Transcript of Learn with the Leaders: Celiac Disease with Dr. Bharat Misra
Recorded Date: March 27, 2023
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All right, so today's talk is about celiac disease first, I have to apologize if the talk is a little bit too technical. I'm going to try to make it less technical, doctors, lawyers all specialists we speak "doctors speak," so if I get too technical, please stop me. I'll clarify things a little bit better.
0:41
Okay, so before we start the talk, I have two overarching comments that I'd like to make. The first is that, as you may know, most patients with celiac disease can't have wheat. And wheat is structurally and culturally such an important part of the western world.
0:58
The first wheat grown was 9600 years ago in what is called the Crescent around Syria. And since then, because of some unique properties, it has become the cornerstone of
human civilization and so not being able to eat wheat is a big deal, You cannot go anywhere, and that's why I think Celiac is such an important disease to talk about. So, I'm a gastroenterologist, as you know.
1:35
So just as a big-picture scenario, the esophagus, the first part of the GI tract, just transports food to the stomach as a blender it basically blenderizes the food. The small bowel is where all the action happens, it's where most of the digestion and almost all the absorption happens. The colon is basically to keep waste matter. So that's like the big-picture scenario. And what happens with diseases is, that you learn how important an organ is when it stops working.
2:22
So, what is the abnormality in Celiac disease? It's this we do endoscopies three days a week and three days a week when I leave the stomach and enter the first part of the small bowel called the duodenum this is what I see. And this is actually very beautiful, it's like 60 shaggy carpet and these are villi. And the villi are very pretty, but they're not only pretty, but they serve a critical function. I learned somewhere from a layperson that if you flatten out all the villi in the small bowel you get the surface area of a tennis court. Every time I'm on the tennis court, I think about that. The villi make an ordinary 26-foot-long tube into an absorption supermachine. It absorbs everything, I tell my patients on Thanksgiving you absorb 10,000 calories the next day you're hungry again.
3:26
The amount of absorption the small bowel is capable of is infinite, and that's why you get 800-pound human beings. Because we evolved at times of great scarcity where most of our food came from plants and plants of very low calories so to absorb them, we created the villi. And we lengthened the small bowel so the villi basically mean a finger-like projection basically longitudinal tubes that are supplied by blood vessels, both arteries and veins and lymphatics. And they play a critical role both in digestion and absorption.
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And what happens in Celiac diseases these villi go away, or they become less numerous. So that is the central disease in Celiac disease or the central pathology in Celiac disease. Okay, so what is celiac disease? It's basically an immune-mediated reaction of the small bowel to an outside allergen. And that allergen is gluten
and this reaction is mediated by the immune system. And you are genetically predisposed to it. That's basically, the disease it's very conceptual. It's not very hard to think about celiac disease unlike say, diabetes or heart disease. Which are very complex Celiac is very simple. And it's also called Gluten Sensitive enteropathy, celiac brew, and some other names. And I learned recently that it was discovered in the second century and that's when this Greek physician named it Celiac. Celiac means gut disease.
5:28
And it was first described by pediatrician Samuel Gee in 1887. The diseases are very found in kids. So, of almost all the initial work on Celiac came from pediatricians.
And that's kind of physiology now. I have to tell you a story about a patient. I saw a patient recently in his 20s or 30s who had diarrhea, and weight loss, many of the classic symptoms. And I asked him a little bit more about his history; he said his parents were in the Army. And they were stationed in Guam, I think. And when the baby was born, he was fine for about six months. After six months, he started having all these GI symptoms, and a very smart pediatrician said to feed him only bananas, and he's going to be okay. So, every month a shipment of bananas would come and he would get the first allotment. They would freeze it, and he basically survived on bananas. And interestingly, that's what pediatricians did about a hundred years ago when they did not know what was causing it. But they knew it was something in our diet. They didn't realize it was something as prevalent as wheat, but they knew if you changed the diet to bananas, patients would get better. And so this story is reflective of how Celiac was diagnosed and treated in the early days before we knew all the pathophysiology and things like that.
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Okay, so what about genetics? Don't read what's on the slide, it's very simple, there are two genes. They have long names (HLA) DR3-DQ2 or (HLA) DR4-DQ8. If you do not have these two genes the odds of you having celiac disease, drop to one percent. That means 99% of patients have one or two or both of these genes to have the disease. So it's clearly a genetic risk. So what is interesting is that five percent of the population in the west and in the United States has these two genes, but only one percent get celiac disease. So there's something else that has to happen in genetically pre-disposed individuals for them to get celiac disease. We're not completely sure what that is. There are some theories about it, and I can talk about them in the question-answer session. So the genetic test is not commonly used for diagnosis, but it helps. The other three pillars make the diagnosis the second part of a genetically predisposed individual. The immune system goes crazy for most of you. When you go back to your high school physiology, you know there are two types of immune the immune system is divided broadly into innate, which is something you're born with, and acquired immune system. Acquired is you get penicillin, your allergy that's an acquired immune system. In Celiac disease, both these systems go crazy, and we know this because multiple antibodies and immune agents are seen in blood in biopsies and in other organ tissues too.
9:06
Okay, so a little bit about who gets celiac. So Celiac is prevalent worldwide we used to think it was limited to the West but it turns out it is not. It's a recent study that in the northern part of India, Celiac diseases are twice as common as in the United States. So, it affects every wheat-eating culture in the world. The worldwide prevalence is about ne percent, and for every one patient, there are seven undiagnosed patients with Celiac. So it is a little tip of the iceberg. We don't know if it's increasing in incidence or we're getting better at diagnosis, but every year the numbers go up because we have better tests. Patients who are first-degree relatives of patients with Celiac are at increased risk and it is associated with some other unusual diseases which indicate that there is a genetic link. Okay, so this is classic Celiac which even a first-year medical student can diagnose. They have severe diarrhea, it's the main symptom of celiac they don't absorb fat. So, they have fat malabsorption, The stools are oily, they lose a lot of weight, and they get different vitamin or neutral deficiencies. You go to the doctor, and the doctor then does a blood test and then recommends an endoscopy. Typically at endoscopy, you see the classic signs and
symptoms. The diagnosis is made, and the patient is, so this is a fairly classic textbook. Celiac unfortunately the other types are more common. This is a type where patients don't really have a lot of GI symptoms, they're not complaining of a lot of weight loss, and diarrhea. They present with other unusual symptoms they have mild anemia, they go to the dentist and say your enamel is bad, their bones become thin, they get arthritis, they cannot conceive and they have neurological symptoms very subtle neurological symptoms, and movement disorders. This requires a high index of suspicion and when you have a high index of suspicion you order the endoscopy where the villi go away and the blood test that's positive. This is the most common, this is subclinical celiac disease.
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Patients don't have a lot of symptoms they had abnormalities in the blood and in the biopsy but they don't have a lot of symptoms. So do they have celiac disease or not? For these patients are it's worth putting them on a gluten-free diet because even patients who say they have no symptoms actually feel a whole lot better. The energy level goes up. What they thought was just arthritis from getting older gets better, their skin texture improves, and their memory improves. So subclinical may not be really subclinical. The symptoms may be so subtle patients just learn to live with them. Okay, this is a potential celiac disease. You have no symptoms, you go and see a doctor and the blood test is abnormal, and you have mild abnormalities in your biopsies but you don't have any symptoms you don't have any malabsorption. Do these patients have Celiac? They don't, so you have to have some degree of symptoms, even mild
symptoms before you call them true Celiac. But they're at risk for celiac. Many patients prefer to go on a gluten-free diet even though it's not recommended for potential Celiac patients. And then there is latent Celiac which is pretty rare. Somebody gets diagnosed in childhood they grow up, and they start eating wheat, and they feel better. We used to think that Celiac can go into remission in some patients. It turns out it's actually pretty rare. There's a recent paper that looked at 80 people with so-called latent Celiac they had an active disease they just did not have a lot of the symptoms. Remember symptomatic celiac disease is the least common. So they continue to have malabsorption. So they truly did not go into remission. This is a refractory Celiac. This is very rare. Fortunately, if you diagnose somebody with Celiac you put them on a gluten-free diet. They don't get better, their biopsies don't improve their serology doesn't go back to normal and they don't feel any better at all. And this is a diagnostic conundrum nobody knows why most people with refractory Celiac are just not following a gluten-free diet. It's actually a very hard diet to follow and most people are just falling through the cracks. But if they do then we have to think of other rare causes of why Celiac is not responsive.
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Okay, so what are the clinical manifestations of celiac? Remember, this is a talk for adults, in kids, they typically present with diarrhea and an inability to gain weight. In adults, typically it's between the age of 10 to 40 years. The classic symptoms of diarrhea, fat in the stool, weight loss, anemia and deficiencies. These are somewhat unusual but when you see them, they're very typical. So there is this rash it's called dermatitis herpetiformis it looks like a small patch of herpes just a bunch of vesicles on the skin and they keep going to dermatologists again and again and again and they get treated, they get better, it comes back, it's very classic for celiac. I saw a patient last year who had had it for six years and had been to three different dermatologists and nobody ordered a Celiac test until she moved to Jacksonville and this very smart Dermatologist said you gotta have this test done. Her test was positive, we put her on a gluten-free diet, and she'd never had that rash again. This is where these are all other manifestations or redness of the tongue osteoporosis anemia and as I said Neuropsychiatric symptoms.
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Now Celiac is associated with many other diseases the classic is Type 1 Diabetes. Type 1 diabetes as you know is in children it's typically because they have antibodies against insulin. It's a very hard disease to treat whenever you see type 1 diabetes you have to order Celiac, and the other big one is autoimmune thyroiditis. Anybody who has autoimmune thyroid disease has to be checked for celiac. The link between the first two and these two in celiac is very tight the others are GI and non-GI diseases where there is a high risk. In other words, whenever I see a patient with microscopic colitis, which is pretty rare. But I always order a Celiac and about six percent of the time it's positive. These are other conditions. So a classic presentation would be a couple goes to an infertility doctor, they can't have kids, everything else looks okay, and one of them has celiac. So Celiac is part of all infertility workups. As you can see, there are so many, Celiac is really all specialists who should be aware of Celiac. For example, if you have idiopathic pulmonary fibrosis hemosiderosis, there's like an eight percent risk of you having Celiac. This is where I think our colleagues need to be educated. It's basically, it's a malabsorptive disorder. So everybody should be suspecting this.
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How do you make a diagnosis? You have to rule out something called non-celiac gluten sensitivity. I'll spend a couple of minutes on this because a lot of people are staying away from gluten. As I've already told you I played tennis and there's a little story behind it Novak Djokovic about four or five years ago gave up gluten nobody knows if he was diagnosed with Celiac or not and since then he won like 250 matches in a row. So all tennis players stay away from gluten. It's like a little thing that athletes have, so what does he have? Well, most likely he has non-celiac gluten sensitivity. Remember most patients with Celiac have no symptoms. With non-celiac gluten sensitivity, as soon as you eat gluten, you feel bad, you have cramps, diarrhea, joint pains. This is a true allergic reaction. You're allergic to wheat and what's interesting is it is three times as common as celiac. Three percent prevalence of non-and that's the reason it's actually good for us, for our Celiac patients too. That's why we have gluten-free on every menu now. It's because these people are ill they feel it the next day they go back to the restaurant and they complain. This is why gluten-free is very prevalent. It's because of non-celiac.
18:37
The other important point is all testing should be done while you're eating gluten. If you stay away from gluten within two weeks, your antibodies drop and may disappear, so it's a very common mistake where we do the testing off of gluten and of course, all the tests come out okay. Okay, so we talked about serology. Again you ignore what's on the slide. Here's the bottom line about blood tests. We have one single test. This test is called a tissue transglutaminase IGA antibody DTG IGA. This one single test, it's inexpensive, it’s done by every commercial lab in the United States and has a 90 to 98 sensitivity and almost 95 to 97 specificity. There are very few tests that can do this, so we now have an easy way to look. So whenever you suspect, doc always suspects you may have it ordered. This test is very rare, so the rest of it is all a little complicated. But the bottom line is we have a great single blood test to make this diagnosis and if you stay away from gluten, it drops.
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So you can also measure if somebody is following a gluten-free diet. In other words, I have patients who go on a cruise and they come back and I always sneak in in the blood test. I know what they've been doing on the cruise, you know, eating gluten.
All right so, what happens during an endoscopy? You remember from the first picture, the beautiful villi which are like this in Celiac disease. This is what happened, this is a very advanced celiac. The villi go away this is the main problem in Celiac and so you can't absorb and this is how it looks like if you remember you can see there are no villi. And there are other markers that are more for gastroenterologists, but basically, the villi become shortened and shortened and shortened until they have advanced celiac disease. So most doctors would accept in rare cases in kids if your TTI is 10 times above normal or if patients don't want to have an endoscopy. An endoscopy is the third pillar in diagnosis. We usually recommend that your stage the disease and then this is very important. The Marsh classification is very important for every Celiac patient who has a biopsy should get this Marsh classification because it becomes your baseline. And in an ideal scenario, you should go from say Marsh 3 to 0. And so that's the bottom line. Okay, what about patients who are on a gluten-free diet and they just don't want to go back on gluten? Then you can do a genetic test, remember what I said if you don't have these genes, you don't have Celiac. That's easy but what if you have the genes then you have to do something called a gluten challenge. You have to give them gluten for between two to six weeks and then retest them. There is a new test which I have not ordered but I just read about. I don't know if it's commercially available.
22:04
What is the treatment these are the six or seven pillars of treatment. Ideally, you should have a dietary consultation and this is where I might need your help. I don't know of any dietitian who specializes in Celiac. I'm recommending online apps. There are online
dietitians who specialize in Celiac most other dietitians don't have a deep knowledge of celiac. They're not very useful in fact, I learn more from my patients than from my dietitians. And here I have a story I tell; the patient she said I couldn’t eat anything and I told her why don't you try Rice Krispies she looked at me she said Rice Krispies has gluten. I'm like really why would you put gluten in? So gluten is in everything it's because gluten is very sticky. It's used as a filler in hundreds of products where it doesn't need to be. So that's how I learned more from my patients about what to do. If you have access to a good dietary consultation, is very important education. The patient has to educate themselves and of course, the pillar of treatment is a lifelong gluten-free diet. That's the treatment and it will put your disease into remission in the vast majority of patients. So you stay away from wheat, this disease goes away and then if you have any nutritional deficiency and then we tell all our patients you have to
become an advocate. You need to be followed up and then if you have access to a clinical trial please participate because as you'll see there is some good news.
23:49
What is a gluten-free diet? The three grains that we need to avoid are wheat, rye, and barley because they contain gluten. They're kind of similar as you know, wheat is a grass and these are very similar to tapioca, rice, corn, buckwheat and potatoes are safe. So any flour made from them is safe. Read the labels. And this is bad news for all the young guys but you can't have beers. You know, actually, I have a patient who stocks gluten-free beer in his house. So I can tell you but they are specially made and they're not made from malt they come from some other source but the regular you can't have it, unfortunately. But distilled beverages vinegars and wine are safe this is very important. Many patients with celiac disease when their disease is active or lactose intolerant because lactase is also seen in the small bowel you can't absorb milk. So they have to temporarily be on a lactose-free diet. This was one of the big confusions. If you look at the history they would stay away from milk and they would get better. So for a long time people thought milk was the culprit. It turns out milk was a secondary phenomenon. Oats is a little controversial even I was not aware of that but oats don't have gluten but they're made in the same factory. So sometimes there is contamination and what I heard was that small amounts of oats are okay. If you exceed a certain amount, then it's a problem. Oats themselves don't have gluten in them and strict adherence is recommended. 30 milligrams per day that's like 10 parts per million so this is very strict in other words. You cannot have gluten in any form or shape. This is inadvertent in other words, you take a multivitamin or a blood pressure capsule that has gluten in it that's where you get this small amount.
25:49
So the lactose intolerance goes away when your small bowel recreates there is a caveat to that. Unfortunately, as you know, the vast majority of human adults cannot digest milk. So if that's your mechanism for lactose intolerant then you won't go back but if you're like you were you were able to have milk before if your disease is in remission, most people can tolerate milk. Then you become like everybody else as far as lactose goes. All right so once you start a gluten-free diet symptoms get better in as little as two weeks. We re-evaluate them after a few months. I learned this when I was preparing for this talk that females can get breast tenderness for three months mechanism. We don't know. And then, it takes a little while to rebuild your small bow. So you repeat the blood test in three to six months and repeat the Endoscopy in six months to two years. Two years is better and that's when you should see all the changes are better. But sometimes patients are very anxious at six months. They've been doing great they need a little positive reinforcement then you can do it at six months. This is another thing I learned as I was preparing for this talk you don't want to re-challenge them with gluten once they get better because it's like any allergen. Once you've stayed away from it for a little while if you re-challenge it you don't have the same reaction that you had before you have a worse reaction. So this happens to anybody like if you stay away from milk you were not lactose intolerant, the next time you have milk, your body will reject it because it's now it's not used to it. So patients like the idea of a gluten-free challenge but medically it's not recommended.
27:35
The gluten challenge is only recommended if your initial testing wasn't a gluten-free diet. See this is different what I'm saying is your testing was done while you were eating wheat and you were diagnosed with Celiac, you got better you don't want to re-challenge that person but let's say your initial testing was done while you were pretty much restricting your wheat then you re-challenge and re-challenge has to be done very carefully. It's done with the half to one slice of bread every day for two weeks and then from two to four weeks one slice daily for six weeks we had to be done carefully But if your initial testing was done when you were on a gluten diet then you don't need to be recharged. A small number of people don't respond and this maybe is mainly due to poor dietary compliance. But there are other diseases ulcerative genitis sibo which looked like a celiac disease on a biopsy and then you go back to the gastroenterologist to rule these other fairly rare diseases. This is the refractory proof we talked about it. It's very rare I think I have only one patient and he's been referred to a Celiac expert to find out why. Okay what additional treatments you have to check for vitamin and mineral deficiencies and replace them?
29:08
Remember, wheat is a main source of fiber in our diet. Whole wheat is a great source of fiber. When you stay away from it people get constipation so you give them psyllium-husk. Many medications, such birth control for example if your absorption is very poor, you have to adjust the dose of the medications. You give them vitamin D and calcium to prevent osteoporosis. And this is very important they all need pneumococcal vaccine, maybe not as much younger patients but older patients, you have to emphasize the pneumococcal
vaccine. Ad then, if you had that skin rash, there's a medication called Dapsone.
Okay, so that's where we are, where are we heading? The future is actually very exciting. This is from a year ago, but there were 22 potential treatments in clinical trials. And they range from pills that inactivate gluten to inactivate the immune system at the level of the gut and then prevent the immune system from spreading to the rest of the body. The entire stage there are drugs being studied. The one drug that went to phase three, we were not part of it, but it was stopped because there was not a big difference between the placebo. This was just a few months ago Lorazotite was stopped, but there are many other drugs coming and they are in phase one phase, two and phase three trials.
30:41
Our interest is that we are doing a phase one trial, as you know phase one is first in humans and we have a spectacular phase one unit. I mean this place is very well run. Some very competent people and they are doing a clinical trial. So it's the drug manufactured by Chugai Pharmaceuticals and it's basically similar to; you're probably familiar with the Remicade and all these biological drugs this is very similar to. That it's a humanized antibody that binds to the specific locus where gluten and this DQ2 Gene bind together and suppresses their activity and it helps patients with celiac disease very early. So the purpose of the phase one study is to see if it's safe or it's basically a safety study and we need patients who have biopsy-proven celiac disease, They must be in remission and they have to have one copy of the DQ2 gene so if you know of people who are interested please spread the word around. This is very exciting, one of the things we learn about wheat is that what has happened is as agriculture has become mass-produced we used to eat 3,000 different types of wheat if you went
from one village to different village that wheat has not crossed that village. So every country had its own wheat. But wheat has been selected for pesticide resistance, and drought resistance so the vast majority of the world now is eating one or two species of wheat. And what that has done is these have been selected for a high gluten content because gluten is what makes Pasta Pasta. It makes it so nice. It's so they've been selected for that purpose and so there is a movement to
go back to other types of wheat. And it turns out the other wheat variants are much less immunogenic.
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And so there's a lot of exciting research on wheat that will not cause celiac disease. This I think is the Holy Grail. But well so there's a lot of research going on in different kinds of wheat. So we need volunteers and this is a pitch for that. And you know volunteers are very important in clinical trials and that's it. Thanks for joining the MedEvidence podcast to learn more head over to MedEvidence.com or subscribe to our podcast on your favorite podcast platform.
