Apples, Pollen, and Itchy Mouths: Solving the PFAS Puzzle

“It's important to recognize that fresh fruits and vegetables can cause local reactions in the mouth and gut. But if they're not causing symptoms of a more severe allergic reaction, don't panic. Chances are good that this is not something that's going to lead to more worrisome features.”  -- Dr. Anne Ellis

Dr. Mariam Hanna sits down with Dr. Anne Ellis, professor of medicine and chair of the Division of Allergy and Immunology at Queen's University, to explore the intricacies of Pollen Food Allergy Syndrome (PFAS), also known as Oral Allergy Syndrome. Dr. Ellis, a leading expert in allergic diseases, guides listeners through the complex landscape of PFAS, offering insights into diagnosis, management, and patient care.

On this episode:

Understanding Pollen Food Allergy Syndrome:

Dr. Ellis provides a comprehensive overview of PFAS, explaining how it affects primarily the mouth and tongue but can impact the entire GI tract. She discusses the common allergens associated with PFAS, such as birch pollen, and the cross-reactivity from fruits like apples and tree nuts.

Diagnosis and Misconceptions:

Explore the diagnostic process for PFAS. Dr. Ellis clarifies the difference between PFAS and other food allergies, emphasizing the role of accurate diagnosis through skin tests and serum-specific IgE testing.

Management Strategies:

Learn about effective management strategies for PFAS. Dr. Ellis shares insights on how to reduce symptoms through avoidance of raw fruits and vegetables and the role of immunotherapy in treating underlying environmental allergies.

Patient Care and Red Flags:

Dr. Ellis highlights key aspects of patient history that may indicate more severe allergic reactions, discussing the importance of distinguishing between local symptoms and systemic IgE-mediated reactions.

Advice for Primary Care Providers:

Gain valuable tips for primary care providers on recognizing and managing PFAS. Dr. Ellis emphasizes the significance of a detailed medical history and the reassurance that most PFAS cases do not require an epinephrine auto-injector.

Tune in to this episode for an in-depth discussion on Pollen Food Allergy Syndrome, offering practical advice and expert insights for both healthcare providers and patients.

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The Allergist is produced for CSACI by PodCraft Productions

Transcript

Dr. Mariam Hanna: Hello, I'm Dr. Mariam Hanna, and this is The Allergist, a show that separates myth from medicine, deciphering allergies and understanding the immune system. A patient came in complaining that they were unable to eat a number of different fresh fruits and vegetables. It was one thing one year, but this year, within a few months, one by one, staples in his lunch or the salad at dinner would cause his mouth symptoms. It came as no surprise when he described his environmental allergies spanning the entirety of spring right through until Fall. The link for many is apparent nowadays, but a few years back, it would give me a sort of delight to explain the association of Pollen Food Allergy Syndrome, or Oral Allergy Syndrome, to patients. A marvelous mix-up between one allergen and the next. Novelty aside, the most pertinent discussions in the office for me are, what we can actually do about it. Nearly a decade ago, we talked about getting people to eat a piece of an apple and increase this over time. Sound familiar? An apple a day, as the old saying goes. Today, there's intrigue again in this topic. After all, eating more fruits and vegetables is driven by growing awareness of their health benefits, sustainability, and the rise of plant-based diets. So, enter the allergist, the bridge between this uncomfortable condition and a healthy diet. Here to discuss this fascinating condition is a returning guest to our podcast, Dr. Anne Ellis, who today will help us leap from our last discussion on allergic rhinitis into today's topic, Pollen Food Allergy Syndrome. Allow me to introduce Dr. Ellis. She's a professor of medicine and chair of the Division of Allergy and Immunology at Queen's University. She holds the James H. Day chair in Allergic Diseases and Allergy Research, and is the director of the Environmental Exposure Unit and the Allergy Research Unit at Kingston General Hospital. She's the current president of the Canadian Society of Allergy and Clinical Immunology, and serves on the joint task force for practice parameters representing the American College of Allergy, Asthma, and Immunology. Dr. Ellis, thank you so much for suggesting today's topic, and welcome back to the podcast.

Dr. Anne Ellis: Pleasure to be here.

Dr. Mariam Hanna: All right, let's start with a brief overview of what Pollen Food Allergy Syndrome, or Oral Allergy Syndrome, actually is.

Dr. Anne Ellis: So, thank you. And it's funny because I've been around long enough now that I did use to refer to this as Oral Allergy Syndrome, and it's always been a bit of a misnomer that I'm glad we fixed by the new language around calling it Pollen Food Allergy Syndrome because it's something that affects primarily the mouth and tongue, etcetera, but really can affect the entire GI tract. So referring to it as just Oral Allergy Syndrome was doing a disservice to our patients who have symptoms from, pardon the phrase, mouth to anus, which can happen for some patients. Others, it is just that local mouth itching that you experience. Usually, when eating fresh fruits or vegetables that are known to cross-react with common environmental allergens. By far the most prevalent is when you're allergic to birch pollen. That particular antigen has a lot of things that are shared in common. They're plant defense proteins. So you can think of it as the birch tree wants to fight off infections from certain infestations. So do tree fruits, such as apple and all the pitted fruits. That's by far the most common presentation that I see, but you can also see birch pollen cross-reactivity with tree nuts, which is when things can really get complicated. Because when people have an itchy mouth after eating almonds, for example, they may be worried that they're at risk for a more severe systemic reaction when really all they are is just allergic to birch. We also see this with patients who have ragweed allergy, which tends to cross-react with the melon family. Grass actually has its own set of things that cross-reacts to, potato being the most common. But the main theme between all of these is you can eat the fruit or vegetable when it is cooked, and you've denatured the proteins within it, but you don't do well with it when it's raw. So it's a classic presentation. When people say, I can eat applesauce or apple pie, but I cannot have a fresh apple, and then we skin test them, we find out indeed they are allergic to birch, and that's how we make the diagnosis. And we can reassure these patients that they're not actually at risk of anaphylaxis at all. They just need to avoid the fresh versions of their culprit fruits or vegetables.

Dr. Mariam Hanna: Okay, let's dig into a couple parts of this. What proportion of our allergic rhinitis patients actually go on to develop this syndrome? Because it's not all of them.

Dr. Anne Ellis: Correct. We don't have great statistics about this. So I can only speak to my personal experience from my practice. I would hazard a guess it's no more than ten to twenty percent. And that's probably on the higher end because of the referral bias for people being sent to me for concerns about actual food allergy, as opposed to just nuisance symptoms that patients don't even bother talking to their family doctor about. We're actually about to publish at this upcoming CSACI meeting, an abstract that's still in press that gives you a sense of a random sampling of 293 patients who are identified as having positive skin tests to various environmental allergens. But it's definitely not the majority of people by a long shot. Yeah.

Dr. Mariam Hanna: Okay, so can you have the reverse? Can you have pollen food allergy and no positive skin test, no allergic rhinitis to be found?

Dr. Anne Ellis: I do see this from time to time, and I'm at a loss to explain it, but it's more on the rare side. Like, I actually... The symptoms are classic. I can eat it raw, but I can't eat it cooked. Their skin tests are negative. I'm lucky enough to be in an academic institution where the hospital is actually willing to cover the cost of serum-specific IgE. So I'll actually go down that route of just triple checking that there's no serum-specific IgE to birch, grass, or ragweed. I'd say it's by far the minority, but I have seen it where I'm like, I don't understand why you're not allergic to something environmental because your history is classic.

Dr. Mariam Hanna: Right. And then, I also will see extremes of age, like in an infant, where I don't expect that they're pollen sensitized at this point. Would you describe that as a possible condition?

Dr. Anne Ellis: So infants are difficult, right? Because you can't get the history out of them, really. So if you've got... And infants tend to get a lot of local reactions to fresh fruits around the mouth generally, but especially strawberries, for example, which is not actually associated with Pollen Food Syndrome. But I do make sure that if any infant has had perioral reactions, let's just try and skin test them to the food of concern. It's negative. Let's just try to make sure that the food goes well into the mouth and there is no around the mouth contact, because you do see irritant dermatitis in that population. As they get older and they're able to verbalize more what their actual symptoms are, you can get a little bit further down into the depths of the reaction, but it is challenging in the toddler age and lower. And I don't see this, generally speaking, as a new problem when you're over 50. So it's usually something that manifests after you're well established into your allergic rhinitis history, then these other things start to come up if they're going to come up at all.

Dr. Mariam Hanna: Are there any parts of the history that are red flags for you when you're talking to a patient that has Pollen Food Allergy Syndrome? You said some fruits don't make sense, so strawberries, for example, don't make sense. So that's probably something else. But are there any other more concerning symptoms that you're looking for? Red flags, outliers.

Dr. Anne Ellis: Yeah. I'm always screening for symptoms that make me more concerned for a systemic IgE-mediated reaction. So I've already alluded to the fact that we don't call it Oral Allergy Syndrome anymore because it can affect the entire GI tract. Very few patients will actually be at risk for anaphylaxis if it's truly just Pollen Food Allergy Syndrome. But if they have had a history of clearly systemic reactivity, hives, angioedema, shortness of breath, decreased level of consciousness, all the things we think of as being typical for anaphylaxis. I will spend a lot more time delving into the diagnostic possibilities when, if a skin test is negative to the fruit, positive to birch, for example, I pursue the specific IgE testing, I will go into doing component-resolved diagnostics for the tree nuts and peanut in particular just to be more confident that this is actually truly just a bad Pollen Food Allergy Syndrome, as opposed to straight up,nope, you have a significant allergy to fill in the blank. And you need to carry an EpiPen and do the usual measures that we'd recommend to all of our patients for outpatient management of anaphylaxis.

Dr. Mariam Hanna: You've mentioned a little bit on the diagnostics already, right? So we're testing for aeroallergens and potentially doing some blood work or serum-specific IgE to some foods. What about the role of fresh food skin prick testing or food skin prick testing with these kinds of classic stories?

Dr. Anne Ellis: Yeah, and I think that's really the backbone for community allergists. These fruit extracts are expensive to keep on hand if you're not seeing this type of problem on a routine basis. Again, I'm blessed by being in an academic center where we do have a good panel of fruits and vegetables on our tray if we choose to order them. But that's what my community colleagues do, is they actually say in their letter, saying, here's your appointment. By the way, if your problem is you're worried about a food allergy, bring a little piece of the food you're concerned about with youso they can do the fresh prick testing, which is actually more sensitive than the extracts that we use as a first screen. So, again, I'm lucky I get to do the extracts first. If it's negative, but I'm suspicious, I will bring people back and ask them to bring... This history sounds so convincing for pear, for example, come back and bring a little piece of pear with you. We'll do fresh testing. Very commonly done, and a very safe procedure when we were talking about fruits and vegetables, different discussion. If you're asking me about shrimp allergy, for example, but we're not talking about that today.

Dr. Mariam Hanna: No side issue. We're going to leave that one alone. Yeah, if they have a positive skin test, but have not had any systemic symptoms and just have classic Pollen Food Allergy Syndrome, how is that changing our management with a positive fresh food skin test, for example?

Dr. Anne Ellis: So I think it doesn't change our recommendations too much, because we always will just recommend avoiding eating the raw version of it. But it helps to make everybody confident in the diagnosis generally. So, look, you've got a positive test to birch. You have reacted to fresh apple, but not to the extract. We've got the diagnosis. You don't have to worry about having anaphylaxis, because the risk of anaphylaxis from Pollen Food Allergy Syndrome is somewhere between one to two percent at best, or at worst, if you want to phrase it that way. But it just helps to make everybody comfortable that we've got the right diagnosis and everybody can walk away knowing exactly what the problem is.

Dr. Mariam Hanna: How strict are avoidance measures necessary for patients that have Pollen Food Allergy Syndrome? Can they have cross-contamination in their salad? Can they pick out the vegetable they don't want to eat? What is that all about?

Dr. Anne Ellis: Absolutely. I mean, again, like I said, the risk of actual anaphylaxis or systemic reaction is so low, you'll be having an itchy mouth if you accidentally eat something that is driving your Pollen Food Allergy Syndrome. I mean, if the history is one where symptoms are more impressive and severe, then I'll caution people to pay a little bit more attention and actually report that food allergy to restaurants, for example, because it's not hard to take pineapple out of a salad, for example. But again, when the risk of a systemic reaction is so low, I just tell people, avoid it or make sure it's cooked. And, for the most part, that manages ninety-nine percent of my patients.

Dr. Mariam Hanna: Okay, that works. Are there any particular medications that patients carry on hand? If we're not prescribing an epinephrine auto-injector, do you routinely get them to carry an antihistamine, as an example?

Dr. Anne Ellis: Yeah, I don't necessarily recommend it, but it's certainly an easy, safe intervention. And again, when it comes to sudden onset symptoms, where it's local to the mouth or throat, I'm a big fan, even in adults, of using the suspensions we have available for second-generation antihistamines. It's a bit of a sidebar, but, you know, a liquid version of a second-generation antihistamine works so fast to resolve local symptoms from sublingual immunotherapy tablets. It's what I've been doing now with patients who have any kind of local reactivity, where I know they don't actually need to use an epinephrine auto-injector, but they're uncomfortable. It does seem to kick in faster just because it's a suspension, it’s treating things locally, it's being absorbed faster. It's an option anyway for things to consider. But again, it's not mandatory if you don't have a history of severe reactivity in the past.

Dr. Mariam Hanna: Okay, fair enough. Now, let's talk about treatments and management. A decade ago, I literally remember talking to people about, like, weighing out a small amount of apple, if apple was their culprit, and increasing this amount of apple. And it seems so barbaric right now, but I'm telling you anyways, we used to do this at some point in time, but what do you do now with your patients that are diagnosed with Pollen Food Allergy Syndrome? If they're particularly concerned about a fruit or vegetable that is their culprit, what are your guidance or recommendations about emerging treatments or what's there?

Dr. Anne Ellis: Yeah, so I think that the real solution is to treat the underlying environmental allergy and specifically. So, moving on to immunotherapy against birch or ragweed or less commonly, grass. I don't see as much of the grass cross-reactive patients.  We have, I mean, it's one trial, but shows that high-dose birch subcutaneous immunotherapy can reduce symptoms of... The study was done for Oral Allergy Syndrome. It's now Pollen Food Allergy Syndrome, but it works. It takes the commitment of the weekly injections at the doctor's office because it is higher doses than we would normally give if all we were doing was trying to treat your hay fever, for example. There are no studies about ragweed and Oral Allergy Syndrome against melon, but I've had great success, anecdotally. When I've put people on subcutaneous immunotherapy, I had one patient who used to have horrible reactions to mango, particularly in ragweed season, and it went away after two years of immunotherapy. And then five years, of course, is enough to usually stop. Studies are upcoming for the sublingual products, so I know there is a study in progress looking at Itulatek, or the birch sublingual immunotherapy product for specifically the treatment of Pollen Food Allergy Syndrome. So that's the primary outcome measure. So that'll be really fascinating to see those results when they come out. Anecdotally, not surprisingly, my patients who do have apple or... fill in the blank... tree fruit Pollen Food Allergy Syndrome, symptoms that I've attributed to the birch allergy. They're the ones who are more likely to have that local itching when you give them Itulatek. But we know that, we can pre-treat with antihistamines, we can get them through it, and we can counsel accordingly. So I don't see it as a contraindication, particularly when I know this indication is being pursued as a possible treatment down the line.

Dr. Mariam Hanna: Do you end up keeping those patients on perennial treatment, or do you just do pre-seasonal, co-seasonal treatment in patients that are doing this kind of management for potentially that benefit for their pollen food allergies?

Dr. Anne Ellis: Yeah, so if it's subcutaneous, it's year-round anyway. If you're looking at the sublingual per product monograph, it's pre- and co-seasonal, as you've mentioned. It really just comes down to their drug plan. Some people prefer to stay on it, and if their insurance company is willing to fund it all year-round, like, I agree, it's easier to never have to start and stop and come back every year to have your next first dose with me. So it's a bit of a mix. It just comes down to literally access and coverage.

Dr. Mariam Hanna: Sometimes I have patients that come into the office with one fruit, and I often wonder in my mind, like, chance of progression. Do we have a good idea? Like, sometimes they're just not bothered by that one fruit. Easy enough to avoid. My rhinitis doesn't bother me too much. Don't want to do immunotherapy right now. What kind of, like, number can I provide in counseling to give them kind of an idea of chance of progression during their life to involving more fruits or vegetables?

Dr. Anne Ellis: I mean, it's a challenging question. I don't think we have that data, to be honest. Our data, even when it comes to just the prevalence of allergic rhinitis, is flawed for Canada, especially in pediatrics, because I know that's the kind of thing you're faced with. We do not have good pediatric epidemiology data for allergic sensitization, let alone actual disease of allergic rhinitis. And attributable to what allergen. It's just not there for Canada. And it's actually... pediatric data is actually lacking globally so I think it's a real call to action. I am not personally aware of any sort of prognostication about whether or not you will pick up other food issues once you have one. I just talk generally about, well, clearly, this is your culprit. Now, just so you know, these are the other kind of things that can come up with birch, but I wouldn't avoid them until you have symptoms.

Dr. Mariam Hanna: Absolutely. Okay. Advice for primary care providers that sometimes have patients that just discuss this with them and they never come to the allergist.

Dr. Anne Ellis: Yeah, I think a really careful history is key when it comes to this. And if it is a fresh fruit, fresh vegetable, doesn't happen when they eat it cooked. You have a history that suggests allergic rhinitis in the spring or the fall. You can probably just reassure patients at that primary care level that this is the most likely condition. Come back if you start to break out in hives or anything that sounds more systemic. But generally speaking, it's a common enough condition now that I think primary care can feel confident in recognizing it and reassuring and giving the right opinions about avoidance and at least eating them cooked so you're not taking those foods out of somebody's diet unnecessarily.

Dr. Mariam Hanna: Fair enough. All right, time to wrap up and ask today's allergist, Dr. Anne Ellis, for her top three key messages to impart to patients and physicians on today's topic, Pollen Food Allergy Syndrome. Dr. Ellis, over to you.

Dr. Anne Ellis: So I think it's important to recognize that fresh fruits and vegetables and tree nuts can cause local reactions in the mouth and gut. But if they're not causing symptoms like breaking out in hives or angioedema or, in other words, swelling or other symptoms of a more severe allergic reaction, don't panic. This is something that you can probably... especially if you have a history of allergic rhinitis or hay fever, chances are good that this is not something that's going to lead to more worrisome features going down the way. But definitely don't be afraid to talk to your primary care provider to confirm with that history that it's all lining up appropriately. The vast majority of patients with Pollen Food Allergy Syndrome do not need to carry an epinephrine auto-injector. That's number two. And number three, if your symptoms are severe, then that's when you need to ask to be referred to an allergist for further evaluation.

Dr. Mariam Hanna: That's perfect. Thank you, Dr. Ellis, for joining us on today's episode of The Allergist.

Dr. Anne Ellis: Thank you so much for having me. It's really been a pleasure.

Dr. Mariam Hanna: This podcast is produced by the Canadian Society of Allergy and Clinical Immunology. The Allergist is produced for CSACI by PodCraft Productions. The views expressed by our guests are theirs alone and do not necessarily reflect the views of the Canadian Society. This podcast is not intended to provide any individual medical advice to our listeners. Please visit www.csaci.ca for show notes and any pertinent links from today's conversation. The "Find an Allergist" app on the website is a useful tool to locate an allergist in your area. If you like the show, please give us a five-star rating and leave a comment wherever you download your podcasts and share it with your networks. Because nowadays we eat apples, but we also treat problems with apples. Thank you for listening. Sincerely, The Allergist.