Dr. Osama Altayar, MD provides a comprehensive overview of celiac disease, who should be evaluated and how we should evaluate patients for celiac disease.
Our first speaker today is Doctor Osama Altar. He earned his medical degree at the University of Damascus Faculty of Medicine in Damascus Syria. He then obtained his fellowship and evidence based research at the Mayo Clinic and completed his residency in internal medicine at the Allegheny Health Network Medical Education Consortium in Pittsburgh, Pennsylvania. Finally, he did his fellowship in Gastroenterology at the Washington University School of Medicine at Barnes Jewish Hospital where he is currently an assistant professor in the Division of Gastroenterology. He is a research interest in celiac disease, which is the topic he will be presenting on today. So, thank you so much for joining us today and letting us learn more about celiac disease. So I'll go ahead and let you take it from here. Thank you very much, Nicole. Thank you for having me here. Um Hi, everyone. I'm Osama OTR. Um So, um I'll start by discussing my disclosures. Um I have uh no financial conflicts of interest, disclose. I work as a methodologies for clinical guideline committee specific, the American Gastroenterological Association. Um I'm going to cover a few topics related to celiac disease. This is not intended to cover everything about celiac disease. But I'm hoping to cover the most important things that may be encountered in primary care or questions that may come up. Um So just a quick concern about celiac disease, we believe that celiac disease was described, you know, long time ago by the iris of Cappadocia and the word celiac actually means abdominal. So in some cultures, it's actually, or in some language that Celi is called the abdominal disease even. Uh because of that. Um Now, since then, our knowledge about celiac disease have evolved a lot, especially in the last century. So in 19 forties, uh and during world war two, it was shown that the gluten free diet was the treatment or the disease. And the connection between gluten or what was called the weak, the wheat factor uh was shown uh by Vy in the Netherlands. Um Later on, we learned about the genetic factors for celiac disease. Then, you know, 19 eighties um uh testing for. So some of the serological tests started before that. But some of the testing, there are more specific, started showing up like anti gliding, anti Indonesia antibodies. And lastly, in late 19 nineties, early two thousands, we start having tissue transco Taine ig A and our knowledge has evolved dramatically since then. Currently, um Celiac disease, we know a lot about the pathophysiology of it uh and how it happens and what happens when it happens. So essentially, people eat gluten, it gets taken up, you know, broken down by enzymes, the enzymes lead to these peptides that develop the, the emanated gliding peptides that get presented to the T cells which unleash an immune system attack on the small bowel. And people develop those symptoms that they have. Uh Now if you look on Google trends, which is a really cool tool where you can compare things on Google trends. So you can compare, for example, Rihanna and Taylor Swift and how often people search them uh or any topic that you want. Um uh This is a comparison between how often people search disease and how often they search gluten free diet and red. And you can see that people were searching both around the same amount. This is specific to the United States of course, but around 2006, 2007 people started searching more about gluten free diet rather than celiac disease. And this is not random, I think, and I'm not certain about that, but that my proposal is that this is not random because around uh uh 2006 also or early 2007. Uh the FDA put a regulation to add labeling for gluten free diet. And you can see how the search for gluten free diet increased since then. Uh However, do all these people that are looking for gluten free diet and are consuming gluten free diet? Uh have CAC disease, are we over prescribing? So that's always a question on my mind is on my practice. Um Now, celiac disease is present everywhere. Um This is like a map of prevalence. Um We believe that the highest prevalence is actually not in Northern European or countries or the US. It's actually probably in the Indian continent. And uh uh um the area of Punjab, this is where the highest prevalence has been reported. Um But it's also been reported in African countries because it's been presumed to be a disease that affects certain populations. But we believe that it affects everyone. So it's been described in African countries, more countries this like even it is not fully updated. Um in the US and globally, the prevalence of celiac disease is about 1%. So about one of 100 people have celiac disease around us when we look at family members um of patients with celiac disease, first degree family members. Celiac disease is present in about 8% of people uh of the family members. Now, cases of undiagnosed celiac disease are more likely to have complications of the disease like osteoporosis. Uh presentations are not G I specific like dermatitis. Her performs chronic fatigue thyroid disorder, autoimmune disease or family history. Now, this is data from the enhance enhance is a large population study uh that checks the uh blood, the serum from different patients across the U in the US. Uh In 2009, 2012, they check cac serologies and you can see here, the ethnicity of the participants, you have Hispanic and non-hispanic populations. And you can see that celiac disease serologically was present, you know, in 1% of non-hispanic white people. But it was also present in every uh uh ethnicity. Uh with the exception of non-hispanic as Asians because there wasn't a lot of patients included. But if you look at all the other uh ethnicities, it's present. So ethnicity should not, ethnicity and race should not exclude somebody from getting tested for celiac disease. Um Celiac disease is a multisystem disease. I know I'm a gastroenterologist. Um uh but I will show you now that celiac disease could affect so many organs. If you read online, even some websites say that there are 198 symptoms that could be caused by celiac disease. Um But from G I standpoint, any G I symptom could be actually related to celiac disease. So, uh uh including but not limited to any patient. I BS could have Celi disease, any patient with dyspepsia diarrhea, even constipation, any change in bowel habits, bloating patients who report lactose intolerance um may have celiac disease. Uh So anybody with symptoms of G I symptoms could have celiac disease, asy uh dermatitis. Her performance is a very specific rash, the rash that is sensitive to gluten. Um And, and it's not diagnosed based on symptoms that respond or rash that responds to gluten. It's a rash that requires a biopsy that shows IgE deposition uh on the biopsy, but it's a very pruritic rash. A patient with a Pavia rash that becomes crusty or pustular rash, um those patients may have celiac disease also. Um because dermatitis performances is essentially virtually diagnostic of celiac disease. Um patients with iron deficiency, folic acid deficiency B 12 deficiencies. So, if you have a patient with anemia with a cause caused by any nutritional deficiency, they could have celiac disease patients with abnormal LFTs. We always think about, you know, hepatitis autoimmune. If thats all these things, one of the labs that should be checked for those patients is actually um uh uh celiac disease serologies, patients with frequent a ulcers, patients with uh uveitis, patients with uh brain fog, chronic fatigue, migraines, uh um some neuropsychiatric symptoms, osteoporosis, especially when diagnosed at an early age should provoke us to think about celiac disease. Um arthropathy, um neuropathy, uh infertility has been reported. However, there's a lot of debate about it and I'll show you some data showing that it's not related. Um but low birth weight for kids for newborns may be related to celiac disease in the mother. Um There are conditions that are associated with an increased risk of celiac disease. Example, we have 1st and 2nd degree relatives. I told you first degree relatives. The risk is about 8%. Um patients with type one diabetes. In fact, in pediatrics, it is recommended to screen for celiac disease. Um at least once especially if the patient has symptoms. Um Some people argue that you should screen people every two years, patients with thyroid disorders. So, if a patient goes on levothyroxine or thyroid replacement therapy, and they're requiring frequent change of dosing, that might be a sign that they have a problem with metal absorption and should provoke us to think of celiac disease. Also patients with adrenal diseases, any autoimmune disease, really Gren syndrome, rheumatoid arthritis, sle and A G I conditions like Crohn's disease, ulcerative colitis and microscopic colitis could be associated with CV disease. Finally, there are some populations that have higher risk for having celiac disease, like patients with Down Syndrome and Turner Syndrome as well. So if we see any of these things, we could always provoke the work up for celiac disease or at least the screening for celiac disease. And I highly recommend doing so because sometimes patients don't think that they have symptoms and they have symptoms and they only realize it once they start the gluten free diet. Um So I'm gonna start with this scenario. We have a 33 year old woman who presents with fatigue, intermittent bloating. She reports that her menstrual periods have been short in duration with small volumes and starting her oral contraceptive pills. Two years ago, her brother was diagnosed with celiac disease a year ago. She has Taylor on exam which prompted you to order blood work and showed iron deficit. She was referred to G I for endoscopy, you're suspecting she may have celiac disease. Uh What test would you do? So how do we diagnose celiac disease? When we think about celiac disease, we usually think about um uh serological markers for celiac disease. We think about symptoms. We think about biopsies. We think about genetic screening um uh or the improvement of systems with gluten-free diet. And hopefully, during this talk, I'm gonna be able to show you why we only look at the objective data and we do not use symptoms in diagnosis of celiac disease. So, serological markers for celiac disease, uh there are multiple markers for celiac disease, serological markers. In the early 19 eighties, I mentioned the the anti gliding antibodies. Uh the native gliding specifically were developed, they have a not a very good sensitivity in 50 80% 90%. It's still available, but it should not be used. Uh Mid 19 eighties, anti Indonesia antibodies, the IG antibodies they're developed also, they are expensive. The other problem with them that they're poorly standardized. However, when they're positive, they are highly specific. But because of this poor standardization, sometimes you may have false positives but when done correctly, they are highly specific. Mid 19 nineties. We hate the tissue trans contaminate IG A which is a test that we should be doing for patients. It is cheaper, it is more standardized, still not very well centered, but it's more standardized than other tests. Uh It is the test of choice, but we should be always worried about IG A associate IG A deficiency. And if the patient has ig a deficient deficiency, we should check the TT Gigg the this transit family IgG. Then we have most recently the amidate glided peptides, IG A and IgG, they are more expensive. They're also highly specific and sensitive but they're not as sensitive as the DPG. Still. This is just a summary of the diagnostic test performance of those tests. So you can see how the native glides they are not the best uh in the meal antibody has a very good the best specific specificity actually, but it's not very sensitive uh compared to the other tests. The TPGIG, which is what we recommend has the highest sensitivity and specificity combined together. Um TT gigag is still not very specific um uh or sensitive the same with glide in IgG. So usually if I have somebody with IG A deficiency, I'll check both TT G and glide in IgG uh diameter glide in peptide IgG. So another you know patient similar to our patient, patient, young man with intermittent abdominal pain, bloating and diarrhea and they have positive TPG did plog test the right tt gig A and it came back positive. What would you do next? Um So the next thing should be really an upper endoscopy, uh an upper endoscopy to obtain biopsies and confirm the diagnosis. Now, there are certain findings that can be seen endoscopically in patients with celiac disease such as um loss of circle of faults, anxiety pattern scalping. These are up for the gastroentero to identify. However, even if a gastro Andrs is described those chains in the biopsies. And here we're talking about uh an experienced gastroenterologist who have seen celiac disease numerous times. The sensitivity is still low and even the specificity is still low. So, if a gastroenterologist says they're scalloping, they're finding concern for celiac disease. We're still looking for the biopsy. We don't use that uh visual uh assessment to um evaluate uh uh for celiac disease. Uh OK. So the Adal biopsies um should be done while the patient is still on gluten uh containing diet. So we do not tell the patient after the serologic test is back to uh stop uh the gluten to start gluten-free diet. We should tell them to continue. And what they show is they show what we call the flattening. This is what you see here. It's called the flattening of the villa because these are the full develop vila and they show flattening the line. And you can see how this dark purple color here. This is the lymphocyte. So sometimes the biopsy will say there's increased intrathecal lymphocytosis and this or borderline and it, the pathologist may sometimes this is consistent with treated celiac disease. What is more important is the villa atrophy, not the intra lymphocytosis. So, biopsies are classified in what we call the marsh classification. The first stage of it is the intra lympho in the presence of those intrepid lymphocytes does not necessarily mean that the patients have celiac disease. In fact, many conditions could cause increased intrathecal lymphocytosis. So, it's usually a combination of things that we used to make the diagnosis. But most importantly, the villa atrophy, but even the vus atrophy could be caused by other conditions. Now, in celiac disease, those chains are patchy. So sometimes you may have somebody who had biopsies and they come back normal. We need to obtain biopsies in a specific way. They should be obtained from two separate parts from the small valve and the deena and need to be labeled separately. We usually recommend obtaining a single biopsy that pass. When gastro and controls do biopsies. We usually obtain multiple biopsies with one pass. We put the biopsy forceps, we take a little bite, then we take a second bite, then we remove the forceps. We usually recommend doing a single bicycle, single bite so we can have larger pieces of tissue to allow us to make the diagnosis. Now, this is just some of the data that I'm to elaborate on what I was mentioning. So one of the studies tried to obtain biopsies from different parts of the duodenum to show how often you see changes. This is the marsh classification that I told you about for the biopsies. One or two is not specific for Celi disease. But three and above three A B and C is specific. And you can see here that um you don't always have findings that are consistent everywhere. So that's why we recommend obtaining from different places. This is 90%. So you can see 80% in one site, 80% 1 side to. And those don't overlap. Sometimes the disease is only in the bulb. Sometimes it's only in the bis small b. Another study also showed the same things that you need to obtain different biopsy because the disease is patchy. Similarly, another study here, it shows that the villa atrophy could be present in the bulk alone in 18% of patients and could be present in the second part in 7% of those patients. The number of patients was very small though in this study, uh however, still, this is very helpful for us to know that we need to buy, obtain bias from different parts. And lastly the importance of a single biopsy technique. And this is sometimes mentioned in the endoscopy report how they obtained the biopsy. But if you have somebody with positive serologies and their biopsies are still not conclusive, they may need to have a repeat endoscopy on a gluten containing diet to make sure that they, we confirm the diagnosis. And I'm gonna explain to you why we need to explain the diagnosis later. So why do we need to obtain biopsy? The specificity of physiologic test as I showed you is not 100% it's really good, but it's not 100%. And the, the test there are sometimes I mentioned, you know, standardization issues with both labs but it's becoming less. But there's there's still an issue of standardization. Sometimes you may have a mildly positive test that is not consistent, that is not very important. And I'm gonna talk to you about the thresholds that we could use a biopsy. Confirmed celiac disease is data suggests that it is associated with more adherence to gluten free diet. There is the concern about over diagnosis. There is a condition that we call potential celiac disease in which the patients have positive antibodies but negative biopsies, um those patients may develop celiac disease but they don't have it yet. And we usually just monitor them um establishing correlation with the serology. So we can see, ok, if the patient has low positive levels and they still have evidence of active disease, we know that that low level is predictive of them having active disease if they have high levels. Um then we know that if their levels drop, they're probably having less active disease. So we can establish that correlation. Um The other thing is missing diagnosis of um or the misdiagnosis of non-responsive celiac disease or celiac disease complications. Celiac disease could evolve into refractory disease when the disease stopped responding to celiac disease. And the first thing we do when we have somebody who's referred for a fracture celiac disease, which happens in about 1% of patients. Is we confirm that their diagnosis was accurate and it requires a reviewing the biopsies from before making sure that the diagnosis was done correctly. Uh Establishing a baseline biopsy. How would the small bowel looks like? Did it have any complications at that time? And then detecting often concomitant diagnosis, especially in older individuals, people diagnosed after the age of 4050. Um We wanna know is there anything else that could explain their symptoms? Sometimes peptic ulcer disease or HV infection. Um And at the end, upper endoscopy is a low risk procedure, which is why we say that's fine, do it, you know, there's no high risk of the procedure. Um The other thing, there are concerns about the legal coverage for gluten free diet and health expenses uh when you don't have, when the diagnosis is not confirmed um by insurance companies. So that's another reason that we obtain it. I don't encounter this issue frequently in some countries. It is. But in the US, referring a patient to a dietician is frequently not covered by Medicare at least. So, um in 2012, the pediatric societies in Europe came up with a protocol to make the diagnosis without a biopsy. And this was recently adopted in the US. And I'm gonna share a little bit more with you about this. So they said that if you have a patient in a child or an adolescent with symptoms, suggestive of celiac disease. You could check the antibodies. As we said, tissue transplant, Tamina and total IG A. This is what we check always. And if it's negative, then the patients have no celiac disease or there's a chance that it's false negative. Maybe they started gluten-free diet if it's positive, they suggested that you repeat it again. And if it's positive and more than 10 times the upper limit of normal. So what is the upper limit of normal? Your lab might say uh negative, less than four and between four and 14, it's weak, positive and 15 is positive. The word we can adapt positive, not weak, positive when we say more than 10 times. So more than 10 times the upper limit of normal. If you're positive to the threshold like cost here, Barnes is 15 and most labs it's about 14 to 15, then you're looking about a little bit above 150. OK? Or 140. Um If it's less than 10 times the upper limit of normal, you should do an EGD. If it's above 10 times the upper limit of normal, they said check the Indonesian antibody status and HL A status, the HL A, I'll talk about it later. But they said if both are positive, the patient have celiac disease. If it's negative and the patient has positive HL A to EGD, then if it's positive and the patient has negative HL A, then you do. Uh you wonder about the uh false positivity. Now, this was changed in 2020 and now they say the same thing, but they don't say check HL A. They say if it's E MA is positive, which is the inome ig. And remember I told you it's the most specific one. So if you have a really highly positive tt gig a more than 10 times upper than normal with a positive Indonesia antibody, you can virtually make the diagnosis of celiac disease. But this is very specific to patients with symptoms, suggestive of the disease, not patients who are asymptomatic with with no other findings that are concerning for celiac disease. If it's negative, then you can obtain, you will need to obtain an endoscopy to confirm the diagnosis. Still. Where does this data come from? This is from pediatrics. How about in adults in adults? There were a bunch of studies done after that evaluating those thresholds. And in the study here, this is from the UK. You can see that this is the 10 times upper limit of normal threshold. This is diagnostic of serial celiac disease. March 3, March 01 and two are not diagnostic. And you can see that above the threshold, most patients had celiac disease and that supports that maybe we could use this threshold in adults with uh celiac disease. What I was going to show you is additional, oh, here we go is additional studies that showed similar findings. Um from that study, they did three cohorts that showed the same findings. Um and then, um then there is a third, another study that was done uh in the, in Finland. And they showed that again that when you have positive tt gig a more than 10 times the upper limit of normal. Um and you have a positive inome antibody and with a positive HL a uh most patients will have celiac disease. They actually identified one patient who did not have celiac disease. And that patient did a gluten challenge. And then their diagnosis was confirmed again, that study from Finland showed similar findings. Um You know that when you have a positive tt gig more than 10 times up a normal with a positive Indonesia antibody, you can make the diagnosis of celiac disease without biopsy essentially. Now, why not biopsy? Right. That's always the question. First, access to endoscopy. Is it easy to access endoscopy? Is it easy to get people to endoscopy? Sometimes it takes weeks to months even to get somebody to endoscopy. As we said, there's high diagnostic accuracy in the right settings. There's low risk uh and asymptomatic individuals may be a hesitant. So if somebody is diagnosed at a young age and child, they are low, considered low risk patients, meaning that the risk of having complications, low or people who are asymptomatic might say, why do I need to do this? It's just a positive blood test the cost of endoscopy and biopsy is also important concern about sedation. But we mentioned, you know, endoscopy is a low risk procedure really um low diagnostic yield or concomitant diagnosis. We said, you know, oh, we could find ulcers but it's really rare based on data, low risk of celiac disease complications. I mentioned fracture ce disease, but it's really 1% of patients with disease that have that variable rate of histologic misdiagnosis. As I mentioned, the biopsy should be done in a certain way. And if not done, you're risking the chance of having false diagnosis that is negative, sometimes um limited access to experienced pathologist. I have many examples of patients that were diagnosed with celiac disease by non experienced pathologist and then our pathologists here, we see a lot of celiac disease said um they don't have celiac disease or the other way around also. Um So there are all these concerns and recently the A G American Gastro Control Association in what we call a practice update. Um They said maybe we could use the PSE diagnosis specifically in patients who are symptomatic. Um And more recently in January 2023 actually, the American College of Gastroenterology said that yes, we recommend upper endoscopy for people with a suspected celiac disease. However, they said that in patients in Children, um a high KTG, as I said, more than 10 times, I keep repeating this number at a certain point, more than 10 times the upper limit of normal and a positive ended mesial antibody in a second sample, maybe a reliable test for Children in asym in symptomatic adults. So, very specifically, people are symptomatic who are not willing to uh to undergo endoscopy. We may use that clog diagnosis too. So we could use this in somebody who doesn't want to do endoscopy. But really, it needs to be very specific more than 10 times of a normal of the tissue transcona ig a not any other antibody and endometrial antibody because the other ones have more false positives. Ok. Another clinical scenario, we have a 34 year old woman with no significant history comes in with intermittent abdominal pain, diarrhea, which started, she started five years ago. She reports that Guri died two years ago as her symptoms were exactly like the symptoms of her coworker who has celiac disease. She noticed some improvement in her symptoms. So she continued to die. Does she have celiac disease? And how would you approach this before I tell you how we approach this? I need to establish a few important things. One, there is something that we used to do previously, which is a gluten challenge. We still do it now. But previously to diagnose celiac disease before we had logic tests, you needed to have somebody with symptoms, then you would biopsy them show that they have findings consistent with the disease. Then they will start the gluten free diet and you rebiopsy them three months later to see if their disease is better and if it's better, you introduce gluten again and see if the disease recur and if the disease recur, you show that it went away and came back with gluten. You say yes, this is gluten uh the C disease and that was called the gluten challenge. So it's a 10 g of gluten daily for 6 to 8 weeks, 6 to 10 weeks. There were a lot of two studies, actually not a lot, two studies that were done on this. And this was in mainly for trials to see how we can do clinical trials in which they um gave people um gluten uh to see if um we can induce celiac disease. Uh we can induce uh findings of celiac disease in them so that our patients with celiac disease. And what they found is that day, three, day three, most people start having symptoms, day 14, after 3 g, at least 2 g, it was three or 10 g, about 50% had changed in their serologies. About 60% had changed in their biopsies by day, 28 majority of patients by four weeks. So this was only for two weeks. So two weeks, no more gluten anymore. Um by four weeks, majority of patients have changed. So we sometimes do this uh as part of our evaluation, gluten shot. The other thing is that I need to start the HL A typing I mentioned to you that around 19 sixties fifties, we established an HL A type HL A is something that we get from our patients. It's present on what we call the antigen presenting cells which present the antigens with it to present the antigen to the immune system and that leads to the immune system becoming active. There are certain HL A types that were found in patients with celiac disease. However, those are not only specific celiac disease, they are present in about 30% of the general population. Those genotypes, those HL A types are called HL AD Q 2.5 and HL ad Q eight. And there's also an HL AD Q 0.2 and there's AD Q 7.5 some of your patients may come to you and say I had a 23 and me test that showed that I have the gene for celiac disease. What I want to show you here that we call these things very high risk and low risk. Ok. But really a very high risk is the risk of 1 to 7 to 1 to 14. So even people with the highest risk of having celiac disease based on HL A type, they're more likely not to have C 7 to 1. So out of eight people, seven of them will not have ce disease, one will have celiac disease. And that's why I explained to many of my patients that the fact that you have HL A that is, you know, consistent with celiac disease does not mean that you will have celiac disease, you're still more likely not to have it. And when you go to the lowest risk, you're talking about one in 200 even one in 2000. Ok. So the use of those HL A tests is really not to diagnose celiac disease. It is used for patients who are in gluten free diet to rule out the disease. So if somebody comes in like our patient that I'm talking about in this example and says I'm a gluten free diet and they're not willing to go against it. I usually suggest starting with an HL A test and I say, let's do this. If it's negative, your body is not capable of having celiac disease. Now, I explained to them orally in advance too. I say even if it's positive, you don't necessarily have celiac disease, but your body is capable of having Celi and I need to do more and I'll show you what is more. It can be used to support the diagnosis. Also, if I have a controversial diagnosis, I might use it and some people are using it for screening family members too. Ok. Response to gluten free diet. Why don't we use diagnosis? So there was a study that was really important that was done in 20 in 2014, 13 on patients without celiac disease. So people who are known not to have celiac disease. They don't have the HL A for it. They cannot have celiac disease. However, those individuals said I feel better on a strip gluten free diet. My symptoms are gone. What they did. They blinded randomized them to gluten-free flour or gluten containing flour, 10 g and then they put them in a two week wash out and they made them switch to the other group. So 10 g of gluten free and 10 g of gluten containing. And then they asked them, what symptoms do you have? About 17%? So six out of 35 had no symptoms, regardless, they were blinded, they didn't know what they were getting. About. 50% had symptoms when they were on gluten free. So they thought they were getting gluten containing flour when in fact, they were getting gluten free flour when blinded, when blinded, only 35% of those patients were able to know that they were getting gluten based on symptoms. In other words, really, the response to gluten free diet does not tell us even if the patient is getting better because of the gluten free diet because majority of patients either didn't have symptoms or had symptoms on the gluten free flour. That's why we should not recommend gluten free diet for somebody without knowing that they have celiac disease. And then there's another study that was done, you know, around the same time, there was an observational study though. So they looked at patients who said I feel better on gluten free diet this time, they went through the whole process. So they looked who had abnormal, uh, blood test, borderline blood test and negative blood test. They, they, who had biopsies and who didn't. Um, and they did HL a testing for them. And at the end, what they found was that about 50% of those people did not have celiac disease, 50% just felt better on gluten. And then we go back to the prior slide and say, well, even those when you blind them, many of them don't have majority will not have response to gluten when blinded to what they're getting. In other words, symptoms do not have role diagnosis, whether it's improvement of symptoms or response to symptoms or even worsening because all we know from this data that we have is that it's not predictive, it is helpful to know that something we should suspect it. However, what we should do is while the patient is still consuming gluten, we should test them. So why is it important to make the aro diagnosis? It's important because there's increased, there's data that suggests there's increased mortality, increased risk of cancer. There is a concern about refractory disease, gluten free diet is restrictive and difficult and there are medications in the pipeline. So mortality was done based on a large observational study and it, it showed that even after adjustment to multiple variables, there is increased risk of mortality in patients with celiac disease compared to their siblings even. So, not compared to anybody. You know, like random people compared to their siblings. There's increased risk of mortality. The risk of malignancy, there are two types, there's risk of small bowel lymphoma and there's risk of small bow, uh, small bowel carcinoma. I tell my patients it's three times more. However, the absolute number is small. So the absolute risk is goes up from three and 100,000 to 9 or 100,000. But this is important, we need to know that you're increased risk of small bow malignancy. Uh And we need to know that you should be on treatment or not the adherence to gluten free diet based on observational studies. This is in Children, teenagers, teenage adults and adults, you can see that the adherence to gluten free diet is uh or non adherence. You can see the percentage is as high as 60 50% in some people because it's not easy. It's very challenging to be on gluten free diet. Additionally, gluten free diet may be associated with nutritional deficiencies. So you have low complex carbohydrate intake, low fiber intake, low intake of vitamin Deb one B two B six and 40. That's why we monitor those patients who are gluten diet even for nutritional deficiencies too. There's also a huge psychosocial impact from disease. I talked to my patients a lot about this because I wanna make sure that we're addressing this for them. But you can just imagine now we're coming for the holidays, Thanksgiving. Uh, uh, uh, uh, Christmas. You know, people wanna feed you, people wanna feed their family and they make good food for them and then it may contain gluten and the patients with celiac disease may, may walk in somewhere and they'll say I'm so sorry, I can't eat the food because I have celiac disease or going to restaurants or even having symptoms. Sometimes we all go to restaurants or eat somewhere sometimes and we get sick. Those patients with celiac disease will feel sick too like people who don't have celiac disease, but they will start thinking, was it because I got exposed to gluten or not? And some people even will develop suicidal thoughts, depression. It's very restrictive and it has a huge impact on the parents of the Children as well as the patients themselves. And that impact spans all age groups. And again, there are many medications in the pipeline. They're all trials. There's nothing in phase three. There was one but it fell out. It's not on phase three anymore. It was excluded. There's a bunch of phase two trials that are available currently. Ok. Clinical scenario for we have a 51 year old woman with history of hypothyroid. Secondly, to Hashimotos has been difficult to manage. As I mentioned, if you have somebody with difficult to manage hyperthyroid, think about celiac disease, she also had alternating diarrhea and constipation. She had a screening colonoscopy ago that was normally ordered tissue trans contaminates. The IG A came back elevated EGD with biopsies confirmed the diagnosis. What would he do next? So this is what we do for our patients. First, we refer them to our CV F dietitian. We have a dedicated CV F disease dietitian here at one U very experienced um seeing a lot of patients with celiac disease, they, they know about it all. I will tell you from my personal experience is that not all dieticians are familiar with gluten free diet. Even a lot of us physicians are not familiar with the gluten free diet. I get question, I see about 102 100 patients celiac disease every year and I get questions that I don't know and I want them to the dietician frequently to say, what do you think is this right or wrong? So it's very important to have a dietitian that is knowledgeable about the disease. Talk to the patient. They assess the history of comorbidities, potential nutrient deficiencies. They give education, they give individualized plan and they follow up with the patients also. Um there are different forms to follow the patients, but there's suggested follow up and diagnosis. Four months, six months, 12 months, we do labs, we even require endoscopy sometimes and I'll show you this. We suggest do an endoscopy for certain people after two years also. But we monitor labs, they meet with a dietitian multiple times. We get a dexa scan to make sure that our patients don't have osteoporosis. We recommend that our patients get pneumococcal vaccination because those patients are at high risk of developing pneumonia. So there are multiple things that we recommend to our patients. This is another schema for the follow up. But the question is, you will see here 6 to 12 months. Should we do an intestinal biopsy? Because sometimes people will do biopsies frequently. You may see patients who are getting biopsied every month, every three months or six months, which I've seen and based on getting every year. And this is a huge debate in the medical community, especially that we have other conditions like Crohn's disease, ulcerative colitis in which we say you have to achieve histologic remission. So why should we re biopsy? The argument to re biopsy comes from studies that showed that rebiopsy, this sizes are actually updated and it's updated because this study here is really new. It was just published a couple months ago and what's been shown that those patients who have persistent active disease have increased risk of mortality. Now, a prior study showed that there was no increase. So this is a debate but there's data now that suggests there is increased risk of mortality. If you have persistent Phil atrophy. As we mentioned, there's the risk of cancers and there's also risk of osteoporosis causing fractures. That's why we tell our patients who have osteoporosis that I wanna rebiopsy them patients who are at high risk for malignancy. So that our patients who are diagnosed at a late age, what is late age after the age of 30 after the age of 40 patients who are still symptomatic. There are multiple patients for whom we suggest repeat biopsy. Now, why? Two years? Not one year, we used to say one year. Uh but if you look at this study, this is in patients who are feeling fine. You can see these are the stages of marsh that are active disease. And you can see that even after two years, many patients may still have evidence of active disease on biopsies. So maybe that doing that biopsy is not helpful unless the patient, there are concerns for fractures or in adherence. Otherwise, it is difficult to interpret that biopsy and and us doing the biopsy may not change the management. So that's why there is a huge argument about should we do biopsy or not. Um So the suggestion is that we do biopsy for patients persistent symptoms. If they have evidence of gluten contamination with urine tests, which we don't recommend tine, their blood tests don't improve. They still have nutrients deficiencies if we think that they are non adherent, but the patient think they're adherent. It's helpful. We need to confirm that if the patient is keen to know about ha if they have u of healing or not um the other, but most of the time I tell my patients, you don't need to repeat the biopsy. I only tell them to repeat it if I have concerns about their disease being active or if I wanna make sure that they achieve remission because they have conditions that put them at high risk like osteoporosis or sur fracture disease. Now, the American College of Gastroenterology um uh and their guideline from January 2023 suggested setting a goal of intestinal healing as an endpoint. Um However, they also said that it's helpful and it should be considered and well, they didn't say should it, it could be considered after two years. So I always have that individualized discussion. I actually had it three times a day with three of my patients saying we should, we don't need to do it for them because they're doing well. And there are no concerns. On the other hand, I had this discussion two days ago with another patient and I said, I think we should do it. They still have elevated levels, they think they're doing everything right and they still have symptoms. So we're doing the biopsy to see if it helps if there's active disease or not. But the H AC G now changed their recommendations from 2013. We said biopsy, everyone in a year to say in tears, consider um uh biopsy, but we even advocate for doing the biopsy sooner. The patient continued to have symptoms and we have concerns about her factories. Ok. So how can we help at the was Adult Celiac clinic? Um If we have a I always, you know, suggest for my uh colleagues who are in primary care that if you have a patient with symptoms that are suspected suspicious for celiac disease, lab suspicious for celiac disease risk factors. As we mentioned in the initial, the initial part of the presentation, get the serologies. What are the serologies? It's tissue trans contaminate ig a total ig a total ig A because you wanna make sure that you don't have ig A deficiency. If they do, you need to check the IgG antibodies. Sometimes I also, if I have high suspicion, clinical suspicion, I'll add the D MA to glide in IgG on top of those. And that's because there's some data that suggests about 10% with isolated patients with isolated glide and IgG positivity may have celiac disease. So sometimes if I have high suspicion, I may do that. Uh If those tests come back positive, I suggest referring the patients here at the wash UC Adult Celiac Clinic. And we don't tell the patients you have to start going to die here at the wash UC the clinic. We try to get patients within two weeks. I've been able to sustain this promise so far. Uh We get patients within two weeks unless the patient says I can't come or for some reason, they can come or if I'm traveling or something. But I usually review all the referrals here. I look at them and say, ok, this is high suspicion. Let's get them into the clinic. We give them to endoscopy within two weeks from the clinic. So essentially within four weeks because a lot of patients are concerned about not certain pre I actually call patients sometimes myself. And I say, listen, I've been doing this for a while. I know you're concerned and you wanna start treatment. But it's very helpful that we confirm your diagnosis before. Move ahead and I can talk to you more in clinic. I even sometimes book the patients for endoscopy, you know the day after the clinic immediately just to make sure that we uh alleviate their anxiety. Um After the confirmation of diagnosis, we get them to see that dietician, which always happens within two weeks. Usually we start them on a gluten free diet. We arrange for a Dexa scan labs for evaluating nutritional status. Um I usually recommend for the primary care office to help with pneumococcal vaccination and screening first degree family members. But I don't send this to the primary care. Just tell them if you have a family member, ask their primary care physician to get screened to screen them for celiac disease. Um uh we can, we follow our patients at least every 6 to 12 months, sometimes every year, sometimes every 18 months, actually, depending on how the patient is doing or every two years. Um And we monitor the labs for active disease and how they're responding to the treatment. And we actually have access to clinical trials. So many of my patients are interested in being part of clinical trials because they want to cure it. They are sick of gluten-free diet. So we try to help them with that summary. If celiac disease is a common, it's autoimmune, it's an autoimmune condition, it's not an allergy uh and may be underdiagnosed, especially in people of color and patients with non classical symptoms. A symptomatic response to gluten-free diet has no role in the diagnosis. The evaluation should be completed to start prior to starting the gluten-free diet and no biopsy of diagnosed celiac disease uh is based on uh uh based on serological testing is an area of controversy, but there's a very strict criteria of it for it. And if it's done, it should be based on an elevated tt gig. A more than 10 times the upper limit of normal combined with a positive Indonesia ig A antibodies and a symptomatic individual or a symptom of symptoms, suspicious or finding suspicious for civic disease. The accurate diagnosis uh uh uh of celiac disease should be done prior to starting gluten free diet. And it's important because of the burden and the outcomes we should not prescribe gluten-free diet unnecessarily. Um I'm happy to take any questions. Thank you. Uh This, these are our contact info here. Uh Please feel free to email me or reach out with any questions. So, uh thank you for your excellent presentation. Um I'm not, let's see what this are the symptoms related to malabsorption. It sounds like antibody levels fluctuate a lot. Is that from non-compliance? Can you repeat the question again? Sure. How I found it. I found it are the symptoms related to malabsorption? It sounds like antibody levels fluctuate a lot. Is that a form? That's an excellent question. So the symptoms vary a lot. In fact, there are about 30% of patients with celiac disease who have no symptoms at all. And those people struggle a lot in following the diet. Why do I need to follow the diet if I'm asymptomatic? Uh Right. We think that this is related to the distribution of the disease. I didn't put a slide on this but the disease sometimes is limited to the deum, sometimes it's just patchy in the jejuna, sometimes it's all over the small bowel. And we believe that the symptoms are related to how diffusive diseases or how severe it is. So, the symptoms are not all related to mal absorption also. Uh some, so many patients have constipation. We don't know why is it related to the inflammatory response that is happening? What? But those symptoms are present. Now, the antibodies fluctuate a lot. Yes. Correct. Um That's why we don't use them for follow up, you know, as a strict thing. But if they normalize, we use that as an issue, especially if the patients asymptomatic. But if I have somebody with persistent positive antibodies despite doing everything, despite them, meeting my C VAC dietician and my CF dietician, tell me they're doing everything. I usually go for a biopsy then to make sure that that positivity is not clinically important. The other thing is a mild positivity less than two times the upper limit of normal is frequently does not go away. So patients may start at high levels and then they run at level 20 or 18 or 22 or 21. And I tell my patients were really anxious, looking at the labs, but especially now, right, people can read the results on their phones and people get really anxious. I say I hear you don't worry, this is seen, we see this frequently. It doesn't mean that you have active disease, but sometimes in those patients, I do a advice to confirm that, but especially if they're asymptomatic, it's not very helpful. It's not very meaning it's clinically insignificant. Thank you for the question. Thank you for the answer. And also I will be sending out a Doctor Altar's bio sheet after this in the follow up email, she will have all of this information on it as well. It's on the screen. Um And if you guys, you know, if you have questions that come up down the road, you're welcome to email me or, you know, we'll have doctor Adar's email address. You could email him to just let us know if you've got a question that comes up down the road. And I, and again, if you're having it, you need a patient who needs help or anything, please always feel free to reach out either by email or call my office. If you haven't had time, call my office, just shoot me an email And, and again, I usually review the charts, my, I review all the referrals myself because I wanna make sure that I'm doing the right thing for the patients. Thank you very much for having me.
