บทถอดความฉบับเต็มของ Episode 15 - How Tick Bites Can Trigger a Life-Threatening Meat Allergy

IgE, which mediates allergic responses. And there are some other cells involved in this. People have talked about natural killer T cells, production of IL-4 during this process, which would skew you to that TH2 response. But it goes a little further for some people, and you develop a true life-threatening allergic reaction to eating red meat. What is Very challenging about this disease is being able to figure out all of that immunology to it, especially because what's unique about Alpha Gal syndrome compared to other food allergies is that the reactions are not consistent and they're often delayed. So normally we talk about food allergies and somebody who needs an EpiPen, you have something like peanut butter if you're allergic to it. If you consume it even at small quantities, you get consistent. quick reactions within minutes to maybe an hour or so that can consist of hives, itching, swelling, problems breathing like coughing, wheezing, shortness of breath, you could have severe vomiting, you can have a drop in your blood pressure, a combination of these symptoms. So a severe life threatening allergic reaction is known as laxis. And if the blood pressure drops, we call it shock. And that's why we have rare instances Of fatal anaphylaxis with food, but with alpha gal syndrome, which is why people carry epipens, right? Exactly, because that's the number one, number two, number three treatment. First line. You have to use epinephrine first, epinephrine fast. And so with alpha gal syndrome, there were many people for many years, actually. It's not this is not technically something that's new. There's been some early observations, even as early as the nineteen nineties. Right. Where people would wake up in the middle of the night with hives or they'd be wheezing And they'd come in to the emergency room in what looked like anaphylaxis, but we didn't know what it was. Right. So we often called it idiopathic anaphylaxis. Hold on to an EpiPen and hopefully nothing happens. And we didn't know what this was. Right. Idiopathic meaning we're not sure where it came from. And the reason it takes so long for it to develop is that unlike a peanut allergy where your skin is sensitized in your mouth, right? You can you can start getting an allergic reaction there. It requires some digestion to break up whatever you've eaten that has the alpha galactose in it. And that's about four or so hours. So in the small intestine, you have these little lipid micelles that that form after you eat some dietary fats. Okay. So they're like little bubbles of fat that your body can transport into your into your system. You can process it and use it as energy, calories. And those lipids will contain that alpha galactose sugar in it. And so it takes a few hours to develop an immune response to this. And so the common story that people have said over and over again and I've heard is that people eat a steak dinner or hamburger for dinner and they go to bed and they wake up in the middle of the night with full anaphylactic symptoms. So sweating, hives, shortness of breath. What else? So a lot of times it's crampy abdominal pain and vomiting and rarely again food food allergic reactions can lead to fatal reactions. And recently in the past year, we have had two confirmed cases, not just in the United States but around the world. So one in New Jersey and one in Australia, where an adult and a teenager respectively passed away from this. ⁓ my God. And I'm not trying to scare people about this because it's that that's not common. But we estimate that close to a half million people in the United States alone have this and many people don't realize that they have it right now, which is why this episode's so important. So please share this episode with people so that they get more information. It's becoming far more common. The reach of this tick is all the way up almost to the Canadian border. Yes. ⁓ from Texas, ⁓ east all the way to Florida, Florida, all the way up to Maine. Right. And all the way across to about South Dakota. Yeah. Now keep in mind when I was initially in my allergy training, I was at Saint I was in St. Louis and we saw a lot of patients with this. Now here in the Chicagoland area, while I have had some patients who have moved here who had Alpha Gal previously, I haven't seen a de novo, a new case of it yet. However, it now appears that there are lone star ticks in this area. And if you're in other parts of the world, there are other ticks that could carry this as well. So this not inherently just an American disease. It it's been reported in Australia, Japan, and in Europe. It it's it's all over the place now. Right. So the CDC did some analysis on potential cases between twenty ten and twenty twenty two. And there have been about a hundred and ten thousand suspected cases. And modeling of this suggests that there may be up to almost half a million Americans impacted. So about four hundred and fifty thousand. And it's and it's a tough one to nail down because First, it's a little inconsistent, right? Exercise, other medications, alcohol use can all impact how and when it shows up. Mm-hmm. And then some people, and not everyone, but some people can get better with careful reduction in exposure to tick bites. Now this can take years and it may not be everyone. Some people may be allergic to meat and meat products for life. So let's go over what those products are. Yeah. So we're gonna put up if you are watching The video version of this, we're gonna put up an image that really has a good sense of where the risks of reactions are, but I will also list it for those who are listening. Right. So the highest risks are going to be clearly mammalian meat products like beef, pork, four legged animals, essentially. Anything that contains their innards, and then it goes down to dairy products like milk and cheese, could also contain alpha gal, although not everybody reacts to dairy products. We have alpha gal syndrome.

And then the lower risk is going to be gelatin containing foods because depending on the type of gelatin, like where it's sourced from, it may contain pork. Therefore, it could have alpha gal in it. Right. And it's not just food, it's also medications. So the one of the big reasons why we actually discovered alpha gal in the first place. Right. So yeah, this is actually a really interesting story back in 2004, right? And I remember reading about this because I was in graduate school about that time when it was officially described in two thousand nine and it made big headlines then and as a budding immunologist doing my research then I thought, Wow, that is that is interesting. It's nice that it's confined to ticks and not mosquitoes. But but woo. So let's let's talk about how it was first discovered actually. It's kind of a fascinating story. Yeah, so because as as we were mentioning One of the main medications that contains alpha-gal in it is a cancer medication for colorectal cancer called cetuximab. So in around 2004, there was a group of physicians, the Platz Mills group at University of Virginia, who had noted that there were many patients who were coming to them that had severe allergic reactions hours after eating beef and pork that they initially were okay with. And they also noticed that there were people who were having these severe allergic reactions to cetimab. And it took a lot of coordination and effort amongst various physicians, not at university of not just at University of Virginia, but at Vanderbilt and where they were able to finally demonstrate that people were having these pre existing IgE antibodies to Alpha Gal. And they knew that Alpha Gal was in cytoximab. And so they finally had a paper published in 2009 that formally described Alpha Gal syndrome, but this was likely again ongoing for many years. prior to this discovery. But like a lot of times in medicine, it takes time for physicians and the public to start to understand this. So even today, many people are not aware of Alpha Gal syndrome, including physicians, which is why we have to keep speaking out about this. Because unless you if you don't know about this, you're not gonna be able to identify the trigger and to be able to properly manage this. And many physicians aren't even comfortable Talking about this right Yeah, and let's let's give credit where credits do. It was Dr. Platz Mills, specializing in infectious disease at University of Virginia, who who first described this. And you can imagine as someone tracking infectious disease or looking for emerging infectious disease, once in a while someone shows up to the ER, symptoms resolve. It was some sort of idiopathic allergic response. And they go home and it doesn't happen again consistently. And so what are some of the emerging treatments that you've seen, Dr. Rubin? So first off, the the traditional ⁓ gold standard of treating is to identify what products could potentially cause you symptoms and avoiding those products and being trained on how to manage anaphylaxis if it was to occur and to have regular follow-up to look at the blood tests, we can actually measure for Ig antibodies specific to alpha gal. Right. So we can track that over time to be able to figure out can we actually try some of these foods. So so as the antibodies drop, then then you may see a window where people could maybe start reintroducing these carefully. Right. So typically what I've done is when I look at the numbers and they look like they're decreasing to a certain amount. I'm not going to say what the number is because then people are going to hold on to it. And it may be patient specific. Yeah. Yeah. But people can have a lot of things going on. Yeah. But the problem is that the numbers we don't have very hard and fast specific cutoffs. Right. ⁓ if you're at this number, it's safe to consume this. Because for those who are able to see the image and we should pop it up again, it's not just a matter of what products you're consuming, but cofactors. Right. So what I mean by cofactors is you you could have other things that exist outside of a blood test that can influence a reaction, like if you are exercising and then you consume something that contains alpha gal, that can make the immune response more robust. Or you're drinking alcohol or you're taking medications known as non-steroidal anti-inflammatory drugs. Those are, you know, fever reducing or pain reliever medications like motrin, ibuprofen, alleve, neproxin, ⁓ not Tylenol, by the way. ⁓ but but those issues come. So it's okay to take Tylenol or it's preferred even. Yeah, except I want to make an exception to this. Gel caps are not necessarily safe for people with alpha gal 'cause it could have gelatin in it. So the see how we're we're talking about a lot of nuance here. And it can be i it's there's a lot to think about for people. So imagine for those who are dealing with this, how much they have to think about in their everyday life right with this. And so I I know we didn't get into the into the treatments yet that are ⁓ up and coming, but but just thinking about how you manage this is difficult. And so now when we start thinking about what are some of these investigational therapies that we're looking into, as an example, there's a group that's creating pork that does not contain alpha gal. ⁓ interesting. Wait, is that like an engineered meat product? Yes, yes. Fascinating. Okay. And so That's a way to help modify someone's lifestyle who really enjoys consuming pork products that that and so we were able to kind of circumvent it this way. Interesting. So you can't cook the sugar out. Correct. All right. So let's talk about ⁓ But there's other treatments. So you talk about some of the ways that you would approach treating it in your clinic. One of the things people can do at home to help reduce, even if you already have alpha gal. reduce the amount of antibodies in your system, right? So you might be able to

talk to your doctor to start trying some foods again safely and or avoid getting it at all is to avoid tick bites, period. Exactly. ⁓ and so, you know, if you must go outside and be in tick infested areas, prumethrine pre-treatment of clothing is kind of the gold standard. Wear light clothing, tuck your pants into your socks, long sleeves. There's an interesting study showing that you may reduce the incidence of Lyme getting Lyme disease if you showered within two hours of being outside. ⁓ Okay. And so that would also likely prevent the lone star tick bites as well. Check yourself over for ticks, make sure your pets are medicated. So if a tick does bite them or if it gets into the house, when it bites them, they die. They don't continue on their life cycle. Yeah. There's there are a lot of different ways to avoid ticks. One of my favorite ways And I've been doing this since I was a kid in Northern California, is we would have like painter's tape, like a blue roll painter's tape by the front door. We'd be out playing with our dogs and whatnot and then kids running around, right? And we'd make like a sticky mitt on our hands. And I think some people sell these now, but we'd do a reverse tape sticky mitt and just run all over ourselves, run all over the dogs, you know, brush the dogs fur backwards a little, look for any ticks. And that that helps too, you know, because they're little, they can be really tiny. When they're not when they're just first getting on you and they're not blood engorged yet? So there is actually one treatment that is technically approved for Alpha Gall syndrome, although we actually don't have clinical trial data for it. So we don't one of the first FDA approved treatments for food allergies that are IgE mediated, meaning the ones that we tell people to hold on to an appi pen for, is omolysimab known as Zolair. And Alpha Gall syndrome is IgE mediated. So it makes sense that this would have some efficacy. So this is an antibody treatment that's given every two to four weeks, and it's either one or two injections. It depends on the body weight and the total blood concentration of IgE antibodies in general. That's how the dosing is done. And it essentially blocks the ability for the IgE antibodies that are in the blood that aren't bound to mast cells from actually. activating mass cells. So it it was studied in peanut allergic individuals who are also allergic to two or more foods, but AlphaGal syndrome wasn't really in the outmatched trial that got this FDA approval. And so theoretically it's biologically plausible that it could help with AlphaGal syndrome, but we don't have the effectiveness data like we do for peanut milk and Use So you don't have to go off label to give it to you, right? And it's investigational still. And there's not there's not clear evidence that it stops the allergic responses. It will blunt the response, which you could But here's the thing. You could almost argue that's yeah, the hospital maybe. But because it's an IgE mediated disease, it's not like a traditional off label use in the sense the problem is for me personally is that because I don't have Alpha Gal syndrome patients in my clinic right now. I I don't have personal experience using it for this because when I took care of patients, this medication wasn't approved yet. And then when I came here, we haven't seen it. So it's theoretically possible to use it. I don't know how effective it is because we don't have those clinical studies. Right. Right. And it's not it's not anticipated that it would be curative, but instead that it would blunt an allergic response. Exactly. Then potentially keep you out of the hospital and whatnot. Immune tolerance induction is another one I'd like to talk about. So this is preclinical, which means it hasn't been tested in humans yet. But there was a small study out of University of Michigan where they gave mice nanoparticle capsules that contained the sugar molecule, the alpha gal, and 10 out of 12 mice had a reduction in antibody production. And I mean we know oral Immune tolerance does work. We know immune tolerance can be generated through exposure to small amounts of things. I will caution though that mice are not people. If mice were people, we would have cured cancer a long time ago. We don't we have similar immune systems, but not directly overlapping immune responses for everything. This is being investigated and it has been working well for Celiac disease. So so there is a clinical stage study with the same technology for celiac disease in humans. So it's an interesting approach and it may work. So there are things that are being investigated currently. Now we've talked a lot about these different management strategies and upcoming treatments that are under active investigation. To our knowledge today, there are no phase three clinical trials for a new Alpha Gal treatment. I want to make that clear because if you're listening to what has been going on recently in the news, RFK Jr. was at a press conference fairly recently talking about Lyme disease and other tick-borne diseases. And he was saying that he's trying to fast track treatments for Alpha Gal syndrome. Yet he never named what those treatments are, which It would be nice to know that so that I could inform my patients, but also we can through from bench to bed side podcasts talk about those things. Right. But it's happy, happy to talk about new clinical advances. Exactly. I would love to know that, but it's not really being transparent if you're not telling us what you're trying to fast track. So I I'm quite frustrated by it because I would love to know if there's something out there that's getting some additional funding and we do need additional funding and research. For Alpha Gal syndrome because it's now probably the tenth most common food allergen in the United States. And growing. Exactly. Especially because the ticks are migrating. The ticks the ticks of carried are migrating

northwards and west and east. I mean they're just they're spreading out from their original habitat. Exactly. So I hope that we will have more research funding and not just even treatments, but testing strategies for this because It's difficult to determine if someone is truly still allergic or not. I mean, in my clinic I've done this. I've had people eat steak at eight in the morning and come into my clinic and sit all day. ⁓ yeah. It's it's not the greatest experience. Not a great way to spend a day. But that's it's essentially what the gold standard is is ⁓ we call a direct oral food challenge. Where you're you're eating a food under direct supervision, but because it's delayed, it's it's tough. And also it's And consistent too. Yes, exactly. So so what's interesting about ⁓ some of the potential treatments is there's a group genetically modified pigs to remove the alpha gal sugar molecule so that's safer consumption for those with alpha gal syndrome. Okay, that is that is fascinating. These pigs were already being bred as part of a program for organ donation, which is something I'm pretty well versed in because I worked on development of tissues and organs. And the de activation of this alpha gal gene was already in existence in these pig populations because turning that off was one of the first critical steps to make them human immune safe. That's fascinating. Yeah. And so the meat is called the so-called gal safe pigs. it's available from a company called Amaru Hills. If you've been on social media lately, you might have also seen some misinformation campaigns. going around trying to convince people that Bill Gates and scientists and they, the collective they, are releasing ticks that contain Alpha Gal into the United States to try and make people vegan. This is this is bizarre. So every time, every time right now, this is tough being a scientist, every time we find something new, we alert the public about it, granted, this was found back in the nineties, years ago. 30 plus years ago. But every time it captures the public's imagination or they start to notice some things going on, a a ridiculous conspiracy theory springs up out of nowhere. And it's just at its core, another attack on science and scientists. We do want to be discovering and characterizing these new things. We can't stick our heads in the sand. And just because we figured out what it is, doesn't mean there was a conspiracy behind it. So we just went through a whirlwind tour of Alpha Gal syndrome in terms of the signs, the symptoms, the immunology, the history behind it, treatment. Which if you want to learn more, I do have a book called All About Allergies that you can check out. Do you have an Alpha Gal chapter? It's in the food allergy and anaphylaxis chapters, but it's not an entire chapter on Alpha Gal alone. But it's in context with other types of food allergic reactions. Interesting. Okay. And so please subscribe to our Podcast from Bench to Bedside. Share this episode widely to help raise awareness about Alpha Gal syndrome. It can be deadly. It can. Unfortunately so. So raising awareness is key. And we are looking forward to seeing you next time. See ya next time. Thanks for joining us on From Bench to Bedside Podcast. We're thrilled to have you here as we explore the intersection of science and medicine. Be sure to subscribe so you don't miss our upcoming episodes where we'll dive deeper into health topics that matter. Until next time, stay curious and stay informed.