Exposome Versus Genome in HS: How Do We Currently Explain Where Disease Arises from?

Area of Science:

• Dermatology
• Genetics
• Environmental Health

Background:

• Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin condition with diverse clinical presentations and causes.
• While environmental factors like obesity and smoking are implicated, they don't fully explain HS development or variability.
• Genetic predisposition is increasingly recognized as a significant factor in HS pathogenesis.

Purpose of the Study:

• To review the evidence for both environmental (exposomic) and genetic (genomic) contributions to HS.
• To explore how these factors interact to influence HS risk and disease progression.
• To propose a unified model of HS pathogenesis integrating genetic and environmental influences.

Main Methods:

• Literature review of genetic studies (familial, GWAS) and environmental/lifestyle factor research in HS.
• Analysis of recent findings on shared biological pathways, including γ-secretase signaling.
• Synthesis of evidence supporting gene-environment interaction models.

Main Results:

• Both inherited susceptibility and environmental exposures play crucial roles in HS.
• Genetic risk variants and environmental factors may converge on common biological pathways.
• A model of gene-environment interaction provides a more comprehensive explanation for HS than either factor alone.

Conclusions:

• HS pathogenesis is best understood as a result of the interplay between genetic susceptibility and environmental exposures.
• This interaction influences HS risk, clinical expression, and disease progression.
• Future research should focus on understanding these complex interactions to improve HS management.