Episode transcript
Time stamps
1:55 – The history and discovery of alpha-Gal syndrome.
4:10 – What causes alpha-Gal syndrome?
5:50 - Foods that may trigger alpha-Gal syndrome symptoms.
8:20 – Potential medicinal triggers
9:55 - Alpha-Gal exposure symptoms.
12:50 - Identifying alpha-Gal syndrome co-factors.
14:12 - How can primary care providers accurately diagnose the syndrome.
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:
And 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.
Well, summer is here, which means barbecues and outdoor activities are going to be more common. So what better time to have a conversation about alpha-gal syndrome, also known as red meat allergy.
Gary Falcetano:
Yeah. This is a really interesting allergy, Luke. So in short, it's delayed red meat or mammalian food allergy that is actually caused by tick bites. But last summer, the whole awareness around alpha-gal really blew up in the medical community and the MLA community as well when the CDC issued their Mobility and Mortality weekly report. And in that report they described alpha-gal its prevalence throughout the U.S. But there were a couple of startling statistics that came out of that report as well. And one of them was that 42% of healthcare providers were unaware of this allergy.
Luke Lemons:
Yeah. And actually 35% reported that they weren't too confident in their ability to diagnose alpha-gal syndrome or even manage patients with alpha-gal syndrome, which is part of the reason why we're so eager to talk to all of you today about the nuances of this allergy and hopefully help you better diagnose and optimize your patient management.
So as we often do in curbside console episodes. Gary, why don't we look back into the history of this allergy and can you tell me a little bit about alpha-gal syndrome's past?
Gary Falcetano:
Of course, we always go to Gary for the past, so I'm happy to do that. No. So again, this is a really interesting syndrome because of the way it was identified and also kind of who's affected by it. So if we go back to the early two thousands, 2005, 2006, it really starts with a cancer drug called Cetuximab. So patients were getting intravenous infusions of Cetuximab and having acute allergic reactions to the first infusion. And as we know, typically we need to be exposed to an allergen first and on the second exposure and subsequent exposures, we typically have reactions if we're allergic. These were patients who were having it on their initial infusions.
While trying to figure that out. There were a few things that came to light. One people in the north, people in the west that were getting these infusions weren't having any issues, but people in the southeast were the patients experiencing these reactions. So that's the first thing that came to light. The second thing that came to light is some allergists in the Southeast were asked to help identify what was causing the allergic reaction. So Dr. Tom Platts-Mills, the University of Virginia, Dr. Tina Merritt in Arkansas, they collaborated to analyze the serum of these and what they're able to identify is there was a sugar molecule, an oligosaccharide, that people were sensitized to, that they figured out were actually causing these reactions.
Luke Lemons:
And so, they know it's a sugar molecule that's causing this reactions. What does that have to do with Southeast America? There's people reacting to red meat down there. The patients who are receiving this drug are reacting down there. Why?
Gary Falcetano:
That's exactly right. At the same time, the allergy practices in the Southeast were starting to see an increase of people who were actually having reactions to red meat and not just reactions to red meat because we've seen that throughout time, but they're pretty rare. These were becoming more common and they were happening in a delayed manner. So they weren't happening right after ingestion, but anywhere from two to six, even longer hours after the ingestion.
So they started trying to kind of figure out why. As any good detective does, they started putting together all the variables and they looked at what's in the Southeast that isn't anywhere in the country. So they started looking at disease prevalences and they saw that Rocky Mountain Spotted Fever was kind of in the same geographic area. So that led them to start investigating ticks and their role that they might be playing in this. And eventually they figured out that the Lone star tick was the tick that was primarily responsible for causing alpha-gal syndrome.
Luke Lemons:
And this is because this tick was feeding on deer, which was passing along the alpha-gal molecule to the tick. The tick would then bite a person and a person would be exposed through their skin to the alpha-gal molecule and then develop a sensitization and an allergy if they were exposed to red meat again via eating it.
Gary Falcetano:
That's exactly right. So we know that alpha-gal is present in all mammals except old world primates and humans. So that's why we're able to be sensitized. When we're exposed to the alpha-gal through the tick bite and through the skin, which is becoming more and more an area that of interest among allergists as a very unique sensitizing route for food allergy in general and certainly for alpha-gal through tick bites.
Luke Lemons:
Can you maybe expand on that a little bit, Gary, on why a patient who maybe is eating red meat is fine to keep eating red meat, but then they're bit once and they're exposed via their skin and now they have this allergy?
Gary Falcetano:
They've never been sensitized because we really don't become sensitized by the food itself. Unlike some foods where we see this, it really does depend on being bitten by a tick to cause
that initial sensitization. So you can go your whole life eating red meat products and then be bitten by a tick. And usually Luke, it takes more than one tick bite. It can be after one. But we know that and we're following patients with alpha-gal, their levels of sensitization actually increase after multiple tick bites. And the more tick bites they have, the more at risk they are for having symptoms.
Luke Lemons:
And so let's talk about some of the foods that may cause these symptoms. We obviously in the name red meat allergy, but it's really mammal meat allergy. So includes beef, pork, lamb, rabbit, whales, dolphins, mammals in general have this alpha-gal molecule within it. Organ meats from mammals. They're highly decorated with alpha-gal. So this is intestines hearts, livers kidneys if you like, pho, tripe in pho. There's also secondary foods as well. So dairy products from cow's milk, cheese, yogurt, butter, flavorings, meat flavorings that come from the extracts of some of these animals as well as cross-contamination on a grill that has cooked red meat. So again, it's summer. There's barbecues happening, somebody cooks up a burger, somebody maybe knows they have alpha-gal syndrome and they cook chicken next to it. There may be exposure there.
Gary Falcetano:
Absolutely. All of these things could potentially contain alpha-gal, but they do contain varying amounts. And we know that patients that are sensitized to alpha-gal may respond to a trace amount like you mentioned, from cross-contamination on a grill or they may be able to tolerate that or even greater amounts of alpha-gal. But if they have a pork kidney, which is, as you said, highly decorated with alpha-gal, that's when they react. So every patient is different and providers really need to tailor their advice to the individual patients for sure.
Luke Lemons:
Before we go into some of the medical triggers for alpha-gal syndrome, I just want to say on the last note on the food thing that pork gut casings from sausages can also cause a reaction. And you had mentioned that these organ meats, they're very, very decorated with alpha-gal. If you're eating a chicken sausage, it may be in a pork gut casing. However, on the packaging they have to say if the casing is from a different animal than the meat contained inside. So that's just fun little fact that your chicken sausages may be wrapped in pork gut casings.
Gary Falcetano:
Absolutely. But before we move to medications and other routes of exposure, I do want to just call out, you mentioned it in passing, but pork is not a white meat despite what the pork industry has tried to tell us for a long time. It is not the other white meat. It is a mammalian meat. It is technically a red meat and people have reactions that have alpha-gal syndrome all the time to pork.
Luke Lemons:
We'll drop the mic right there for pork is a red meat and move into some of the medical triggers.
Gary Falcetano:
So the number one medical trigger would be Cetuximab. We already talked about that's how the syndrome was identified. Cetuximab is loaded with alpha-gal they've even used in some of the early investigations. They actually used diagnostic assays with Cetuximab to help diagnose alpha-gal syndrome. We actually now use the diagnostic assay for alpha-gal now contains bovine, so cow. Thyroglobulin, which is also highly decorated with alpha-gal. And that's how the current assay is manufactured.
Luke Lemons:
And there are other products that may be a risk for patients with alpha-gal. Particularly anything containing gelatin like vaccines, plasma expanders, there's enzyme replacements, anti-venoms, heparin, and even sometimes the casings around pills that contain acetaminophen and other common drugs.
Gary Falcetano:
Yeah. The gelatin capsules that may be produced. And then finally, even bovine or porcine heart valves. So there's definitely been some research around those and potential rejection of those in alpha-gal syndrome patients.
Luke Lemons:
And what's interesting on that front is they're in the process of making knockout pigs to make these valves so that don't have alpha-gal within them. But this also means that we may have alpha-gal free bacon in the future for everyone who has an alpha-gal allergy.
Gary Falcetano:
Something very exciting for our alpha-gal syndrome patients. No one needs to go through their life without bacon.
Luke Lemons:
Right, that's for sure. And so let's talk a little bit about the symptoms these patients might experience when they are exposed to alpha-gal.
Gary Falcetano:
We put the symptoms into two buckets, chronic and acute symptoms. And we've already talked about how this is potentially an anaphylactic type of reaction. So all the typical symptoms that we see with anaphylaxis, whether that be skin symptoms such as urticaria, angioedema, respiratory symptoms, wheezing, up to and including hypotension and cardiovascular collapse.
But I think what's more important to discuss. Maybe not more important, but certainly something that isn't as well known is that people may be having chronic symptoms that have alpha-gal syndrome. So people with chronic urticaria, people with unexplained chronic GI issues. As a matter of fact, our GI colleagues have even published a clinical practice update that speaks to the importance of assessing alpha-gal sensitization in people with IBS or irritable bowel syndrome.
Luke Lemons:
And so, when you mentioned that it's chronic or acute symptoms, is this because patients react differently? You had mentioned earlier that some patients may not react as severely as other patients.
Gary Falcetano:
Yeah. I think being a syndrome, it really has variable clinical presentations. So absolutely they can have chronic kind of symptoms, especially if they're ingesting red meat on a regular basis. Or they may have very acute severe symptoms. And I think one can certainly progress to the other depending on the quantity of alpha-gal containing products that they have. Luke, there's one other thing that I wanted to mention that's very specific to alpha-GAL diagnosis and that's people that are bitten by ticks often report that tick bites were very itchy and they're itchy for
prolonged period of time. And when they have reactions to ingesting mammalian or red meat products, that area, that old area of the tick bite seems to start itching again, which I think is very unusual to this type of presentation.
Luke Lemons:
That is very interesting because they're being sensitized and as they're being sensitized, there's more antibodies there and it starts to itch. Another interesting symptom of alpha-gal is midnight anaphylaxis as it's called. Because there's a delay often in a reaction, if a patient does eat, let's say a steak for dinner two to six hours later when maybe they're in bed, they may wake up having anaphylaxis.
Gary Falcetano:
It always had this great term. Midnight anaphylaxis, not great if you're having it, but an interesting term. But it also may just be midnight symptoms. It may not be full-blown anaphylaxis. And I think that's where there's been some recent mentions in the literature that we have to be careful. There's a lot of people that are taking diphenhydramine to help them sleep at night. So the diphenhydramine may actually be partially masking those symptoms that they're experiencing from the alpha-gal reaction.
Luke Lemons:
Exactly. And what about some cofactors involved, Gary?
Gary Falcetano:
Yeah, so we know with almost any food allergy that cofactors can certainly play a role. But with Alpha-gal in particular, we seem to see alcohol as being the major cofactor. So people can have a nice steak and a glass of water and not have any symptoms, but they have a steak and a glass of wine and they end up exhibiting symptoms. So here, alcohol is a cofactor is pretty important to be asking about.
Luke Lemons:
And then there's also aspirin is another cofactor, of course, tick bites, right?
Gary Falcetano:
And the more tick bites you have-
Luke Lemons:
Yeah.
Gary Falcetano:
The more likely you are to have more severe reactions.
Luke Lemons:
And interestingly enough, exercising is a cofactor.
Gary Falcetano:
Yeah. Not unlike we talked about in previous episodes week-dependent, exercise induced anaphylaxis, but there are other food allergies where exercise is an absolute cofactor to the expression of disease.
Luke Lemons:
And so we can see after going over all these symptoms and all the ways that people may react to it, that this syndrome, this reaction to alpha-gal can be really confusing, not only for a patient, but maybe even for a provider trying to narrow their differential diagnosis of why this patient is having chronic IBS syndromes, why they're reacting when they have a glass of red wine and meat. It's a very nebulous disease state. And so Gary, with your clinical perspective, how can primary care or other HCPs really go about identifying and diagnosing this syndrome?
Gary Falcetano:
So it all starts with a high index of suspicion. So we mentioned the Southeast as being really an epicenter for this syndrome, but it's spreading. So we know that the Midwest is becoming increasingly a hotbed of alpha-gal activity. So in places like Eastern Oklahoma, Missouri, Arkansas, these are all states that have seen a large increase in alpha-gal cases. But we've seen alpha-gal, a couple of other hot spots, so Long Island, New York, upstate Minnesota. So again, speaking to, that's not an area where we think there is Lone star ticks in upstate Minnesota. So there may be other vectors there. But Luke, we were talking earlier about travel. We have very mobile populations these days.
Luke Lemons:
Yeah. And so when you do ask a patient if they've traveled out of state, let's say that you're practicing in Montana, and you ask your patient if you've been traveling in the past six months, three months, et cetera, if they said that they had visited, let's say Arkansas, and ever since they came back from Arkansas, they just get really bad stomach issues whenever they have bacon, that should be a red flag. They came from a hot spot of where we see a lot of alpha-gal patients. And so maybe it's time to do some diagnostics related to alpha-gal.
Gary Falcetano:
And the diagnostics are very straightforward. So again, once we have a suspicion, we don't want to screen everybody in the country, but certainly if they're having symptoms that may be consistent. So that's either acute symptoms or the chronic symptoms that we talked about. Chronic urticaria, chronic GI issues, especially related to red meat ingestion. Now it's time to test. And there is a serological assay that is specific for ImmunoCAP, and they're typically tested in what are known as alpha-GAL profiles by the major laboratories.
So they include things like beef, pork, lamb, as well as specific testing for alpha-gal because you may just have... There's a small percentage of people that just have protein-mediated standard beef allergy or lamb allergy and don't have alpha-gal. But in the majority of these cases that we're seeing, it's really the alpha-gal that's driving the sensitization. So very easy, simple test to order from any laboratory to help confirm the diagnosis.
Luke Lemons:
And that's just in-vitro testing, correct, Gary?
Gary Falcetano:
Yeah. So something interesting here is that skin testing with the mammalian, the meats, is not reliable at all to diagnose alpha-gal. So you really have to do an in-vitro blood blood test specifically for alpha-gal.
Luke Lemons:
And there's other tests too, that can help providers understand a patient with alpha-gal syndromes, specifically tryptase. A patient who has alpha-gal syndrome tend to have elevated levels of tryptase at a bit greater frequency than patients who don't have alpha-gal.
Gary Falcetano:
Exactly. And we know that tryptase, when you have elevated tryptase, you have an elevated risk for a more severe allergic reaction. So testing tryptase is important. And finally, a total IgE as well. And most of these laboratories include a total IgE with their alpha-gal profile. And that's important because looking at the absolute levels of alpha-gal related to the total IgE can also aid in the diagnosis.
Luke Lemons:
And this type of testing can be done by primary care providers, allergists, really anybody out there who normally orders blood testing. It's a very valuable tool, especially because like we had mentioned this nebulousness of alpha-gal syndrome to narrow a differential diagnosis. And I love what you said earlier, Gary. A high index of suspicion for unidentified anaphylaxis, for IBS, for chronic urticaria, especially in the southeast, central, and northeast parts of America. Having this healthy suspicion and the diagnostics to help narrow a diagnosis is invaluable.
Gary Falcetano:
Absolutely. And I think too, we mentioned it quickly, but idiopathic anaphylaxis, often a diagnosis that comes from the ER. People are sent back to their primary care clinicians to allergists with this diagnosis because they haven't been able to figure it out. And with that delay that often happens, sometimes it can be difficult relating the ingestion of the mammalian meat to the symptoms. So anybody with idiopathic anaphylaxis should be tested as well to help rule out alpha-gal syndrome.
Luke Lemons:
And when a patient is identified as having alpha-gal syndrome due to history and diagnostics, it is important that they're prescribed an epinephrine auto-injector because this is a food allergy and patients can react as severely as other food allergies.
Gary Falcetano:
And once the syndrome has been identified, a referral to an allergist, a referral to a dietician, to help patients really manage their disease, identify all of the various forms that we can potentially be exposed to alpha-gal. And once we've done all that, there is kind of a silver lining to alpha-gal syndrome in that patients actually, if they're not exposed to subsequent tick bites, their levels of alpha-gal may drop to the point that they're actually able to tolerate mammalian meats once again during their lifespan. But all of this is, it's important to be sure you're working in conjunction with a clinician to have that evaluated on an ongoing basis.
Luke Lemons:
Yeah. And not being exposed to all those tick bites may mean not camping as much this summer or hiking around, which I love the outdoors, but if it means I can eventually eat bacon again, I would gladly spend my summer inside for a little bit.
Gary Falcetano:
Well, Luke, if I was your clinician, I might recommend you just take some precautions against the tick bites and still get out there and maybe still avoid the bacon anyway.
Luke Lemons:
Well, thank you for listening to this episode on alpha-gal syndrome. On our episodes page, you'll find an interpretation guide, actually, for diagnostics for alpha-gal syndrome, as well as a presentation from Dr. Tom Platts-Mills, who really did the seminal work and understanding alpha-gal. And this presentation is from the Quad AI, or American Academy of Allergy Asthma and Immunology. We'll also have there a link to the CDC's Morbidity and Mortality weekly report that mentioned alpha-gal and really started the media around it last summer, as well as the AGA clinical practice guidelines that mention testing for alpha-gal if patients show chronic IBS symptoms. Again, thank you for listening and until next time.
Gary Falcetano:
Thanks so much. We'll see you next time.
Announcer:
ImmunoCAST is brought to you by ImmunoCAP Specific IgE Testing and Phadia Laboratory Systems products of Thermo Fisher Scientific. 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.
