The BILLION DOLLAR Itch Industry | Dr. Brian Kim

Summary

Dermatology Undressed: A Provocative Podcast by SkinTellAgent
Episode: The BILLION DOLLAR Itch Industry | Dr. Brian Kim
Host: Dr. Lindsay Ackerman
Guest: Dr. Brian Kim
Release Date: July 1, 2026

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Episode Overview

This episode explores the misunderstood yet profoundly impactful phenomenon of itch, delving beyond the surface sensation to unveil its intricate biology, evolutionary roots, and the transformative impact of recent scientific discoveries on patient care. Dr. Brian Kim, a powerhouse in itch research, joins Dr. Lindsay Ackerman to challenge preconceived notions about itch, reveal its connections to major systemic diseases, and discuss new targeted therapies that are revolutionizing dermatology.

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Key Discussion Points and Insights

1. Dr. Brian Kim’s Unlikely Journey to Itch Science

• Personal Path ([03:50]):

  • Dr. Kim candidly recounts how his journey into itch research began unintentionally during his postdoc while investigating atopic dermatitis (eczema).
  • He and his lab uncovered entirely new immune cell types in the skin, including innate lymphoid cells and basophils, which proved central to type 2 inflammation—a core driver of eczema.

  “These were collectively very important sources of what we refer to as type 2 inflammation... which is kind of a theoretical, abstract concept back then. Well, it turns out these pathways are critically important for causing atopic dermatitis.” — Dr. Brian Kim [04:43]

  • Dr. Kim describes how a focus on “vestigial” (seemingly obsolete) cells led to meaningful clinical breakthroughs as these cells turned out to be crucial in chronic skin disease.

2. Evolutionary Purpose and the Science of Itch

• The Hidden Value of Itch ([08:38]):

  • Itch is highly evolutionarily conserved – found across many species.
  • Its fundamental importance is reinforced by its persistence in the animal kingdom, even if underappreciated in modern life.

  “If a vestigial thing in modern day is causing misery in my patients, then I'm going to care about it.” — Dr. Brian Kim [06:53]

  • Dr. Kim explains itch not as a minor annoyance but as a subtle but critical environmental and internal warning system: Scratching expels parasites; widespread itch can signal internal illness.
  • Nursing Home Example ([09:47]):
    • When residents can’t scratch (due to debility), infestations like scabies spread unchecked.
  • Hunter-Gatherer Example ([10:36]):
    • Itch drives us to avoid subtly dangerous environments (like mosquito infested areas) without immediate flight like pain or fear would.
  • Itch signals both external dangers (parasites, irritants) and internal states (organ failure, systemic disease).

3. Debunking Myths: "Stop Scratching" Is Bad Advice

• Powerful Reflex ([13:06]):

  • The oft-repeated advice to “just stop scratching” is a myth that ignores the fundamental, reflexive nature of itch.

  “You can't. You really can't... Itch is an unbearable desire to scratch. Unbearable. But the other thing that people forget, it's a reflex, so you don't have to be awake to scratch.” — Dr. Brian Kim [13:11]

  • Even while asleep or unconscious, people scratch.

4. Itch as a Neuro-Immune Phenomenon

• Revolution in Understanding ([14:13]):

  • Itch is not merely skin-deep but a sophisticated conversation between the immune system, nerves, and the brain.
  • Dr. Kim's lab proved that type 2 inflammation (long-known in allergies, asthma, eczema) directly provokes neural itch signals—spanning dermatology, immunology, and neurology.
  • Scratching creates micro-barrier breaches, automatically triggering type 2 inflammatory cascades and itch-specific neural activity.

  “There is a particular kind of signal that goes from the immune system to the nervous system that triggers itching. And that really uncorked a whole field... led to therapeutic developments that were unthinkable back then.” — Dr. Brian Kim [17:11]

  • The skin serves as a diagnostic window into internal disease (kidney, liver, or bone marrow breakdowns can present solely as itch).

5. Itch as Symptom and Systemic Clue

• Pathological Itch Without Rash ([19:43]):

  • Internal diseases (e.g., chronic kidney failure, liver dysfunction) can present as generalized, relentless itch—even without a visible rash.
  • Dermatologists often become key detectives for these “inside out” itches.

  “Someone with that disease... may have no other symptom prior to itch. And when they have this diffuse itch that doesn't coincide with a rash, it leads us as dermatologists to start working that up.” — Dr. Lindsay Ackerman [19:51]

6. What Makes Chronic Itch Different?

• Acute vs. Chronic ([21:36]):

  • Ordinary, momentary itch (like a bug bite) is protective and transient; chronic itch is arbitrarily defined as itch lasting more than six weeks but can be devastating well before that.
  • Chronic itch may or may not align with visible disease and warrants a tailored, sometimes investigative, approach.

  “Chronic itch...it’s not really one symptom... Itch is such a common symptom across so many diseases.” — Dr. Brian Kim [23:03]

7. The Billion Dollar Itch Industry: Therapeutic Breakthroughs

• Industry Shift ([24:19]):

  • Itch—long trivialized—now commands major investment and innovation, with roughly half of dermatologic drug development addressing itch biology.
  • Patients report that itch is more intolerable than pain and even disrupts sleep (unlike most medical pain).

  “You can sleep through chronic pain... What itch tells you is, holy crap, there's a parasite in you. You need to twitch all night long until your body kicks this thing out. But imagine there's no parasite and your body thinks that forever.” — Dr. Brian Kim [25:37]

8. From Lab to Life-Changing Therapies

• Landmark Findings ([27:09]):

  • Dr. Kim’s seminal discoveries revealed inflammation signals (notably IL-4 and IL-13 cytokines) directly activate neural itch pathways. Blockade of these (with drugs developed in tandem with pharma) has led to rapid, dramatic relief for previously untreatable patients.
  • Pharmaceutical companies now view itch as a legitimate, prime treatment target—not a mere nuisance.
  • Because some cellular targets are vestigial, blocking them brings high efficacy with minimal side effects.

  “The beautiful thing about studying something that’s rather vestigial is that if you're able to also zap it, the good thing is you have very little in the way of safety or side effects.” — Dr. Brian Kim [30:31]

  • Vivid patient stories: Years, even decades, of disabling itch relieved in days or weeks—with frequent tears of gratitude from patients.

  “I've had patients cry in my office just saying, I cannot believe this finally happened.” — Dr. Brian Kim [31:31]
  "I have a patient... who literally every time she comes back in for follow up, tells my medical assistant, whomever it is in the room with me at the time, this doctor saved my life." — Dr. Lindsay Ackerman [31:55]

  • Medicine has advanced from simply prolonging life to also restoring quality and meaning to life.

  "I think the era we're living in is now we can treat patient, we can diagnose patients, we can treat them, we can prevent them from dying, but how do we make their life meaningful and worthwhile and high quality? And that's the era we're in." — Dr. Brian Kim [32:58]

9. Redefining Success: Patient-Reported Outcomes

• Patient-Centered Revolution ([33:21]):

  • The traditional physician-centric view is shifting: Modern clinical trials now prioritize patient-reported outcome measures (PROMs) to capture real impact on symptoms and quality of life—not just visual assessment of skin.

  "We're incorporating all of these metrics... that focus so highly on the symptomatology because really, in the end, we care a lot less about what they look like. It's a lot more about what they feel like." — Dr. Lindsay Ackerman [33:43]

10. Hope for Patients: The Future Is Brighter

• Validation and Accelerating Progress ([34:51]):

  • Patients with mysterious, relentless itch are now recognized to have a legitimate, treatable medical condition—not simply psychological distress.
  • The pace of therapeutic discovery is accelerating, with basic science directly informing novel, effective treatments—fueled by patient feedback.

  "I'm not interested in forming expert opinions. I'm not interested in publishing... All that really matters is, can you develop a therapy that’s new, that separates from placebo?... A lot of the ideas we got came from our patients." — Dr. Brian Kim [35:12]

  • Memorable story: A patient’s itch vanished within 30 minutes of a novel medication, and subtle feedback led to critical mechanistic insights.

  "He said, it's this buzzing feel like electricity. Well, guess what? Your nerves are electrical cables. They work on ion channel gradients... He was describing exactly what the drug was supposed to do." — Dr. Brian Kim [37:09]

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Memorable Quotes & Moments (with Timestamps)

• “If a vestigial thing in modern day is causing misery in my patients, then I’m going to care about it.” — Dr. Brian Kim [06:53]
• “Stop scratching.” / “You can’t. You really can’t... Itch is an unbearable desire to scratch. Unbearable. But... it's a reflex, so you don't have to be awake to scratch.” — Dr. Brian Kim [13:06–13:11]
• “There is a particular kind of signal that goes from the immune system to the nervous system that triggers itching… led to therapeutic developments that were unthinkable back then.” — Dr. Brian Kim [17:11]
• “You can sleep through chronic pain... What itch tells you is, holy crap, there’s a parasite in you. You need to twitch all night long until your body kicks this thing out. But imagine there’s no parasite and your body thinks that forever.” — Dr. Brian Kim [25:37]
• "I've had patients cry in my office just saying, I cannot believe this finally happened." — Dr. Brian Kim [31:31]
• “Medicine... now is, how do we make their life meaningful and worthwhile and high quality? And that's the era we’re in.” — Dr. Brian Kim [32:58]
• “All that really matters is, can you develop a therapy that’s new, that separates from placebo?... A lot of the ideas we got came from our patients.” — Dr. Brian Kim [35:12]
• “He said, it’s this buzzing feel like electricity... He was describing exactly what the drug was supposed to do.” — Dr. Brian Kim [37:09]

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Important Timestamps

• [03:50] — Dr. Kim explains how his career shifted toward itch through eczema research.
• [08:38–12:52] — Evolutionary basis and value of itch; why it’s conserved across species.
• [13:06] — The myth of “just stop scratching” and its impossibility.
• [14:13–17:11] — Itch as a neuro-immune dialogue; from barrier breach to brain signal.
• [19:43–20:52] — Itch as a sign of hidden internal diseases (kidney/liver/bone marrow).
• [21:36–24:11] — Defining chronic itch; clinical and research perspectives.
• [24:19–27:09] — The explosive growth of itch-focused pharma and the “billion dollar industry.”
• [30:31–31:31] — The dramatic, tears-of-joy transformations patients experience with new therapies.
• [33:21–34:16] — The shift toward patient-reported outcomes and a new metric for success.
• [34:51–37:09] — Moving from skepticism to hope; science led by listening to patients’ real experiences.

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Conclusion

This episode presents a deeply human and scientifically rigorous dive into the world of itch, cementing it not as a trivial nuisance but as both evolutionary legacy and window on systemic health. Dr. Brian Kim’s research illuminates not only the mechanisms but the immense suffering—and healing—possible in chronic itch. The podcast concludes on a note of optimism for patients: not only are their struggles legitimate, but rapid therapeutic progress means the days of unrelenting misery from itch may soon be over.

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For listeners:
If you or someone you know suffers from chronic itch, this episode affirms both your reality and your hope—highlighting that science is listening, evolving, and delivering relief in ways almost unimaginable just a decade ago.

Transcript

[A]

Thank you to Sanofi and Regeneron for generously supporting this episode of Dermatology Undressed, a provocative podcast. Sanofi and Regeneron had no influence on the selection of the faculty nor content development. Sanofi and Regeneron share a scientific commitment to research in type 2 inflammatory skin diseases. This podcast is for educational purposes only and is not medical advice for personal medical care. Please consult a qualified healthcare professional. Welcome to Dermatology Undressed, a provocative podcast. I'm Dr. Lindsay Ackerman and and today we're diving into a topic that might sound simple, but it turns out to be anything but itch. If you have ever had a mosquito bite, you've had a taste of it. But for some people, itch isn't just a moment. It's a medical mystery, a daily torment, and now even a billion dollar focus for the pharmaceutical industry. Here to help us peel back the layers is Dr. Brian Kim. Dr. Kim is one of the world's leading physician scientists in the field of itch biology, a dermatologist whose groundbreaking research has fundamentally changed how medicine understands the relationship between the skin, the immune system and our nervous system. His accolades are abundant as he serves as the Saul and Claraquest professor of Dermatology and Vice Chair of Research in the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City. There he also directs the Mark Levwald center for Neuroinflammation and Sensation. Through pioneering work in neuroimmunology, Dr. Kim has emerged as one of the most influential voices uncovering the science behind chronic itch, a symptom long dismissed as trivial, but one that can devastate quality of life for millions of patients around the world. His laboratory has been instrumental in identifying that itch is not simply skin deep, but rather a highly complex communication network between immune cells, sensory nerves and the brain itself. And moreover, his lab has uncovered pathways that now serve as targets for some of the most transformative therapies in dermatology. But what makes Dr. Kim's work maybe the most compelling is that it bridges worlds from molecular science and translational medicine to the deeply human experience of suffering. His research has not only reshaped scientific understanding, but has directly influenced the development of therapies aimed at relieving relentless, life altering itch. Widely published in premier scientific journals and internationally recognized for his contributions to dermatology and Immunology, Dr. Kim represents a new generation of physician scientists helping redefine how we think about symptoms that medicine once overlooked. Today, he joins us to unpack one of the most universal and most misunderstood symptoms in medicine, Itch. Brian, thank you so much for being with me. For those of us itching to have this conversation, I feel like we have arrived.

[B]

Thanks for having me, and thanks for the incredibly flattering intro.

[A]

Yeah, well, it's an honor to have you. I hope you know what sort of a difference you are making. I mean, it's kind of hard potentially, when you're on the inside actually doing the work. But your lab has done so, so much to unveil what itch really is all about, especially in pathologies that deeply, deeply affect people's lives, like chronic itch in skin disease. So just let's talk about something that we've all experienced, the urge to scratch. What drew you to make this really your life's work?

[B]

Yeah, well, it wasn't as intentional as it might seem. You know, my career has been fairly linear. It's been kind of solving one thing after another and in a linear line. But really, it started with I kind of ran into an existential crisis. Well, my big question during my postdoctoral fellowship as a dermatologist was, this is back in the day, it's hard to imagine, but can we solve atopic dermatitis? And back then, the majority of people said, probably not. Seems like a bit pie in the sky. And as an immunologist, I just wanted to figure out what causes inflammation and the rash in atopic dermatitis or eczema, as simple as that. And at that time, we were able to make what I thought at that time were pretty seminal discoveries, which is we identified entirely new cells that we didn't even know that were in the skin called innate lymphoid cells. We described other cells that come from the blood, rare cells that were considered vestigial cells when I was in medical school called basophils. These were collectively very important sources of what we refer to as type 2 inflammation, or. Which is kind of a theoretical, abstract concept back then. Well, it turns out these pathways are critically important for causing atopic dermatitis. And then at that point, in many ways, I had kind of solved what I had sought out to do in a matter of about four years. Not everything, but kind of what I thought was kind of the Valhalla of atopic dermatitis. Everything else at that point felt a little bit incremental. If I did anything else. And then. And then I said, why don't we figure out what causes itching?

[A]

Yeah, I mean, I just want to, like, pause and say, for the audience at large so that they recognize how instrumental that work was. You were quite literally identifying cells that were residing in the skin as a source of disease that we historically used to think of as really being, like, you say, vestigial cells, cells that were sort of once present and relevant in the human condition and no longer so. Is that right?

[B]

Yeah, absolutely. These cells were interesting, particularly in lymphoid cells, because they were cells that we literally did not know existed until around 2010 at all, period. And then it was 2013 when we published on them in the skin. And the criticism at that time was that they look a lot like T cells. And many people understand T cells are important in hiv. You lose your T cells and you get infection. So some of the critics were saying, well, it seems like, Brian, you like to study vestigial things. These are things that actually probably are not that important. But, you know, it always grounds me that I'm a physician, especially being in academia, because we get caught up in weird stuff all the time. Like, you know, we get caught up in, oh, what awards did you get, what paper, which journal did you publish in? Well, you know what, every Monday morning when I see patients, that's not what they care about.

[A]

They.

[B]

What they care about is how can you help me feel better? And that really grounds me. Right. And so what I said back then is that I don't know if. I don't know what the kind of hierarchy of great science is, but I said, you know, if a vestigial thing in modern day is causing misery in my patients, then I'm going to care about it.

[A]

Right, right. I love. I mean, this is why we get along. I mean, ultimately, when we show up every day, it's that person that, you know, you walk in the room, you don't know what's behind door number two, but you know that you're armed with probably a skill set that they're looking for to help them, to help them feel better, to look better, to, you know, face the world with greater confidence and greater quality of life.

[B]

Yeah, I hope so.

[A]

Yeah. So I'm gonna. I'm gonna go back to this whole vestigial thing. Cause I really like this. This portion of the topic. Basically explaining to the audience that, you know, sometimes. And actually I'll. I'll digress for just a quick moment and say, when I started medical school, the dean of students came in the very first day of medical school. And so this is now, gosh, 20 plus years ago, 25 years ago. No more than that. Anyway, nevermind. And he walks in and says, now it is incredibly, incredibly important that you will need to know everything you're going to learn over the next four years. And yet 50% of everything you learn will be obsolete by the time you graduate. The problem is you don't know which 50%. And so here we are, right, having thought of something as a no longer relevant portion of our immune function or constitutional human condition. And now it was 2010, as you say, that you identified these cells are really not just present, but really relevant to the chronic burden of disease. And so do you think that there's an evolutionary advantage to itch? Is there some reason why this exists?

[B]

Definitely. Our lab's in the business of looking at things that were overlooked but that are highly evolutionarily conserved, meaning that in every species, we've preserved it. Right. And so the premise is that if that's the case, it must be important, even if we don't think it is. And can we figure out a way that it's important? So, yeah, we do think so. I mean, itches, sensation's really, really important. And one of the things that I often say when I give a talk is we give a lot of credit to the five sensations, so much so that we refer to sixth sense as this kind of abstract concept. But we really have probably thousands of sensations in the body, and itch is certainly a sensation that we haven't really thought about. And.

[A]

Oh, yeah, sorry to interrupt you, Brighton. So the five senses, just historically, again to refer for our audience, would be five senses.

[B]

Sight, hearing, smell, taste and touch. And you could say itch falls into touch, but it really doesn't. It's its own. It's not even pain. So, you know, we just went after itch specifically. And of course it's important because if you think about what as a dermatologist, there are a couple anecdotes in which you can immediately figure out that this is very important. Let me give you one example. We know that if you're in a nursing home, if you put scabies mite in a nursing home, it will rip through a nursing home. It will be epidemic immediately. Why is that? Is that the mechanical mobility of patients in nursing homes is incredibly limited. In fact, they can't even scratch very well. Well, scratching and twitching, these are really good things. Even coughing here and there, these are things that, when you're sleeping, keep those insects and parasites away. So the idea that you scratch once every hour even, is a great thing. If you were as still as a corpse throughout the body, you would get infested immediately, you would get bites. And if you get bites, you're more likely to get various different viruses. So it. It is important. It's just not important. The way we think of, say, vision. Right. Which is very obvious, or even pain, you know, if you touch a hot stove, you're going to have a burn itch is not that critical for immediate survival, but it is very critical in very subtle ways. And I'll give you another example if you are. If you think about when we're hunter gatherers, or if you want to think about it that way. If you're going on an expedition and you're trying to hunt something and there's something bad in the environment, there are mosquitoes that carry diseases. You don't want it to be like an aversive bee sting. Like, if everything's a bee sting, immediately that tribe would have just ran away and never came back. But you actually need a very subtle cue that tells you, hey, this is uncomfortable. We don't really want to hang out here for too long, but we still want to do what we need to do and get out. So we need to hunt. We need to get the animal and get out. So it's a very subtle way of telling your body what's going on in the environment, but it's also a very subtle way to tell your body something might be wrong as well.

[A]

Yeah. And this is why mosquitoes can carry disease. And so getting out of that environment. Right. Can be helpful. You don't want.

[B]

You don't want it to be where you encounter a mosquito and you run away.

[A]

No.

[B]

Right. You want it to be that you say, look, it's uncomfortable. I don't want to hang out, but I have some things I need to get done. It's a very subtle external cue, but it's also a very subtle internal cue. Right. So now let's get back to this hunting tribe. I have kidney failure and my kidneys are bad. How would anyone back then would have known that? There is no way. But now I'm itchy, I'm scratching. And there's actually a primal instinct, not just in humans, but even in animals, that they want to actually stay away from scratchy people. And that's a good thing because then they say, you know what? We probably shouldn't take Brian on this hunting expedition instinctively. And that, that way I don't become a liability. Right. So. So there's lots of ways in which itching is actually very important, I think, for survival, But I don't think People have thought about it this deeply.

[A]

Yeah, no, I love it. I love it. These are great examples. So if you. I love this. If you had to bust one myth about itch wide open, and maybe you've already spoken to it, what would it be?

[B]

Stop scratching.

[A]

Okay, That's a myth. Why is that?

[B]

You can't. You really can't. And I even say it to my daughter. My daughter has eczema. And I say, stop scratching. And I'll say, stupid thing to say. You know, itch is an unbearable desire to scratch. Unbearable. But the other thing that people forget, it's a reflex, so you don't have to be awake to scratch. So if you can scratch in an unconscious state, you know, you can't tell an unconscious person not to scratch.

[A]

No, you're. You're absolutely right. It. It does feel reflexive and. And probably in more limited forms has a component of it that is reflexive and yet volitional to hold back on. If it's a solitary or two bug bites on your ankle, maybe you can start the scratch and then choose to stop. But you're absolutely right, it does initiate itself as a reflective mechanism. So then tell me what is. You've done so much research in this. What is actually going on underneath the skin, like this redefinition of itch as this neuroimmune mechanism?

[B]

Yeah.

[A]

Talk to me about that.

[B]

Yeah, there's. Yeah. Even before I get to that, you know, I think it's actually a hard thing to fully understand when people say, what exactly is it? You know, I can give definitions and say it's a reflex, but the more ways in which you think about itch, it's actually helps you to start to get the big picture. And one thing I'll also say is a lot of people forget that you can only really itch in certain places. Places. It's really in the kind of superficial surface of your skin or other areas like the eyes. It's really areas that directly face the outside world, and it's in the superficial area. So in other words, you don't itch in your joints, you don't itch in your muscle, and you don't really itch in kind of your organs like liver. So it's really something where it only. It's. It's quite elegant because your body's designed for you to experience this sensation only in areas where you can actually scratch. I could imagine if I itched in my liver, that would be absolutely miserable, though I don't think anyone has ever. So that's where you start. So then the question is, what actually causes itching? And we could go on and on for days about what are all the different causes. But my background in immunology was really, we started to understand actually that for these body surfaces or barriers that actually face the outside world, and this extends beyond the skin and even the eyes, it actually extends to even hollow organs like the airway, is that whenever there's a barrier breach, there is a particular kind of inflammation that these barriers default to. So in other words, when I scratch my skin, if I simply scratch my skin, it'll default to what I described earlier in the Pocket podcast, which is type 2 inflammation.

[A]

So by scratching, by the physical manipulation itself, you are breaching that barrier. Presumably, you know, maybe part of the surface cells are getting underneath your nails. You break down that barrier, and then it stimulates inflammation.

[B]

But not just generic inflammation. It stimulates a particular kind of inflammation that we refer to as type 2 inflammation. And that's hardwired into our body. And one of the things that we always recognize early on, having that background in immunology, was that whenever there's type 2 inflammation, there's kind of twitchy behavior. There's either itch in the skin or there's coughing in the airway, or there's diarrhea in the intestine, there's sneezing in the upper airway. And we just asked a very simple question early on is, could the this kind of inflammation be the direct neurologic trigger for itch? The short answer, summarizing years of work, was yes. And that's really kind of how our lab started, is that there is a particular kind of signal that goes from the immune system to the nervous system that triggers itching. And that really uncorked a whole field. It didn't just uncork a field of dermatology. It uncorked multiple, multiple fields across medicine, but also led to therapeutic developments that were unthinkable back then. And so, you know, yeah, it was quite remarkable.

[A]

Largely, you know, it's absolutely remarkable, largely unthinkable because no one actually even had recognized that these cells were existent in the skin that were driving that type 2 inflammation, many of those cells. And so we talk about the stimulation of breaking down the barrier of the surface of the skin leading to a specific type of type 2 inflammation driven by many cells, T cells, but also cells that were, again, once, long ago, thought of as no longer relevant. And so those cells are activated, and they drive that signal from the peripheral part of our body, the outermost portion up through our spinal column into the brain to give our brain that sensation of itch. But tell me a little bit more. I mean, you alluded to the fact that this, you know, not just uncorked a field within dermatology, but uncorked a whole myriad of science in, you know, neurology, immunology, other fields as well. Let's go even deeper and, and help me understand, help our audience understand how itch also can be a sign not just of breaking the barrier from the surface, but of internal disease. Are there, are there mechanisms that you've explored that look at like itch? You had said earlier, the person with kidney failure, they generally itch all over.

[B]

Yeah, absolutely, yeah, we're very interested in this. In fact, there was a drug that just had phase two success. It's barreling towards FDA approval in primary sclerosing cholangitis, which is a liver disease where your bile gets backed up. And this was just announced last week, there was success in that area. So some of the worst cases of itch that I see are in patients with, on dialysis who have had kidney failure. Patients with different kinds of liver diseases where their liver fails and treatments have been very much lacking in those areas. So this is more of an inside out itch. And this speaks to the fact that there are many ways in which we arrive at it. Itch is a critically important sensation for, particularly for animals too, because they will get infested very quickly if they can't scratch.

[A]

Yeah. And I think this is a perfect window just to remind the audience. Again, you mentioned the liver doesn't itch. And thank God it doesn't itch. That would be, you know, really miserable. Couldn't access it easily. But the liver alternatively can be the source of itch and when it, you know, is misfunctioning or has a disease, it causes us to itch. And that's where the skin can also be this incredible signal and into other internal pathology and helps save a life. Right. Someone with that disease, primary sclerosing cholangitis, may have no other symptom prior to itch. And when they have this diffuse itch that doesn't coincide with a rash, it leads us as dermatologists to start working that up. Why are you so itchy but you have no rash on your skin?

[B]

Right, Absolutely, yeah. The other way in which many patients itch is they'll have problems with their bone marrow. So it's a great kind of cue that something is wrong in general, whether it's from the Inside of your body or maybe even in the environment or an allergen or an irritant. These things will signal to you that something's wrong. It's somewhat of a subtle cue, but it's an important cue.

[A]

Yeah. And again, back to the evolutionary advantage. I suppose that itch is really providing us some signal of, you know, what we ought to be in tune to. So what is the difference, or has your lab uncovered any distinct difference between what we would qualify as regular itch? Oh, I have an itch, you know, or an itch on my ankle. I had a bug bite to that. Relentless, unable to quell itch that is absolutely ruining patients lives. I mean, we have patients that walk in that say, I haven't slept in weeks, I have not had any night's rest. I can't find focus at work, you know, I, I can't get rid of the signal. And there's just nothing we figure out. So their liver and kidneys are fine. What is the distinct difference between those two types of itch?

[B]

Well, I think that, you know, we itch. You know, I'm, since we talk about itch, I'm itching right here and I scratch my face. But fortunately it goes away. I scratch. Scratching is a way to alleviate the itch and acute itch, transient itch, we all experience it. And I said, that's a good thing. You want to be a little twitchy, you, you don't want to be a statue, otherwise you will have problems. And I think that's a good thing. It's a good thing to itch a little bit. And when, if you have an, if you have animals, if you have a dog, they actually scratch quite a bit because they're furry. And it's very protective for them against things like mites. But where it's somewhat arbitrary, what we call kind of chronic itch or pathologic itch or disease itch. And unfortunately it's hard to really define that. So in the field of dermatology, we somewhat arbitrarily designated itch lasting greater than six weeks as chronic itch. Okay, that's, I don't think that's a definitive definition. They're patients who itch for three weeks and they're miserable and it's not going away. I think they should still be treated. It's hard to describe them as kind of help, healthy transient itch in that scenario. But I think it's just a kind of a reasonable, practical, arbitrary switch point that we've designated as six weeks where we say, okay, now we really got to do something about this. But then you get to what are the causes of it? And there are many different causes of that. Just because we call something chronic itch doesn't mean that we know exactly what's going on. And it certainly doesn't mean that we know that they're all the same and that the treatments are all the same either. So that's where things actually, we now have to start to understand what are the different kinds of chronic itch. And there are many, many kinds. And to be clear, I started my itch Clinic in 2014. And you know, Lindsay, as you know, we train to become dermatologists, and we have quite a wide range of skill sets. So when I decided to do that, a lot of people thought I was crazy. They said, you know, this is a very good specialty. It's a lucrative specialty. The idea that you would just hone in on one symptom, though it's not really one symptom, seems very risky. It seems very niche and all that. But it really worked out well because actually, itch is such a common symptom across so many diseases. So actually, I actually remember walked into a conference recently, I looked at all the findings, pharmaceutical booths in the room at a dermatology conference. Actually, half of them were right in the mainframe of our biology.

[A]

Yeah.

[B]

And half of them, you could argue, were itch drugs. So really, it wasn't niche at all. And this is actually a really big thing now.

[A]

It's a huge thing. You know, this is called the billion dollar itch industry at this point, and for good reason. I mean, itch is one of those things that's been overlooked for so long. It is among the most tormenting of our patients. Cadre of symptomatology. Right. Patients arguably sometimes prefer pain over itch because the relentlessness.

[B]

Almost always.

[A]

Yeah, almost always. Pain is actually easier to manage.

[B]

Yeah, it is. And that's evolution, too. So that's the other thing that people don't realize. They think of pain as bad, but when they think of pain, they're actually thinking of acute pain. Yeah, okay, sure, if I break my femur, that's horrible. Okay. But that's not medical pain. Mostly most of medical pain is chronic pain. It's low back pain. You know, it's things like migraines and things like that. These are horrible. Okay. Don't get me wrong. I get chronic migraines. That's a horrible thing. But you can sleep through chronic pain. In fact, evolutionarily, you're meant to sleep through chronic pain. And that's part of the problem of pain. What you're trying to do is after you've broken your femur and things have stabilized, what your body's trying to do, the pain is telling your brain, hey buddy, sleep, recover, rest.

[A]

Yeah.

[B]

What itch tells you is, holy crap, there's a parasite in you. You need to twitch all night long until your body kicks this thing out. But imagine there's no parasite and your body thinks that forever.

[A]

Right. And hence this intentionality of the industry to find a, to find a cure, a target which you've helped tremendously with. I mean, I would say that probably in my 20 year career, among the most rewarding things is this evolution of what we've seen in the past several years, where we can actually take someone's itch away. And whether that's atopic, dermatitis, bolus, pemphigoid, you know, you name it, a number of things. This has become a focus of work that is tremendously valuable to us. Tremendously valuable. I mean, so, so frustrating and difficult and heart wrenching to treat these patients. But forget about us. I mean, for the patient population struggling with this relentless symptom, it has been absolutely game changing. So I suppose, and I love that you say, you know, you went to this conference and saw, you know, itch as probably, you know, in the middle of the lane of all of your work, was the focus of all pharmaceutical companies. What would you say has been, you know, and you may have a few of these things, some of the more landmark findings in your research as far as targets to treat itch. And we don't have to talk about drug names, but you know, just how you found these things and then the targets, you know, those targets being pursued by pharmaceutical companies to help patients.

[B]

Yeah, it was actually quite fortuitous because pharmaceutical companies, and there's actually a deeper lesson in here that we can get into depending on what you want to talk about. But these drugs were already in development, so they were kind of barreling along. But unbeknownst to the pharmaceutical companies, these drugs were actually not just anti inflammatory drugs, but they were quite literally acting on the nervous, nervous system. And when we discovered that particular pathways like cytokines like IL4, IL13 act directly on the nervous system, that helped us to realize there were other molecules, enzymes called JAK kinases or Janus kinases that actually also signal to this. And there were targets already in development to block these pathways and what this allowed us to do. But even before the drugs were approved and it is fortunate that I was somewhat tenacious about talking to the pharmaceutical companies. I was able to actually convince them that, hey, these drugs that you have are not working the way you think that they do. And, you know, I was only an assistant professor. I was pretty green back then. You know, there was no reason for them to believe me.

[A]

By the way, nobody succeeds without tenaciousness, my friend. Nice job.

[B]

That's true. That's true. Yeah. So, no, it was, it was. It's been quite a journey. I do have, you know, even when you were introducing me, you know that I have. I mean, almost every day I've kind of a pinch myself kind of moment because, you know, I grew up thinking that I would die before any discovery would lead to therapeutic advance. Right. And then someone would later do it. But, you know, I've lived it multiple cycles now. And it's a. And it's not like I've been doing my. I've only had my lab for 2012 years. So I, I really feel kind of heartened by this, that, you know, I feel like I can do this multiple iterations more. But, you know, that really just uncorked these therapeutics for itch. And these are among some of the best therapeutics for itch. And. And then people started taking it really, really, really seriously. Right. So it was no longer this kind of niche thing. It wasn't this funny thing. It wasn't this kind of phantom system symptom suddenly became very real. And now the pipeline's really opened up. Now you have pharmaceutical companies that are saying, you know, we want to focus on this. This is not a peripheral thing. This is something that we see is very important. And you actually now see, even insurance companies put this in as a metric. You might ask, why, right? So why would insurance company care? Well, at the end of the day, even insurance company. Even for insurance companies who are often, you know, trying to be very cost conscious, you know, no matter what, patients are their clients, right. If their patients are not happy, it's going to affect them. And I think they've already caught on to the fact that satisfaction, as you said, fulfilling satisfaction in terms of improvement is something they hear about. It immediately triggers a reaction. And people say, hey, I really like that I can get this drug. I like that I can see this physician who can treat me. I know this because this is now coming back to me and I'm hearing about it. And at first I was very surprised. So. And, and then the other things about these drugs, I'll say is they're great drugs. And then now I'll go back to the vestigial thing. The beautiful thing about studying something that's rather vestigial is that if you're able to also zap it, the good thing is you have very little in the way of safety or side effects. So it's kind of a beautiful scenario.

[A]

Right, right, right. It's that narrow lane of what you're looking for. Maximum efficacy, effectiveness, minimal downstream effects that would be in any way adverse. And so patients not just tolerate these drugs so fantastically, but they get such intense relief. Yeah. And you're right, that vestigial piece is actually key. It brings us back full circle. You know, the fact that that cell line isn't really alive and active and doing anything else that's requisite to our body's functions allows us to take it out of the picture as a target.

[B]

Absolutely. And so, yeah, I agree with you. And I'm sure you've experienced this many times over with these patients that, you know, they've been itching for 10, 15, 20 years and in a matter of a week they're better. I've had patients cry in my office just saying, I cannot believe this finally happened.

[A]

No, I, I, I can't emphasize what you just said enough, that, that experience of being with someone whose symptom of itch is relieved and them quite literally, I mean, it happens all the time. Crying to you about what an impact you've had on their life. I have a, a patient who I'm thinking of right now, who literally every time she comes back in for follow up, tells my medical assistant, whomever it is in the room with me at the time, this doctor saved my life. And I'm thinking, did I save her life? And this patient happens to have prurigo nodularis. And our intervention alleviated all of her signs and symptoms. That's a very, very, very tormentingly itchy condition. And she said she saved my life because I could not exist in the state I was in. Yeah, yeah.

[B]

Well, you know, I think about medicine and you know, I've actually mentioned this before, that in the old days, like, yeah, say in the 1800s, the mark of a great physical physician was someone who could, this is real. In the, in the 1800s, if you're, if you're a world class physician, the defining feature was that you could diagnose someone, hold their hand and tell them when they were going to die. That was considered cutting edge. Right. And then you came with the antibiotics, you had the kind of revolution of treatments and then it became that you could treat patients, diagnose them, and then treat them and prevent them from dying. Right. I think the era we're living in is now we can treat patient, we can diagnose patients, we can treat them, we can prevent them from dying, but how do we make their life meaningful and worthwhile and high quality? And that's the era we're in.

[A]

Yeah. And as a, you know, I'm a principal investigator in multiple trials, and we really have revolutionized the approach to metrics that we're utilizing in these trials. Right. So, you know, the paternalistic, forgive me, but paternalistic history of medicine was we would walk in the room as dermatologists, and from 15ft away, we'd basically tell people how well they were doing. We would look at them, we'd size them up and down. Oh, yeah. And your score is now an X, where formerly it was a Y. But now we're incorporating all of these metrics, these scientifically validated metrics that we call pros, or patient reported outcome measures that focus so highly on the symptomatology because really, in the end, we care a lot less about what they look like. It's a lot more about what they feel like. And I mean, we're not going to dismiss that patients want their skin disease to resolve, but indeed, if their skin disease resolves, and we even have additional metrics to say that if their skin disease resolves and they're still miserable with their symptomatology, they're not getting to that quality of life metric that we're aiming for.

[B]

Absolutely.

[A]

Brian, I couldn't be more grateful. I'd love to ask you a final question, if we may. And just for a patient who's listening, you know, we've talked about itch maybe being the sign of something really meaningful. We're not here to dismiss all itch, as you know, it's very important. And it may unveil internal pathology, but not all itch is that way. Some itch is just pathologic. It's just a signaling mechanism that really ought to be downshifted or shut down. And so for that patient who's listening right now, that just feels absolutely tormented by itch. What is it most that gives you hope for that patient today?

[B]

Oh, yeah. I have so much hope. So I think the patient you're talking about, if I had to give them a diagnosis, there are many, but the kind of classic would be a patient with chronic pruritus of unknown origin. And there have been, there's been a Lot of skepticism about, do you really even have a disease? Do you? Is this in your head? Is this psychological? The vast majority of itch that I have seen is not psychological. It's real. And I think the great hope is that the science that we and other labs are doing are advancing very, very rapidly. And the business that we're in, quite frankly, is, and I say this all the time, that I'm not interested in forming expert opinions. I'm not interested in publishing kind of what we call white papers. All that really matters is can you develop a therapy that's new that separates from placebo? And I quite mean this. That's the way in which we actually go from saying, is this even a disease? Oh, yes, it is. This is a disease. And now we can treat it. And that's the fastest way that we figured out how to do this. So it's actually not that academic at all. It's just kind of, let's just get it done and let's figure it out and listen to our patients. And I want to be very clear. A lot of the ideas we got came from our patients. And I'm not saying that to be emotional or sentimental at all. I have stories of when we first, for instance, figured out the Jak inhibitors would work for itch. A patient told me. I remember he said he'd been itching for 20 years. Itch went away within 3, 30 minutes. That would be unbelievable, right? It was hard to believe.

[A]

Yeah.

[B]

But then.

[A]

But we see it. It's really real.

[B]

It is. And here's the part that really got me, though. He said, I take this drug twice a day, but I start to get this feeling at night that's not itch. And I said, what's the feeling? And he said, it's this buzzing feel like electricity. Well, guess what? Your nerves are electrical cables. They work on ion channel gradients. That's exactly what they do. I thought, this guy is not making this up. I mean, he. He knows what's going on in his body.

[A]

Yeah.

[B]

Dealt with the molecule at this point. Right. So he said, as soon as I take the medicine, it goes away again. And he was right. I looked at the peak activity of the drug. It was within 20 minutes. He was describing exactly what the drug was supposed to do. So, you know, at the end of the day, there's great hope. I think we are able to. It's nice we can take the science to patients. We have to listen to patients. And that's why I still see patients, even though I have a very active lab. So that will be my very hopeful kind of answer to your question.

[A]

I love it. I frequently find myself saying we are in the people pleasing business and as much as I have invested in research and a number of extracurricular activities in my career as well, the greatest joy I get is from know sitting with a patient in a room and solving an issue that, you know, I've listened to that they've been comfortable enough to share. It's it's such an honor and such a privilege. And thank you. I really, I am so grateful that you gave us this time today. Brian. Thank you to Brian Kim for shedding light on a symptom we all know but few truly understand. So if this conversation made you think twice, the next time you feel the urge to scratch, then we've done our job. Don't forget to subscribe, rate and share this episode of Dermatology Undressed, a provocative podcast. Until next time, stay curious, stay kind, and keep peeling back the layers. When the skin speaks, it's never just skin deep. This is Dermatology Undressed.