Diagnosis and management of eosinophilic oesophagitis

Eosinophilic oesophagitis patients are often symptomatic at the time of eating, whereas in GORD symptoms usually occur after eating or at night-time. And that could be something that can differentiate between GORD versus EoE.

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Eosinophilic oesophagitis. Not only is it a mouthful to say, but it has also been something of an enigma of a disease for many generalist clinicians. It’s a disease that was only identified in the early ’90s, but now is a major cause of upper gastrointestinal illness, just behind gastro-oesophageal reflux disease, with prevalence estimates having quadrupled over the time since it’s been discovered. What is it? What causes it? How do we pick it up and how do we treat it?

I’m David Liew, your host for today. And here to tell me more about this disease is Dr Varan Perananthan, a gastroenterologist at The Alfred in Melbourne. He’s written on this subject for Australian Prescriber and I’m very glad to welcome him here to the podcast today.

Thanks, David. It’s really good to be here today.

So tell me, what exactly is eosinophilic oesophagitis?

Eosinophilic esophagitis is certainly a mouthful. So, I think for brevity it might be easier if we just call it EoE. EoE is essentially, it’s a chronic inflammatory condition and it’s a non–IgE-mediated form of food allergy. And as you said, the prevalence of this is increasing due to multiple issues, but for the most part, we actually don’t know why it’s increasing overall. And often patients will complain of dysphagia, but increasingly the first time that patients are diagnosed with this condition, they actually present to the emergency department with a food bolus and end up having an emergency gastroscopy.

And it’s usually at this point when they’re diagnosed, and the specific food allergies are fairly varied, but the implicated antigens or the known triggers for EoE include animal milk proteins, wheat, eggs, soy, nuts and seafood. And usually, it’s one of these antigens, but in rare cases it can be one or more of these antigens. And what happens is, when a person with EoE is exposed to these antigens, it causes an inflammatory response, much similar in terms of the pathogenesis of asthma, but over a period of time, it causes remodelling to the oesophagus, to the point that, in fairly advanced disease, the oesophagus actually kind of looks like a trachea.

That is certainly intimidating. I wonder, though, why we haven’t heard about it more until recently. It seems like it wasn’t recognised at all till the 1990s, and then all of a sudden it seems to have escalated. So, where was this problem before and why are we only hearing more about it now?

I think there’s a few reasons for this. The first reason is that the cause for EoE is likely a combination of environmental and genetic factors. For example, amongst first-degree relatives, there is a genetic predisposition to develop EoE, or if there’s a history of asthma or hay fever, often those diseases go hand in hand.

One other aspect as to why this is being picked up is also due to technology. There’s been an improvement in terms of high-definition endoscopy and being able to recognise the endoscopic features of EoE, and also improvements in terms of diagnosing, in terms of pathology as well. But, ultimately, the reason why there’s rising prevalence is not really completely understood.

Okay, so, let’s talk a little bit more about how this might come about. Are there other things that we should be looking for which are a little bit more subtle?

Yeah. So, commonly patients will report having dysphagia mainly to solids. There’ll also be food bolus impaction, like I talked about before. Often, patients can also have some heartburn, regurgitation, and vomiting, and there can be also pain on swallowing as well. These are often the common symptoms which are implicated with EoE.

And I guess we diagnose a lot of gastro-oesophageal reflux disease (GORD). What should we be looking for to differentiate EoE from GORD?

Ultimately, in terms of EoE, you need histopathological confirmation. So, if you were to have these symptoms, patients should have a gastroscopy and, following a gastroscopy, the gastroenterologist or the endoscopist should take some biopsies of the oesophagus, and ideally in 2 to 3 separate areas of the oesophagus. And the diagnosis of EoE is made on having an eosinophil count over 15 per high-power field. This is in comparison to reflux, where it’s still possible to have elevated eosinophils, but not greater than 15 eosinophils per high-power field. The symptoms of GORD are usually more like heartburn, regurgitation, chest pain, and acid taste in your mouth. But, these same symptoms can also occur in eosinophilic oesophagitis.

One thing that’s mentioned in the literature is that eosinophilic oesophagitis patients are often symptomatic at the time of eating, whereas in GORD, symptoms usually occur after eating or at night-time. And that could be something that can differentiate between GORD versus EoE.

Another thing to consider is being on a PPI [proton pump inhibitor]. PPI is one aspect of treatment for EoE. So, if your symptoms were to improve on a PPI, that doesn’t necessarily mean that you have reflux. It could still mean that there could be EoE as well.

So, overall, what it comes down to is, if you’ve got concerning symptoms, the next step is to get a gastroscopy, and the next step is to get a histopathological diagnosis to differentiate between EoE or GORD. And if there’s a history of asthma or hay fever for example, you’d start to think more along the lines that this is likely to be EoE, rather than GORD. But regardless, as mentioned, biopsies are needed for confirmation.

Okay, and what about with some other eosinophilic diseases? For example, eosinophilic granulomatous with polyangiitis (the old Churg–Strauss syndrome). Sometimes that peripheral eosinophilia on the blood count can tell us a little bit about disease activity or help us with diagnosis. Is that at all helpful with this eosinophilic disease?

Yeah, so, interestingly in EoE it’s uncommon for eosinophils to be raised in serological investigations, but there are a whole host of other diseases, as you’re aware, that can cause raised eosinophils. For example, something quite rare is eosinophilic gastrointestinal disease. So, that’s infiltration of eosinophils in other parts of the gastrointestinal system. And in those circumstances, how we differentiate between eosinophilic gastrointestinal disease versus EoE is to take biopsies of the small bowel and the stomach as well. Because, if there was raised eosinophils in the small bowel as well as the oesophagus, that can change your picture as to whether this is truly EoE or not.

How clear-cut is EoE on biopsy? I mean, sometimes we know histopathology can be a little bit hard to interpret. Is this one of those diseases?

When it comes to EoE, it’s always good to have a pathologist that has an interest in gastrointestinal diseases to definitively confirm the diagnosis of EoE, but it’s not always possible.

So, thinking about the histopath, are there classical features that really help to seal that diagnosis of EoE?

The main histopathological feature, as mentioned, is the raised eosinophils. So, over 15 eosinophils per high-power field for the most part is usually diagnostic of EoE at the exclusion of other gastrointestinal diseases, which also cause raised eosinophils elsewhere. Some other peripheral features which are seen on biopsy include eosinophilic micro abscesses, which is indicative of active inflammation. There’s also basal cell hyperplasia as well, and spongiosis, which is also intercellular oedema, which can also be seen on EoE as well.

So, once we’ve got that typical picture on biopsy, once we’ve been able to make that diagnosis, how do we go about dealing with this? What’s the basic approach to treatment?

The way that you manage EoE is you have a frank discussion with your patient, and often these discussions are done by gastroenterologists, and there’s 2 ways that this can go. Ultimately, EoE is a non–IgE-mediated condition, and it’s due to specific food antigens. So, one approach is a dietary approach, which I’ll talk about in further detail shortly. From a pharmacological point of view, a PPI twice a day is usually what’s instituted as the first treatment. And if there’s improvement in symptoms, plus if there’s a histopathological response with PPIs, lifelong use of PPIs is often what’s needed. But recently, in the last 2 to 3 years, there’s been a new medication, which is essentially a swallowed topical corticosteroid, which is now first-line therapy as well.

So, if you’ve got raised eosinophils over 15 [per high-power field], you can get patients on this oral swallowed budesonide, which can result in a significant improvement in symptoms. And after induction of treatment, after 8 weeks of being on this treatment, patients are re-scoped to see if there’s a histological response, and if there’s a histological response, patients can continue on that treatment, to ensure that they go into remission.

So, those are the two commonly used medications currently available.

Coming back to a dietary approach, a dietary approach is also another valid way to see whether there’s improvement from an eosinophil point of view, and this is in association with a dietitian. How it works is trying to identify the specific antigen which is the cause for the EoE. And sometimes, that’s fairly difficult to identify, because it’d be hard for a patient to exactly know what the food antigen is which is causing their symptoms.

The two most common causes for EoE are dairy-based or animal milk protein-based products, or wheat. And then, the less common food antigens are eggs, soy, nuts and seafood. So, with association with a dietitian, there’s a few approaches that can be employed where foods are eliminated until it’s identified what the specific antigen is, and that’s identified through doing multiple scopes, after a period of 6 to 8 weeks after a specific food antigen is excluded. And then, once it’s identified as to what the specific food antigen is, then lifelong, that should be excluded from a patient’s diet to prevent there being a build-up of the eosinophils resulting in the complications of EoE.

Let’s talk a little bit through the pharmacological approaches. You mentioned budesonide, so just to be clear, this is the same active ingredient that we get in our asthma inhalers. Is that right?

Yeah, correct.

And so why can’t we just take bits out of our asthma inhalers, and make them up into something, and swallow that?

Funny you should say that. So, prior to this new medication being widely available through the PBS [Pharmaceutical Benefits Scheme], what we used to do was this thing called the budesonide slurry, and what we would do is get the patients to get the budesonide nebulising solution, and we’d ask the patients to mix it with a viscous mixture using Splenda, so using fake sugar and water, creating what we described as a slurry, ask patients to swallow that, and that would coat their oesophagus, and then result in the anti-inflammatory aspects of steroids.

The only issue with the budesonide slurry was there was obviously going to be differences in terms of how efficacious it is. There’d be differences in terms of concentration, exposure to the oesophagus, so it wasn’t really uniform. So, this new medication is a lot easier and simple for patients to use. It’s a pill that’s placed on the tip of the tongue, and then a patient leaves it in their mouth for about 20 to 30 minutes, and allows it to slowly dissolve, and that coats the oesophagus.

So, what about in terms of the risks from this? We’re certainly cautious about inhaled budesonide. Are we still worried about the same types of things, in terms of candidiasis?

Candidiasis is one of the main side effects when it comes to taking the swallowed topical corticosteroids, and that’s something that we educate the patient about. There’s no way to try and limit the risk of candidiasis, because you want maximal exposure from the steroid in order to coat the oesophagus. Literature talks about it occurring about 16% of the time with patients and, in these certain circumstances, treatment for the candidiasis is required, while also taking the topical corticosteroid as well.

So, who would we consider oral budesonide for over proton pump inhibitors?

What it comes down to is a discussion between you and your patient. Sometimes, patients prefer going straight to the swallowed topical corticosteroid, mainly because of its high efficacy overall compared to other management options.

Other patients, they prefer taking the PPI instead. Not all patients will respond and say they don’t respond, then the answer’s fairly simple: then, you go to the swallowed topical corticosteroid, and more often than not, most patients, not all patients, but most patients will get remission on the swallowed topical corticosteroid.

So, let’s move on to proton pump inhibitors. Now, it seems fairly logical as to how they might work in gastro-oesophageal reflux disease. They reduce acid secretions – it’s really easy to explain to patients. What about in EoE? How do PPIs work in EoE?

As you know, it’s not an acid reflux disorder, and it’s really interesting that PPIs seem to work in EoE. And the reason that PPIs likely work is that it potentially modulates the immune response and inhibits pro-inflammatory cytokines, so interleukin (IL)-6, IL-8, and tumour necrosis alpha as well. And it’s likely that these anti-inflammatory effects are mitigating eosinophilic inflammation.

So, actually, it’s not the pH effects specifically that may be resulting in reduced eosinophils, but at the same time, there could be an element where reflux itself is also contributing to the inflammatory cascade. So, essentially, what it comes down to is that no one really knows why PPIs seem to work in EoE, but it’s likely because PPIs modulate immune responses and inhibit pro-inflammatory cytokines.

Well, it sounds like a disease that’s very much still in evolution in an exciting way. So, where do you think that the advances are really going to come in EoE in the future?

There’s several promising avenues of future advancements. The first aspect with EoE is trying to understand the underlying pathophysiology, including the role of immune dysregulation, as well as genetic factors. This is a big component, because we don’t really understand why the prevalence of EoE and other atopic conditions are increasing amongst our patients and our community.

Another aspect in terms of future research is the development of novel diagnostic techniques. So, there’s a lot of research that’s been looked into specific biomarkers and also imaging modalities, especially in the diagnosis and monitoring of EoE. The third area would be advances in terms of targeted therapies, so that’s the new biological agents, which are specifically targeting key inflammatory pathways, which potentially could be implicated in EoE. The fourth aspect is trying to improve the patient experience in terms of diagnosis, management and ongoing monitoring, and improving general quality of life.

Well, it sounds like a really exciting time to be working in this space. I’m sure that there’ll be plenty more to say when we update this article in 10 years’ time and have you back on the podcast. Thank you so much for joining us today.

No, thank you, David. Really appreciate it, and appreciate your time.

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Varan Perananthan was a clinical pharmacology trainee participant on the Australian Prescriber Editorial Executive Committee between 2023 and ’24, and I am on the Drug Utilisation Sub Committee of the Pharmaceutical Benefits Advisory Committee. I’m David Liew, and once again, thanks so very much for joining us on the Australian Prescriber Podcast.