Pathogenesis of hidradenitis suppurativa: From susceptibility to chronicity.

Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease characterized by painful nodules, abscesses, draining tunnels and scarring, with substantial effects on quality of life. Although the therapeutic landscape has expanded with biologics targeting TNF, IL-17A and IL-17A/F, many patients do not achieve sustained disease control, and chronic, draining tunnels remain difficult to treat. Recent data support a more integrated view of HS as a heterogeneous, stage-dependent disease in which inherited susceptibility, modifiable risk factors, epithelial dysfunction, immune activation and microbial ecology converge. In this review, we summarize clinically relevant advances in HS epidemiology, genetics, immunopathogenesis and microbiome research. Global studies highlight substantial variation in prevalence, sex distribution and clinical phenotype across populations, suggesting differences in risk architecture and disease expression. Genetic studies have moved the field beyond rare γ-secretase-associated familial disease towards a polygenic model involving follicular and epithelial regulatory programmes, antigen presentation and immune regulation. Single cell and spatial studies further indicate that HS pathogenesis evolves from epithelial stress and perifollicular inflammation in HS-prone skin, through IL-1-, TNF-, neutrophil- and IL-17-associated acute inflammation, towards chronic immune-stromal niches characterized by epithelialized tunnels, B cells, plasma cells, tertiary lymphoid structures, NETosis and fibrosis. In parallel, microbiome studies suggest that dysbiosis, particularly anaerobe-rich and biofilm-like communities within tunnels, acts primarily as an amplifier of chronicity rather than as a proven initiating event. Together, these findings support a shift from single-pathway models towards stage-specific and patient-stratified approaches aimed at earlier diagnosis, rational treatment selection and prevention of irreversible tissue damage.