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.

Keywords: OMICs; data integration; genomics; hidradenitis suppurativa; proteomics; public repositories; transcriptomics.

Figure 1

Genes associated with susceptibility and progression of hidradenitis suppurativa. Susceptibility to the disease is caused by mutations in genes involved in keratinocytes homeostasis having a role in maintaining the integrity of the epithelial barrier. Common polymorphisms in genes encoding for proteins involved in the immune response have been associated to severity of the disease and influence the inflammatory and chronic phases. The disease model depicted is based on the most accepted model reported by Berna-Serna and Berna-Mestre (54) for hidradenitis suppurativa.

Figure 2

Integrated OMICs pipeline set up for disclosing the actors involved in hidradenitis suppurativa pathogenesis and proposing a personalized treatment for the patients.