Skin Deep: What's New in Treating Chronic Skin Conditions

Transcript generated by AI

Announcer 0:00

Welcome to the MedEvidence Podcast. This episode is a rebroadcast from a live MedEvidence presentation.

Dr. Mitchell Rothstein 0:06

Today is an especial pleasure for me because I've known Dr. Bernhardt for the nearly 40 years that I've been here, and he's clearly, in my judgment, the best dermatologist in town. And at the same time, he's also made part of his practice clinical investigations. And to take that on, on top of having a clinical practice, it's kind of a special slice of the medical community. Not every physician out there is willing to take on the extra responsibility of doing clinical studies, especially working as a principal investigator, because then you're in charge and responsible for all the patients that you're putting in the study as well. And luckily, Dr. Bernhardt has been doing that for years, even before he joined our group during his training. So it's a special privilege for me. So and this is a topic that actually I have a lot of personal connections with as I'll let you know as we go on. So just uh out of curiosity, how many of the people in the audience have had trouble with their skin before? Just as a show of hand. So it's a it's a common problem. And what we're gonna talk about.

Dr. Michael Bernhardt 1:13

Well, you know, the interesting thing with atopic derm is it's connected to your field,

Dr. Mitchell Rothstein 1:18

absolutely.

Dr. Michael Bernhardt 1:18

Which is asthma. You know, the connection between uh atopy and and asthma is one of the hallmarks. In fact, that's one of the basises that you use to make the diagnosis.

Dr. Mitchell Rothstein 1:28

And that's kind of what happened to me. But before I get into me, let's uh talk a little bit about... so, what we're gonna generally gonna do is we're gonna talk about some of the latest evidence-based treatment options that are available for uh two conditions. And there's kind of been a tidal wave of therapies in the dermatology space, starting kind of with psoriatic arthritis and then atopic derm and now hidradenitis suppurativa. Now, even though I'm not a dermatologist, I practiced that for a number of weeks before I said it. So I'll just say HS so I don't mispronounce it from now on.

Dr. Michael Bernhardt 2:02

That's what we do in the trade with HS.

Dr. Mitchell Rothstein 2:04

All right. And then with Dr. Bernhardt's help, we're going to talk about some practical uh baseline strategies, kind of over-the-counter, a common sense approach, and then some of the more complicated approaches to these conditions, primarily focused on atopic dermatitis and HS. So which of the following is true concerning atopic dermatitis? So this will be uh audience participation. One, it's one of the most common chronic skin conditions in the United States. How many believe that that's true? Show of hands. Number two, it can occur at any age.

Dr. Mitchell Rothstein 2:40

It's associated with what we call type two inflammation that Dr. Bernhardt's going to talk about a little later. These are all gimme's. It can have a devastating effect on quality of life. And the all of the above. So we're going for all the above.

Dr. Michael Bernhardt 2:59

All right. Good job. Good job, everybody.

Dr. Mitchell Rothstein 3:02

So to get started with it, when we're talking about atopic dermatitis, really kind of what is that and how do we approach it and how do we kind of break down the different components of it.

Dr. Michael Bernhardt 3:15

So, you know, it's it's actually uh people ask me all the time, when are you going to retire? Right. And I usually say, not as long as I'm still breathing. Because you know, I've been doing dermatology since 1981. I started my residency in 1981, so that's what, 45, 46 years. And it's only been in the last about four or five years, we've really got things that work. And a lot of it is due to the hard work that that people in the research community have done doing these clinical trials. And of course, the the pharma companies that invest the time and the money hire the geniuses to figure out what these molecules are and create it such that we can do clinical trials. But in the last five years, we've we've finally figured out what makes this thing happen, and we've got the medications to treat it. So we always used to approach it from the the outside in, you know, topical steroids, creams, moisturizers, and there's still a place for that, right? But the bottom line is this is an inside-out situation. We know that there's chronic inflammation in the skin that's what we call type 2 inflammation, just like there's chronic inflammation in the lungs that give you asthma, it's really the same process, just a different body part. And we know that the way I like to think of it, and the way I try to explain it to people, is that if you can visualize a swarm of bees around the dermal-epidermal junction, right? These little swarms of bees are all these different inflammatory cells that degranulate and release all these kind of noxious chemicals that hit the skin and cause this whole inflammatory cascade. And the problem with just topical steroid management is you don't get to the nexus of what's really driving this swarm of bees to attack and hit the skin. And that's where the systemic therapies kind of come into play. And we know that as a as a consequence of atopic dermatitis, we know that the outer part of the epidermis, uh the which is what we call the stratum corneum, and the outer part of the epidermis, there are little cells that called granular cells. And if you think of them as like little cement dump trucks, their job is to dump the intercellular cement into the outer layer of the skin to seal off the barrier. And we know that in people, these things are called Odland bodies. We know that in atopic dermatitis, these people have defective Odland bodies, so that the cement that's supposed to seal off the outside is fractured, it's cracked. The stimulation to make endogenous or or normal skin

Dr. Michael Bernhardt 5:55

proteins that fight off bacteria is impaired. So instead of being able to fight off staph, the skin actually becomes a magnet for staph aureus. And not only does that cause infection, but staph also drives inflammation. And you're not going to clear all that with just creams. You need the systemic agents.

Dr. Mitchell Rothstein 6:18

Now, when you see somebody that's having staph infections in their skin, are there who are the people that you're primarily looking at as being kind of susceptible to having this dysfunction in their skin? Uh who are these people?

Dr. Michael Bernhardt 6:32

Well, you know, we know that that atopic dermatitis kind of has three onset peaks, right? It can start as is in the pediatric age group, and just like this beautiful little child where it's just around the cheeks and on the face, that's really a common presentation in the pediatric community. And then you can see it in the adolescent stage and young adult stage, and then in the senior stage. So it can occur pretty much in any phase of life. When we're trying to figure out if someone has atopic dermatitis, the challenge is that biopsies and blood tests only help you so much. It's really what we call a clinical diagnosis. You have to put the whole picture together. So you ask for things like, is there a history of asthma? Is there a history of hay fever? Is there conjunctivitis? Are there food allergies? They have abdominal pain from time to time. Other people in the family do they have it? Has it changed since you moved into that new house or put down the new carpet? Do you have pets? Did you just move here from Arizona and your body's not used to all the airborne inflammatory agents that we have in in this community? So all those things play a role in terms of trying to figure out who's at risk. Now, in terms of the specific infection component, so one of the things that happens in TH2 inflammation, right? TH2 is is really kind of cool because you have these different molecules that drive it. And when you talk to some of the pharma companies, everything is taught in terms of linear. This does this, does this, does this. Really in immunology, that's not true. In immunology, and modern dermatology is really immunology, dermatological immunology. And it's more like a series of interlocking gears. One cell does one thing which drives another, it drives another, but there's a lot of overlap and redundancy, so it's really not linear. So one of the things that happens in type 2 inflammation, we have these little cells called T cells. They're white blood cells, and their job is to help fight off things that don't belong in the body. And they start out kind of neutral, what we call null cells. And under the influence of the main molecule that's driving type 2 inflammation, which is interleukin-4, interleukin-4 converts these null cells into actual type 2 cells that drive this whole inflammatory cascade. And as a consequence of these type 2 cells affecting interleukin-4 levels, production of antimicrobial peptides drops. So pretty much anybody with this is at risk for skin infection.

Dr. Mitchell Rothstein 9:08

Yeah, you know, and it's an interesting point that you made earlier about the association between type 2 inflammation and asthma. And even now with COPD, we're seeing this type 2 inflammation in those patients. And one of the markers that we use is blood, you know, peripheral blood eosinophil counts. But I don't remember seeing that being an issue for atopic dermatitis patients. Is that something that I've missed or we're just not seeing in that patient population as well?

Dr. Michael Bernhardt 9:35

You know, I think that that it depends on who the clinician is who's working up those patients. I mean, in my practice, I check eosinophil counts, I check IgE levels. If it's negative, does it mean they don't have it? No. Okay. But if it's positive, if people have an eosinophil count, and if they have an IgE level, to me that's that's you know, we need to be on systemic therapy. So I use it as kind of a benchmark.

Dr. Mitchell Rothstein 9:58

So and we're both from the age, obviously, where we didn't have that many treatment options for atopic dermatitis or eczema, which is the street word. And you hear advertisements all the time about treatments for a eczema, over-the-counter treatments, and whether or not they have a lot of um value or not is kind of still something that's up in the air. I mean, people may get an immediate response or they may get a bad reaction to a lot of these compounds, but none of them have under really gone any rigorous testing. So when we're talking about the triggers like you had just described for atopic dermatitis, we basically, I mean, kind of for a broad purposes have broken them up into kind of four different areas. What what would from what you're saying, I would assume that the overactive immune response is now the kind of dominant issue that we're looking at in all of these patients.

Dr. Michael Bernhardt 10:52

Yeah, and the barrier dysfunction is kind of collateral damage,

Dr. Michael Bernhardt 10:55

you know, from the overactive response. You know, like I was talking about the the the granular cell layer, the odland bodies, which is the little dump trucks in the skin. One of the things that one of the intercellular cements that they make is something called ceramides. And you see a lot of products advertised with ceramides. And if you're not using a moisturizer with ceramides, you're you're really only doing half the job. So any moisturizer really should have ceramides in it. The skin has like little fence posts in it that bind these ceramides. And in normal people, these chains are like 20 or 40 carbon lengths, but in people with atopic dermatitis, they're 10, 12, 14 carbon lengths. So not long enough to do the job. And sometimes these shorter chains can actually be pro-inflammatory by themselves and actually add fuel to the fire. So, in terms of trying to repair barrier dysfunction, of course, most of it's going to be done by being on the right drug. And then secondly, you do want to avoid harsh soaps, right? You want more of a neutral soap because you don't want to strip the skin because the skin's already damaged. So we I usually recommend, you know, white fragrance-free dove soap. I like a uh moisturizer with ceramides. And what I tell people is you got about five minutes from the time you get out of the shower till the skin has set. The skin is kind of like cement. You know, if you've ever done any kind of construction work and you've seen cement harden, the skin does the same thing. So when you get out of that shower, you've got about five minutes before the skin hardens. And once it hardens, you're really not going to get as much of an effect from the moisturizer. Now, that doesn't mean rush out and slip and hurt yourself. No, get out, pat yourself dry, and then put the moisturizer on. So a mild soap like Dove, using a moisturizer with ceramides. As far as clothing, again, you want to avoid some of the harsh clothing agents. So we usually recommend things like all free and clear. I think Costco and Sam's have have their generic equivalent to it. Makes it easier on the skin. And then the everyday home triggers, you know, stress, of course, you know, there's no magic bullet for for controlling stress.

Dr. Mitchell Rothstein 13:03

Not yet.

Dr. Michael Bernhardt 13:04

Not yet.

Dr. Mitchell Rothstein 13:05

So it's funny that you talked about the effects of harsh uh soaps and other things. I remember as a kid, I had uh developed eczema and had asthma as a child. So when I was about 10 years old, and the treatment at that time was cornstarch on my bed sheets. And also to stop the itching, I was told to sit on my hands. So it was tough growing up, but with those are your only options until we then went to I had body radiation done. And then are they still doing psoralen therapy, light therapy for eczema, or not more, not anymore?

Dr. Michael Bernhardt 13:41

Uh we use narrowband UVB. We don't really use the psoralen anymore because they're kind of, you know, associated with with skin cancer formation. So those those are just like for really, really, really extreme cases. But narrowband UVB works, but the reality is you could lay outside for five minutes to get the same effect as you would coming into your office three times a week, and then you don't waste 12 co-payments a month.

Dr. Mitchell Rothstein 14:05

Well, I remember the summer when I was out in the sun, my eczema would clear up, and it was fantastic. But once I stopped being outside, and I had significant fabric sensitivity also. So I still have t-shirts that are 40 years old because they didn't irritate my skin, and so I kept them. But for the for the major symptoms that you see in the office, they're primarily centered around what it appears the phys is is this a pattern recognition kind of situation along with symptoms that you kind of make the diagnosis on?

Dr. Michael Bernhardt 14:36

Yeah, the symptoms are just like what's laid out on the slide. They're pretty straightforward. I'm not going to insult everybody's intelligence and read it by a line item. So that's pretty straightforward. The idea of telling someone to sit on their hands, I mean, that's like telling me don't cough. Right. You know?

Dr. Mitchell Rothstein 14:51

I didn't say I was happy. I wasn't happy with that treatment, but that's that was what I was offered.

Dr. Michael Bernhardt 14:57

I think in my residency, if I had said that in front of my department chairman, I probably would have a different career path. That wouldn't have gone over very well. You know, and the problem with cornstarch is you know, cornstarch can actually induce yeast cantidiasis, so we try to tend to stay away from that. .

Dr. Mitchell Rothstein 15:13

But it felt soft and silky and not irritating. That's an indicator of how lousy our treatments were back then. I mean, really. But it's what I used to call institutionalized mediocrity, or what we had was just ineffective. Yeah. So in terms of diagnosing atopic dermatitis, are you uh how

Dr. Mitchell Rothstein 15:30

often are you doing skin biopsies on patients?

Dr. Michael Bernhardt 15:32

We do it on occasion because there's a there's a mimic, you know, T cell lymphoma is a form of skin cancer that in people in our age group, particularly between the gym short area, nuance it, you have to be alert to that, uh, because you don't want to miss that. So I'll do biopsies when I'm suspicious of that. It's also nice just to show that the biopsy is not gonna say you have atopic dermatitis. It's gonna show a pattern. And that pattern is gonna show swelling in between the cells, what they call spongiosis. It's gonna show that kind of swell intercellular swelling, and that you have to take as kind of a form first, and then you do your labs. But the most important thing when I teach the residents is you've got to get the history. This is a history-based and physical exam-based diagnosis.

Dr. Mitchell Rothstein 16:18

Old-fashioned medicine.

Dr. Michael Bernhardt 16:19

Yeah, yeah, just practicing just regular old good medicine and be aware of the mimics, have those always on your mind. In terms of patch testing, patch testing has a role when you can elicit a history of, you know, hey, you know, I use the soap and I can't control my itching, or my wife bought gain or tide or some other kind of detergent, and now I can't stop clawing. Okay, fine, you rule up perfume, sensitizers, preservatives, things like that. And that's when we're referring to someone over to allergy. And and I'm not very shy about doing that. If someone needs it, we do it. Yeah, we do that. But the interesting thing is that people that have a tendency towards a low threshold to contact dermatitis, at least half the time they have an atopic background. If you do get the history, you can dig that out.

Dr. Mitchell Rothstein 17:04

That is that's fascinating. And it makes sense. I mean, people that are kind of have their immune system set up that way to be hyperactive, that's what happens. Yep. So when we're talking about characteristics, when you you're seeing patients in the office, this is I I don't know how relevant this really is now with the advent of biologics, but you're kind of stepwising you're stepping your therapy up based on their symptoms and presentation. Do you kind of divide them into categories like this to justify the use of the medications?

Dr. Michael Bernhardt 17:34

Yeah, I mean, and let's say, for example, a a 17-year-old kid comes in who's just got some itching on the bend of the elbow. Okay. They're sleeping well through the night, they're functioning, the schoolwork's not being disturbed, they're not so miserable that the whole family unit is disrupted. A topical agent is fine for something like that. But when you get into the moderate disease and severe disease where people are getting blisters, scratching themselves till they're raw, uh, they're they're not able to concentrate at school, they're miserable at home, they can't sleep, then you're really in the systemic therapy bucket, and that's probably probably about 35 percent of what I see is kind of mild. And then the rest tend to be moderate or severe because a lot of times the the mild ones will be intercepted by the primary care of the pediatrician. So people that are coming to me are people that have usually failed that kind of of baseline.

Dr. Mitchell Rothstein 18:25

Yeah. So you're seeing kind of a skewed population as as more severe disease. Sure. And uh and are are we still using these and and this was just to kind of show that in in the back office we have a number of different vehicles for kind of disease sets which help us kind of guide severity and follow the disease course. Are you using things like this in the office to follow patients' progress?

Dr. Michael Bernhardt 18:47

More subliminally.

Dr. Mitchell Rothstein 18:48

Okay.

Dr. Michael Bernhardt 18:49

Not overtly. I mean, this is more of a research tool.

Dr. Mitchell Rothstein 18:51

Okay. So again, getting back to kind of the basics, like you said, moisturizers often. And I I knew for myself that if I got out of the shower and used toweled off, but my skin was still damp, that I got the best absorption of moisturizers at that time. If I waited like an extra five or ten minutes, I escaped that absorption window without even kind of understanding what was going on. But I also found that a lot of the creams and the carriers were very kind of greasy and they made you feel even kind of worse than they did before. And are there over-the-counter products that you're recommending in terms of-

Dr. Michael Bernhardt 19:29

there's a couple of product lines that I like. Vanicream is a really good product line. Cerave makes a good product line, and cetaphil with ceramides. Those are those are kind of my go-to's. Aveno makes a good one also. If like an Aveno eczema cream. Uh but those are all kind of supplements. I mean, that's not gonna solve the problem most of the time. If that solves the problem, then that's not really an acute problem.

Dr. Mitchell Rothstein 19:53

Okay. So beyond the skin, we talked about this that people that have chronic itch um do suffer from that. And I remember, just for my not making this all about me, but just when I was growing up, I was the kid that always had long-sleeve shirts in the summer because I didn't want to show everybody that you know, everybody saw all the sores on my arms, and it had a huge impact on my sleep. And even into adulthood, Mike, I was talking to one

Dr. Mitchell Rothstein 20:20

of my kids the other day, and they said they remember coming into the room and seeing all these little spots of blood all over the sheets on my side of the bed, and they didn't understand where that was. And it's because I was scratching in my sleep, and my sleep was interrupted. But so it affected me, it affected my wife, obviously. And it's I guess I've traumatized my children yet again without without knowing it. But and I think that's one of the things that pushed me into sleep medicine was that my sleep was so messed up from the eczema that we went further than that. So let's see.

Dr. Michael Bernhardt 20:51

You know, the um the psychosocial is is there's been a couple of really good articles. I'm putting a talk together for next year's Florida Academy of Derm about mental health aspects of skin disease. And atopic derm drives a lot of psychosocial issues. There's increased suicidality. And people with atopic derm, it's been isolated as an independent variable for suicidality. Interesting study out of Korea, right, which showed that they looked at at people over 65 with with atopic dermatitis, what they found is that in all the whole population base, the risk of they looked at Alzheimer's and dementia. And they found that in all variants of Alzheimer's, there's a huge uptick in people that had a baseline of atopic dermatitis compared to the non-atopic dermatitis population.

Dr. Mitchell Rothstein 21:39

I wish you hadn't told me that.

Dr. Michael Bernhardt 21:41

But you know, it just brings the question of with all these things. One of the things that goes through my mind is right, what's the overlapping of these inflammatory processes, you know, and and some of the TH-17 inhibitors, which some of the TH-17 mechanisms, which we'll be talking about in when we talk about HS, also play into a role with Certain neurological conditions. So there's this overlap.

Dr. Mitchell Rothstein 22:03

Yeah. I mean, every as the bottom point here demonstrates in pulmonary disease and GI disease, we're now understanding that, you know, when we trained, it was, okay, you have this problem in this organ system, so we need to treat that problem. We weren't understanding that that problem really was derived from a larger kind of systemic inflammatory process. And now I don't know if there's a medical condition that we don't define as a systemic inflammatory process. So our whole approach is kind of getting ahead of the egg instead of trying to pick the egg up after we fried it and fell on the floor.

Dr. Michael Bernhardt 22:38

So like I said, the immune system is a series of interlocking gears. Absolutely. Which system it decides to hit, bam, that's your disease process.

Dr. Mitchell Rothstein 22:45

Absolutely. Among the biologics and the JAK inhibitors that are out, or do you have a kind of a go-to when you're when a patient is moderate to severe and you know that they're going to require systemic therapy that you like to start with because you've seen the best results with that?

Dr. Michael Bernhardt 23:03

Well, you know, dupixent's been around since what, 2018. We did the phase two clinical trials with that, I think, back in 2013-2014. So we were f we're I've been familiar with that drug for 12 or 13 years. Over a million patients worldwide are on [that] drug. And it's a great drug. I mean, it it 65-70 percent of the time it's a it's really pretty much of a slam dunk. I mean, there are certain things you have to be careful of. There's been cases of episcleritis and conjunctivitis. There was, I think, one case of blindness in Florida. There's been about four or five percent of people that get joint pain when they're on it. But other than that, it's it's really a slam dunk drug. It works really well. Now, everybody's different, so one drug may work for one person, may not work for others. The thing about dupixent is it treats both interleukin 4 and interleukin-13, which are two different inflammatory pathways, an atopic dermatitis and an asthma. But in some people who aren't candidates for whatever reason for dupixent, there are several pure interleukin-13 inhibitors that block peripheral inflammation. There's an interleukin-31 inhibitor called the Nemluvio, and interleukin-31 basically drives itch. So it really helps block the itch cycle. And that cohort, those are all injectable agents. And those are really kind of like the first pass drugs go to. And then people that are either not a candidate for injection because they have a history of anaphylactic shock from exogenous envenomations, or they just can't stick themselves, or they're vasovagal, they can't stand the thought of an injection. The JAC

Dr. Michael Bernhardt 24:40

inhibitors, which are pills, are kind of the next line. JAK inhibitors are great drugs. The problem that we have with the JAK inhibitors is unfortunately the FDA has painted a class warning on all these drugs based on a study from about 10 or 11 years ago using a non-selective JAK, you know, JAK123 inhibitor ZELJANZ, where patients who were on Xeljanz plus methotrexate had a higher incidence of DVTs, deep vain thrombosis, blood clots, cardiovascular disease, than people that were on a TNF inhibitor like Enbrel or Etanercept or Remicade plus methotrexate. So as a consequence of that one study, there's a class warning on the drug. And you know, the problem is whenever you even though there is two very good articles, one last year in the European Association of Dermatology and Venereology that looked at abrocitinib, which is a JAC-1 inhibitor, and one that came out this year in the Journal of the American Academy of Dermatology that looked at uh RINVOQ, which is a upadacitinib, and showed that on low dosage in people under the age of 65, there was no safety signals.

Dr. Mitchell Rothstein 25:45

That's fantastic.

Dr. Michael Bernhardt 25:47

But we still have to and there was a meta-analysis in November 2024 journal JAMA dermatology showed the same thing, 14,000 patients, 45 studies, no safety signals. Now, when you go up on the dosage, yeah, the safety signals is things you have to be cognizant of. And the people over the age of 60, 65, you have to you have to prove that you need the drug. The risk has to be worth the benefit. And the risk is not worth the benefit, we don't use it.

Dr. Mitchell Rothstein 26:13

And that and that's true of most of the drugs that we're bringing to market anyway. I mean, that's not that unusual. And just again, not to make this all about me, but eight years ago, I got my first dose of a biologic, and two weeks after I had that dose, I realized I wasn't itching. For the first time in my you know, conscious life, I no longer itched. It was like a miracle medication. And-

Dr. Michael Bernhardt 26:34

-great feel, great feeling.

Dr. Mitchell Rothstein 26:36

Yeah, it was yeah, great not feeling. It was it was really remarkable.

Dr. Michael Bernhardt 26:41

No, I've had people come into me that were literally when they when they were clear, they would cry. They were so they're feeling so well, they were just like crying that the itch because the itch was you know, most studies show itch is worse than pain. People would rather be in pain

Dr. Michael Bernhardt 26:55

than itch.

Dr. Mitchell Rothstein 26:56

I didn't know that. So I'm not a fan of either category. But uh so we'll finish with atopic dermatitis and move on to HS, which is also one of these kind of disease uh things. And just some to keep you guys awake, we'll just do a little questionnaire again concerning HS do any uh who knows what HS is? Okay, so that's gonna make these these questions hard to answer if you don't know what it is, but do your best. So we know that HS is also an inflammatory skin condition, and a lot of times it has been associated with poor hygiene, which is not necessarily the truth, is caused by infection of a sweat gland, which is also not the truth, is caused by obesity, which is also not the truth, not caused by associated with, but not caused by, and can have a major effect on quality of life, which just like atopic dermatitis is the correct answer. So, Dr. Bernhardt, not all skin conditions are the same. Some are more surface seen, but some uh act a little bit deeper. And I'm hoping that you can kind of tell us a little bit more about HS and how we approach it now.

Dr. Michael Bernhardt 28:06

So the old term for HS was acne inversa. And that gives you a good psychographic, because it has kind of an acneform appearance, and it's usually in the armpits, the area below the breast, and in the groin. The average onset is typically in the mid-teens. Most people that have this bounce from primary care to urgent care to the ER for about 10 to 12 years before they come to someone who actually knows what they're looking at and how to treat it. And it's a terrible disease. I mean, this this disease absolutely, unequivocally destroys a person's quality of life. Yes, it is not contagious, it is not an infectious disease, and while it's not caused by obesity, probably 85 to 90 percent of the patients that I treat are obese with us. So it's driven by obesity. And the reason is that adipose tissue or fat tissue is a big reservoir for a molecule called interleukin-17. Interleukin-17 drives the inflammatory pathway that leads to certain things like psoriasis, psoriatic arthritis, and hidradenitis. And the more obese you are, the more adipose you have, the more 17 stores your body has to release, and it will drive that inflammation. That's why studies from Europe, right, and and now in this country too, where people have been on GLPs and they drop 50, 60, 70 pounds, they can reduce their dependency on some of these biological drugs that are specific for HS.

Dr. Mitchell Rothstein 29:35

Yeah, it's remarkable. Uh so when and a lot of times people are misdiagnosed, as you were saying, it takes seven to ten years to make the proper diagnosis. And a lot of times people are treated for ingrown hairs, right? That's kind of one of the most common misdiagnoses, and people kind of stick with that for years and years until they come to somebody who actually understands what's going on, so they never get relief. And as I understand that, not being a dermatologist, there is, you know, like any other disease, some have much more progressive, aggressive kind of courses, other people have more indolent kind of stable courses. Is that true? Or...

Dr. Michael Bernhardt 30:10

Pretty much. Pretty much. That's that's reasonable.

Dr. Mitchell Rothstein 30:14

So and it's affecting more females than males and about a seven-year diagnostic delay. And one of the things that I found fascinating was kind of the disease itself and the amount of aggressive pathology that's going on that these patients have to suffer through.

Dr. Michael Bernhardt 30:32

So a couple things. One is definitely obesity is a trigger. Cigarette smoking is a trigger, testosterone is a trigger. Because if you look at this picture, the cells that line the follicle, those are ver y, those are very sensitive to the presence of testosterone or or androgenetic hormones. And they'll swell, they'll form a plug. The sebaceous glands that that create oil will will be stimulated to make more oil. And now this, this oil has nowhere to go. Can't make it work its way up to the surface because the the pores blocked. That's what we call follicular occlusion. The highway is is blockading.

Dr. Mitchell Rothstein 31:08

And that's that keratin plug that you're talking about.

Dr. Michael Bernhardt 31:10

And so it just in the bottom right, it just blows out. And you know, the skin doesn't like all that liquefied oil in it any more than your coronary

Dr. Michael Bernhardt 31:20

arteries like plaque building up in the coronary artery, so it'll thicken up and form defense mechanisms against that.

Dr. Mitchell Rothstein 31:27

And then those when it blows up like that, that can actually uh that's pus actually that's developed under the skin, and that can track into sinuses and they can interconnect and-

Dr. Michael Bernhardt 31:38

It'll lead into surrounding areas, and then it'll scar down. So HS is really kind of a biphasic disease. The initial phase is driven by interleukin-17, and then once the inflammation kind of dies down, there's another sequence of inflammatory mediators, interleukin-1 and transformation growth factor beta, to drive the scarring phase of it.

Dr. Mitchell Rothstein 31:58

So that's uh and again, like all conditions, we have different ways medically kind of to characterize them into mild, moderate, severe. And this kind of ignition, though, even if you had somebody with mild disease, treating them locally without an anti-inflammatory agent, is that still the reasonable approach, or will you go right to the?

Dr. Michael Bernhardt 32:17

You know, if someone comes in and they just have follicular plugs like acneform plugs, I'll usually tell them to go get laser hair surgery, because that'll that'll kind of nuke the process or because it's a hair follicle that's really the order of. You nuke that follicle gets better, right? If someone has just like a single abscess, I'll probably just manage them on antibiotics. But once the people start coming in with two or three or four abscesses, you're really in moderate disease and you really need more aggressive therapy because you're going to be miserable and it's not going to get better on its own. It's not going to go away.

Dr. Mitchell Rothstein 32:47

And even compared to atopic dermatitis, this is mu a much more kind of aggressive, disabling condition because of the thing.

Dr. Michael Bernhardt 32:54

Oh, it's horrible. I mean, imagine having having your whole gym short area full of this and trying to go out on a date, right? Or trying to go into the office and sit down and squish, it breaks open and you have to leave. It's a terrible disease. It it impairs people's ability to function, it impairs their ability to work, it destroys the person's sex life. It's terrible. It's a terrible disease. So I, you know, when I was in Tallahassee, before I came back to Jacksonville, I was I was helping run a dermatology residency program for about three and a half years. And we were doing the complex medical clinics, and I was seeing three to five patients with this every single day, which is absolute disaster, HS. And so we got very adept, and I got very adept at dealing with and training the residents. And we I used everything that's on this smorgas bord. And what I found is that, you know, the you really you're in the world of s of Coseytyx or Bimzelx, secukinumab or bimekizumab. I mean, those drugs really work. My experience with that adalimumab was was mediocre at best. The small molecules, spirono lactone, metformin, yeah, you know, they they're okay, but they're not going to really be the cat's meow. And the same with the antibiotics. You can use the antibiotics for a quick hit and run. Or if someone just has an isolated lesion, fine. But when people have three, four, five, six abscesses, checking them with antibiotics. That's, you know, 1980s technology in the 2026 world. Deroofing works. I've done deroofing. About 87% of people that have a lesion opened, curated, and quarterized, that lesion never comes back. But the goal really is to get them on one of the biologics. And we've got some newer drugs coming out down the pike. We've got some selective JAK- 1 inhibitors that have just finished passing phase three trials that are about to be announced, which may not be quite as effective as as Bimzelx, but will have a a different safety range.

Dr. Mitchell Rothstein 34:46

So we're moving and a cream form, too, right?

Dr. Michael Bernhardt 34:49

Yeah, we're doing a clinical trial right now with it, but that's more for mild to moderate with Opzelura, which is already approved for atopic dermatitis, and vitiligo, we're using it in mild um HS. But they're coming out with an oral version also sometime within the next year. Companies are starting to gear up for that. And I think that's going to be effective. And it'll be nice to have five or six drugs in our toolkit. You know, before during the COVID pandemic, nothing was getting approved, so the only thing we had was Adalimumab, which is Humira. Not, in my experience, it was mediocre at best, but we got the approvals for Cosentyx and Bimzelx, and they've been a real game changer. But you have to be careful there are certain populations that you can't use a 17 inhibitor on. So it'll be nice to have multiple options. Most important thing is that when people have HS is still a disease that's in the closet. And the most important thing is people really need to get to a learned intermediary and not bounce from ER to ER to their OB or to their PCP. They really need to go someone who knows what the what they're dealing with.

Dr. Mitchell Rothstein 35:51

Yeah. And I was going to add uh just to support what Dr. Bernhardt was saying, was that having been a dermatology patient myself, if you have or know somebody that's having problems with chronic recurrent skin conditions, you gotta stop them from going to Walgreens and getting that cream off the aisle or whoever they're seeing, they need to have somebody else take a look at them because this, this could easily be a misdiagnosed issue that we can now uh treat effectively. And as Dr. Bernhardt was saying, the GLP-1s that we're finding multiple uses for, besides just diabetes and weight loss, have also had a significant effect on these patients with HS.

Dr. Michael Bernhardt 36:31

The GLP is, I think, going to be the miracle drug of the 21st century. You know, there's a there's a inflammatory cascade by called NF kappa beta. So NF kappa beta is like a little circuit board inside the nucleus. You press that button and the whole inflammatory cascade lights up. You shut that button off, the whole inflammatory cascade shuts down. Well, we found that these GLPs downregulate this whole NF kappa beta system. So it shuts down in TH1-driven disease, TH17 driven disease. So it's not just about weight loss. I mean, the the there's also, again, dementia data that it may decrease risk of dementia. These drugs are miracle drugs.

Dr. Mitchell Rothstein 37:13

Yeah, and right now we're actually doing a bunch of studies with GLP1s, including some weight loss studies. But as you can see on this list, we're looking at it for patients with heart failure and obesity. We're looking at patients with osteoarthritis as well as patients with sleep apnea and people that have had failure with heart.

Dr. Michael Bernhardt 37:33

I've got a bad knee. Well, you might hear that thing crunch? Yeah, yeah. Yeah. Well, yeah, patients of I don't know about the obesity part, I've got I could we could jack up my BMI so I could qualify.

Dr. Mitchell Rothstein 37:43

All you need is a BMI of 27

Dr. Mitchell Rothstein 37:45

with a comorbidity or 30.

Dr. Michael Bernhardt 37:47

I qualify.

Dr. Mitchell Rothstein 37:48

So if you're there, you get to be in the studies. But I I think uh with that, we've had a kind of a rapid fire round of activity with Dr. Bernhardt. Thank you very much for your expertise on this.

Announcer 38:01

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