 program entitled “Incorporating New Medications into Acne Treatment.” I’m Dr Hilary Baldwin, and I’m the medical director of the Acne Treatment & Research Center in Brooklyn, New York. Our discussion today is going to focus on diagnosis and new options for treating acne. Joining me today are 3 well-known colleagues and good friends: Dr Fran Cook-Bolden, who is a clinical assistant professor of dermatology and director of FCB Dermatology and Wellness in New York; Dr James Del Rosso, a dermatologist who practices is Las Vegas, Nevada; and Dr Julie Harper, a dermatologist practicing in Birmingham, Alabama. Let’s go ahead and begin.

Let’s start with you, Julie. What is acne vulgaris, when does it start, and who gets it?

That’s a big question, Hilary. We have plenty of time to talk about this, but I would think of acne vulgaris as being an inflammatory skin condition. It can involve the face, the chest, and the back and shoulders. We see it at almost any age. It’s certainly most prevalent during adolescent years, and adolescence has moved down recently. Earlier, we might have said ages 12 and up, or 12 to 19, but we now have products that are FDA approved down to age 9, and we can see acne down to age 7. If you see acne before age 7, you’ve got to be a bit worried about whether there could be a potential hormonal problem in the background that needs to be worked up. We can see it in young kids, but keep this in mind: if you get it between the ages of 1 and 7, that period is when you would be suspicious of an underlying cause. People 7 years of age and older can get acne, but we see it in the adult years as well. In that adolescent age group, I would say that most people have some amount of acne in their lifetime, it’s that prevalent.

Regarding what it looks like clinically, we all know this, but acne presents with red, inflamed bumps, papules, and pustules. There is also comedonal acne, which are the little blackheads and whiteheads that we see with acne. It’s an inflammatory condition. We can see it in almost any age group. The last thing I would say about it is that it stinks; nobody wants to have it.

 Fran, why don’t you continue here with this discussion of the prevalence of acne? What do you see in your practice in terms of the distribution between the teenager and older patients?

Hilary, as Julie mentioned, acne is common in adolescents. It’s considered a disease of adolescents, although we know we can see it in all age groups. It’s the most common skin disease in the United States, affecting 50 million Americans, and it affects 80% of Americans at some time in their life. Because it’s considered a disease in adolescents, there have been a lot of studies that have examined the prevalence in adolescents and reported it at almost 95%. I challenge that a bit because if you have a patient who has an occasional comedone or papule, then that can go to 100% prevalence of acne at some point in the patients’ lives.

As Julie said, you can get acne at any other age. I would like to supplement by saying this: it’s common in patients from infancy to 2 years of age, which is largely because of effects from the mother. As Julie said, it’s rare in young children, so it’s rare in toddlers from 3 to 5, or up to 7 years of age. It’s common in preadolescents, which is the age group of about 6 to 13. When we talk about age ranges and prevalence, they’re all over the place in studies. They sometimes include adolescents in those numbers, and we know it’s extremely common in adolescents, which includes patients from 14 to 18 years of years of age. It’s common in young adults, and I’m going to put that in an age range of about 19 to 40. It’s somewhat common in adults between the ages of 41 to 60. In my practice, most of my patients are young adults, adults, and a lot of adolescents as well. It’s rare in seniors.

Acne: Who, What, and When?

 Julie, I remember that paper you and your team [at the Dermatology & Skin Care Center] wrote about the incidence of acne in adult females, where you said about it presents in about 50% of women in their 20s, 30% of women in their 30s, and 25% of women in their 40s. Adult females are particularly impacted by this. What do you see in your practice?

I see an awful lot of adolescent acne, and I definitely see people coming in younger. I see people coming in who are 8 or 9 years old who have acne, but that adult female population is for real. I don’t know if it’s because I’m an adult female dermatologist, but I see a lot of adult females who come in with acne. In the adult population, acne is skewed more toward the women.

I’ll look at my young men. Let’s say that we have somebody on isotretinoin, and it’s a young man who is 18 years old. I feel like I can look at him and say, “You’ve got a pretty good chance, once we get you clear, you’ve got a pretty good chance of staying clear.” If I see a young woman in that same situation, I think all of us on the call recognize that acne in adult women can linger. I don’t know if it’s the hormonal fluctuations, but I would look at that young woman and say, “You may have to do this again at some point, or you may be on some other treatment.”

Thank you for remembering that study. We worked hard on it. It was easy to remember. We didn’t mean for it to work out like that, but it was 1 out of 2 women recalled having acne in their 20s, 1 out of 3 women in their 30s, and 1 out of 4 women in their 40s. That’s a nice, easy way to remember that. You can use information that like in clinics because what do our adult females say to us when they come in? They say, “This is not fair. I should not have acne at this age.” You can at least say, “You’re not alone. You’re not alone. We have evidence that this is something that affects a lot of our adult females.”

Yes, and we have to remember that some studies have shown that, if you have acne at age 25, then you’re likely to still have it at 45. We always call acne a chronic inflammatory disorder, but in adult females, it’s particularly chronic, isn’t it?

When you tell an adult female at age 25, “Don’t worry, it will go away at menopause,” they’re not exactly pleased by that information.

Have you seen what I like to call “last hurrah” acne? It happens for a woman who hasn’t had acne since her teenage years, and right at the perimenopausal period, all of a sudden, all heck breaks loose with inflammatory lesions.

I definitely see that in my practice, Hilary. I see a large number of adult women, and I can tell you that I have personally gone through that. I won’t tell you where I am right now in that cycle, but I have definitely been through that and see it all the time.

I don’t know what that means. What do you think it means, Julie? We always call acne in adult females hormonal acne, as if all acne isn’t hormonal. What does it mean when a 50-year-old who hasn’t had acne in the last 30 years all of a sudden gets pimples? Any idea?

No, but it means she’s not happy about that, I can tell you that. What you just said is right on: people want to label 1 type of acne as hormonal acne. We need to remember that all acne is hormonal. If it was all just about hormones, particularly circulating hormones, all men would have acne, and only some women would have it. It’s clearly not about circulating hormones, but all acne is hormonal. What we think is going on with women is that we have such fluctuations of hormones. It may be a change, and we’re certainly changing our levels of hormones around the perimenopausal area, but that’s a total guess. It’s a total guess. We don’t have this all figured out.

Julie, you’re right on point. With myself, I would say that during that perimenopausal fluctuation when a lot of things are going on, that’s when that acne manifested itself. You’re right on point. When you’re getting that perimenopausal hormonal surge or hormonal fluctuation, that’s when we also see that increase in acne in older women.

I see it as like a teeter-totter. When we’re young, we have a lot of estrogen and just a little androgen. As estrogen slowly sinks down toward the horizon as we get older, that little amount of androgen that didn’t bother us before is all of a sudden driving the ship, so to speak.

Prevalence of Acne in Adult Females

 Julie, tell us a bit about the impact of acne on the quality of life with your patients [at the Dermatology & Skin Care Center].

This is a super important thing to talk about when we talk about acne. In the medical world, we’re so quick to talk about these ideas: Are we going to decrease lesions? Are we going to decrease bumps? Are we going to improve the overall appearance of the acne?

You know what? The whole reason we treat acne is because it bothers people. It’s not just to reduce bumps; it’s to improve their quality of life. There is no subset of people who have acne who are not bothered by it.

Now of course, there are going to be some individuals who aren’t as bothered by it as others. That’s just their nature, but I would say that patients in any age group are bothered by this, and all genders are bothered by this. It’s not something that we can isolate to 1 group of people. We have data out there that acne is associated with depression. It’s associated with anxiety, embarrassment, and social withdrawal. In patients in adulthood, we’ve seen more information recently where it can be associated with unemployment or even the perception of being passed over for a job, or staying home and not dating. These are big impacts on quality of life.

I always like to personalize this, and I apologize if you’ve heard me say this before. No, I don’t apologize for that. I’d like to remind us of this: how many zits on your face does it take to mess up your day a bit? If we’re honest, we don’t say, “It’s about 5.” We say, “1.” Remember that when you’re looking at your patients in clinic. I’m totally guilty of part of this. I had an epiphany several years ago. I came out of an examination room, and I guess I was fairly arrogant, and I was like, “I do not understand why that person is not happy. They are a good 60% better.” It then hits you like a ton of bricks: who wants to be 60% better? Who wants to go from 10 lesions down to 4? No, we want to be clear. For the quality life issue, when you’re looking at your patients and seeing acne on them, try to personalize it and realize that this is something that bothers people. You don’t have to have a lot of acne for it to bother you.

 That’s extremely true. Fran, what do you see in your practice? Who’s the most psychologically impacted by their acne? Is it the teenager or the adult woman with new onset acne?

Hilary, I would normally say that, because of the number of adult women who I see, the adult woman is more impacted. This may be because they feel like saying, “I’m so far from teenage years that there’s no way that this should be happening.” I’m like Julie, and I apologize if I’ve told you this before, but I had a recent episode with my daughter, who’s now 30 years old, who has never had any significant bouts with acne; she had the worst acne ever. It was a real wake-up call for me as the mother of a daughter who had pretty good skin all of her life, and I could see the impact on her and the anxiety it provoked in me.

There is actual collateral damage when you’re dealing with someone who is suffering from acne, whether they just have a few comedones or papules. Just like Julie, we see patients, and we say, “Why aren’t you happy that you’re better?” That’s what I was saying to my daughter: “I’m treating you, and it hasn’t been that long, but you’re getting better.” I could see the impact it was having on her day-do-day function, and that impacted me. Talking about anxiety and being under pressure as the dermatologist, it was out of this world.

I don’t know. Because it is something that is more chronic in women, I definitely think it’s the women who suffer more because it can last so long and be so aggressive in women as you get older, which we don’t see that much in the men.

Impact of Acne Vulgaris on Quality of Life

 Why don’t we talk a bit about the diagnosis of acne? Let’s start off with some contributing factors that may be present, like genetic components or perhaps environmental components. Jim, what do you think about that? If a patient sitting in front of you with acne, are there more genetic or more environmental predisposing factors for this particular patient?

The patients often think that it’s “environmental” because they think it’s something that they’re doing, something they’re eating, or something they’re using on their skin. A lot of times, it’s the parent though. I hate to say it, but it’s usually a mother. It’s sometimes a father, more so nowadays than in the past, who is implicating it by saying it’s the patient’s diet or what they’re eating or drinking. The patients will sometimes have questions about that. There’s definitely a genetic component to it, but we don’t always see or hear that when I see patients who have more severe acne. Many times, one of the parents or both will have had severe acne at some point. I think about that as a factor, but it’s so common that it’s something that many people are going to go through. How they individually respond to the inflammatory changes that are going on dictates the severity of their response.

 Yes. I remember seeing a statistic once, and I looked back and tied to find it again, but it was that severe acne begets severe acne. There is at least some increased incidence of severity in the parents reflecting severity in the child. It is also that adult female acne begets adult female acne. That’s the statistic I can’t find any more. Do you think that’s true in your practice?

 I remember that, for a lot of the women who have acne, the way that they arbitrarily defined adult female acne years back was 25 years of age and older. With some of the pharmaceuticals that they were trying to target, especially topical agents, they would break it down from adolescents to adults, adults being 18 years of age. It’s not like you’re 17 years and 364 days old, so you have adolescent acne, and now 1 day later, you have adult female acne. If you separate it out, you might say that, for women who are in their mid-20s and beyond and have acne, about 75% of them have the same type of acne that they had as teenagers. A smaller percentage have acne that started when they were in their early to mid-20s or maybe even later, and they didn’t have much acne when they were teenagers.

For a lot of these patients, they have acne, and it just never shut off with a lot of the female patients. There are patients who come in who tend to have that “classic hormonal acne,” which is a term I don’t like because all acne is hormonal. I heard Julie say that this weekend in a talk, and I couldn’t agree more. They have that band, that U-shape type of presentation that’s very inflammatory in nature and not very comedonal.

But a lot of the women who have adult female acne have the typical papules, pustules, and comedones that are on the face above the jawline, and they may also have truncal acne, so I don’t know if that’s totally true.

Contributory and Predisposing Factors Influencing Acne

 Fran, anything to add on the clinical manifestations of acne that you see in your practice?

Julie gave a great review of the clinical manifestations of acne. We have comedones, which can be whiteheads or blackheads. That depicts whether they’re open or closed. The open comedones are oxidized, which turns them black, and that’s why we call them blackheads. We then have papules and pustules. If there’s pus in them, then we call them pustules. Some people refer to papules as pimples. When the inflammation and swelling are deep in the skin, then a nodule or cyst can develop. The nodule is solid, and the cyst is filled with sebum or pus, but both are tender. There are different forms of acne. Acne mechanica is from friction or rubbing, which we see in athletes. We also see it from anything: wearing a cap or a hat on a regular basis can cause the acne mechanica, or even a scarf.

Then there are your more severe forms of acne, such as acne conglobata and other severe forms of acne where you primarily have nodule, cysts, and scarring with the connected channels underneath the skin. When we talk about acne, we’re most commonly classifying it as mild, moderate, or severe when we are talking to our patients and in general conversation. When we’re doing research on acne, we include that almost clear category or that clear category when acne is totally resolved. Those are the most common forms that we see.

I’d like to add something though. I’m glad Fran mentioned the mild, moderate, and severe cases. The fact is that, when we’re seeing patients, we’re seeing them in a small snapshot of time. I’m talking about in clinical practice, not in research.

We’re looking at the patient on that day, but unless they have acne at the far end and couldn’t get much more severe, if they’re in the middle, I always magnify that by 25% or 30% because I may not be seeing them on the day that it’s at its worst. If I only treat what I’m seeing on that day, I’m probably going to be chasing from behind. Is it OK if I ask a question, Hilary?

I still see patients who come in who were going to another dermatologist, and I never like to be thinking, “What the heck was that person thinking with this?” I’m sure people are sometimes saying that about me when one of my patients goes to somebody else. When the patient has a diagnosis of acne, and you go into the room, and you go, “I don’t think this is acne; I think this is rosacea.” I see that, and I don’t want to say that it’s all the time, but I see it more so than I would expect to. Are you noticing that?

 Yes, I see that quite frequently, and I walk in the door, and I’m thinking, “I’m sitting down to have a rosacea conversation,” and I find out that I’m sitting down to have an acne conversation. I see that quite frequently, and when it comes from a PCP [primary care provider], I’m not terribly surprised. I’m surprised when it comes from a dermatologist. What about you all? Do you see that too?

I’m surprised, but I also don’t know what it looked like when they went to the other doctor.

 That’s a good point because it does change over time.

That would have been what I would have added. I’m glad that my Alabama patients aren’t going out to Nevada to see you Dr Del Rosso.

If I’m honest, I’ve had patients like that, where I’ve seen them at 1 visit and thought, “This is rosacea,” but then I see them at a subsequent visit and say, “You know what, there is now this component of acne as well.” Those things can coexist. I know that doesn’t happen often, but there are times where my charts talk about an overlap between those.

That’s possible because, with acne, you can sometimes manifest with just mostly inflammatory papules. It can look just like rosacea with few comedones, and the next time they come in, just like you said, you then see more lesions that are consistent with a diagnosis of acne. It depends on what we’ve all said: what the provider saw when they saw them at that point in time.

 Yes. That’s especially true for darker skinned patients where the erythema might have been overlooked. You see the papules and say, “This is acne,” without going further and asking about symptomatology. “Is it burning and stinging? Do you feel hot to the touch?” There are also ocular changes and other things that may be present in a patient with rosacea.

This whole conversation reminds me of something you said a long time ago, Hilary. This is one of the most memorable stories in my dermatology career.

You’re going to know exactly what I’m talking about. Something we’re talking we’re talking about here is examining patients. We can sometimes be so quick about that because this is a diagnosis that we can make from across the room 95% of the time. There was an old survey done that showed that our patients sometimes feel like we’re not looking at them closely enough. Dr Hilary Baldwin is sneaky, so after hearing that, she would say that she would take her magnifying glass. She wants to build the confidence of the patient, so she would take the magnifying glass and get very close to the patient, and that makes them feel like we’re looking closely, and of course we are. The rest of the story, Hilary, was that you would be planning your dinner for that night or something like that when you did it.

 Yes; 10 full seconds of thinking about what I was going to cook for dinner that night.

We don’t always have time to think about that either, but we do want to be sure we’re examining the patient. As we all know, the comedonal acne is the key finding. Most of the time, we’re going to see it. We know that the ratio between comedonal and inflammatory acne shifts over time. Our youngest patients are mostly comedonal: they have acne in the T-zone, they have them in their ears, and then over time, that shifts. With our adult female patients, you’d sometimes have to hunt pretty hard to find a comedonal lesion. They may have shifted more to where they have inflammatory lesions.

To Jim’s point, that adult woman sometimes comes in, and on the day she sees you, she doesn’t have any. She’ll tell you, “If you would have seen me last week, I had 2 huge knots on my chin.” We have to look closely, and we have to take a good history.

There are other things that can mimic acne, other than rosacea, which can definitely mimic acne, but you should look for the comedones. It can sometimes be perioral dermatitis when we have that lower face involvement. Granulomatous rosacea could look like acne, and pityrosporum folliculitis could as well. None of these are perfect. Lupus miliaris disseminatus faciei could as well. These are things that could look somewhat like acne.

I’ll say another thing that I see every now and then: true epidermoid cysts. Somebody comes in who has been on isotretinoin for a long time, and they won’t stop it because they have 3 lesions that won’t go away. When you look and examine more closely, those lesions are not going away unless we excise them.

On the subject of examinations, we have to recognize that, if we don’t ask to look at the trunk, we’re not going to be told.

Many of these patients have truncal acne, and the severity is discordant. It could be severe on the face, mild on the chest, moderate on the back. The idea is that it’s far more common in men than women, but we know that’s not true. A lot of the time, they don’t necessarily tell us about truncal acne. We have to ask to be able to examine their chest, back, and shoulders, or else we won’t know about it.

Clinical Manifestation and Differential Diagnosis of Acne

 Another thing that’s different about the face and the chest are the common sequelae that can occur after the acne lesions have resolved. Fran, what kind of stuff do you see in your practice? Is there a difference between the trunk and the face in terms of scarring, hyperpigmentation, and the like?

Hilary, in my practice, I see about 60% of patients with skin of color. I would say that the most common sequelae that I see is post-inflammatory hyperpigmentation: the dark spots that we see on the skin. In my fairer patients, I see post-inflammatory erythema, pretty commonly. In terms of distinguishing the face from the trunk, truncal acne is likely to scar. I would say that I see much earlier scarring with truncal lesions, which is why I want to make sure that I look for it and diagnose it instead of waiting for the patient to complain about it. Some won’t complain about it because it’s covered up, and they’ll wait until it gets bad and start to scar before they bring it to my attention. I want to make sure that I capture that from the very beginning of the lesions.

One of the sequelae that I want to talk about, going in another direction, that Julie talked about already. Something we don’t think about when we talk about sequelae of acne, is that psychological sequelae: embarrassment, impaired self-image, low self-esteem, frustration, or even anger. They get mad at us because it’s not clearing up quickly enough. They are also angry at themselves. They don’t understand, or their parent doesn’t understand why they’re having this acne.

In addition to physical sequelae, which are commonly post-inflammatory erythema, post-inflammatory hyperpigmentation especially in darker skin, and scarring that we can see in anyone, I always think about that psychological sequelae that Julie talked about earlier when I’m treating patients.

On the physical side, there’s a type of scarring on the trunk with little white atrophic scars that I’ve never seen on the face. I think they are called albopapuloids; there’s a term for them, and I don’t think I’m remembering correctly. I’ve seen it in the book 

. You see it every once in a while, and I have found nothing that helps that.

I’ll also ask all of you. This is certainly going back to what Fran mentioned: I find that a lot of my patients with darker skin, especially Black females, will tell me that, “I know the acne is going to go away, but it’s these dark spots that bother me the most.” As we know, those are very challenging. On the psychological side, that bugs them because they hang around for months.

 Alison Layton, [MB, ChB,] wrote an interesting article several years ago now that was called, “Scarred for Life,” and it was about exactly your point, Julie and Fran. The point was that, even once the acne is gone, and even if there are no physical scars, the psychological scarring of having had acne in the patient’s earlier life stays with them forever, and it sometimes changes the paths that they take in life. It’s certainly nothing to be sneezed at.

Common Sequelae and Potential Complications of Acne

 Jim, let me start with you. Briefly, how do we tie in the medications that we’re going to pick to treat these patients based on what we know about the pathophysiology of acne?

We always want to target as many of the pathways in the pathophysiology as we can. I like to see all patients on a topical retinoid. I like to utilize benzoyl peroxide as often as I can. We have some good formulations of benzoyl peroxide that are well tolerated.

Topical antibiotics, as long as benzoyl peroxide is there and being applied at the same time, not separately because they don’t always get them on. These can both help, but benzoyl peroxide and retinoids are still fundamental. We have other agents. We have dapsone and others that are helpful. We now have clascoterone, and it is going to be interesting to see where it fits in.

We have a topical minocycline, and I might utilize that before I put the patient on an oral antibiotic, if I thought they need an oral antibiotic, to see what type of an effect I’m going to get. If it’s not enough, then I could always change. I like the old fundamentals from the beginning: a topical retinoid, even if you have to build it up because of tolerability issues, and benzoyl peroxide. I like both of those a lot.

 You’re attacking the problem from multiple directions. Is your eye on the pathophysiology? Are you thinking, “I’m going to use this for the follicular hyperkeratinization? I’m going to use this to kill 

Yes. I’m trying to target most of those things, but I also think that it’s more conceptual. These are not static: I’m a big believer that the inflammation is there before you see the lesions.

It lasts longer, even when the papules and the pustules flatten out, and you just have an area of discoloration. You know that 

 is sitting there, even if it’s dead, and it’s still promoting inflammation. That’s why we have a persistent inflammatory erythema and pigmentation. It’s not immediately post-inflammatory: the inflammation doesn’t shut off overnight. You have to treat more aggressively up front and go longer than you might think you need to, with a good combination approach.

Jim, that’s a great point. Many years ago, [Rebat] Halder, [MD] did a study looking at post-inflammatory hyperpigmentation that was a result of acne and skin of color. I’m sure you’re all familiar with the study.

Absolutely. We think that, with post-inflammatory hyperpigmentation, there’s no active disease going on, but when they did the biopsies, there was tons of inflammation in those lesions. You’re right, we definitely have inflammation going on well before we can see it. Even as you have precursor lesions, microcomedone, and comedone, there can be some inflammation associated with those, and we see that. We’ve learned how to understand that process clinically and apply it to what we’re seeing, as well as the post-inflammatory hyperpigmentation. It’s not so surprising with the post-inflammatory erythema.

 In general, what we’re talking about here, getting back to the pathophysiology of acne and the 4 pivotal factors in the pathophysiology of acne, we’re talking about grabbing medications, 1 from column A, and 1 from column B, trying to make sure that we’re attacking acne from different directions. We use something to decrease inflammation, something to unclog the pores, something to kill 

, and something to reduce sebum. We know that, with the average dermatologist, the average successfully treated patient with acne is on 2.53 medications for Pete’s sake. Something that you will all agree with is this: when we see patients who come in out of the dermatology specialty, let’s say, they are often on multiple medications that influence only 1 of the pathophysiologic factors of acne. I see patients coming in on topical clindamycin and oral minocycline, ignoring all the rest of the pathophysiology of acne.

Selecting Treatment Based on Pathophysiology of Acne

 We have a couple of new tools to play with in our acne toolbox, so let’s briefly discuss the new kids on the block. Julie, I know that we have a recent approval of clascoterone 1% cream, which is an antiandrogen. How is this fitting into your armamentarium? How does it work?

It’s not fitting in yet because it’s not launched to us. It has been FDA approved, but it’s not something—at least as of the time of this recording—that we have available to us. It’s supposed to be available in the first quarter of 2021. It’s really interesting. I want people to think of it like this even though it’s not exactly this: Think of it like a topical spironolactone because it is going to competitively block the androgen receptor. It’s going to compete with testosterone or DHT [dihydrotestosterone]. If you think about, go back to the 4 main things that we’re trying to target in acne: follicular plugging, inflammation, 

Where would these antiandrogens potentially work? They would definitely work for sebum and inflammation. There’s a chance that, through an indirect effect, it might even have more impact than that. When you’re thinking about plugging this in, you’re thinking about sebum and inflammation first.

One of the unique things about this product is this: Because it gets high skin concentrations, not just high blood concentrations, this is going to be the first androgen blocker that we can use in not just women but men as well. That’s something unique about this. Again, hear that part: This is going to be an antiandrogen that we can safely use in men. In fact, in the studies, about 38% of the people in the studies were men.

In the studies, it was enrolled down to the age of 9, but this is a product that is now FDA approved down to the age of 12 for acne vulgaris. It’s nice that we’re going to have something that we can use in not just female patients but also male patients.

In addition, in the extension study, they included trunk. After they completed the typical phase 3 blinded pivotal trials up front, when they did the 1-year extension, they allowed treatment on the face and trunk. It was effective in both those locations.

Interesting. Getting into some of the other newer agents, Fran, have you used the micronized tretinoin lotion? What do you think makes it different from other tretinoin formulations you might have used in the past?

I have used it, Hilary. Tretinoin is a staple of the retinoids in treating acne; however, tolerability has always been a challenge in treating acne. The fact that it’s a lotion formulation, and this is the first lotion formulation of tretinoin, allows for easy spreading and use in large areas in addition to small areas of the body. In addition to using it on the face, we talked about how truncal acne is a real, prevalent thing, and we have to look for that and find that. This is a medicine that we can now use easily on the truncal areas. The unique lotion incorporates what they call a polymetric honeycomb matrix, which is a large, repeating matrix that helps provide a uniform distribution of both the tretinoin as well as moisturizing and hydrating ingredients. That way, with the tolerability issue, the dryness, and irritation that we’re used to talking about with retinoids that has been historic, we’re not finding it with this molecule. It makes it a great product for those with tolerability issues and those with sensitive or dry skin in our adult female patients. Those are the areas where I’m finding it helpful.

The other point about that particular formulation is that, in the studies, retinoids have typically been in the protocols. The patients have been told to apply at bedtime. In this case, they were not. The tretinoin lotion could have been used any time throughout the day. They didn’t necessarily have to apply it in the evening, and they got the efficacy that they got with patients applying it at any time during the day that they wanted to.

 This is very helpful, especially with our teenage population. I like to say this: see drug, use drug. The more rules you give the teenage patient, the less likely they are to use the stuff.

Newly Approved Topical Therapy: Clascoterone Cream 1% and Micronized Tretinoin 0.05% Lotion

 Julie, can you tell us a bit about trifarotene cream?

Trifarotene cream is a new retinoid molecule, so it’s not a reformulation of something that we’ve had: it’s a whole new molecule. It’s also the first new retinoid molecule for acne in over 20 years. It’s nice that we have this newcomer to use in the armamentarium to treat our patients with acne. There are a couple of things to know about trifarotene. The first is that it is selective for the RAR gamma receptor. I’ll be honest, I’m not certain how important that is. But the RAR gamma, which is the retinoic acid receptor. That is found predominantly in the skin, so it stands to reason that you would want to target the 1 in the skin if we’re trying to treat a skin condition. It is gamma selective.

The other thing that is interesting, though, is if you look at the concentration of trifarotene. I’m going to say a bunch of 0s, and I’m not messing up, OK? It’s 0.005%, and I don’t know of another topical off the top of my head that has such a low percentage. What that means to us is that it is potent at this low concentration, and what that also can means is that it has low systemic exposure when it’s applied to a wider surface area.

I’ve got to say this: They studied it in exactly the same way they studied facial acne. They studied it in truncal acne, so they didn’t do just part of the assessment. If you had moderate acne on the face to begin with, you also had moderate acne on the trunk. We were then going to look at success rates on both the face and the trunk separately and look at lesion count reduction. It was not just the IGA [Investigator’s Global Assessment] success rate, but it was also lesion count reductions on the trunk and face.

In the end, this was something that jumped out to me. I don’t know if this is as important to everyone else, but when we’re treating truncal acne, we sometimes step back a bit, and I don’t know if that’s just our bias. We all assume, “It’s going to be hard for them to rub something on their back, and the back may not doesn’t respond as well as the face anyway.” You know what? At least in this study, it was a defined area, and when you look at the results in this study, the acne on the trunk did just as well. It responded as well as the acne on the face, and it responded as quickly as acne on the face. It makes me look at this and say, “Maybe I don’t have to alter my treatment plan totally as I move from facial acne to truncal acne.” There are products that are going to do double duty, and we have data to show that. I’m glad we’ve talked about truncal acne a lot, and I’m glad we’re getting some data there. Yes, trifarotene cream has probably studied truncal acne—I’m going to go ahead and say it—better than any of the others because it used all the same parameters that it was using on facial acne.

 Yes. We have an additional topical retinoid. We’re very retinoid rich lately. It’s tazarotene 0.045% lotion. Fran, have you used it? What’s different about the epidermal delivery system?

I have used tazarotene 0.045% lotion. Tazarotene has been around for a long time, and it’s been known. It’s had the reputation as the strong retinoid when treating acne largely because of challenges with tolerability. This epidermal delivery system of tazarotene 0.045% lotion allows it to be what I call the gentle giant: It was created using this novel polymetric emulsion technology that I mentioned before. The benefits of this new technology are that the lotion is highly spreadable. Although there weren’t specific studies done on the trunk, you can use it on the face, but you can certainly use it on the trunk, the chest, and the back. It’s spreadable, and it allows for more efficient delivery of tazarotene deep into the skin while reducing that potential for skin irritation. Tazarotene has had the stigma of being that intolerable retinoid that you can’t use on sensitive skin.

 The overall story with these new topicals is that we have greatly improved tolerability across the board, probably because of some of our technologies that go into the manufacturing of these great vehicles. That includes moisturizing agents, and it includes more spreadability and micronization of the particles, which is something we see in the next and last product that we’re going to discuss today: topical minocycline 4% foam. Jim, what has your experience been with this medication?

They overcame the challenge of trying to formulate a topical tetracycline in general. We’ve had topical tetracyclines, meclocyclines, and tetracycline, and they all flopped for a variety of reasons when trying to create a topical formulation. With minocycline, the challenge is to get it to be solubilized. You have to use a lot of lipid. Yes, if they put it in lard, the lard could deliver the minocycline. That would be OK, but nobody would want to use lard on their skin. They have to formulate it in something that patients would actually use that would solubilize the minocycline to deliver the minocycline, and they did that with the vehicle formulation that they came up with. They found some oils that are barrier-friendly that also help solubilize them in the cycline. They were able to do that.

The other part of that that’s important is the concentration of the 4% minocycline foam, which is the 1 that’s FDA approved once a day for the treatment of acne. The concentrations are very high in the epidermis and the dermis, so you’re not getting the systemic exposure that could lead to antibiotic resistance in other parts of the body, and you’re not getting systemic exposure that could lead to systemic adverse effects that you might get with oral minocycline.

What was interesting is that a lot of people ask about minocycline hyperpigmentation because you’re getting high concentrations in the skin. I was 1 of the investigators on this particular formulation, and we did see postinflammatory hyperpigmentation focally that we would see related to acne. It is the same with the 1.5% that has been evaluated for rosacea, and it has been recently approved for rosacea. What we did not see in these studies was this: None of the patients was getting the minocycline-associated pigmentation, that diffuse slate-gray color, brownish pigmentation, or even focal-blue hyperpigmentation that we see in scars has not happened in the clinical trial. This all adds up to be an advantage in addition to the levels that get so high in the skin that they appear to get to the mutant-prevention concentration, which means they’re beyond a range where you can select some resistant organisms. The levels are so high that when bacteria try to replicate, the levels are much higher than any of those bacteria could withstand. There are data to suggest that that is the case. We don’t have all the data we need on that.

Newly Approved Topical Therapy: Trifarotene 0.005% Cream, Tazarotene 0.045% Lotion, and Minocycline 4% Foam

Another thing that certainly helps with compliance is the frequency of dosing. Jim, can you tell us about the new oral antibiotic, sarecycline? This is our first new-molecule antibiotic for the treatment of acne since 1971.

Sarecycline, as you know, is in the tetracycline class. It’s called a third-generation. We had doxycycline and minocycline as second-generation tetracyclines, which other than a few exceptions, were indicated for the treatment of infections. These were the various gram-positive infections, gram-negative infections, and other types of organisms. They were grandfathered in for the adjunctive treatment for severe acne, but that was not based on formal phase 2 and phase 3 clinical trials. They’ve been around a long time, and they’ve certainly been helpful to us and continue to be helpful to us, but they are broad spectrum in terms of their antibiotic activity.

Fast-forward to sarecycline, which we’ve had since 2018. Sarecycline has some structure activity changes that alter its antibiotic profile. It has a narrow spectrum, defined in this case as being active against 

]. This year the FDA allowed the company, after it provided more information, to put something in the package insert about its activity against what it calls 

. It’s the same organism, and they made a statement in vitro that it has a low potential for resistance in spontaneous mutation strains of resistant organisms. They make that statement. It also has activity against staphylococci and streptococci and even methicillin-resistant strains of staphylococci, but it has not been evaluated and approved for that. It’s been FDA approved only for the treatment of acne. It has negligible activity against gram-negative organisms and several anaerobes.

When we’re utilizing an antibiotic, in this case a weight-based dosage once a day, down to the age of 9, it is shown to be effective for the face with some secondary evaluation also effective for acne vulgaris on the trunk, primarily for inflammatory lesions. We’re not trying to reduce organisms in the gut or in other microbiomes. Where we’re targeting the skin, we have less selection pressure against gram-negatives in the gut, for example. That’s believed to be an advantage: You’re going to have less selection pressure and fewer of the typical tetracycline-associated adverse effects that we’ve sometimes seen with the others. It’s not always that often, but they can certainly become associated. With things like vertigo, we didn’t see any vertigo, or room spinning, as we sometimes see with minocycline. It did not happen with sarecycline. Photosensitivity was also very low. GI [gastrointestinal] adverse effects like nausea, vomiting, abdominal pain, and esophagitis were also low. Vulvovaginal candidiasis was low. Yes, they can happen, but it’s low. There weren’t head-to-head studies, but if we look at comparative rates, there’s a low risk of those adverse effects. You have the antibiotic with less antibiotic resistance advantage, you have the low adverse-effect profile advantage, and you have approval down to age 9.

When we’re talking about micronization as we have with many of the medications that we just mentioned, we can’t leave out the newer formulation of isotretinoin with Lidose technology with micronized particles that increase the surface area so that the medication is more bioavailable. Studies have shown that with this particular medication, the bioavailability is 50% higher than with the nonmicronized formulation of the Lidose technology isotretinoin, which in turn was already giving you better bioavailability on an empty stomach than conventional generic isotretinoin was giving. The implication is that, because the bioavailability is so good, you would be able to dose it on an empty stomach, as opposed to dosing it on top of a 50-gram fat meal, which of course makes obesity the No. 1 adverse effect of isotretinoin. This also gives our patients a choice, and we’re not giving them any kind of rules. As we said before, when you give a teenage patient rules, the chance of them not complying with their medication regimen is increased. Here is another situation of see drug, take drug.

Newly Approved Oral Therapy: Sarecycline and Micronized Isotretinoin

Let’s talk briefly about what’s coming up and if there are any other unmet needs or gaps that we need to fill. Jim, you always have your ear to the pipeline. What’s in our future?

There are a couple of interesting formulations that people are working on. There’s a sponge formulation, which I can’t say too much about, that people are working on. We also have to remember that we have some good over-the-counter formulations. We have a 5.5% benzoyl peroxide formulation that’s been proven to be as effective as a branded benzoyl peroxide–clindamycin formulation. It’s sometimes hard to get stand-alone benzoyl peroxide, so we have to remember that.

What about the new microencapsulation of benzoyl peroxide and the possibility of combining it with tretinoin? How do you feel about that?

With the microencapsulation technology, you are correct: There is a microencapsulation technology that microencapsulates not just 1 big microcapsule but multiple small ones with different active ingredients as well. In the case of having the benzoyl peroxide 3% with a tretinoin in the same formulation, it had good efficacy in terms of the active vs the vehicle in clinical trials for acne once a day. That’s encouraging, so that’s going to be an important addition. There is also the combination formulation of topical minocycline foam with adapalene 0.3% that has completed its phase 2 trial, which is basically using the same as the 4% minocycline formulation as far as the vehicle. There’s a combination product in development with the topical minocycline and adapalene.

We have a lot coming up. Julie, are there any unmet needs that you can think of? Are there things we still need to see?

There are always some unmet needs. The first would be that I would love to have an absolute cure for acne, especially 1 that does not have teratogenicity as a potential adverse effect. I would also like to give our patients easier regimens. Right now, things are once a day or twice a day, but if you look at the biologics in psoriasis, what’s happened is that we’ve gone from once a week to using the drugs every 12 weeks. If we had something in the acne world that was easier for our patients to be adherent with, that would be helpful. Those are the things that I would think of.

 When we’re talking about the future, the future is here today in telemedicine. Have you guys been using much telemedicine in treating your patients with acne? Fran, have you been doing that in your practice

Hilary, I have. During the beginning of the coronavirus pandemic, it was vital to shelter in place and focus on safety. Telemedicine took the front seat during that time, but it’s been helpful, and a lot of providers have continued it. I certainly have because there were still many people who were suffering from various forms of acne even during the pandemic. Telemedicine provides us a means for patients to consult with their providers, to be evaluated, and to start, continue, or adjust the therapy that they’re on. However, it’s not 3D, and I know that’s been 1 of the complaints of it: It doesn’t allow for the procedural interventions that we commonly do in acne. We can definitely guide our patients and make adjustments. I’ve found it helpful in allowing us to help our patients. I have continued to use it, and it’s not going to go away.

It’s not going to leave my office anytime soon, especially for follow-up visits. Many people around the country have the advantage of having a parking lot for patients to come into. I don’t have such an advantage in Brooklyn. Parking is terrible, and being able to offer telemedicine for follow-ups is not going to leave my office any time soon. The patients seem to appreciate it. There was a bit of pushback to begin with, but they’re then acquiescent. Are you guys doing it in Nevada and in Alabama?

Our group is doing it. I have personally chosen not to take on tele-dermatology. We have some clinicians in the group who are doing it.

I have done it. I did it mostly during the 6-week shutdown period, and I was so thankful for my patients with acne at that time. I found my patients with acne and rosacea were the easiest to see via telemedicine. I’ve said on more than 1 occasion that there were some pluses. You could say, “I want to see the cream that you’re putting on your face,” and then they go with their phone or their laptop, and you’re going into their bathroom. They pick up the tube and say, “This is the 1.” It was nice to be able to do that, but we’re pretty open in Alabama, so I’m not doing much of it right now. The exception is for those patients who are in college, and they want to be able to do their follow-ups. Before, you’d always have to figure out when they are you going to be home, and we can now do a telemedicine follow-up visit. We’re certainly doing some, and I’m thankful for patients with acne because they’re the best patients to see by telemedicine.

 In New York, you do a lot of driving, and as you mentioned, there’s a lot of difficulty with parking. Those patients find it helpful, and they are grateful.

Nobody wants to get on public transportation.

Yes, exactly. We’ve pretty much rounded out the entire topic of acne. This has been an excellent discussion. We certainly hope you found this information to be valuable to your clinical practice. On behalf of my 3 good friends, I thank you all for watching this 

Incorporating New Medications into Acne Treatment