Episode 21: Do we dare dream of a future where eczema and food allergies can be prevented?

Eczema and food allergy are closely intertwined, particularly when it comes to questions of prevention. We know that eczema tends to be the first condition to emerge in the atopic march and there is growing evidence that controlling eczema may actually prevent some of these downstream conditions. Likewise, if we can learn how to prevent eczema so that it never develops in the first place, we may be able to prevent all of the conditions in the atopic march: food allergies, asthma and allergic rhinitis. Find out more on this episode, hosted in partnership with the Food Allergy Fund 2022 Summit, with guests Dr. Peck Ong from Keck School of Medicine, Dr. Aikaterini Anagnostou from Baylor College of Medicine, and Dr. Jessica Hui from National Jewish Health as we delve into how to prevent atopic conditions, starting with eczema. PS. If you like our podcast, consider supporting it with a tax deductible donation.  Read the transcript.

• Transcript

  Welcome to the spring 2022 food allergy fund summit. I'm Korey Capozza, Executive Director of Global Parents for Eczema Research and a parent to a child with moderate to severe eczema. I'm happy to moderate this session today on atopic dermatitis, food allergies and prevention. With me today are three accomplished researchers and experts on this topic.

  Dr. Peck Ong is Associate Professor of Clinical Pediatrics at the University of Southern California and an attending physician in the Division of Clinical Immunology and Allergy at Children's Hospital in Los Angeles. His most recent research focuses on food allergy and eczema prevention. Dr. Ong is also on our Board of Directors. So welcome Dr. Ong. 

  Dr. Aikaterini Anagnostou is a Professor of Pediatrics at Baylor College of Medicine and Texas Children's Hospital. She serves as the Director of the Food Immunotherapy program and her research interests include preventing and treating all forms of allergic disease. She currently leads research projects on food, immunotherapy and anaphylaxis and the microbiome.

  So welcome Dr. Anagnostou. 

  Thank you. 

  And finally we have Dr. Jessica Hui, she is a pediatrics and internal medicine trained physician and an Assistant Professor in the Department of Pediatrics at National Jewish Health in Denver, Colorado. Her research interest is in the origins of allergy and she has been a co-investigator for two large multi-site studies: The Sunbeam and the SEAL trials, which are both studies involving young children and examining factors associated with allergy and development. Welcome Dr. Hui.

  I'm excited to delve into this topic today because increasingly we're seeing that eczema and food allergy are closely intertwined, particularly when it comes to questions of prevention. We know that eczema tends to be the first condition to emerge in the atopic march or manifestation of allergic conditions that tend to follow one another over time.

  And there is growing evidence that control of eczema may actually prevent some of these downstream conditions. Likewise, if we can learn how to prevent eczema so that it never manifests in the first place, we may be able to prevent all of the conditions in the atopic march, which includes food allergies, asthma allergic rhinitis, and so on.

  So there could be a kind of four for one in that type of approach. I want to start off today by asking the panel to help explain why so many children with eczema go on to develop food allergies. What puts them at such high risk? 

  Children with eczema, definitely at high risk of developing food allergies. And we explain this by looking at how the food is presented in early life to the infant. So there is the hypothesis called a dual hypothesis. That basically says that if you expose infants in early life to high doses of food allergens by mouth. So the oral route, which is our normal route for introducing foods, generally, then your system guides them towards tolerance of that food.

  But if that doesn't happen, the infant gets exposed to food allergens through skin, which is exactly what infants with eczema suffer from. Then you have an improper, sort of antigen presentation of the food to the immune system and that kind of skews the response to the immune system towards sensitization and potential food allergy.

  I think this has also been confirmed by further studies that looked into household dust and levels of peanut protein in the house dust and found that kids who have eczema, broken skin and are exposed to household dust with high levels of peanut and not orally exposed to peanut, developed peanut allergy.

  So I think that the broken skin and the fact that the antigen is presented in a different way than it's supposed, to puts these infants at risk. Not all infants with eczema will develop food allergy. That's very important to note. And generally we find that those who are most at risk are the ones that have severe eczema early on in life, the first three months of life or so.

  So thank you for that thorough explanation. 

  Yeah, I could add to that. Um, so it was very interesting that the most severe infants with eczema, they tend to have food allergy. That's a very important point because one in 20 healthy children, it’s likely we have food allergy. On the other hand, if you look at eczema, at least one in five, regardless of any severity. And that rate goes up as the severity of the eczema goes up. So for the moderate to severe eczema infants, it goes up as high as one in three. The very severe, even higher than that.

  So I think that gives the indirect evidence that the barrier actually it's a very important part of desensitization. I'll just add the skin, if it's disrupted in any way, There's a lot of ways for different allergens to penetrate and really skew your body towards that inflammation to create more of that allergy type of picture. 

  And, there have been studies done. For example, the LEAP study, they showed that the severity and the duration of eczema within the first year of life really was a predictor of subsequent peanut allergy by age one. And so it's a known concept and a known phenomenon.

  Yeah. I think it's really interesting, where we've thought of the skin is just this wrapper on the body in the past. But I think we're really learning that it's really the interface with the immune system, where the immune system can be trained, or imbalanced if that training isn't happening properly.

  I wanted to ask about this age window, that seems to be particularly important in the first year of life. Is that a kind of a critical period for food allergy and eczema? And should we be targeting that age in particular, in our prevention? 

  Yeah, that's a really interesting point. And I think we are seeing a window of opportunity as we call it in our prevention food allergy studies.

  And it appears to be really early on in life sometimes much earlier than we initially anticipated. And it is that reason that made us change our recommendations for feeding, for instance. And now we encourage parents to introduce allergenic foods around four to six months of life, in order to catch that window when the immune system is more malleable and any intervention can have long lasting effects.

  Recently there was a study looking at early life immunotherapy in young infants and toddlers, up to the age of three, four years old. And again, it showed that the earlier you introduce the better your outcomes for therapy as well, because it appears this early window is most important if you want to intervene successfully and have long-term positive outcomes.

  I think a good example is the introduction of peanut, if we look at the eczema babies the risk is at least 20% for peanut allergy at six months onwards. And if the eczema increases by eight months the chance of having peanut allergies for the very severe eczema is as high as 50, 60%. And so it does vary with age and severity. So there is definitely a window of opportunity. Earlier the better, and these data comes from the NIH sponsored study at Hopkins.

  I think it's really useful information for parents who have a child with eczema and contemplating, or having a second child to know that window of opportunity where we really need to focus. And be careful about exposure through the skin. We've heard the phrase through the skin allergies begin, and I like it because it's easy to remember and I think it is a good rule of thumb that it's really important to have a shored up skin barrier early in life to prevent this exposure of the immune system to allergens that maybe trigger it to overreact.

  If we can improve that skin barrier early in life, maybe in this critical window by treating eczema or by reinforcing the skin barrier, can we prevent perhaps both eczema and food allergy? What does the science tell us about that?

  We all have heard about two studies, very well done studies which basically tried to apply moisturizer early in life in these high risk babies, trying to prevent eczema. We found out that even applying moisturizer early, we were not able to prevent it. So I think the secondary question was food allergy, but I think that's not a hundred percent confirmed. The moisturizer leads to more food allergy or less food allergy.

  Dr. Hui, I know this is what you're in part studying with the SEAL study. 

  SEAL is a study looking at emollients and topical steroids on the skin barrier intervening early in life and seeing if that does prevent food allergy and eczema.

  In this study, the infants are randomized to three different arms. Two are proactive and one's reactive. And so in the proactive arms, either they receive Aveeno emollient cream plus a topical steroid or a trilipid cream plus topical steroids, or the reactive arm is just standard of care. Once they have an eczema lesion they get evaluated by their pediatrician. What we're doing is enrolling infants up to three months of age. intervening as soon as possible once they have any sort of dryness on the skin or eczema but before they have a chance to develop allergies. So it doesn't necessarily have to be eczema. If their parent has noticed dry skin, or their doctors, they can enroll. And so in this study, they're getting both the hydrating factors of two different types of emollients. A trilipid based EpiCeram, um, or an Aveeno based cream plus the topical steroids that they apply regularly to the skin. 

  And I mean, we're excited about it because I think, just to see: Is it the type of compound that you're using early in life that could prevent allergies? 

  And I think it's a really valuable study, given, actually, some preliminary findings from your colleague and the pilot study phase, which did find a difference between different types of moisturizers.

  So it raises the question. Could it be in those earlier trials that involved early moisturization of kids with eczema to prevent food allergies? Was the right moisturizer being used? And is that sort of critical here? I think the other question that maybe not entirely sure of yet is the actual application practices of the parent may matter.

  We talked about peanut dust in the home or dust mites in the home. If you're applying moisturizer to a baby’s skin and introducing those things and the application process: might that also be a problem for Staph aureus or some of these other things that we know are associated with eczema.

  So I think those are some unanswered questions as we pursue moisturizer therapy as an intervention, but for sure, it's an interesting approach and makes logical sense if the problem is a compromised skin barrier, shoring it up should indeed prevent food allergies. So I think we're really excited to see the results of that trial as it progresses.

  Yes. And, just applying moisturizer or steroids is fairly benign. And so if it turns out that doing this can be a preventative measure, that would be huge for the field. Because we do it all the time. And so that would be very exciting, right?

  Not knowing if it prevents eczema (a), but there's also a treatment piece here because, as a parent of a child with moderate to severe eczema who developed an infancy. I'm putting moisturizer and cream on a tiny body several times a day. And in fact, we don't know which one is likely to help or perhaps make the eczema worse. We don't have that basic question answered. So hopefully there'll be some insights on that question as well from the field trial. So I think your study, the addition of the anti-inflammatory, whether it's proactive or reactive makes a lot of sense.

  And I think it will add to our knowledge on the studies that have failed. 

  I agree. Yeah. That's, the hard part is, you have positive studies, you have negative studies, but there's always a factor in there where maybe it wasn't the complete picture. And Korey, as you mentioned, yeah, if a mom eats a peanut butter sandwich and then applies cream on their chest, potentially she's introducing peanut allergan through a broken skin barrier. So those are all important factors to consider. 

  Yeah, it's really interesting to look at combinations of treatments as well, because I think we were all very excited when the initial studies came out. The really small ones that show such encouraging results and everyone was all about moisturizing early and everything. And then we did not really expect the larger studies to be negative. So I'm excited about the SEAL study. I look forward to the results. I think we'll learn a lot from it. 

  Can you talk a little bit about the timeline for that one? I think you're still in the recruiting phase, but when might we start to see some results?

  Yeah, we're still in the recruiting phase. Some of the kids are past six months old. We follow them through age three. And so part of the protocol also includes, double blind, placebo controlled oral food challenges, things like that to actually look at the endpoint of, is there a decrease in food allergy?

  It'll be at least a handful of years before our last enrollee turns three. But I'm sure we will have interim news, even as some of our subjects turn one. 

  Yeah, it's really cutting edge work. And I think it's exciting, given the size of the trial, I wanted to pivot a little bit and ask you Dr. Anagnostou, to talk a little bit about the relationship between the gut and allergic diseases. And this is also a really exciting area because we know that the gut microbiome is imbalanced in people with eczema and food allergy and small pilot studies have suggested that fecal microbiota transplant may offer benefits for these conditions. Very intriguing. What are the most promising strategies for addressing the gut microbiome imbalance and atopic conditions. And could we possibly prevent both conditions through this type of strategy of addressing the gut microbes?

  Yeah, this is an excellent question. And you're right, Korey, we have those same studies showing microbiome dysbiosis in subjects that either developed food allergies in future, or already have food allergy. So there is definitely an imbalance there, and generally you tend to lose your good bacteria that help the immune system of the body go towards tolerance. And then you develop a number of others that you don't really want to have. 

  So it does make sense that if you replace your dysbiotic microbiome with a healthy microbiome, you could potentially reverse that process if you are talking about prevention and early life intervention, or you could cure it, as a form of therapy and they have been some small studies that have looked at different ways of doing this one, as you mentioned, is the fecal microbiota transplant. 

  We all know that this is a therapy that has been used for a very long time. And it's very highly efficacious and has also been used in a small, recent study in infants with allergic colitis and it successfully induced remission. in those infants. And very recently there is this very exciting study that Dr. Rachid has initiated where she took 10 healthy adults with peanut allergy. And gave them all fecal microbiota transplant in the form of a pill, to replenish their microbiome with good bacteria. At the beginning before they received any therapy, they were all reacting to levels less than about half a peanut. And then they would test it one month and four months after treatment.

  And now they were reacting to much higher levels anywhere between one to four peanuts. So their threshold of reactivity, as we call it, has definitely increased just with this single intervention. Which is obviously very exciting and we're looking forward to the end results. but also important is that this intervention appears to be safe.

  So they were no adverse allergic reactions, no anaphylaxis, no significant concerns. I believe some of the subjects had some sort of gastrointestinal type symptoms, like maybe nausea or some diarrhea at something like this, but nothing major that would tell us to stop trying this type of intervention.

  And I'm sure that larger studies will come through looking at other food allergies as well, not just peanut. 

  There was a study that came out last year looking at fecal microbiota transplant for atopic dermatitis as well. And it was a study in mice. So it was not in humans yet, but also very intriguing large effect size with the mice and also long-term rebalancing of the immune system was one of the key findings.

  So I think this is a really intriguing area for both conditions and potentially something that might lead to prevention or cure down the road something, for sure, to watch. 

  There's also been a lot of discussion about pre and probiotics and mixture pre and post biotics, also called symbiotic. So just to define these things probiotics are live bacteria, that, that are good for you. And they can be given as a supplement. There've been a few sort of small studies again that have added probiotics and formula milk, given it to infants with good results and outcomes. 

  Prebiotics the same. Studies have looked into the addition of prebiotics into the diets and they have shown some good results. 

  The only issue with those studies is, there are small and there are few. We need again, larger studies in order to make recommendations. So I often get asked in my clinic . Should I be giving my infant pre or probiotics or a mixture? And all I can tell them is that we don't have a firm recommendation right now because we're lacking data on the subject, but it doesn't look like any of these additions would do any harm, so I just cannot really say. because we're just not there yet. 

  Thank you for that overview. I think this is a question of very high interest to parents. We hear about this all the time. And one of the key questions that I think needs to be answered is which strains are helpful at what dose? 

  There are some different species that have already been identified as being protective in a way like bifidobacteria and lactobacilli. And those have been used as well in the studies with formula supplementation. It's really interesting. How many questions we still have about this area: What dose, what species, could it be that we actually need different species for different populations? Because it is highly likely that different geographical regions have different prevalencevin human microbiome. So I think we do need larger studies and we need them from many different areas of the world, not just one, in order to be able to make more from recommendations in the future. 

  The reason of the importance of the strains is because these bacteria, they work different. Some strains, they benefit the patients by just modifying the immune system while other strains, they actually kill the bad bacteria. So the way they work and the mechanism is also different.

  Yes. And thank you for that comment, I can well appreciate the complexity of trying to figure this out with the wild west nature of the microbiome and all the different strains, doing different things. Sometimes helping each other, sometimes fighting each other. It's an exceedingly complex field that I think we're just on the edge of starting to understand so more to come there and some intriguing findings. I think. In the area of atopic dermatitis. We're also interested in topical probiotic therapy. In ways that you can rebalance the skin by using topical medications. So that's another area. I think that's exciting and intriguing.

  I wanted to switch gears and ask about this interesting relationship between atopic dermatitis and Staph aureus bacteria colonization and food allergy.

  And so Dr. Hui, I wondered, I wondered if you could talk about your research that found an association between eczema, fall birth and Staph aureus colonization and food allergy. Walk us through that study and what are the implications for this topic, which is eczema and food allergy prevention.

  And yeah, you're right. There's a lot of literature out there about Staph aureus and eczema and food allergy. Even saying that Staph aureus colonization precede some of these atopic conditions. And so we know Staph aureus disrupts the skin barrier. It's associated with severity of eczema associated with food allergy. And there are other studies saying there's a higher risk of eczema and food allergy in children born in the fall and winter months. And so what I wanted to do was examine this phenomenon further while also including the rest of the atopic march. 

   I also looked at Staph aureus skin colonization. And so we found that those children with skin cultures, positive for Staph aureus had a higher prevalence of fall and winter birth especially the fall. The thought, though, is that Staph aureus skin colonization can magnify this phenomenon of fall and winter birth association potentially leading towards progression along the atopic march.

  There's a lot of details we still don't know. For example, if we treated Staph aureus in infancy, does this prevent atopy? There's a lot we do know about Staph aureus, but a lot that we don't know. So I think Staph aureus colonization is a factor associated with severity and progression of atopy among many other factors. So, if we treat it, what happens? It will be interesting to see. 

  Yeah. Another, I think, intriguing line of inquiry and Dr. Ong, you did some of the groundbreaking work on this area, what are your thoughts on the relationship between Staph aureus, eczema and progression to food allergy?

  The studies done at National Jewish is very groundbreaking. It's very interesting that they looked at the, eczema patient with food allergy versus those without food allergy. And they were able to show that those with food allergy actually had increased Staph aureus. So that's a very important finding. It does suggest that these bacteria do contribute to the food allergy development. So I think the issue is too complex at this time because we also dealing with the good bacteria and bacteria like Staph aureus. So the interaction, and then with the immune system. And I think this is a very exciting area that we can target in terms of preventing food allergy in the future. 

  Yes. I agree with that and I think there's a lot of options here. I think in the past we've been stuck on the idea of killing the Staph with antibiotic therapy or whatnot, but in this new era we're looking at how we can manipulate different strains to crowd out the Staph or amplify good bacteria. And so I think there's new tools in the toolbox that we're developing that are beyond just using, say an antibiotic to kill Staph when we know there's interplay here that's more complex. And that approach alone is unlikely to be sufficient. Cause we do see in especially children with Staph colonization that unless the microbiome is replenished, the Staph will just hide out and come back. So it's a really  an interesting area, I think, at the intersection of dermatology, allergy, immunology, and microbiology and certainly something that our group is very interested in, 

  I'll also add that treatment of atopic dermatitis with topical corticosteroids that has also been shown to decrease Staph aureus colonization in patients with eczema. So it is important to do your standard care for your skin, hydration of the skin, using the proper medications and all that. ‘Cause topical corticosteroids, in addition to being anti-inflammatory can also decrease the Staph aureus colonization. 

  And why do you think that is? Is it just about shoring up the skin barrier so that it's a less hospitable environment for Staph? Because we also see that happening with the new biologics, like Dupixent, they've been shown to actually reduce the presence of Staph and to rebalance the microbiome of the skin. So it's interesting, like, treating the underlying inflammation seems to rebalance the microbiome. I've always been curious about. 

  In eczema, the inflammation actually increased the risk of the Staph aureus colonization. So that's why it’s so important to decrease that inflammation in order to decrease the Staph.

  Yes, that picture is starting to emerge um really treating the underlying inflammation and the eczema as a key strategy to also addressing the microbiome imbalance. All of you do interesting research on this topic or adjacent topics, I wanted to ask: What's the most exciting research going on right now related to eczema and food allergies prevention. And what can we expect in the future?

  I'm personally very excited about all the early food introduction studies. I know we have a lot of data about peanuts, a little less about egg allergy, but we're also looking now at all the other food allergies. And it's interesting how, when we talked about the window of opportunity before, we see different food allergens, potentially having different windows of opportunity in different times at which we may need to intervene. So for instance we think that milk and egg possibly have an earlier window of intervention for prevention compared to peanuts. I'm really excited about that. I'm most excited about fecal microbiota transplant.

  Actually, I think the idea behind that: Reconstructing your microbiome in a way that it's now beneficial to you is actually very appealing. And I'm really hoping that there will be positive, sort of, outcomes in the future. And this will become a more widespread type of therapy. 

  Yes. And I think one thing that's promising about that line of research is the opportunity for prevention and also treatment and long-term remission for some of these conditions as well. So both really interesting for the early food introduction. I know we have some work to do to get parents comfortable with that. Certainly there's still probably some anxiety around introducing allergenic foods early in life and fear of a reaction. But I know that there's good guidelines around that. And a lot of help for parents who are interested in pursuing that. Dr. Ong, or Dr. Hui, any comments on exciting areas of research?

  Yeah think the microbiome area is very interesting. So if we can improve the microbiome of the skin, why is that important? Because the skin, now we know it's the organ of sensitization. So can we improve the barrier, decrease the inflammation. And the question is how do we do that? Whether it's anti-inflammatory treatment, which sometimes can be problem because some of these anti-inflammatory medications have side effects. But the micro-biome, if we can modify the information by doing that without much side effects, I think that would be very exciting.

  Yeah, and very exciting, I think for young children and parents of young children, who have huge concerns about safety. So I really appreciate that comment. Our organization just did a survey on treatment decision-making among parents of children with a atopic dermatitis, generally more severe atopic dermatitis, and this question of safety risk is really at the top of the pile in terms of concerns and considerations. Dr. Hui, could you talk about the Sunbeam trial, which I think is so fascinating. 

  Yeah., Sunbeam is another early life study, an observational study, so there's really no interventions or treatments. We enroll pregnant women and then follow babies from birth through age 3. And, the fathers are also able to participate in this study. And the goal is to really identify prenatal and early life markers of high risk for food allergy and eczema. And so there's questionnaires, biological samples, environmental samples, like skin swabs, collecting water from the home. And then we also perform skin prick testing to allergenic foods and environmental allergens. We'll then look and see which children develop eczema, food allergies, wheezing, environmental allergies... And really the goal is to identify what markers in early life are there for allergy.

  And I think this is important because we can see what sorts of prevention strategies we can then implement, there's several sites across the country. And ultimately there will be 2,500 mom and baby peers enrolled. And so we'll be able to learn quite a lot from this. We'll be able to really data mine and understand, why development of eczema, why development of food allergy occurs. 

  Yes. And for our listeners on the podcast, it's a huge opportunity I think, to contribute to science. It's the nurses' health study for infants, I think we'll learn so much from this longitudinal study. That's really looking at the origins of allergic diseases and taking a really thorough, systems biology approach to it, but so exciting. So five years from now, we are going to have huge leaps in our understanding of these conditions and really hats off to the researchers that are pursuing this. It's what's needed right now. 

  I think parents are constantly asking the why. Like why the severe asthma, why the allergy? And we can start to answer it with this extremely thorough approach that's being proposed. Thank you. 

  Yeah, I think these environmental studies like Sunbeam are extremely valuable and sometimes we forget how simple interventions can make a significant difference. So we're all familiar with the hygiene hypothesis that basically says that we have seen such an increase in allergic diseases over the last few decades, because our way of life has changed so much. We no longer live in farms. We've moved to urban environments, we live in more sterile environments. We use more antibiotics, more harsh chemicals, our diet has changed, we use a lot of processed food now, a lot of high fat sort of food. And sometimes it is just those little things that we could potentially do to help ourselves and our children, like for instance eating a healthy high fiber diet. Now we know that certain bacteria, since I was talking about the gut before, can ferment fiber, and they can turn it into what we call short chain fatty acids. And these are substances that will guide the immune system towards low allergenic response to foods rather than allergy. So simple interventions like this potentially limiting unnecessary use of antibiotics, limiting use of harsh chemicals, et cetera, et cetera. So I think sometimes part of the answer at least lies in simple measures. It's not the whole answer. And of course we need a lot of research to understand the complexity behind the causes of allergic disease but I still think that sometimes we forget simple interventions that may actually make it better. 

  Yeah, thank you for that. And I think, in addition, there may not be one big thing. It could be a bunch of little things that are additive in a critical window to be able to know what those things are and to target them together. Like it could be exposure to antibiotics, plus, air pollution is compromising the skin barrier plus skin product use, et cetera, et cetera. And so really understanding the relative risk of these different things and knowing that critical time periods for preventing exposure could be the answer.

  And hopefully we'll find that out soon. 

  This has been a fascinating discussion. Thank you everybody for being part of this panel today. I think we touched on a lot of really intriguing ideas and it's a hopeful picture, I think for eczema and food allergy prevention. Thanks to the excellent work that is going on in your labs and with collaborators and researchers across the country.

  So thank you everyone for joining us today and listening to this session at the 2022 Food Allergy Fund Summit.