Gerald Lee, MD (Host): Hello everyone, and welcome to another episode of Allergy Talk, a roundup of the latest in the field of allergy and immunology from the American College of Allergy, Asthma, and Immunology. For today's episode, we'll be reviewing more articles from Allergy Watch, a bi-monthly publication which provides research journals to college members from the major journals of allergy and immunology.

And for those listening to the audio version, we are releasing video versions of Allergy Talk as well. So, you can catch us at the ACAAI YouTube channel at youtube.com/allergist. And you can earn CME credit by listening to this podcast by going to education.acaai.org/allergytalk. And finally, we have the ACAAI community on Doc Matter, where we can continue to learn about these articles.

Hello everyone. My name is Gerry Lee. I'm an Associate Professor at Emory University and assistant editor of Allergy Watch. And today, once again, I'm joined by Dr. Shyam Joshi, the Editor-in-chief of Allergy Watch and Associate Professor and Section Chief at Oregon Health and Science University. Shyam, welcome back to Allergy Talk.

Shyam Joshi, MD: Thanks so much for having me, Dr. Lee. I really look forward to our conversation today.

Host: And for the third chair, we're once again to be joined by Dr. Vivian Hernandez-Trujillo, the Division Director of Allergy and Immunology at Nicklaus Children's Hospital, a clinical professor of pediatrics at Herbert Wertheim School of Medicine, and Assistant Editor for Allergy Watch. Viv, welcome back to Allergy Talk.

Vivian P. Hernandez-Trujillo, MD, FACAAI: Thank you so much. I'm really excited to be here and have a great podcast today

Host: Okay. And now, it's a vodcast, so everyone can see how you present these awesome articles. And you've picked a really important one to start with. You know, we're all in our bubbles when we treat food allergy. But when we do surveys like this, we understand the whole landscape. So what have we learned about some of these surveys amongst adults?

Vivian P. Hernandez-Trujillo, MD, FACAAI: I'm really passionate about disparities, and I think that one of the things that we really still are lacking, we're starting to better understand disparities, I feel like in children in food allergy. But as far as adults, I think there's really a void. So, that's one of the reasons why I thought this was an important one to talk about.

So, we know that food allergy disproportionately affects communities of color in the US. And this was a survey that actually looked at adults specifically, right? So, it was a self-reported survey. So, it was self-reported allergens, anaphylaxis knowledge, you know, are they familiar with epinephrine? Are they familiar when to use? The results really showed some interesting things. So, food allergy rates to common allergens were affected by race and ethnicity. They actually found that shellfish was the most common food allergy in Blacks. But also, that there were higher rates of tree nut and peanut, which has been previously reported, right, in Black versus White participants.

Race and insurance also were important as we would expect to be predictors as far as, like, anaphylaxis knowledge, with Blacks and Hispanic Latino participants recognizing fewer symptoms, which obviously is something to keep in mind. I think here's a good time to just think for a moment when we're talking about signs and symptoms, if we're talking about respiratory symptoms, and we know that Blacks and Latinos as well have higher rates of asthma. When one thinks about respiratory symptoms, the whole concept of the diagnosis of anaphylaxis may be missed because they may be thinking, "Oh, my asthma's acting up." It's not part of the food allergic reaction, right? So, that was one thing I thought that was important to point out. And then, uninsured and publicly insured subjects also had lower rates, for example, of epinephrine auto-injector prescriptions, which obviously that's concerning because we want to address these disparities. We want to talk about addressing the inequities, which is one of the reasons I thought that this was an important survey to talk about. And then, Black and uninsured and publicly insured respondents also had lower odds of actual allergist-diagnosed food allergy, right? And as pediatric and board-certified allergists, we know we do a really amazing job of educating. And I think that if you don't have the opportunity to see someone who can really take the time, we can take the time and talk about and help people understand and educate.

So, I think that also is another important point. So really, like, their conclusions were that differences obviously in self-reported food allergy, they differed by race and ethnicity, unfortunately. And then, anaphylaxis symptom recognition, access to epinephrine auto-injectors, and then food allergy-related, healthcare utilization, those were all important factors. So, I feel the reason I wanted to talk about this today is it gives us some more information, especially in the adults.

Because again, food allergy, I think a lot of people, especially as a pediatric allergist, we focus a lot on food allergy in kids. At the end of the day, I was one of those food allergy in kids that's now a food allergy adult. And I think it's important. These are things that can help us, right? It's a survey. There's always going to be limitations. I think one of the things that, especially as a Latina, that struck me is it was only in English. So, there's information about Latinos and maybe Spanish-speaking only that weren't able to complete it, which really would be beneficial to better understand. But I really commend the authors, on this, and I think that it's something to consider and further look into. I don't know what you guys thought. But I think, again, food allergy in adults is something that we have to keep on our radar and talk about.

Host: I mean, I do see a lot of patients at Grady, mainly uninsured individuals who get assistance from the county. And yes, I see a fair amount that have misconceptions of food allergy, have not had access. So, this is the first time they're getting evaluated or tested or - maybe they were panel tested and it was actually co-sensitization to dust mite, cockroach, and not shellfish. Like, I've seen it the whole gamut. Like, you know, accepted and not diagnosed or overdiagnosed. And so, you know, it really starts with expertise, and that's like the heartbreaking thing about that. These tests are very confusing. These situations are confusing. And there's not enough allergists to meet the need. I always wonder, Viv, what do you think we could be doing to help address this? I feel like there's just not enough of us, or maybe we're not using our voice well enough?

Vivian P. Hernandez-Trujillo, MD, FACAAI: I think we do need to, like, raise our voices. And there's a lot of noise. There's a lot of inaccurate information and misinformation. You know, I myself, let's say I do a lot of advocacy in Spanish. I'm not doing enough of it. Even though I do, I think we do need to raise our voices. The experts in food allergy are the board-certified allergists. Make no mistake about it. And I think that that's something that is important.

The more we can educate—and it's not only educating. Like, we may think, "Okay, well, you know, like, the healthcare professionals," they need education as well. There's a lot of misconceptions. A lot of the misinformation is not just coming from the TikToker who thinks that they're expert and they're not. It might be coming from other trusted, but they just haven't been educated. So, it's about educating at every level and really trying to do outreach.

I think one of the things I honestly have enjoyed since I was a resident, I do outreach at community fairs, and I go to the underserved areas. I enjoy that so much. There's questions that are asked, there's conversations, and it's talking, right? It's in talking one-on-one. But yeah, I think public service campaigns obviously would be wonderful. And not only in English, but in other languages. I talk specifically about Spanish because that's what I can speak. But in other languages as well, there's a huge, huge need. So, I think there's a lot that we can do, but we definitely need to own this space as where we can make a big difference.

Shyam Joshi, MD: And I agree with you, Gerry, on there's just not enough of us. There are not enough allergists out there. I know the college and the academy are putting some money behind increasing fellowship spots, which is tremendous. But it will take additional advocacy for us to continue to expand our fellowship programs across the board so we can meet that demand.

There's going to be a shortage across the board for many of the subspecialties, both in medicine and pediatrics. But that doesn't mean we have to fall in line with all of them. I think we can keep pushing, we can keep supporting. And really whoever's out there listening to this, support your local fellowship programs.

Even if you're not part of the academic center, have the fellows come to your clinic. Go spend some time with the fellows. Anything you can teach them about community practice, about advocacy, about fairs that you could go to, all that stuff is going to make a big difference in their career going forwa.Rd

Host: Well, I'm, I'm really glad you mentioned the fellowship training grants. I was actually very lucky to be selected for one. I told the college that, you know, we have a situation where we're short of allergists. We don't have enough training programs, but people want to be allergists. We're at the situation there's one in four trainees don't match. We actually want to train them. It's not like we're trying to be selective here. We want as many people to help these individuals as possible and to serve the public. We're talking about conditions that are 10% to 20% of the population at least. So again, I'm glad our national organizations are part of this. I'm glad that that is a vehicle for us to engage in advocacy. Obviously, we can do stuff locally. So, this is a great discussion. I hope everyone listening or watching can think about ways that we can address this issue together as a community, and then also maybe build our profession to expand slots hopefully.

So, again, let's go to the next article, Shyam, I think I thought this article was very interesting when I reviewed it, so I'm glad you selected it. So, let's talk about what could be hiding underneath severe anaphylaxis.

Shyam Joshi, MD: I would say in the past five years plus, there's been this push to better understand systemic mastocytosis. Part of it is because we are seeing a lot of questions from our patients about mast cell disease in general. But this article is really going to be talking about systemic mastocytosis or clonal mast cell disorders.

So, the title of the article is Prevalence of KIT D816V in Anaphylaxis or Systemic Mast Cell Activation. it was by Hartmann, et al. And as you said, Gerry, you reviewed this in Allergy Watch. And so this was published in JACI back in February of 2026. The basis of this is really around talking about clonal mast cell diseases.

So, there's advanced clonal diseases like aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasms, and mast cell leukemia. Then, you have this kind of subcategory of non-advanced SM, which includes indolent, smoldering, and bone marrow-specific mastocytosis. The statistic always blows my mind that one in 5,000 people have SM. That's a lot. There's a lot of people out there that have SM.

Host: That's a lot. I did not know that either. My goodness.

Shyam Joshi, MD: I think originally, we'd traditionally thought it was one in 10,000, which is still a lot. But with this increase in attention to SM, the estimates have gone up to one in 5,000 people. But the key features of clonal mast cell disease is just this clonal expansion of aberrant mast cells. And most of these are associated with a gain-of-function D816V KIT mutation. And about 95% of adult cases have this mutation specifically. And over the past decade, we've switched over from this lower sensitive testing in peripheral blood to this high sensitivity ddPCR testing, which you can get through ARUP, you can get through Mayo Clinic Labs, you can get through LabCorp. But not all D816V tests are this high sensitivity. So just double-check wherever you're sending it to make sure that you are sending it to this higher sensitivity testing. Oftentimes the end diagnostic, you really do still need a bone marrow biopsy based off the major-minor criteria from the WHO.

The diagnosis of SM is often delayed because sometimes the tryptase level isn't high enough that you can get your hematology colleagues to do the bone marrow. Sometimes the tryptase level is just not high enough that it's on our mind or primary care's mind if this could be SM.

And then, from a patient perspective is, do I really want to go through a bone marrow biopsy? That seems very invasive. Do I really want to do it or not? So, there have been a lot of studies looking at, can we help predict which patients have SM before we do this whole process? And so, this was called the PROSPECTOR trial. It was a prospective multi-center from 22 different locations across the US and Europe, which is pretty impressive. To be enrolled, you had to be 18 and older, and you had to have evidence of systemic mast cell activation by one of three criteria.

One is you have the hymenoptera group. So, these are patients who have moderate to severe anaphylaxis due to an hymenoptera sting. The second group is the 20% + 2 Tryptase group. So, you had some cause of anaphylaxis, moderate to severe, with cardiovascular involvement. And you had to have an increase in tryptase of 20% of the baseline, increase from the baseline plus two. And the third group is the cardiovascular group. So, this is patients who've had anaphylaxis with involvement, with cardiovascular involvement, plus another organ system, and they had to have a baseline tryptase level above eight and none of these patients have a history of SM.

And what they were looking for is, in these populations, how many of them were D816V positive on peripheral blood? And what is the prevalence of hereditary alpha-tryptasemia in this group as well? Which we'll talk about that in a second. They were able to enroll 381 patients, which is fantastic. Mean age of 53, 60% female, mostly white, 77% white. And most of these patients ended up coming from Europe, about 77%; the rest from here in the US.

And so, what they found was that out of all of these patients, only 4% of them had peripheral blood positive D816V. Additional five patients, so another about 1-2% percent, had detectable levels, but not above the minimum threshold of what's considered positive. and they found that it was pretty equally distributed between the Hymenoptera group, the 20% + 2 group, and the cardiovascular group. But the prevalence of hereditary alpha-tryptasemia in this enriched population of anaphylaxis was 36% with fourteen percent being in the Hymenoptera group.

Fourteen of those in the Hymenoptera group, 17% of the 20% + 2 group, they had HAT. And then, 60% of the cardiovascular group. Remember that the criteria for the cardiovascular group is that they had to have had a baseline tryptase level above eight. So it's going to be an especially enriched population.

Other interesting findings were that patients positive for D816V levels had a baseline tryptase of anywhere between seven and two hundred. And eighty percent of the patients that had a positive D816V had a baseline tryptase level below 20. So, we have this magical number in our head that 20% is that cutoff of when we should start thinking about SM. But in this study, 80% of the patients had a baseline of less than 20. So, that should not be a screening tool for us to determine, should we test this pe rson further or not?

Of the hereditary alpha-tryptasemia patients, nine of the 61 patients, that had a baseline tryptase level between eight and 11, so 15% of those patients had a hereditary alpha-tryptasemia, and about 75% of the patients that had a baseline tryptase above 11 had hereditary alpha-tryptasemia, which makes sense.

Another interesting finding that they mentioned was those patients that had elevated baseline tryptase levels, but negative peripheral D816V mutations on peripheral blood, many of those patients, 81% of those patients that had further evaluation did end up having systemic mastocytosis.

So, it is, if you get somebody with an elevated tryptase and you do the HAT testing and the HAT testing is negative, that should automatically trigger you to have to figure out why this tryptase is elevated. And if you do that extra work, a lot of the times you will end up revealing that these patients truly do have SM.

And the question is why? Sometimes SM can be isolated to the bone marrow, and those mast cells that have this specific mutation are just not found in an abundance enough quantity in the peripheral blood, so you're just going to miss it that way. But if you do go through the whole bone marrow process, do the high sensitivity testing on the bone marrow, you're going to pick it up. And our testing, while it's high sensitivity, it's not perfect sensitivity. And so, there's still room for improvement in terms of getting some better blood work.

And the last thing I just want to mention is that the NIH has this nifty calculator. has a very long name, the Basal Serum Tryptase Clinical Cutoff Assigned by Local Copy Number blah, blah, blah, blah, blah. But it's called the BST calculator. And if you just type that in, NIH BST calculator, and it incorporates the fact if you have a patient, you put in their baseline tryptase level, you put in how many alpha copies they have, beta copies they have, based off of your HAT testing, and it'll tell you, "Hey, this patient's really high risk. Like, you need to figure out what's going on" versus, "Oh, they have multiple extra alpha tryptase gene copies and their tryptase is 25. That probably explains it." That doesn't mean you shouldn't necessarily do additional workup if you feel like clinically there's still a need for that. But it does give you an idea of which patients should you go after and which patients maybe you don't need to go after as aggressively.

I thought it was just a really good, well-thought-out perspective study. It reinforced some of the information that we have. We still can't make perfect conclusions on what hereditary alpha-tryptasemia really means. We still think of it as a lab test right now. Is it a condition in itself? We can't say with any certainty, but there's just more and more data showing that patients that have severe anaphylaxis have an enriched population of those with HAT. More to come on that. Hopefully, we'll get some more and more data and some more clarifying causation data in the future.

Vivian P. Hernandez-Trujillo, MD, FACAAI: I'm so happy that you picked this, because I think what you said is absolutely true. I think we're all shocked that it's one in 5,000. I wouldn't be shocked if it's one in 2,500 actually. I think it's much more common. But like you said, we're using certain cutoffs and values that when we see that, "Okay, well, they don't have it," well, maybe they do. So, I think it's wonderful that you brought this one up. And Gerry, I'm glad that you reviewed it, because I think that it's important. There's no question that these patients need to be identified for many reasons.

Host: Yeah. It's just listening to the patient. I think, you know, we all have that spidey sense that the labs don't make sense, the testing doesn't make sense, that, you know, there's always that little gray zone, but your gut drives you to start pushing. And I think this is giving us free license that, yes, we should follow our instinct. We know what anaphylaxis is like, and this one is a little bit of an outlier. This one is very severe. You know, I know what anaphylaxis is. I think this is a great article to remind us , yes. I mean, it's really hard to go to someone that you are not performing the bone marrow examination, you know?

And so,when you have something like this, you can absolutely start those conversations from an evidence-based approach, which I think is very persuasive. So, great. Thanks for bringing this to attention. And we'll try to put the calculator in the show notes as well.

I'm going to take the liberty of taking the last article. And this is something I've been very interested in. I've been reading so much about the epithelial barrier hypothesis. I think it's so fascinating. We have just been so interested in the explosion in atopic disease s- you know, since, you know, the mid-20th century. And we all know it cannot be due to genetics, right?

There is something fundamentally changing in our environment, in our lifestyle that is driving atopic disease. And as you know, one of the factors that underlies all atopic disease, it always starts with the epithelial barrier. So, I think of our skin and mucosa. We all know that all of our patients have eczema because we know epithelial barrier dysfunction of the skin is the largest predisposing factor to wheezing and food allergy.

And again, similar findings are being discovered in other mucosa. You know, Benjamin Wright's preliminary research on eosinophilic esophagitis and, you know, dishwasher products. And so, this is sort of extending it to laundry. And I was very interested to read this article. So, it's entitled Fresh Clothes, Hard Breaths: Laundry Washing Habits, Detergent Softeners, and Impaired Respiratory Functions in Children with Wheezing. And this is coming out of Turkey. This is published in Annals. And again, really we are looking at the ingredients in common household laundry deterrents. They contain surfactants like sodium lauryl sulfate, bleaches, all sorts of fragrances, and you know this, right? Enzymes, you know, we have to break down, you know, certain proteins on our clothes. And we know that some of these substances can injure epithelial barriers, right?

And so, this was a case, control cross-sectional study where they wanted to quantify the usage habits and those ingredients. And is there any association with respiratory symptoms? And they chose wheezing preschoolers. And not only they identify the wheezers, but they want to do objective measures. And so, they use a technique called impulse oscillometry. As you know, little pre-toddlers, I mean, little toddlers, they cannot do spirometry. It's very difficult. But, you know, for impulse oscillometry, all you have to do is breathe in and out. It's a very simple procedure. You know, it's kind of silly. You put your hands on your cheeks. It's kind of fun. And again, you can get airway obstruction data.

So again, they have 80 wheezers, 80 gender match controls. Average age was about 54 months, but it was based approximately three to six years of age. These were children. The wheezers were having cough, wheezing, or heavy breathing, two episodes longer than three days, with one in the past year. And they ruled out everything. Like, you had to had no active health symptoms, no other chronic disease. You can't be on medicine. You've had no recent illness, no allergies. You can't be around secondhand smoke. I mean, they really tried to narrow it down to just wheezing.

And so, during the visit, if they were identified to be one of these wheezers, they enrolled in the study, they did impulse oscillometry, and they did questions about amount of laundry detergent, amount of softener, frequency per week, and then the brand to identify the ingredient list. And then, they looked at all sorts of ingredients. Generally, there's different buckets. There's the preservatives. We know about methylisothiazolinone—I can't even pronounce it. I apologize—MI. There's surfactants like SLS or lauryl sulfate, fragrances, linalool, limonene, et cetera, water softeners, bleaches, and soap. And so, the results found that of the chronic wheezing toddlers, those 80 toddlers compared to controls, they actually did not use more detergent

they used more softeners, so the fabric softeners. And they had more exposure than overall to certain MI preservatives, surfactants, and fragrances, and bleaches compared to controls, and less use of soap-based detergents.

And so, when they looked at airway resistance, airway resistance was higher in the wheezers, obviously, especially in those using laundry detergent and softeners with those additives, especially preservatives. And the most interesting thing was that actually those wheezers were often likely to choose fragrance-free detergent, but then it was like free reign on the softener. Does that make sense? Like, there was sort of this pressure that we got to go free on one thing, but then the softener did not have that same meticulousness So, overall, as you know, this is very preliminary data. We're just trying to understand that. Just understanding the exposome of infants and children is just hard to wrap around. There's so much product out there. There's no guidance. Like, no one is telling allergists to routinely recommend against the use of certain products. As you know, when we tell eczema children what to use on their skin, like, you know, there's some general guidance like, you know, avoid fragrance. But like a deep dive in ingredients and which ones they should avoid, we've never received guidance because there's not a lot of research on this epithelial barrier hypothesis. S,o we need more stuff like this. We need to understand, can we protect babies and children from things that are causing atopic disease? And, again, I'm begging for more people to investigate this. It has been constantly an interest of mine as an allergist. Eczema and all these conditions we're always treating on the back end, like let's just treat with medicine. But on the front end, what do we avoid? What do we reduce? You know, the avoidance part of allergy is foundation to our specialty. And again, I just hope we—this is a call for more people to investigate this sort of research.

Shyam Joshi, MD: Yeah. I think this is a pretty simple message that we can incorporate right now, right? These studies are really hard to do. We've done this for atopic dermatitis and using creams and using tons of topical steroids of very early onset. And It's been mixed data, so they're just really hard to do. But this is a pretty low-hanging fruit. While we don't have the amount of data, none of us, what we'd really like, we can tell people lighten off the softeners." And that could make a difference. So, I think this is enough for me to change my practice a little bit.

Vivian P. Hernandez-Trujillo, MD, FACAAI: I agree. I think the take-home for me, you know, we're all really good and as a fellowship training program director, we always ask about, "Is it the fragrance-free detergent?" But we don't talk about the fabric softeners. We don't talk about the sheets, right? The dryer sheets. So, this is a take-home for me to start asking those questions. And to your point, Gerry, like we are very reactive. We're becoming more preventative in many ways. Well, this is one way that we may actually make a huge impact. And I agree, it's low-hanging fruit. Like,, this is something that we can institute tomorrow when we're in clinic. So, I think it's fascinating as well.

Host: Yeah. I mean, I think no one will be grievously harmed if, like, we don't have an artificial scent coming out of our clothes. I mean, maybe I'm just being biased. I think no one's life will be horribly affected. But if we save children from atopic disease, it is absolutely worth it. again, very preliminary to say this, but it's something for all to consider.

And again, if you've had thoughts on this, if this is something that you've seen in your practice, please send us a message. We want to hear your feedback. Our email is allergytalk@acaai.org. And again, if you like what you're hearing, please rate us on your podcast app, on YouTube. And, don't forget about CME credit. That's education.acaai.org/allergytalk. And of course, there's other articles we didn't get to, and you can read those at college.acaai.org/publication/allergywatch.

Well, again, I enjoy doing this very much. I love the articles. Hang on for the next one, and we'll see you next time. Enjoy the rest of your day

The ACAI is presenting this podcast for educational purposes only. It is not medical advice or intended to replace the judgment of a licensed physician. The college is not responsible for any claims related to the procedures, professionals, or products or methods discussed in the podcast, and it does not approve or endorse any products, professionals, services, or methods that may be referenced.