Immunopathogenesis of Hidradenitis Suppurativa: Updated Review

Introduction and Objective. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease characterized by follicular occlusion, painful nodules, abscesses, sinus tract formation, and scarring, primarily affecting intertriginous areas. Although previously considered a disorder of the apocrine glands, HS is now recognized as a complex immunoinflammatory condition involving dysregulation of innate and adaptive immune pathways. This review aims to summarize current knowledge on the immunopathogenesis of HS, with particular emphasis on recent molecular and cellular insights relevant to targeted therapy. Brief Overview of Current Knowledge. The initiating event in HS is follicular hyperkeratosis, leading to follicular rupture and secondary inflammation. Disease progression is driven by persistent immune activation, dominated by Th1/Th17 polarization. Key mechanisms include increased expression of proinflammatory cytokines such as IL-17, IL-1β, TNF-α, and IFN-γ, activation of the complement system, especially C5a, and dysregulation of antimicrobial peptides. Aberrant interactions between keratinocytes, fibroblasts, plasma cells, innate lymphoid cells, and T-cell subsets contribute to chronic inflammation and tissue destruction. Summary. Hidradenitis suppurativa is a multifactorial immunoinflammatory disease in which follicular occlusion initiates a complex immune cascade. Identification of biomarkers and therapeutic targets, including IL-17-driven pathways, complement components, and CD2–CD58 signaling, supports the development of personalized, mechanism-based treatment strategies. Improved understanding of HS immunopathogenesis may enhance disease stratification and clinical outcomes.