Dr. Evan Dellon describes eosinophilic esophagitis, an allergic condition of the esophagus which causes a person to have trouble swallowing food. In addition to describing the symptoms of this condition, how it is diagnosed, and how it can be treated, he and Dr. Falk also talk about the risk factors for EoE and why the incidence of this condition is increasing.
“When you can look back at pathology samples from the 70’s, 80’s, and 90’s, you just don’t see the level of inflammation in the esophagus, with eosinophils. People didn’t see the findings in the esophagus when they did endoscopies in the 1980’s. Something has clearly changed. The incidence is increasing. It’s becoming more and more common.”
– Dr. Evan Dellon
Falk: Hello, this is Ron Falk for the Department of Medicine at the University of North Carolina. Welcome to the Chair’s Corner.
Today we welcome Dr. Evan Dellon who is an Associate Professor of Medicine and Epidemiology in our Division of Gastroenterology. Dr. Dellon specializes in eosinophilic esophagitis, more commonly known as EoE. He treats patients at UNC with this condition, and he is involved in a number of research studies that study EoE, as well as clinical trials testing a number of therapies. Welcome, Dr. Dellon.
Dellon: Thank you. It’s a pleasure to be here.
Falk: So–what on earth is eosinophilic esophagitis? And why don’t we all know about it?
Dellon: It’s interesting. It’s a new condition, and it was first reported in case reports in the late 1970’s. People didn’t really know about it, and there were only a few cases until the early 1990’s, and then cases started to accumulate. People have really only known about it for about two decades. It hasn’t really gotten into the general practice until the last ten years.
What it is, it’s an allergic condition of the esophagus, and it’s a condition where eosinophil cells, which are white blood cells involved in fighting infections but also an allergy response, infiltrate into the esophagus. Normally they’re not there at all. When you do an endoscopy and take the biopsies, you see many of these cells. At the same time, patients have symptoms due to this inflammation in their upper GI tract. That’s what leads them to the endoscopy. It’s a new condition, combining symptoms of esophagus problems and findings on biopsy of a lot of the eosinophils.
Falk: What would a patient actually complain of?
Dellon: The presentation across ages is a little bit different. I treat primarily adolescents and adults, and they have trouble swallowing, or “dysphagia.” Patients might have food sticking, they might feel food going down slowly. If you ask closely, a lot of people have had symptoms for years and modify the way that they eat. They might eat very slowly, take small bits, chew their food very thoroughly, drink a lot of liquid to get food down, and because they modify their diet, they might not feel their symptoms are very severe. But if food sticks, it can get stuck outright and not come up or down and then they go to the emergency room for food impaction. It turns out that EoE is now the most common cause of food impactions in the emergency room.
Falk: What’s a food impaction?
Dellon: Food impaction is when you swallow something that you’re eating, and it gets stuck in the esophagus. And it can’t come up—people can’t get it to come up with vomiting or regurgitation, and it won’t go down. It’s very, very uncomfortable.
Eosinophils…and why they are invading the esophagus
Falk: So let’s come back to this whole concept of what is an eosinophil. Eosinophils are also found in a number of pulmonary, or lung diseases. What do eosinophils do when they invade tissue?
Dellon: They have a lot of different functions. In the GI tract, eosinophils are normally found in the stomach, small bowel, and colon. We think they’re there in health, probably to prevent parasite infections, and help the GI lining work normally. When they come into the esophagus in high numbers, they do a number of things. They have a lot of toxic chemicals and factors that they contain. When those are released in the esophagus, it causes swelling, it causes irritation with the lining to become very delicate. It can tear, and then that in turn causes scar tissue to be laid down. Over time you can get strictures or blockage of the esophagus, and that’s sometimes why food sticks. Sometimes the entire esophagus can become very narrow, almost like a straw. It can become very difficult to swallow.
Falk: What drives the eosinophil to the esophagus, this unusual place for it to be?
Dellon: That’s a question that’s being looked at quite a lot by researchers. We don’t really know. We think EoE is caused by allergies. In a lot of people, it seems to be food allergies. We know that, because if you take away a lot of different foods or give people an allergy-free diet, many of them get better right away. We also know that it can be caused and driven by environmental allergies, like pollen or other things in the environment. We know a lot about the type of allergy reaction that is triggered. It’s very similar to allergic skin problems, like eczema, or allergic lung problems like asthma. But we don’t know why yet for a patient why they might get the condition.
Falk: But if it wasn’t recognized, other than case reports forty years ago, what’s the allergen in our environment now that is making these cases the most common cause of food impaction coming to an emergency room? It sounds like the incidence of this disease, perhaps unrecognized in the past, but now quite prevalent, is being driven by something in the environment. What is it?
Dellon: Absolutely. That’s the million dollar question. When you look back—we’ve done this here, and other places have done this—you can look back at pathology samples from the 70’s, 80’s, and 90’s, you just don’t see the level of inflammation in the esophagus, with eosinophils. People didn’t see the findings in the esophagus when they did endoscopies in the 1980’s. Something has clearly changed. The incidence is increasing. It’s becoming more and more common. It’s about one in two thousand now. Actually, what we do, if you’re getting an endoscopy for any reason, in your esophagus or stomach, there’s about a seven percent chance that EoE might cause your symptoms. It’s becoming more common.
What may cause it in the environment? Well a lot of things have changed in the environment over the last thirty years. The food supply is very different, there’s a lot more monoculture of crops, there are different pesticides in use, different ways we raise animals—with hormones, or other things in their feed. These could all be contributing to environmental factors. There may be differences in pesticides or air pollution. These are all interesting hypotheses that we’re doing some research actually to test, but nobody really knows. It’s thought that maybe it tracks with other allergic diseases which are increasing, like asthma, and eczema are all increasing. That’s where the theory lies right now.
Falk: It sounds that food may be at least one of the culprits, because if elimination diets, or getting rid of foods over the course of time help, it sounds like it really is potentially something we’re ingesting.
Dellon: Yes. In kids, the food elimination diet was initially looked at. That’s where people started to feel that it was a food allergy-mediated problem. Now we know that adults respond to these kind of food elimination diets.
Food elimination diets and other treatments
Falk: Describe a food elimination diet.
Dellon: There are several kinds, actually. It would be nice if you could go and have some allergy testing and figure out what foods you might be allergic to that cause EoE. The frustrating thing now, is that the allergy tests that we have, where you do skin prick tests with food allergies, are not very good at predicting what causes EoE. They’re actually less good than a coin flip-they’re not very accurate.
So what we do now is an empiric elimination diet, where we know, for many people, what the triggers are, and we recommend what’s called a “Top Six” food elimination diet, where patients are asked to eliminate dairy, wheat, egg, soy, nuts, and seafood.
Falk: That’s a big list.
Dellon: It is a big list. Those are the top six food triggers in EoE. This is not a diet that most people can do on their own. They have to work with a nutritionist. It’s very doable. It’s actually a pretty healthy diet. It’s a lot of lean meats, fruits, and vegetables. Almost like a Paleo diet in some respects.
Falk: What’s a Paleo diet?
Dellon: Unprocessed foods, foods that would have been available when cavemen were around, that you can eat. So it does tend to be healthy. Of course, it is hard to do. It’s hard to eat out, hard to eat processed or prepared foods. People have to learn how to cook. There are a lot of resources out there to help with these kind of diets. So in children in particular, it’s very common to do these diets. I would say here, at our center, about a quarter to a third of my adult patients elect to do this kind of a diet.
Falk: So before you go on a diet that you may not want or is not easy to do, the diagnosis happens how? By endoscopy?
Dellon: Yes, the diagnosis is a combination of two things. The first is the clinical presentation. So like I mentioned: adults-mostly trouble swallowing. Kids actually have many more symptoms that we call non-specific in that the symptoms can reflect many diseases. Kids might have heartburn, or abdominal pain, or vomiting. Babies might have failure to thrive- or growth problems, or feeding difficulties.
So once you have someone you’re seeing with those kind of symptoms, then you proceed to the endoscopy. There are some typical changes in the esophagus that we can see with swelling, or irritation, or scar tissue. Then we do the biopsies where we take little pieces of the esophagus, and send them to the lab to look at it, and they can see the eosinophils under the microscope.
Falk: Can you tell when you’re doing the endoscopy that a person has presumptive eosinophilic esophagitis?
Dellon: The endoscopy can be pretty suggestive. About ninety-five percent of the time, patients have some of those findings that I just described. But there are some patients, especially as you get younger, that it may look pretty normal, actually, and you need the biopsy to tell the whole story.
The other thing about doing the diagnosis is, not just EoE can make eosinophils go into the esophagus. This is where it gets a little bit confusing. Turns out there are other causes that can give you eosinophils in the esophagus and elsewhere in the body. When I’m trying to diagnose people with EoE, I have to think about these other causes. The most common cause, actually, is reflux disease. When people have acid splash up into the esophagus, it causes non-specific irritation, and eosinophils come in as part of the injury and healing process. You’ve heard me list some of the symptoms—heartburn, vomiting—those can be common signs of reflux. And reflux, if it’s severe enough, can cause trouble swallowing. So we always have to consider whether reflux may be playing a role.
Then we also will use medications in the proton pump inhibitor class, which are anti-acid medications, not only to treat for possible reflux, but it turns out those medicines have a very interesting anti-inflammatory property which can clear the eosinophils from the esophagus. So there’s a few steps in some thinking before you can make the diagnosis. The biopsy itself doesn’t give you the whole story.
Falk: Let’s talk again about other forms of therapy. You talked about food elimination diets, going back to the cave, hunting and gathering. Are there drugs that seem to work, are there FDA-approved therapies?
Dellon: Right now there are actually no FDA-approved treatments for EoE. Every medication that we use, every treatment that we use, is pretty much off-label. The good news is there are a lot of possible options for medicines in the future that hopefully will get an FDA indication, but right now, nothing is FDA approved.
Thinking about treatment overall, there are three main categories, that we usually call the “Three D’s.” We already talked about one of them, which is diet. The next one is drugs, and the other one is dilation, or stretching the esophagus. Dilation is done when you have a blockage or a stricture, or scar tissue, we can stretch out the esophagus and allow food to go down. That’s very important, because it helps take care of the scar tissue. But it doesn’t do anything for the underlying inflammation, so that has to be treated with diet or with drugs.
I’ll make one other point about the diet. The goal is not to do this very restrictive diet forever. It’s actually to do it, see if it works—which it does for about two thirds of people or more. Then, add back foods one at a time to find the trigger. So long-term, people may only have two or three foods that they have to eliminate, not all six.
Falk: What’s the most common food that remains eliminated?
Dellon: The most common is dairy. That’s a trigger in at least fifty percent of people. And then wheat and egg follow pretty closely after that.
Then when we think about drugs, it’s actually pretty interesting. What we use are considered topical steroid medications. It’s akin to taking cortisone cream and rubbing it on a bug bite. It takes away the redness and the irritation—but we don’t have a cream that we can rub into the esophagus. So what we’re stuck with is adapting asthma medications. We might take an inhaler with a steroid, like people breathe into their lungs with asthma. Instead of breathing it in, patients will puff it into their mouth and swallow it, and it coats the esophagus. You can also take asthma medications that are in a liquid form that are used in asthma nebulizers and instead of making them into a vapor, you take the liquid and mix it into a syrup and swallow it. And that coats the esophagus. Those are actually pretty effective as well.
At least two thirds if not more, of people tend to have a response to that, and they’re pretty well tolerated.
Falk: How about steroids? Oral prednisone?
Dellon: Prednisone works systemically, the problem is it causes a lot of side effects with long term use. So, apart from very, very rare cases, with people who are very severe or malnourished, we tend not to use prednisone. You could use it for a few weeks, but then you’d have to transition to something else.
Clinical trials in EoE
Falk: You mentioned that there were drugs that hopefully the FDA would approve sooner or later. That means that there must be active clinical trials that are underway. Can you tell us about some of those?
Dellon: Yes, that’s one of the really exciting things in the field right now. There’s a critical mass, I think, and a lot of interest to test new drugs. There are quite a few clinical trials going on. For the topical steroids, this is really an engineering problem. How do you get this medication to the esophagus, minimize getting it into the lung, minimize the amount of medication that’s exposed to the person’s whole body? There are new formulations, there are syrups that stick to the esophagus lining. In Europe they’re testing a dissolvable tablet of a topical steroid. Some very interesting and promising new delivery mechanisms.
Two of those studies are actually in stage three, so hopefully that’s the last stage before FDA approval. Within two or three years there will be hopefully something that’s approved.
The other thing in terms of medicines is we’re learning a lot about how EoE is caused, in terms of the various factors in the body. There are a number of biologic medications, antibodies that block some of the factors that cause EoE. There are some medicines that target against anti-IL-13, and anti-IL-4, factors that are pro-inflammatory that bring eosinophils into the esophagus. There’s another medicine that blocks a main factor that helps eosinophils grow and mature in the bone marrow called anti-IL-5. That’s just been approved for asthma and has previously been tested for EoE. So some of these medications are quite exciting in theory, but it’s still pretty early, and we don’t really know their role yet for this condition. Then there are other newer medications that may block some of the other factors that cause EoE. There’s one that blocks a prostaglandin that’s being studied. So it’s very exciting-there’s a lot of new things on the horizon.
Falk: If you’re listening to this podcast and you want to participate in a clinical trial, what should you do?
Dellon: It should be pretty easy. If you’ve got EoE, you can go onto our web site for our esophageal center. We have a whole page outlining the different studies that are open right now. We’ve got an email for research which is email@example.com. That goes to our research staff.
Known risk factors
Falk: Are there known risk factors? Are there predisposing kinds of factors that would make it more likely for you to get the disease?
Dellon: There are. EoE, first of all, is more common in men than in women. It’s about three to one, men to women. We don’t really know why that is. There are some studies in genetics that are starting to sort this out. That’s an easy risk factor to know about. In terms of race, it’s seen more commonly in white people rather than other races. But here at UNC we have about fifteen to twenty percent of the patients who are African American. It’s rarely seen in people of Asian descent and of Hispanic descent, interestingly enough. Again, reasons for that are not well known.
It can run in families. There are some genetic predispositions that some gene mutations have found. It’s certainly not a one gene disease, it looks to be a complicated disease with multiple mutations that can cause it, but within families there’s about a three percent risk between either a parent and a child or a child and their sibling. Again, that’s compared to about one in two thousand in the general population. So there is some elevated risk in families. Then if you look at other risk factors, there’s a lot of associated allergic disease. These patients– in kids maybe up to eighty percent, in adults, maybe up to sixty percent– would have asthma, or at least one of asthma, or food allergies, or eczema, or environmental allergies. They do travel together.
Then the other thing is, what could be some other interesting risk factors. Not just sort of the demographic. So this is an area that I have done some research in. Working with some colleagues at the School of Public Health here, we’ve done some relatively large epidemiologic studies and have found that EoE tends to be relatively more common in rural areas, rather than in urban areas. It’s actually the opposite of what you usually think about for allergic diseases. It may point to something in the environment. Is there something in terms of vegetation, or temperature, or we’ve shown some differences by climate zone? Or something that’s used in those areas, in that environment, that may predispose?
Falk: Is it more in southern climates than in northern climates, or the other way around?
Dellon: It’s actually most common in dry, arid climates. And a little bit more common in colder climates than in temporal. When you break down diagnosis by those climates, you see a peak around June or July, and in colder climates it’s shifted further, with a peak at about August, and in the hotter areas it’s shifted a bit earlier. It may be indicating something in the environment.
Another interesting thing is, we’ve associated EoE with a lack of H. Pylori infection. H. Pylori is an infection in the stomach that’s been in people for millions of years, and we know it causes gastric cancer and gastric ulcers and small bowel ulcers. That’s something that’s been really wiped out of the environment over the last twenty or thirty years. So maybe, rather than something increasing in the environment, something getting taken away. It’s another interesting hypothesis.
Falk: We all need to live, with mutual respect, with various bugs that are part of not only our gastrointestinal tract but every mucosal surface. That’s really strange. Can you imagine the eradication of the bug is attributable to gastric inflammation of one kind or another, is the driving force behind the condition? We will all be taking pills that have H. Pylori.
Dellon: It’s been associated with an increase in asthma and eczema too, so it’s very interesting.
Support for EoE
Falk: People who have this entity, EoE, especially adults, and they suffer the symptoms you’ve described, the concern of course is they don’t know what’s causing them. They’re probably not willing to go to the doctor. Then they get a food impaction and have to go to the emergency room, that’s almost an end stage moment. What can you do to help with earlier diagnosis? What suggestions can you make to people who really are trying to battle this condition?
Dellon: I would say that, the first thing is, it can affect anybody of any age. There have been infants who’ve had the condition, and older people. But children, adolescents, young adults—that seems to be the peak until around forty years of age. If you have symptoms of trouble swallowing, that’s always abnormal, and you should really seek out medical care. Many patients who I talk to have had symptoms for years and they’ve always been told, “Oh, it’s your teeth” or “You just don’t chew carefully enough” or “You eat too fast.” But usually when a food is sticking when you swallow, it indicates an underlying problem. You should really get that checked out. People can go to their primary doctors, tell them about their symptoms, and then get referred to a GI doctor, or they can call a GI doctor and have that symptom evaluated as well.
The other symptoms-heartburn, or if you’re younger, abdominal pain, weight loss, or vomiting, these are all symptoms that would be concerning to a doctor hearing about them. It makes sense to get them checked out. I would say over the last ten years, most, if not all GI doctors know about this condition now. But the condition is still uncommon enough in the general population. Many non-GI doctors don’t really know about it. Allergists know about it a lot. But there is a delay in diagnosis.
One of the reasons for talking about this is to get the word out, and there’s quite a few resources that patients who are having symptoms or who have the diagnosis could use. There are actually patient advocacy groups and foundations who have a lot of knowledge about the condition and have great sites. There’s one called the CURED Foundation-it’s the Campaign for Urging Research in Eosinophil Disorders. There’s another organization called APFED which is the American Partnership for Eosinophilic Disorders. Those web sites can help with symptoms and a lot of resources, for example, for doing the diet for elimination.
Falk: And there are Facebook groups too, is that right?
Dellon: There are Facebook groups throughout the country. There’s one in Charlotte, a very large group, for eosinophilic esophagitis and other eosinophilic diseases, and that’s one to check out as well. The other thing I would note is that we have a collaborative between GI and allergy providers, dieticians, and nutritionists in North and South Carolina called the Carolinas EoE Collaborative, or CEoEC. They have a web site as well, and this is a referral network. It helps patients find doctors who specialize in this condition and it also helps doctors help patients who might transition. For example, if a child is turning 16, 17, 18, going to college and they need to transition from a pediatric to an adult provider. This collaborative helps with that, and it’s also a platform for research studies.
Falk: Dr. Dellon, thanks so much for spending time with us today.
Dellon: Thank you for the invitation.
Visit these sites for more information on EoE: