Hidradenitis suppurativa: a comprehensive review of pathogenetic mechanisms, clinical phenotypes, and evolving therapeutic paradigms

Abstract

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, recurrent, and debilitating inflammatory skin condition characterized by deep-seated nodules, abscesses, fistulating sinus tracts, and scarring, primarily affecting apocrine gland-bearing skin. Historically dismissed as a disorder of poor hygiene or mere follicular occlusion, contemporary research has redefined HS as a systemic immune-mediated disease with profound implications for patient quality of life and metabolic comorbidities. This exhaustive review synthesizes the most current understanding of HS pathogenesis, which is now recognized as a multifactorial interplay of genetic predisposition, follicular hyperkeratosis and occlusion, dysbiosis of the cutaneous microbiome, and a profound dysregulation of the innate and adaptive immune system, with a prominent role for interleukin (IL)-17, IL-1β, and tumor necrosis factor-alpha (TNF-α). We meticulously detail the clinical spectrum, from prodromal manifestations to advanced Hurley stage III disease, emphasizing the nuances of phenotype classification and the critical importance of early diagnosis to mitigate disease-associated morbidity. A principal focus is dedicated to the rapidly expanding therapeutic landscape, moving beyond traditional antibiotics and surgery to include biologic agents that target specific inflammatory cytokines, with adalimumab (anti-TNF) as a cornerstone and emerging evidence for secukinumab (anti-IL-17A) and apremilast (PDE4 inhibitor). We further examine the robust association of HS with cardiometabolic syndrome, inflammatory bowel disease, and psychiatric comorbidities, advocating for a holistic, multidisciplinary management approach. This review consolidates evidence from recent clinical trials, consensus guidelines, and mechanistic studies to provide a foundational resource for clinicians and researchers navigating the complexities of this challenging disease.