Hidradenitis suppurativa: epidemiology, diagnosis, molecular pathogenesis and therapy

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease with a global prevalence ranging from 0.3–1%, characterized by recurrent nodules, abscesses, and sinus tracts that culminate in irreversible tissue fibrosis. Despite its impact on patient quality of life, the transition from acute inflammation to chronic tissue remodeling remains poorly understood. Comorbidities frequently accompany skin alterations. HS pathogenesis is complex and involves innate immune cells, Th1/Th17-cell responses, and B-cell mechanisms, which lead to irreversible skin damage with tunnel formation. This review synthesizes current knowledge on HS epidemiology, clinical features and molecular mechanisms driving its development and progression, with a focus on the pathogenic role of adipose tissue, and specifically of adipokines, on inflammation and tissue destruction. We delineate how systemic metabolic dysfunction, often associated with obesity, synergizes with local inflammation to alter the balance between MMPs and their tissue inhibitors TIMPs, thus contributing to a perpetuating circle of inflammation and fibrosis. Furthermore, we explore the impact of conventional and targeted therapies on the interruption of broad or specific inflammatory and fibrotic pathways to reduce disease activity, and restore skin homeostasis. Vice versa, we illustrate how the dysregulated metabolic-inflammatory axes influence the therapeutic outcomes emphasizing how the adipose tissue microenvironment modulates the response to conventional and targeted therapies. Finally, we discuss how targeting the interplay between metabolic health and tissue destruction represents a promising frontier for preventing the permanent skin damage in advanced disease, offering the potential for more tailored and effective intervention strategies.