Episode 29: Exposures to chemicals in our environment and the allergy / eczema epidemic

ResearchCauses

Apr 20

Written By Global Parents for Eczema Research

What do microplastics, dishwasher rinse-aid, air pollution and processed foods have to do with eczema? Join us as we explore why allergic diseases were rare for our grandparents but now affect two billion people worldwide. Explaining the link is our guest, Professor Cezmi Akdis. He is a global leader in immunology, specializing in allergic diseases, editor-in-chief of Allergy, and a Professor at the University of Zurich in Switzerland. (If you like our podcast consider supporting it with a tax deductible donation.) Read the transcript.

Itch
Lynita: [00:00:00] Hello and welcome to the podcast.
Today. Our topic is itch. Itch is the number one symptom of eczema that parents and caregivers want help with. But as yet, there just don't seem to be great answers.
My name is Lynita Howie. And joining me is the founder of global parents for eczema research, Korey Capozza.
And our guests today are Dr. Shawn Kwatra. He is an associate professor of dermatology and director of the John Hopkins Itch Center in Baltimore. He is an international leader in chronic itch, inflammatory skin diseases and skin of color research, and he has written a book entitled, living With Itch.
And joining him is his wife, Shivani Patel. She is a practicing pediatric dermatologist, a member of both the American Academy of Dermatology, and the Society for Pediatric Dermatology. Thank you both for joining us today on the podcast.
Shawn: Thank you for having us. Yeah. Thank you so much for having us.
Why?
audioLynitaHowie31854483669: I guess [00:01:00] the first question I want to ask is why do we itch?
Shawn: If you think about itch generally why does it happen? Well, you need transmission of the impulse of itch through nerves. But what we are often finding with eczema, is that there's a cross between the nerves and the immune cells. And so the itch of eczema happens because of that crosstalk and that happens because of an impaired skin barrier so if you have less of a barrier, then you have more exposure of these nerves to pollutants, or substances that can set off this pathway.
Moisturizer alleviating itch
audioKoreyCapozza_GPE11854483669: Okay, so I'm gonna share a personal
experience and ask about the. Biology of it. So my son has eczema. I have never had eczema, but I developed it around my and , I have so much empathy and sympathy more than ever because it's so vexing and it keeps you up and it's just an awful feeling.
But when I put moisturizer on [00:02:00] it, like a thick moisturizer, my sense is that. I'm blocking the nerves that are, interacting with whatever exposure is triggering it.
Shivani: Absolutely. moisturizers really help skin barrier. So if you have a broken barrier, you can seal it with that moisturizer. Because eyelid eczema is very prone to environmental pollutants and people have horrible seasonal allergies in the springtime, their eyelids will flare.
This actually happens to me as well. Every spring but that moisturizer really helps cuz it does create that barrier and it seals in those little cracks.
And the skin that we can't see and helps put that barrier there so that you're not getting as much exposure to some of those environmental allergens.
audioKoreyCapozza_GPE11854483669: Right, in the context of itch, is it performing some role in blunting the crosstalk between the immune system and how like there's more nerve interaction at the surface. I was curious.
Shawn: Absolutely after I take a shower and I tell my patients, after you take a shower, you should be packing in that moisturizer fast because that dense water layer is then gonna [00:03:00] protect.
The nerves from being set off and also the immune cells interaction with those nerves. So I view it as absolutely a protective layer. And you're talking about the eyelids. Eyelids are arguably the thinnest area on the body in terms of the skin. So they’re probably one of the most prone sites to having, external factors set off those nerves in that itch transmission pathway.
Because, itch is a cycle. There's neurotransmitters, there's immune cells and then there's factors outside. But you wanna be able to break that cycle. And if you stop the itch message via, water barrier, then that can be a great way to shut off. The problem happens is when you let those, immune cells get irritated and you have a lot of inflammation, Some moisturizers luckily have anti-inflammatory properties as well, like glial, oatmeal based moisturizers and. But sometimes it's not enough. I view it as a really important step. For all our eczema [00:04:00] and itch patients to protect against random pouts of itch.
audioKoreyCapozza_GPE11854483669: Yeah, it was such an insight for me because I, kind of understood more what my son is experiencing and that, the moisturizer is important for moisturizing the skin and showing up the skin barrier, but maybe it's also just blocking that tingly feeling of, nerve interacting with the environment in a dysregulated way. So it was really interesting.
Recurring trigger itch
audioKoreyCapozza_GPE11854483669: So If you have eczema somewhere and it's itchy and you develop that link between the skin and that spot and your brain, it seems like when you have a trigger, like itch or something, it goes back to that spot where it was, it's like, the groundwork has been laid and the body just follows that, highway that's been built in a way.
Is that true?
Shawn: Absolutely. So there's types of immune cells called memory T-cells, and they actually are localized in certain areas of the body and they already have an impetus or stimulus to be able to secrete their contents very easily. And so some of the [00:05:00] research that has been emerging, it’s focusing on how do you eliminate these sources of memory, TCEs.
And that's not just eczema, but psoriasis vitiligo. It's a hotspot for research in general.
Scratching when no flare
audioLynitaHowie31854483669: I noticed with my son, particularly when he gets irritated, he'll naturally go back to that behavior. Even when skin looks great
Is he itchy or is it just a learnt behavior?
Shivani: It's gonna be a little bit of both. So if you actually biopsy those areas of skin that appear normal, there is a lot of immune dysregulation underneath that is causing that immune pathway to still be activated. And so you can get that itch there, even though the parents aren't seeing a rash.
Shawn: And, and I would add also that, I also have eczema. And seasonal allergies and asthma as well. And one thing is when I get stressed, I actually
break out an eczema on it, itch uncontrollably, really even to this day. The [00:06:00] nerves that go out to the outer layer of the skin, they're called a delta fibers, they traverse from that nearly outer layer of the skin through to the the spinal cord, and then upwards towards the brain. not not just one way though. If you have stress, then you can start that. Its transmission pathway from up down.
And these neural and immune pathways are entirely connected So that's probably why stress is one of the major contributors and aggravating factors in itch.
Lynita: And I think you've just answered a question from one of our parents, Vanessa from Australia asked why is each worse when we're frightened, anxious, and nervous. I also just wanted to comment you've all talked about experiencing eczema.
Verbalising -> Burden of itch
Lynita: And I think it's really important that people. With eczema can explain to parents. What it feels like. My son had eczema.
I did not. And he could not verbalize how he felt. [00:07:00] so it's really important to share that with parents
audioLynitaHowie31854483669: we can visually see they're irritated, but we don't understand.
Shawn: I think it's so important. Burden to have that level of empathy and respect for what folks may be going through. We actually tried to assess the overall burden of itch and actually the overall burden of itch was as severe as having chronic heart failure or having a stroke.
And you're a young child developing and you can't sleep because of the itch. You not only will have a lot of different emotional difficulties but you can also interfere with development.
Shivani: Absolutely, we see, a lot of these links between growth parameters set this age just, because of that itch.
Deciding to progress treatment
audioLynitaHowie31854483669: What you've. Just said has kind of led into a question that I did really want to ask and it's: When do you make the decision to progress from just using topical steroids again and again and again and say it's time for this child to step it up ? .
Shivani: Really key is, atopic dermatitis or eczema that's [00:08:00] uncontrolled. We’ll have some kids who have seasonal flares, but then we have kids that, they're filling that refill every single month. Squeezing that last bit out and that's not really controlled. Um, a lot of it is also dependent on parents, when you talk about eczema and kids, it's not just the kids that are affected, it's the whole family. So that's the time that you wanna really start thinking about moving on.
Topical Non-steroids
Shivani: We have, a lot of topical, non-steroidal agents,
Like ruxolitinib, tacrolimus, pimecrolimus, these are really great to use in those situations. So an area that's constantly flaring, you can have a maintenance treatment that, prevents you from having to use too much of that topical steroid.
I think it's great that we know now its safety use topical calcineurin inhibitors. Tacrolimus. Pimecrolimus. .
audioLynitaHowie31854483669: So that is encouraging to see that there are treatments that are now proven safe that can be used.
Shivani: One thing that I think helps with itch is, uh, simple soak and smear technique.
So we'll do that for a lot of our younger kiddos. Where, you're taking a tub of Vaseline, smear it all over them [00:09:00] after a bath, doing a wet pair of pyjamas followed by a dry pair on top.
We also do have other therapies available like phototherapy or light therapy, which has been around for, for so long. And it still works great for eczema amount and it still works for the right patient.
But when you see that it's impacting everybody in the household because we can't get it under control, you have to really start thinking about systemic therapies. And one of the ones that we go to at this age is Dupilumab because it
is approved for children six months and older.
It can really help with eczema and the itch that's associated with it. , compared to 10 years ago, 15 years ago, we were using a lot of older agents that had a little bit more toxicity associated with them and really weren't getting great results.
Shawn: Just a few years ago we were using very dangerous drugs that have poor safety profiles. Things like cyclosporine, methotrexate that, really were not. Good drugs to be using in children. And luckily now with the emergence sub dupilumab and other [00:10:00] drugs falling behind it, we're able to get control of disease in these patients because of those consequences.
Itch is the no.1 need to treat
audioKoreyCapozza_GPE11854483669: I wanted to ask a quick question about treating itch, It's, the symptom that patients and parents care the most about.
So is something really an eczema treatment if it doesn't address itch, like I think eczema treatments need to tackle itch.
It's the hallmark and the most troublesome symptom for patients and caregivers. But, are there standalone treatments for itch at this point or are we really tackling it within the context of addressing eczema severity more globally?
Cuz to be honest, that's one of the reasons why we hesitated on doing a podcast specifically on itch cuz we didn't wanna tell people and there's nothing for you.
Shawn: So you have to think about the origin of itch and there's many different causes. There's neuropathic itch there's systemic related itch. There's inflammatory itch, so eczema is a form of inflammatory [00:11:00] itch.
One of the ways I think about atopic dermatitis is that it is the rash that itches. And the reason I say that is because it's not usually itch completely in isolation. It's itch also in the context. Of inflammation, type two, inflammation. I L four I L 13 I L 31 are some of the cytokines that are very important.
So I believe if you have a therapeutic that's targeting those specific cytokines, you are targeting the itch of eczema. So there are some therapeutics that are specifically only targeting itch. But In atopic dermatitis. I don't believe those are
gonna be the appropriate therapeutics.
And so even new therapeutics in development, like there's an agent, topical Roflumolast or Zareb, which is a topical cream in development. There's another one approved called Eucrisa. And these agents are targeting those cytokines. There's another drug called Tapinerof. [00:12:00]
Which is targeting cytokines, but in a little bit different mechanism. The JAK inhibitors target those same cytokines. So I think that in atopic dermatitis you have to be focused on the origins. And like Shani was saying earlier, if you do biopsies of normal appearing skin, you still have inflammation that's interacting with the nerve.
audioKoreyCapozza_GPE11854483669: It's been. Hard develop treatments for itch, and I wondered why is it so much harder than, say, developing a treatment for pain,
Shawn: I think the main problem has been the recognition of itch as a devastating independent disease state, honestly, even me, someone who treats itch patients. When I tell some of my colleagues or friends, they don't have a lot of respect. Sometimes I can sense for the degree of burden these patients have and the work that we're doing, and so subsequently I think there's been less respect for the disease, and that's led to less funding. Itch is gaining steam now, there's an itch scale that's validated from [00:13:00] zero to 10. So now these therapeutics, you can see how they line up. And that's helping to increase awareness. But we're also doing a job at the front lines trying to emphasize how important itch is. Dantes Inferno referred to chronic itch as being one of the realms of hell. And a village, in India that had this triangular cage with an itch causing substance, and they've placed folks in that cage as a deterrent. Or punishment and even one of being in that cage, they found is more of a deterrent to subsequent crimes than being in prison for 10 years.
audioLynitaHowie31854483669: Wow.
Shawn: Having folks, really have the right degree of recognition. I think pain's terrible. I think itch is worse.
So I think unless you experience it yourself or the loved one, it's hard to have that empathy. And so now we're catching up. With research resources from the N I H industry is getting really focused on it as well. So it is the golden age for itch [00:14:00] therapeutics now.
audioKoreyCapozza_GPE11854483669: That's good news. That's a hopeful note. And I do think a lot of patients prefer pain to itch. You hear them say that actually cause pain. To distract from the itch so it's very telling.
Shawn: It's the all point is scratchy, right?
audioKoreyCapozza_GPE11854483669: Yeah. I mean, that's proof in the pudding.
Staph and itch
audioKoreyCapozza_GPE11854483669: I had a quick. Question about the role of staph in itch. Cuz we know staph, aureus, bacteria is more pronounced on the skin of people with eczema. And it seems like throwing gasoline on the fire of eczema, it makes it harder to treat and under control.
And has this exacerbating effect, but what is it doing to itch, if anything?
Shawn: So there have been studies on eczema patients in general, and when folks are having flares, that’s when their staphylococcus aureus levels are the highest. So when you're having a flare, having these bad bacteria on your skin is gonna exacerbate disease.
These staph species release proteases [00:15:00] that also activate. Itch. So Staph Aureus has direct interaction with the nerves. We've been learning a lot more about dysregulated microbiome and how the dysregulated microbiome directly interfaces onto the nerves.
So our lab is doing a lot of research on the skin microbiomes, how it directly activates itch. And then also one very unique area is, we're actually spending some time looking at the gut microbiome.
Because the vagus nerve travels all the way to your gut, and that can also be an area where the itch signal can be transduced.
So it's very interesting that these dysregulated species can release a lot of the substances like proteases that can then trigger these responses. Also the eosinophil is oftentimes associated with significant itch because it has a number of different granules it releases that then set off the nerves. So that's how systemic this is in nature.
And we're treating these patients, I'm [00:16:00] talking a lot about, what are they putting on their body? Are they doing bleach baths if they're having flares of their disease because of those staph species? What food are they eating? What are their stress levels like? And then talking about systemic and topical drugs that are able to reduce inflammation and protect the barrier with moisture.
And then what type of factors are in their environment in terms of pollutants or allergens. That's why eczema is so complex.
audioKoreyCapozza_GPE11854483669: yeah, it's fascinating how there's so much more communication than we realized between the skin, the brain, the gut, the immune system, and that the body has the ability to send signals across all of these different areas in such a complex way, even involving the bacteria that are hanging out, in and around the skin and the gut.
So it seems like a pretty complex picture to disentangle, but it's definitely not just, clearly a skin issue, which I think is really important for people to understand.
Shivani: Yeah, we have a lot of [00:17:00] parents come in who ask for that one thing they can eliminate to just cure their child's eczema.
And I think what Sean just said is showing how difficult that is because it's such a multifactorial disease you've got that , interplay between the skin, the brain, the gut, bacterial load, environmental allergens, genetics, pollutants, your environment, your stress.
All of those things are playing a role into every flare that you're having.
Shawn: It would be great if there was one simple fix, but sometimes you go barking up the wrong tree and you can create more problems. I know Shavani, you deal with this too.
Shivani: Yes. We have a lot of kids that have this regimen of antihistamines. .
Antihistamines
Shivani: And they're still itchy, they're still flaring. This itch is not histaminergic. And I tell parents, all you're gonna do is, make your kid drowsy enough to fall asleep. So they can't itch, but they're still itchy.
Shawn: An antihistamine is something we'd all like to exist.
A drug that reduces itch quickly and safely, but it doesn't actually work in atopic dermatitis to reduce itch pathways,
We know that folks who even take a low dose of non-sedating and [00:18:00] histamines. Maybe at a greater risk of even having dementia. So you have to factor that in and you have to know it's not being targeted to the underlying disease. , non-sedating antihistamines in particular, I think do absolutely nothing in atopic dermatitis.
Maybe a placebo effect, and then sedating Antihistamines are not something either of us really encourage a lot of, especially an era where we understand the underlying neuro immune dysregulation and we have therapies that can address it very directly.
So that's another one of the dogmas that has been hampering care, I think.
audioKoreyCapozza_GPE11854483669: I think it's so important to get the word out because in addition to dementia for adults, there's ADHD and different issues that have been linked to their use in kids, but it's still so widespread.
So widespread. I bet most of the eczema kids in our group have been on serious antihistamines one time or the other.
audioLynitaHowie31854483669: I'm guilty as well,
I'm really glad you've brought this up because I think it's really important to keep revisiting these standard beliefs that we need to change.
Shivani: Yeah, I, I agree.
Lynita: [00:19:00] When are we at a time, but I just have one question from a parent that I wanted to ask. Tania from New Zealand wants to know why itch is more persistent at night. We all notice it.
Shawn: it's a great question. There are many things that factor in one when you're busy during the day, you have less of a focus on those specific sensations. So these nerves are transmitting itch, pain, temperature, vibration.
So if you're likely to also have your mind be distracted. Secondly, there's also
circadian rhythms in release of pro-inflammatory mediators.
So in a lot of our studies, a lot of these patients have had excessive release of many of these neural and also immune secreted mediators at night. So there's a number of different factors that can make it more announced tonight.
Lynita: That's really interesting. It makes sense that we're less distracted at night, but I didn't know about these pro inflammatory mediators. That we can release at night. And that expert patients may be releasing more.
Thank you. Well [00:20:00] times up. Thank you both.
audioLynitaHowie31854483669: This has been a really great chat. And I think you really summed it up to say that itch is just not respected as uh, comorbidity of the disease. And thank you so much for dedicating your research to improving our understanding of it. You've got a lot of parents cheering you on on the sidelines, that's for sure.
And Shivani, thank you so much for dedicating your life to helping our kids as well, because we need people like you that are empathetic and compassionate. And it's you guys that help us get through this this trauma of living, with eczema. So thank you.
Shawn: Thank you so much for having us and for anybody that's out there. You can also follow us on social media Shivani@pedsderm. And I'm at Dr. Shawn Kwatra on Instagram and also on Twitter. And, very excited that so many folks are interested about itch and eczema.
And it's a great time for everyone, for patients, for providers, also giving us great joy [00:21:00] to see folks getting better. Yeah, absolutely.
Shivani: Thank you guys.
audioKoreyCapozza_GPE11854483669: Thank you everybody.
Lynita: Thank you so much.