Two Docs Talk: Acne

Narrator: 0:01

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased evidence, proven facts powered by ENCORE Research Group and hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren: 0:17

Hello, I'm Dr. Michael Koren and I'm very excited to lead another session of Two Docs Talk, which is part of our MedEvidence platform. I'm particularly excited today because I have a great guest Dr. Michael Bernhardt is here with me.

Dr. Michael Bernhardt: 0:32

Thank you.

Dr. Michael Koren: 0:33

Michael and I have known each other for a few years now. Michael is an amazing dermatologist. I trust my own skin to him.

Dr. Michael Bernhardt: 0:40

Thank you.

Dr. Michael Koren: 0:41

And he's also a great researcher and I've worked with him in the research realm here at Jacksonville Center for Clinical Research. So we're going to talk about an area that is probably the bread and butter of dermatologists and is something that is now getting a very high tech spin, and that's the treatment of acne.

Dr. Michael Bernhardt: 0:58

Correct.

Dr. Michael Koren: 0:59

So what I'm going to do is we're going to walk through what is acne, who does it affect all the basics, and then we'll eventually get to the elements that are really exciting, which is, new ways of treating it that may be more effective than what we have now.

Dr. Michael Bernhardt: 1:14

What's interesting is that as a dermatologist, the stage we're at in terms of treating acne is kind of similar, in my opinion, to where we were in terms of treating psoriasis back in 2005, 2003. Before the biologics had the big impact and, of course, we did some of the studies here Taltz, Cosentyx, all these drugs were huge game changers for psoriasis and I still think that in a way, we're still in kind of a early phase of understanding, even though this is ubiquitous problem. According to the people that are promoting the study. I think that the target range is over 230 million people that globally with acne and it creates a lot of morbidity more than people realize the physical impact in terms of scarring, psychological impact in terms of state of being, state of mind, particularly in vulnerable teenagers who have self-esteem issues as a rule to begin with. So if something could be done to bring acne care to the 21st century, that would be great.

Dr. Michael Koren: 2:23

Yeah, exciting, so let's break it down for our audience. So let's start with the definition of acne and what is the cause of acne.

Dr. Michael Bernhardt: 2:31

So acne is inflammatory condition that affects the sebaceous glands and the first step is comedone formation and the analogy.

Dr. Michael Koren: 2:41

Before you get to that, so does it just affect the face or is acne everywhere?

Dr. Michael Bernhardt: 2:43

It could be the trunk, it could be face back chest, it could be small. Just sun exposed or any place, doesn't really matter? Anywhere it goes anywhere, there's a follicles is at risk, and so the first step is a plug into the pore. The analogy that I make in the office is I tell people to kind of close their eyes and visualize a Coca-Cola bottle that's about three quarters full of soda. Because, just like a soda bottle has a tapering, we screw the cap on, the follicle has a tapering and that area is called the isthmus, and where the isthmus of the follicle is, the cells will proliferate, choke off. The follicle prevents that fluid, which is not soda but it's semi-liquid wax or sebum, from coming out of the follicle, lubricating the skin,

Dr. Michael Koren: 3:30

Right so, and we talk about bacteria being an important part of it. So can you explain that a little bit to folks?

Dr. Michael Bernhardt: 3:38

So you know, the skin is not a sterile envelope, which is something I explain to patients all the time. There are fungi, there are viruses, there are bacteria that are normal inhabitants on the human skin, and one of the key players in acne is a bacterium called Propionibacterium acne, or P acne, for short. There are several different strains of this organism, and it's been found that one or two strains are particularly pro-inflammatory, and there are particulates of the organism, what they call cell surface markers, as well as what's called opsonizing particles, which are clumping particles, and those are the parts that are the target of this vaccine that we're looking at.

Dr. Michael Koren: 4:15

So just a little bit more about the epidemiology. We think of acne as something that teenagers get, but it's more than that. So explain why it's teenagers. Explain a little bit more about other times in life when you're prone to acne and maybe explain why you are prone to that problem at that time. So why, are teenagers more prone, or why are other people more prone?

Dr. Michael Bernhardt: 4:34

Well, I mean, first, off the myth that it's only a teenager disease, right, and 40% of people that are new onset acting patients, women between the ages of 24 and 64. So in almost half the patients it's an adult onset. It is common in teenagers, right? So what plays a role? Obviously the hormone flux plays a role and certainly we know that, acting like an hydradenitis supporativa, we know that the cells that line the follicular epithelial cells, are particularly sensitive to the presence of testosterone or progesterone in those, you know, proto hormones. Why? Certain, there's different reasons that are speculated. We know that in hydradenitis, for example right, we know that which is almost a cousin of acne, a more severe cousin of acne, we know that those cells are exquisitely sensitive to testosterone. We know that in that population there's a high incidence of hyperinsulinemia and insulin resistance. We know that in women, for example, there are certain sexually-based differences in terms of immune response, killer cells versus T-cell-driven responses. How that plays an acne, that it hasn't really been translated over yet, but at the gut level I think some of that plays a role. So in the teenage years, when those kids are growing and hormone levels are in a state of flux, sensitivity to the presence of hormones or a state of flux causes changes.

Dr. Michael Koren: 5:59

Interesting and you said sometimes women at later stages in life are prone to this. How about men? Any time in their life in particular, where you see that they're more or less prone?

Dr. Michael Bernhardt: 6:10

Mostly teenage in my experience, but I do get older, you know, people post 20.

Dr. Michael Koren: 6:15

So there's no men-o-pause that causes acne.

Dr. Michael Bernhardt: 6:18

Why is it menopause, it should be girlopaust, right?

Dr. Michael Koren: 6:23

Yeah, that should be the opposite, right? Yeah, right, interesting.

Dr. Michael Bernhardt: 6:28

When I was out, when I practiced for a yard in Arizona, big market out there everybody's on testosterone supplementation for quote unquote overall health. So a lot of nodulo-cystic acne. Even the women and new on-set in men. So definitely testosterone plays a role.

Dr. Michael Koren: 6:42

So guys that may take extra testosterone to live forever or to build their muscle mass, they would be prone to acne.

Dr. Michael Bernhardt: 6:48

Yeah, and it could be really tough to treat. Interesting, especially if they don't want to come off the testosterone.

Dr. Michael Koren: 6:53

Okay. So let's pivot a little bit to the treatment elements and we're going to get much more into that, but just from a general sense. So as a general physician, I have knowledge that you use topical things and then eventually you use antibiotics if it gets bad. So just walk us through that in a very fundamental way.

Dr. Michael Bernhardt: 7:10

Sure. So treatment is kind of based on what you're seeing, no different than in your field, cardiology. So what's the reality in front of you? So if someone has maybe five to 10 small plug pores, what we call closed colonies, right, we're not going to go on systemic therapy for that. So that's the kind of person where you want to exfoliate the skin and modify the lining of the pores. So that's where things like retinol A, adapalene, all these retinoids retinoids are derivatives of vitamin A that are designed to modify the texture and the quality of the follicles.

Dr. Michael Koren: 7:45

And that has a big following. Now, for other reasons, retinol A, I know a lot of people think it helps with wrinkles.

Dr. Michael Bernhardt: 7:50

It works.

Dr. Michael Koren: 7:52

Does it work? I've heard it's been evidence-based to prove that it works for wrinkles as well as acne.

Dr. Michael Bernhardt: 7:59

I haven't read the evidence-based date on it. I've just been using it for 40 years and I've seen it. It definitely works. You can tell who's using it and who's not using it and it's really a pretty benign drug when you think of all the drugs that are out there. But it definitely works, smooths out wrinkle lines, but it also exfoliates, kind of modifies the follicle, which I think is probably gut level. I think it's having an effect on fiber blasts. I don't know if there's been any research into that, but I think that's what's driving a lot of the youthful approach to it. So that's usually step one is a retinoid to topical antibiotics and the topical clindamycin which drives down the P-acne's population and also acts as an anti-inflammatory. If someone has a more advanced condition where they start getting little lumpy bumps, we call endermatology nodular cystic lesions, which in plain English translates into lumpy bumps.

Dr. Michael Koren: 8:52

Those are the kinds of In teenage speak. Is that pizza face?

Dr. Michael Bernhardt: 8:58

Sure, sure, yeah, and it could be tough, though it could be tough on those kids. So when they come in with the nodular cystic lesions and the excessive oil secretion, which is what's been called pizza face, that's when oral antibiotics come into play, because for non-inflammatory lesions antibiotics don't work. I mean, antibiotics work A by driving down the propionic bacteria, but a lot of these drugs block meta-proteinases. That's one of the things that doxycycline does. That's why we use it in rosacea a lot. It's because it downregulates metalloproteinases 8, 9, and 10, which are pro-inflammatory collagenolytic molecules. So we're using it as much for anti-inflammatory basis as we are for bacteria kill. So that's when we use it for the nodular cystic lesions. And if they don't respond to that, that's when you start getting into the world of isotretinoin. Now, the other drug that we're using a lot, particularly in our female population, is spironolactone, aldosterone. It is a great hormone blocker and I started using it a lot more the year I was in Arizona because it was a big treatment out there and I brought it back and we use it as a mainstay in our practice and probably I have as many young ladies on Spyro as I do on Doxycycline.

Dr. Michael Koren: 10:17

That's just fascinating from a sort of historical perspective and how drugs develop. So something that was really built as a hypertension drug is now being used by you for acne and being used for me for congestive heart failure and it works great for acne. It works great. It's a pretty safe drug. It raises your potassium level. You have to watch for that.

Dr. Michael Bernhardt: 10:35

You've got to keep an eye on that, yeah, but a pretty safe drug. It's like monoxidil.

Dr. Michael Koren: 10:39

Yeah.

Dr. Michael Bernhardt: 10:40

Right, it meant that it was a blood pressure drug, and now we're using it at 1.25 or 2.5 milligrams for hair restoration.

Dr. Michael Koren: 10:46

Interesting benign drug. Yeah, so we're going to end this session with one last question. Actually, we'll do two questions. The serious question is that if we have pretty good treatments, do we need something new or are there some limitations of the current treatments?

Dr. Michael Bernhardt: 11:02

Well, I can't say them before. I really think that we're 20 years behind what we need to be in terms of acne treatment. I think we could be doing better and I think we owe it to our patients to do better. I don't think kids should have to be in a situation where they have to try five or six or seven different regimens before we get to the sweet spot. They should be able to walk in and we should be able to have an immediate slam dunk. And the fact I was having a discussion with another DERM about this at the investigators meeting for the injection and I was making the point that I think we're doing the best we can. But, in all honesty, for our patient population, if we're doing the best that was out there, patients would not have to go on isotretinoin. No, patients would not have to be on a spirolactone. We should be able to have an easy slam dunk, like we do now in the psoriasis world and the topic dermatitis world.

Dr. Michael Koren: 11:52

Interesting, and so the not so serious question is when we started this session, you were telling me that you hadn't done a podcast before. I'm a first-time podder. Right, and that you needed to be poddy trained. I've been poddy trained, so do you feel potty trained at this point? I feel very relieved. With that, we're going to end this session and we look forward to you sticking with us for our next discussion on this really interesting topic.

Narrator: 12:12

Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidence.com or subscribe to our podcast on your favorite podcast platform.

Narrator: 0:01

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased evidence, proven facts powered by ENCORE Research Group and hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren: 0:17

Hello, I'm Dr. Michael Koren and this is Dr. Michael Bernhardt, and we're here for another session of Two Docs Talk, but in this case we're in our second section. We established in our previous section that you are now fully poddy trained. I'm poddy trained. Our last talk was his first podcast and this is now Michael's second podcast and he's I am much relieved. He's used the facilities and now we're here to talk about acne. But from the perspective of some of the clinical research work that we're about to embark on, and just for those of you out in the audience, Michael and I have worked together for a long time. Michael is a tremendous dermatologist. We've worked together in clinical trials for a number of years and Michael is leading a project here in Jacksonville which we are particularly excited about, which is using messenger RNA vaccine type technology to treat acne. So why don't you help our audience understand first why this is necessary we talked a little bit about that on the last session, but to catch everybody up and then why you're excited about this particular trial.

Dr. Michael Bernhardt: 1:24

I think it's really cool. And the reason I think it's cool is that right now the state of the art in acne is topical medications. Oral antibiotics escalate to Spironolactone, escalate to Isotretinoin. All good drugs. But you know Bernhardt's first law of drugs any drug can do anything to anyone at any time. Everybody's an independent variable.

Dr. Michael Bernhardt: 1:46

And I always tell patients that drugs are double edged shorts. They can help you, they can kill you. So we know there's side effects to all these things. There's morbidity, there's downtime. Mom has to take her little cherub to the dermatology office. It means she's got to leave work, he's got to leave football practice, they've got to come back. So there's a cost to it and in time there's an opportunity cost to the family and there's a pharmacy cost and there's morbidity to it.

Dr. Michael Bernhardt: 2:14

Acne can be very psychologically damaging, a study that was done at a Denmark about 10 years ago actually surprised me because it showed it was more psychologically damaging to teenage boys than to girls. Now I would have thought the opposite. So acne can be very psychologically damaging. It can lead to things like depression, suicidal ideation. So it's not a benign or strictly cosmetic issue.

Dr. Michael Bernhardt: 2:40

Poorly controlled acne that can lead to scarring and have severe consequences to the patient. My concern is I still think we're in the world of the 1980s and the 1990s in terms of our biotechnology for treating acne. I would love to see us being able to do better. So the concept of having an mRNA vaccine that's targeting specific particles of the Propionibacterium acne's bacteria, which is what we think is the pro-inflammatory trigger for people with acne, is really exciting. And in this study, what we're doing is we're looking at the usual people people over the age of 18, people that have significant comorbidities or conflicting comorbidities that would disallow from the study. Specifically, people that are past-accutane patients would probably not qualify and we're looking for people that have lesions that are approximately 20 to 25 inflammatory plus 20 to 25 non-inflammatory lesions.

Dr. Michael Koren: 3:43

We're not looking for the moderate acne, severe acne or somewhere in between.

Dr. Michael Bernhardt: 3:48

Yeah, it's cut, moderate and severe. I mean someone who has five or 10 cominones is not, you know, severe enough to merit this.

Dr. Michael Koren: 3:56

Just like in the real world In a typical clinical trial, somebody will actually count them to make sure people qualify, I would imagine.

Dr. Michael Bernhardt: 4:02

We do. We'll be counting specifically and there's a standardization of the criteria across the whole study. So it's not going to be an arbitrary judgment and we're looking for people that really need the help, just like in the real world. If someone came in with three or four pimples, I'm not going to be thinking about a vaccine, just like if someone has one palm unit of psoriasis in the elbow, I'm not going to roll out one of the biologics, right?

Dr. Michael Koren: 4:26

So if somebody comes to you and says my prom night is in five days, can you help me with this study, the answer would probably no. No, then it would be a chemical peel, right, or a light chemical peel.

Dr. Michael Bernhardt: 4:38

So the thinking with this is that we will inject people at day eight, re-inject them at day 56, following them out for about seven, eight months, and we're looking to see at least what they call an IgA two level reduction in terms of combinatorial or legional count, and that will be our primary endpoint.

Dr. Michael Koren: 4:57

Cool, cool. So this is early phase research. So when we do research, we typically do it in what we call phases, phase one being first in humans, phase two being a period of time when we're trying to find the right dosage of whatever therapy that we're using, and then phase three being the broadest phase where we really get to the efficacy and safety of the product.

Dr. Michael Bernhardt: 5:21

This is a phase one, phase two combo, so it's really phase, yeah, and so that's exciting.

Dr. Michael Koren: 5:26

It gives people access to something that is pretty new, and this is using messenger RNA type technologies. I understand it Correct. So there's lots of people that have had that at this point, we know, with all the vaccine work that's been done, you know both in the room Included, yeah, so we know that messenger RNA is different than DNA products.

Dr. Michael Koren: 5:45

I know people get that confused. Messenger RNA is really the messenger. It doesn't affect your genes. This is just the message between your genes and the parts of your body that make things happen, and we can now do things to allow our body to protect ourselves by sending the right message.

Dr. Michael Bernhardt: 6:03

Is that a fair way of describing it? Correct, and that's? I'm glad you brought that out, because that's a big misperception out there.

Dr. Michael Koren: 6:08

Yeah, yeah. So we're excited to be part of that and applying it to dermatology is that new or is that something you've seen with other products?

Dr. Michael Bernhardt: 6:15

I think this is the first thing that I've seen in my experience that we're approaching from a gene-based. Now there is a phase three melanoma vaccine in trials, but that's a different. Yeah, cancer, different ballpark, you know. But as far as general dermatology, yeah, this is the first vaccine-based treatment I've seen.

Dr. Michael Koren: 6:32

Okay, and so you started to talk a little bit about the advantages of this type of concept versus the quote 1980s 1990s version of treatment of acne. So am I oversimplifying things by saying this can be a shot that keeps you free and clear for six months eventually, or a year? so what do you think?

Dr. Michael Bernhardt: 6:52

Yeah, we're looking to see what the long term is going to be. Yeah, but I mean, my thinking is, if two injections get you basically acne-free, what's the downside?

Dr. Michael Koren: 7:01

And how would that compare with antibiotics, for example? Or?

Dr. Michael Bernhardt: 7:06

Antibiotics you use it or lose it. Now you have to use it consistently and nine times out of 10. The minute you stop, within a week or two, you're back to square one. So that's why it's all patients this is a use or lose at treadmill.

Dr. Michael Koren: 7:17

Right, n ow we do a lot of work in clinical trials here and obviously I've been very involved with it from a cardiovascular standpoint. Do you think there'll be any challenges getting people who have skin conditions to get involved in clinical trial? What's your experience and perception?

Dr. Michael Bernhardt: 7:34

Our experience has been. Since we're targeting 18 and above, I think it's going to be a lot easier to get people in. I think that adolescence is tough because it's a family strain. The kids can't drive themselves, they've got school, they've got sports, parents have to take off from work. But since we're targeting an older cohort, I don't think it'll be an issue.

Dr. Michael Koren: 7:54

Now you've been a PI in other acne studies quite a bit more of. Tell us a little bit how the patients have perceived that. Do they enjoy the experience? Do they get things out of it that may not be apparent to the average listener?

Dr. Michael Bernhardt: 8:09

I think they do. I think they do. It's helpful to be in a clinical format because it's a structured format. There's accountability. If you're not using the drug, we know it. If you're non-compliant, we know it. There's been studies. Steve Feldman out of Wake Forest did a great study about 10 years ago. We put a censorship in a bottle of tetracycline and found that 34% of people who would look them straight in the eye and say I did everything, you did never even open the bottle.

Narrator: 8:36

We know that compliance is a challenge particularly in the teenage population.

Dr. Michael Bernhardt: 8:41

Not out of malevolence on the part of the patient. Just they're busy.

Dr. Michael Koren: 8:44

They get a lot of other things going on, again.

Dr. Michael Bernhardt: 8:47

Two shots from the vaccine will be easier, I think, than having someone go through the three or four step ritual that we routinely prescribe for acne.

Dr. Michael Koren: 8:57

So there are huge compliance advantages potentially for something that uses this type of technology.

Dr. Michael Bernhardt: 9:02

Absolutely. Two injections and you're done.

Dr. Michael Koren: 9:04

How about downsides? We always like to be balanced in these discussions. Can you think of any downside of this type of technology?

Dr. Michael Bernhardt: 9:11

Risk of reaction to the injection, injection site reactions, allergic reaction to the injection, and that would be immediate.

Dr. Michael Koren: 9:17

So it's unlikely, sure, it's unlikely that this would happen and we have an extra fair amount of experience from this, from our COVID vaccines that use messenger RNA technology. It happens very, very infrequently, but not impossible, that there's immediate reaction, but can you think of any?

Dr. Michael Bernhardt: 9:33

They're looking at the pericarditis / myocarditis in terms of whether that's going to be an issue with this vaccine. We don't expect it to be based on the technology and the fact that we're not using an agent that has a spike protein, but they're looking at that and that's an area of special interest to the group that's researching this.

Dr. Michael Koren: 9:54

Are there other technologies out there that you are aware of that are trying to treat patients with acne using newer concepts?

Dr. Michael Bernhardt: 10:02

We're using red light therapy where you paint Melphalan, which is a variant of one of the topical PDT acids. You paint Melphalan on you, let it sit for about 15, 20 minutes, put the patient under red wavelength of light for 10 minutes per side. There was just an article that was published last month in the Journal of the American Academy of Dermatology out of China, where they did that weekly and got a six-month clearance level that was similar to someone who'd been on Isotretinoin. So we've started doing that in our clinic over in Tallahassee with patients also.

Dr. Michael Koren: 10:34

Interesting, Interesting. Let's also just make sure that we're covering everything. Some of the questions we get, especially when we talk about this high-tech stuff. They say, well, aren't there simple things? I got an interesting question in my last presentation to a live audience at the local TV studio. They said well, can a supplement do all this? Why do we need all this expensive high-tech stuff? Let's answer that fairly. Can we just change your diet and the acne will go away? Is there a supplement that make it go away? If that, worked.

Dr. Michael Bernhardt: 11:07

I wouldn't be seeing patients with it because everybody tries that before they go, by the time they get to me, I'm ahead of a residency clinic. By the time they get to me, they've seen the minute clinic, they've seen their primary care doctor, they've seen one of the other dermatologists in town, and then they're coming to us because they're end stage. So if any of this simple treatment worked, they wouldn't be coming to me. So I guess the answer is in our population none. Now maybe there's a cohort out there that have done the simple things. They're better. I don't see them. That's great. And the population that we treat? The answer is no.

Dr. Michael Koren: 11:43

So I will leave it this final concept. So I loved the fact that you talked about that. We're still kind of stuck in the 80s when it comes to acne treatment, and we talked about this a little bit before we got on the podcast that we're both musicians that happen to love music from the 80s. So there's some good things from there that we'll keep on going back to and there's other things that need to evolve and get into a more modern phase, and it doesn't mean that you throw away the old stuff, but there's certainly room for some of the new stuff.

Dr. Michael Koren: 12:16

Absolutely right, yeah. So with that in mind, Michael, thank you so much for being part of this. I learned a lot. Hopefully our audience learned something during the discussion. I'm sure they did, and you're always welcome back, and if there's anything we can do to support your very, very interesting research, please let us know. Thank, you.

Narrator: 12:33

It's a pleasure. Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidence. com or subscribe to our podcast on your channel, your favorite podcast platform.