Abstract
Chronic inflammation and dysregulated epithelial differentiation, especially of hair follicle keratinocytes, have been suggested as the major pathogenetic pathways of hidradenitis suppurativa/acne inversa (HS). On the other hand, obesity and metabolic syndrome have additionally been considered as an important risk factor. With adalimumab, a drug has already been approved and numerous other compounds are in advanced-stage clinical studies. A systematic review was conducted to detect and corroborate HS pathogenetic mechanisms at the molecular level and identify HS molecular markers. The obtained data were used to confirm studied and off-label administered drugs and to identify additional compounds for drug repurposing. A robust, strongly associated group of HS biomarkers was detected. The triad of HS pathogenesis, namely upregulated inflammation, altered epithelial differentiation and dysregulated metabolism/hormone signaling was confirmed, the molecular association of HS with certain comorbid disorders, such as inflammatory bowel disease, arthritis, type I diabetes mellitus and lipids/atherosclerosis/adipogenesis was verified and common biomarkers were identified. The molecular suitability of compounds in clinical studies was confirmed and 31 potential HS repurposing drugs, among them 10 drugs already launched for other disorders, were detected. This systematic review provides evidence for the importance of molecular studies to advance the knowledge regarding pathogenesis, future treatment and biomarker-supported clinical course follow-up in HS.
Highlights
Introduction published maps and institutional affilHidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly at the axillae, inguinal and anogenital regions [1]
Among the 109 detected genes/proteins out of the 386 genes/proteins detected without restrictions, which fulfilled this requirement, 43 differentially expressed genes (DEGs) have been described in 2/4 targets in two articles, seven in 3/4 targets (CXCL10, IL6, IL17A, IL36A, IL36G, S100A8, S100A9) and none in all four targets (Table 1)
Additional 10 DEGs have been described in 2/4 targets, in a diversified direction
Summary
Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly at the axillae, inguinal and anogenital regions [1]. A consistent finding, regardless of disease duration, is follicular hyperkeratosis, leading to follicular rupture, inflammation and possible secondary bacterial colonization. The deep part of the follicle appears to be involved. HS is further associated with an initial lymphohistiocytic inflammation, granulomatous reaction, sinus tract formation and scarring [2]. An inflammatory process coupled to impaired barrier function and bacterial activity were detected at the follicular and epidermal keratinocyte and at a minor iations
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