The Genetics of Acne.

This review addresses the genetics of acne vulgaris, the most common skin disease. It is characterized by the presence of comedones (blackheads), papules, and pustules. The condition is associated with sebaceous glands in the face and chest, which produce an oily substance called sebum. In developed nations, acne affects over 80% of adolescents. Mild disease usually resolves spontaneously. More severe acne can leave permanent, disfiguring scarring and strongly affects quality of life. In those cases, medical intervention is warranted. To date, antibiotics and retinoids (synthetic vitamin A derivatives) are the mainstays of treatment. Depending on the severity of the condition, these drugs may be administered either topically or systemically. Whilst generally effective, they do come with significant drawbacks. Antibiotic use for treating acne is contributing to antimicrobial resistance. In addition, indiscriminate eradication of the skin microbiome negatively impacts skin health. Retinoids are teratogenic and have other undesirable side effects, such as skin irritation and increased UV sensitivity. Thus, there is a clear need for effective interventions that target the underlying disease mechanism, minimizing side effects. Rapid progress has recently been made in understanding the mechanisms underlying acne. For decades, it was assumed that blackhead formation results from the accumulation of sebum in the hair follicle opening, due to increased sebum production at the onset of puberty. Subsequent colonization by the commensal bacterium Cutibacterium acnes then was thought to cause inflammation. It was also postulated that this micro-organism could induce blackheads. There are, however, several problems with this supposed sequence of events, not the least of which is that it doesn't explain how retinoids work, or why sebaceous glands associated with blackheads are atrophic and hence produce less sebum, not more. Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne. Together with insights from mouse models, this new perspective is transforming the way we think about acne and its treatment.