Therapeutic Guidelines Gastrointestinal

There's now a huge list of disorders of gut–brain interaction, and they cover every segment of the gastrointestinal tract. So the best known one would be irritable bowel syndrome, but functional dyspepsia is another. And then there's various other things like functional chest pain, functional constipation and diarrhoea, functional heartburn, a large number of different syndromes.

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Hi, I'm Dr Justin Coleman, a GP in Brisbane, and yet my main job is in the Northern Territory where I'm Director of Education for the GP program. I therefore spend plenty of time on the road and in airports and have come to realise the importance of restrooms or, for Territorians who don't understand such euphemisms, dunnies. Never underestimate the advantages of ready access to suitable public toilets for our biology, psychology and sociology, because all three of those bio-psychosocial aspects are particularly crucial if you're suffering from a condition affecting either end of your gastrointestinal tract. With me today to talk all things from top to bottom is Professor Chris Rayner, a gastroenterologist at the University of Adelaide. Welcome Chris.

Thanks Justin. Nice to be here.

And Chris, you were on the expert group who extensively revised the new seventh edition of the Gastrointestinal Therapeutic Guidelines. In your travels, you must have had plenty of people who really appreciate access to public toilets.

I can think of a few people that I've had that conversation with, Justin, the people with chronic diarrhoea, particularly those who suffer from faecal urge incontinence. Then at the other end of the scale is the people that travel as part of their work and won't use public toilets and develop constipation as a result. So there's a couple of ends to that spectrum.

All right, well no need to delve anymore into us travellers and our bowel problems. Let's instead jump straight into the seventh edition of TG Gastrointestinal and see what's new. Now, something I've never diagnosed in my life thus far, but may in the future is eosinophilic oesophagitis, which I probably only heard about a few years into my medical career, but the guidelines have more and more information on this.

Eosinophilic oesophagitis is something that presents typically with dysphagia and often we get younger people presenting with recurrent food bolus obstruction. It was something that's been recognised for much longer in the paediatric group, but we're certainly seeing it in abundance in adults now. And in fact, there's no age of life where you can't be diagnosed with eosinophilic oesophagitis. And the fundamental thing is that this does seem to be a kind of food allergy. There are a number of foods that are more likely than others to promote this condition, but there's also substantial crossover with gastroesophageal reflux disease. So I think they're the key things to remember about this condition.

And importantly, when we are thinking of therapy in the guidelines, there's also a reasonable treatment for it, which always helps.

There is. Now, first-line therapy for eosinophilic oesophagitis is proton pump inhibitors. And I talked about the crossover with reflux disease, but there's also potentially some immune-mediating effects of PPIs in themselves, interestingly enough. But in fact, the second-line therapy that we always used to prescribe was topical corticosteroids. And having those in a formulation that was suitable for this purpose was difficult. We would get people to use inhaled corticosteroids, but to try and swallow them after they’d impacted in the back of the throat rather than breathe them in deeply. But the difference now is that on the PBS we have got access to a oral disintegrating budesonide tablet. It's an authority item. It does need to be prescribed in conjunction with a gastroenterologist, but I think this is going to see a great improvement in our ability to treat this condition.

Very good. I will certainly continue to keep a look out for it. We've got a few topics to get through, so we'll skip straight onto Helicobacter. Of course, as Australians we're proud of that particular discovery over in WA a few decades ago. The thing which gets me a little bit about Helicobacter is, if it's present, do we always treat it? And is the correlation with symptoms always there?

I think we need to look very carefully, Justin, at why we're testing for it and what we want to achieve by eradicating it. We need to remember that up to half the world's population is colonised by Helicobacter. So this is by no means an uncommon organism. There's even some evidence that there might be benefits from Helicobacter. Perhaps it's helped prevent obesity, it probably helps prevent acid reflux disease. So we always want to think why we're eradicating it if we choose to do so. We want to do it in peptic ulcer disease and we want to do it in people who have got risk factors for gastric cancer. Often that depends on their being in a high-risk ethnic group, particularly those from East Asia. Those who have had gastric lymphomas are another category of people for whom Helicobacter should be eradicated.

Then you get people who've got dyspepsia and have Helicobacter. Now, usually we would attempt to eradicate in that circumstance, but we need to do so remembering that in fact the number needed to treat to improve dyspepsia is really quite large. So certainly don't expect that it's highly likely that you will improve dyspeptic symptoms by eradicating Helicobacter. And if in fact people have reflux symptoms, they may actually get worse when you eradicate Helicobacter. It's something that's not clear cut and needs careful individualised consideration. And I think, Justin, the other challenge for us in the Australian environment is that we've got one available combination therapy for Helicobacter containing a PPI, clarithromycin and amoxicillin. If people are resistant to any of those drugs, then we need a second-line therapy. And these are in fact rather cumbersome to prescribe in Australia.

We'll move on now to antiemetics. One thing I noticed when looking at the way you've set out the lists of antiemetics in this new edition of TG is that there really are different pathways in the body that cause nausea and possibly vomiting even separately to those pathways. And of course the different drugs treat different pathways. So how does that tie together in terms of which drug we use first and second line for this?

I think it tells us about the diverse causes of nausea. It also tells us why there's no one antiemetic that is guaranteed to fix everything. Like many mechanisms in the human body, there's multiple pathways involved. And addressing just one of them doesn't always solve the problem. But I think it's useful to be aware of which class different antiemetics are in and therefore, if one hasn't worked, maybe swapping to a different class is a good strategy.

In the new edition of Therapeutic Guidelines, as you've said, we've laid out the antiemetics by class. So we've got 5HT₃ receptor antagonists of which ondansetron is probably the best known. We've also got the dopamine antagonists, which are also familiar to people, metoclopramide being one of the most commonly used and prochlorperazine. But we should also consider in-hospital use of droperidol, one of the favourites of anaesthetists in the postoperative setting. Antihistamines can have antiemetic properties and people would be familiar with using promethazine for that purpose. And then there's a number of other pathways which have more specialised indication. For example, neurokinin pathways where the only available agent there at the moment is reserved for post-chemotherapy emesis.

I'm always pleased to see when promethazine still makes the list. It's something I think my mother gave me when I was a kid and there probably wasn't much evidence for it back then, but it looks like the wisdom stood the test of time.

The one little gem that I picked up from the discussions, Justin, was that there's a little bit of evidence for nasal inhalation of isopropyl alcohol for mild nausea. The mechanism of action is not entirely clear, but it does seem to be effective for reverting mild nausea.

Talking of age-old remedies, I'm sure you used to pour something onto a rag. Is there anything any of us would keep in our back cupboards? Any particular alcohol which might work better than others do you think?

I'm not sure whether sniffing the ethanol gel works as well as isopropyl alcohol. I don't know about the evidence for that.

I was thinking of something rather more expensive and tasty.

[Laughing]

Now, functional gastrointestinal disorders have also received quite an update and certainly in my drug and alcohol work I used to do in Geelong, I became very familiar with cannabinoid hyperemesis syndrome. But I guess in gastroenterology you would see a lot of these because certainly these are the sorts of things where there's nausea without a particularly evident reason or even if the original reason is evident, it's quite difficult to treat and it goes on for weeks and then months. And they're certainly the sort of people I'd be referring off to you.

There's now a huge list of functional GI disorders now called disorders of gut–brain interaction, and they cover every segment of the gastrointestinal tract. And they're complexes of symptom-based diagnoses and they involve syndromes with some chronicity, so arbitrarily six months or more in duration.

And just examples of those?

Best known one would be irritable bowel syndrome, but functional dyspepsia is another. And then there's various other things like functional chest pain, functional constipation and diarrhoea, functional heartburn, a large number of different syndromes.

Okay. The antidepressant drugs feature here, and I'm wondering whether that is in their role as an antidepressant, or is it something entirely separate?

It's certainly true that people with anxiety and depression are more prone to presenting to doctors with functional gastrointestinal disorders. However, when we look to use these classes of drugs as what we might call neuromodulators, we are really using them at a different end of the dose spectrum from what you would use if treating depression. So to give an indication, I would often start someone on only 5 or 10 mg of amitriptyline at night, whereas for treating major depression, they might be on 75, 100, 150 mg of amitriptyline. So I always emphasise that to patients that I see that we're using it for an entirely different purpose. We're using it as a symptom-modifying agent. And the positive thing about that is we can hopefully have a lower side-effect profile.

Looking at coeliac disease now, you mentioned earlier the rise of the inflammatory sort of disorders and things. Coeliac certainly has been on the rise in our modern society.

Maybe one in 70 people in Australia have coeliac disease. The majority of those won't have been diagnosed. Often people think of it as a disorder that will present with weight loss, diarrhoea, but in fact, that's the minority of the people that we diagnose in adulthood at least. One of the most common methods of diagnosis is to see people with an otherwise unexplained iron deficiency and the duodenal biopsy gives the diagnosis away in that setting. Increasingly, we see people with early-onset osteopenia and osteoporosis as well where this ends up being the diagnosis.

The tests will be familiar to most GPs. Although these days, what's the role of genetic testing? I think it's more as a ‘rule out’ than a ‘rule in’. Is that right?

Yeah, that's absolutely right, Justin. So the genetic test is not a test that will tell you whether someone's got coeliac disease. In fact, if you've got HLA-DQ2 or DQ8, you're in common with about 40 or 50% of the population. And it means you could get coeliac disease, but it's not helpful diagnostically. So really, the only value for us in that test is if you get a negative result in someone who you think might have coeliac disease, it tells you almost certainly that they don't have that disorder.

Right. Okay. So we do fall back on the coeliac antibodies, I guess with the caveat of if someone is IGA deficient and then followed up with a gastro biopsy.

Yeah. The other caveat is people who are already on a gluten-free diet where the antibodies will tend to go away. So it does present as a problem when people are put on a gluten-free diet before the diagnosis of coeliac disease has been firmly established. So I'd urge people probably to steer away from that course and seek to make the diagnosis. And the reason for that is that there's such a fundamental shift in lifestyle for someone to be truly gluten free that I think you really want to know whether you have coeliac disease or not before embarking on that course.

Life is generally easier for people with coeliac disease because of the awareness of gluten-free foods. But on the other side of the coin, many restaurants view it as a lifestyle choice rather than a medical condition and aren't necessarily as stringent in their gluten-free preparation as they might need to be for looking after people with coeliac disease.

Let's move on to diverticulitis and diverticulosis. Diverticulitis is sometimes manageable without antibiotics and there's an outline in the guideline as to what sort of things, if they're not present, you can safely manage without antibiotics.

In essence, it's people with uncomplicated diverticulitis who might be suitable for this conservative antibiotic-free approach, at least initially. So uncomplicated diverticulitis is diverticulitis where you haven't got free perforation or peritonitis, you haven't got overt sepsis or septic shock. And you haven't got an abscess larger than 5 cm in diameter on your CT scan. And if all of those criteria are filled and you're not immune-compromised, you haven't got right-sided as opposed to left-sided diverticulitis, then you could consider having an antibiotic-free approach with the caveat that, if things haven't improved after 72 hours, then that's considered an indication to in fact start antibiotics.

And do you find that everyone after their initial episode requires a colonoscopy?

So it's quite common, Justin, to be referred, people who've had their initial episode of diverticulitis with the query, do they need a colonoscopy? The feeling in people with complicated diverticulitis, in other words, those who've had positive blood cultures, perforation, large abscess, septic shock is, yes they should have one because evidence suggests that about 10% of these people will have a colorectal cancer. So they should have a colonoscopy about six to eight weeks after their acute diverticulitis has resolved.

In the group with uncomplicated diverticulitis, in fact, there really is a very low prevalence of colorectal cancer, only about half a percent, which probably doesn't differ much from the general population. And so if they haven't got any worrying imaging abnormalities to suggest a shouldering appearance or some inflammatory mass that's persisted, if they haven't got atypical symptoms and if they've recovered nicely from their episode, then they don't routinely need a colonoscopy. And I think we need to remember in the modern era that when people have had a CT scan almost universally with this presentation, we've got a bit more confidence than may have been the case in years gone by.

We might finish the podcast on iron deficiency and its treatment. What's new in terms of iron preparations for iron deficiency?

So I think the first thing is that it's important to replace iron adequately and many people will be able to do that orally. There's evidence now that, if people have trouble tolerating a daily oral supplement, then alternate daily may be pretty much just as good as daily supplements. And there are also some liquid formulations now, which some people seem to tolerate better than tablets. But there will be a group of people for whom they get intolerance of oral preparations or the oral preparations just don't seem to be doing the job of adequately restoring their iron stores. And increasingly our threshold for giving these people intravenous replacement is being lowered. So in gastroenterology practice, we're using a lot of intravenous iron now to, in a short, sharp way, fully restore people's iron stores. And then we've got a much better baseline to evaluate whether they're still dropping their iron stores very quickly or in fact whether they now seem to be iron replete and will stay that way for a long period of time.

And anything in particular to watch out for with the different preparations?

I always consent my patients about the risk of brown staining of the skin in the event of extravasation. It can be irreversible. So that's important, especially if you're dealing with a hand model. There's a very small risk of anaphylaxis. This is much lower than some of the older preparations like iron dextran, but there will be a small percentage of people who get flushing or dizziness or light-headedness, particularly in the first minutes of an iron infusion. And this is normally self-limiting. There will be a small proportion of people that will have some quite unusual symptoms of weakness. And it's now increasingly becoming apparent that some people will develop hypophosphataemia in response to intravenous iron infusions. And this may account for some of those odd symptoms. It appears that ferric carboxymaltose may be worse than some of the other preparations in terms of inducing hypophosphataemia. And one group of patients particularly at risk is those with renal impairment.

Excellent. Professor Chris Raynor, it has been a delight talking to you and running very quickly through a large number of topics and giving us little handy snippets about each. Thanks for coming along today.

It's been a pleasure, Justin. Thank you.

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My guests’ views are their own and don’t represent Australian Prescriber, and my views are certainly all mine.