Unravelling the complex pathogenesis of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a complex inflammatory disease, with rapid advances being made in our understanding of the complex immunological pathogenesis of the condition. New insights into the genomic landscape of HS have identified a number of genes that contribute to the development of HS in a polygenic manner, contributing to inflammatory dysregulation and alterations in epidermal stem cell fate in the follicular unit. These genomic variations can explain unique aspects of the disease such as the development and presence of epithelialized tunnels and abnormalities in wound healing. From genetic and translational studies, it is likely that these genetic alterations predispose to an innate immune dysregulation that can be triggered through sex hormone-responsive transcription factors with hormonal changes such as puberty, pregnancy and the menstrual cycle. The role of sex hormones in HS also has direct effects upon the development and maturation of inflammatory cells such as monocytes, which has the potential to explain differential patient response to treatments such as interleukin-23 antagonism. The role of adipose tissue as an active immunological organ also plays a role in the immune dysregulation seen in the disease. Fibrotic tissue and immunologically active fibroblasts play a significant role in the perpetuation of inflammation and development of adaptive immune dysfunction in the disease. The cutaneous and gut microbiomes play significant roles in the activation of innate immunity, although conflicting data exist as to their central or peripheral role in disease pathogenesis. Overall, our understanding of disease pathogenesis in HS is moving toward a more nuanced, complex paradigm in which patient heterogeneity in presentation and immunological characteristics are moving closer to the identification of therapeutic biomarkers to guide therapeutic modalities in the management of this burdensome condition.