Jasmine Frisina
Welcome to this evening's webinar, from Diagnosis to Treatment managing coeliac disease and irritable bowel syndrome. My name is Jasmine, your RACGP representative for this evening. We are joined by our presenters, Dr Brandon Baraty and Dr Sulak Anandabaskaran. Our facilitator this evening is Dr Vani Arjunamani. Before we get started, I would like to make an acknowledgement of Country. We recognise the traditional custodians of the land and seas on which we live and work, and we pay our respects to elders past, present and emerging. I would also like to acknowledge any Torres Strait Islander and Aboriginal colleagues that have joined us online this evening. I would like to introduce you to our presenters for this evening. Dr Brandon Baraty is a University of Sydney medical graduate and a Sydney gastroenterologist who earned his FRACP in 2017 and completed a unique fellowship in advanced IBD and IBD Imaging in Canada. He is the Head of Discipline at Macquarie University Hospital where he is also a University Lecturer, Director of Endoscopy at Ryde Hospital and the current leading expert in New South Wales for intestinal ultrasound. Dr Sulak Anandabaskaran is a Sydney gastroenterologist who earned his FRACP in 2020 after completing his training at St Vincent's and Liverpool hospitals. He is currently completing his PhD at the University of New South Wales, where he is focusing on improving treatments for Perianal Crohn's disease. Dr Anandabaskaran consults at Sydney gastrointestinal specialists at Eastwood as well as Nepean Private Hospital. We are also joined by Vani who is our facilitator for this webinar. Dr Vani Arjunamani has been a full time clinician for over a decade. She enjoys evidence based chronic disease management and preventative health care in high risk populations. As an RACGP supervisor, she imparts a systematic approach to multi-morbidity to her registrars. She champions general practice to medical students from the University of Sydney. Her passion is to encourage chronic disease management and central to women's health. Welcome to all of our speakers and I will now hand over to Vani who will go through the learning objectives.
Dr Vani Arjunamani
Thank you Jasmine. Welcome everyone. Today we are going to discuss the use of coeliac gene tests. We will be discussing, monitoring and ensuring compliance of patients with coeliac disease. We will also discuss how a GP can help the gastroenterologist before referral, and discuss the collaborative management of our irritable bowel syndrome patients between the GP and the gastroenterologist. We are really looking forward to this talk, and so first I will hand it over to Dr Brandon Baraty to start off.
Dr Brandon Baraty
Good evening and thank you for inviting me to come and speak with you again. As gastroenterologist, even we tend to sometimes forget that managing coeliac disease can be a bit of an art not only to understand it, but also to be able to manage it properly. We are going to let you guys ask some questions by chat throughout and at the end as well of both presentations. We will just get everything started if that is okay with a first poll question for the night. Jasmine, would you mind putting up the poll? Excellent. We will give you guys a few seconds to answer. This is like our first year exams. I have made it really tricky by wording it that way, and I think I got a few of you. Interesting results are coming in. I am seeing them. We are at about 65 of you answering out of 100, so just give you a few more seconds because we do not want to spend too much time on these. Do you mind stopping the poll there, Jasmine? Thank you. So about 50% have said iron deficiency risk and 50% all of the above, and yeah, the all of the above was the trick one that always got us on our MDT questions, isn't it? The reality is actually only iron deficiency. There are lots of illnesses and syndromes and things that coeliac disease is actually linked with, but fortunately there is no real COVID risk infection risk increase, there is no MS increased risk and there is no Parkinson's disease increased risk by having coeliac disease. Let us go to the second poll please. Do gluten proteins cross into breast milk? This is great. Thank you for all participating. We have got almost all of you. Just give you a couple more seconds. We can end the poll there. About 40% said yes and 60% said no. The reality is, even though we do not understand what this means, it does cross into breast milk. The data regarding perinatal and breastfeeding time and when it is time to introduce gluten into the diet is actually unfortunately quite poor from the data and at this point from all the different literature out there, the one that seems to be consensus is introduction of gluten containing foods somewhere between four to six months of age, but at the same time as breastfeeding. That seems to may have some protection for those people who have susceptibility. Let us go to the next one if we can start the poll on that one as well. In patients with biopsy proven coeliac disease, if we do gene testing like HLA DQ2/DQ8, almost 100% will have those genes, but what about the person that has not had biopsy, has not had serology and they come and see you with just some symptoms and you are wondering if the first test to do is the gene testing. Let us say you have only done gene testing, no serology and no biopsies and forget family history. It is a naive diagnosis, and naive patient, what percentage do you think of those that you have tested for The genes will end up actually having the phenotype. It is harder. Everyone is taking a little bit longer to think about this one. Okay, that is pretty good. Let us stop that poll there, please. About 15% have said 90-100%, 50% have said 25% and 25% have said 2.5%, and only 7% have said 0.25%. Reality is, out of all those that you test for gene testing without doing any other tests or having any other reason to do them, only 2.5% will actually have the phenotype. This is different between different countries and if you look at different literature, it will be somewhere between 15% to 50%, and in Australia the stats. Thanks for participating. Hopefully that got you got warmed up. Enjoy your gluten full meals as you watch this talk now. Coeliac has been around actually for a very long time. The diagnosis of coeliac disease came much later, but the idea that there are symptoms causing things like the bloating, the pain and diarrhoea related to food has been around for a very, very long time. Even in World War II, a paediatrician noticed that when supplies were low for wheat containing products that in the pedes population symptoms were a lot better, and as bread supplies return, all of a sudden all these people were coming back with children of the same symptoms, and there was a linkage proposed between wheat containing products. It was not, of course, until the 1950s, before the actual link with gluten was made. It affects the world worldwide about 1%, Australia somewhere between 1% and 2%, and women are unfortunately just like most other autoimmune diseases, a little more at risk than men, and then there is always the question of oats. You guys, I am sure, get it all the time. Wheat is classic, right? It is got the gliadin in it and causes problem. We often put rye and barley in the same category because we know and these products actually have these proteins in them called prolamins that are either Secalin or hordein or gliadin, and these things actually cause a T-cell response that leads to the cascade of inflammation and the downstream issues that are linked with it. Oats are a little bit complex. They first of all, in a small population they actually have a protein in them that can cross-react with those same T-cells, but it is quite low, but unfortunately in Australia and all over the world, they are often manufactured or processed in areas where there are wheat containing foods as well. There is usually contamination. There are lots of options out there that do not have the same issue. Now why is this? We are not quite sure, but if you guys remember from back in the day the idea of ploidy or multi ploidy, wheat when it was first kind of starting to get cultivated had different types, ones where it had the husk that was really thick or husk that was really thin with really nice thick grains. Now as human beings, whenever we try to cultivate or to take the ones and collect the ones that had the thin husks, all the grains will fall out, and the ones that had really thick husks always had really thin or small grains. There was a lot of crossbreeding, and the wheat has actually gone from being a 4N or 2N kind of ploidy to being a 6M ploidy with multiple chromosomes that produce the protein. We are not sure if this has something to do with it or not, but that is one of the theories out there. Whatever it is, eventually what happens is you produce this protein and our body cannot really deal with it very well. It does not degrade it very well. It crosses through and actually causes an immune reaction. Part of this immune reaction involves not only the adaptive, but the humoral immunity, and with it, there is IL-15 production, which we will talk about later as well, but this leads down to a lot of T-Cells that are resistant to down escalation when the cascade has started, and so the cascade continues as long as the protein keeps coming in, as long as the gluten keeps coming in. This activity continues for a very long time, and it creates a system wide issue. It is not just a gut issue. It actually causes issues for the body. You get villous atrophy, you get malabsorption and you get the ongoing inflammation complications. Like everything else, as an IBD specialist, everything genes are just a small proportion of things, and it is obviously going to be a lot more complex than that. There is data growing in this field still to this date, but environment, the microbiome and maybe maternal and perinatal influences can be involved. We are not quite sure, but there is a chance that most things lead to the microbiome, which then eventually leads to disease activity. I started making lactobacillus salivarius yoghurt way back in like 2016 or something, because that is the first time I heard that a lactobacillus can possibly be linked with coeliac disease and prevention of coeliac phenotype, and unfortunately, even now it is been almost a decade later, we still do not have very good data, seems to be that some lactobacillus and Bifidobacterium can help protect and there are some bacteria that may be actually increasing the risk if you have the gene to get the phenotype. This is very unclear. Unfortunately, the data out there is still quite poor, so you will see that there are multiple correlations and associations, but generally it tends to be small numbers or there can be a lot of confounding in the data. The age at gluten induction, which we briefly mentioned is a huge one. They are really trying hard to figure this out, but so far it is quite conflicting data. Infections have been suggested. There have been some protective effects from various helminths. Unfortunately, this is still a growing area, but reality wise we just do not understand it well still to this day. The interesting part is about 50% of children, even though they have the gene, they have the serology, they have actual some disease symptoms with ongoing gluten in their diet, they will actually get completely normalised, and similarly, in about 20% of adults with coeliac disease who later on resume gluten, they seem to have no problems at all, and that does not quite make sense, not the pathology that we know. And what are we worried about? Well, the main thing we are always worried about is malignancies. Coeliac disease for a very long time since all of you were in med school and I was in med school, the main thing that worried us about was things like non-Hodgkin's lymphoma. There is indeed an increased risk of malignancy with coeliac disease. The non-Hodgkin's lymphoma again in literature is variable throughout the world, but it can be as high as ten times the risk of the general population. More recently, as gastroenterologists, we have relaxed a little bit because when we look at the data more, especially as gluten free diets and things are becoming more accessible, it is probably a lot lower. The hazard ratio somewhere around the 1.21 range. The reason for the lymphoma risk comes back to what we talked about with the IL-15. It causes lymphocyte clones to increase, and that is when you get errors and that is when you get answers. Now the cancer risk is there, but it is probably the least of the worries, in fact, some of my patients that are really good and compliant patients, if they are having a birthday party once a year that they just want to have a little bit at that point, I usually tell them, there is some risk, but if you are compliant the other 364 days of the year or whatever, then it is probably okay, but you can have eye problems. You get obviously some malabsorption from vitamins and that can cause eye problems. You can actually get immune related eye problems as well from having active coeliac disease. You can have neurological symptoms not only the anxiety and issues that you get from having a chronic illness, but also headaches, which they are suggesting could be linked to some of the malabsorption but also to the inflammatory cytokines that are being released, and there are some clues that maybe conditions like epilepsy can be. Endocrine, we most people know about thyroiditis problems, the link with type one diabetes, about 5% of type one diabetic patients have thyroid or have coeliac disease, but in these cases going on a gluten free diet some majority time does not show any improvement in those illnesses. There is even IPH and respiratory medicine with those usually with very severe coeliac disease, but you can actually get problems with lungs and this does improve when you get gluten avoidance. Liver, it is interesting for us we do not often see it, but in our cases of primary biliary cirrhosis, primary sclerosing cholangitis, some of us are making the suggestion that people go onto a gluten free diet, and sometimes we actually are seeing that the transaminases are actually decreasing and theoretically supposed to do that from literature as well. Reproductive is a big issue. People who have coeliac disease or people who do not know they have coeliac disease and have infertility are often tested for coeliac nowadays because we are becoming more aware, but yes, the inflammation from simply eating gluten products can even lead to spontaneous abortions and infertility. This is what often we see at our rooms when they come in. There is this intensely itchy rash that happens at these extensor portions, and that is from the IGA deposits, and that one is usually a pretty big giveaway that people have coeliacs, and that one resolves beautifully when they are on a gluten free diet. There are a minority of cases of people with coeliac disease who will have the ongoing rash despite a gluten free diet, and those ones need special medications. The new thing and the new problem we are having is there is a lot of gluten free products out there. It is a two-edged sword because yes, it is helping with their coeliac disease, but the types of food to make it palatable, they are adding a whole bunch of things to them. Often people are actually getting a lot of empty calories with the gluten free products or they are getting malabsorption. The rate of metabolic syndrome has increased dramatically when they look at the data all over the world. When you have more gluten free products and they have this choice. It is probably another one of those things that is got a lot of confounding because as you improve their coeliac disease, they are going to be absorbing nutrients a lot better, so maybe the weight gain that they are seeing is part of that, but I think looking at the ingredients on a lot of these products, there is usually either more sugars or more fats and things like that to make them palatable. There are also now dental problems as well. There is a lot of enamel loss with some of these. When you get a patient who has coeliac disease, please make sure to recommend that they see their dentist regularly as well. Active disease, loss of villi, you are not getting absorption of a lot of things B12, iron, folic acid, vitamin D, zinc and magnesium plus others, and then the strict diets kind of doing the same thing. The breads and cereals that are gluten free are really low in magnesium. They do not have the same fortification, so you are getting similarly some of those same symptoms despite them being on gluten free like the dry ice and things like that. Dietitians at this day and age are a must for people being put on strict gluten free diets. The confusing part and I do not want to take too much time on this because this will be a whole hour discussion on its own, but we can answer some questions about it at the end is that there are lots of conditions that cross over. There are mimics, right, so IBS and non-coeliac gluten sensitivity can cross over as well as people who have wheat allergies, a true wheat allergy where you do IgE testing and it is there. Non-coeliac gluten sensitivity is those patients who have normal serology, normal biopsies, normal gene tests and normal wheat IgE, but when they are have gluten or wheat products in their diet, they get specific symptoms. When they remove the gluten from their diet, those symptoms improve, and when they are rechallenged, which is our usual way of testing things, all those symptoms come back. The problem with this is that somewhere between almost half of like 20-45% of patients that have symptoms will self-report food allergies. I am sure you guys will know people that come in and say, look, dairy caused me problems and things like that and these people are really important for them to have a very systematic approach to their symptoms because simply sometimes people just have faecal loading. They have a fibre and water imbalance. The transit period for the bowel has slowed down. They eat products that bacteria love to produce gas with like dairy or gluten, and all of a sudden they are now dairy and gluten sensitive and they are avoiding it. Now they are getting various malabsorption again similarly. It is very important to be systematic about these people, and they can be quite challenging because you get a proportion of people that may actually have coeliacs on top of all this that their coeliacs is not giving symptoms, but all of a sudden they are avoiding eggplant and everything is better. They are having gluten and still having the malabsorption. If that happens and gets confusing, that is where we come in, but it is important for you guys to be aware that there is such a huge crossover in these things, and we do need to change our mentality a little bit in medicine in this regard, because usually we label an issue a disease and we usually have some sort of medication or therapy for it, but now we are getting a lot of these illnesses where we just essentially name symptoms are non-coeliac gluten sensitivity and things that we do not have an easy treatment for, and we have to be open to the idea that that this is a microbiome or an immune issue that we just have not identified properly. We only have about five minutes of time left, so there is obviously on previous RACGP lectures that I have seen and especially letters and things like that, the exact pathways for how to diagnose coeliac disease essentially for us as gastroenterologists we are a little bit different. We use gene testing as a tiebreaker, for example if serology is positive, but biopsies are negative, we tend to use gene testing, but for you guys, if you do have patients that cannot do a gluten challenge or will not be willing to go on gluten, there is no point in doing serology because it is going to be all negative, and in those cases, it may be worth it to start with that the opposite of what I said, which is to start with the gene testing, but if they can have gluten in their diet and have a biopsy or have gluten in there and have serology, that usually will be better, again, it comes down to our original training from med school. You really have to go with pre-test probabilities and decide, and that is what these charts are designed for. In the charts, they often in small writing have the discussion about a multidisciplinary team and a dietitian, but I think if you are having patients that have coeliac disease, please at least once, they need to go and see a dietician and get some advice hopefully more often than that as well. Follow up and compliance. Look, people either have good compliance or poor compliance and I think everyone can view it as that. You either have that patient that is really good at doing the gluten avoidance or not. In IBD, we get these clients that we think are not on steroids, but they are taking steroids all the time. It gets really complex and it can be the same with the coeliac patients. You are going to have a small proportion of those that are really poorly compliant who are well, who might even do a gastroscopy on and biopsies will be very mild march classification of disease, and then you can have people with really good compliance no matter what they do they get severe disease that goes all the way down to the ileum, and we need to put them on a strong immunomodulators and things like that, but the general rule is if you think they are having good compliance or you think they are having poor compliance, if there is no signs from their nutritional factors or peripheral signs, then serology is not a bad way to start. In places like Canada where I originally came from, Gastroscopy is at the time a lot improved now, but at that time we are a bit more hard to come by, they use serology, so if you use serology and you use it and you see an increasing serological marker, than possibly means that they are having more gluten in their diet or they have been less compliant with their dietary factors, what you need to do at that point is to re-educate and then please get a dietitian involved. It probably is a good time at that point. If you are worried that there is active disease to see a gastroenterologist again for reassessment. A lot of people with very minimal symptoms will have significant inflammation when we do the biopsies, and those are the people likely at risk of getting lymphomas because they are probably feeling great and continuing to have gluten in their diets, but again, it becomes one of those doctor situations. Please assess them with peripheral signs like rashes and things, look at their nutritional factors and then do some serology, and if there are any questions please refer back to us. What about the future? Well look, so far nothing has been very good. I am quite disappointed in a lot of things that you can actually find on eBay and things like that now as well, where they suggest that if you eat this tablet before you have gluten, that you are not going to absorb the gluten and it is not going to have any effect, and the science behind it, the logic behind it is interesting, and there are actual multiple trials going on with various ones that may be successful in the future, but for now they do not seem to be as successful as we think. There are various tolerance forming treatments that may be coming up that will be interesting, and I think realistically we need to actually understand the microbiome better and understand how the disease pathophysiology works before. I am going to just stop a minute early there and pass it on to my colleague who is going to talk to us about IBS.
Dr Sulak Anandabaskaran
Thanks, Brandon, and I just want to thank RACGP for giving me this opportunity. This is my first presentation under this CPD series, and I am here to talk about irritable bowel syndrome, and the title I have labelled as an irritable gut or an irritable mind and understanding the connection, which hopefully will give you some idea about how IBS works, and I am again going to start with a poll question, and essentially this is a clinical scenario, very similar to a patient that you may encounter in practice. You have a 28-year-old female who visits your practice with a two-year history of diarrhoea and bloating requiring intermittent laxatives. Her bowel symptoms open up to three times daily, but there is no history of nocturnal diarrhoea. She has noticed blood on wiping intermittently for the last year, however, no history of bloody diarrhoea. Her weight has been stable. She has a past history of depression previously treated with citalopram, which is now being tapered off and she is no longer on any regular medications and is a non-smoker. Her father had a recent colonoscopy at the age of 65 and was picked up to have colonic polyps. I guess the question is this is a patient that you are seeing in practice and as a GP, what do you think is the next best investigation for her? Vani, I cannot actually see how many people have voted unlike Brandon, so I am not really sure.
Dr Vani Arjunamani
We have got about 67% of people.
Dr Sulak Anandabaskaran
Maybe we will give it a little bit longer given it is a long scenario to read, so. Why do not we call it the adjustment and if you could just show me those results. Perfect. It is a split between a predominantly blood tests, including full blood count and CRP. Colonoscopy at about a fifth of you and faecal calprotectin a third of you. It is a reasonable split, and I think clearly abdominal ultrasound is very low in 1% and which I think is a very reasonable. I think that the difficulty of irritable bowel syndrome, which I will hopefully cover through, and I think in this context I completely agree that, the question was the next best investigation, I think in a young patient, you would expect you would obviously do blood tests, which I think is a very reasonable. I think the one that probably is going to tip us towards referral to a gastroenterologist or a colonoscopy is probably the role of calprotectin in someone who has had predominantly a diarrhoea history with intermittent constipation, and I will cover more of this as I speak along. If you were to go ahead with the calprotectin, it returns normal at 24. This is my next question. And then she comes to see you six weeks later and her symptoms remain persistent. Let us assume that you have also done blood tests, and that is unremarkable. What do you feel is the next best management option for her here? So dietitian referral, referral to a gastroenterologist, start on a fibre supplement, start on an antidepressant, reassure her that this is likely irritable bowel syndrome and the symptoms should resolve with time. I should just let you know there could be more than one answer here. I think when it is closer to 100, Jasmine, I am happy to close the poll and we can show the answers.
I suppose referral to a gastroenterologist is the majority, and it is a very reasonable option. I will cover more about management. There are a lot of different moving parts to management of irritable bowel syndrome. Starting off with a gastroenterologist referral is reasonable. At the same time, a dietitian referral is again very reasonable and I will talk more about that. When I was thinking, I thought all three of these options are very reasonable, and I think that covers predominantly majority of you with your answers there.
Irritable bowel syndrome. It is a chronic gastrointestinal disorder. It remains the most commonly diagnosed gastrointestinal condition because it does account for a large proportion of our referrals and probably a large proportion of gastrointestinal complaints with patients that come to see you in GP practice. The overall prevalence is probably estimated at 10-15% with the overall prevalence of IBS in females higher compared to males, and it is associated with other conditions such as fibromyalgia, chronic fatigue syndrome, gastroesophageal reflux disease, functional dyspepsia, non-cardiac chest pain and psychiatric disorders. I do not know if many of you have seen this, but this is a Netflix documentary that was actually, I think one of the top watched episodes for some time. It was Hack Your Health: The Secrets of Your Gut. Irritable bowel syndrome on the whole is gaining a lot of traction, whether it is on social media and a lot more understanding around it. We as specialists have changed how we manage it based on the understanding of its aetiology is evolving. It used to be predominantly doing a gastroscopy and colonoscopy, making sure it is not bowel cancer or inflammatory bowel condition and leaving at that to now understanding more about the aetiology and really tailored therapy, which I would cover around what we think is the predominant aetiology. It is complex with no real clue to objective assessment to diagnose one versus the other of these causes. There have been various proposed mechanisms, including food sensitivity, gut motility, visceral hypersensitivity, some evidence around microscopic intestinal inflammation, alteration in faecal microflora, post-infectious phenomenon after gastroenteritis. There is some evidence around genetics and psychosocial dysfunction is a very key cause here as well.
When we look at genetics, there has been some evidence that showed having a parent with IBS was a great independent predictor of IBS than having an affected twin. A study of about 5000 twins showed that the rate did not significantly differ between monozygotic twins and dizygotic twins, showing that the genetic association is not so strong. However, having a family history in a parent being possibly stronger, and the genotyping studies have shown that there could be a serotonin transporter gene that could be altered in some patients, which could affect intestinal peristalsis. Again, showing the serotonin pathway that seems to be a recurring theme when it comes to irritable bowel syndrome. When we look at post-infectious causes that we know that patients after they have gone through an acute gastroenteritis episode, there is about a sixfold risk of developing long-term irritable bowel syndrome symptoms and the theories behind that include malabsorption, whether there is an increase in lymphocytes in the gastrointestinal tract or antibiotic use during the acute illness.
Intestinal inflammation. There is some pathology around lymphocytes and increased lymphocytosis in patients in their colon and small intestine. Mast cells and with this allergic phenomenon and eosinophils have been shown in some work again in terminal ileum, jejunum and colon in IBS patients. Tumour necrosis factor which is really an inflammatory phenomenon which has been shown in some patients in high amounts by patients' peripheral blood cells. That is sort of the inflammatory pathway. In terms of gastrointestinal motility, there is no strong pattern around this specific type of motor activity that has emerged as a marker. We do see prolonged transit time in patients with constipation predominant IBS and an exaggerated response to cholecystokinin or meal ingestion that is what stimulates our gut after eating in patients with diarrhoea predominant IBS.
When we look at alteration in faecal microbiota, there have been animal studies that have shown that if you were to inject microbiome from an IBS like animals to germ-free animals, there is this increase in colonic hypersensitivity after transfer of those microbiota. The evidence around SIBO is overall conflicting. There might be some benefit in constipation predominant IBS, but very limited evidence. Visceral hypersensitivity that is an exaggerated response to a meal or a similar cause, we see patients predominantly complain of excess gas and bloating in this context. The picture there shows you that if you look on the left, we have a 56 mL gas. This is a study with CT that was done and then the same patient with 86 mL of gas, which is not a significant increase in gas volume. However, you can see visible distension confirmed on CT and related it to more diaphragmatic descent and breathing patterns. These all become important in some of the treatments around anxiety and stress and gut hypnotherapy, which I will talk more about.
I have left the key factors to last, which are the key ones we think of initially. Food sensitivity. Yes. When they looked at positive food skin prick testing in patients and when they challenge them with the same foods, it did not exacerbate symptoms. We do have a lot of patients sometimes turning up with skin prick testing and avoiding certain foods. It does not always translate to that. We know about you probably heard everything about low FODMAP diet so far. It works and I will talk more about that. It again goes into about these fermentable, oligo-, di-, monosaccharides and polyols, which tend to cause excess gas and hypersensitivity when they are they fermented in the gut. Gluten sensitivity. Brandon covered this. Again, there is an overlap, and we do have patients who avoid gluten in the absence of diagnosis of coeliac disease who find it beneficial. There is thinking that expression of the HLA-DQ2/8 with the absence of coeliac disease confirmed on biopsies or absence of villous atrophy, those patients still can benefit from gluten avoidance.
Psychological dysfunctions. Patients with IBS tend to exhibit anxiety, depression and somatisation. Again, it brings this role of serotonin. Overactivity in the brain we know leads to this corticotropin releasing factor and the signalling system. There are small studies which have shown that intravenous administration of the CRF increases abdominal pain and colonic motility, again, showing the mind-gut axis in play. We do diagnose it sometimes based on symptoms, but there is a formal diagnosis through the Rome IV criteria which is IBS is defined as recurrent abdominal pain on average at least one day per week in the last three months, and it needs to be associated with at least two of the following, including related to defaecation associated with a change in stool frequency or associated with a change in stool form, and the Bristol stool chart. We tend to look at patients with constipation predominant IBS more fitting into the type 1 and type 2, and patients with diarrhoea predominant IBS fitting into the type 6 and type 7. Some patients can have mixed bowel habits where they do not have a predominance towards one or the other, and sometimes it is unspecified.
Diagnosis. Like we talked about with the case, it is difficult what is the best first test to do. I think it is variable. On balance, routine blood tests, coeliac serology depending on how long the symptoms have been going on for stool microscopy are a reasonable starting point. The role of faecal calprotectin versus faecal occult blood testing depends on patient's age. In the younger patient, I tend to lean more towards calprotectin. In the older patient, when we look at over 40, we could lean more towards FOBT testing. However, faecal calprotectin is positive in the context of a bowel malignancy as well. Abdominal ultrasound, I will discuss a bit more. I think it has got some role if you think there is a biliary feature to the pain. CT scan, again, it really depends on the symptom. Gastroscopy and colonoscopy definitely have a role. Capsule endoscopy and MR enterography are probably not a good first-line test and is best left to the gastroenterologist to decide after the endoscopic investigations. I would say consider the full blood count, liver function, iron studies and coeliac serology if still on gluten-based diet. If they are gluten free, consider HLA DQ2/DQ8 testing. If diarrhoea or mixed IBS, faecal calprotectin is a good test as a first line and less than 50 is the cutoff, but also if they are less than 50 years of age, there is an MBS rebate on that for all of you. The role of endoscopy in terms of gastroscopy and colonoscopy, I tend to look more for the red flags of progressive abdominal pain, rectal bleeding, bloody diarrhoea. Nocturnal symptoms are always a worry. If they are waking up at night to open their bowels or with pain. Early satiety, weight loss, all the other usual relevant family history and obviously iron deficiency. Abdominopelvic ultrasound, if it is more typical of an irritable bowel syndrome picture related to issues with defecation or change in bowel frequency, looking for gallstones in the context is very low yield. However, if it is an isolated bloating in women, I think it is always important to think about abdominopelvic ultrasound to rule out ovarian pathology. There is a symptom severity score, and you can use this when they present if you think the diagnosis is a likely IBS to grade. This can this can be used then to assess progress with whichever treatment pathway we form.
In terms of management, education and reassurance is key. A lot of patients can be very anxious and worried about you know what the symptoms mean and it is important to establish a good therapeutic clinician/patient relationship. The management and progress monitoring can take quite a few months, if not years, of them seeing you frequently. Dietary modification. Food diary and dietician referral is very useful. If they have predominantly bloating and visceral hypersensitivity, avoidance of gas producing foods +/- lactose avoidance and a low FODMAP diet is very useful in this context. Gluten avoidance can be helpful like Brandon has already discussed. If they have a diarrhoea predominant IBS, then increasing the fibre in their diet and adding in fibre supplement, whether that is Metamucil, psyllium husk and/or probiotics. In terms of laxatives, if you are looking at a constipation predominant IBS, Movicol or Macrogol stool softener is very useful. I tend to avoid the stimulant laxatives with Coloxyl and senna or bisacodyl just because dependence tends to increase and as a result you are better off using stool softeners. Whether that is Movicol. Lactulose can help, however, can lead to sometimes bloating, especially in this patient population.
In terms of management with pharmacotherapy, SIBO treatment or small intestinal bacterial overgrowth treatment. We look at rifaximin has the most evidence around this but still limited. There is a dosage of 500 mg twice daily that has been generally suggested. However, you can go up to 1500 mg on a daily basis or 500 mg three times daily. Usually it is a two-week course of treatment over 14 days, but there are a proportion of patients that improve only to regress and they may need retreatment. In terms of IBS with diarrhoea predominance, mebeverine or antispasmodics can have some benefit. However, the long-term efficacy is not established. If I see eosinophilic inflammation or lymphocytic inflammation, that is an inflammatory process and any of the biopsies that we do as part of endoscopy or colonoscopy, there is some role for H2 blocker. That is your nizatidine and/or H1 blockers or antihistamines. If you see lymphocytic, it is more a steroid-based treatment can be helpful with budesonide. Constipation predominance, prucalopride has some benefit but it comes with its own side effects. You do need to monitor sometimes for QT prolongation and headaches can initially happen at the start of therapy. Faecal microbiota transplantation. There is only one good study around it so far. In Australia, it is expensive. There is some evidence around early symptomatic benefit at three months which was not sustained at 12 months.
Just a few important studies. In terms of management, a low FODMAP diet plus traditional dietary advice versus a low carbohydrate diet versus pharmacologic treatment was compared. You have got three different arms there. This was a single centre study, I believe, in Sweden. Essentially they saw improvement across all three groups at four weeks, a very short timeframe to improvement and no difference was noted across the IBS subtypes where there was constipation mixed or diarrhoea predominant in the responders. It is useful across the board. At four weeks, as you could see, about half to three-quarters of the patients responded with improvement in their IBS symptom severity score. At six months, there were still ongoing responders in the dietary groups. They did not follow the pharmacotherapy group at six months. The dietary group even at six months did show benefit in the responders.
In terms of management with pharmacotherapy, this was a study that was published just recently and it was looking at amitriptyline at low dose versus placebo. Essentially the participants were started on a dose of 10 mg knocked, dose titration over three weeks of up to 30 mg at nighttime and over 60% of patients had response compared to a placebo group response, which is actually, if you look at it, relatively high on 45%, but the difference in the improvement across amitriptyline was significant. However, 80% of patients were either diarrhoea predominant or mixed IBS. We do not know whether it has a role in constipation or unspecified IBS.
Finally, I just want to clarify about emerging therapies. Mirtazapine has some role, especially if patients have diarrhoea predominant along with nausea. Mirtazapine we think has some effect in relaxing the pylorus. It has some benefit in that context. Duloxetine especially have abdominal pain as a predominant symptoms, yet overall the evidence is still more for amitriptyline. I would tend to more towards that as a first line, pharmacotherapy, Gut hypnotherapy has some benefit. There is a small randomised controlled trial which showed benefit as much as low FODMAP diet, and you have got a lot of emerging app based therapies. I had to look the other day on Apple Store and there is a lot of different applications. We have a few Australian ones, including Nerva and the low FODMAP diet by Monash University, and both have been shown to be beneficial based on their evidence. It is not obviously randomised control and it is small scale. It is I think personalised. I guess I should just finish off by saying that I do tend to I think low FODMAP diet seems to be a major part of management in terms of the pharmacotherapy, I tend to say there is a second line when it comes to gut hypnotherapy or app based therapies, I think I tend to preference them if patients are showing associative features with psychological symptoms, including anxiety and stress, I think that is where those can be quite beneficial. I think IBS is a common presentation for both general practitioners and gastroenterologists, and there is importance of us not just working with the patient, but also working with each other. It is important that we rule out other pathologies, and to be aware of the red flags, obviously nocturnal symptoms, weight loss, rectal bleeding. In terms of investigations initially, I think ion studies, coeliac serology, basic bloods and then decisions around faecal calprotectin, especially if it is a diarrhoea predominant picture and then decision around gastroscopy or colonoscopy with referral to us, diagnosis using the Rome IV criteria is useful to make a formal diagnosis. The pathophysiology is multifactorial and based on what we feel is the belief is the more predominant aetiology, we can guide our treatment algorithm accordingly. With management, do not forget the basics. Fibre important, water, exercise and good toileting habits. I have got a picture there of things that patients can use to improve, and in terms of first line therapy, I think short term dietary modification, we have seen benefits in low FODMAP diet as soon as four weeks, patients do not need to restrict them to for long periods before they see the benefit and they can help guide and that usually with the plan with low FODMAP diet, it is obviously working with the dietician and the plan is to reintroduce some of the FODMAPs gradually at about the three month mark. Second lines, there may be a role for low dose amitriptyline. Yes, side effects need to be considered. It is sedating, and you do get some anticholinergic side effects, so slow titration and ongoing monitoring while you increase the dosage is very useful in that context.
Dr Vani Arjunamani
Thank you Dr Anandabaskaran and Dr Brandon Baraty for a lovely talk on coeliac and irritable bowel syndrome, and thank you Dr Baraty for answering a lot of the questions there. There were questions regarding, I think someone has written can children have irritable bowel disease? Maybe they are referring to IBD as well as coeliac and IBS, so how young can patients get diagnosed with coeliac or IBS or IBD? To both of you.
Dr Brandon Baraty
I will let Sulak answer the IBS question, but as far as IBD essentially can be within months of being born, unfortunately it can be very early, and they have significant failure to thrive. Coeliacs as well, I am not a paediatric gastroenterologist, so they will probably better at answering it, but from literature, and in our teaching, essentially anywhere as soon as gluten is being introduced in the diet with less breast milk, so somewhere between six and nine months can be as early as having coeliac disease diagnosed, and that is usually those stories of the dad saving the child by going on a potato and meat diet and things like that, but yeah, unfortunately all three of these and I think Sulak will be able to explain it to you except for in kids, we just have to remember that probably seeing a specialist is more important because there is a lot more conditions. Everything from juvenile polyposis syndromes to abdominal migraines and things that we do not see as often in adults can be on top of everything else. It is important to see a specialist in that case.
Dr Sulak Anandabaskaran
Inflammatory bowel disease can be diagnosed very early on, and we know that in fact the paediatric population the earlier the diagnosis the more aggressive the disease is, so it is important that in the paediatric population that we do separate the patients who may have IBD, and it might be difficult to diagnose in children when you do not have a clear cut history and when you are going through a parental history. Generally, paediatricians tend to avoid colonoscopy and gastroscopy in the paediatric population and I think they can usually, I cannot speak for who they would screen and who they would not screen, but generally they have got similar things like Brandon said, failure to thrive, weight loss and those are the sort of the key red flags and/or abnormalities or family history may guide them, whether they should be screened with a gastroscopy and colonoscopy or could be managed initially as irritable bowel syndrome and predominantly the children tend to present with constipation or diarrhoea.
Dr Brandon Baraty
The other thing is that we have not really discussed it much because it is not really a topic for tonight, but intestinal ultrasound is obviously a new paradigm change. In paediatrics, we are getting a lot more intestinal ultrasound which makes complete sense to be using it logically in them. As you can see inflammation or someone with IBS, you see no inflammation and you see like complete faecal loading despite the fact that they have had three bowel motions, so in paediatrics world, luckily it is changing in that way as well.
Dr Vani Arjunamani
Just for the coeliac serology, in a patient who is gluten sensitive, is avoiding gluten and is happy to do the gluten challenge, how long do they need to take the gluten before you can have a like an accurate coeliac serology?
Dr Brandon Baraty
Serology is quite variable because as you guys will remember immunology, each person can have a variable, that is why we have variable phenotypes of coeliac disease that can be months, so generally the minimum that they say is one month in literature of like active challenge, but for us as gastroenterologist before gastroscopy sometimes we can get away with it within two weeks because on biopsies we can see results. Ideally if you can do it for longer, just depends on how bad the symptoms are, it would be better, but really it is a hard one when they do not want to do it.
Dr Vani Arjunamani
I have got less than a minute. There is a question on what kind of exercise is good for gut pathologies and how do you do gut hypnotherapy?
Dr Brandon Baraty
Every exercise is good. You go right to hypnotherapy.
Dr Sulak Anandabaskaran
As simple as 30 minutes of walking is beneficial. Gut hypnotherapy all the evidence is very variable. There is like what the randomised controlled study I mentioned which showed benefit as good as diet showed six one-hour hypnosis sessions. What that means is difficult to tell because every psychologist practices differently, and I think it is just variable, which is why I did not want to go too much into the details.
Dr Vani Arjunamani
Thank you so much Dr Anandabaskaran and and Dr Baraty and I will hand it back to Jasmine.
Jasmine Frisina
Thanks, everyone. I would like to extend my thanks to Brandon, Sulak and Vani for presenting and also everybody who joined us online. We do hope you enjoyed the session, I know I did, and that you also enjoy the rest of your evening. On another note, a friendly reminder that this is a CPD activity. Please complete the survey that follows the webinar. Once the webinar ends, you will automatically be redirected to complete the survey. We will also include a link to the survey as well as a copy of the presentation slides in the following email that we will be sending through in the next few days. Whenever you choose to do the survey, you do only need to complete it once, and that brings us to the end of our session. Thank you and good night everyone.