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.
[Music] Welcome to the Australian Prescriber Podcast. An
independent, no-nonsense podcast for busy health professionals.
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.
[Music]
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.