Episode transcript
Time stamps
01:18: Hypotheses on Allergy Development
05:38: Prevalence of Food Allergies in Children and Adults
08:36: Concept of “Outgrowing” Food Allergies
08:46: Importance of Accurate Allergy Diagnosis
11:04: Food Allergy Tolerance Development in Children
12:55: Importance of Reevaluating Teenagers for Allergies
14:52: Food Allergy Tolerance in Adults
16:00: Respiratory Allergy Tolerance in Children and Adults
17:31: Indoor Allergens and Tolerance
18:06: “Thanksgiving” Effect Explained
18:48: Recap of Allergy Development and Tolerance
19:04: Respiratory Allergies in Older Adults
19:55: Importance of Allergy Workup in Older Adults
20:39: Allergic Triggers in COPD Patients
21:09: Summary and Key Takeaways
Announcer:
ImmunoCAST is brought to you by Thermo Fisher Scientific creators of ImmunoCAP™ Specific IgE diagnostics and Phadia™ Laboratory Systems.
Gary Falcettano:
I'm Gary Falcettano, a licensed and board-certified PA with over 12 years experience in allergy and immunology.
Luke Lemons:
I'm Luke Lemons with over six years experience writing for healthcare providers and educating on allergies. You're listening to ImmunoCAST, your source for medically and scientifically-backed allergy insights. On this episode of ImmunoCAST, we're going to be talking about how allergies develop over time and potentially how they resolve. It's well known that allergies change over time, and so Gary and I want to take a deeper dive into how being aware of the way in which they do this can help healthcare providers provide patients with the most up-to-date diagnosis.
Gary Falcettano:
Yeah, Luke, the debate of regarding the underlying etiology of food allergy and continues to evolve. But we do know the body's responses to specific allergens are known to change over time with both food and environmental allergens emerging and resolving at every life stage.
Luke Lemons:
So why don't we start with how somebody may become allergic? There's a few different hypotheses and theories out there, because the truth is there's not one answer on why somebody becomes allergic.
Gary Falcettano:
I think the current thinking is, as you said, it's probably not any one of these in particular, but certainly a combination. The top three though are, and we've discussed these in the past, at least some of them, the epithelial barrier hypothesis, the barrier disruption hypothesis, the hygiene hypothesis, and the microbiome hypothesis. Why don't you remind our listeners look a little bit about the epithelial barrier dysfunction hypothesis?
Luke Lemons:
Yeah, so when we look at the epithelial layer, whether it's in our skin or in the gut or in the lungs, if that barrier is damaged or irritated, it's easier for allergens to penetrate through and set off an immune cascade. So this could be in the form of atopic dermatitis, for example, in a young child through the skin, they may be exposed to allergens more and develop a sensitization and later an allergy.
Gary Falcettano:
Exactly. And if we think back to our climate change in allergy episode, we discussed how pollutants can actually disrupt the epithelial barrier.
Luke Lemons:
It's so interesting that through pollution, somebody may become more allergic because they, let's say, just grew up in an environment where there's a lot of smog around them. Looking at the hygiene hypothesis, again, the environment affecting the way in which somebody is exposed, this is a theory in which the immune system becomes overactive because it's not reacting to as many pathogens as it normally would. So as somebody who's maybe in a very sterile environment.
Gary Falcettano:
This hygiene hypothesis has been around really since 1960s, but it continues to be a pretty relevant explanation of why there are increase in allergies, whether that be because of less exposure to microbes in the dirt, children playing outside. There's been studies that looked at genetically identical populations that one was a farming community and the other from a more suburban environment and the farming community children seem to be considerably protected from development of allergy.
Luke Lemons:
Even just with family members and bodies around children growing up with older siblings have a lower incidence of allergic diseases compared to those with smaller family, maybe most likely due to the early exposure to microbes from everyone else in the household at the time.
Gary Falcettano:
It's about challenging the immune system. If it's not being challenged, it tends to go off the rails and start attacking things that it normally wouldn't attack like peanuts or pollens.
Luke Lemons:
And the third hypothesis is the microbiome hypothesis in which the microbes in our everyday life and in our gut and everywhere affect the way in which we develop diseases.
Gary Falcettano:
This comes down to really dysregulation or what is known as gut dysbiosis, a change in the natural healthy biome when we're talking about food allergy in the gut, which seems to precede the development and manifestations of atopic disease.
Luke Lemons:
Antibiotics might play a role in that as well. If a patient is on a lot of antibiotics, the microbiome that would otherwise maybe help them from developing an allergic disease could be destroyed and they may be more susceptible.
Gary Falcettano:
It definitely gets disrupted. And the more antibiotics of patient or child is exposed to, the more likely that that microbiome is going to change from one that contains a healthy distribution of bacteria to one that has an overgrowth of certain potentially disruptive pathogens.
Luke Lemons:
And it's not just the microbiome, right? It's actually the nasal microbiome too. I never really thought about it, but it makes sense. Yeah, of course. We have a microbiome.
Gary Falcettano:
Of course. I mean, we have microbiomes on our skin, mucous membranes, obviously in the gut. We came across this when we were doing some research for today's episode. There was a paper by Chung and Colleagues that was published in Jackie, one of the preeminent allergy journals in 2021. In this paper, they actually discussed the nasal microbiome and how it related to the development of pet allergy.
Luke Lemons:
They found that if there was a higher abundance of this certain microbe, it was associated with not being sensitized to pet allergens and correlated with a lower expression of inflammatory genes, actually, so the expression of genetics.
Gary Falcettano:
Exactly. So epigenetics and those two bacterium, socorna bacterium and staph epidermis were both associated with an absence of pet sensitization, which I think is really interesting.
Luke Lemons:
I can't wait to learn more as we continue to understand the microbiome and it's a relationship. But now that we've gone through the ways in which maybe patients are developing allergic diseases, why don't we talk a little bit about the prevalence, Gary?
Gary Falcettano:
Yeah. We know the prevalence of say food allergy in children is around 11% with the most common allergens in young children to be milk, egg, wheat, and soy. And then when we look at adults, that number's around 8%.
Luke Lemons:
And of the adults that do have a food allergy out there, about a quarter, 25% of them developed that allergy during adulthood.
Gary Falcettano:
We typically think of food allergy as a childhood disease and maybe adult food allergy as a continuation of that childhood disease. But what you're saying is a quarter of adults with food allergy developed it as adults?
Luke Lemons:
Yes. Yes. Actually, of adults who did have a food allergy when they were younger, they ended up developing another food allergy as an adult. So being an adult doesn't make you safe from developing a food allergy. We see it quite often here.
Gary Falcettano:
That's an important take home for sure. And I think that number was, it was close to 50%, right, of adults with food allergies since children developed another one in adulthood.
Luke Lemons:
Yeah, and there's a few theories on why that might be. One of them is that adults are exposed to a lot more co-factors than children that could lead to allergic sensitization like alcohol or we talked in the past episode about exercise and how that may induce anaphylaxis sometimes.
Gary Falcettano:
Sure. And even hormonal influence, right? Medical changes, et cetera.
Luke Lemons:
And when it comes to the most common allergens for adults, it's really shellfish, milk, peanut, tree nut, and fish. Those are the top five there Again, it may be that a child isn't eating a lot of shellfish as a kid, you're not giving your kid a lobster roll. You're giving them scrambled eggs. So a lot of people when they first start eating shellfish, it's one of the first times they're sensitized and then later develop an allergic.
Gary Falcettano:
Exactly. And I think we've seen that it definitely differs in different populations, right? In certain geographic populations where fish is part of the diet earlier on, we tend to see more fish and shellfish allergy in children.
Luke Lemons:
We also are seeing that too right now in America, I believe it's sesame, right? There's a rise of sesame allergy. And part of the theory there is that our diets have expanded and a lot more people are eating sesame at a younger age than ever before.
Gary Falcettano:
Yeah, absolutely. So allergies change over the lifespan for lots of reasons. And some of that is just new exposures.
Luke Lemons:
And looking at respiratory allergy, we see that there's a prevalence for rhinitis. 30% of adults have it, 40% of children, it's actually the fifth most prevalent chronic disease. And so those numbers are very close, but it's still a majority of Americans have some sort of allergy, whether it's food or respiratory.
Gary Falcettano:
Absolutely. And when we talk about respiratory allergy, we also to can't forget about allergic asthma. We know that about 25 million Americans have asthma and 60 to 90%, depending on if you're adults or children have allergic triggers that drive that asthma.
Luke Lemons:
Looking at these allergies, what does it mean to actually outgrow them having a patient who has outgrown an allergy?
Gary Falcettano:
So you know what, before we talk about outgrowing or developing natural tolerance or tolerance to an allergy, I think we really have to talk about is the diagnosis correct to begin with?
Luke Lemons:
That's such a great point because looking at whether somebody had developed a tolerance, had they actually developed a tolerance or were they not initially diagnosed correctly?
Gary Falcettano:
Yeah, there's pitfalls.
Luke Lemons:
There's pitfalls as in everything. Yeah. But have you seen in your experience, Gary, as some pitfalls?
Gary Falcettano:
We can look at it from two different angles, right? One is self-diagnosis. So we often see patients self-diagnose based upon what family members may be saying or what they're reading on the internet. The other side of that is when we get a diagnosis from healthcare providers that maybe it was made based upon empirical basis based upon history alone, and we've talked about this multiple times in previous episodes, but we can't make an allergy diagnosis.
And this is backed up by all of the current guidelines that in order to diagnose allergy, you really need to have a strong clinical history, and then you correlate that with an accurate test of sensitization. And for primary care, that means a blood test because that's the allergen sensitization test that's readily available and used throughout the world.
Luke Lemons:
And then looking at the testing too whole allergens are definitely great, and they have their place within a practice and understanding allergy. However, we've talked under component episodes that some molecular components within whole allergens are maybe less severe for patients. So a patient who gets a peanut whole allergen test when they're younger, they might come back as positive or elevated levels, but we don't know if they're reacting to a molecular component that is less severe and they may be able to actually still eat and tolerate peanuts. So it's also important to consider component resolve diagnostic blood testing as well when looking at that initial diagnosis.
Gary Falcettano:
Absolutely. We know whole allergens, and we've said this before, right, are very sensitive. So when we get a negative whole allergen test, we can be fairly confident that that's not the issue. That whatever we've tested for is not causing the symptoms. But when we get a positive test and the clinical history is not clear, that's where allergen components help us be more precise in the diagnosis and more specific.
Luke Lemons:
Exactly. And so looking at a tolerance than, now let's start with food with children. It's milk, egg, soy in wheat that are the most common ones to outgrow. In milk, we see that by age 12, about 64% of these patients have developed a tolerance for egg. It's about 80% by age 10, soy is 50% of patients by age 7, and then wheat, it's about 66% by age 12 that they've developed tolerance. So that's half if not more for those four allergens.
Gary Falcettano:
Exactly. Definitely a majority of patients will develop tolerance by adolescents. There are certain markers though, within those certain allergen component markers within some of those allergens that can help to predict the development of tolerance. So for instance, we know with milk and egg, the more stable protein, so ovomucoid in egg, casein in milk, especially higher levels of positivity for both of those can be predictive of a more sustained allergy and less opportunity to develop tolerance.
Luke Lemons:
Again, it's like shouting from the roof. It's a component resolved diagnostics when it comes to understanding this stuff. It gives you so much knowledge.
Gary Falcettano:
So much more information. Right, exactly. As we've talked about before, when you have the full picture or at least a more complete picture, it really helps guidance and management decisions be made on a better informed basis. But you know what? Luke, you mentioned milk, egg, soy, and wheat as being the ones that are most likely to develop tolerance. What about the others? Peanuts, tree nuts, fish and shellfish.
Luke Lemons:
So those four that you had mentioned, there's less likelihood in the allergy being resolved with shellfish being the lowest at 4%, developing a tolerance after 10 years. But peanut, tree nut, fish, all of these allergens, if a patient does have a sensitization and allergy to them, they might have that for life.
Gary Falcettano:
And we see anywhere from 15 to 25% potential of developed tolerance with the peanuts, tree nuts and the fish. But that brings us to teenagers. We said most of these, the first four milk, egg, soy, and wheat resolved by adolescents even up to 20% or so of peanuts, tree nuts will also resolve. So that really brings us to the point that it's very important to continue to reevaluate teenagers for their continued allergy. And that's for a couple of reasons.
Luke Lemons:
Yeah, I mean, they're at a point in their life where they have gained freedom. They have a car now, they may be going to college or something like that, and they're about to embark on their life and they need a checkup. They need a checkpoint in their allergy diagnosis to understand did they outgrow that allergy? Do they still have that allergy? Did they not get a great diagnosis when they were younger? Maybe this is a good opportunity to confirm that, "Hey, you don't actually, you never did have an allergy."
So it's important to evaluate this population. There was actually an interesting study we were looking at and of this high risk group of individual teens, 17% of them did not carry their epinephrine and knowingly ingested foods that they had been told to regard as risky. When asked why, they reported that they felt different from their peers.
Gary Falcettano:
I want to seem surprised at this number, but I'm really not. We know that the teenage years are really a time when children start to rebel. They start to have more risk taking behaviors. So I think that really does confirm exactly what you were saying, Luke, that it's really important at this point in their lives to, number one, confirm that they actually do have this and they're at high risk and communicate that to them. And then the flip side of that is if they aren't and we are able to clear their allergy, it allows them to live a little bit less encumbered life and go out into the world with a little more abandon.
Luke Lemons:
So what about adults developing some sort of tolerance for food allergy?
Gary Falcettano:
Yes. So this is also interesting. As we mentioned, we don't typically think of developing food allergy as an adult issue. We're definitely seeing more and more of adult food allergy. As a matter of fact, in one population-based study, they actually surveyed 40,000 adults, so age 18 and older, and 19% of the respondents believed they were food allergic. Interestingly enough, when they actually delved into their symptomatology and were more precise in their history, they actually found that only half of those, or about 10% or so actually had convincing IgE-mediated food allergy symptoms.
Luke Lemons:
And this is why with even adult patients to make sure that they've gotten the correct testing when they were diagnosed originally, and were correctly diagnosed using clinical history as well with the testing.
Gary Falcettano:
Well, for sure. I mean, you mentioned 25% of adults developed a food allergy in adulthood, right? So I think it's so important to confirm what they believe is going on and also identify maybe new food allergies that have developed.
Luke Lemons:
Exactly. And respiratory, I know we've been talking more about food right now, but respiratory tolerance, it's a little bit inversed compared to food because we were saying that children with food allergy, the majority will outgrow depending on the allergen, but here children grow into allergies more.
Gary Falcettano:
Well, they do, and that comes back to the atopic march, and I know we've mentioned this before, but we typically see atopic dermatitis, early food allergy being as some of the symptoms that children experience very early in life. And then as those tend to decrease over time because they're developing tolerances, we see environmental allergens and environmental allergy rhinitis, potentially asthma actually go up as they go through childhood and into adolescence.
Luke Lemons:
Part of this too is because you have to be sensitized and then exposed again to have that immune response. And so children who are born and they experience their first spring with a bunch of pollen, for example, looking at pollen, they're not going to maybe react that first pollen season. But then on the second round of exposure, the next year is when you might see symptoms in young pediatric patients.
Gary Falcettano:
That's exactly right. So when we do in-vitro serological testing, most clinicians will avoid testing for pollens during that first year, 18 months of life because they really haven't been exposed enough to be sensitized and develop allergy. But certainly by the time you hit two years old, and as you get older, the more exposures that you have, the more likely you are to develop a sensitization and potential allergy.
Luke Lemons:
And so what about indoor allergens, Gary?
Gary Falcettano:
Some of the indoor allergens like pets and dust mites and cockroach and mice, if they're in your house, you're exposed to them constantly from birth. So you certainly can develop allergy and sensitizations at a young age. And this is really interesting, some allergic individuals will actually develop tolerance over time with continued exposure. So their symptoms start to decrease over time. And then if they stopped being constantly exposed to that allergic trigger, their symptoms may actually be worse when they're re-exposed to that trigger.
Luke Lemons:
This is called the Thanksgiving effect. Imagine a teen or a young adult going to college. They have a dog, they've grown up with dogs their whole life, and now they go to college and for a year maybe more, they're not exposed to dogs. Maybe their friends don't have dogs, they're in the dorms, no pets allowed. When they come back for Thanksgiving and to their family pet, they actually show more severe symptoms. They've always been allergic in a way, but they came back and they've actually experienced the symptoms.
Gary Falcettano:
Yeah, they've kind of developed a moderate tolerance being constantly exposed. And then when they're not, their immune system reacts a lot more dramatically when they're re-exposed at Thanksgiving. And it's pretty common. This isn't a very isolated thing. It actually happens quite a bit.
Luke Lemons:
And so to recap, with teens and children, we see that they end up gaining more allergies as they get older. And so there's not really that tolerance. But, looking at older adult populations, we do seem some sort of respiratory allergy tolerance developing.
Gary Falcettano:
This is termed an immunosinescence, right? Where the immune system becomes less reactive, less responsive over time. I mean, we see this with, for instance, the high dose influenza vaccines that are required in older populations in order to achieve a similar immune response. As we age, we know the immune system does become a little bit less active, less responsive.
We actually looked at two studies that demonstrated a decrease in allergic sensitizations over time. One looked at Japanese cedar-specific IgE sensitization in two different groups. So in an 18 to 39 age group, and then in the sixty-plus age group. And in the younger age group sensitization was around 30%. That declined to about 10% in the over 60 age group. So definitely a drop in sensitization, but there's still quite a few significant allergic older adults.
Luke Lemons:
And it's important to evaluate these adults too. To your point, we see the immune system not be as active. While that may be something that is bad when it comes to influenza in other disease states with allergies, it's a benefit.
Gary Falcettano:
While these studies and decreased responsiveness of immune system in older adults is encouraging, these studies provide us with some insight into the prevalence of ATP In this group, the authors are clear that it really shouldn't deter us from pursuing appropriate workup for allergic causes in individual patients because we know that the prevalence of allergic diseases, allergic asthma, and even allergic triggers with COPD is certainly something that occurs in this population and really impacts their disease.
Luke Lemons:
Yeah, 30% of patients with COPD have allergic triggers, and that's terrifying, especially at certain ages where a bad pollen season or exposure to a cat or something, a dust mites even could really put them at a high risk.
Gary Falcettano:
I think we don't think about that often, but just like we've talked about on our allergic asthma episodes, there are multiple things that can cause airway inflammation and make symptoms worse, whether they be non-allergic triggers, allergic triggers. When we're talking about COPD, the same actually holds true.
Luke Lemons:
I know we've talked about food allergy, respiratory allergy, prevalence, tolerance. I think the biggest takeaway here is that allergy is not a static disease. That's whether a patient develops a new allergy or whether it's changed over time and they've maybe gained tolerance. Allergy is not just one and done forever.
Gary Falcettano:
Exactly. And the importance of actually confirming that we actually have an allergy too. So we need to know that first before we start evaluating how it changes over time.
Luke Lemons:
Because to the point made earlier, if a patient wasn't accurately diagnosed, then it just muddies the water completely when looking at the best way to manage their disease or if they even have this allergic disease. So that comes with using component-resolved diagnostics to confirm what type of molecular component in a whole allergen they may be allergic to. Looking at history, obviously, clinical history, it's like you said, Gary, all the guidelines say it's clinical history and diagnostic testing. And on those patients who maybe do have a lower risk molecular component, sensitization, a referral for an oral food challenge to maybe show that they can eat an allergen that they maybe thought they were allergic to.
Gary Falcettano:
Exactly. And on the respiratory side, when we're talking about specifically where we do have components like in pet allergy, knowing their risk, right and knowing how likely it is that their allergies are going to change over time and become potentially more severe, like developing asthma after a young child just has rhinitis. That's another way that allergen components really help to give us more information.
Luke Lemons:
Yeah, it's clearing the air on patients who maybe had an unsure diagnosis, patients who are experiencing new symptoms, and then just evaluating, to your point, tolerance over time, I mean, teens, we talked about them. They're about to go into the world and they're going to take the burden of taking care of themselves. It's no longer mom, dad who are taking them to the doctor to visit and do a checkup. They have to take their health into their own hands.
And those older adults too, who may have conditions like COPD and asthma, just evaluating them and making sure that their allergies are under control and that they have the information they need to stay safe because allergies can be impactful to these other comorbid conditions. And for those who are maybe interested in, we mentioned component Resolve diagnostics a few times. We do have a link on this episode's page below this episode on whatever streaming service you're using.
There's a link to this episode's page. We have a lab ordering guide, which has labs in your local area based on zip codes, the most up-to-date lab codes for labs that you use. And we will also have on this page a good patient-facing article. But honestly, it's really good for anybody who wants to continue to learn more about tolerance and its development. It's all around how allergies over time. And it's a good read, and you can find that again by clicking the link below this episode. Thank you for listening to ImmunoCAST, and until next time, don't forget to subscribe and share.
Gary Falcettano:
We'll see you next time.
Luke Lemons:
Bye.
Announcer:
ImmunoCAST is brought to you by Thermo Fisher Scientific, creators of ImmunoCAP Specific IgE Diagnostics and Phadia laboratory systems. For more information on allergies and specific IgE testing, please visit thermofisher.com/immunocast. Specific IgE testing is an aid to healthcare providers in the diagnosis of allergy and cannot alone diagnose a clinical allergy. Clinical history alongside specific IgE testing is needed to diagnose a clinical allergy. The content of this podcast is not intended to be and should not be interpreted as or substitute professional medical advice, diagnosis or treatment. Any medical questions pertaining to one's own health should be discussed with a healthcare provider.
