32 Studies Supporting HS as an Auto-Inflammatory Illness
A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS . Based on recent data, an integrative viewpoint is presented on the pathogenesis of HS.
Current evidence highlights a complex multifactorial pathogenesis (5). A key triggering factor is the occlusion of the hair follicle, caused by keratosis and hyperplasia of the follicular epithelium leading to cyst development (6, 7). Subsequently, the cyst will rupture, causing a fierce immune response and inflammation that, depending on the severity, may progress to abscess and sinus tract development and scarring (6, 7). The name of the disease implies that sweating and bacterial infection are a fundamental part of the disease process. This is misleading and now considered a misnomer: no evidence has been found showing that HS is triggered by events in the apocrine or eccrine glands. (8). In addition, HS can occur with several co-morbid immune-mediated inflammatory diseases (IMIDs), notably inflammatory bowel disease (IBD) (9).
Clear evidence suggests the involvement of pro-inflammatory cytokines in immune dysregulation in HS, with elevated levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-17 and interferon (IFN)-γ observed in HS lesions (5, 10, 11). Data also indicate the involvement of T helper (Th) cells, which accumulate in HS lesions, in the pathogenesis of HS (11, 12). In addition, studies have shown that antimicrobial peptides (AMPs) like cathelicidin (LL-37) and human β-defensin are increased in HS lesions compared with normal skin of HS patients (13). The use of TNF-α inhibitors such as adalimumab and infliximab have been associated with improvements in immune dysregulation in HS and support the importance of local molecular drivers in the pathogenesis of HS (1, 14, 15).
Furthermore, mutations in γ-secretase genes, whose gene products act on many substrates including Notch (16), suggest that Notch or other substrates of γ-secretase may play a role in the pathogenesis of HS. Interestingly, γ-secretase knock-out mice are characterized by a phenotype of multiple cutaneous cysts, a key feature of HS (17). To date it remains unclear whether the effects of Notch on follicle development or its immune role play a significant role in HS pathogenesis.
Rapidly evolving understanding in the auto-inflammatory arena is needed to improve awareness of HS, disease management, and ultimately improve patient outcomes.