Pathophysiology of hidradenitis suppurativa

Abstract

The pathophysiology of hidradenitis suppurativa (HS) is not well understood. Some of our knowledge comes from clinical and epidemiological observations, along with studies of the histopathology and immunohistochemistry of affected skin. More recently, cutaneous molecular studies and transcriptomic analyses have provided additional information regarding inflammatory processes. The chronic cutaneous inflammation, systemic symptoms, and associated comorbidities suggest that HS should be classified as an immune-mediated disease, rather than a primary infectious disease. As such, a proposed integrated disease pathway is presented. At a fundamental level, there appears to be a primary abnormality in the pilosebaceous-apocrine unit, which leads to follicular occlusion, perifollicular cyst development that traps commensal microbes, and rupture into the dermis. This can trigger an exaggerated response of the cutaneous innate immune system. Initially this is an acute event, but ongoing intermittent disease activity can lead to recurrent inflammatory nodules and dermal tunnels. Once underway, the cutaneous inflammation is very difficult to turn off, leading to suppurative inflammation in whole anatomic regions. As the disease progresses, we propose that there is recruitment of the systemic immune system perpetuating the chronic cutaneous inflammatory process. There remains much to be done to understand the pathogenesis and immune signature of this challenging disease.

Proceeding report of the third symposium on Hidradenitis Suppurativa advances (SHSA) 2018

“…Additionally, there may be shared immune responses with other chronic cutaneous diseases including abundant AMPs, inflammatory cytokines (IL‐1, IL‐6, IL‐17, IL‐12/23) and Th17/T‐reg dysregulation. These findings propose several molecular targets for therapeutic interventions in HS …”

Successful control of hidradenitis suppurativa with verapamil: a case report

“…The pathogenesis is not still understood; genetic predisposition, bacterial infection, hormones, obesity, and smoking play a role. Recently, an immune response dysfunction has been identified, involving pro‐inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐10, IL‐12/23, and IL‐17 . In patients with Hurley stages 2 and 3, elevated serum levels of TNF‐α, IL‐1β, and IL‐10 have been measured .…”

“…In patients with Hurley stages 2 and 3, elevated serum levels of TNF‐α, IL‐1β, and IL‐10 have been measured . Several clinical trials with biologic agents such as anti‐TNF‐α (adalimumab), anti‐IL1 (anakinra), and anti‐IL23 (ustekinumab) showed an improvement in patients with HS . In 2015, adalimumab was the first TNF‐α inhibitor approved for moderate to severe HS.…”

Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model

“…In our studies, the subcutaneous fat layer was removed from HS lesions and some samples were thin sections of epidermis and partial dermis. Using full‐thickness skin might have produced a more representative phenotype, particularly as components in the deeper dermis are central to HS pathogenesis . Another option is to use reconstructed three‐dimensional skin grafts with dermal scaffolds (e.g.…”

“…Using full-thickness skin might have produced a more representative phenotype, particularly as components in the deeper dermis are central to HS pathogenesis. 1 Another option is to use reconstructed three-dimensional skin grafts with dermal scaffolds (e.g. fibrin or collagen).…”