Chapters Transcript Video Pediatric Celiac Disease: Bridging Guidelines and Clinical Practice Telly Cheung, MD discusses celiac disease for children. Thank you all so much. Let me share my screen. OK, that looks, that looks good so far. It looks good, yep. OK, fantastic. Well, um, thank you all again. My name is Kelly Chung. I am an assistant professor of pediatrics in the division of gastroenterology, hepatology, Nutrition. Thank you, Maria, the CME team, and everyone for having me here. Uh, my background, I am, uh, one of the providers in the celiac disease team at UCSF, and I'm working on program development as well as improvement. My goal today is to talk about pediatric celiac disease and to bridge guidelines, current research, and our understanding of celiac disease to clinical practice. I do not have any financial disclosures. Here are some of our learning objectives. Firstly, we'll identify the current gap in celiac disease. Specifically, we'll identify the critical gap at our institution at UCSF and the Bay Area that spans multiple counties. What we find is that inadequate clinical access is an area of improvement needed for children and our households that manage celiac disease. Uh, in terms of our other learning objectives, we're going to aim to recognize the pathophysiology and epidemiology of celiac disease. We're going to define. The evolving clinical presentation. Excuse me. And lastly, we'll review the screening and diagnostic criteria and treatment approach. We'll try to contextualize the key role that pediatricians have in celiac disease and specifically in the screening for celiac disease. We'll start by presenting a case. So here we have an eight year old female that presents with recurrent abdominal pain associated with nausea, diarrhea, headaches, and musculoskeletal aches. They present to your pediatric office and you do your history and physical. Starting with the history, they define their abdominal pain as intermittent, paringbilical pain over the last few months. It occurs a few times per week. It ranges from mild discomfort to severe episodes of crying. It's often worse with appetite. However, there are no clear food triggers. For the diarrhea, it seems to coincide with abdominal pain and increased bowel movements. For the headaches, it appears to recur monthly for the last few years. It's worse with bright lights. It improves with sleeping in a dark room. There there appears to be a component of blurry vision, but no vomiting or fevers. In terms of the musculoskeletal pain, this patient endorses having her left middle finger swelling. It uh uh occurred suddenly and no subsequent trauma or initial trauma, nor difficulty bending with the finger. She has had this diffuse knee, shin, feet, and hip pain over time as well. When you ask about her medicines, family medicines, her family history, medicines, etc. She takes Tylenol and ibuprofen as needed, as well as albuterol as needed for exercise-induced asthma. She's otherwise a healthy 8 year old, previously termed, has had resolved eczema as an infant. There is a family history of migraine headaches for maternal aunt as well as mother. When you ask her about herself and her family members, she lives with her mother, her father, her older sister. She has good friends at school and is doing relatively well, and she enjoys playing soccer. You open up her growth chart, and these are the graphs that you see. So on the left side is her weight and the right side is her height. The stars indicate that period when they started that initial evaluation and subsequent weights and heights are where she has developed over time. So we focus at the onset. Uh, over time for her weight, she's been mostly in the 50th percentile for weight, notably when she comes to your office, it seems to be a down trending a touch, a little bit closer to the 25th percentile for weight. Her height has fluctuated, anything from the 65th percentile, maybe a number in the 90th percentile. Truth is somewhere probably in the middle. This pediatrician also initiates a workup. They start with looking at her hemoglobin, which is 12.9 with an MCV of 81, platelets of 306, white count of 7.8. Her inflammatory markers are normal. Her electrolytes are normal. Her liver enzymes are appropriate. Her thyroid studies also were normal, and her ferritin and vitamin D look normal. Uh. Notably, this pediatrician does obtain the serologic markers for her, and what we do find for her is that her tissue translutainase IgA, one of the serologic markers we look for in celiac disease, was markedly elevated, greater than 100, and we point her eyes to the reference range, and the upper limit in this case for this for this lab was 3. We also had obtained a deaminated gluten peptide IGA. It was known to be 121 with an upper limit of 20 for this reference lab, as well as a serum IGA. It gives us a reference value. This was relatively normal, 138. So, now with this case, we have an eight year old female with recurrent abdominal pain, diarrhea, extraintestinal symptoms found to have positive celiac serology. So as a pediatrician, what do you do next? Diagnose celiac disease. Treat by recommending a gluten-free diet. Refer to gastroenterology. By the end of this talk, my hope is you'll have answers to this question, and we'll review the case at the end of our talk. My hope is that in addition to our learning objectives, we'll, we'll review the data to strategize your approach as a pediatrician. We'll discuss when to refer to GI and steps in between the referral process. And what I'll highlight for this case, and it'll come up again as we talk about the clinical presentation of celiac disease, is this 8-year-old has extraintestinal symptoms, headache and musculoskeletal pain. And not an obvious picture of growth failure, right? There might be a slight down trend in her weight, but I wouldn't define her as growth failure by any means. Lastly, I'd like to commend this pediatricians, astute workup. Uh, they had screened for celiac disease, and that will be a focus, um, as we get to the end of our talk as well. So starting with our first learning objective, uh, my hope is to identify here missed opportunities for screening and intervention. I'd like to define this, this gap. So, uh, I completed my fellowship at UCSF in pediatric GI and as part of my fellowship project, I did a retrospective chart review. I looked at over 10 years of data between 2013 to 2023 at the time. In the San Francisco Bay Area, I looked at all our patients under or with or under 18 years of age with celiac disease positive serologic markers, and what we found is that probably less than 10% of all potential children with celiac disease were seropos. And identified at UCSF. If we do some math and look at the socio-demographic population we have in the Bay Area, among of which is 7.7 million people, and say we estimate the number of children of those 7.7 million people, we're missing about 20,000 kids with celiac disease. That's about 90% of kids. This data does align where Celiac with other countries where celiac disease is underdiagnosed worldwide. Um, the next question that begs is, why are we missing diagnoses of celiac disease in children? And in the consideration for this question, there are a few thoughts I've had. Number one is maybe they've been referred and they're waiting to be seen by GI. I would say that most of our referrals in GI are usually um seen. Our, our patients are, are seen by us in GI. There is a waitlist and there's a time period to that, but we often see our kids. Number 2, patients maybe are screened, diagnosed, and seen outside of UCSF in Oakland. Um, I think about our friends and colleagues at UC Davis, Stanford, and other pediatric centers, but is it possible for them to, uh, contain the other 90% of our population? Maybe, maybe not. And then thirdly, maybe patients are presenting or not seeing their physician for symptoms or maybe they're asymptomatic. So there could be a level of patient education and advocacy that we'll continue to work on in GI. And then option 4, maybe we're not screening enough as pediatric specialists and potentially in our community, and this is the area that we'll focus on that in my area of interest. It includes all of us in GI, endocrinologists, specialists, and pediatricians. So, taking a step back, what I'd like to do is talk about the uh definition of celiac disease and talk through the pathophysiology, how it presents, and a bit of the epidemiology. So first off, celiac disease is an autoimmune disease, and it's one that's triggered by dietary ingestion of gluten in genetically susceptible individuals. This definition is very specific and it does touch upon important features that will, that will continue to readdress. Um, it does incorporate the dietary ingestion of gluten. That's an important factor, and it's among our patients that are genetically susceptible. And to give you just a very broad overview of what that looks like, say we had completed an endoscopy or a camera study for one of our kids with celiac disease and say they did not have gluten ingested in their diet at the time. So on the left picture here, if we moved our endo endoscope into their duodenum, this is probably what we would see a normal small intestine or duodenum. With the normal folds of the duodenum, and if we looked at a little bit at the tissue level, it should look more or less like a shag carpet. We see those, the intestinal brush border with the microvilli that protrude, protrudes and is important for absorption of micronutrients, nutrients, and etc. Among that genetically susceptible individual where they do ingest dietary gluten, they can present with the picture on the right side. So, Uh, what we see here is, um, what we describe as duodenal phyllis blunting. So if you look on that top left corner of this, of the right picture, it does look like there's this frayed off component to the, to the small intestine, almost as if the villa are not as robust or not as long. And that is part of the pathophysiology of celiac disease. And we'll talk more about what that looks like, uh, endoscopically in the OR. This is what we can see with celiac disease. The gold standard still is to take biopsies, look at it under a microscope, and that gives us the definitive diagnosis. But these are some things we can see, um, as part of the, as part of that pathophysiology. The next component I'd like to talk about is, uh, differentiating gluten-related. Disorders does matter. So here on the left side is a figure that I tried to use to represent what's, what are some categories that we can use to define gluten-related disorders. So on the left side is autoimmune diseases, and that's where celiac disease fits. We talked about it being an autoimmune process. In the middle is an allergy category, and what I consider a gluten-related disorder relative to allergies is, say, wheat allergy. Wheat is one of the six major food groups in our diet, wheat, eggs, soy, fish, um. Uh, nuts as well as dairy products. Uh, a wheat allergy in this case is in the name allergy. I consider this, um, that IgE mediated anaphylactic type response, often with respiratory signs. That's not exactly what celiac disease is. And what I'll add and clarify here, and I do think that specificity matters here, is celiac disease isn't necessarily an allergy to the strictest sense. It's an autoimmune disease. Um, and I think that specificity should be used to help us as clinicians understand celiac disease and ultimately for our patients, uh, our kids and our households understand celiac disease. On the far right is where gluten-related disorders are classified as, say, non-immune and non-allergy. These are the scenarios where we have patients consume gluten. They are symptomatic, however, they don't have particularly the serologic screening positive markers that we can see in celiac disease, nor do they have intestinal injury. With that said, they still have symptoms when they, when they consume gluten. And that does and may have an overlap with some of our disorders of gut-brain interaction, uh, and this is, is an important and large category. Here is an article uh that comes out of JPGN Journal of Pediatric Gastroenterology and Nutrition in 2016. This is the most recent guideline for celiac disease. I say most recent as Um, time often outpaces our guidelines, and in our pediatric society, we're working on developing more recent updates to our, to our guidelines, but as a reference for pediatricians and our audience here, this is a good one. JPGN in 2016, it's the celiac Disease NAS began guidelines. And what I'll highlight here is this, uh, table characterizes some of the presentations, uh, of how each of these categories present celiac disease, non-celiac gluten sensitivity, and wheat allergy. What I'll just highlight in this blue box is wheat allergy or WA has again, the respiratory symptoms of an IG immediate reaction. And that's not often what we see in celiac disease. And this aspect does matter because celiac disease has morbidity and mortality to it. Uh, for among our children, we think about growth failure and among teens and adults, we think about osteoporosis, infertility, and GI cancers. Here's a very busy slide of the pathophysiology of celiac disease, and I'll try to summarize it as simply as I can, and I'll highlight a few numbers as, as they'll show up on the screen to pinpoint areas of where um we can generally categorize how the pathophysiology presents. So first you have food, right? Food, gluten is a protein. It's a protein that's found in wheat, rye, and barley. And as we consume gluten, we first masticate it. As it gets masticated, it passes through the esophagus into the stomach, and ultimately to our small intestine. When it does reach the small intestine, for number one, The gluten is in our intraluminal space, and as that gluten passes through our epithelial layer of the small intestine, it passes intracellularly, and as it passes intracellularly among our patients with that genetic susceptibility, there's an autoimmune reaction. There's an enzyme called tissue transglutaminase. It leads to a diamidation chemical process to ultimately create an immunogenic antigen. That antigen binds to HLADQ2 and DQ8, which are hap haplotypes that are important in part of that immune cascade, and that ultimately leads to the downstream effect of an innate as well as an adaptive response. Um, there are a number of interferon gammas, IL-2, IL-21 that I won't dive deeply into, but ultimately this inflammatory reaction leads to the development of antibodies. So on the bottom right, the antibodies to that tissue translutaminase, which is why we look for TTG or tissue translutaminase IGA. We have the enzyme and we develop antibodies to the enzyme, and it's ultimately what we use to screen for celiac disease. And then secondarily, um, as that immune response progresses, we have lymphocytes and other immune cells, um, end up in the epithelium of the small intestine, and that leads to the injury to the small intestine that we can see with our eyes in that first endoscopic picture I showed you and ultimately under the microscope. And you notice here that purple brown cell that says IEL along that, um, along the epithelial layer. IEL is intraepithelial lymphocytes in the, in the, in the epithelium where the lymphocytes are. And that is, uh, as we count those cells, that's one of the diagnostic criteria we use histologically to diagnose celiac disease. So it's kind of a big picture. I hope to just summarize it as, as succinct as possible. As we think about now the epidemiology of celiac disease, it is high. So prevalence is the total number of individuals with a disease, in this case celiac disease. Based on a systematic review and meta-analysis that was published in 2018 in Clinical Gastroenterology and hepatology. Again, these guidelines and, and studies quickly outdate us. We're in 2026 now. This is 8 years old. However, it's the most comprehensive data that we have had, and what it tells us is that if we look at celiac disease globally, the percentage or the global prevalence of celiac disease is 1.4% of the global population. This amounts to about 100 million individuals worldwide that are serro positive. About half of this, 0.7%, are biopsy proven to have celiac disease. The truth of who does and doesn't have celiac disease is probably a bit in the middle, as not every patient that is serial positive for celiac disease has the capacity or access to a gastroenterologist to get biopsies and get diagnosed. So again, we generally use the number of about 1% as prevalence for celiac disease based on area, based on location, state. This might vary a little bit, but generally about 1%. So 1 in 100. 1 in 100 for any disease is relatively high. What I'll highlight second is if we look at this map, we see a lot of blue colors and these are effectively quartiles that looks at the countries in which we have data. This includes the US, Mexico, parts of Western and Eastern Europe, including parts of Latin America. What we see here or what we don't see here is actually missing data in South, most of South or a lot of South America, Africa, as well as Asia. As we continue our epide epidemiology research and define the prevalence in other countries, we'll have a better sense, with the data we have now, again, our estimate is about 1%. The other important factor with celiac disease is incidence. So incidents are effectively new cases over a time period. This is a publication or figure that comes out of the publication of the American Journal of Gastroenterology in 2020. And what we see if we look at the time period between 1950 to 2020 and we look at the y axis, which is the new cases, if we follow one color, we're following one country, and we see that the incidence or the new cases of celiac disease has generally risen over time. The neat part of this figure is that if we can also compare colors, so we can compare colors and effectively compare countries and look at the incidents comparing countries. One of the um features of this study is that I won't highlight too much, but what I'll say is they did divide out this um incidence among adults and pediatrics. And what we find is that among pediatrics, we have about nearly double the incidence of celiac disease. So we're looking for it and we're diagnosing it more in in our pediatric population. And I think that ultimately affects how we think about it as pediatricians, as gastric pediatric gastroenterologists, um, and how we move forward. What I'd like to highlight next are risk factors. So Celiac disease has multiple risk factors, and this is a relatively busy slide. I'll try to summarize it as best I can as well. So in the blue arrows are two of the more, I would say most important factors here. Gluten, as I mentioned in the definition, is dietary gluten is necessary for the disease. And then number 2, genetics. So as I mentioned, those HLADQ2 and DQ8 molecules, those are important as effectively when I talk to, talk about it with patients, they're Lego pieces, Lego pieces that are important for the immune cascade, uh, those are important for the development of celiac disease. In studies that we've looked at twins, concordant studies, we look at twin A and twin B with um identical genetic information, we find that the concordance is about 75%. Meaning 25% or 1 in 4 of those twins has discordants where 1 may have celiac disease and the other doesn't. What that tells us is that celiac disease, despite the dietary component, despite the genetic component, has an environmental, environmental component as well that I don't know if we have fully understood yet. And this is where the rest of the factors here come into play. For every, every study, for every one study that shows that there might be an association between the diet, pregnancy, place of living, infection, socioeconomic status associated with celiac disease, there's another study or more that showed maybe there isn't a difference. A lot of these studies are observational in their design. And the general consensus is that there might be individual risk factors that may that reflect confounders that are not fully measured by these factors alone. Um, so it's difficult to say what these factors are. What I will highlight is one place of living or effectively even race and ethnicity. What I'll say is that there is a misconception that celiac disease, um, historically is, is a condition primarily in young white children of North European descent. These findings over time likely suggest more of diagnostic tendencies or even clinician bias of whom we do and do not screen. Um, what I rather us do is shift that, uh, that, um, conception and use some of the more, uh, well studied risk factors that we will talk about, such as high risk associated conditions, clinical presentation, and potentially even their genetic presentation. Um, I want us to recognize that there is a potential bias in screening celiac disease based on race and ethnicity because this is such a, such a, uh, nuanced area that has noisy data. In terms of genetic susceptibility, it's critical for the development of celiac disease. More than 98% of patients generally have one or both of these haplotypes, HLADQ2 and or DQ8. On the figure on the right, if we take 100 people, 100 individuals in the general population, and we look at it as a 1010 by 10 row by column table or graph. Uh, about 35 of those 100 patients or individuals will have these markers, HLADQ2 and or DQ8. About 1 in those 35 will have celiac disease, or about 3% of the genetically susceptible will have celiac disease, or 1% of the general population. What we use for this clinically is that um in some cases where there is ambiguity or equivocal findings, genetic studies, if they're positive, tells us that there is a risk for celiac disease, but doesn't necessarily mean they have it. However, if there is a negative genetic testing for these haplotypes, then it's much, much lower likelihood. So the negative value is much more useful for us. Uh, what I'd like to highlight also is that CR disease is associated with many conditions. I try to categorize this into four major categories family history, autoimmune disease, genetic syndromes, and immunodeficiencies. Uh, next column are some of these conditions, and on the right side are the estimated prevalence of, um, of these conditions in celiac disease. If we use celiac disease again, 1% prevalence, it gives you generally how many folds increase relative um for these conditions to have celiac disease. So anything from looks like 2 times to up to even 10 times increased fold of having celiac disease when we have these conditions. What I'll highlight here in the orange or yellow arrow is first-degree relatives with celiac disease, we generally quote anything from 5 to 10 times increased risk. These are our biologic mother, biologic father, and or siblings. And then also I'll note other genetic syndromes, Down syndrome, Turner syndrome, Williams syndrome. I highlight these because our pediatricians and other specialists may see these patients sooner than we do in gastroenterology. So what I like to highlight as pediatricians and specialists. They have a key role in screening these high-risk populations. And I mentioned high-risk populations because um it is uh the more common approach or more common population cohort that we diagnose celiac disease in our, our current period. Um, how does celiac disease present? It is evolving over time. This is a busy slide, but again, I'll try to summarize it. On the left side are how adults generally present. On the right side is how pediatric, uh, kids generally present, and in the middle is how they share some of the symptoms and signs. In blue, highlighted boxes are the extraintestinal manifestations, and in the green box is the gastrointestinal manifestations. What you'll notice is that there seems to be a lot more blue than there is green, right? Where there's uh oral or mus muscucutaneous presentations. Logic presentations, hematologic slash anemia, dermatologic slash skin findings, and musculoskeletal findings. As you remember, our 8 year old case, our 8 year old female that we presented in this case had also musculoskeletal pain as well as headaches. And if I were to ask, what is the quote unquote classical presentation of celiac disease. I would think that the majority would say probably a child, an infant with malabsorptive features, abdominal distention, stomach pain, diarrhea, growth failure. That had been our classical phenotype of how it's presented, but that has changed over time. Um, what I'll highlight first is that along the right side here, uh, short stature is one of the common ways children can present. Along the left with the yellow arrow anemia is how teens and older adults can present, often with iron, B12, and folate deficiency. And along the green arrows are how both the children, adults, and teens can also commonly present headaches and fatigue. Um. With that context of the classical presentation, what we do find actually is that they don't account for most cases of celiac disease in this now, as I talked about in our previous slide, diagnoses are now older, older age, as well as presenting with extraintestinal symptoms, and that's about 60% of our cases. What I try to do here is also present that uh information in another way. We know that celiac disease is heterogeneous, and this is mostly to highlight, uh, this table comes from the New England Journal of Medicine in 2026. This was celiac disease as a The clinical presentation was just published in the New England Journal of Medicine last month. So within the last month, it has been a highlight and an interest for us in medicine. Here's a table that identifies the extra gastrointestinal manifestations of celiac disease, and here are the common manifestations. There also is a second half of this, or rare manifestations, which just for brevity I don't show here, but this is a good reference for others to go to in terms of the most recent case presentation. Uh, what I try to highlight here, again, uh, the main point is if you can name an organ system, celiac disease can and will affect that organ system. The arrows here are to highlight again the common presentation among kids, delayed linear growth, delayed puberty, and a presentation of iron deficiency anemia. What I'll highlight next is here the the serology and specifically as a sensitive and specific marker for celiac disease. Here are some of our important players. Here, tissue transluaminase, shorn TTG or TTGIGA ordered with a serum IGA. One of the highly sensitive, specific, and cost-effective ways we use to screen for celiac disease as one of our first-line testing. As we think about again, as I mentioned earlier, equivocal cases or cases that depend on age, endometrial antibody or EMAIGA is one of those second line testing that we can use. Um, not the huge focus of this talk, but what I'll mention is, um, outside of North America, our Europeans have developed guidelines that use serologic diagnoses, using blood markers as opposed to only, um, biopsies. Here in the North America, we still, um, favor our endoscopic approach to diagnose celiac disease. Uh, what I'll note also for deaminated gluten peptide is that it is among the right age, less than or equal 3 years old, helps us increase the sensitivity and specificity of diagnosed celiac disease when there is suspicion. Um, here's a table that comes out of that guidelines in 2016 for JPGN. I put in red lines, the serologic markers we no longer use. In the past, these have been used, anti-lenin antibodies. They're not sensitive, not specific. They are not used now. What I'll highlight in the yellow arrow is TTGIGA. What we see is that the sensitivity is about 90 to 100% and the specificity is 95 to 100%. Without diving too deeply into the epidemiology of what that means, effectively, negative TTGIGAs are generally true negatives and positive TTGIGAs are generally true positives. The takeaway from this slide is, uh, as a first-line test, tissue translutaminase IGA with at least once a serum IGA is an important way that we use to screen for celiac disease. Um, here's another article that I'd like to, for us to go through a little bit. This was published in pediatrics in 2025, so relatively recently, and, and one of the uh results or conclusions of this study was tissue transisertamminase IGA, when it's greater than 10 times the upper reference limit for that test, it correctly diagnoses celiac disease in about 95% of kids. Meaning 95% of kids with that super high TTGIGA um ultimately are predictive of having those biopsy findings consistent with celiac disease without necessarily doing the biopsy. Um, this is one of the largest multi-center retrospective studies in the US. It included for celiac disease and included over 4000 kids. What I'll highlight as a nuance is that this 95%, which effectively defines positive predictive value, was based on the prevalence of celiac disease seen in GI referral centers, so not necessarily community pediatric offices or the general population. Um, the analogy I'll bring is if we had 100 individuals, children come to our pediatric clinic and 100 individuals come to our, our GI clinic, which group is more likely to have celiac disease? Probably the latter, right? In GI clinic, we're filtering all our patients with likely or potentially stomach pain, diarrhea, growth failure, extra GI symptoms, whereas maybe in, in our pediatric office we're seeing the general population, and we know that's about 1%, right? We're doing well child checks and all that. The conclusion here is that we can't exactly extrapolate this high predictive value or the good good performance of this test directly to pediatric offices, because, and this is a core tenet of statistics, is the positive predictive value of a test is based on the prevalence of that disease. And if our prevalence may be filtered and higher in the GI clinic, it gives us a much better test in that case that may not be replicated in a pediatric office. Here's another way that I tried to show this in a table. We know that the prevalence of celiac disease is about 1%. Using this study and using the data behind it, if a TTGIG is greater than 10 times upper normal limit, with the prevalence of 1%, we would have a positive predictive value of 65%, meaning we would misdiagnose celiac disease using only blood markers about 35% of the time or 1 in 3 kids. As that prevalence increases, that positive predictive value increases and our percentage of misdiagnosing reduces. Um, the key here is with positive serology markers, consult your gas gastroenterology friends to diagnose celiac disease and helps us limit misdiagnoses and also allows us to proceed with the next step, which is our gold standard for diagnosing celiac disease, and that's with biopsies. Here is a picture of our small intestines, specifically the duodenum. On the left side is a zoomed out picture. On the right side is a little bit closer to the epithelial layer. And what we see here on the left side is the broad strokes are the villa itself, those long expected structures that we do see. They're blunted, and hence we say the word or the description villus blunting. So they're shorter relative to where they could be. And on the right side, those arrows point to those lymphocytes that's in the epithelium, hence intraepithelial lymphocytes. Here, the diagram counts at least over 30 IELs or intraepithelial lymphocytes with phyllis atrophy, and that defines MRS 3B score, which is a histologic score we use to classify and diagnose celiac disease. Um, one of the takeaways here for our audience is, uh, if there's a suspicion for celiac disease, if there's positive markers, um, advise families to remain on a gluten-containing diet until evaluated by a gastroenterologist. This allows us to talk about endoscopies. It allows us to talk about the performance of tests. It allows us to, uh, ideally avoid late diagnoses or delayed diagnoses in those equivocal cases. So once we have a diagnosis of celiac disease, what we know at this time is that the gluten-free diet is the only available treatment. So this is a picture that comes out of the journal JPGN in collaboration with their European friends, published in 2024, and it talks about the gluten-free diet. In our multidisciplinary clinic for celiac disease, we work with ourselves, our nurse practitioners, our dietitians, and our social worker. What we do is we talk about a gluten-free diet. We talk about the social dynamic of changing that diet relative to the household, relative to schools, and other social settings. And that just as we try to talk about how we can add foods to the diet, it's not always my favorite conversation to take away X, Y, Z from the diet. Usually it doesn't lead to a very fun place for families or kids. Um, Here's a picture that allows us to pick and choose or even double down on foods that are fresh, uh, fresh or naturally gluten-free for families, and these are some of the conversations we have in our clinic. Uh, what I'll highlight here is that although the gluten-free diet is the available, only available treatment, it has limitations. Um, it's a dietary treatment that's required for treatment of celiac disease, but it's not necessarily healthier nor balanced. Among the, uh, non-naturally gluten-free options, generally, we see potentially higher sodium content, sugar, fat, and lower fiber content as well. Um, if you've been to a grocery store and seen the gluten-free and then the non-gluten-free options, you'll notice like, wow, the gluten-free options are more expensive, and that is what we have studied and seen as well. These are older studies, but what we have seen is gluten-free foods is about 1.8 times or almost 2 times more expensive than gluten-containing options. And this is why I think about diagnosing celiac disease and being sure about the diagnosis is important because it impacts families socially, but also financially. And then lastly, we know that a gluten-free diet can impact the psychosocial life, social events, relationships, schools, work, and we have studies that suggest that caregivers that manage that have kids with celiac disease often have a lower quality of life as well. So it begs the question, is there a better treatment for celiac disease? And that's a question we've been asking for at least the last decade, if not longer. So pharmacotherapy is the future for celiac disease and it's in in it's phase 1, phase 2, entering into phase 3 direction in terms of clinical trials. This is a figure that comes out of Gastrology 2024, and I've just mentioned that this volume actually does a specialized whole issue case about celiac disease and goes through probably a dozen if not more articles by well-regarded clinicians as well as research and celiac disease. If you're looking for reference, this volume for gastroenterology is excellent. This diagram comes up, comes out of that paper, and what I try to do here is categorize big, um, uh, um, what is it? Exactly, categories for pharmacotherapy. Number one, the first one is here, intraluminal therapy. So, um, as we think about, for example, the analogy is lactose intolerance or lactase deficiency, we think about adding a lactate enzyme to be able to help us metabolize lactose. Here we have glutenases, and these are exogenous molecules that when consumed help us break down gluten that's consumed in the body. We also have gluten binders or effectively medicines that help sequester sequester gluten when it's consumed. We have intraepithelial uptake mechanisms as well. As I mentioned, as gluten passes from the intraluminal space past the cell into the intracellular space. That's where the immune reaction occurs. There are tight junction inhibitors that help us maintain that, um, that structure, avoid that permeability that leads to the downstream immunity. We also have biologics. And that often is more commonly associated with, for example, inflammatory bowel disease as an area of active research and effectively how do we block that inflammatory response. That is an important mechanism as well. Next is, um, as we talked about, after the gluten enters into the intracellular space, there's a chemical reaction with tissue transaminase, as well as actually molecules that leads Of the downstream autoimmune effect. We have medicines that target the tissue transfer remities, and we have medicines that target the HLA molecules that helps us effectively dampen that immune response. And then probably the most interesting and one that I don't know if I fully understand yet, but immune modulators. These are effectively, uh, medicines given subcutaneous or IV that can help us induce tolerance or re-induce tolerance. The way I imagine it is effectively like a vaccine to help us tolerate gluten, and that's a really exciting part of of prevention I would foresee. Uh, what I'll leave here is just a, just an example of what glutininases can look like in recent clinical trials. So this was published in 2022 in gastroenterology, and the drug at the time was Latin glutanase or IMGX 003. What they did in this, in this clinical trial was they took a group of healthy adults. With celiac disease, well-controlled celiac disease, and gave them gluten and then also gave them one of the two, the placebo or the medicine. They measured their urine and they looked for gluten in their, in their body. And the GIP or gluten immunogenic peptide is one of those ways that we can look for gluten in the research setting. In the blue dotted line here, we see that among patients or individuals given the glutanase, their gluten levels are relatively undetectable. Along the placebo, they were detectable in the body, meaning that this glutanase was effectively degrading the dietary gluten in their body. And when we look at the outcomes of that population that received the drug, there was a 60% reduction in the intraepithelial lymphocytes at 6 weeks. And also decrease symptoms at 2 weeks. Um, the latest news I heard has been, this is again, finishing up its, um, phase 2, maybe entering into phase 3 trials. I'd be remiss to talk about new medicines without also recognizing the health disparities that come from new drugs and the disproportionate barriers with accessing new drugs. I think about it in the context of less access in rural or lower socioeconomic regions. I think about clinical trials maybe underrepresenting racially minoritized communities. I think about the high outpatient costs. I think about the lack of insurance coverage that prevents access to the medicine and potentially even Um, or health literacy and knowledge about these therapies. And it comes full circle ultimately to say that screening and diagnosing celiac disease in children from all socio socioeconomic backgrounds is critically important. So we have um all our patients having access to these new drugs. And I come back to this as well. Our pediatricians and our audience here has a really important role in screening for celiac disease. If we think about the downstream effects of improving screening, we can improve the accuracy of our diagnosis and ultimately reduce comorbidities, of which are some listed here, uh, promoting growth and nutrient recovery, restoring bone health, treating anemia and hepatitis if present, reducing the comorbidities as a, as a child and future as an adult, allowing us to then screen our highest risk group, which is first degree family members, which have 5 to 10% increased risk for celiac disease. Reducing the socioeconomic economic burden among families that may not need, costly gluten-free diet, and lastly to expand access for children to clinical trials and future first in class treatments. And this is where that opportunity does exist, and it's a space that isn't fully defined yet. So this slide comes from my mentor, Dr. Marissa Stahl. She's a pediatric gastroenterologist in the Children's Hospital of Colorado, my alma mater, and she presents this slide. What could celiac disease screening look like? Um, as pediatricians here, we, right, we follow, um, in terms of a child's path. There's a lead screen at some point and a prepubertal lipid screen. These two areas are potential, um, time points where we could screen a TTGIGA and a serum IGA to look for celiac disease. We know the comorbidities, we know the mortality. Is there an opportunity to screen? Potentially. Um, giving you another flavor of this, this is a slide presented a few years ago by Dr. Carlo Catasi. Um, he's a prominent Italian researcher, and he proposed this way to screen for celiac disease, in Italy. Starting with our neonatal period, we looked for actually. DQ2 and or DQ8 at that time, we know that about 35 or up to 40% of the general population have these, these genetic markers, and among those that are positive, it gives us a way to troubleshoot when to screen if they're asymptomatic or to screen if they're symptomatic at any point. Among those that are negative, again, 98% and more are unlikely to have celiac disease. This would miss less than 5% of all cases is what was described by Dr. Katasi. And again, this gives us potentially a pathway for us to understand screening and the future of celiac disease care. So to summarize again, I'll talk about, I talked about a number of things, but here are the pearls. Number one, screen for celiac disease in children with both classical and non-classical symptoms. These could be recurrent abdominal pain, arthralgias, anemia, hepatitis. Screen for celiac disease in kids with risk factors, first degree family members, type 1 diabetes, thyroid disease, genetic syndromes. Use tissue transaminase IgA and serum IgA as your first line studies. Um, order single body tests, single antibody tests, um, and this helps to reduce some of the false positive cases and costs. I've asked some of my colleagues in celiac disease just because there's so many possible orders that we can have, right, when we order for celiac disease. Um, our general direction is to order, single test as opposed to a panel of tests, and hopefully this can help reduce costs. Uh, revert to gastroenterology if serology is positive and allows us to have a nuanced conversation about the performance of tests, potentially diagnostic endoscopy, what the gluten looks like. We have access to our multidisciplinary clinic that can also help our patients thrive. Um, I didn't talk too much about this, but as we think about that evaluation, as we think about the micronutrients that are not absorbed in celiac disease, looking at iron and looking at vitamin D, uh, can be useful. And lastly, advise family members to maintain a gluten-containing diet if there's a concern for celiac disease and they're being evaluated by GI. I'll end with a few last slides. There's a wealth of resources and support available for children at risk of or diagnosed with celiac disease, and this is what our center has been working on for the last year and more. I'm one of the camp, one of the camp physicians at Camp Celiac. This is a yearly camp that's at Camp Arroyo, and it's a fantastic haven for kids. It effectively allows kids to see and experience normal camp activities with other kids with celiac disease. Uh, it's a fantastic, um, community event. Usually, it's one, it's an event that fills up relatively quickly. Uh, usually it opens in about May, or excuse me, in January period, and, uh, end of January, start of February. This year we have our event in July and it continues annually. We've collaborated with our National Celiac Association to, to develop a Effectively a mentor mentee buddy system for kids and with under the supervision of of adults and parents. It's called our celiac chat program, and it's one that we started and continue to develop just because we know that social stigmatization and social, social isolation is really a prominent feature of celiac disease. We have our newsletter that we send out quarter. and developed. We have our registry that's at least over 100 patients strong now and allows us in the future to give our patients access potentially to clinical trials. We've collaborated with our National Celiac Association, Celiac Disease Foundation. I'm one of the webinar committees for our Society for the Study of Celiac Disease, and next Monday, I believe we'll be doing another talk about Um, are, uh, the best of or the best abstracts and research and clinical data that came out of our Digestive Disease Week 2026, that was just sometime earlier this year. Uh, if you're interested, feel free to send me a message. I'm happy to share that link with other, others. Uh, as part of my fellowship program, we developed the gluten-free Initiative for Thriving or Gift program. We asked families with celiac disease, what would you like if you needed supplies, and with some funding, we obtained some bento boxes. Clipboards, notebooks, uh, thermoses, and we give them to our families with newly diagnosed celiac disease. Uh, and then lastly, we've collaborated with our Celiac Disease Foundation to um provide a resource for families that screen positive for food insecurity. They get access to a food box, um, delivery system, and it's one that we're proud of. So here are some other working ideas that we're going to develop over time. This is a way for us to improve our case finding for celiac disease. It's something I'm continuing to develop and hope to share with others soon and or develop this directly into our electronic health records. Um, if others are interested in this, reach out to me as well with my email. I'm happy to share this as well. Other interventions we have in mind, which I don't, which I won't talk too much about, but a smart, smart referral form, effectively putting that protocol into the referral process, giving families a gluten-free pamphlet as a debrief, but not necessarily a initiation of the gluten-free diet and giving this resource to our pediatricians. We're talking about developing our nutritional class or module. We're talking about an e-consult program for celiac disease. There's a lot of things in the, in the way. Um, so to finalize the last few slides, we have our 8 year old again, recurrent abdominal pain, diarrhea, extra GI symptoms found to have positive serology. Ultimately they were referred to GI who proceeded with their upper endoscopy. We found on the left side here, so the Early portions of their duodenum, we call it the bulb. We had that appearance of a scalloped appearance, right? If you take a shag carpet and you just shave off parts of that, that villa, this is what we can see endoscopically with their eyes. Actually, the distal part of the duodenum looked normal. Under the microscope, she had IELs greater than 50. She had villous atrophy consistent with celiac disease. So in this case, we re-screened her at that time to give us that starting point prior to starting a gluten-free diet. She had positive serology markers. She had disaccharide ACEs that was consistent with likely a secondary lactase deficiency. In our multidisciplinary clinic, we started a gluten-free diet, talked about micronutrients, calcium, iron, folate, B12, all those things. We've helped them set up a 504 plan, and we asked them to ultimately reconnect with their pediatrician to screen other first degree family members, and we'll continue to support her. Here are some of the people in our celiac disease team, um, and there are other dietitians that are not pictured here, but they perform important work for us. Here are some of our references. Uh, thank you all and happy to take questions. Created by Related Presenters Telly Cheung MD View full profile
