Dr. Adam Farmer - Gastrointestinal Symptoms in EDS

action I'd like to thank the ehlers-danlos Society for their kind invitation to to have me here today and it's wonderful to be here with you all ladies and gentlemen to share this conference so I've got some challenges this morning it's reasonably early it was Friday night in Vegas last night I'm sure you had all the wonderful time at the ball many of you have to check out of your rooms this morning so I appreciate if some of you may drop off but I hope to keep you inspired and enthused so what I'm going to talk about today really is how we developed the link between EDS and GI symptoms and it was fascinating to see how many of you to Lara's question put your hands up and that's really been our experience in clinical practice I'm going to look at some of the implications of chronic abdominal pain and how to treat it and maybe not how to treat it look at some of the pain pathways that are involved in the Genesis and maintenance of that pain and look at some treatment approaches so I want to take you on a road of enlightenment and this was a patient my mentor and I professor Kasim disease at baths and the London saw nearly ten years ago now and we were the 16th set of gastroenterologist that this lady had been to see and she came into our into our clinic room in her wheelchair and she had multiple symptoms for many years and I never like to ask why people learn wheelchairs they're getting a little bit embarrassed about asking that question but Kass even said why in a wheelchair and she said well I have this connective tissue disorder called ehlers-danlos syndrome and this really was our first index patient that got us thinking could there be a link between these connective tissue disorders and the seeming myriad of GI symptoms so what do good doctors do they go back to the literature and we found this paper from Rodney Graham and Alan Hakeem which have been published in rheumatology about three years prior to us seeing that patient and what we found to our amazement that actually in patients with joint hypermobility syndrome is was the nomenclature at the time actually GI symptoms were very common so we started looking into this then in a little bit more detail and somewhat more systematically than we had done before so we looked at our cohort of patients that were coming to a tertiary referral neuro gastroenterology clinic in London and to our quite profound shock and amazement we found that nearly half of the patients coming to our clinic had evidence of joint hypermobility and this was something that we hadn't thought about and hadn't looked before but once we started looking we started finding it and moreover we found that those patients who had a cause or an explanation for their symptoms was much lower in those with high permeability than those without so we then began began to characterize the gastrointestinal symptoms in patients with EDS then in a larger cohort of patients and we looked at nearly 600 patients who came to our clinics and we asked them to complete a number of validated questionnaires looking at bowel symptoms some of their musculoskeletal symptoms autonomic symptoms and some of their anxiety and depression scores and we also classified them as to whether they had evidence of generalized joint hypermobility and JHS we also had to have some positive control groups so we had a proportion of those patients who didn't have hypermobility some that did and then we also had a positive controlled root group from the Rheumatology clinic as well and if we looked at the prevalence of the various symptoms across these groups we can see that particularly abdominal pain heartburn so reflux type symptoms and waterbrush were very common but also feeling full after they've had a meal so what we call postprandial fullness but when we compared and looked at a trend across these so we presumes that those that had mild generalized joint hypermobility were slightly less had less severe clinical phenotype than those with rheumatological II diagnosed joint hypermobility syndrome we can see across all of these symptoms that actually there's a trend across the spectrum from normal to severe disease when we look at some of these symptoms in somewhat more detail we can see that constipation diarrhea delayed gastric emptying or what we refer to as gastroparesis are really common symptoms in patients with joint hypermobility syndrome when we began to delve down a little bit further and start trying to put some diagnostic labels on these patients we could see that particularly the functional bowel disorders were very common and this is when we adjusted the data based on age and gender differences or we can see that those with joint hypermobility syndrome have approximately one and a half times higher risk of having one of these disorders in comparison to the general population but not surprisingly abdominal pain was also very common and disorders where patients have difficulty evacuating and opening their bowels was also common and I have to be honest with you this came with a great deal of skepticism in the gastro community this was something that was particularly so our clinic particular to our referral patterns and actually we were by and large shouted down by a number of groups that said this is just a you know a false association is not really real so we were delighted to see the experience from from the Mayo Clinic so they published a paper in 2015 where they described 20 years of experience in nearly 700 patients with EDS and very similar to our data over half of these patients had some form of GI manifestations and again the most common ones were abdominal pain nausea constipation heartburn and irritable bowel like symptoms so I hope you can begin now to see that there's a pattern here it's not just one Center in London this is seen in a number of centers now and there's data from France again which replicates there so I think the tide is really changing in terms of really educating the gastroenterology community is the link between these two disorders but what about the difference in terms of EDS another connective tissue disorders such as Marfan's and this was some fascinating data which some of you may have taken part in that was been published in abstract form in a digestive diseases week earlier this year so this was a group of nearly 2,000 patients with EDS and 600 patients with mal fans and they compared the symptoms and diagnosis across these two groups and you can see here that the EDS patients had much more IBS much more IBS with diarrhea or constipation but again heartburn and functional dyspepsia which is characterized by feeling full after eating and pain in the upper portion of the of the tummy as well as cyclic vomiting so actually this does seem to be something that's reasonably specific to EDS when you compare it with Marfan syndrome well if we just think about abdominal pain now and this is really very important because this is often very very difficult for your physician to treat it certainly we've shown data that increases in prevalence and severity with the increasing severity in the EDS phenotype there's an idea amongst doctors that actually we don't really have much to treat patients with it's really a symptom based diagnosis there's no useful test and way to make a firm diagnosis and even this these factors are even compounded by the fact that even the great and good across these disorders fundamentally disagree on the underlying cause of Simmons so you heard a lot yesterday about criteria based diagnosis in EDS I want to just talk you through now the criteria based diagnosis in irritable bowel syndrome or IBS so this was first proposed by Manning in the late 70s where IBS was considered to be linked with abdominal pains somehow related to change in bowel movements it was generally relieved by defecation a little bit of abdominal bloating incomplete evacuation diarrhea with mucus and so on and so forth and I think this diagnostic criteria has changed over time with the kruis score in the mid 80s and subsequently the systemization of this diagnosis through the Rome foundation now in its fourth iteration which was published last year and I think this has a number of salient messages for the diagnostic criterion EDS in that this diagnostic criteria is by no means perfect but what it has helped particularly the GI field do is compare apples with apples in research studies so actually it has improved the homogeneity the similarity of participants in research studies that really has abled us to translate results from clinical trials into improved patient outcomes but some of the helpful are things to come out of this I think if you think about the diagnosis of IBS so it's got to be there for a period of time these patients often have frequent consultations for non GI symptoms so that you know you think about the musculoskeletal symptoms particularly saying into EVs lots of medically unexplained symptoms and that stress often a quick aggravate symptoms there are some alarm features which we always think about particularly those in the older age group a short history of symptoms weight loss nocturnal symptoms and so on and so forth and that might point you to a diagnosis that's not IBS and may be more like a cancer or something and more sinister but if we now delve into the roams for diagnosis of IBS this is now defined as recurrent abdominal pain at least one day a week over the last three months which is associated in or related to defecation in some form associated with a change in frequency or form of stool and this criteria has to have been fulfilled for the last three out of six months so this diagnosis that was published last year has really fundamentally changed how we diagnose IBS and it's become a much more stringent criteria and the main change in that criteria is that patients have to have pain at least one day a week in the rome three criteria it was three days per month so it has raised the bar and I would argue that actually this is very similar to what we've seen now in the 2017 EDS classification does that mean that patients who do not meet that diagnostic criteria don't have bothersome symptoms no of course it doesn't but it really does help us as academic clinicians to begin to perform clinical trials and perform research which ultimately we hope ends up in patient benefit so we can begin to subtype irritable bowel syndrome broadly speaking into into four groups so those patients who have IBS with constipation those who have IBS with diarrhea they're fairly self-explanatory but there is a large group in the middle there they're alternate from one to the other what we call the IBS mixed there's also a smaller group call IBS U or IBS and classic unclassified which doesn't quite fit into one of those three aforementioned categories but if we look at the epidemiology of IBS across the world we can see that actually this is a prevalent disorder so if we're thinking in the u.s. it's about 15% a little bit less in the UK a little bit more in Europe but I would argue that it's around about the mid-teens in terms of the population prevalence in in adults and if you look at the age in which this diagnosis is is generally made it's a diagnosis of young adult life by and large and that's why I say if you're having a patient presenting with symptoms de novo over the age of 50 one might think that actually this you'd think of an alternative diagnosis before IBS but it actually occupies a huge burden of disease so certainly in primary care approximately 3% of all consultations are for IBS and you think 3% that's not very much but if you think of the hundreds of thousands of primary care consultations that happen across the US and Europe every day actually this translates into a huge burden of disease and moreover in secondary care approximately 40% of patients who come to secondary care with unexplained symptoms subsequently get labeled with the diagnosis of audience what predicts that healthcare seeking well certainly in my experience and the evidence would suggest that actually chronic abdominal chronic tummy pain actually is the greatest predictor for healthcare seeking and also what triggers that referral from primary care into secondary care while it's severity in chronicity of symptoms and as well the patient's beliefs what is the patient worried about they often feel a lack of reassurance and they're always worried is the underlined cancer in terms of the socio-economic impacts IBS probably reduces work productivity in terms of patients missing days from work or school and there's this emerging concept of presenteeism so patients actually do make it into work but when they're at work then they're not productive and the annual healthcare costs in the US per IBS patient are in the order of $5,000 so if you translate that's up 3% of primary care consultations $5,000 per patients 50% prevalence in the u.s. I hope I can convince you ladies and gentlemen that this actually costs the u.s. a huge amount of money per annum and indeed the latest estimates suggest that worldwide IBS costs in the order of 14 billion dollars for the global economy so this is a huge socio-economic burden but if you think about quality of life in these patients and if you just see here you can see in the Green Line healthy those with reflux disease in the purple and then in the gray those with diabetes and where do you think IV s comes in relation to these three other prevalence conditions one of them being health well not surprisingly it comes right down here so actually this has a huge negative impact on people's quality of life so where are we in explaining this disorder well broadly speaking there are four aspects to IBS and chronic abdominal pain the certainly aspects centrally so psychosocial abnormalities there's changes in motility I the speed of movements within the within the gut changes in sensation and sensitivity of the gut and changes in how those signals from the gut that go up to the brain are processed but ultimately the end result of this is pain and discomfort so I'd like to now introduce you to a concept known as the brain gut axis and this is a circuit of communication that goes from the gut to the brain and back again and this is intimately involved in the perception of the internal state so what's going on in the background in terms of your in terms of your gut and this could is considered to be a key component of how symptoms appear and are maintained in patients with IBS and not surprisingly there's a considerable interest from academics and indeed the pharmaceutical industry how we can use these targets to understand pathophysiological mechanisms and ultimately develop more targeted treatment interventions so if we just go down to a smaller level now down to the gut itself and the gut is an amazing organ and I would say that because I'm a gastroenterologist but it is truly amazing organ it has its own nervous system which we refer to as the enteric nervous system and this has a substantial sensory innovation that conveys information from the guts up to the brain but it also coordinates and integrates a bewildering array of reflexes and behavioral responses and actually there are more neurons in the enteric nervous system than there are in your spinal cord or indeed in the brain of a cat so the gut is a very nerve rich in so from the gut these nerves can broadly speaking they send to the brain in one of two ways either via the sympathetic nervous system or the parasympathetic nervous system and these two nervous systems have important important features so this final or the sympathetic nervous system really is involved in the perception of pain inhibition of digestive function so it slows the movements of the bowels down in contrast to the vagal system which actually is involved in physiological sensations so hunger when you feel full control of motility within the gut but also can influence behavior and food seeking and so on and so forth so actually the nerve communication to the brain is actually more than just pain it's also involved in many other physiological sensations as well so when it gets the spinal cord these nerves ascend in a number of pathways I won't bore you with the details but safe to say they're at least three main pathways in which these signals arrive in the brain and within the brain itself there are a number of important areas for the discrimination of pain so the sensory discriminatory aspects of pain is the sensation and quality of the pain the affective emotional shown in these areas is around how the pain makes you feel and finally the third dimension of pain is around cognitive model ative aspects of what that pain experience makes you learn so I know that if I put my hand in some boiling water it will hurt so I generally will avoid doing that and that's the cognitive model ative aspect of the pain but as I said this is a circuit of communication and what goes up must come down and again there are three broad pathways that can modulate the amount of information that's coming up from the brain so this is called descending inhibition but if we bring that all together now stress whether that's pain psychosocial stress infection activates a very complex response from the brain mediated in part by the automatic or the autonomic nervous system with its two branches that I mentioned before namely the sympathetic and the parasympathetic branches which then impact on the enteric nervous system but we also know this communication is influenced by personality factors can we also be influenced by by genes and more recently this idea that the bugs in the guts the microbiota can also change this communication of as well so what happens when this all goes wrong so any disruption at any level of that circuit with communication can can lead to symptoms which can change the move the speed of movements in the gut and lead to this concept called visceral hypersensitivity so this is the leading hypothesis or or proposal in explaining the development of symptoms of chronic abdominal pain and this can happen either in the periphery or in the central nervous system and has been described in EDS so what do I mean by visceral pain hypersensitivity and I apologize is probably a little bit early to show you these kind of slides but but do bear with me so the large bowel is composed broadly of four parts so on the right hand side you have the ascending colon which then becomes the transverse colon and then it comes down the left-hand side and what's termed the descending colon to the sigmoid and rectum and then back to the outside world and if you pay healthy volunteers and IBS patients enough to take part in these kind of studies you can actually put a balloon in their tail and and begin to inflate the balloon then you ask patients and healthy controls then when they report pain and this was perhaps the Sentinels seminal study from Bill whitehead in Chapel Hill where he showed that patients with IBS were much more sensitive to balloon distension in their tail than normal healthy controls and this is what we would term visceral hypersensitivity so this increased sensitivity of the gut in this case to mechanical distention is actually very common in IBS patients but enough of the science now how do we manage the patient with chronic tummy pain well I think it's a real challenge and often seen by many of my colleagues as a Cinderella speciality and what I mean by that is that patients often get told there's nothing wrong it's all in your heads get on with it get out of my clinic and actually that's no good for anyone least of all the patient and I think giving the eds patient a GI diagnosis is actually key because they're often been round the houses we spoke yesterday and I think it's a lovely term of this idea of a diagnostic Odyssey and actually this is what we have to move away from now we can only do that really through through more research and education but I think the key aspect to managing this abdominal pain well is actually the doctor-patient relationship and many of us drop this phrase out ad nauseam but I think it is absolutely key if you can explain to your patient many of these ideas particularly around the brain gut axis and visceral hypersensitivity then this actually really takes you from a starting point which is much better and may improve outcomes and I think you know we can't do this all all on our own and I'm very lucky to have a clinical psychologist who works with me as well as a specialist nurse who can help support patients through that that journey as well but also educating the patient as to the multi-faceted nature of this disorder so the problem might not just be in one particular place and we need to adopt a global and a holistic approach to improving treatment but also saying that you know what I have not got a magic one that's going to make all your pain and all your problems go away we can work together to make things better but ultimately this is about setting rational and achievable treatment goals so I think this is something that sadly many of you here today will be familiar with so you have a patient who asked chronic unexplained symptoms they become pretty disenfranchised because they've seen lots of doctors who can't find anything wrong the doctor gets frustrated so what do they do they do another set of investigations another MRI excluder Graham - you know testing another serum level of rhubarb for example you know these multiple investigations don't help anyone and hey oh what a surprise the outcomes two treatments are poor so what does the physician do well I've got nothing to offer you I'm going to refer you one to two doctor X and so the cycle continues and I would argue that actually good management of EDS is not about drugs and and anything like that it's really around these three specific aspects which I would regard as time so spending time with your patients and I appreciate particularly in the National Health Service in the UK or an increasing pressure to see our patients more quickly you've got to end Perth eyes with your patients you know I only took me half an hour to to get up and out this morning but I imagine for some of you here this morning it maybe took two or even three hours to get to get down here so I think we as clinicians have to empathize with our patients and validate that the patient's symptoms are real it's not all in their head of course it's not is some of it in the head yes of course it is because we're not just a set of joints a GI tract a cardiovascular system where one person and I think that's absolutely key but in terms of the pain itself taking a comprehensive history looking at some of the chronology of the pain weathers relationship to surgery infection or in traumatic life events and I think one thing that still fascinates me about this association between EDS and GI symptoms is that you know you're all born we're all born with our connective tissue yeah and there's some patients who taught along quite nicely with no symptoms at all or something happens that then actually has a major impact on the development of symptoms and what that something is I think remains to be remains to be seen a few targeted investigations can be useful to exclude specific diagnosis but actually fobbing the patient off we're saying we're going to do more tests we're going to do more tests it's not is not helpful in terms of in terms of drugs I do think they they have a role particularly low dose try cyclic antidepressants particularly amitriptyline is very good for pain management us and our some of the newer serotonergic nor adrenergic me up taking hitters such as duloxetine I think psychological treatments also definitely have a role and a benefit and also some of the newer therapies so drugs like pre goblin and gabapentin also have a role if we look at some of the literature in IBS so this is a technique called Metro analysis so investigators look at all the results that have ever been published on a particular subject callate them all together and see whether over a number of studies whether they work or not and broadly speaking if that little black diamond box is to your right then the treatment works and certainly there is a suggestion that try cyclic antidepressant can be very good for reducing global symptoms in IBS but also pain as well so actually these are very useful drugs the precise mechanism action is is as yet unknown I don't think these need to be high dose drugs but they should be used at night because they can make patients feel sleepy and high doses indeed may lead to worsening side effects a word about the SNRI so serotonin or adrenaline have been implicated in chronic pain mechanisms and newer agents such as duloxetine and venlafaxine are promising this small open label pilot study you can see here in the blue line this is average pain scores that over 12 weeks of treatment these pain scores go down some of the newer treatments gabapentin and pregabalin using a number of chronic pain conditions perhaps most notably fibromyalgia and certainly there's good basic information of in in terms of those balloon studies in the rectum to suggest actually gabapentin can increase pain thresholds and make people less bitterly hypersensitive and I know that the Mayo Clinic uses lots of Corti pin for pain management and this improves global symptoms but it's often limited by side effects there are a number of psychological treatments out there which I think again have a major role I think part of my problem in in the UK is accessing these treatments but certainly particularly with the IBS literature probably the best treatment that we have is actually got focused hypnotherapy but again it's limited by access and local expertise and certainly I think if you have a patient who's not improving after three to six months then this is something you should think about and some of the newer drugs that have been developed for IBS certainly worth a mention there's a drug called in Akutan which in the US I think its trade name is Lin's s and this it really simulates an infectious diarrhea to treat constipation you largely stays in the bowel so it's relatively side-effect free I think it's got a very interesting mechanisms of action that it produces or what we call a secretory diarrhea by getting the gut to shift salts and water out into the gut to make stools softer and easier to pass but it also through a number of complex mechanisms can reduce pain and firing in those in the enteric nervous system even in the guts this has been nicely shown in the two phase three studies both in the u.s. you can see here that Slimak low tide in the Purple Line versus placebo or dummy medication and the black line both cause the reduction in symptoms but Lineker tide was to been placebo over this six-month trial this was then repeated in another study again in the US which showed that lineker tide had a reduction in pain symptoms but what was interesting in this study after 12 weeks the patients who were on line' at low tide then got reran demised to either stay on the necklace idle gone to placebo and everyone who was on placebo then got the lacquer tied and as you can see here nicely those that were on the appetizer then got for SIBO the tummy pain started to come back as shown by the black line from weeks 12 to 16 I just wanted to talk a little bit now about one of my major bug bears in pain management particularly in in EDS this is around opioids and pain management so opioids strong painkillers things like oxen or moxa Contin morphine tramadol etc etc and this these have been the mainstay in the treatment of pain particularly those patients with acute severe pain yet whilst they're efficacious in moderate to severe pain of the cancer origin actually the amount of research showing that their improved quality of life and pain in the long term in non-cancer pain is absolutely limited or over actually opioids many of their side-effects limit their usefulness they often make patients feel very drowsy they have lots of side effects in the GI tract and actually over time can worsen pain and this is some data from from the US looking at what's now turned to the opioid epidemic and as you can see here in the blue line if you look at the deaths from heroin per 100,000 population in the US there's definitely an increase from 2009 up to 2014 but if you compare that to the red line ie the deaths from prescribed doctor prescribed opioids per hundred thousand that heroin line is solutely below that okay so my feeling is that actually lots of this is actually doctor or what we call iatrogenic in it in its nature and I think we need to think very carefully about starting these medications they're really easy to start very difficult to stop and actually if you think about these symptoms or the side effects rather of opioids within the GI tract particularly in patients with EDS who already have many of these symptoms you know these side effects are common affecting probably 90% of people who are on these medications include constipation nausea and bloating so if you already have these Simpson's anyway and you get put on one of these medications it's going to exacerbate and make these symptoms worse but there's no evidence to suggest that chronic opioids improve the quality of life pain scores or indeed your ability to carry out your activities of daily daily living so there's this idea now that abdominal pain can be caused by opioids and I would yeah you'd be quite right to say to me well you've got a painkiller how can that cause pain but a number of mechanisms now have been proposed to suggest why actually patients on long-term opioids their pain actually gets worse and the opioids themselves can interact with the pain system broadly speaking through a number of mechanisms to make it make it more sensitive there's this idea and this recently proposed diagnosis of narcotic bowel syndrome which is characterized by worsening chronic abdominal pain which is often treated with high dose narcotics again this is one of the problems that I think we're going to run into with many of our patients further down the line and this is incredibly difficult to treat and trying to detoxify patients off their narcotics and their opioids it's very very difficult indeed certainly my experience and that of others so one of the pressing questions so I'd like to give you the gastroenterologists view of what the pressing questions are so what will be the impact of the new Rome 4 criteria on GI Simpsons in combination with the new 2017 heads criteria and I think this remains a remains an open question my feeling is we've raised the bar in functional GI disorders and in IBS I think actually GI symptoms will become even more common in those heads and patients with heart mobility spectrum disorders I still don't think we fully understand the underlying cause of symptoms within the GI tract in patients with EDS and I think this is work that it's ongoing in in our group at the moment what are the ways of best managing patients all the evidence I presented to you today is derived from other conditions which may or may not be related to EDS in the underlying nature so what is the best way of individualizing patients for for-4 EDS treatments in terms of their GI symptoms and finally how do we educate physicians and gastroenterologist sirs so the association between EDS and GI symptoms that is clear a clear association and I think you know that that's incumbent on on on the likes of me and and and others to to try and spread the word but I I would have said if I'd given this lecture to a group of doctors 10 years ago a little bit three or four in the room but we recently had a symposium at the British society of gastroenterology where we had a room the size of this equally equally full so I think the word is spreading and people are beginning to take this on board so Leighton gentle I know I've gone a little bit over time but thank you for your patience this morning I hope I've convinced you that GI symptoms are common and abdominal pain is complex I think treatment options are evolving but doctor-patient relationship is key avoid opiates where we're possible and we need to develop EDS GI specific treatment algorithms thank you very much indeed so Adam you've actually finished with lots of time so you know what that means lots of questions the easiest thing to do if you don't mind is if everyone who has a question could come up to the front here and then we can in save me trying to look for hands and not knowing and what order people put them up so I know that there's some empty chairs if it's too much for people to stand but that would also help me running around the room thank you we shall begin what kind of structural changes do you see in the gut how often have you seen jejunal diverticulum and how do you treat bowel obstructions with this problem okay so should we sit down for an hour in brief so yes I have seen judy Muldaur particularly there often a cause of something called SIBO small intestinal bacterial overgrowth and SIBO that's often very resistant to treatment the biomechanics within the gut can vary considerably between between patients but we won there at severe end of the spectrum we see EDS associated with chronic intestinal pseudo obstruction we also see it with changes in small bowel and gastric and large bowel motility and forgive me your third points this problem and with difficulty is the honest answer I think lots of it's just supportive supportive care resting the guts I often use pre color pride it's called reservoir in the UK which actually stimulates the gut as a as a propulsive agent but doesn't work in all patients and can induce side effects if short-term narcotics are have to be used for pain how effective our narcotic antagonist drugs such as move antic okay so can I just explain what moment ik is to the rest of the audience so mo venting or naloxone all as its trade name is essentially the antidote to opiates and the theory behind the development of a lot of sakal is that it's attached to it to a big protein molecule so it doesn't cross into the central nervous system what we term the blood-brain barrier so do you still get the beneficial effects in terms of pain killing as the opiates but without the constipation so I use a lot of moment ik I think it's a useful drug it comes as a once daily once daily tablet I don't think we use it early enough in the treatment algorithm but hopefully they'll be paper in there in The Lancet in probably six weeks or so which will address some of those symptoms but I do use it and I think we should be using it much more how do you found the paper I'll send it to Laura we like I said yesterday we have lots of medical articles on our website so if you just look down at medical articles you can find that and others there yes I was curious if there's treatment options for when your esophagus struggles to push food down and there's no other medical explanation for it and then my second one was whether there's any connection between increased production of stones like gallbladder stones or kidney stones and yes so I'll deal with a second one first if I may so we haven't found any increased gall stones or the kidney stones in EDX patients when you control for age and gender so they're both so certainly gall stones are more common in females of later middle age but when you control for that we haven't seen a seen the difference esophagus is very difficult to treat so work from my colleague professor Daniel sip forum has shown in the EDS that actually the squeezes the pressure of the squeezes the esophagus makes is much less but we haven't yet got a specific drug that's going to improve the squeeze in the gullet and my usual advice to my patients is eat smaller meals chew your food well take plenty of water with the meal because you don't want to put the gullet under too much stress can you tell me please how EDS effects the following one and elongated : the gall bladder sphincter of Oddi and the mesenteric artery okay so this is this is something I get asked an awful lot so a patient comes to see me and had a colonoscopy but for something completely different and they come and say oh the the doctor told me I had a large floppy bow I don't know what that means in the normal length of the colon is considerably has considerable variability between individuals and I think whether patients with EDS have longer bowels no one no one knows that it hasn't been hasn't been described as yet sphincter of Oddi dysfunction there's a diagnosis that's made much more here in the US than it is in the in the okay generally speaking it's a diagnosis that people tend to pick up after they've had Bank gallbladders taken out for it for another cause again it's very difficult to treat opiate soft and make it sphincter of Oddi worse because they cause spasm of the the sphincter it's itself the recent data from Peter cotton in the u.s. suggests that making a cut in the sphincter doesn't help any more than a sham procedure so that's a study called the episode study so I you do have so it depends what you mean by mesenteric artery syndrome if you're talking about celiac axis de no sis and mesenteric angina some patients get pain after eating I don't see that more in hypermobile EDS but certainly I have seen it quite a few patients with median arcuate and pigment syndrome so this is when on one of the ligaments wraps around the mesentery I have seen a few cases of varies I'm just gonna interject with the question that we get asked a lot and I'm not sure where the research is on it what do we know about gi association with the other rarer types of EDS at this stage very little I think you're right that that is one of the one of the research questions but it's about resource resource management really in the sense that there's not many of us doing it and we've got to describe the common things first before we get to the to the nuances the abstract I've presented from the Harvard group juju Dinis group does suggest that GI symptoms a little bit more common in comparison to EDS one and two as they referred to it in that and that's article that's not been published yet but it's in abstracts for thank you could you please speak about the role of gluten in the diet okay excellent excellent question so so I'm gonna take talk a little bit about gluten specifically and then talk about the diet generally because I think it's a very important point so there is a paper from a few years ago from an Italian group suggesting that celiac disease which is an allergic response to gluten is more common in patients with EDS that data hasn't been replicated yet to the best of our knowledge and hasn't been our experience but many of our patients say that actually even though they don't have celiac disease we've excluded that actually get better if they avoid you know they feel better off a gluten free diet so my view on these things always is that if view it's not going to do you any harm and you get some benefit from it then go ahead with it and particularly this idea of a condition called non-celiac gluten sensitivity which is gaining traction in the in the literature other dietary interventions so there's a number of them out there again haven't been well studied in in EDS I can give you our experience from in London we find the low fodmap diet so fodmap is an acronym for fructose ala goemon ago mono disaccharides and polysaccharides fermentation produces gas gas stretches the gut that produces pain and discomfort and that diet seems to be particularly helpful for those patients with marcel dysfunction then a low histamine diet can be helpful but again these haven't been systematically systematically studied and I can give you my my personal experience but the hard evidence I think is just not yea got yet there and something we really need to look at and I just wanted to add because I know that professor Aziz is looking into this so I've spoken about this and Heidi's spoke dr. Collins spoke about it yesterday another area to look at and it does need more research and evidence is vitamin C high-dose I don't know if in your clinic you've had experience of that week as when I profoundly disagree about this right which is good which is good I don't think it helps at all he's a great advocate of high-dose vitamin C because of its antioxidant properties I think lots of it's how you phrase the question to the patients I would say this hasn't worked has it and he would say this is a did it work yeah of course it did so so it's how you phrase the question but again needs needs systematic systematic study do you have any information on visceral hypo sensitivity as opposed to hypersensitivity so in the study we published a few years ago with my colleague Mark Scott suggested that there are some patients with EDS whose tail ends are under sensitive to putting they're putting a balloon in again why that might be the case we don't know the majority were the hypersensitive end but again there's a was a spectrum but there were some patients who were whose sensitivity was less now is that a function of the connective tissue diagnosis is that a function of what drugs people were taking it at the time of that testing I think remains to be remains to be seen but you're absolutely correct there are a group of patients particularly when we think about the tail-end who are whose sensitivity is is less for sure I wanted to ask you when you prescribed opioids to patients are that was a portion of your discussion if you consider a couple key points with this specific population I'm seeing brought up the graph that showed the increase in overdose deaths from prescription narcotics however I wasn't sure if there was clarification that primarily a lot of those prescribe medications are abused or diverted not not taken as the patient is intended to be taking them also a lot of them are related to illicit ly manufactured fentanyl which is not the same as physician prescribed opioids additionally the long term Studies on opioid long-term efficacy are pretty limited to the general population and how do you take that information into consideration when considering EDS patients and in particular I'm pretty clear on using opioids in pain management I don't use them at all I think that there are much better ways of managing chronic chronic pain I'd agree with you entirely that much of that data is skewed by diversion not using opioids for the for the prescribed indication however I would counter that argument and say that particularly in the u.s. the development of oxycontin and oxen or and these kind of drugs has really probably fueled this and and the and part of the problem is that that we go back to the world who all good World Health Organization the pain ladder which you may have heard of which is essentially a step up approach to the management of pain this was developed in 1982 for the treatment of cancer pain nothing about non-cancer pain to the best of my knowledge it's never been validated in non-cancer pain but every physician uses it in that in that context please don't think I'm saying that opioids don't have a role at all I personally don't never prescribed them I think they should be used in the smallest dose possible for the shortest period of time and actually acute pain they can be very helpful indeed it's just in chronic pain the number of patients that I have looked after who forgive me for using this term but I'm going to use it anyway who become opioid cripples is remarkable and this is all doctor induced and that's just a you know a sad fact that doctors are trying to help but in fact we're making the patient more us over time I think in EDS I think this remains to be to be to be seen how best to manage particularly muscular scapel pain I can give you my experience in chronic abdominal pain in in need yes that we just don't don't use opioids at all yes could you comment that is there a higher incidence of intussusception in adults with EDS and any kind of experience with that follow-up studies of pediatric patients so the data suggests that probably isn't but I see a number of patients who have you know recurrent episodes of intussusception some of those have first presented in childhood and sometimes that's their first presenting feature actually of their of their EDS that's subsequently diagnosed so again it particularly I think our discussions yesterday were helpful this and this is what we've got to get to doctors if you've got a young person you know a lady of 16 or 17 who has an intussusception or who has an unexplained rectal prolapse you know why would someone that age have those kind of that kind of presentation so it's we have to take the next step and think well why has that has that happened and that's more of the key one of the key educational aspects that I alluded to so for ets patients that have had their gallbladder out what after-effects have you seen in what recommendations would you give to them so my feeling is that make sure the indication is is really absolutely spot-on to have the ball banner taken out a few stones floating around in a gallbladder generally speaking are going to do anyone any harm and impacted stone or infection in the gallbladder cholecystitis is a different kind of a fish but make sure that you know you're not getting a surgeon whipping the gallbladder out for a little bit of tummy pain that may or may not be be related and sphincter body doesn't seem to be more common in EDS patients I think it's probably over diagnosed poorly managed again people often use opioids which often makes the problem worse well they do see quite a lot of and this isn't just to patients with EDS is patients developing diarrhea after their gallbladders taken out and they all get told that they've got IBS with diarrhea go away live with it where in fact they actually have a condition called bile acid malabsorption bile acid malabsorption or bam is it's shortened name which actually the treatment of that is very different to the treatment of our best and we've published a meta-analysis a couple of years ago now showing that if you have a hundred patients with who have a diagnosis of IBS with diarrhea probably thirty five of them will have bile acid malabsorption why is that important symptoms are very similar it's just the management is very different for those two conditions so I do see a blot of bile acid malabsorption yes I have a four six and ten year old grand children who have EDS the four year old doesn't even like to eat anymore because he says that he'll get a belly ache from eating anything that can be done for them except me relax so again it's difficult for me to comment directly on the pediatric population for the don't look after these patients but certainly I would suggest that they need to look into why that's happening rather than just throwing medications that's it and particularly you know some targeted motility studies can be can be quite and helpful one of the sad things that then I see an awful lot in my patients who are transitioning from pediatric care into adult care is that you see a lot of patients who are diagnosed with an eating disorder who in fact a hyper boat mile and have delayed gastric empty or gastroparesis so that their food car exit from the stomach because the stomach doesn't contract it's it's there that makes them feel sick and then there and then they're sick and that those kind of patients I feel incredibly sorry for because they get labeled with a completely different diagnosis which then often you know if you say something enough patients take it take it on board and that those group of patients can be very difficult to treat but I would think about maybe other stimulants beyond just just Mike relax and Senna dulcolax the newer drugs are licensed and children yet so thinking of bucola pride the latter time really the frost own and I'm sure they could be used off off-label but there are things beyond just throwing more laxatives at patients Matt but I think the key question is to ask mold why is this why is this the case hello I was wondering if there was any studies or anything being done with GMO products and the fact that we're eating pesticides I mean foods they're labeled as pesticides that corn and what it's doing to our gut flora and the fact that they're then there these companies are producing new bacterias and labeling them you know in copyrighting them and now that's changing our gut flora this is Michael disease started with my gut by this so again that's a really interesting that's a really interesting question that I get in to the best of my knowledge there isn't any research looking at lancelin but but as I said him in my main lecture that you know the question is you have your connective tissue from birth not all patients have symptoms from from day one and actually what's the trigger to turn someone from being functionally okay to having you know desperate symptoms and I think you know that's one of the key outstanding questions and in my mind when I think the idea of you know GM foods is a potentially is as a hypothesis to to cause that trigger is certainly an interesting one we have less GM foods in the UK if any and we still see the same prevalence of GI symptoms need yes so you see here that in diet cannabis and diet has been what's helped me I've been able to really believe and I can get rid of IBS so cannabis can be can be helpful in in chronic pain management we have the nasal cannabis spray obviously cannabis is remains a Class C drug in the UK so it's against the law you're not allowed to use it unless it's for medical purposes but one of the problems I find with cannabis use in EDS patients is they often get this syndrome called cannabinoid induced hyperemesis so they get lots of morning vomiting which is relieved by a hot shower which often then gets erode the label the cyclic vomiting but actually it's due to cannabis use but that's not everyone do you and your experience have you ever seen an association between malrotation congenital mallet a ssin and EDS diagnosis later and if so do you have any suggestions post resection of how to differentiate between the pain of just functional bowel pain and a serious complication over so we've got one patient who came to us with their EDS diagnosis but who had had malrotation of the gut so just to explain what malrotation of the gut is essentially where the gut is transpose the the other way around so as the baby's developing in the womb the gut doesn't quite twist properly to form its final resting place it can be very difficult to to treat when you've had a surgical reception and differentiating sort of standard pain from obstructive pain can be very difficult in patients but the problem is the the things people jump to as they come through the door of the ER is to do another CT scan and this makes me really anxious in in particularly my younger patients who come to me in their mid-twenties and they've had 25 CT scans already you know this dose of radiation mounts up over time I think was something we need to be really careful about by and large in our patients actually watching and waiting symptoms usually subside on their own and then if they don't then that that shifts the balance of risk and benefit towards cross-sectional cross-sectional imaging but I think in terms of a technological development you know the next major kid on the block is going to be MRI motility studies some great work going on in Robins fellows group in not need others using this technique rather than esophageal manometry and gastric emptying studies and all the rest I think this is going to transform our field from a measurement pointedly MRI met an MRI motility so it's using MRI to measure motility and function within within the gut I haven't seen any research from the US so it's still in its infancy and it's not so not a clinical technique but I think in in five years time it will be the go-to motility technique

Channel: The Ehlers-Danlos Society

Views: 21,321

Rating: 4.7962465 out of 5

Keywords: iMovie, Ehlers, Danlos, Ehlers-Danlos, hypermobility, gastrointestinal, connective tissue

Id: _PYok9zjEuc

Length: 61min 32sec (3692 seconds)

Published: Wed Oct 18 2017