Casey Butrus, PharmD: Steve, I want to transition to the next question and ask you about the pathophysiology of acne, so our audience has a good understanding of the background. Acne has a complex pathophysiology that involves many factors. Could you give a high-level overview of the 4 factors involved in the pathogenesis?

Steven Feldman, MD, PhD: I can do that because 30-something years ago when I was a dermatology resident, 1 of my coresidents had to give a presentation to the department and chose to give a talk on the pathogenesis of acne. He talked about the 4 classic causes: too much oil production, hair follicles that get clogged, bacteria, and inflammation. When I heard that talk, I’m like, as a scientist, how do they know that’s what’s causing it? But those are the 4 causes considered to be involved in acne. To support that, those causes go along well with how we treat acne. The treatments we use attack 1 or more of those 4 causes. There are other ways of looking at it. You could look at acne pathogenesis in terms of being genetic or environmental. Where genetic studies find high levels of genetic association based on twin studies. One twin study found 80% of acne is genetic. On the other hand, it can be environmental. For example, if I see a young woman who’s incredibly fit looking and has sudden onset acne, I wonder, is she taking a supplement that has androgens in it? Is that suddenly causing her acne? We had so much knowledge about the genetics of acne. Roughly 50 genetic loci have been associated with acne. Are they all related to those 4 classic things: androgens, follicular blockage, bacteria, and inflammation? I’m not sure we know.

Casey Butrus, PharmD: Thank you for that explanation. Would you be able to elaborate more on the hormonal cause of androgen? Do you normally see that in just women, or is it common to see it in men as well?

Steven Feldman, MD, PhD: It almost has to be central. The androgens have to be very close and central to acne. We know that for several reasons. One is when you get acne. You get acne when the hormones go wild, and that creates increased sebum production. Sebum is a prerequisite for acne. Other things that might cause high levels of androgens are going to cause acne. The androgens might not just affect the amount of sebum produced, the oil that’s produced in those facial oil glands, but it can also affect the differentiation of the hair follicle that may contribute to acne. Something important I learned during my PhD training is if you give somebody a specific inhibitor of something and it blocks the problem, then you know that thing that you’re blocking is critically important. We know if you give androgen blockers to patients with acne, you can make acne better, which proves that acne is, at least part, an androgen-driven process.

Transcript edited for clarity.