Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses and draining tunnels commonly affecting the axillary, anogenital, inguinal and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the tumour necrosis factor (TNF)-alpha and interleukin (IL)-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications; systemic therapies, including repeated and/or rotational courses of systemic antibiotics, retinoids and hormonal therapies; and various surgical procedures. The anti-TNF-alpha antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers. This review explores the pathophysiology, current therapeutic landscape and outlook of hidradenitis suppurativa (HS). We present new insights into disease pathophysiology, with an overview of the contributing pathways, cell types and cytokines, as well as several promising therapeutic targets that have emerged in addition to TNF-alpha, providing an up-to-date overview of the diverse and evolving treatment landscape. Additionally, this review identifies future areas of focus to improve management for patients with HS.

Automated summary

Hidradenitis suppurativa (HS) is a chronic, disabling, and debilitating inflammatory disease with limited treatment options. The pathophysiology of HS is not fully understood, but TNF-alpha and IL-17 pathways play important roles. Currently, multiple promising therapeutic targets are being explored.