157: How Your Immune System Can Trigger Skin Rashes w/ Heather Zwickey, PhD

Not many of us have heard of immunology, but it can actually give us some real insight into why we have skin rashes. My guest today is here to explain all about it.

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My guest today, Heather Zwickey, earned a Ph.D. in Immunology and Microbiology from the University of Colorado Health Sciences Center.

She went on to complete a postdoctoral fellowship and teach medical school at Yale University.

At the National University of Natural Medicine in Portland, OR, Dr. Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developing programs in research, nutrition, and global health, among others.

Dr. Zwickey applies her immunology expertise to natural medicine research, and she currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences worldwide.

Join us as we talk about how the immune system and cytokines can be related to skin conditions.

Did you know about the relationship between your immune system and your skin? Let me know in the comments!

In this episode:

  • What is immunology?
  • What are cytokines, and how do they relate to the skin?
  • Why does inflammation show up on different areas on different people?
  • What is the connection between filaggrin and cytokines?


“Your immune system is not only keeping you safe from infections, it's also keeping you safe from cancer. It's keeping you safe from autoimmune diseases. So it's the system in your body that's really promoting what we might call health.” [2:16]

“Everything that happens in your gut is going to happen systemically, because your immune system then travels through your blood, and through your lymphatics to the rest of your body, because it has to defend your whole body.” [10:05] 


Find Dr. Zwickey online here

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Healthy Skin Show ep. 155: Oral Allergies + Cross Reactivity: How It Can Trigger Itchiness + Hives w/ Rakhi Roy, MS, RD, LDN

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157: How Your Immune System Can Trigger Skin Rashes w/ Heather Zwickey, PhD FULL TRANSCRIPT

Jennifer: Hi, everyone. Welcome back to the Healthy Skin Show. Today's guest is someone who can talk all about the connections between immunology and what's going on with your skin. And if you're like, “What is immunology? I don't get it.” Well, basically, we're going to be talking about how you think something's going on on your skin. Say you have an eczema rash on the outside of your arms, and we're trained and conditioned to think that the rash and the issue that you need to focus on is in those areas. But today's guest is going to help you understand why that is probably not necessarily the case. And we're going to really dive deeper into the whole immunology piece, and we'll have her breakdown what immunology is, if you're not familiar with that term.

Jennifer: My guest today is Heather Zwickey. She earned her PhD in Immunology and Microbiology from the University of Colorado Health Sciences Center. She went on to complete a postdoctoral fellowship, and teach medical school at Yale University at the National University of Natural Medicine in Portland, Oregon, Dr. Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developed programs in research, and nutrition, and global health, among others. Dr. Zwickey applied her immunology expertise to natural medicine research. And she currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences and podcasts everywhere across the globe, and it is an honor to have her here. Thank you so much for joining us, Heather.

Dr. Zwickey: Thanks for having me.

Jennifer: So of course, I got to ask the first question, since I already sort of preface the conversation. What is immunology, for those who are not familiar with that term?

Dr. Zwickey: So I think historically, the way that we've thought about immunology is that the immune system is what keeps you safe from infections, but it's more than that. Because your immune system is not only keeping you safe from infections, it's also keeping you safe from cancer. It's keeping you safe from autoimmune diseases. So it's the system in your body that's really promoting what we might call health. And it is interacting with what we might say is the nervous system.

Dr. Zwickey: So, we might think of neurotransmitters and those sorts of things. It also interacts with your endocrine system. That's your hormones. So think time of month, and all of that sort of stuff. And it interacts with all of the other systems in your body as well. So its job is to determine when you encounter something, is it safe or is it not safe? And I think of that as the primary role of the immune system. If you think all day long, you're breathing, you're eating, everything you're encountering, your body has to know if it's safe or not safe. And the immune system is making that judgment call.

Jennifer: And is that the basic response? It get looks at something and says, “Okay, you're fine. You're cool?”

Dr. Zwickey: Yeah.

Jennifer: But then it might see something else and be like, “Whoa, hold the phone. We need to call out the police force. We need to deal with this threat.”

Dr. Zwickey: Exactly, exactly. And it's really hard jobs, because think about it, you had breakfast this morning. It needs to know that breakfast was safe whereas if you, after breakfast, walked into a field that's being sprayed with pesticides, it needs to know that the pesticides are not safe. So, it's constantly discriminating between what is safe, and what do I need to respond to?

Jennifer: With the goal to protect you.

Dr. Zwickey: With the goal to protect you, yeah.

Jennifer: But sometimes things go haywire.

Dr. Zwickey: Exactly, yeah, sometimes things go haywire.

Jennifer: And so, what would that look like for an immune system that's gone haywire? Would autoimmunity be one of those instances?

Dr. Zwickey: Yeah, so in the case of autoimmunity, well, we can think of many things where the immune system goes a little bit haywire, right? So autoimmunity is one, and in autoimmunity, your immune system mistakenly thinks you're dangerous, and it starts to attack. But let's even talk about allergies. Why is pollen dangerous? It's not.

Jennifer: It's not, huh?

Dr. Zwickey: Your immune system … yeah, no. And so, why is it attacking pollen? Because your immune system causes allergies. Now what's really an interesting little phenomenon is that in countries where there are worms, that infect your gut, you don't get allergies, because the same type of immune response that you have to a worm is the type of immune response that you have to pollen. And so, if you're distracted with worms, then you don't worry about the pollen. It's like in America, we've become so clean. We no longer have worms, so our immune system is like, “Oh, well in that case, I'll just attack that pollen instead.

Jennifer: That is super interesting. And I think too, that's the other reason why we … There's this asthma, atopic thing going on where we've talked on a previous episode … I want to say it was with Dr. Maya Shetreat. I think she touched on very briefly this concept of cytokines. So are you able to clearly explain to us what are cytokines? Because they're important. I feel like it's an important part of this process. What are they, and how do they get … What makes them, or what triggers them to be released? For somebody who knows nothing, who's like, “I've never heard of that before,” how would you describe them to … I mean, in regards to skin, especially.

Dr. Zwickey: Yeah, so let's start with what a cytokine is. So first of all, let's spell it, C-Y-T-O-K-I-N-E, cytokine. The cyt part, the C-Y-T part, that's cell. And kine is for communication. So this is how cells of the immune system communicate with each other. And if you think about it, a cell doesn't have a mouth. It doesn't have eyes or ears. And so, in order for it to communicate, it needs some other way to talk to another cell. And so, what it's learned how to do, it's kind of interesting.

Dr. Zwickey: A cytokine looks like a little miniature baseball, and the other cells have little miniature baseball gloves. And so, when a cell wants to talk to another cell, it throws a baseball at it and hits it. And if the cell has a glove, it can catch the baseball, and it can respond, but if it doesn't have a glove, it can't respond. So all over your body, there are these cells throwing baseballs, and there are cells with gloves, catching baseballs. And you've got this communication pattern happening with that form of communication, because you don't have a mouth, you don't have eyes, you don't have ears on those cells. And so, that's how they communicate. They get beaned with a baseball, and then they know, “Hey, I'm supposed to do something now.” So, that's how a cytokine works.

Jennifer: And so, for someone who has these atopic issues, or eczema, or even lots of allergies, and asthma, where does the cytokine piece come in? Because I feel like this is one of those parts to the equation that oftentimes is overlooked. It's just like, “Take some Zyrtec.”

Dr. Zwickey: Yeah, so there's lots of different processes that happen, but let's start with the fact that your immune system has different kinds of responses. So you can think about this as having a multi-car garage. And if it's a beautiful sunny day, you want to take out the convertible. And if it's snowing, you don't want the convertible, right? Then, maybe you want the truck, all right? So your immune system has these different vehicles parked in the garage, ready for different types of things that you can respond to.

Dr. Zwickey: So if, for example, you get a viral infection, then we need to pull out a particular type of immune response to fight that viral infection. Maybe that's your Jeep. So you're going to pull that guy out. It's rugged. It can go over the rough terrain. It can fight that viral infection. If you have worms, now you need more of a tank. So, we pull out the tank to fight the worms. But remember your allergy, your atopic disease is imitating a worm response. So essentially what's happened is you have pulled out the tank cytokines. You've pulled out that combination, and you're throwing baseballs at the cells that should be responding, just in case you have worms, only you don't have worms. So the cytokines, where they're actually being made is most often in your gut.

Dr. Zwickey: So why in your gut? Well, 80% of your immune system is in your gut, because that is the number one way you are exposed to things. Think about it, most of the stuff that comes into your body is coming in through your mouth. And so, usually what your immune system has to do, is it has to discriminate between what's coming into either your lungs or your gut as either dangerous or not dangerous. So your immune system is mostly in your gut.

Dr. Zwickey: So now, why is that showing up on the skin? Well, everything that happens in your gut is going to happen systemically, because your immune system then travels through your blood, and through your lymphatics to the rest of your body, because it has to defend your whole body. It can't just defend your gut. So even though the initial reaction is happening in the gut, it's driving everything else that you see in the body, including what's on the skin. I like to think of it as, if you put gasoline in your car, it goes to the engine, but it still drives the windshield wipers, and every other part of your car, too, right? And the alternator can't go around, and the wheels don't go around unless you have the gasoline, even though the gasoline is just in the engine. It's not in the wheels, but your wheels are going around because you put the gasoline in the engine.

Jennifer: So with that said, because this is fascinating, and by the way, I love these analogies. They're really easy to understand. Oh my goodness, the cytokines is like a baseball. That's so great. I love the way that you explain that, because it's very simple and I think it's easy for people to understand. And it's okay if you don't know, I don't know the answer to this, and it's something that people ask me, why would we know that a lot of these issues are driven by inflammation, right? And so, the cytokines play a role in can play a role in that inflammation. But do we know why maybe inflammation can show up in certain areas, like maybe only end up with the atopic dermatitis on your back, or on your legs, or around your eyes? Any thoughts on that?

Dr. Zwickey: We know a little bit. We don't know everything, but we know a little bit. So first of all, let's talk specifically about atopic dermatitis. So there's some certain things that we know. There are proteins on the surface of your skin called defensins. Defensins are designed for if a bacteria or virus lands on your skin, they're going to just chomp it right up. But they also keep all of your normal microbes that live on your skin from overgrowing. So how do we control our defenses? How do we have this population of daggers on our skin that can fight off infection, and keep our normal microbiome from overgrowing? Well, we need a cytokine.

Dr. Zwickey: And the name of the cytokine for that is called Interleukin-22. We abbreviate it IL-22. How do you make more IL-22? So, so what happens is you make IL-22 in your gut, and it goes to your skin, and it says, Hey, make more defensins, because we've got some overgrowth of our normal microbiota on our skin. What happens is when you take vitamin D, vitamin D, it sends a message in your gut to the cytokine, Interleukin-22, “Hey, baseball, go and knock all those skin cells into making more defensins, right? And so, Interleukin-22 acts like the baseball, or it is the baseball, and it goes to your body, and it starts throwing baseballs at your skin to say, “Make more defensins.” Now we know one of the things that's happening with people with atopic dermatitis is that they do not have enough defensins in areas of their skin. And as a result, they're getting an overgrowth of normal microbiota. So, that's one of the things that's happening.

Jennifer: Wow.

Dr. Zwickey: And it's vitamin D related. Interesting, huh?

Jennifer: Wow, that is fascinating.

Dr. Zwickey: Yeah, and we know that roughly … well, historically it's been 90% of the population that is vitamin D deficient, but the most recent stats say it's closer to 65% that are vitamin D deficient, but they change the numbers of what deficiency looked like. So I think that's-

Jennifer: Yeah, that's true.

Dr. Zwickey: …one of the reasons that we saw that happen. But anyway, so vitamin D deficiency could be one of the contributing factors to atopic eczema. Now the next thing is, we know that when you get the rash and the hives that it's being caused by certain cell types. So the cell types that have the baseball gloves for the cytokines. So what cell types are causing those? Well, we know mass cells and eosinophils are the big culprits, and these are just cells, like you drew cells in high school. They just look like those things you drew in high school. It just happens to be that these particular cells have, well, we call them granules, but you might call them grenades inside them. And when they blow up, then you see an outbreak on your skin in that location. What's interesting is we don't know how those cells wound up in those locations for different people. So I used to have a bit of an allergy to chocolate. And what was interesting is … I know how depressing, right?

Jennifer: I know, that's really sad. I would be really sad.

Dr. Zwickey: Yeah. Well, I don't still have it, although I still have a little scar from it, but I had two cells that responded. And I know that because every time I would eat chocolate, I would get two hives on my hand, right on the back of my hand. And my students could tell that I had had chocolate, because these two hives would appear. And they'd be like, “Dr. Zwickey, you ate chocolate,” right? Why right there? Why? Who knows? It could've just as easily been on my shoulder. It could've just as easily been around my eyes. That's the part we don't understand. We don't understand why cells in a particular area for a particular person show up where they do. We know the process of what causes the rash. We know the process of the gut involvement. What we don't know is why that spot?

Jennifer: Can I ask you another question about-

Dr. Zwickey: Sure.

Jennifer: And I'm asking, because I actually don't know the answer, but it was a thought that came to my mind as I'm listening to you. So there's the protein, filaggrin, that is made that helps us with our skin barrier. And Dr. Peter Lio has told me repeatedly, and he said it on the Healthy Skin Show that inflammation hijacks the gene, filaggrin, from producing healthy filaggrin. So I would just assume that there is a connection here then between the cytokine issue.

Dr. Zwickey: There is.

Jennifer: And so, could you just … is there a simple way to explain-

Dr. Zwickey: Yeah, sure.

Jennifer: … how cytokines could hijack your body's ability to make almost this protective protein that your skin needs?

Dr. Zwickey: Mm-hmm (affirmative). So when you get an infection, your immune system is designed to go through a process to eliminate the infection. And the first part of that process is called inflammation. And with inflammation, you have three very specific cytokines. They are called Interleukin-1, IL-6, Interleukin-6, IL-6, and TNF alpha. So this combination of cytokines, they actually are responsible for you feeling sick when you get sick. You know how you're like, “Oh, I feel terrible?” Yeah, it's those three proteins that go to your brain, and tell you you're sick, and make you go back to bed. But those three proteins are also circulating systemically in your body, and they're driving an inflammatory response.

Dr. Zwickey: So let's think about what historically an inflammatory response was. This was, if you went to battle, this is the response that is going to start your wound healing, right? If you are running from a tiger or a lion, this is the response that's going to help you, should you get caught. It's going to help your skin heal, right? So, these inflammatory proteins go right to your skin, well, likely because of how we evolved. Now, when they go to the skin, their biggest concern is not, “Does your skin look healthy?” You're running from a lion. We don't care if your skin looks healthy, right? What they're doing is they're turning on proteins and turning off proteins that are not necessary for you to be running from a lion, and turning on proteins that should you be caught, you're going to be able to defend your barrier, your barrier function, right? And frankly, a rash doesn't matter from a barrier function perspective. So, that's what those inflammatory proteins are doing, and that's why they're doing it.

Dr. Zwickey: Now, here's the problem. Maybe you didn't have an infection, but you've got this inflammation process going on. Why? Well, we know right now in the United States, three of the top reasons we have for chronic inflammation have to do with your diet. You might be eating a food that causes inflammation in you, and you're not aware of it. Or, you might be eating a food that causes disruption in your intestinal permeability, and you're not aware of it. Or, you might be eating a food that is just downright inflammatory, like trans fats, and you're not aware of how much trans fat you actually get in your diet. Those things alone will cause those three proteins to be produced. We also know that obesity causes those three proteins to be produced, because the cells in the fat actually make those proteins. So you could have chronic inflammation, because you're overweight, because you're eating something you shouldn't be eating, that you're not aware that you shouldn't even be eating that. It's specific to your body. And then the next major cause of chronic inflammation is stress. Stress.

Jennifer: Stress is huge.

Dr. Zwickey: Who doesn't have stress right now, right?

Jennifer: I know.

Dr. Zwickey: Yeah, we all do. So part of our job is to get those proteins under control. And one of the pathways that does that is our resolution pathway. The resolution pathway is stimulated by fish oil and Omega-3s. And how many Americans don't get enough Omega-3s in their diet?

Jennifer: A lot, a lot.

Dr. Zwickey: Yeah, exactly. So here, we're in this situation where we're in a scenario where we have high stress. And so, we're making the inflammatory proteins. We're not giving ourselves enough of the nutrients we need to shut them down. And we're not being able to remove ourselves from the stressor. So we don't have that way to shut it down. So, we're in this chronic inflammation and when we have the chronic inflammation, it's turning on and off the proteins that are important for our skin integrity.

Jennifer: Man, all right. So first of all, my mind is blown. I have a million questions for you, yet we're out of time, surprisingly.

Dr. Zwickey: So, we'll talk again some time.

Jennifer: I mean, we're going to have to talk again if you're open to that, because I feel like we're unpacking. I feel like we just had the basic conversation. I'm sure you could talk for for hours on this. And I think what would be interesting, too, you had mentioned at the beginning. We're not going to talk about this today, but maybe the next time. This is my hope. We could also talk about that connection, you said, between the immune system and the hormone system.

Dr. Zwickey: Sure.

Jennifer: Which I think would be really fascinating, because there is a hormonal component to this for some people.

Dr. Zwickey: No question.

Jennifer: So A, okay, so I just want to recap my takeaways, because I want to make sure we've … We've thrown a lot of information at people. So A, we're looking at the importance of vitamin D. So, you got to get checked, and I'm not going to add as a clinical nutritionist, if you don't have a gallbladder, there is a real good chance, especially if you're not getting out in the sun, you may be vitamin D deficient.

Dr. Zwickey: Oh. Well, 90% of people are vitamin D deficient. You want your vitamin D levels between 50 and 80. So, go get checked and see where you're at.

Jennifer: Yeah, and then also [crosstalk 00:22:52].

Dr. Zwickey: Another thing to remember there's genetic differences between people with their vitamin D receptors. And so, for some people, you can be taking a vitamin D supplement, and you think, “I'm fine, I'm taking my supplement,” but if your receptor is not a high affinity receptor, you might need to double or triple your dose to get enough vitamin D. So go get your levels checked, so you know where you're at.

Jennifer: Yeah. And then, the Omega-3 piece to this, which you can get from food, if you eat … Cold water fish is a great source of Omega-3s.

Dr. Zwickey: Mm-hmm (affirmative), flax.

Jennifer: Flax, yup. I like ground flax, just not if you're constipated, everybody. Or excuse me, not if you have diarrhea. If you have soft stools dieting, ground flax is going to be a little tricky, probably going to make it worse. But for constipated folks, it's great. And for those you poop just fine, awesome. For those you who can't swallow pills, food options can be a great source, but some people may need to supplement at times. Because we have to keep in mind, if you have spent years not paying attention to this, and all of a sudden you wake up and you're like, “Oh wait, I might be low,” or, “I am low,” it might be tricky with just food alone to get those wells refilled.

Jennifer: So sometimes you need a little help, but just, I want to thank you so much for being here. I want to make sure everybody can connect with you, and learn more about you and your work. So they can find you over at HeatherZwickey.com. You're also on Instagram, HZwickey. We'll put these links in the show notes, so it's easy for everybody to get in touch with you. But thank you so much for having this conversation. This has been super fun for me to nerd out on. So, I appreciate you being here.

Dr. Zwickey: You're welcome.

“Your immune system is not only keeping you safe from infections, it's also keeping you safe from cancer. It's keeping you safe from autoimmune diseases. So it's the system in your body that's really promoting what we might call health.”