Victoria Martin - Cow's Milk Protein Intolerance and Allergic Proctocolitis

[music] Welcome to another episode of Balsounds, the pediatric GI podcast, the official podcast of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition, or Naspian. My name is Jennifer Lee. Pediatric Gastroenterologist at Nationwide Children's Hospital, and I'm joined by my co-host, Dr. Peter Lou. Hi! Hi, Peter! How's it going? Oh, doing great today. I think that it is getting close to spring break. Well, this is a big year for us because this is the first year my kids are in public school. Uh-huh. So we actually have a real spring break. Ooh, ooh, ooh, ooh. And so when you get there with Emma, by the way, you not only have to put your schedule in advance, because everybody wants spring break off. Yes. But we were very lucky to get it. Shout out to my division. And we're going to Puerto Rico. Oh, awesome! What are you going to do? Where are you going to go? The rain forest, the beach also. Eat all the food. It's going to be amazing. Yeah, it's going to be awesome. Yeah, I love traveling with the kids too, because they're the perfect age to just like explore. And it helps you see the world through their eyes. Sure. Yeah, we're really looking forward to it. I'm so jealous. Bad money is also from Puerto Rico. Oh, perfect. Yeah, that's another big positive for Puerto Rico. But yes. I have to have the non-explicit version of the songs for my kids. Are they explicit? So we wondered that once and we looked it up. Yes, they are explicit. Yeah. Well, and the funny thing is, I don't know if you know this, but my kids were in foreign language immersion daycare before we moved to Columbus. Yeah, you mentioned that. Yeah, and they were like fluent in Spanish before we got here. You know, reawaken the stuff they learned when they were, you know, 15 months. Non-explicit, just in case. So we don't know what's going to be great, but we are going to trip right after this comes out. Yeah, where are you going? We're going to Amsterdam to be at the graduation. We're going to be at the graduation of a girl who did her PhD studies with us in Columbus. Oh, is it Desray? Yes. Yeah, okay. Yeah, so that's, that'll be awesome. Oh, man, yeah, you have to let me know how that is. Anyway, so today we have a really special guest. Yeah, Dr. Tori or Victoria Martin. Yeah, so we were in the same fellowship class. So every fellow's conference, we would hang out, we have some mutual friends. We once hung on and bars Lana together. Yeah. Yeah, we went to New York. But not in a conference, right? Yeah, it happened to be there on vacation and like I was traveling with one of her good friends. So yeah, it was awesome to have her. So Dr. Victoria Martin is an assistant professor at Harvard Medical School and the co-director of the pediatric gastronology section in their Food Allergy Center, as well as the associate program director of the fellowship there at Mass General. So we have heard a come talk to us about a really cool topic that's near and dear to my heart because one of my kids had this was Cal's Mo Protein Intolerance. Yeah. So Emma had that too. So yes, we see it all the time. Yeah. But it's like shocking how little we like really know about it. Yeah, and it's really cool to hear about the research that she's doing and what's going to be hopefully coming in the future. And she gives this kind of like sneak peek about what she's looking into and it was really exciting. And it's like, you know, by putting my daughter on, you know, a milk and soy protein free formula, was I setting her up for Food Allergy in the future. But anyways, yes, it's an awesome episode. I like had so much fun talking to her. Yeah, me too. And I think this is going to be good for not just pediatric gastroenterologist, but also for general pediatricians. And if you're a parent or a mom or a dad who's, you know, who has a kid with Cal's Mo Protein Intolerance. Or someone who may be having a baby soon. Yeah. And the crazy thing, this is one of the few episodes that I think I might change my practice like immediately, based on what we talk about. Oh, yeah. So without further ado, on to the show, on to the show. Dr. Tory Martin, welcome to the Bell Sounds podcast. I'm so excited that you're here. For those who don't know, we're in the same fellowship class. She is like way more accomplished than me, but we did start out at the same time. But it's so good to have you on the podcast. So welcome. Thank you so much. It is really good to be here. I made sure that there was some like anti paparazzi out in front of my house, just in case like for after this drop. Oh, man, after this comes out, your life will never be the same. Yeah. Yeah, I'm ready for an amazing place. Yeah. So first question for listeners who don't know you, how would you describe yourself in one sentence? So this is so hard. And I guess sort of reflective of me, it's going to be a run on sentence, which is that I am a thoroughbred Boston. I'd like to think I'm funny, but I'm secretly a pretty closeted introvert. I'm a foodier food lover, but a washed up tennis player with a really like on again off again relationship with exercise of other forms. And because I had two kids under two during the pandemic, if I had other interests, I don't know what they were. I don't remember. Oh, I have a follow up question to that. Peter and I have recently been talking a lot about pickleball. Oh, oh, actually, I'm really good. Oh, okay. Wow. Oh, wait, we don't want to play that. Did you add a humble to your one-star one liner? Yeah, you know, I actually took that out in a self-reflective moment. Pickleball is amazing. And the best part of it is that we started playing because you can play with people of like wide ranges of physical. Yeah. So like we play with my parents and they like, we're all kind of on relatively even ground. So yeah, I'd say that's the only on in my on again off again exercise relationship. 100%. Oh, man. Okay, we're going to do it. Awesome. Yeah, honestly, Tori, I've only played twice in my life, but I'm like 100% all in. I just can't find people to play with. So that's again 2020. Oh, right. Let's do it. You know, do you show it? I'll put it in my bag. Yeah, I mean, like, you know, so back in the day, there was whatever the soccer game, semi-colon versus Collins or whatever. This is the new thing. You know, this is the new generation. It's pickleball. Yeah. So Bristol equivalent is a pickle. Maybe we can change the name to be poop. No. No. Okay. Well, let's move on before things pick up. This pickleball. Okay. So a new question for our guest. So Boston is a beautiful city with so much to see and do and you said you were a foodie. So what is the one thing we need to see or do or eat when we visit you in Boston that the average tors might miss? I mean, I don't know what seeing anything and just eat if it were up to me. I mean, I don't know if it's a good foodie. But I would say, the food is really hard to choose. I think sort of a tie between like you have to have good seafood with your in Boston. But you also like have to stop in the north end. And you know, at least some classic canola. You just have to eat all the things. Oh, and then brunch all the branches. You have brunch. Okay. Okay. Okay. Okay. So north end brunch seafood. I mean, that sounds. Yeah. I know scenery, like I don't know what just look at a picture, but you can't get the same. Well, you can like eat at the scenery, but like you just have to be eating. Oh, yeah. You can get the same just by getting a recipe and making it. No. Are you kidding me? No. Okay. Okay. Yeah. No. All right. Jen, I'm that's like very disappointing said that. I like bringing controversy to the podcast. Yeah. Like changing the name of pickle ball to poop related. That's too much. I don't want to brag on your behalf, but one award and ask began award to study our topic today. But how did you develop your interest? How did that come all come about? So literally just like a fellow and fellow's clinic, I was really struck by how many kids and this probably differs geographically, but like how many kids we saw in clinic. With some some version of milk protein allergy. And you know, I'm like that annoying fellow that asked a lot of questions. And so every question I asked the answer was like we we don't actually know. And I was really struck by the fact that there's no primary data about this disease that is like. I don't know for me was like 20% of the kids I saw in clinic. Maybe more. And so that's sort of how it all started. And then just by timing in 2015 when leap was published. You know, which was that sort of landmark study showing the importance of early introduction of peanut. And that being sort of importantly preventative for peanut allergy. Then I started to really wonder like are we actually part of the problem. Restricting so many kids diets for this thing that we don't even like understand or know where it what it is. And so that really was like an additional catalyst and sort of what drove a lot of that. I've been working on some. And just to clarify, are you primarily research now or you like split pretty evenly? Yeah. And so I spend 80% of my time researching this and then I love out like realistically not of these percentages out of that. So like so my contract. So 80% of my time is doing research and the other 20% is in clinical. And so I do a little bit of general GI, but mostly it's not a lot of time in our feeding team, which you know we can talk about but ends up with like a lot of kids with food allergy. So that's sort of a good marriage of my interests. And then I'm the associate program director for the fellowship. All those things definitely don't add up to 100, but in theory if they did that, how it would be sounds like a job of three people. But, uh, say wait a second, but that's awesome. Remember when I said at the beginning, I don't have any other interest. Chico ball and all those hats that you just described. Okay, so I want to talk about naming and terminology. So first of all, what should we call the disorder that we're talking about today? Is this cow's milk protein intolerance or cow's milk allergy or milk and soy protein intolerance or food protein induced procto colitis or allergic procto colitis? Woo, so many options. So what do we actually call it? Yes, so many options and they're all bad. You know, so I use a couple of different things. I think the most sort of agreed upon language right now is this food. protein-induced allergic proctocolitis. Unfortunately, the acronym doesn't roll off the tongue nor can you pronounce it. So I think a lot of people and I sort of fall back to saying AP for short. The milk protein intolerance term I use sometimes when I'm seeing a baby that's a little more vague. We're gonna talk about this, I'm sure, but these sort of fussy, refuxy babies, but aren't having a lot of those lower GI symptoms that really suggest actually a proctocolitis. And so those are probably the two terms I use. I think the term I would not use is chasmal protein allergy, because I think that both suggests an IgBD-rated process which this isn't and also confuses families and makes them think that this is like gonna be a lifelong or life-threatening allergy, which it decidedly isn't. I'm open to suggestions, better terms to champion. Well, Peter already said I'm not a lot of renamed things. So what's your take on this? Well, I like that, like the milk protein intolerance. I try to, I also make an emphasis not to call it an allergy, 'cause it just confuses families. And adding protein in there is important too, because I think a lot of my patients think, "Oh, it's the same as lactose intolerance, which is not." And you mentioned earlier, we didn't know a lot about it. So I'm not gonna say how many years it's been since you and Peter finished fellowship, but what have we, (laughs) so what have we learned about since then? What is our underlying pathophysiology? And the thing that always comes to mind are these tight junctions, but maybe I'm totally misremembering that. So we don't know very much the study that I'll reference the most is our study here, which is called GMAP. I gastrointestinal microbiome and allergic fractal colitis study. (clears throat) And this is a thousand infant prospective cohort that we've been following since I started. And so we enrolled a thousand healthy babies that are primary care practice and have followed them for development of AP. And so the oldest kids are now about seven and we're following them until they're 18. - Wow. - And so, I hope to be able to contribute a lot more over the years to what we know now. But prior to GMAP, there was no study looking at this population really specifically or prospectively, we can talk about what there was. And so we know that it's not IgE mediated, right? These aren't kids where IgE testing is helpful, probably 'cause they're young, but also partly 'cause it just doesn't seem to track with IgE. We know that historically when we used to scope them more often for diagnosis, that there was this sort of eosynophilic predominant histopathology, which is what made us think that this is allergic in some way. And also, you know, it used to be called eosynophilic colitis as well and babies. And that's kind of it. And, you know, a subset of kids where back when we used to scope them more often where we like really thought this is what they had, like only some of them would have that histopathology. And so then what were the rest of them? I think like no one knows. And like that's kind of all we got in terms of in terms of pathophysic and the allergic understanding at the moment, but I'm hoping to change. Wow, that is crazy. 1000 babies. I can't even get track of my own two babies. (laughing) For 18 years, that's incredible. I mean, but it is. We're trying. I mean, it's also kind of going back to what you said about how there's allergic proctocolitis, but that doesn't fit everybody either 'cause some don't have proctocolitis. And they, yeah, so it's like all these heterogeneous forms of milk protein intolerance. But it's weird that they all would also kind of follow the same natural history and get better. I don't know. It's fascinating. We'll have to do like an update, maybe like in a couple of years. It's all just our seven, so we can wait 11 years and I'm just getting wait until 18. We'll follow Dr. Martin over time. And yeah, we only have one person to follow. So, okay, moving on though, how do we make this diagnosis? Like as a pediatrician or a pediatric GI, and are there any tests that you think are helpful? Like stool calls or fecal culpratectins or sigmydoscopy, what do you think about that? - Yeah, I'll touch a little bit on how we do make this diagnosis and also how we should make this diagnosis and I think they're different. So I think right now, classically, this is made by sort of people identifying the symptoms, right? So often a fussy baby, an irritable baby, maybe a baby that's difficult to feed, who shows maybe symptoms of reflex, maybe not, and then sort of traditionally shows symptoms of looser stools, mucus in the stool, and blood in the stool that's either occult or gross. By definition, this diagnosis should be challenge proven and here's where we get to what we're not doing. So if you read the international guidelines about milk allergy, which are called the IMAP guidelines, which I'll refer to a bit, there is a required challenge that's one month after symptom resolution. So that means you meet a baby, you take milk out of their diet and we can talk about what that looks like. They get better, you say great, I think that's what this is, but we need to do a challenge to prove it and you reintroduce that milk protein a month later and see if they, if they're symptoms recur. Large chunk of kids will not respond to the challenge. And I think whether that means that they actually had milk protein intolerance or allergic proctocytus, and it's just that transient, or that means that it wasn't that in the first place. I'm not sure we know and I'm not sure it matters, but that challenge is super important and it's what we're not doing. So I'll tell you that wasn't required for our diagnostic criteria in GMAP because it's not the clinical practice in GMAP it is an observational study and it's not what people are doing generally in the States. And we got a lot of pushback from the allergist reviewers of a lot of the journals assigned to review this because they said like, well, this isn't challenge proven so how do we know what we're dealing with? And while it's a fair criticism, challenges are not what anyone's doing. At least that certainly wasn't most of the practice that I saw. And so I think that's a really important piece and we can come back to it. A cold blood testing, so, you know, again, not validated for this indication. There's a great study from Chile, but it's translated into English from a couple of years ago where they looked specifically at this question and a third of their healthy controls had black positivity in this age group. And so I don't know if there have been larger studies, I haven't looked at this in a little bit. It's sort of like what the incidence of a cold blood positivity is in babies but so I use it because it's objective, especially in that fussy baby that's not having like obvious symptoms in the stool, but I also take it with a pretty big grain of salt. And it's not something I follow for resolution. I don't repeatedly guile kids. If they seem happier and better, I don't pay attention to whether they're still guile positive or not personally. And Calprotectin is not helpful and we have some data about this from the cohort that I'm hoping to submit to NASPAGAN that I can share sort of more broadly, but it's not particularly helpful. - Partly because the age group, the range is super, super wide. So I think it's hard to interpret. - So going back to the stool occult, like what's in there? Like is that something you send for everybody or like the family had reported? Oh, there's like mucus and some blood. - Or like do you just do like a one or do you do like three in a row? Or how do you do that? - Yeah, I think doing more than one like separated by a week or two without any clinical changes on why is a approach, I think it helps probably your sensitivity a little bit. - I think to be honest, like most of these kids already have it by the time they come to us, right? So I don't feel like that decision is usually up to me and so I actually don't guile very often 'cause either they already had one and that's why they're coming and I don't follow it unless there's some reason that I'm sort of questioning what we're doing, but often I don't. The flexic I reserve for the really unclear cases, like the kid that I can't get better and I'm starting to question whether this is actually a polyp or some other cause that we're misunderstanding because I think generally we can make these decisions without needing a scope. That said, it would be so interesting to see all their histophilology and I like, you know, in thinking about like if you could do randomized controlled trials of this someday, you'd have to wonder if that would be your endpoint or not 'cause all of our other endpoints are so slippery, but hard to imagine that that would be something that an IRB would think was appropriate or that we would think was appropriate if it's not standard of care and someone invasive. - Right, right, right. - Yeah, pretty invasive. So, okay, so I had one of my two kids who had some pretty significant intolerance and I was breastfeeding. So this is a question that's kind of near and dear to my heart. So tell me what you do as far as recommendations for a mom who's exclusively breastfed and then what if they take milk out and they're still having a lot of symptoms, then what do you recommend? - Yeah, so hugely important that we don't contribute to the best of our ability with disruption of a breastfeeding relationship and an exclusively breastfed or partially breastfed infant, something also super near and dear to me. So first thing is you cannot leave that initial visit and not tell that mother that the milk that she has in the seven freezers in her basement that she hasn't told you about is still gonna be good and important and wonderful. A few months from now, even if it isn't right now, I like start with that out the gate because the number of people that come to see me that like poured that down the drain like sobbing is like so tragic and terrible. So I think it's super important to explain to folks that this is probably pretty transient at the beginning. I always start with just milk out of the maternal diet. The data on soy is not great and I think it's just adds a lot more complexity. And I think the real question is like how long do you wait? And I wait as long as they will let me. So my personal opinion is that these kids will get better or worse and they will really declare themselves if they're gonna get worse enough that you have to do something about it. And so I'm a huge advocate for watchful waiting in general. So if I see like a healthy, happy, thriving baby who comes to me because there was some blood in the stool one time, like I definitely don't die to eliminate that kid right away and I watch them and drag my feet. And then if I'm gonna get sick, If we take milk out and they come back to see me three weeks later and they're not really sure they're better, you know, if they're showing signs of oral aversion, if we're losing weight, if there's like major sleep disruption, like other things to make me worry, then we talk about what to do next. But I try really hard to drag my feet because I think a lot of these kids could just get better with time. And I think we often add more things to the maternal restriction diet and then pat ourselves on the back when they get better a few weeks later. And actually they may be just we're going to get better a few weeks later and we celebrate that we also removed egg and soy because we're so smart and in reality maybe neither of us had anything to do with anything. There's really no data about foods beyond milk for this disease and there's no controlled data to show sort of timeline or which you should do next. It's so interesting. You know, and as I'm thinking about that, I have to go back because I'm having like PTSD moments here because like I'm telling this like it was really hard. So you know, I empathize with a lot of my patients' mothers especially because for example, if I had milk and I would re-challenge her for my own sanity also, like it was a pretty clear change in her entire behavior, how she was, what her stools were like, and it was really, really challenging for me. So also because I felt like she was in pain. And when you were talking about this challenge a month later, I mean, that's actually really hard. I think sometimes to ask a parent to do that, especially if their child was so symptomatic beforehand. It's a super hard sell, but I think it's really interesting. It is absolutely standard of care and the entire rest of the world and we are the only holdout that doesn't do it. And I think what I talk to families about is that like look, there's really good data out there that a huge percentage of these kids won't react to the challenge. If that's not your kid and if they react, we're sorry we put them through it, but they can get better super fast because we know exactly what the problem is and we should talk about how that challenge is done. But like for example, if it were you Jen, I wouldn't say, go eat a bunch of ice cream tonight. I would say, pull a bag out of your freezer, use that. And if there's a reaction, like that's going to wash out super quickly and you can continue nursing, you're milk-free milk. I think there are ways to really control how long the experience of that reaction may be for families. And in my experience, I talked to them about like the long term risk of diet elimination and the leap study and I gene-veated food allergy later. And that's really pretty motivating to folks to say like, okay, I see the value of having as many antigens back in my kids' life as I can, as early as I can. As a sidebar, there was another study going on that was an attempting to enroll babies for this. And the study literally couldn't enroll because so many kids didn't challenge positive. And so it's really, really remarkable how many of them a month later aren't behaving the same. And like I said before, I don't think that means it wasn't real the first time. I think there's just, there's a few different ways to think about why that might be, but it makes it a particularly important step. Yeah. That's fascinating. That's fascinating. So for any of our listeners who are moms or dads or anyone like, I think the key here, if you're wanting to breastfeed, like we do not want to disrupt that relationship. I think it's also like, you know, I mean, I feel like we're starting to think about this for all kinds of diets that we prescribe that every diet has a downside. They're not like free of consequences, especially when it's like in a young infant and a mom who's breastfeeding. And you know, I feel like there's many different, totally potential consequences here. So to your question about like the sigmoidoscopy, the last time I did one was on a baby who the mom was extremely committed to an explosive breastfeeding relationship. And I was completely supportive of that. And she and I, but mostly she had gone through a whole series of food eliminations to the point that she was eating. She was on like nine food elimination, something crazy. And see, it wasn't sustainable. And so, and some features of the baby symptoms, like the volume of blood made me wonder if we were like barking up the wrong tree. So we did a flexig and turned up. It was like, you know, textbook, eosinophilic predominant, clearly allergic. And I think another important thing to know is what I did with that mom is we did alacare, you know, so we did a fully elemental formula and we did a wash out period, but she kept pumping and we did it for three weeks. Baby was awesome. And we went right back to the diet mom was on before and that baby did awesome. And so I don't think that like the, I think again, I think this is just something that's pretty transient and maybe not so hard to shift. And we can talk about what we think that means for pathophysiology. But obviously I have some opinions about thinking that that maybe microbiome mediated at least in part. And so I think just important to know that like once you find that treatment that works, I don't think it means that you're stuck with that for six months to a year. In fact, it really shouldn't mean that you're stuck with that. Oh, we need to talk about formula then because think about like all the shortages. Yeah. Well, that is the next question that we were planning on asking. So okay. So going back to you, you will ask families to or moms to eliminate milk and not like all these other things, unless and work stream circumstances. So I feel like our practice here is we typically will switch the baby if their formula fed straight to like a more extensively hydrolyzed formula. And that's like what it says in a reflux guidelines. But what do you think about that? Do you usually start by just going to soy and cut out milk alone or do you also make that more a bigger jump? Yeah. So we should talk about like, I don't know, I feel like there should be like BS before the shortage. In before shortage times, I never did soy partly because that was our classic teaching partly because there's this cross reactivity and you know, genicity that kids with milk allergy are supposedly more likely to be soy allergic. And hey, that's completely extrapolated from my gene mediated data, which this we know this isn't. And B, if you read the literature that there is out there, there's like a super wide range and I think we really don't know. So soy is super constipating for a lot of kids, depending on what your sort of bowel habits are with these kids. Sometimes that just makes things more challenging for families. So I did it sometimes during the during the shortage for sure and with varying success, I'd say, but I also more often move to an extensively hydrolyzed formula. If there's a kid that I think is really showing signs of allergic proctoplytis or of intolerance. Yeah. Okay. So it's least something we should think about and make like a good one to so yeah. And yeah. And wait, I guess a lot of times before my patients get to me, they've played like formula relit. I don't know if you've experienced that also right? Yes. Two days on this formula. So if you are going to switch to say we try soy and then we feel like, oh, that's not working. What is that timeframe that you typically recommend? Yeah. So in the exclusively formula side kid, it's a little easier right because you're not waiting for proteins to like wash out of the breast milk supply. But I just keep trying to drag my feet with all these changes as much as families will let me because I think a lot of things get better with time. I would say a minimum of two weeks, but like ideally three or four before I talk about deciding that something really with the wrong thing. And I'd say I'm comfortable with that time being a little shorter in the exclusively formula side infant. Okay. Awesome. And so is that the same? So, you know, we had briefly mentioned the reflex guidelines and switching to an extensively hydrolyzed is part of that. And so how long should a baby with reflux symptoms? So we're not talking practicalitis, but reflux symptoms be on that extensively hydrolyzed formula. Yeah. So this has even like less data, right? And is even more slippery. And I think to your point, Peter, these guidelines were based on a concept that a diet elimination was a risk-free decision compared to acid suppression being a risk-filled decision. And I think that that's probably not fair given what we know now about diet elimination and long-term risk of food allergy. So to be honest, I talk to my family is about in a purely reflexy infant. I talk to them on equal footing about allergen elimination and acid suppression as both interventions that in my mind have similarly concerning risks and benefits. And I talk to them about both. And we walk through shared decision-making and decide together. So that's probably the one thing I do that's sort of like out of guideline sync, but I would argue that piece of those guidelines probably needs to be updated since leap because those were all pre-leap. Yeah. I feel like leap has changed everything. It went to come to an infant diet. Oh, man. Yeah. But to answer your question, Jen, I think I'd say like I think two to four weeks is probably the same. But then those kids I think should have a challenge too because you're making the argument that you think they have a non-IG media and milk allergy whenever you want to call it. And those all require by international guidelines a challenge a month later. And so if you're going to do it, I think the key for all of these changes is like you have to then ask whether what you did is tell something that was important. So no, I totally agree. I think a lot of the patients that I have, I can think of that have come to clinic recently have been switched to an extensively hydrolyzed formula. Now they're having trouble finding it. They've been on it for months and months. It hasn't made any difference. So sometimes that can be a little hard. I think we're really good at saying like, oh, if this isn't working, we'll go up the ladder, right? And I think what we're not good at doing is saying like, oh, if none of these worked, like maybe we're barking up the wrong tree. Like maybe this is just reflux that has nothing to do with this milk protein or, you know, depending on the circumstance. So I think questioning that diagnosis and challenging to confirm is a super important part, no matter which kind of branch of algorithm we're on. Yeah. I like that concept of like not dragging your feet, but like giving it time and not jumping to. That sounds much nicer, maybe. Yeah, there you go. Taking your time, right? Being patient. The tincture of time. Yes, especially with something that we know that's going to resolve over time. And so talking about that, so like, what is our understanding of the natural history of this disorder, this milk protein intolerance? And you had mentioned that even a month later, people may not, babies may not have any issues. So when do you, like for like a typical case, you know, they are feeling a lot better after, you know, removing milk, whether by formula or in the breast milk, when do you recommend trying to gradually reintroduce that? So first, I think it's important to separate in your mind challenge from reintroduction. Yeah. And so the vast majority of kids that come to me have never even had the challenge, even if they're six months old or something. And so I consider that a challenge, even if it was four months ago, I mean, it becomes sort of semantics, like, is a challenge or reintroduction at that point, but it doesn't matter. So the short answer is, if it's been a month since they've been on that treatment and they're better, today's the day, try to convince them of a challenge. And then let's say they're challenge proven, right? Like I've taken care of them from the beginning, they reacted to a challenge. They were two months old when we made the diagnosis. So the IMAP guidelines say six, say, sorry, nine to 12 months of age and six months after symptom resolution, there's not really any primary data to support any of this. So that's just sort of like out there. I think it's a reasonable place to start. I start around six months, depending on the kid. And I'd say that the factors that affect when I think about this have something to do with severity. So the kids that come to me that are severely allergic, maybe I see them in feeding team, because they fell off the growth chart they had massively grossly body stools, like I'm probably a little slower about reintroduction in that kid. Then the kid that felt like, we kind of did this for reflux, and we weren't really convinced this is what we were doing. The right diagnosis and treatment in the first place. The guidelines, because they're based on sort of IgE concepts, recommend a milk ladder. And so starting with the baked product, and there's no data to say that we should be doing that for an on-igimated allergy. So I don't think it's unreasonable, but I think it also may just prolong the process. And so again, I sort of decide that based on severity and how sick the kid was at the beginning. I would say I do this differently if you're breastfed or formula fed. So if you were a breastfed infant, like I said before, I do one of two things. I there pulled that old milk out of the freezer that was from before mom was eliminating her diet. That's a super easy way to introduce. And I do it sort of two ounces at a time over a couple of days and see, watch for symptoms. And then when that's going really well for a week or two on full frozen breast milk, then let mom sort of finally eat whatever she wants. The other option, if there's no frozen milk is just to do yogurt, like directly to baby. So if baby's eating solid foods, I do a bite of yogurt, a couple of days in a row, slowly increase your dose. And if they do great with that slug of milk protein, then they're going to do fine with mom sort of liberalizing her diet. Again, the rationale for doing that is just that if it doesn't go well, you didn't sort of give them two weeks of meeting another washout with mom's supply. Excessively formula fed kids, it's a little easier because you can just buy another formula and mix it in or you can do the yogurt strategy with those kids as well. And so I think either is reasonable. I haven't had much issue with WIC except that like, or prescriptions. I just make sure that like I don't switch until I'm convinced it's going to work. And so I either like hand the sample a formula if I'm trying doing it that way or do the yogurt strategy and then only make the switch when I'm really convinced that like everybody is doing well. No, I ask that question to be added there because there is one WIC I can think of that really wants you-- they push you to do those challenges starting at six months, which is fine. But they will not commit at least my recollection. It's been a few years now. But they wouldn't actually continue the hydrolyzed formula unless you've done the challenge of starting at six months, even for the severe kids. So we definitely had to-- Wow. So whatever WIC you're thinking of is ahead of all the-- I know. The turns out they were correct. They're trying to save money, but they're also medically correct. Yeah, it's something that we've tried during the shortage, again, that we tried to be a lot more judicious about as a group, as like are we appropriately trying to get kids on sort of more standard formulas as quickly as we can because we can literally help the supply chain by not having kids that don't need it anymore on these formulas. So-- You know what I mean? A story. So Emma was on Alentom, which was-- I remember that. Where she was going all over trying to find it? Yeah. Like there's one time when Leslie went to like eight targets in a row because there's sales-- Oh, and then she like bought all of them. She bought all of them. Yeah. And they were two physicians. And we're both like, oh my god, it is so expensive to buy this stuff. It is. But then the shortage happened. Yeah. And I have all these like formula samples that were sent by a company that sponsors one of the fellow conferences. So we just gave Emma like all the samples. Yeah. Like all these different formulas. And anyway, she was fine. Yeah. So yes, she was like, I think nine or 10 months. Well, a point about that, right? There's some pretty disturbing data about the degree to which the formula shortage affected our patients of minority families of lower socioeconomic families. And I think in particular, folks that can't just go out and pay that $300 on eBay that like that can of Medicare was going for. And so I think being-- I think there was some widened disparities there that we should all be mindful of and careful of and pay attention to. And I think, again, just making sure we don't have kids on things that are expensive and not in their best interest for any longer than we need to, no matter who they are, is something really important. OK, kind of along that line, I remember having this conversation with Iver Hill that I had clinic with all the time. And sometimes we'd have babies who would be on an exclusively hydrolyzed or formula. Or mom is eliminating food in her diet. And the baby still has intermittent, grossly visible blood. And we would kind of talk about, like, do you actually even need to treat this? Like, do we have to? What happens if we don't? Yeah, so awesome question. Would love to do that prospective study. Not sure. Again, we'd be allowed to, but I think it's a really important question. So in GMAP, it was observational, right? And so 20% of kids' family is elected not to do any diet elimination and to watch fully weight. A lot of them did, like, probiotics or some other things that they tried. And that 20% of kids got better just as fast as the group who did any diet elimination. Now, observational study not randomized. And so you could hypothesize. And I think probably it's true that, like, that subset were not the severe kids. Those weren't the kids showing up with, like, blood full of diapers, probably, that the parents said, like, well, just watch, right? But there's definitely something to be said for that. And I do wonder how many of these kids, if we, in Peter's terms, leave it time, would just self-resolve. I think it's really hard to know. So let's say that guag positivity or grossly buddy still is even a better example. You know, some degree of inflammation in the GI tract, like, is that bad? It's hard to imagine that's good, but it's hard to know. There's really no good data to tell us what to do. And so I use other signs. You know, happy thriving baby, pretty intermittent. I'm OK watching that baby. You know, aversive, miserable, uncomfortable baby. Like, no, I probably would watch that and would think about next step. So I really try to treat the baby. I also think some of these kids have, like, a fish or sometimes that has like a streak of blood in the abyss. And you know, it's not exactly a perfect science to establish that. And I think that made, you know, we maybe completely barking up the wrong tree with diet elimination in some of these kids with, like, a periodic streak of blood. Especially when, like, the, like, there's no, like, strict diagnostic criteria. Like, the presentation is, it covers, like, so many different things. Pretty much anything abnormal, like, why don't you just try this? That's lame cows. Yeah. So, I mean, but what about, like, you know, we talked a little bit about, you know, concerns about if we cut out stuff from a baby's diet, does that increase the risk of an Ig-media, you know, Ig-e-media allergy in the future? But what do we know about, like, if they did have milk protein intolerance in general, at all, does that or tend anything in the future? Like, does that increase the risk of allergies, if, you know, or whatever? Wait, before you answer this question, I think Peter's really asking, did you read a paper I published when I was a med student? Like, all these years ago, or whatever. No. I'm just kidding. There is a seminal pain. Peter, do you want to, do you want to give us a summary of your fellowship? It's actually a medical school. Miguel Saps gave me a list of 2,000 patients to call. I remember this. I did it. And I was like, what did you, Peter? I don't want to talk about it. So, this is not about me. This is about you. Yeah, but you were asking the question about, aren't we a team that you published? This is a team. We're all a team. They had, maybe, an increase your risk of functional GI disorders, OK, but maybe. Yeah. I don't want to talk about that. Yeah, so I think this is super interesting. So, I'm going to answer all these questions over the next 18 years. You have to have these ask every year. So, right now, what we know is kids with allergic proctokolitis as diagnosed in our cohort at least are at an increased risk for having eczema. That's not terribly surprising, but we should talk about that a little bit more about what that means. And absolutely have an increased risk of Igmediated Food Allergy, which is completely contrary to what the textbooks say, but like pretty clear in our data set and published in 2020. And so, I think that is what gives me real pause for all these decisions that we make. I think an important question is, like, is that because they have a disease that puts them at risk based on shared pathophysiology, like egg-smuck kids with eggs that are more likely to have pseudologies, right? Or is it because we're diet eliminating them for this, like, really critical immunologic window over the first. year or is it full, suspect it's full, but I think of kids with AP, like true allergic proctocolitis as the same bucket as kids with eczema in the sense that like their risk is increased. And if you remember like the original leap study, that was really at high risk kids and those high risk kids were just find as by their degree of eczema. And so similarly, I think about these AP kids as the kids that are so important to get other allergens back in. And so just to plug here for like say you're seeing that kid at that six month visit, you're not ready to do reintroduction quite yet, but they're eating solids. Like I spend time in my GI visit talking about peanut introduction and that kid and we certainly should be doing I think peanut and I think there's reasonable data for egg too. Even before we're ready to talk about reintroduction of milk, like let's get these other foods in nice and early. And so I start talking about that at four month if not before with that population. There's some retrospective data that kids with AP are more likely to have EOE, but looking backwards from kids with EOE and we're looking to see if we can validate that prospectively, although our numbers are probably going to our ends going to be pretty small for EOE, obviously in a healthy cohort. There was a little bit of murmuring in the literature about increased risk of IBD. I haven't seen that really corroborated. And the functional stuff I'm super interested in and we're looking at a lot. So in GMAT, we're currently looking at functional constipation rates in those kids and whether or not that correlates with milk introduction, right? Like is it really about milk at all? I think it's a super interesting hypothesis that these kids have irritated or irritable guts early on and that makes them much more likely to be sensitive later to any sort of sensation. And we're also looking at lots of psychiatric metrics, but particularly like anxiety and temperament. And I'm super curious like how that made track and like in what order those things may. That really is. Can I ask you to add something in if you haven't? Yeah, no, no, no, no, I just think this is so important because I have been talking a lot about my, you know, I think that the diets that we prescribe for different things like a little FODMAP diet, for example, for IBS can be super, super helpful, but it can be. It can. So hard. Yes, so hard. But I also think that sometimes we may inadvertently stimulate in a negative response or interaction with food. So I'd be curious in your patient cohort too, like, you know, thinking about eating disorders later in life or disorder eating or disorder relationship with food and what that might look like. If, you know, you have a parent who's so worried that has been removing so many things from their diet, how does that translate over time? Just curious. Yeah. And even like even earlier on in life, right? Like are these parents more worried about doing peanut because we've had like, I think so in my clinical practice and so I'm asking you and none of them are doing peanut, even though we have no data to suggest this shouldn't have anything to do with peanut allergy. Like why aren't they getting that same early introduction advice? And so yeah, I think we make, I think we make a lot of families and kids pretty stressed about this. And I think if it's really so transient, it probably doesn't warrant that degree of thanks. Gosh, I tried to introduce peanuts so many ways with my daughter, like literally so many ways. Anyway, you can get peanut into a child. I tried she would not eat it. Well, she has I.G. I did. Oh, she's yeah, she has like a I.G. like allergy to peanuts. They're super interesting data about that. And I think it's a super cool concept, right? I think we've always thought that kids would not like or have an aversion to a food after their allergic because they have bad associations. But actually, there's lots of anecdotal and even reasonable body of evidence that some of them have an aversion to it before they even present allergic to them. I literally described it. And in one point, I was like, okay, you know what? You know what? Everybody university loves that has peanut in it. Captain Crunch peanut butter. And Mark is like, you cannot feed that to a six-month-old. I'm like, watch me. So I blended it. I literally tried to get peanut in her in any way that you could. And she would not eat it. Wow. Everything else. Her favorite food were color greens, by the way, which is not. But she would not eat peanuts. I lost all credibility as a parent when Leslie founded about the leap study on Instagram. And Emma was already six months old. And I was like, oh, yeah, I remember that. I went to a grand round. They talked about it. And she was like, how come we're not doing that for our child? So the next day we had like, because I think the original study was those like bomb us snacks or whatever. Yeah. Yeah. We had bags and bags that we she ordered online and like, but I won. Okay. So the other thing that she ordered online was all these allergen powders. I don't know if you've seen those. Nick now they have products where it's like 17 allergens all combined in one powder. You like put it in there, you know, whatever their food. So like, I mean, obviously there's not data for all those things. But Dr. Martin, what do you think? Is this something that we should be? I'm not saying we're like encouraging families to do it. I'll tell you what I did in my own kids. And as much as that reflects what I think we should do. And, you know, I used I use real food. I didn't use the powders because I think there's probably things to be offered in the real food in the way that it comes microbiome. And otherwise that may be beneficial in as much as it's feasible. But like, you know, you can't give your six month old like all kinds. So like thinking about creative ways to do that. And I marched through in the order in which, you know, food allergies tend to present in kids, you know, frequency wise. And so, you know, we had, we did have like all seven allergens into our kids by seven months. But like, this is what I do for living. So that's not surprising. I think the powders are like, they're pretty expensive. Like, I think they work and they're theoretically great. I just think that like, you can probably accomplish a lot of it with like what you have at home and a blender. And a few key products to know about, like, there are some mixed tree nut butters that are awesome that even sort of use like peanut butter. You can melt warm peanut butter so that it gets really liquidy. And that can be easier to incorporate in kids food. Peanut powders really easy to find online on Amazon and is great and smoothies and stuff like for grownups too. So isn't just like a product that you use like this much of and then goes bad in the back of your pantry. So but yeah, I think, you know, trying to incorporate these woods in an age appropriate way as best you can makes good sense. I think for a family who says like, I can't do that unless I go use the system. Great. Like youth the system. But I tried to do it mostly in real food in our kid. Oh, man. That's fascinating. You know, if you made an Instagram account about this, if you like, you'd have a million followers. I don't know about that. Instagram doesn't pay as much. You have to do YouTube. Okay. So moving on. So this, I think this topic is so important. And it's something that we all deal with every single day in our practice. Really, I mean, I feel like I can't think of a clinic where I haven't had at least one patient who has come with concerns for intolerance to the cow's milk protein. And so thank you so much for spending this time. I wish I would have been in fellowship with you too. I feel like you would have been super fun. But looking back, looking back at your career, what has been the most valuable advice that you have received and what advice do you have for our listeners? Okay. I have a couple. I can't do this one for trainees. I would say, you know, somebody told me to like, choose the mentor, not the project. And while I'm really, really excited about the topic that I study, I chose it because there was an incredible mentor to follow. And I think that if you can find and build that a mentorship team around you that is incredible and cares about you, that's incredibly valuable. So I'd say that's number one. You know, there's like some saying by probably someone famous, like, if you love what you do, it will never feel like work. I would like amend that. Like I think if you love what you do, it won't feel as much like work. But it's also okay to care about your family as much or if or more than your work. And I think finding that balance that we all strive to find with family is super important and a balance life of the happy one. Surround yourself with good people and mostly it'll be fun. I like it. I like that. Yes. So good. So okay. It's so good to talk to you. And it's been, it's been too long since we've talked. What do you think? Let me back. What are the main three? This is like a challenging question. We just just decided to add like right before you your episode. So what are the three main points our listeners should take away from today's episode? Okay. Point number one, milk protein allergy or intolerance or allergic proctocolitis or whatever you want to call it, we're almost certainly over diagnosing it. And we can help that problem by following the guidelines and most importantly by challenging patients a month after we diagnose them and they're better and by reintroducing them as soon as we think they can tolerate it. Number two, I would consider as much watchful waiting and shared decision making and taking your time with each step and not not playing formula or dietary elimination relapse. Jen Coindit. I like that term. I'm gonna use that now. Number three, if there's anyone listening to this who is actually as excited about this topic, I would love to hear from you. GMAP is really big and we have a long time to go and we love to collaborate. So Peter, you want a lot look at functional GI disorders with us? Like let's do it. And so really truly, please reach out because I'd love to continue thinking about these sorts of collaborations and understanding this to be better. I love it. That's awesome. So good. So good. Thank you so much again for joining us. So I'm famous like right now. Like this is the moment. No, well, I would say that there's very few episodes that people would actually end up changing their practice as much as your episode. You know what I mean? Well, actually the biggest thing I'm gonna do right now, is getting clinic next clinic. Uh-huh. It's use the terminology of challenge versus reintroduction. I love that. Yeah. To me, that's my biggest takeaway that I want to change my practice because just calling it a challenge, which is a little less scary potentially, especially I think that that terminology will be really important. Yeah. Well, I think it's just you can take it out of yourself and say the international guidelines say that we can't make this diagnosis without a challenge. And it's a really important one because some kids are already over it and then they don't need to be on this diet for a long time and you can potentially prevent long term IGV data life-friendly allergies. That's my like two sentence. That's hard to argue against, right? And so yeah, man. And then some of them are going to be really pissed at you and back in their miserable. But you like set out that plan ahead of time and then you're like, okay, now we know what we're dealing with and now it's legitimate to like make these changes in your life for sick to mind months. But at least we know going into it. That's the right thing. Thank you guys so much. It's so fun. What a great episode. She's so good. Yeah. She's so good. I think it makes the rest of our fellowship class across the country look bad. How successful she is. Oh no. She is what we aspire to be. Gosh, we really want to thank Dr. Martin for taking the time to sit down with us. We really hope you enjoyed as much as we did. So good. And if you don't already, be sure to follow us on Twitter and Instagram at @BowlSounds and on Facebook at @PediatricGiPodcast for the latest news and updates on upcoming episodes. And if you like what you heard and you want to support the podcast, it would help us out if you did one or all of the following three things. Tell a person about the podcast, leave a review on Apple Podcast to help others discover our podcast and on the Buzzsprout page, there's a link to support the show by making a donation to the NASPEG and Foundation. You can get there at www.naspghan.org. The money you donate helps support some of the amazing things the NASPEG and Foundation is doing, including supporting pediatric ER research and public education programs. And as always, the discussion of using recommendations of this podcast, the sole responsibility of the hosting guests and subject to change the advances in the field. Thanks for listening. Thanks. Bye. [Music]