Insights into the Pathogenesis of HS and Therapeutical Approaches

Abstract

Hidradenitis suppurativa (HS) is a debilitating, chronic, (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. Although pathogenic mechanisms responsible for HS have not yet been fully elucidated, it is a multifactorial process whose main target is the terminal follicle. The role of the inflammatory process (and consequently of cytokine milieu) and of several other factors (genetics, lifestyle, hormonal status, microbiome, innate and adaptive immune systems) involved in HS pathogenesis has been investigated (and often defined) over the years with a view to transferring research results from bench to bedside and describing a unique and universally accepted pathogenetic model. This review will update readers on recent advances in our understanding of HS pathogenesis and novel (potential) medical therapies for patients with moderate-to-severe HS.

Hidradenitis Suppurativa: The Influence of Gender, the Importance of Trigger Factors and the Implications for Patient Habits

“…Overall, the observed improvement in disease activity during pregnancy may be traced back to an increase in serum levels of (i) (in late pregnancy) interleukin (IL)-1 receptor antagonists (IL-1RA) and soluble tumour necrosis factor alpha (TNF-α) receptor (TNF-R), anti-inflammatory molecules neutralizing the effects of both IL-1 and TNF-α, respectively, and (ii) progesterone, which inhibits T helper (Th) 17 cell differentiation and promotes differentiation of Th2 and regulatory T (Treg) cells ( Figure 1 ). On the other hand, pregnancy may worsen HS symptoms by increasing (i) the activity of sebaceous and eccrine glands and (ii) body weight, which in turn is associated with an increase in mechanical friction, insulin resistance and secretion (from adipocytes) of pro-inflammatory cytokines, including TNF-α ( Figure 1 ) [ 1 , 153 , 154 ].…”

“…Abbreviations: BMI, body mass index; SES, socioeconomic status; MMPs, matrix metalloproteinases; TNF—α, tumor necrosis factor alpha; TNF-R, tumor necrosis factor receptor; IL, interleukin; cAMP, cyclic adenosine monophosphate; IGF-1, insulin-like growth factor 1; AR, androgen receptor; TS, testosterone; DHT, dihydrotestosterone; 5-α R, 5-α-reductase; IL-1RA, interleukin 1 receptor antagonist. Information extracted from references [ 1 , 44 , 55 , 56 , 57 , 58 , 59 , 61 , 64 , 74 , 80 , 93 , 94 , 125 , 153 , 154 ].…”

“…Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil’s disease, is a debilitating chronic skin disease of intertriginous areas [ 1 ].…”

Pediatric hidradenitis suppurativa

“…However, the mechanism for this remains unclear 25 . Historically, rationale for the association between BMI and HS have included mechanical friction, increased perspiration, and a relative increase in androgens produced by adipose tissue 26,27 . Yet, clearly obesity alone does not explain why an individual develops HS in that there are a significant portion of affected pediatric patients with normal BMI.…”

“…25 Historically, rationale for the association between BMI and HS have included mechanical friction, increased perspiration, and a relative increase in androgens produced by adipose tissue. 26,27 Yet, clearly obesity alone does not explain why an individual develops HS in that there are a significant portion of affected pediatric patients with normal BMI. It is plausible that factors that place children at risk of developing obesity may also increase the risk of acquiring HS.…”