← Derms on Drugs
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- [00:02]
A
Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine. The best educational platform in dermatology and provided at no cost to medical providers. Derms on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Zyrus from Docs Dermatology, and each week I'm joined by my residency buddies, Dr. Laura Faris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know about to be on the cutting edge of Durham. And you'll actually have some fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify and other major podcast platforms. And a reminder, there is a video component to the podcast. It has the key figures and tables from the articles we talk about. And this episode is supported by Lilly, a medicine company. So we are so excited to have a special guest this week. We've got Dr. Agoo from, I believe, Johns Hopkins, although I probably should have confirmed that before we started the podcast. And we are going to be talking about, about ccca, which is something that, you know, we all see all the time. It is a really difficult thing to manage and, and Dr. Raghu has done some incredibly interesting work that is super clinically relevant. So, so excited to have you on Dr. Agu.
- [01:21]
B
Thank you so much for having me. You already scored one point because you said Johns Hopkins and not John Hopkins. Ah.
- [01:28]
C
Okay.
- [01:29]
A
That's pretty good. That's pretty good. I, I did interview at Hopkins for my prelim year way, way back in the day, but I didn't get into Hopkins Durham, so I didn't, didn't, you know, didn't go there. But. All right, let's. Let's get into it. We're going to start, we're going to start with an article from Dr. Patton. Dr. Patton. And this is, I believe, one of Dr. Raghu's articles. Dr. Patton, why don't you go ahead and get us started?
- [01:55]
C
Yeah. So my Deep Dive paper was titled Using Disease Symptomatology to Guide Treatment in Patients with Central Centrifugal Cicatricial alopecia. Introduction of CCAT scoring tool by Kadri et al. Dr. Agoo was a senior author and this was in the February 2025 edition of Skin Appendage Disorders. What is the CCAT? It's the CCCA Clinical Assessment Tool. And it's pretty straightforward tool to use just.
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A
By the way, that is a very sad journal.
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B
Sad.
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A
All right, go ahead, Pat.
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B
I'm sorry. That.
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C
That was the level of comedy that you can expect for the rest of the show.
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D
That's the hit or miss comedy part.
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B
Yeah.
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C
That's a big mess.
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B
Yeah.
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C
Yeah. Figure one, outlines of the scoring system. You evaluate patients based on disease progression. Pain, pruritus, erythema, scalp resistance. The scalp resistance can only be done if you perform injections at the visit. So if you don't do any injections, you have to leave this score out. So disease Progression is either 0 or 2. Initial visit always gets a 2, and the rest of the symptoms are graded on a 0, 1, or 2 scale. So the high score is either a 10 or an 8. If you don't do the injections, you can't do the resistance, so it can only be an 8. I will confess, I don't think I've ever appreciated differing scalp resistance to tack injections. I think I treat a fair amount of ccca, at least for a white boy, and I've never appreciated a difference between patients or in the same patient on different visits and how hard or easy it is to inject tack. That is definitely something I'm going to keep in the back of my mind when I. When I'm treating these patients. Now, the authors applied the scale retrospectively to 82 patients with CCCA over a period of one year's.
- [03:42]
A
My first question here. So when you're doing this score, if you don't inject on a given day, say they, I don't want an injection today or for whatever reason, do you change the way that you interpret the scores?
- [03:59]
B
That's a great question. So it's not meant to be used like a salt score, where you add up all the parts and come up with a final score, because the goal is to get to zero. Right. So have. Have no symptoms. And so really what we do from visit to visit is we're looking to see if you have any activity. Now, if we don't do the injections, we just have less information, so we can't tell you, okay, you got a perfect score. Because we just don't know how much resistance we see in your scalp. But if you still have itching, then you're still active. And the idea behind this score, which is twofold, is one, can we, now that we have all these options on the table, can we use your disease symptoms to GRA. To guide which treatment we use? And two, do you really have to get injections forever? And ever and ever until the end of time. When in every other form of hair loss we, we generally say, look like you look good, we don't have to do anything. You know what, let's start peeling away your anti inflammatories, your immunosuppressants. CCCA was kind of like the one disease where we're like, well, because it's never really angry, we just keep going, right? And so this is a way to peel patients off of treatment. So we kind of look at it differently than we look at other disease activity scales. And we're like, how high can it go? Because if you're this high, then we can put you on dupilumab, or if you're this high, then you can get, you know, an anti IL17. With CCCA, we're like, how low can you go? Because going to treat you. But at some point we'd like to know if we could just give you. If we could step away. Because you, you probably can. For most patients, as long as you're playing close enough detail to their symptoms.
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A
So the initial question is just zero or not zero. And if it's not zero, you're doing something. And if it's zero, you're probably. If it's. If they're not starting to keep using their topicals or their systemics or whatever, probably.
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B
Okay. So that's why at the initial visit you get a two. If this is the first time you've been assessed by a dermatologist for ccca, well, then you're worse than your baseline. And we're going to treat and we want all zeros for three consecutive visits. So that's about 12 months. And then we start to space out your treatments. Then we start to pull off some things.
- [06:23]
C
Okay, how, how easy, how coachable are. If you're working with residents, for instance, are they in judging that resistance, like, do.
- [06:34]
B
Great question. Yeah, all of the. Almost everything on the scale is somewhat subjective, but that's the most subjective. Now I will tell you, CCCA is really the only condition that I've experienced a bent needle with injections. I mean, truly, like where I have to toss the needle and I'm like, we just can't get into your scalp. Okay. It's that fibrotic. And that is just like, it just is what it is. Right? Like if you're bending a needle. So that's what we give a score of to that high score. So if you're really like using a ton of force and you're bending your needle, you have to toss that to two. And over time my residents are like, okay, and you have to start from, I treat alopecia areata. I'm giving injections to non scarred scalp all the time. I know that it should go in fairly easily. And what you have to do is you have to insert the needle before you push. Right. Because if you're just like, then you don't get to assess. But when you're trying to assess the resistance and you're just starting to notice the force that it requires to get the needle in, you start to notice it really quickly. And so I'll let my residents start to inject and they'll say, Dr. Agu, it's hard right here. And I'll inject as well. And I'm like, yeah, you're right. Like that's a one.
- [07:50]
A
See this? There's, I, I bet there's huge inter observer variability. Patton's got such weak little girl hands. When I say little girl, I'm talking like a three year old. Not like women have weaker hands than men, but like little. Probably to him every, it's, he'd probably.
- [08:06]
C
I have like a, I have a two handed syringe device because it's really difficult.
- [08:13]
B
So. And it's okay, right. If it's, if there's inter rater variability there. I think the biggest thing that comes from this scale, when you're dealing with scarring, alopecia, that hardly ever regrows.
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C
Yeah.
- [08:27]
B
When patients are coming in and seeing you religiously, they need to know that it's worth it. Right. And for derms, you know, like when there's no red, we're like, it looks so much better and the patient has all this pih and they're like, what? And you're like, no, no, you have to understand like. Right. And with the scale, I mean you, you know, now we implement it for every CCCA patient. You really see the patients, you're like, wow, you're getting better, your itching has decreased, your scalp pain. And then you see the patients who aren't responding to therapies now and you can really like quantify it and say, gosh, you've had this same itch score, you have the same erythema score for three visits. Like we need to add in something else. But patients, when you say, hey, your scores are going down, they're like, that's awesome. Right. And so, so much of it is just trying to turn a visit that is mostly qualitative a little bit quantitative. So you can give patients just better feedback that this is, this treatment is working. Because the other thing we did in that paper is we looked at standard therapies. We're like, okay, well, we're doing this. Doxy and clol. Did they change? And those work? Right. Standard therapy.
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A
Let's, let's go back to Dr. Patton here for a second. So, Dr. Patton, tell us. Yeah, keep going. About the article.
- [09:44]
C
Yes. So let's see table one. Wait, no. So they, they followed the. These patients, and over the course of treatment, most patients, 88% had an improvement in the CCAT score. 12% of the patients either had no change or worsening in the CCAT score. So, you know, some numbers, you could say, like, look to your patient. Most patients have some improvement. I think you have to coach them a lot on that. It seems to me like hair loss improvement means my hair's coming back. And, and that's not really the, the point of this scale. Right? You're not going to get hair growth. So, you know, coaching patients at the beginning, like, here's what our goal is. Here's where we expect to see improvement. Here's where we're probably not going to see improvement. I really like table one because it really just broke down what percentage of patients are given what particular therapies. Because, like, for me, I'll do TAC, like 5 megs per mil, and I do oral minoxidil. If they don't want to take a pill, then I throw in topical minoxidil, maybe a topical steroid. I kind of stopped doing doxy. I've never done metformin, except for one time because the resident suggested it. I think I'm probably going to do that more routinely. But if you look at the numbers, so tack. 96% of patients receive dial tac. So, you know, I'm giving that to most of my patients. I think I'm in line there. 96 also either topical or oral minoxidil. 56 got topical, 40% got oral. 68% of patients were treated with topical clobataz. And then there were lower percentages of patients treated with metformin or doxy. I was kind of surprised at doxy, especially given the table you have later where you're like that central box. This is my first treatment. Tack, topical steroids and doxy. Doxy was only given to like 17% of patients, at least in. When you looked at responders. Is that, was that a low number when you were going through?
- [11:43]
B
It is a low number. But I will tell you, doing. Implementing this disease activity scale has led me to doing doxy more. Right. Because what we did with those recommendations that was based off of literature data. Doxycycline is a dual anti inflammatory and anti fibrotic treatment. So what we were doing is we're kind of just looking at cases in our institution and saying, let's see how people were treated. But when you start to understand, like, where the activity occurs, right? The pathophysiology. Now when I do this scale and I see perifollicular hyperpigmentation, which is a 1, pericular erythema is a 2. Because CCCA is POSI inflammatory. So if you're seeing any bit of erythema, like, that's a lot, right? And now when I see persistently elevated inflammation, I'm like, oh, you have a one here. Doxy. And it works great, right? So I feel like if I were to rerun this, I would have a higher proportion. And that, and that spiel that you mentioned, critical. I think anyone who runs an alopecia clinic, you have to, you see scarring alopecia, you have to have your spiel down, right? And the spiel is, look, this is scarring. We don't measure success by hair regrowth. We measure success by disease stability. But then also we measure success by decreased inflammation. And so you're actually getting better. And that's why we are giving you oral doxycycline. That way, they're not like, I took this, but my hair looks the same. You say, no, that you actually had a little bit of inflammation that was visible and that's now gone away. And so I think it makes the visit easier because patients don't have to harp on hair regrowth as the only, like, measure of success, which they did like, 15, 20 years ago, patients would doctor shop and they'd be like, I saw this derm. They were great. But my hair looked the same. And it's like, actually that's, that's the goal, right? And if you don't explain that to them up front, they leave very dissatisfied.
- [13:45]
C
What? So if a patient comes in and they don't have any, let's say on the pruritus and erythema and pain, I, I guess you haven't done injections yet, so you couldn't grade that. Everything's a zero. I mean, you would give them a two because it's their first visit there. But with those patients, without the symptoms, without the, the pruritus erythema, do you kind of say, like, we're, we're at the end Stage, and I'm sorry it's scarring, but I don't know that there's anything we can do at this point that will improve anything.
- [14:18]
B
I think one of the things that's important to patients is, is, like, being honest with them when you feel like there's not a lot that's going to change their quality of life. So let's say someone has like 60, 70% scalp involvement and they're in a wig. For those patients, I often choose not to treat. I think that scalp injections are just far too painful and that even when you look at a patient and tell them this is not meant to regrow hair, they think, well, maybe there's just a chance. But if reliably, you cannot get them out of a wig, those patients. I say, as of 20, 25, we just don't have treatments that are going to be able to reliably reverse the extent of disease that you have. And I think it's just important to say that it's a hard conversation right there. There are very few tough conversations in derm, but this is one of them, and we just have to have them. I think if I have somebody who has very limited disease and maybe it's their first time seeing me, but they've seen a dermatologist for years, and they're like, look, I was seeing so and so 15 years ago. I stopped going because I felt like the treatments weren't working. I'm coming to you for a second opinion to see if there's anything new, but it hasn't changed. I won't give them a. I give them a zero, right? If they're reporting that it is it, I can tell you, you know, definitively I've gotten this diagnosis before. I was getting treatment before, and it hasn't changed. I'll give them a zero. But if they came from their bedroom and they're like, God, I really should see a dermatologist, I give them a two. If they've never been assessed by dermatologists before, never receive treatment, then they are by definition worse than their baseline. I want them to treat for at least 12 months. If they have mild to moderate scalp involvement. Again, if they have widespread involvement, I just talk to them about, like, you know, we try to see if we can write a letter for a wig. But I try to be upfront with them and let them know that I don't want them to torture themselves to keep things the same.
- [16:12]
D
So we had reviewed a paper, gosh, maybe a couple months ago that was out of Mount Sinai retrospective study of low dose doxycycline and their like take home message was this is important to do early on in the source of ccca. And so you know, one would you, it sounds like you would probably agree with that and then too I guess like.
- [16:36]
A
But yeah, the other message was we should be using a low dose that we don't need to use 100 bid.
- [16:42]
D
Yeah, that was my other question is do you agree just yay doxy or do you think here's the, you know, here's the dose that I would do.
- [16:52]
B
I've transitioned to low dose doxygen for scarring alopecia as well, just based on that data and the patients that I've put on low dose oxy are doing well again, I use the, the CCAT to guide me. So if they don't have any inflammation, like let's say someone comes in there early and they don't have any inflammation, they don't have any itch, maybe they just have scalp resistance and they're insulin resistant, then maybe I'll start with topical metformin. Right. I won't necessarily do doxy. We kind of play around with things. Right. But if I feel like doxy is a great option for them, then I, I will do low dose. If this is someone who's responded to 100 milligrams maybe in the past.
- [17:32]
A
Wait, what, what, what, what's. So what, what does low dose do mean to you? Is that 50 once a day? 20B ID. What's.
- [17:39]
B
I've, I've started at 50 bid.
- [17:41]
C
Okay, right.
- [17:42]
B
I've started at 50 bid. But I do think you can go lower than that.
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A
But ever do 50 QD? Why not 50 QD?
- [17:50]
B
Well, immediate release has a short half life. Right. And, and so that's the thing is I think if you're trying to get full day coverage, just doing it once a day is tough. Extended release is just, would be ideal. But it's very difficult to get coverage.
- [18:04]
A
Do you ever do the 20? Because you can get the 20 cheap. Do you ever do 20 bid instead of 50 bid?
- [18:10]
B
I do for my rosacea patients, for my scarring alopecia. I haven't gone down to 20. I should. Right. These are things that it's like, you know, I could probably go down even lower. But when I do it, these are my really symptomatic patients, I'm like, let's do 50 and see if it works.
- [18:25]
A
Okay.
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B
A year from now you may catch me and I'm like, I'm down to.
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A
20 yeah, yeah, fair. Okay, Patton, what else you got from this paper?
- [18:34]
C
That was pretty much it. The last figure that just. It's that nice algorithm center box. And then like Dr. Agoo said, maybe it's a patient's with a high insulin resistance. And so you start thinking about metformin in those patients if they're itchy. Adding a systemic antihistamine just kind of a really nice, like, you know, easy how I'm going to approach my CCCA patients. I thought it was a really helpful article.
- [19:03]
B
Thank you. I'm glad it was helpful. I mean, you know, we, we talked a little bit about how derma is so nice because there aren't that many algorithms, but I think scarring alopecia is so hard. I just think it's such a hard visit. Right. It's really emotional. We don't have great restorative treatments. And so I think it's just nice to get a little bit of a guidance because there are these options. It's kind of like, well, where do I start? And that's really the take home of the paper. If you start really asking patients just systematically, how many times a week are you itching? How many times a week do you feel pain in the central scalp and just starting to grade them and then just saying, okay, well this person's good except they're really itchy. I'm going to try really high dose of tyrosine and see if we can knock that out.
- [19:47]
A
What's really high dose antihistamines mean to you?
- [19:50]
B
Yeah, like twice daily Zyrtec instead of. Or Cetirizine instead of.
- [19:53]
A
Once a day you can say Zyrtec on here. We're allowed to do brand, so you know.
- [19:59]
B
Yeah. So twice daily Zyrtec is what I'll do.
- [20:01]
A
Okay.
- [20:02]
B
And it works. It's just compliance is tough. Right. For these patients who don't have like a allergic rhinitis. Right. Those patients are taking it every day. No big deal. But it works very well for that. I'll try doxycycline. It can be tough. And there is a very rare subtype of CCCA called like form Thrust CCCA where patients will just, instead of like smooth scalp, they'll just have like a tuft of hair that keeps breaking right in the middle. Those patients tend to be very symptomatic. They tend to be more symptomatic than your average CCCA patients. And those patients, you gotta try, you gotta cycle through all types of things to really get that itching to calm down. But once you do Then that hair starts to grow back.
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A
Now, one other question I have for you from this article. In the algorithm, you talk about plaquenil hydroxychloroquine, but it's not in the table, which made me think that you don't use it all that much.
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B
Wow. Yeah, I will never use it.
- [21:03]
C
Okay.
- [21:04]
B
I put that in there for buddies of mine who, like, use it. I don't. I don't use it because, look, doxycycline. Again, the data is there, right? We a lot of that literature on its anti fibrotic effects and it downregulates CGF beta. That's from the acne literature. It can remodel. It can do collagen remodeling. So, like, I. I need a little bit of, like, I have to understand the pathophys a little bit before I just like, yep, throw it on. Because the patients ask are like, well, what's this doing? And I'm like, yep, some T cell mediated inflammation, which we don't know for sure is part of CCCA at all. But, you know, so that's not for me.
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A
Okay. But I'm glad. I'm glad I asked because I was like, I don't use hydroxychloroquine in these papers.
- [21:52]
C
I don't.
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B
That was very deductive. You're like, but you did. It's on the table. So, like, yeah, I'm not.
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A
Here we go. All right, let's. Let's move on. Dr. Farris, what do you got?
- [22:02]
D
All right, so I have actually two papers. They're both case series from JAD case reports. And so they both are talking about using topical metformin for cccca. There's too many C's in there. Okay, so the first one is adjuvant use of topical metformin with standard therapies and recalcitrators central centrifugal cicatricial alopecia. A case series. This is from Williams et al from Georgetown. And then the second one is also out of Hopkins. And this is Dr. Agu's paper. It's a Royer et al. Hair regrowth and two. So this is actually, I was like thinking, this is interesting. You actually say hair regrowth and 2 patients with recalcitrant CCCA after use of topical metformin. So, you know, this is really getting at the fact that, like, we're talking a lot about, you know, inflammation. And I think, you know, my go to is usually like, how do I stop the inflammation? Is it doxy? Is it steroids? Is it topical? Blah, blah, blah. But, like, fibrosis is really. It's like such a prominent aspect of this. So. Yeah. So in the first one, Williams et al, three cases all had histologically confirmed ccc, and they were all treated with doxy topical steroids, one with tacrolimus, and then all with topical minoxidil with inadequate response. And then they all were given compounded 10% metformin at night. And then they said that they all showed visible hair regrowth in six to 10 months. And then in your paper, Crystal, that was two. A case of two women who basically had had, like, years of unsuccessful treatment with ILTAC topical steroids. One patient, viviscal, which reminds me, I'm going to ask you about supplements. But then they both got 10% metformin. And so, you know, and both. And then both of your patients also improved. So, you know, it was interesting because I think that, like, the hair regrowth thing is a little subjective looking. You know, you look at the photos and it's not. We don't have a SALT score. We don't have a great way to do it. It's like. And I like. I was like, wow, you're really getting regrowth. Because I'm like, stabilization. That's my goal. I would say they both. In both papers, the cases were kind of maybe modest regrowth, but definitely not worsening.
- [24:33]
B
I don't know. What.
- [24:34]
D
What do you think when you.
- [24:35]
B
Yeah, yeah. So I think most hair specialists who over time have come to accept that there are going to be a subset of patients with scarring alopec who, if they're really lucky, do get regrowth. Ccca. I think of the, like, big three. Let's call the big three. Ccca, Lichen, plano, Pilaris and frontal fibrosing alopecia. Right. Of the big three, CCCA is probably most likely to grow. FFA is probably second. And then LP is really tough. Okay. LP will like, really, like, just singe. Like, it's like, it's. The scalp has been burned. Okay. But regrowth is difficult to achieve in any form of scarring alopecia. And when you talk to patients, they say, well, what's the chance I'm gonna get my hair back? I tell them there no chance. That's visit one. Because if I tell them 10%, that's all they hear, right? And then when I'm like, oh, my God, your scores are going down. You have less inflammation. They're like, yeah, but what about that regrowth you promised. I say, look, this is a scarring alopecia. We can't reverse the damage that's been done, but we can at least make sure that the next five years look better than the last five, five years. Okay, now series, that first one I published in 2018 and we had previously written a microarray, we had done a microarray study where we just tried to define ccca, like what is ccca? What does it look like? And I wanted to see if it looked like diseases of abnormal scarring. Right? So these are things like keloids, focal segmental glomerulo sclerosis, systemic sclerosis, where fibrosis outpaces inflammation.
- [26:10]
A
Right?
- [26:10]
B
You get a little bit of inflammation. But anti inflammatories aren't super helpful because really the big issue is fibrosis. Right. And CCC had a lot of disease overlap with these classes of diseases. And metformin has been used in many of them and been shown to have anti fibrotic effects. So it was like, okay, well let's compound it, put it on the scalp. These are patients, they didn't fail treatment, they were on standard treatment, they weren't inflamed, but they were like, please, please, please can I regrow my hair? And I was like, well, we can try this. And they got better. Now one of those patients used metformin for about 12 months, did better and once she stopped, she lost that progress. Last year we published an rna, we published a sequencing study on the use of oral method.
- [27:01]
A
We're going to get to that one.
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B
Right? And so because that's the thing with case reports, right? Is that like you're like, okay, like we think it looks better, but if the general takeaway is like, should I promise regrowth to patients at ccca?
- [27:17]
D
No.
- [27:18]
B
Are there enough patients that improve with metformin that it should be considered a reliable option? Yes, especially because it like has almost no side effects. When we talk about the paper, the other paper, I'll talk to you about some more research that we're doing, but there is a way to I think identify who are going to be the best candidates for topical metformin versus all the other adjuncts that we can do as well.
- [27:45]
D
Great, that'll be interesting.
- [27:47]
B
Yeah.
- [27:47]
D
Well, hang on, I gotta, you know me, I gotta come up with like the, the resident take home what's like the nugget of basic science you can take out of here or you know, noteworthy facts. So I thought, you know, important to know there is an Increased incidence of uterine fibroids among women with ccca. So those that's fibroproliferative. So that all fits mechanistically like you said, we want to know. Metformin has been shown to be helpful in other fibrotic things like pulmonary fibrosis and then the, you know, the gene to know or the, the enzyme. So metformin activates AMP or ampk, which is adenosine monophosphate activated protein kinase. And we know that that's actually under expressed in about a third of patients with ccca. So mechanistically it makes sense. The science makes sense. I know we're going to get to hear a ton more about it, but I thought that was really good stuff. And now we can hear about it with oral metformin.
- [28:52]
B
Yeah, yeah.
- [28:53]
A
So let's just. So the oral metformin paper, this. I'm a big metformin fan. I got interested in it back whenever the first information was coming out about it might make people live longer. Right. Metformin's got reasonable data for acne.
- [29:09]
B
Longevity medicine.
- [29:10]
A
What's that?
- [29:11]
B
It's a longevity medicine.
- [29:12]
A
Right? Longevity medicine. It's got good data for hs, good data for acne. Okay. Data for acne. So when your article came out, I was like, ooh, okay, so now we should be putting everybody on. So my, my biggest question. So this was a 12 patient series. It was like eight of them. It did significantly better on the oral metformin. When do you. So at this point is essentially everybody that you see with CCCA on metformin of some form and if so or whether or not how do you pick between topical and oral? Do you think one works better than the other? Like what's, how do you differentiate?
- [29:51]
B
Great question. Probably everybody could be on topical metformin because you're going to. And I compound it with Clobatas all. Okay, that's at this point what I do. In the case series it was just metformin, but I compound with Clobatas all and I'm just like, look, you have both. If I think of metformin primarily as an anti fibrotic, though it does have anti inflammatory activity and a compound with clobazol. So sure.
- [30:13]
A
Wait, wait, do you have a bespoke compounding pharmacy that does this or is there somewhere that our listeners can be like, because I, I send my 10 topical metformin to Medrock, which is like 35, 40 bucks. Is there somewhere that does metformin or do you just do that and then have Them pour some clobazole in or what do you do?
- [30:33]
B
Yeah, good question. No, I send it to custom scripts in Florida. So they, you can call them, they pick up the phone every time you can send it to them. They're making it for hundreds of patients, I can guarantee that. So I send them a lot of my hair compounds.
- [30:47]
A
What's it cost?
- [30:49]
B
About $35.
- [30:50]
A
Oh, so the clobazole metformin combo is still only about 35 bucks?
- [30:55]
B
Yes.
- [30:55]
A
Are they. I'm sure you're not using Emma since you're at a, an academic practice, probably an EPIC or something, so. Yeah, I guess the other thing is I don't know if they're an Emma or not.
- [31:05]
B
Well, it's a. That's a great question because I kind of just type it out and send it to them and they just get it electronically. Okay, so that's a great question, but I know a lot of people who use their pharmacy and they're very straightforward. So that's where I send my compounds too. Now, how do I decide who. So when we did that case series, did 12 patients, four of them. We did pre and post biopsies for bulk RNA sequencing. And with the pre and post biopsies, the minimum time between sampling was six weeks. But to assess clinical regrowth, we waited six months. Okay. Because like, clinical regrowth takes time, but from a molecular standpoint, you can start to see those changes quickly. And when we had defined CCCA in a microarray study back in 2017, we were like, these are all the pathways that are up and these are all the ones that are down. And in these patients, it's all the same gene ontology program. So you're just like, oh, well, let's see the pathways that are up and the pathways that are down. And it was literally all of them flipped. It was, it was crazy. Low dose metformin, 500 milligrams, once a day, literally it just flipped everything. The fibrotic processes went down, hair cycling went up. We saw pathways implicated in wound associated hair regrowth. Right. So metformin was really doing what it was supposed to do. Now at that time, I was putting patients on it and I'm doing the study because I don't know if it works. Yeah, right. That came out of giving talks about topical metformin. And at the end of every talk people would say, well, what about oral? And I'd say, I don't know, I've never tried it. I'm a dermatologist, I like creams and then finally I was like, you know what, I'll put people on oral. I don't know if it's going to work. And it did. Now we'll be publishing a paper soon. It seems to work better in patients with insulin resistance than in patients without insulin resistance. Right, okay. And that sounds intuitive, but it's a little bit of a bummer too, Right? Like, I would love it because it's so safe. Right. It is a longevity medication decreases your risk of dementia, getting cancer, all these great things. But for ccca, it probably is not going to work that well in patients who don't have insulin resistance. I do want to share. If there are residents listening, this should be on the boards. By the way, what I'm about to say, whoever's in from the abd, I hope you're listening to. So I think in medicine, when we talk about insulin resistance, because this is going to be relevant for psoriasis, hydratonitis, acanthosis, nigricans, ccca, a plethora of other diseases, dermatologists, we, in the entire house of medicine, we are uniquely positioned to identify patients with hyperinsulinemia. No other specialty is going to see it. And what ends up happening is that when people think about insulin resistance, they think, oh, high glucose levels. I'm going to check your A1C and I'm going to see if it's abnormal. If it is, then I'm going to do whatever. But the problem is, when you have young patients under 40, they are very, very efficient at producing insulin, like their pancreas, just like every other. Every organ is more efficient. They're pumping out a ton of insulin. So if you have two patients who have a glucose of 100 every day over three months, those A1Cs are going to be identical. But if one person needs an insulin of 10 to maintain that glucose and the other person needs an insulin of 50, we would all be like, oh, well, that person's more resistant to insulin. But all we do right now is check a 1C. So that's why when we see these 20 year olds with acanthosis nigricans and we're like, well, this is associated with prediabetes. And they're like, stop right there. My A1C is 5.3. I don't have prediabetes. And we're like, gosh, why do we always say that their A1Cs are normal? It's because they're 20 and if you check their insulin levels, they are through the roof. And it's insulin that's driving that epidermal thickening and dispigmentation. It's not glucose. And so we check a Homa IR. So we check an A1C and we check a Homa IR. A Homa IR is just a calculation that puts in a ratio between of your, of your instantly, your fasting insulin to your fasting glucose. These are $10 tests, right? They're cheaper than a CBC. You get both values, you plug it into Google and it gives you a Homa IR score. If it's greater than 2, that's abnormal. So I send these patients, I've seen HS patients, they have a fasting insulin of 100. And even when I try to put in the calculation, I get an error sign. I'm sending them to endocrine and they're like, what is going on in derm? How are you finding all of these people with elevated insulin? Because they don't make it to endocrine until they're 40. Their pancreas tires out, and their A1C is now 12.
- [35:59]
A
So wait, so you just literally, you order insulin level and glucose level, plug it in, tell the patient you gotta be fasting, go first thing in the morning, and then you get those two back and just Google, what's it called? A homa.
- [36:14]
B
A homa ir.
- [36:16]
A
What's HOMA stand for?
- [36:18]
B
Homeostatic of metabolic. I can't remember the A. Insulin resistance. So, so this is the thing. So I, I tell this to my patients, right? I'm pre diabetic. I'm a very slim pre diabetic. I've checked my own home ir, I make almost no insulin. And I'll have patients who have an A1C that's identical to mine or lower, and they have skin tags and acanthosis, nigricans and boils. And we're getting the same, like, counseling and it makes no sense, right? And they're like, well, your A1C is only 5.7, but those patients, their A1C is like 5.7, then it's 5.8, then it's 6.1, then it's 10. And, and it's because eventually when their insulin tires out and all of that goes away, they are the, they, they spiral into very uncontrolled type 2 diabetes very quickly. And it's all an evolutionary advantage, right? If your body high levels of insulin and you hold on to a ton of fat in a period of famine, like, I'm dead. Right, Right. But, but you, if you have evolved to hold on to fat so that's why the like people have trouble losing weight. So that's why GLP1s are, are like magic. Right. But derm is the only specialty that's going to see hyperinsulinemia manifest.
- [37:41]
A
All right, so, so let me see here. So you, what I hear you saying is kind of at this point, you do a HOMA IR if they are insulin resistant, you then do oral metformin. And I assume that means that if their homa IR is normal, you do topical metformin or do you do not metformin at all?
- [38:05]
B
Yes, I'll do topical metformin with clobatazole.
- [38:07]
A
Okay.
- [38:09]
B
And yeah, and that's it. And sometimes I'll do like clobatazole alone, but usually I'll put them together. Okay.
- [38:14]
A
And I did, by the way, while we were I looked it up in custom scripts is in Emma.
- [38:21]
C
Great.
- [38:22]
A
So for all of our listeners, it's easy to send scripts there. You might want to call them and set it up before you just to make sure some of this, you know, custom scripts pharmacy in somewhere in Florida. Well, Springs, Florida, I think. So they are doing it. So you have people just use clobatazole, metformin QHS pretty much indefinitely.
- [38:46]
B
Well, until their scores hit zero. Right. So because I, I, I think committing someone to indefinite treatment, especially because I do think CCCA burns out, but yes, for the foreseeable future, for sure.
- [39:00]
A
And so you have them, they got to get to zero for like a year before then you'll start taper, weaning things off.
- [39:09]
B
Yes.
- [39:10]
A
And all right, let's.
- [39:12]
C
So hold on real quick. I, I AI'd this Home IR Homeostatic Model Assessment of insulin resistance and the, the ranges they give. I'm just curious if this is kind of your understanding of the homa ir. Less than 1, you're good. Greater than 3, that's your high risk. And then you kind of have between one and three where it's like early insulin resistance, significant insulin resistance. Is it like anything above one, you start having that conversation.
- [39:41]
B
Or two, they can get a GLP one. Right. So anything about they can get a GLP one. But, but in practice, above three is really where you're going to start to see issues. So like, if someone's like a 2.5, I'm like, if you wanted to stick with your topical metformin, that's fine. Right. Because it's the equivalent of probably having an A1C of like 5.75. Right. It's not like, you know, have to rush to do something. But, but I would encourage you to try it for all your acanthosis nigger cans patients because they're almost always going to have normal A1Cs because they're young and it's their insulin. And that's also, you know, I, I ask, when I give lectures, I say, do we ever wonder why we call it a disease of prediabetes and not a disease of diabetes? It's because their insulin levels are high. Because by the time you have diabetes, your insulin levels are coming down. Or even if you have type two, they're just not enough to control your glucose. So that's why we see it in young people with prediabetes. It just means that your insulin, you're pumping out insulin efficiently enough to change your skin.
- [40:50]
D
So then would you anticipate, because I think we don't have enough sort of long term, you know, use of GLP1s. But would you anticipate that they will be associated with a lower incidence of ccca?
- [41:05]
B
Great question. I think I, you know, I haven't gotten that question before and I would love to believe yes, because now I'll get to my theory. I think I published this in Jad actually, the, you know, Dr. Elson was very kind to let me just publish my thoughts. And I actually think that CCCA is fibrotic pattern hair loss. Okay. And one of the things about CCCA is we've tried to figure out why is it much more common in black women. Right. And that's why hair practice, hair practices were like the initial place to look. Right. I think very reasonable. You're like, okay, well, this is the first thing. But, you know, Elise Olson, years and years ago was just like, I think a lot of scarring, alopecia might be fibrotic pattern. But like, you know, who knows? We published a study just a couple of years ago looking at ethnic variation in female pattern hair loss. And we were really trying to identify South Asian patients because these patients are definitely disproportionately impacted with pattern hair loss. Right. And we, we saw that it was appearing 20 years sooner in South Asian patients. But the other thing that we found that was really interesting is that so black women and white women present with pattern hair loss similarly. Bi temporal recession is the most common area. Some people get part widening. But black women uniquely will get pattern hair loss in the vertex in isolation. Right. In absence of other areas of involvement. So a primary vertex predominant pattern hair loss. Of the patients who had that, 95% of them were black women. We had one white woman who had that. And so now pattern hair loss in the vertex responds more favorably to any treatment oral minoxidil propecia in men. So it's, it's a good area to have pattern hair loss, but that discrepancy alone can account for so much of the discrepancy we see in CCCA in black women compared to in other races. And so then it's like, well then what would make someone develop scarring pattern hair loss or CCCA versus just regular pattern? And it could just be like metabolic disturbances. Right, because metabolic disturbances, hyperinsulinemia and hyperglycemia will increase fibrosis in organ tissues. Right. That's why, that's why diabetes is terrible. Look what it does to your nerves, look what it does to your kidneys, right? It just, this is how it damages that. Yeah.
- [43:32]
A
I thought a few years ago there was like some gene that they discovered that like everybody with CCCA had this mutation.
- [43:42]
B
Yeah, yeah, you're talking about the PADI3 mutation. They found it in about a quarter to a third of patients. And it was a heterozygous mutation that didn't stop protein and that would be okay. But we already know of diseases where you get a complete knockout of the PADI 3 and that's uncomfortable hair syndrome. Right. Which is a pediatric genoderm that improves naturally with age. And so one of the things about PADI 3, I think multiple things are true. One, we don't understand how like a partial mutation would only lead to scarring alopecia in older black women when a full mutation leads to non scarring reversible hair loss in predominantly non black kids. So it might be a true, true, unrelated. We also, with Dr. Roya actually we did a scanning electron micrograph study where we took the hairs of patients and we were like, well maybe some of these patients do have, you know, plead trianguli at canaliculi, right? Which is like the finding that you see in this process, uncomfortable hair syndrome. And out of 21, did you know one patient? So it's like, I think it exists, right? But like maybe there are a whole host of risk factors, but probably PADI 3 is not enough enough to explain 100%. But, but maybe there are various risks that someone could be born with that would make it such that when they start to develop age related hair thinning, which starts when women are in their late 20s, just like CCCA, right. That just sends them down a fibrotic pathway. And so maybe you know, GLP wants and all these things, right? Could help decrease the incidence of that. So that's my current theory.
- [45:25]
D
You have a paper when I was trying to read up on this, I think that said that, you know, the theory was perhaps ccc and maybe it was data. CCCA is more associated with poverty than race and ethnicity. Was that your paper or was that somebody else who published that?
- [45:43]
B
That is such an interesting paper. That is an inversion of my paper I actually published that FFA is associated with affluence and not race. So I'm in, I'm in the DMV area where we have a lot of well to do black patients. So I'm happened to be in the one place, I think the best place in America to ask this question. And all of my patients with FFA for years have been educated, professional women. And I see hair loss in people from all walks of life. I accept Medicaid and my FFA patients are always, no matter what their race is. And so we finally did looked at the data. We pulled census data and we looked and we, you know, we did logistic regressions. We controlled for so many variables and the best predictor, besides just being a woman, the best predictor of getting FFA was, was being in the highest income. There's like four different brackets in the census data. And race completely fell out. There's nothing to do with race, all to do with affluence, which we don't see in medicine.
- [46:53]
A
Well, I'm going to jump in and give you some now. Now my unfounded theory on ffa. So here is what I believe, and this goes completely with the affluence concept. What is unique about your frontal scalp, like right here? What is most unique about it environmentally? Because we know FFA has got to be an environmental disease because it didn't exist in a meaningful way when we, when the three of us were residents. This gets, this gets more exposure to chemicals than any other spot on your body. So everything you put on your face gets here. Everything you put on your hair gets here. The rest of your face, the rest of your scalp only get half the exposure as your frontal scalp. I think we, we're barking up the wrong tree because we're looking for like one chemical. I think it is the cumulative. All of the chemicals you put on your face, all the chemicals you put in your scalp, they add up to like a toxic. We're gonna kill those guys right there.
- [47:51]
B
It's possible and certainly like with the affluence like you have, you can afford more stuff. It was first described in Australia and I think we have to pay attention to that. The sunscreen stuff does not exist in Korea. Okay. And in, you know, derm. The derm research in Korea is huge. Right. And so is the alopecia research community. And there was. There are a few papers where they published like the burden of alopecia. FFA is almost non existent there.
- [48:19]
D
And they've got lots of skin care products.
- [48:21]
B
Right.
- [48:22]
D
So it's not just.
- [48:23]
B
Yeah, yeah, well, that's the thing. Right? And so. And then when I was training too, when I see ffa, they bring in residents. Hey, come and take a look. We got some frontal fibrosis alopecia for the listeners. I finished residency in 2015. Okay. And during my training, we were still pulling in people. FFA is everywhere.
- [48:46]
A
Everybody.
- [48:46]
B
I mean, everywhere. Right. It is already become. We used to, when I was training and when I first started, we used to call. We would say frontal fibrosis alopecia is a subtype of lichen Plano Pilaris. No, you see 10x FFA over LP, right. It's totally environmental. I have my own theories.
- [49:07]
A
I do think I'm cutting it off right there because we are going to have you back on to talk about ffa. That's going to be a whole new episode. Because this is.
- [49:16]
D
Yeah, we totally should. That would be great.
- [49:18]
C
Oh, we.
- [49:18]
D
There's no way to differentiate FFA and lpp. We got. Yeah, we only really scratch ffa.
- [49:24]
A
We're going to do all kinds of stuff. You are the. I. I don't want to say anything that's getting in trouble with other people. This was so much fun. This is so much fun.
- [49:34]
B
Good, good. I hope it's helpful. I'm just trying to give at least one clinical nugget, you know?
- [49:38]
A
Oh, you gave. You gave lots of them. That was fantastic. All right, let's. Let's jump over to, I guess, last quote, last thing here.
- [49:45]
B
So do we.
- [49:46]
A
Do you talk to black women about hair care practices at all with ccca, or do you like. Is that just unnecessary burden to be like.
- [49:57]
B
I think it's a great. I mean, that's a phenomenal question. Right? Because when I was training, that was.
- [50:03]
A
The counseling hot comb alopecia.
- [50:06]
B
Right. And now if I mention it, it's in a different way. Right. You're already dealing with one form of hair loss. Let's not add a second. Let's not add traction alopecia, and let's not add really bad breakage. Because I will tell you, with these patients, as you say, you start treating them for two or three years, the CCCA will start to get better. And then the reason they're in a wig is because they have no hairline and they've pulled it all out. You can camouflage hair loss in the middle. You can camouflage a decent amount of hair loss in the middle. You can't camouflage frontal. Frontal alopecia. And so that's why I talk to them about hair care practice.
- [50:45]
A
I can't wait to have you come back on to talk about traction alopecia and frontal fibrosing.
- [50:48]
B
Al got a lot to say. I told you.
- [50:51]
A
All right, let's. So let's. Let's move on to. To what is generally everyone's favorite section of the podcast. Dr. Patton, you got any good trivia for us?
- [51:00]
C
Well, I think it's great trivia. It's black hair and entertainment. Oh, we try and do. Yeah. What was I. Yeah. Pop culture. Because a lot of times the scientific stuff we talk about, we don't know what we're talking about. But pop culture, we're strong with. All right, ready? This 2002 movie, we're also old. So I feel bad for all these young people that come on because they're like, I wasn't born yet. This. This 2002 movie starred Ice Cube as Calvin Palmer, who inherits his father's business and looks to sell it to make quick cash.
- [51:45]
B
Is it Friday? Next Friday?
- [51:48]
C
No, it has to do with hair. I. I kept the theme.
- [51:53]
B
Oh, oh, oh, he's a barber. Oh, my God. I can't.
- [52:01]
C
Barber shop.
- [52:03]
D
Barber shop.
- [52:04]
B
Barber shop. Oh, that was a good one. Oh, me.
- [52:08]
D
I don't watch enough movies, so I'm Was not gonna get.
- [52:10]
B
I do.
- [52:12]
C
Yeah. Apparently there were SEO. I never saw it. I've seen clips of it because there's some pretty funny, like, rants that I saw in some of the scenes. So, yeah, pretty funny clips. Never seen the whole thing. And it actually did well enough that there were one or two sequels, I think.
- [52:28]
B
I didn't watch the sequels, though, so.
- [52:30]
C
All right, what is the Name of the 2009 documentary produced by Chris Rock detailing many of the hair care practices of the black women?
- [52:39]
D
Good hair.
- [52:41]
C
Good hair. That tie. Nice job. Never saw that either. Is that worth watching? Have you seen it?
- [52:49]
B
It was really good. I think it was good because I think it was really a conversation starter. But since 2009, hairstyling practices have changed so dramatically that it's already. It would be obsolete. Like, it would not. Oh, wow. Yeah.
- [53:02]
C
Okay.
- [53:03]
B
Yeah.
- [53:04]
C
All right. One of the members.
- [53:06]
A
Because you and I have been doing our hair the same since 2000, 1989. I. I used to be in my hair every day.
- [53:15]
C
I moved my part over, like a little bit.
- [53:19]
D
The comb over, we call that. That's not moving apart. That's a comb over.
- [53:23]
C
Well, okay. Tomato, tomato. But I'm gonna. Okay. All right, number three, final question. One of the members of this famous female rap duo developed her iconic half shaved hairstyle as the result of a burn that occurred from a hair styling mishap.
- [53:40]
A
Salt and pepper?
- [53:42]
C
Yeah, salt and pepper. Nice job. Yeah. Apparently your sister just got her cosmetologist license and applied like a perm or like a relaxer and did it incorrectly. Burned off the side of her hair. And so she just kind of shaved it and then went with this look that a lot of people wound up imitating.
- [54:03]
B
Yeah. Wow.
- [54:05]
C
Pretty funny.
- [54:05]
D
That's cool.
- [54:06]
B
Good questions.
- [54:07]
A
Push it. One of the greatest songs ever made.
- [54:10]
B
Oh, yeah. It really is relevant.
- [54:12]
D
That could be our new theme song. We'll think about that.
- [54:17]
A
All right. Dr. Goo, thank you so much for coming on today. This was a fantastic, fantastic discussion. Really kind of appreciate your expertise and. And what you're doing out there in the world. And I want to thank all of our listeners for joining us this week. And we hope you learned a few things. We hope to laugh once or twice. And mostly we're hoping you're planning to join us next week. Until then, I'm Matt Zyrus.
- [54:39]
C
I'm Tim Patton.
- [54:40]
D
And I'm Laura Ferris. And we are Germs on Drugs.