric comorbidities. Single-cell transcriptomics confirmed the enrichment of keratinocytes and immune cells (B cells, plasma cells, M1 macrophages, and T cells) with proinflammatory profiles in HS lesions. Keratinocyte dysfunction further implicated a compromised epidermal barrier in disease pathogenesis. While transcriptomic studies have advanced mechanistic understanding and highlighted therapeutic targets-such as the IL-1β-TH17 axis and B cell signaling pathways-methodological heterogeneity limits cross-study comparisons. Integration of multi-omics data and standardized phenotyping will be essential to identify robust biomarkers, stratify HS subtypes, and guide personalized therapeutic approaches.

Keywords: hidradenitis suppurativa; pathomechanisms; targeted treatment; transcriptome.

Figure 1

Overview of the methods and characteristics of patients in the reviewed studies. (A) Types and corresponding proportion of analytical methods used in the 16 studies. (B) Summary of the patients’ demographic data most reported among the studies, including sex, smoking status, age, and BMI (the mean values for age and BMI were calculated using the average values of the individual studies). (C) Areas from which HS skin samples were collected (the number also indicates the frequency of reporting of the anatomical site): 1—axilla (n = 6/16) [21,22,24,25,33,36], 2—inguinal (n = 5/16) [21,22,24,29,33], 3—pubic (n = 5/16) [21,22,24,29,33], 4—buttock (n = 3/16) [21,24,33], 5—inframammary (n = 3/16) [21,24,33], 6—neck (n = 2/16) [24,33].

Figure 2

UpSet plot showing the overlap of differentially expressed genes (DEGs) across tissue types in hidradenitis suppurativa. The dot–line matrix below the vertical bars represents all possible intersections between tissue-specific DEG sets: each column represents a specific combination of tissue types (lesional skin—blue, perilesional skin—purple, non-lesional skin—green, and blood—pink), with filled dots indicating which tissues are included in that intersection. Vertical bars indicate the number of shared DEGs across those tissues. Horizontal bars depict the total number of DEGs identified within each individual tissue type, ordered by increasing DEG set size. The plot illustrates both unique and overlapping gene expression patterns, highlighting the extent of molecular dysregulation beyond clinically lesional skin.

Figure 3

Exploratory assessment of the HS transcriptomes of skin and blood samples, showing the gene categories by tissue type for the (A) upregulated and (B) downregulated gene lists of patients with HS relative to healthy controls (IG—immunoglobulin gene, lncRNA—long non-coding RNA, miRNA—microRNA, miscRNA—miscellaneous RNA, snRNA—small nuclear RNA, snoRNA—small nucleolar RNA, TR—T cell receptor gene).

Figure 4

Enriched Reactome pathways in upregulated (A) and downregulated (B) DEG lists for each HS tissue type when compared to healthy controls; the pathways shown were obtained following weighted set cover redundancy reduction; all pathways had a p-value < 0.05, but those for blood tissue had a non-significant FDR value, i.e., >0.05.

Figure 5

Single-cell transcriptome of keratinocytes. (A) Gene categories for upregulated and downregulated genes in the keratinocytes of patients with HS (IG—immunoglobulin gene, lncRNA—long non-coding RNA, miRNA—microRNA, miscRNA—miscellaneous RNA, rRNA—ribosomal RNA, scaRNA—small Cajal body-specific RNA, snRNA—small nuclear RNA, snoRNA—small nucleolar RNA, TR—T cell receptor gene). (B) Enriched Reactome pathways for upregulated and downregulated genes in the keratinocytes of patients with HS when compared to healthy controls. The pathways shown were obtained following weighted set cover redundancy reduction. All pathways had a p-value < 0.05, but all downregulated and 1 upregulated pathway had a non-significant FDR value, i.e., >0.05.

Figure 6

PRISMA flow diagram summarizing the article selection process.