An Integrated Approach to Unravel Hidradenitis Suppurativa Etiopathogenesis

Abstract

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease involving hair follicles that presents with painful nodules, abscesses, fistulae, and hypertrophic scars, typically occurring in apocrine gland bearing skin. Establishing a diagnosis of HS may take up to 7 years after disease onset. HS severely impairs the quality of life of patients and its high frequency causes significant costs for health care system. HS patients have an increased risk of developing associated diseases, such as inflammatory bowel diseases and spondyloarthropathies, thereby suggesting a common pathophysiological mechanism. Familial cases, which are around 35% of HS patients, have allowed the identification of susceptibility genes. HS is perceived as a complex disease where environmental factors trigger chronic inflammation in the skin of genetically predisposed individuals. Despite the efforts made to understand HS etiopathogenesis, the exact mechanisms at the basis of the disease need to be still unraveled. In this review, we considered all OMICs studies performed on HS and observed that OMICs contribution in the context of HS appeared as not clear enough and/or rich of useful clinical information. Indeed, most studies focused only on one aspect—genome, transcriptome, or proteome—of the disease, enrolling small numbers of patients. This is quite limiting for the genetic studies, from different geographical areas and looking at a few aspects of HS pathogenesis without any integration of the findings obtained or a comparison among different studies. A strong need for an integrated approach using OMICs tools is required to discover novel actors involved in HS etiopathogenesis. Moreover, we suggest the constitution of consortia to enroll a higher number of patients to be analyzed following common and consensus OMICs strategies. Comparison and integration with the findings present in the OMICs repositories are mandatory. In a theoretic pipeline, the Skin-OMICs profile obtained from each HS patient should be compared and integrated with repositories and literature data by using appropriate InterOMICs approach. The final goal is not only to improve the knowledge of HS etiopathogenesis but also to provide novel tools to the clinicians with the eventual aim of offering a tailored treatment for HS patients.

Pleiotropic Role of Notch Signaling in Human Skin Diseases

“…The exact etiology of HS is yet not completely unraveled; however, both genetic and environmental factors are known to trigger the development of the disease. A recent article by Tricarico et al reported an exhaustive overview of the genes involved in HS susceptibility [ 93 ], highlighting that about 35% of HS patients present a family history of HS. Mutations in NCSTN , PSENEN and PSEN1 genes, respectively encoding for NCSTN, PSENEN and PSEN1, have been identified as the most common genetic variants involved in HS familial cases.…”

KLICK Syndrome Linked to a POMP Mutation Has Features Suggestive of an Autoinflammatory Keratinization Disease

“…In 2010, mutations in genes encoding γ-secretase subunits (NCSTN, PSENEN, and PSEN1) were reported in patients presenting with hidradenitis suppurativa (HS) (36). The essential subunit of the γ-secretase complex, an endoprotease complex, catalyzes the intramembrane cleavage of integral membrane proteins, such as Notch receptors, and amyloid-beta precursor protein (37). γ-Secretase deficiency could also regulate inflammation by processing important cytokine receptors such as IL-1β R1/R2 and IL-6R (37).…”

“…The essential subunit of the γ-secretase complex, an endoprotease complex, catalyzes the intramembrane cleavage of integral membrane proteins, such as Notch receptors, and amyloid-beta precursor protein (37). γ-Secretase deficiency could also regulate inflammation by processing important cytokine receptors such as IL-1β R1/R2 and IL-6R (37). HS caused by mutations in genes encoding γ-secretase subunits was suggested to have features characteristic of an AiKD (9, 38).…”

Romatoloji̇k Hastaliklarda Hi̇dradeni̇ti̇s Süpürati̇va’nin Önemi̇

“…TARTIŞMA HS, geleneksel olarak ter bezlerinin bir hastalığı olarak görülse de, şu anki anlayış genetik olarak duyarlı bireylerde tekrarlayan mekanik stres nedeniyle oluşan foliküler epitel bozukluğudur. HS patogenezinde düzensiz immünitenin primer rolü olduğu ortaya konulmuştur (9). Birçok çalışma, lezyonlu deride interlökin (IL) -1 beta, TNF, IL-17 ve IL-10 pro ve anti-inflamatuar sitokinlerin yüksek seviyelerini göstermiştir (10).…”