Episode 005: Diagnosis and management guidelines of Celiac disease
Guests: Dr. Talia Zenlea and Dr. Nadia Griller
SHOW NOTES
Priscilla Matthews
Thank you so much for tuning in again to Scope Notes, your gastroenterology-focused medical education podcast created by learners for learners. For any new listeners, I’m Priscilla Matthews, a current second year Internal Medicine resident at Queen’s University in Canada and I am joined by co-host Huaqi Li, a current first year Internal Medicine resident at the University of Toronto. Our amazing faculty advisor is Dr. Paul Tandon, a staff gastroenterologist and clinician scientist in Inflammatory Bowel Disease at the University Health Network and Sinai Health in Toronto. With Scope Notes you can look forward to monthly episodes covering all things GI, including practice guidelines, research reviews and special career topics. We will be specifically featuring prominent gastroenterology staff from the University of Toronto and across Canada for their expert opinions. So come join us from your favorite podcast streaming app. We would also like to extend a big thank you to the Division of Gastroenterology and Hepatology at the University of Toronto for their generous support of this podcast.
With all that being said let’s move on to our episode.
So today’s episode will focus on the current diagnosis and management guidelines of Celiac disease. We are very fortunate to be joined today by two leading experts in the field, Dr. Talia Zenlea and Dr. Nadia Griller.
Thank you both for being here. We are very excited to have both of you on today’s Scope Notes episode.
Huaqi Li
Very excited to have both of you on the podcast today. So just to get started before discussing this important topic, could you tell the audience a little bit about yourselves, your training, your research background and how long you've been in Toronto?
Dr. Nadia Griller
Thanks so much for having us. So yeah, a little bit about me. I did my undergraduate medical training at McMaster, but from there, through Internal Medicine, and Gastroenterology and advanced training, I've been at the University of Toronto. So, I've been around for a while. You know, my academic focus is really as a clinician teacher. Day in and day out, I have and supervise medical learners of all levels, from undergraduate medical students - teaching them clinical skills; how to take a blood pressure, all the way through to the advanced GI trainees, where I put a lot of effort and focus into helping them hone their endoscopy skills in particular. And in terms of my practice, I really see the whole breadth of gastroenterology.
Dr. Talia Zenlea
Thanks for having me too. So, as you said, my name is Talia Zenlea. I'm a gastroenterologist at Women's College. I did my training all in the U.S. My husband's American. So, we went to medical school at UVM - University of Vermont. We did residency and chief residency at Yale New Haven Hospital, and then I did a three-year GI program at one of the Harvard hospitals called Beth Israel Deaconess Medical Center in Boston. We then had a kid and stayed and worked for a bit in the states. So, I worked at Brown, where I was the director of IBD in one of their practices called the Women's Medicine Collaborative, and from there, moved to Women's College Hospital, and I've been here in Toronto now for over 10 years. I'm really focused on being a clinician. So, I - like Nadia - I'm also on the clinician teacher pathway. My teaching interests sort of have changed and evolved over time. But most recently, what I'm most excited about is doing endoscopy teaching for expert endoscopists in a program through the Canadian Association of Gastroenterology called the SEE Program. So that's really been one of the more fun things that I've been doing over the past couple of years. But I also have a role with Cancer Care Ontario, as the colon cancer screening and endoscopy lead in our region, which also offers some sort of fun and interesting teaching opportunities to endoscopists in terms of their colon cancer detection and optimization in endoscopy and then obviously the usual stuff with precepting learners of all levels in the medical school.
Priscilla Matthews
Great. Thank you so much to both of you for sharing about yourselves. We'll go into our discussion of Celiac disease. So, Dr. Zenlea, can you start us off by providing a brief introduction to Celiac disease, including the epidemiology and pathophysiology?
Dr. Talia Zenlea
Sure, Celiac disease, as most of you know, is a small bowel disease. It's characterized by mucosal inflammation, villous atrophy and crypt hyperplasia, triggered in genetically predisposed individuals by gluten. So, it's an immune mediated response, and it occurs in the presence of specific autoantibodies. So, the prevalence is approximately 1% in most populations. There's certain parts of the world where it's considered less prevalent, but over time, that's sort of changing, and we're now seeing prevalence in most populations. I would say that it's still considered low risk in Chinese, Japanese and Sub-Saharan African populations, but the prevalence is rising across the board. I should say that the incidence is also rising with higher rates of diagnosis, which has been attributed to a few things: both increased awareness and testing, but also a rise in autoimmunity, and that's been demonstrated by seroprevalence studies in asymptomatic people. Earlier studies showed that most people with Celiac were actually undiagnosed, but that seems to have shifted in recent years, so also increased awareness and better diagnosis.
Huaqi Li
Thank you so much. I think that was a great overview about Celiac in general. Dr. Griller, could you touch on the intestinal and extraintestinal manifestations of the disease?
Dr. Nadia Griller
Sure so, you know, one of the first things that we always have to think about as gastroenterologists - is Celiac Disease is really the asymptomatic patient. So, we shouldn't forget those patients who have Celiac disease but have no symptoms of it. And two of the most common populations in which this may occur are patients who have a family history of Celiac disease. So, for example, a first degree relative who has celiac and again, this person may be at risk and should be screened for Celiac disease, and also other populations that have again, a higher prevalence of Celiac disease, such as those with Type 1 Diabetes. The first symptom of Celiac disease may be no symptom. Then, when we think about intestinal symptoms or intestinal manifestations of Celiac disease, what commonly comes to mind are those patients who have weight loss, diarrhea. In children, we think about a failure to thrive, or those who are not going through puberty or meeting their growth curve. But really you can have any myriad of gastrointestinal symptoms related to the disease. Then we think about symptoms that may be related to the complications of Celiac disease, so for example, profound fatigue related to iron deficiency anemia. And then, when we think about extraintestinal manifestations of Celiac disease, there really are a ton of them, and some that, you know, have come to light over time and weren't so obvious at first, such as issues with fertility or recurrent miscarriage. You know, with respect to extra intestinal manifestations, again, you could write a whole long list by thinking about things like depression, arthralgias, hepatitis (mild elevation in AST and ALT), and then, of course, that pathognomonic rash to think about dermatitis herpetiformis, which is that intensely pruritic, vesicular rash typically seen on the extensor surfaces of the elbows and knees.
Priscilla Matthews
That's great. Yeah, I've yet to see a patient with that rash with Celiac disease, but that'll definitely be an interesting one if we do come across it. Moving into diagnosis, Dr. Zenlea, would you be able to touch on the diagnostic algorithm for Celiac disease, for patients on a normal diet?
Dr. Talia Zenlea
Sure, and I'll just say for dermatitis herpetiformis, as you will eventually see it, because it's not one of those rare things that you'll go through your career never seeing, and when you do, it's so exciting, because you're like, this is a slam dunk, and you just feel like such a hero. Okay, so in terms of diagnosing Celiac disease, it really depends on the population. So, you mentioned that we're first going to talk about people who are eating gluten, so that's the majority of patients we see, but I'm sure we'll talk about later, patients who are off a gluten containing diet, which is not an uncommon scenario either. So again, this differs for adults and kids, but we're initially looking at serologic screening in a low-risk population where the probability of a Celiac disease diagnosis is low - serologies are adequate. So, the best serology is tTG-IgA, Endomysial antibody is also a great serology, but it's more expensive and not as widely available. If that comes back negative, and it's a low probability patient to begin with, that's adequate, and you can stop. If you're really, really worried, you can repeat it a second time, or even go directly to a small bowel biopsy. But that, I'd say, is rare. You'd have to have a really, really strong clinical suspicion, like maybe somebody with dermatitis herpetiformis, or something where you're more convinced, but for the most part, people with Celiac disease will have a positive serology, and then you confirm the diagnosis with the small bowel biopsy. In some populations, particularly in kids, guidelines suggest that you don't need to do a small bowel biopsy if you have elevated serologies greater than 10 times the upper limit of normal in two separate samples. So, you can also consider that approach in adults who are declining a biopsy for whatever reason, or you think it's contraindicated or high risk for some reason.
Priscilla Matthews
Okay, perfect. Thank you for going through that. And I think something that I previously wasn't aware of, is that when you order the tTG, it's also important to order the IgA level, because tTG is an IgA type antibody.
Dr. Talia Zenlea
Yeah, so that's a really good point. So, and another thing to think about just to consider, is that many people with Celiac also have selective IgA deficiency, and so you do have to think about that. Now, IgG based serologies aren't as good. So again, they're neither as sensitive nor as specific. So that's a circumstance in which you know you may want to consider a small bowel biopsy if the patient's deficient in IgA. There's two other considerations. The first is that people can have, they don't necessarily have to have total deficiency in IgA. So sometimes people just have slight deficiency in IgA, so it's low but still detectable. So, I just try to interpret the tTG-IgA in that context. So, you would expect the elevation of their tTG-IgA to be proportionate to the degree of their IgA deficiency, meaning it might not be 10 times the upper limit of normal - it may be a little bit less, but if they have a slightly low IgA to begin with, then I would still consider that positive. The second consideration with IgA testing is that many labs automatically include it in the assay. So, it’s a reflex test. For example, Lifelabs in Toronto, I imagine this is true of Lifelabs across Ontario if not across Canada, when you order a tTG-IgA, and it comes back negative, they reflex test total IgA, so you don’t have to order it, but it will report that in the results.
Priscilla Matthews
Okay. And one more point about testing is that do you do the HLA testing in a decent number of patients, or what situations is that reserved for?
Dr. Talia Zenlea
So yeah, HLA testing can be really useful. So, the caveat with HLA testing is that the vast majority of people in the general population who don't have Celiac are going to have a positive HLA, DQ2 and/or DQ8. So, most people have a positive test, and a positive test is not helpful, but HLA testing can be very helpful if it's negative. So, a negative HLA, DQ2 and DQ8 doesn't make it impossible to have Celiac, but makes it extremely unlikely, usually around the order of less than 1 in 2000 so it can be very helpful if negative. But I always talk to people ahead of time because we're used to a positive test ruling in a disease, and that's not the case with this test, so I make sure they understand that a positive test doesn't mean anything, and that the test is most likely going to be positive. So that's not helpful, but it certainly is helpful when negative. So, in certain circumstances, it's definitely worth ordering when there's diagnostic uncertainty.
Huaqi Li
I think that was a great discussion about the serology and the testing. Dr. Griller, you were mentioning in terms of the extraintestinal manifestations, potentially hepatitis as a presentation. Were there any other types of lab findings in individuals with Celiac disease that you would look out for that typically we might not think about?
Dr. Nadia Griller
Yeah. So, you know, when thinking about what are the other abnormalities that you might see on blood work, it's helpful to just go back to basic physiology and think about the small bowel, where Celiac disease affects the small bowel, and what is absorbed there. And so, the first and classic finding on the blood work is typically iron deficiency. We know iron is absorbed in the duodenum and Celiac disease predominantly affects that first portion of the small bowel, but there are, of course, many other vitamins and minerals, that may be malabsorbed in the setting of Celiac disease, so ordering those other things to test the levels, to supplement them, if needed, and then to screen for the potential complications of chronic malabsorption of these factors. So, calcium and vitamin D, which may lead to osteoporosis. Low levels of iron and vitamin B12, which can, of course, lead to anemia. So, on the CBC, you may see a low hemoglobin, or potentially a high or low MCV. The hepatitis associated with Celiac disease, which typically presents with a mild elevation in AST and ALT. So those, I think, are the most important additional blood work to check in these patients. And the nice thing is that typically, all of these abnormalities resolve on a gluten free diet, as we withdraw that insult, and the small bowel starts to heal, and that absorption picks up again.
Priscilla Matthews
That’s great! We mentioned endoscopy earlier in the conversation, and so Dr. Griller, I'm hoping you can tell us about when we would pursue endoscopy, and what some of the endoscopic and potentially the histological findings are in Celiac disease.
Dr. Nadia Griller
Sure. So, you know, typically, we're performing a gastroscopy and small bowel biopsy to confirm a diagnosis, and then once on a gluten free diet to reassess for small bowel healing. And again, just as we may have a patient who's completely asymptomatic, you may find absolutely no endoscopic features of Celiac disease on gastroscopy, so that small bowel can look completely normal. And it's important in the appropriate clinical context to remember to take those samples, usually four bites in the second portion of the duodenum and two bites in the duodenal cap to assess for Celiac disease, which can be patchy and is why we take a number of samples. And so again, endoscopically, it can look completely normal. If you are going to see endoscopic features, then you may look for a mosaic pattern to the mucosa. And if you do have any sort of dye or methylene blue, and you were to instill that into the small bowel, you can see that pattern that comes out beautifully. You may have scalloping of the duodenal folds and then blunting, complete blunting of the folds altogether. When you take biopsies and they look at them under the microscope, there's really three findings that the pathologist is looking for. So that's increased intraepithelial lymphocytes, crypt hyperplasia and villus blunting. And so, they'll classify Celiac disease based on the Marsh criteria. So, the Marsh criteria is on a scale of 0-3. So, 0, there's really no abnormalities seen. 1 starts with increased intraepithelial lymphocytes. 2 adds in crypt hyperplasia, and 3 adds in all findings. So that's increased intraepithelial lymphocytes, crypt hyperplasia and villus blunting. And then in 3 there's a subcategory - ABC - dependent on the degree of villous atrophy, with Marsh 3C being the most severe, complete atrophy of the villi.
Huaqi Li
Thank you so much. And does that classification system correlate at all to disease prognosis or trajectory?
Dr. Nadia Griller
It does tell you about the sort of the severity, as to which the small bowel has been affected, but it doesn't necessarily prognosticate who's going to respond and have bowel healing and who's not. So, you can still have a severe Celiac disease and complete atrophy that heals very nicely on a gluten free diet.
Huaqi Li
Perfect. Thank you. I think our next question is for you. Dr Zenlea, regarding gluten free diet, we mentioned this a couple times, and it's a big part of the treatment for patients with Celiac. I was hoping you could touch on your experience with patients. How do you typically recommend it, whether or not you involve a dietician?
Dr. Talia Zenlea
Sure. So, a gluten free diet is the only treatment for Celiac. So, anyone with a diagnosis of Celiac, that's the recommendation. I always involve a dietitian, and if it's available, an expert dietitian, because a gluten free diet is really confusing. And I can, I've always had this practice, but I can actually speak from personal experience, because one of my kids has Celiac. And so, what I'll say is, it's doable once you know, but there's just a lot that most people don't know and that you're not going to figure out from Googling and I myself, as a gastroenterologist, didn't appreciate some of these nuances. Now they're easy, but you'll only know them if somebody teaches it to you. And we as gastroenterologists often don't have the time in our busy clinical practices to do this teaching, and it's also hard to absorb all that information all at once. And so, it's important to have a dietician both so they can have multiple sessions with the patient, two so that they can go over food diaries or do a deeper dive into what foods that patients have at home, and also to allow the opportunity for patients to try it and then come back once they have questions. But ultimately after a few months of doing this, most patients actually find it quite easy.
But just to give you an example of some of the nuances, or some of the challenges that I find is that at first it wasn't obvious to me which foods have gluten. So obviously, people know that bread or wheat or flour is going to contain gluten, but it didn't occur to me to look at chicken stock to make sure that it doesn't have barley in it. The other consideration is one of cross contamination. And I think this is misunderstood. So, I think it's misunderstood on both ends of the spectrum. So, for one, I know, I came home and was we need to throw away, or we need to get a whole different set of cooking measuring cups and spoons and cooking tools, because we can't have my son with Celiac eating from the same stuff that all of our gluten is touching. And we actually did that. I bought, whole new measuring cups, measuring spoons, pots and pans. So that level of cross contamination isn't enough to trigger an autoimmune response, and especially if you're washing those items, obviously you have to wash the items. So, and I say that because some restaurants don't do that. So, they'll boil a big pot of water and then stick in two different colanders, one with the gluten free pasta and one with the pasta, or they'll have a big communal fryer with the same oil and then with the chicken fingers and the potatoes. So, the potatoes are inherently gluten free, but if they're sitting in a pot of oil with chicken fingers that are breaded, then I wouldn't even call that cross contamination. That's contamination. That's, actually putting flour on the food, or, similarly, we just went to a chicken wing place that was like, yeah, yeah. We'll do a dry rub, or a gluten free whatever for the kid with Celiac. But we use the same bowl that's full of flour that we toss the other wings in. So that's not cross contamination via the bowl. That's you're putting flour on the gluten free chicken wings. But once you've rinsed that bowl, that's not a concern.
So cross contamination really involves more than a crumb, and in fact, there's actually been some studies in pediatrics even looking at shared toasters. Where there - it's more contentious whether there's direct contamination, and even there, it was felt to not be significant to trigger Celiac disease. Most people would still advocate for a unique toaster because that's where you're putting crumbs of bread. So, the risk of actual contamination is higher, but I think that it's sometimes overstated, and you certainly don't need whole new cookware.
The other thing is some of the labels are confusing. For example, sometimes a label will have an ingredient that appears to be a gluten containing ingredient, but then have a certification, like an official designation that's being gluten free. So that food is okay, even though it has this questionable ingredient in it, for whatever reason it means they've taken out the gluten or it's been made to be gluten free. Then there's also, people can write gluten free on an item, and that's not a certification. So just because a company says their food is gluten free, if it's not certified gluten free, you don't know that it's gluten free. So that can be confusing to patients, too. And then there's food items that don't appear to contain any gluten containing items but have a may contain statement that says may contain gluten. So that's really confusing to patients, too, and we would advise them to stay away from that. But how would they know that if there's no gluten containing items, if we hadn't told them that?
So, all these nuances, all of this just to say, that these nuances need to be communicated to patients, and we need to recognize that they're sometimes non intuitive and can be hard to remember. And so, I do think that a gluten free expert dietitian can be really, really helpful. The other example is with oats. So, oats are a naturally gluten free item. So, oats do not contain gluten. It's like a banana. It's naturally gluten free only because of the farming process, sometimes the gluten, the wheat, can get into the crop of oats, and so lots of oats can contain small amounts of gluten. And so, unless they're certified gluten free oats, we would probably advise patients not to consume those foods. And then a small subset of patients can actually just have cross reactivity to actual oats, and we don't really understand why that is even when they're certified gluten free. So again, these things are best discussed with an expert dietitian so the patient can put their best foot forward.
Huaqi Li
It sounds like there's a lot of complexities there. I think there's a lot of discourse between the toaster and the oats that I've heard before, so it's great to have some clarification. I've seen some patients where they, you know, despite counseling, despite dietitian, they're still having quite a bit of a hard time maintaining the gluten free lifestyle or diet. Do you have any supportive measures or tips that you typically use to counsel these patients?
Dr. Talia Zenlea
You know, I find it hard - it's true, you know. So, my son has Celiac. He's on a gluten free diet. The rest of us don't have Celiac, and we're not on a gluten free diet, and there's no question that his baguette doesn't taste the same as mine, and so that's hard, like those foods are tempting and they taste good, and the alternatives aren't always great. So, for me, I feel like I have a bit of an advantage, because I do have a kid with Celiac, so I'm always sort of looking for great gluten free options and alternatives, and I'll often share that with patients. Most communities have resources for patients. Like here in Toronto, we have Gluten Free Garage, which is this annual event where a lot of gluten free vendors come from across the province to sample and showcase what they have. But I do feel for people with Celiac because it's hard. Sometimes you just really want that food, and your gluten free alternative doesn't taste the same.
It can also be hard socially, it's awkward. My kid is turning 13, and it was different when he was a kid and parents micromanaged everything that they ate, but now, when he's going to a party, I'm often not involved, and he's not always comfortable, asking the hosts to order him a totally separate pizza that costs $35 and so it's tough, and socially, you don't always want to say that, you can't eat what everybody else is eating. So, I just try to empathize with that, offer support and kind of give whatever strategies I've come up with over the years to help but also recognizing that there are situations that are just going to be awkward and expensive, and you also might not be eating food that you love or that's healthy. Like sometimes I tell my kid, worst comes to worst, eat a bag of Doritos. I would never tell that to my other kids, but for this kid, we know that's safe, and we know that's there so, and we know you like it and it's going to keep you full, so just eat Doritos if worst case. So, you just have to sort of go with it. And then I also kind of - not that I'm ever encouraging a patient to not be adherent to their gluten free diet - it's of utmost importance, but it's also important too that they recognize that this is not an anaphylactic allergy. So, if a mistake does happen, it's okay, and you get to start fresh the next day, so don't worry about it. You can't un-eat it. And thankfully, this is not anaphylaxis, and so nothing catastrophic is going to happen.
Huaqi Li
I didn't realize Doritos are gluten free, so that's a big takeaway for me.
Dr. Talia Zenlea
Not cool ranch ones. Now, again, this is why having an expert dietitian is important. So, we know Doritos are gluten free, but we don't know that every Dorito is gluten free. I don't know if Doritos in the States or in Mexico are gluten free, so we're always sort of checking labels.
Dr. Nadia Griller
I was just going to add in as well that, you know, when patients are first diagnosed and they go gluten free, especially if they're symptomatic, they're often really willing to stick with the diet because they feel better. But in the patient who's completely asymptomatic, and you found Celiac disease, that can be a bit of a harder sell, because they're like, well, I feel great. This doesn't bother me. So why? Why must I go gluten free? And the other factor that comes into play that I found is cost. So, it can be really expensive. Talia, as you pointed out at the restaurant, for example, the gluten free option is often a lot pricier, and so it can be a barrier to going out and enjoying a meal with friends, because what are your options, and are you going to be able to afford them? And the same is true of your everyday groceries. So, there is a tax credit that patients can access in Canada to try and get some money back for these more expensive gluten free options, but it's incredibly onerous, and I don't think I've had a single patient who successfully applied for it.
Dr. Talia Zenlea
Just quickly, so lots of patients come to us already on a gluten free diet, and that's what prompted the referral, that they'll have had a symptom, implemented a gluten free diet, feel better and told their family doctor about it, wondered if they have Celiac, and then the family doctor doesn't know what to do because they're already on a gluten-free diet, so sends them to us. So, I'd say that's not an uncommon scenario, especially because there's widely available online information targeted at the lay population of how to manage IBS symptoms, which often overlap with Celiac symptoms like bloating or altered bowel habits and many of those diets contain an element of gluten limitation, or even being completely gluten free. So, it's not rare that our patients will have already tried a gluten free diet, particularly the ones who are symptomatic. So, the way I approach this with patients is about exploring what their goals are. So, the first thing I'll say is, even if you're on a gluten free diet, if you haven't done it with an expert dietitian, chances are you're probably having some small amount of gluten and so we can probably still screen you with a tTG-IgA.
It again, might not be 10 times the upper limit of normal, but you again take it in the context of gluten limited diet. So even some elevation of tTG in that context is likely suggestive of Celiac. But let's say it isn't, or let's say the patient's just really doing a great job with their gluten free diet, and it becomes a conversation with the patient about how much they care about the diagnosis and why. So, if you're already on the treatment, you don't need to confirm the diagnosis. So, if their tTG is undetectable, I can conclude with confidence that they either don't have Celiac or it's perfectly treated with the diet that they're on, and if they're planning to always stay on that diet, they're already committed to the treatment. There's no need to confirm the diagnosis. When we would confirm the diagnosis is if at any point down the road, they elect to liberalize their diet and want to stay on a more liberal diet. That's when it would be important to screen them for Celiac, and that's when the test would be more valid. So that's a conversation I have with the patient.
Sometimes it can be a bit circular. So sometimes the patients will say, well, I really want to know whether or not I have Celiac. And I say, okay, then let's do a gluten challenge. And they're like, but I can't do a gluten challenge, because anytime I have any small amount of gluten, I feel terrible. So, there's no way I could do that. And then the conversation becomes, well, then why? If you're committed, it sounds like you have a long-term commitment to the gluten free diet, at least for now. Like the expression I use with them is it's forever for now. If at any point down the road you want to reattempt this experiment, go for it, you have my blessing. This is not anaphylaxis, so try every now and then to have gluten, and if you can tolerate it, then that's the time that we’ll screen. These are also the patients in which an HLA test can be useful, but again, reminding them that the majority that a positive test doesn't screen them in. It's only a negative test that screens them out, and most of them will have a positive test. But in these patients, when there is a negative test that can be really helpful for them, it means they, for sure, don't have Celiac. The other discussion I have with the patient is, do you really want to know that. If you feel amazing on a gluten free diet are you going to be upset if you don't have Celiac? And sometimes the answer is like, I don't think patients usually would volunteer that the answer is yes, but I've certainly been in circumstances where that's quite frustrating and disappointing to the patient, because a diagnosis of Celiac feels more legitimate to them. It's unfortunate that that's the case, but I can understand where they're coming from.
Huaqi Li
Dr. Zenlea, the gluten challenge. How long is that, typically, and what does that look?
Dr. Talia Zenlea
So, the longer the better. But obviously we're not talking on the order of years in case they actually do have Celiac. So, we usually tell them to do the equivalent of half a piece of bread or a cup of pasta every single day for at least two weeks. I like it to be a little bit longer, and almost always ends up being longer, because the wait time for me for endoscopy is never two weeks. Usually looks more like a couple of months. So, I tell them, enjoy all the gluten until then, try to have at least that much, or until the symptoms become intolerable. But we also have to understand that they may call me and say, my symptoms are intolerable today. That doesn't mean I can get them in for an endoscopy today. They can certainly show up and get their serology done that day, but the wait time to endoscopy is obviously less flexible. So we usually try to book an endoscopy, like 6-8 weeks later, and hope they can make it until that point.
Priscilla Matthews
I think that discussion was actually really useful, and thank you, Dr. Zenlea and Dr. Griller for sharing some of those nuances. I definitely did not recognize how much thought goes into maintaining that gluten free diet. This is kind of an aside, but when patients start, if they reintroduce gluten to their diet by accident or because they choose to have like a meal that they're craving, do they tend to notice symptoms, right away? Or does it differ patient to patient?
Dr. Talia Zenlea
I think that differs patient to patient, as Nadia alluded to, like many patients with Celiac, have no symptoms. It was diagnosed in some other way, and so they feel fine when they eat gluten, and they don't know when they're exposed or not exposed. Other patients have a more immediate reaction. We sometimes see patients who didn't have symptoms leading up to the diagnosis, but then after they've been gluten free for a while, they do get symptoms when they have gluten. Obviously, there's no immediate small bowel damage, that takes time and persistent exposure, but there is probably like a cytokine cascade and more of an immune mediated, immediate response. And the idea is it could lead to net secretion of water, diarrhea, pain and bloating. So, patients may have those symptoms immediately. The other symptoms that are sequelae of small bowel injury, they're not going to see unless that exposure is repeated.
Priscilla Matthews
And then I guess this kind of leads into our next question, which we have for you, Dr. Griller. How do you establish mucosal healing? What's the process for that?
Dr. Nadia Griller
So, to establish healing, I re-biopsy. I'll take a step back and say that, you know, typically when patients go on a gluten free diet, there is a sort of a sequence of events of improvement that we see. So, in the symptomatic patients, the first thing is they start to feel better, and that's probably a reflection of that cytokine cascade being shut off. And then we see an improvement in the serology, so that antibody titer starts to come down, but the actual mucosal healing can take a long time. In adults, we may never see complete reversal back to normal without any findings. And so that healing takes place over months to years. And while I do go back in and redo a gastroscopy and re-biopsy to document healing on a gluten free diet - we don't do that right away. I know the guidelines recommend doing that around the two-year mark. I'll say I do that in my patients anywhere from 18 to 24 months out, and I take the same samples that I did at the time the diagnosis, and then again, look at it under the microscope with the pathologist, and also document those endoscopic features, which, again, hopefully, if there were some and we've had healing, we see that endoscopic improvement as well. But it is, of course, important to document mucosal healing, because that should reduce the risk of potential complications such as persistent malabsorption, leading to extra intestinal manifestations like osteoporosis and this risk of small bowel lymphoma.
Priscilla Matthews
When do you typically repeat the serologies? And is that something that is monitored on an ongoing basis, or just once? And are you looking for a percentage drop or completely normal levels?
Dr. Nadia Griller
So, I'll typically repeat the serology at six months, and I'm looking for complete normalization of serology. And if you have a persistent elevation in serology, then you should be wondering about first and foremost, gluten exposure, whether intentional or inadvertent. And I think that comes back to how complicated this really can be for patients, even in the person who's most diligent in trying to follow this strict gluten free diet, it can be hard, and you may have inadvertent gluten exposure simply because they don't know that this product is cross contaminated. And so that's again, where that expert dietician comes in. So, if you repeat the serology in someone who sort of swears up and down that they're adhering to their gluten free diet, then the next step is to re-involve a dietitian and say, hey, let's do a dietary review. Let's try and identify potential sources of gluten for this patient.
Huaqi Li
Thank you so much. I think that segues nicely into one of the other questions we had about gluten detection devices. It sounds like this is obviously a chronic disease and needs ongoing management and monitoring. Is that something that typically you've started using in practice or you've heard patients ask about?
Dr. Talia Zenlea
So, there's no validation to those devices. They're not shown to be effective or reliable. And the best way to know if a patient's being exposed to gluten is to have an expert dietitian do a dietary review. And for patients who swear up and down, it's almost always something easily identifiable. It's what I was getting at before. It's just so you don't know what you don't know, what's obvious to the dietician most likely wasn't obvious to the patient in that scenario. I've had a patient who cooked a lot of Indian food, and in order to get the right spices, was getting them from Amazon or from specialty grocery stores that weren't subject to Canadian food labeling laws. Here we’re required to certify something as gluten free and have a may contain statement. In other countries, including the US, that's not the case, and so they didn't realize that some of those spices were likely cut with flour, which is often the case with spices. So, it just didn't occur to them. And why would it? Because the spice isn't supposed to have flour in it. And then it was very easy to redirect them to a Canadian manufactured version of that spice that was close enough in taste and had a certification on it that it was gluten free, and the tTG came down. So, what may seem like an impossible scenario to the patient, to the expert dietician is often something quite easy to identify. And I'd say that though certainly cases of refractory Celiac are possible, I can think of one case that I've ever seen in my entire career of true refractory Celiac, and these patients are sick. This is not like an ambulatory person with an elevated tTG. It's almost always because of the inadvertent exposure to gluten. So, getting back to your original question about these devices, they'd be amazing if they worked, but they don't work, and we often don't need them.
Huaqi Li
That's great. Thank you for the clarification.
Priscilla Matthews
And just to wrap things up, we have one final question for Dr. Griller, and that is about the role of things like probiotics and also other supportive measures like vaccines. Are there any of those that you implement in your practice?
Dr. Nadia Griller
I think the question of probiotics is complex, and we know that the microbiome is important, not just for Celiac disease, but for a lot of conditions, even outside of the realm of gastroenterology. But when we think about the GI space for other conditions, like inflammatory bowel disease in particular. And we know that when we study these patients who have these particular diseases, so Crohn's disease, Ulcerative Colitis or Celiac disease, and we look at their microbiome, we do see certain, I'll say, signatures, in terms of the specific populations of bacteria that seem to cluster and suggest, well, maybe there's dysbiosis here, and it's appealing to think that we could take a probiotic and alter the microbiome to either prevent disease from occurring in the first place or to treat a disease that's already manifested. But at this point, we just don't have enough information to make a recommendation about which probiotic in which patient.
The best, sort of the “aha” moment for me, and the way that someone framed this for me that made it really easy for me to understand as a physician and for patients to understand, this is what I usually tell them is a preceptor who told me - it's common knowledge and the general population understands that we don't just pick any antibiotics for any infection. We pick a specific antibiotic for a specific infection. And the same is kind of true of probiotics. We should be picking a particular probiotic to have an effect in a particular condition, but we just don't really know what that is yet. And so, I think that's going to be future study, and really exciting, and I think we will get there, but we're not there yet.
Huaqi Li
That's a great way of thinking about it. I haven't heard that comparison before, so that's a great takeaway.
Priscilla Matthews
Well that pretty much sums up the highlights of the ACG guidelines on the diagnosis and management of Celiac disease. To our listeners, thank you for listening. Thank you so much Dr. Zenlea and Dr. Griller for a very engaging conversation.
That’s it for our episode today. Thanks so much to our listeners for tuning in and join us again next month for another informative discussion. Come check out our website scopenotesGI.com where we will be posting our show notes for each episode and other resources. Follow us on social media for the latest updates @scopenotesGI on X or formerly Twitter, and Instagram.
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