Episode transcript
Time stamps
0:56 – The importance of the EAACI guidelines.
3:52 – Guideline recommended questions to ask during food allergy history.
3:47 – Asking patients about time and duration of symptoms.
6:04 – Explaining the role of co-factors in allergies.
9:15 – How food preparation may impact reactions.
10:12 – Cross-reactivity between food and pollen or dust mites.
13:07 – Combining food history and diagnostic testing.
14:29 – Diagnosing using testing with allergen components.
20:08 – What to do if there is an unclear diagnosis.
Announcer:
ImmunoCAST is brought to you by Thermo Fisher Scientific, creators of ImmunoCAP™ Specific IgE Diagnostics and Phadia™ Laboratory Systems.
Gary Falcetano:
I'm Gary Falcetano, a licensed PA with over 11 years experience in allergy and immunology.
Luke Lemons:
I'm Luke Lemons with over five years of 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 newsroom episode of ImmunoCAST, Gary and I will be discussing the brand-new guidelines that came out a few months ago from the European Academy of Allergy and Clinical Immunology, or EAACI. These guidelines are around the diagnosis of IgE-mediated food allergy, which honestly, it's a big deal. The last time we had food allergy guidelines here in the U.S. released was 14 years ago.
Gary Falcetano:
Yeah, that's crazy, isn't it? We've had a couple of minor addendums, but we haven't had full guidelines since you had hair, Luke.
Luke Lemons:
Yeah. Yeah. Man, that's a distant memory for me. It's been 10 years for the EU where these guidelines are actually coming from, but even though this isn't an American publication, this paper has authors from people all over the world, including America. Because of this time difference, any food allergy diagnosis guidelines coming out right now is valuable to clinicians.
Gary Falcetano:
Oh, for sure. The authors on this paper are really world-renowned food allergy experts, as you said, from all over the world, including the U.S.
Luke Lemons:
Yeah, and now is the time that we should probably be talking about this. We're seeing the prevalence of allergy increasing over the past two decades. 32 million people in America have food allergies, and there's less than 5,000 allergists out there to help deal with all this. So any clinician that sees a food allergy patient in front of them is going to find some value in this paper.
Gary Falcetano:
Exactly. With those gaps, Luke, it's especially important on primary care providers to really help fill the gaps that are there and really be comfortable in managing and diagnosing food allergy and really knowing when to refer those patients for more specialized care by the allergist.
Luke Lemons:
These guidelines, they're very long. Gary, and I know you're really busy, so we're not going to sit here and just read all the pages of this to you, but we've decided to zero in on two parts of this paper, specifically, the questions that they recommend providers ask patients when they're doing a good structured food allergy history. We're going to be looking at some of the most impactful or maybe overlooked questions that you might have not considered. Then we're going to go into talk about what these guidelines say about the current role of diagnostics as well as where they recommend newer types of diagnostics, hint, hint, allergen components of where that fits in with the food allergy diagnosis.
Gary Falcetano:
For sure. But before we get started, I think it's important too, to discuss how these guidelines came to be. So this wasn't just a bunch of food allergy leaders that got together. They utilized a systematic literature review and a meta-analysis to look at all of the available evidence really for the past 14 years and to make evidence-based recommendations that are very strongly supported by the literature.
Luke Lemons:
Yeah, so this contains everything in the past 14 years, so we're super excited about it, and let's jump in. So looking at all the questions that this guideline presents to providers, Gary, is there any that stuck out as impactful to you, or I guess, set off alarm bells and you're like, ""Oh, my gosh, that's a really interesting thing," that maybe not everyone is asking?
Gary Falcetano:
Yeah, so I think most clinicians are pretty solid when it comes to history-taking. But when it comes to food allergy history, these guidelines really call out a little bit different things to focus on. Let's talk about a few of those. So I think the first thing that really jumps out at me is looking at timing and onset, so the speed of symptom onset and the duration of symptoms after you ingest a suspected food. We know that with IgE-mediated food allergy, this is usually something that happens pretty quickly, within the first few minutes up to two hours after eating a suspected food. If it happens a day later or two days later, that's not typically IgE-mediated. There are always exceptions to the rule. So we know with alpha-gal syndrome, you and I have discussed this in the past, and we'll do a future full episode on it, but that's the delayed red meat allergy, so a delayed reaction. We can see symptoms occurring three six hours, even as long as eight hours after ingestion of a mammalian meat.
Luke Lemons:
So the question they offer up verbatim that they recommend is, "Were the symptoms immediate, usually within a few minutes and up to two hours after eating, three to six hours for alpha-gal allergy, and did the symptoms resolve spontaneously?" That two hours after eating is really important to know. But again, you had mentioned that there's always an exception. Sometimes if the food was eaten within two hours, it may be linked to a cofactor, which is another question they recommend you ask patients about.
Gary Falcetano:
Yeah. So with IgE-mediated allergy, we know that one of the hallmarks is reproducibility., So every time you eat the food, you have those symptoms. But once again, that's not always the case because cofactors can interfere with that. So when we're talking about cofactors, we're talking about things that make you react and have an IgE-mediated reaction to a food only in the presence of cofactors. So you may eat that food without a cofactor, have no symptoms. You eat it in the presence of a cofactor, you have symptoms. Luke, what are some of those cofactors that we talk about?
Luke Lemons:
Yes. So the guidelines, they position it like this. They say you should ask a patient, "Did the reaction only occur when the food was eaten within two hours? Was it linked to exercise, alcohol, aspirin or non-steroidal anti-inflammatory drugs, acid-suppressant medications, sleep deprivation, stress or hormonal factors?" So there's a lot there. There's a lot there.
Gary Falcetano:
There's a lot there. We really don't know all the reasons that cofactors impact how people experience their symptoms to foods they're allergic to. We understand some of them for sure, such as the acid-suppressant medications. We know certain proteins are denatured by stomach acid. So if your stomach acid is suppressed, those proteins will be absorbed intact and you can potentially have a reaction. I think, though, there's a couple of other cofactors that we actually have some diagnostics for. So when it comes to exercise and wheat allergy, there's this syndrome called wheat-dependent, exercise-induced anaphylaxis. Again, just like you were saying, Luke, you exercise within several hours after consuming wheat, you have symptoms. If you don't exercise, patients typically don't have symptoms, and there's a diagnostic for that.
Luke Lemons:
Every single one of these cofactors could be its own episode of ImmunoCAST-
Gary Falcetano:
For sure.
Luke Lemons:
... to dive into, even the alcohol one when it comes to alpha-gal syndrome.
Gary Falcetano:
Yeah. Yeah. We know alcohol certainly is a cofactor with numerous food allergies, but with alpha-gal, there's a strong correlation. We've seen case studies where patients tolerate a mammalian meat or red meat without issue unless they decide to have a glass or two of red wine with that steak and then they have symptoms.
Luke Lemons:
Yeah, and all this is mentioned in the guidelines as well, so it's a really interesting piece of literature. Another question that they highly recommend that you ask is around other atopic diseases that patients might have. So for example, "Are atopic dermatitis, seasonal perineal allergic rhinitis, asthma and urticaria present?"
Gary Falcetano:
Yeah, and this is for a few reasons. We know that allergic diseases, there's this concept of the allergic march, and we typically see highly atopic children present first with atopic dermatitis related to foods and then that progresses to rhinitis and maybe even eventually asthma. So having atopic dermatitis is becoming more and more recognized as a big risk factor for developing food allergy later on. That's because of sensitization through the skin of food allergens that are in the environment.
Luke Lemons:
When it comes to these food allergens, how they are processed as well may affect how a patient is reacting, which leads us to the next that Gary and I thought was really important to mention, which is, was the food raw, cooked or processed, and does tolerance depend on the cooking method? Again, hint hint, this might have to do with allergen components, which is going to be an episode in the next few weeks that you'll be able to see. But yeah, Gary, if you want to talk a little bit about this.
Gary Falcetano:
Yeah, exactly. So, again, we always go back to history. So if a patient can tolerate a food in a cooked form but not in a raw form, that starts leading us to think that this is potentially that they have a sensitization to a protein that actually is denatured by cooking or high heating. We see this with eggs and milk. There's certain proteins there that patients may be able to tolerate if they're denatured by baking and certain proteins that are resistant. So that means they can't tolerate any form of the food. The same thing we see oral allergy syndrome or pollen food allergy syndrome where patients who are sensitized to a pollen will have symptoms in their mouth and upper GI tract when they consume foods that have similar proteins to those pollens, but they get denatured by the stomach and then they don't have symptoms once they've been denatured by stomach acid.
Luke Lemons:
Yeah, and so a patient who's saying, "Oh, I have no problem eating cookies, but I can't drink a glass of milk," well, that should send off some alarm bells that, "Oh, there might be a specific allergen component involved when it comes to the denaturing in the stomach of that protein." You had mentioned pollen and oral allergy syndrome, and when it comes to cross-reactivity, this is another thing that EEACI, the guidelines that they hit home on, is the patient sensitized to pollens, latex or house dust mites? If so, what is the potential for a cross-reactive food allergy?
Gary Falcetano:
Yeah, exactly. As I mentioned previously with the pollens, we know that patients who are sensitized to peanut may only be sensitized to a protein that's similar to a birch tree pollen protein, and that protein can be denatured by stomach acid. So those patients with that type of peanut allergy typically can tolerate peanuts pretty well. Go ahead.
Luke Lemons:
I was going to say, so well, can you tell me about the dust mites then? Why are they talking about cross-reactivity with food allergy and dust mites?
Gary Falcetano:
I knew you wanted to talk about that.
Luke Lemons:
That's my favorite topic.
Gary Falcetano:
Yeah, so there's a protein in dust mites, actually, in cockroaches as well and in shellfish that it's the same in all three of those types of either foods or insects. It's tropomyosin, and it's a really highly conserved protein that, as I said, is found in shellfish, dust mites, cockroach, and it causes cross-reactivity between the three. But sometimes cross-reactivity is insignificant and sometimes it's significant. In the case tropomyosin, it's significant. So if you're sensitized to dust mites and allergic to dust mites and it's because of this tropomyosin protein, if you have a tropomyosin positivity in shellfish as well, it puts you at risk for a fairly severe phenotype of shellfish allergy.
Luke Lemons:
Yeah, I love that bit of information because it just reminds me that the shrimps, they're just bugs of the sea in a weird type of way.
Gary Falcetano:
It's so true. When I practiced in Maine, I used to take care of quite a few lobstermen, and they always refer to their lobsters as bugs.
Luke Lemons:
Oh, man. Well, again, these are just some of the most interesting and maybe overlooked questions that Gary and I think should be drawn to your attention. So when did symptoms start? Was there maybe a cofactor involved? Is there any other disease states contributing to this? How was the food processed? May cross-reactivity with another allergen be involved here? So after clinicians ask these questions, Gary, and they get this structured history and they see a patient where they're thinking it might be an allergy and it's time to test, what do these guidelines say about the role of diagnostic testing after structured history?
Gary Falcetano:
So a lot of what they say is not new at all. It confirms what we know, and we've talked about on this podcast now for multiple times. They really confirm the importance of taking a good structured history, as we just discussed, and combining that with diagnostic testing. You can't really diagnose a food allergy with just history alone or with diagnostic testing alone. You really need to do the two, and you have to base that diagnostic testing on the history. We want to test for those things that we suspect the patient is allergic to.
Luke Lemons:
Yeah, and they outline that the first-line tests are skin prick testing and specific IgE in vitro blood testing. They're both recommended by these guidelines as those first-line tests.
Gary Falcetano:
Exactly. They consider them interchangeable. Just like we've known from other guidelines, other position papers throughout the years, they confirm that they're both first-line tests. They both will accurately document specific IgE sensitization, so the presence of specific IgE to a certain allergen. But as we know, a positive test doesn't always mean someone is clinically allergic, so we really have to combine it with symptoms. Then if there's any questions, we work down the diagnostic paradigm or the diagnostic algorithm.
Luke Lemons:
Speaking of specific IgE in vitro testing, they also recommend allergen-component testing, which is a specific IgE in vitro blood test for tree nuts and peanuts. So Gary, I know that we're going to have an episode down the line all about food allergen components, but can you speak a little bit about tree nuts and peanuts and why they might recommend the components be used?
Gary Falcetano:
So this is really the first time we've had a systematic literature review, meta-analysis that confirms the utility of tree nuts and peanut allergen components as being very clinically useful in the diagnosis. We know there's a lot of other components out there that are being used every day by clinicians to help get to the diagnosis, but to have a large systematic literature review and meta-analysis that confirms at least the components that have been out there for a while, the tree nuts, the peanuts, I think this is really exciting that we have this level of evidence now.
Luke Lemons:
In these components, they just allow providers to get more details around a suspected allergy, so more details around a suspected allergy like hazelnut, cashew, peanut, et cetera, and also... Sorry.
Gary Falcetano:
No, I was just going to say because I really neglected to mention the specific IGE testing for the whole allergens is very good at ruling out. It's a very sensitive test. So when we have a negative, we can be fairly sure that that's not the allergen that's causing the symptoms, but the specificity for whole allergens isn't as good as we'd like it to be. That's where the components come in because they really add specificity to the diagnosis.
Luke Lemons:
You had made the analogy once before when we were talking about pet allergen components that it's like a stew. The whole allergen is the stew, but then the allergen components, or the carrots or the other vegetables in it. So is the patient reacting to the stew as a whole or is it only the carrots in the stew? So this is the value of allergen components, but I want to speak a bit about what you said about ruling out certain allergens. So this is something that the guideline also mentioned, which is ruling out IgE-mediated triggers in food.
Gary Falcetano:
So there's a lot of different causes of adverse reactions to food and IgE-mediated type 1 hypersensitivity is only one part of that. So specific IgE testing, whether that be skin or blood testing, is really good at ruling out whether IgE is playing a role. But there are certainly lots of other things that can cause us to have symptoms. For instance, being lactose intolerant, not having that enzyme that allows us to digest lactose. Caffeine intolerance, there's multiple other things, tyramines and cheeses that can cause symptoms. So once we rule out the most severe types of adverse food reactions to the type 1 hypersensitivity reactions, we can go down a whole path to try to figure out what's causing the patient's symptoms. We love our fun facts, right, Luke?
Luke Lemons:
Yes.
Gary Falcetano:
So there's one type of non-IgE-mediated trigger that I think people will find really interesting, and that's scromboid poisoning.
Luke Lemons:
Scromboid?
Gary Falcetano:
Yeah.
Luke Lemons:
That's a shape, right? It's four sides, a rhomboid?
Gary Falcetano:
A scombroid poisoning is not easy to pronounce. I always want to put an R where it doesn't belong and make it scromboid poisoning, but it's scombroid.
Luke Lemons:
Scombroid, got it.
Gary Falcetano:
Yeah. Scombroid poisoning is actually an adverse reaction to bad fish. So people think they're actually allergic to fish, they're not. They're just having an adverse reaction to a fish that's spoiled. So when fish starts to go bad, and for lack of a better word, starts to decompose a little bit, some of the larger fishes produce histidine. Histidine, when we consume histidine actually gets converted to histamine, which means we show symptoms that look very much like allergy after ingesting bad fish, but it's actually us just converting histidine to histamine and showing all those histamine-like symptoms.
Luke Lemons:
It's so interesting because it's not an IgE-mediated reaction, but you still get the same thing that causes those reactions, which is histamine.
Gary Falcetano:
Exactly.
Luke Lemons:
But it's just like a metabolic or a different way of our body making it. Another thing that these guidelines mention around food allergy is they talk about food sensitivity testing or IgG testing. So I'm going to let you talk about that a bit, Gary.
Gary Falcetano:
Sure. So we have to make sure we enunciate this as well, right?
Luke Lemons:
Yes.
Gary Falcetano:
So it's IgG, as in Gary, testing. This is not indicated at all, but for the diagnosis of food allergy. So we know IgG is one of the immunoglobulins. It certainly has its uses in medicine, but every major guideline, including this most recent guideline from our European colleagues is very clear that it should not be used. IgG, as in Gary, testing, should not be used for diagnosis of IgE-suspected, IgE-mediated food allergy or food allergy in general.
Luke Lemons:
Yeah, and I like how you said that there's a specific place for IgG testing, just like there's a specific place for HDL testing, but HDL testing doesn't tell you anything about a food allergy. It tells you maybe to stop eating foods with high cholesterol or maybe that you're doing a good job, but it can't be used to diagnose an allergy. Likewise, IgG cannot be used to diagnose an allergy, and so the guidelines just want to make that extremely clear.
Gary Falcetano:
For sure.
Luke Lemons:
Lastly, the guidelines talk about oral food challenge. So they say that a medically-supervised oral food challenge is recommended to confirm or exclude food allergy in patients with an unclear diagnosis despite IgE sensitization tests. So can you talk a bit about what does an unclear diagnosis, Gary, and what does it mean despite IgE sensitization tests?
Gary Falcetano:
Sure. As I mentioned, the whole extract testing is very good at ruling out, but not as great for ruling in because we could definitely see sensitizations without clinical allergy. Once we do whole extract testing. If we have components available for certain allergens, once we look at those to try to increase specificity, oftentimes we still aren't sure, right? The clinical history might be a little cloudy. The testing isn't really showing us by a preponderance of the evidence that we have an allergy or not. So we may need to go to an oral food challenge, which is still considered the gold standard in food allergy diagnosis. That's obviously done in a medically-supervised manner, usually at a specialist's office. That's the way we truly rule out or rule in an allergy when we can't do it any other way.
Luke Lemons:
To recap on these takeaways that the guidelines present around diagnostics, it's combining history with diagnostic testing. Specific IgE in vitro blood testing and skin prick testing are both recommended as first-line tests and are utilized by primary care. Well, at least specific IgE blood testing is utilized by primary care and allergists and specialists alike. They recommend allergen component testing for things like tree nuts and peanuts, and also ruling out IgE-mediated triggers, and then not using IgG, as in Gary, testing, and of course, making sure to refer for an oral food challenge or to conduct an oral food challenge when there is any question on the diagnosis. If you want to read these guidelines, we really recommend that you do. You can click the link in this episode's description to be taken to this episode's web page where we have a bunch of other references related to these topics. We'll actually put the 2010, yes, that's when it came out, the 2010 NIH guidelines around food allergy, as well as these EEACI guidelines on the diagnosis of food allergy and a lab ordering guide if you were interested in ordering testing with allergen components.
Gary Falcetano:
Yeah, I would only add, Luke, great summary of these guidelines. There has been one addendum to the 2010 guidelines, so just to not think that we haven't been doing anything for the last 14 years, and that addendum was around the early introduction of peanut, to prevent peanut allergy. I think we're going to do a future podcast on that, but it just reiterates how important it is to not avoid potentially allergenic foods early in life.
Luke Lemons:
So more on that in the future, but thank you so much for listening to ImmunoCAST today in this newsroom episode. Again, subscribe, share, tune in and keep an eye out for our next episode, which is going to be around cannabis allergy. Thanks, everyone.
Gary Falcetano:
Thanks so much. We'll see you next time.
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.
