The Genomic Architecture of Hidradenitis Suppurativa—A Systematic Review

Abstract

Hidradenitis suppurativa is a chronic, suppurative condition of the pilosebaceous unit manifesting as painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin. Great strides have been made at elucidating the pathophysiology of hidradenitis suppurativa, which appears to be the product of hyperkeratinization and inflammation brought about by environmental factors and a genetic predisposition. The identification of familial hidradenitis suppurativa has sparked research aimed at identifying underlying pathogenic variants in patients who harbor them. The objective of this review is to provide a broad overview of the role of genetics in various aspects of hidradenitis suppurativa, specifically the pathophysiology, diagnosis, and clinical application.

Circulating microRNAs in Hidradenitis Suppurativa

“…According to extensive genetic analysis, only a minority of patients have a monogenetic diagnosis [ 21 ]. Consequently, epigenetic phenomena may influence HS.…”

Interpreting the spectrum of gamma-secretase complex missense variation in the context of hidradenitis suppurativa—An in-silico study

“…GSC variants with a structurally deleterious impact on protein structure are highlighted red in ball and stick mode in Figure 4. In comparison, four (namely p. Gly61Val (Duchatelet et al, 2020), p. Gln216Pro (Zhang et al, 2013), p. Glu296Gly (Xu et al, 2016) and p. Gly576Val (Duchatelet et al, 2020) [residues in ball and sick mode highlighted in green]) of the ten NCSTN missense variants reported in HS are deleterious (40%, χ 2 = 6.01, p < 0.05) (Pace et al, 2022). The criteria for deleteriousness is illustrated in Supplementary Table S1.…”

“…Conflicting results have also been obtained with regards to differential expression of genes coding for proteins of the GSC in serum and skin (Wang et al, 2010;Zouboulis et al, 2021). Therefore, despite a putative monogenic disease driver in a subset of HS patients harboring pathogenic variants, predominantly in genes coding for the protein subunits of the ɣ secretase complex (GSC) (Pace et al, 2022), the exact nature of the genetic risk in the disease remains elusive.…”

“…Importantly, the molecular etiology of HS and fAD do not directly overlap. Of the GSC protein-coding genes, monogenic HS is mostly related to pathogenic variation in NCSTN (OMIM: #142690, Acne inversa, Familial 1), unlike fAD which is predominantly associated with PSEN mutations (Xiao et al, 2021;Pace et al, 2022). Additional loci involved in HS include PSTPIP1, MEFV, NLRP3, IL1RN, NOD2 and POFUT, although their relevance to disease has been disputed.…”

Platelet-Rich Plasma and Acellular Dermal Matrix in the Surgical Treatment of Hidradenitis Suppurativa: A Comparative Retrospective Study

“…This devastating disease has a significant impact on many aspects of patients’ lives [ 7 ]. The cause of hair follicle plugging is still unclear and subject to scientific debate, although immune and genetic factors, particularly variants in genes encoding ɣ secretase complex proteins ( NCSTN encoding nicastrin; PSEN1 for presenilin-1; PSENEN for presenilin enhancer; gamma-secretase subunit), hormonal fluctuations, and environmental risk factors are believed to play a role [ 8 , 9 , 10 ]. The most common sites for hidradenitis suppurativa are the main folds of the body, including the axillary and inguinal regions, the skin of the buttocks, the sub-mammary area, and the neck, waist, and inner side of the thighs [ 11 ].…”