Morristown Hospital Pediatric Grand Rounds Vascular Ehlers-Danlos Syndrome

good morning everybody today it is my absolute pleasure to introduce not one but three grand rounds speakers today um the first is someone who i know quite well and for quite a long time shane dr shane morris uh dr jay morris is a pediatric cardiologist who wears many hats um it is actually pretty unusual in our field for somebody to be an expert in so many amazing things um her hats include cardiac imaging fetal cardiology cardiac mri she is an aerotopic expert and an nih-funded clinical researcher um shane did her training at stanford university and ut southwestern for medical school she also has a master's in public health from harvard medical school um shane and i actually first met in 2005 when she was my chief resident at boston children's um where she was much beloved she completed her cardiology fellowship at texas children's hospital as well as an advanced imaging fellowship back at boston children's shane is currently at texas children's where she's been on faculty for many years she is the director of both fetal cardiology and of cardiovascular genetics and so i'm very excited to have her here today i'm also very excited this is me uh mrs green is the mother of a beloved patient of ours here in pediatric cardiology isabella and she's going to apparent perspective uh as a parent and advocate for her um my pleasure any right uh the director of the vets movement which is part of the marfan foundation which she joined together with them in 2019 thank you so much we're very much looking forward to your talks you anjali for the nice introduction and heidi's going to start our session today thank you everybody for having me today to share with you my daughter's story and our family's experience that led us to the diagnosis of vascular ehlers-danlos i'm just going to give a little background on isabella so isabella's a twin she was born at morristown hospital she had premature rupture of the membranes at 33 weeks and was delivered at 34 weeks spending roughly three weeks in the nicu for feeding and growing um at the time of her birth i recall thinking her eyes were so big and her skin is very see-through you could see her all her veins and she looked like almost like a see-through fish so within a few weeks from bringing them home from the hosp from the nicu she developed an umbilical hernia um and we started noticing like there were light streaks of fresh blood in her stool there were these unexplained um dime-sized bruises that i would find along her thighs and legs she slept with her eyes half open and she vomited all the time uh multiple times a day whenever um whatever the suggested amount of food was for her age she would consume half of that and then eventually throw it up so um i would bring these concerns to the pediatrician and uh the response was always it's normal she's a preemie as she gets older her skin will thicken up she's growing while at minimum rates she's still growing it wasn't until um a year our one-year visit that she completely fell off the growth curve even her uh um smaller like a lower than normal growth curve so we were referred to st joseph's hospital in patterson along with gi at morristown the gi um they did an endoscopy and i remember the doctor coming out and telling us that wherever the endoscope touched she would bleed so that was strange but now now it makes sense but i remember thinking well that's strange um she did feeding therapy at st joseph's and even with therapy um and she had she started improving with eating there is still that concern that she's getting older but i still see her veins and i see them on her chest it looks like a road map i see them on her back on her neck i would strap her in her car seat and i would notice petiki eye along her neck small like bruises um at one point she just fell and slightly bumped her head on the coffee table so that was an emergency room visit and the doctor said that he had to put extra stitches to kind of hold it together um so deep down i felt like this something is just not right i felt that i know it's hard having twins and i know it's overwhelming but something just didn't feel quite right so i brought it up to our pediatrician again and my husband and i were told she's perfectly healthy and all these troubles she'll eventually grow out of them when she's seven and eight and since bleeding was a concern of ours we would refer to hematology to do a um a von wilder brand panel so the von wilder band panel came back normal uh the doctor at that time just leaned over and said um your daughter's perfectly fine and enjoy her so we did and we um we have been and fast forward through all that it's now she now turned eight and um all the concerns are still there and i'm thinking in my head you know it all the feeding has gotten better her vomiting has gotten better but um it's toned down but everything else is still there so i did some research um don't cringe but i did some research on google and i um vets came up and it checked he checked off all those boxes i mean sleeping with her eyes open globeless ears um the visible veins and even just looking at the images it mat it it matched so perfectly and it was it's just reading how rare it was so i thought well what what are the chances so i went back to the pediatrician and i said look i i may be crazy maybe all this is just a series of coincidences and this is who she is but maybe there really is something more and there's something more going on with her that can explain can explain everything that's happening so uh we did the connective tissue panel and isabella came back positive for vascular ehlers-danlos um she also has the splice type mutation which we found out is the most severe form of veds with the lowest survival it was at that time that we also learned about aortic dissections spontaneous ruptures spontaneous bowel ruptures and kind of how life-threatening her condition is um we quickly moved into action with the help of the vets movement and other families from across the country um helped us put together isabella's care team so she is now followed by dr hal dietz at johns hopkins and dr talaya at morristown and it was shortly after her diagnosis that we experienced our first kind of um event where she just fell and uh ended up breaking her nose so not knowing kind of what to do now that we know the diagnosis i called dr dietz and he said take her straight to the emergency room so we went to morristown's emergency room i had my vet's passport and a letter from johns hopkins explaining her condition and that she needs to be seen right away dr dietz's concern was that not so much her nose but um that there might be a possible brain bleed um and we should kind of get her get a ct right away to get ahead of the game so um we went to the hospital this was may of last year and i had my documents in hand and we waited for five hours in the emergency room for her to get the cat scan and as a parent i was trying to explain to the medical staff like no she's trauma there might be something else going on and i i i know now what i know the risks that are associated is it just uh couldn't can it be a brain bleed could it be another rupture somewhere else and all these scenarios are going on in my head and i remember thinking at that time was i had spoken to several families within the vets community that have lost somebody that has have lost the child just waiting in the emergency room and i know i can't i can't control i like we can have the best medical team and there is no doubt in my heart or mind that we don't have that right now and i can't control a rupture or something spontaneous from happening to isabella but what is so hard is that knowing the spontaneity of vets and i may lose her at some point but i don't want to be left with is there is was there something more that i could have done uh that grief of wondering um had she gotten a quicker response from the emergency team would that have changed her outcome um and like i said i know there's without any proven um treatment those are those are concerns you know knowledge is power but it's also crippling in the event that um if you're just sitting there waiting for the team to to know and just knowing that it's so rare um also um [Music] when you have everything in hand it just it is scary so that is kind of our story with the vascular eds so i am hoping today my goal is not just um knowing kind of the missed signs that sometimes it is if you look at them in isolation they might be normal but if you put them together maybe there is something else but also more importantly is just kind of giving hope that if i do come into the emergency room that she will get the care that she needs so she has a better chance at um survival and that is that is my hope for today so thank you everybody for giving me this opportunity thank you heidi so much for sharing your story it's really powerful and i think it's it's really important because it's such a rare condition and i i think most people don't know a lot about vascular eds so we're going to now switch and i'm going to talk a little bit about vascularity yes and katie's going to talk about the end about her personal experience but we're going to review vascular eds for those of you who didn't know about it once or who never really learned too much about it so are my slides visible yes yes perfect great so um so as was mentioned before we're going to talk about vascular eds which we call vents and which is a very high risk vascular condition and is very hard to recognize and so we're hoping that by bringing this to you guys you can possibly recognize the next patient that comes across and know how to care for them so um i've noted a disclosure i am on a scientific advisory board for a clinical trial for vets which i won't be discussing today so the objectives of this are to recognize when to suspect vets as a diagnosis to know how to construct a care team from families affected by beds and other rare conditions and to identify risk stratification tools and treatment strategies in events so what what is vascular eds or vets so first of all i'm going to take a step back to ehlers-danlos syndrome types so there are many types this isn't even a complete list of what we call ehlers-danlos syndrome and this is really an old nomenclature of people who might have had some flexibility but they're not really that related genetically the three as emergency room doctors pediatricians cardiologists that we will see the most and think the most about and that have the most likelihood of affecting the cardiovascular system are these three hypermobility type classical type and vascular type and what most people think when they hear eds is hypermobile these are the people who are super flexible they have autonomic dysfunction they have postural orthostatic tachycardia syndrome chronic pain they can have some mild cardiovascular features besides the pots usually they have a normal echo or maybe it's borderline aortic root dilation the etiology is not known there is not a genetic focus for hypermobile eds and they do not suffer from aortic dissections so this is what this is 99 of eds that you're going to see classical eds is pretty uncommon it's caused by a different gene and the collagen 5a1 and collagen 5a2 genes these are people they're not as flexible but they have abnormal skin so they get hernias atrophic scars they can have abnormal prolapse they can have joint hypermobility but it's not like in the um in the hypermobile group these are the ones that have stretchy skin they can also have borderline dilation and they have this cigarette paper-like skin too so this is classical eds this also does not cause aortic dissection so the cardiovascular involvement in classical eds is minimal what we really want you to distinguish us from is vascularity s which used to be called type 4 eds and we're going to do a deep dive today but big picture is the unique features of veds are that they can tend to have very easy bruising and bleeding they're prone to organ or vessel rupture acrogeria which is aged hands and feet prominent eyes thin lips and small chin and these are just some pictures i'm going to show you later it's actually very very hard to recognize the facial phenotype in beds and the aortic pattern the challenging thing in vascularity is they like classical and like hypermobile they tend to have a normal echo but despite a normal echocardiogram they can have massive aortic dissection or rupture or tear of any of their small artery small or medium-sized arteries as well so while we can dismiss especially as a cardiologist we can dismiss hypermobile and that classical edas often from clinic or see them every few years patients with beds are at risk at any time in their life of sudden death from vascular rupture so what are the genetics so this is an autosomal dominant inherited disorder it's caused by a change in type 3 pro collagen which is called the call 3a1 gene it's autosomal dominant so you only need one gene to have affected and even though it is always genetic it's not necessarily inherited so it can be inherited from a parent or it can be spontaneous a spontaneous mutation called de nova now about 50 of the known call 301 mutations we see are inherited and 50 are de novo and this is super rare this is estimated to be one in fifty thousand to one and two hundred thousand now that's very different than hypermobile eds which is it which is expected to be one to three percent of the population one to three percent one in a hundred so collagen is this tough fiber like protein that makes up about a third of the protein in our body and type 3 collagen is all over our body and it's extensively in skin lung uterus intestine and the vascular system and as you remember i said that type 3 collagen is what's altered in vascular eds and so basically there's this triple helix that collagen forms and and you need normal structure of type 3 collagen to make these curves so make this triple helix and this forms these collagen fibrils which form collagen in your body if there's an alteration in this protein this isn't full the right way it doesn't make this right triple helix and then you have more fragile collagen type 3. so what about it in kids so in children the features most commonly identified as the reason for testing are one family history a parent unfortunately and in my clinic i follow about 60 children but one of the most common reasons i see is that a parent has died at a young age and we get testing and we find out that the child is affected they can also not everyone has signs but they can have signs and these are like heidi shared with us easy bruising hematomas thin skin they can have joint hypermobility but it's it's never joined hypermobility in isolation and unlike adults presenting with a critical event a dissection a rupture a bowel perforation is uncommon it definitely can happen but that is less common versus adults the vast majority of adults because it's so unsuspected present with a life-threatening event now it is very common for child abuse to be suspected given significant bruising in some cases so a lot of these children like heidi mentioned you can just touch them and they'll bruise and so at least four of my families have been had child protective services called on them and it's something to think about if you're examining someone you know these children do not have increased risk of fractures so if you're examining a child that doesn't have long stance that you're worried about child abuse doesn't have long-standing fractures they tell you a long-standing bruising history please keep this in your differential so how what are some things that we can see we're going to go through lots of the features that help recognize so infants with this condition can be born with clubbed foot hip dislocations they can have amniotic band syndrome or limb deficiency also reported in the newborn period are a pneumothorax a collapsed lung they're more prone especially upon cpap and caloric stenosis we don't know why pyloric stenosis but it seems to have an increased prevalence in fats so um i want to show you this so this is a facial facial pictures of some of the patients who have been lovely enough to donate pictures for our research and for education and as you can see at first glance these kids are adorable they're super cute they don't look dysmorphic like we think of a lot of genetic syndromes but i am going to try to point out some of the facial features so it's very common to have these large deep set eyes they often if you can see have an extra fat pad underneath the eye or really dark circles under the eye because the eyes are so deep set it's very common they're very prominent we think it's actually lack of fat sort of around the eye makes them look more deep set they tend to have a thin pinched nose a smaller nose than would be anticipated in their family and also small thin lips you can see that almost everyone's picture has very thin lips tend to have a small chin and they can develop gum recession and fragility even as a child but i tell you it's very subtle you know we say okay the features are big eyes and a small nose and a small mouth well for a lot of people this is what makes you that's like a very attractive finding so it can be very very hard to pick up they look nothing like marfan syndrome nothing like louis deets syndrome they tend to look non-syndromic so the features can be very subtle now these are a lot of our some of our adults in our studies and you can see as they grow i think it's even harder to pick up the features so these are some some young adults and a couple of older adults you can see they still have the prominent eyes and the narrow nose one thing i wanted to point out is if you've noticed the last two pictures almost everyone i showed you is either caucasian or hispanic and there is this picture of crystal a woman unfortunately we lost a few years ago to vets who's african-american but in our research studies in our registries and our cohorts we are definitely deficient in people of african-american heritage and there's no reason genetically that it should be less prevalent in those communities and what we're all afraid is happening is that this is being under recognized because one of the first cues is thin thin skin and see-through veins and then it's being under-recognized and we're probably losing people without a diagnosis so just something to bring up but something we're constantly working on is trying to increase increased knowledge to recognize this in people of darker skin so what are the most common features in children so like i said prominent veins prominent eyes easy bruising and hind foot deformity or it could just be flat foot so these are the most common but we're going to go through a few of the other features now a secret piece of history that you're taking is as heidi mentioned almost 100 of my patients sleep with their eyes open i know that i don't even think this has a medical name and we don't really understand why but it's a really really common feature and if it's something you're suspecting ask them this and parents will be blown away but um that's extremely common in children with beds so um this is a mentioning of the skin you can see in all three of these people the veins are really easily seen the most common place is the upper thorax or the lower back and you just see veins everywhere now again this tens on people have fair skin it's more evident the skin is also soft it can be very soft and doughy but not stretchy like in classical eds and it's very prone to easy bruising tears and your hands also look very aged if you look on the far right this is a hand you know that looks like a hand could be from a 60 or seven year old and i think this is from a 20 year old so and if you look at this foot i'm this is showing a large bruise but this is from a great time you can see that it's um there's the limbs look older so one thing that's also interesting and this is a research that we're about to publish is pre-term birth is actually much more common in beds than in the general population so if you look at this bar graph the right bar is the general population pre-term birth birth before 37 weeks is prevalent in about 14.8 percent of the population when we look at beds it's almost 50 and we think this is because the amniotic sac is actually made from the same tissue as the fetus and that's the same dna so we think the amniotic sac is actually much more fragile because the collagen is not normal and that's why they most likely have early preterm delivery but it's 50 so another thing in your history taking to increase the suspicion so let's talk about echocardiography so historically if you look at papers on beds they'll say the echo is normal and for the most part yes that's true if you look here the the first pie chart is percent of echo abnormal so 73 of kids around that around three quarters will have a totally normal echo now the ab the abnormal incidence is actually increased though compared to the normal population and if you look at our cohort we do see some subtle abnormalities so aortic dilation alone is present in about 10 but it's subtle chds actually has increased prevalence and so some of the congenital heart diseases that have been found in kids with beds or bicuspid valve seems slightly increased above the one to two percent epsine anomaly asd subaortic stenosis and left superior vena cava now none of those are in the same cardiac family so we don't really understand why that's increased but we do see that and the likelihood of having both chd in your exhalation is also slightly increased compared to the regular population so what so now we know someone has beds what are complications or emergencies we need to worry about so the biggest one is aortic dissection or rupture or arterial dissection or rupture so i'm going to go through and i know you guys probably know this but through the difference between aneurysm dissection and rupture because sometimes it gets a little cloudy so an aneurysm is a dilation of part of a blood vessel so looking on the left the this is the arterial system of the body and any of the arteries can be affected in beds an aneurysm this is a root aneurysm this is an ascending aortic aneurysm is where the area is dilated but not torn this dilation here this is an example of a dilation in the iliac arteries now this has zero symptoms you have no idea you have it it doesn't cause any symptoms until there's a tear so this can only be found on imaging now an aortic arterial dissection is when there is a tear into the wall so if you remember the arterial wall has three layers an intima a media and adventitia if there's a tear not through all three but through one or two layers and someone bleeds into the wall and it causes this second lumen or false lumen this is a dissection this is an example of an aortic dissection but it can happen anywhere in any of the arteries and it creates two passages so you have the true lumen and the false lumen and this lumen can fill with blood it can clot it can also make this wall compress so this is it happens in a medium-sized artery for example the renal artery you can have renal artery ischemia or if this happens in the iliac artery or femoral artery you can have occlusion of blood to the leg and can have major symptoms and can be life-threatening we can also have arterial dissection in the head and neck vessels so this is an example of a carotid dissection and you can see as the blood fills this false lumen you lose blood flow in the true lumen and this causes signs of a stroke of an ischemic stroke so these are very important now sometimes if this is in the vertebral arteries a little bit lower and posterior it can just cause severe neck pain without without stroke-like symptoms so now a rupture is when when there is a tear through all three layers this is when the blood is not going into the wall of the aorta but is going directly out into the lung field into the mediastinum this can happen i've lost patients from a subclavian artery rupture into the chest wall um and so this is obviously that most people who have an arterial rupture do not survive versus a dissection can be treated with emergency surgery if you get care right away so the one thing is if you suspect a dissection or rupture or an aortic aneurysm an x-ray will not pick up any of these an echo will only pick up the aortic root but as i mentioned in beds you can have aneurysms or dissections anywhere in the body so doing echocardiography is never sufficient and so you must use ct or mri now if it's urgent a ct is what you need if you're doing screening imaging which is what we do in clinic and an mri is acceptable and especially probably preferred for children given that there's no radiation so there's something very rare um called a carotid cavernous fistula that can happen and this is almost pathopneumonic for beds so this is when you have your your internal carotid artery passes through your cavernous sinus right behind the eye there is a situation in which this can have a perforation and bleed and it causes this bulging of your eye redness of your eye it looks like it looks like this like an injection it causes significant pain blurry vision weak eye movements and this has to be embolized to be treated this is an emergency and if you see this it's you have to think of beds it's very high in the differential so um lymphothorax is actually quite common in beds mainly in older children and young adults and we've all seen pneumothoracies from multiple causes but this should be considered in your differential so if you see a spontaneous pneumothorax with no explanation make sure to ask about bleeding history family history um these other things we've mentioned now they can also have complications including hernias especially in the groin the inguinal area and recurrent or subluxation of the joints i have a young man that i care for in el paso texas and he has chronic hip dislocations and they just keep popping out of its sockets and these had to have bilateral hip surgery for these and one of the most that one of the most scary things and also often patho mnemonic for beds is intestinal rupture so children can come in with belly pain people say it's reflux it's functional pain but they can actually have outright perforation of the intestines and may have to lose part of their intestines the treatment is usually to repair or resect the intestines sometimes it can be monitored if it's a very very small and heals but most the time people need surgery and sometimes have to get a colectomy so it's very important if you have a patient diagnosed with beds that they've met with either gastroenterologist or a colorectal surgeon who's familiar with beds to sort of so they know some of the community if this does happen so um hematomas and vein ruptures are really common um you can have just these huge hematomas from minor injuries or just spontaneous you can see these are three pictures from real patients that have beds um again you can see this mild algeria so looking for these big these big bleeding episodes and they do these do go away but they're quite painful and can last weeks so what about caring for a child with feds what do we make heidi mentioned that she made her care team so i took this from the vets movement site which is one of the um as katie mentioned and you'll hear from katie at the end which is one of the advocacy organizations for beds and this is the model they mentioned oh this is the adult model i'm going to modify it a little bit to the peds model so we have it's really really important to have a local advocate that's usually going to be the primary care doctor a local advocate for care this is often a general practitioner a pediatrician and they really focus on the care but they should have a network a team of people who are familiar with beds and in adults this is a vascular surgeon but as most of us know there are not many vascular surgeons in pediatrics even at texas children's where i work we consult with a vascular surgeon at the adult hospital so most cardiovascular care is provided by pediatric cardiologists for children with feds so you have your pediatric cardiologist you have your geneticist or sometimes like in our program this is a combined clinic so we work together you have a general surgeon or gi doctor this is someone who could treat the bowel preparation and any other health care providers depending what the child is affected by and the the main primary care person can reach out to these people and get connected at any time now sometimes natural connections just occur so where the cardiologist or the geneticist forms more of this role but we really want to make sure that someone who is close and has access to all the hospitals all of the care is really involved with each child's care you know sometimes we'll have people call from another state and say will you be my main cardiologist or we'd be my main contact and that's not really the safest thing to do we are available to help consult available to help guide available at any time but you really want to make sure the local healthcare system in your town your community knows what to do and to encourage this for patients this is our there's not a lot of evidence about what to do in bed so i will tell you what we sort of do when we have a patient with vascularity as how we care for them so we make sure to confirm the genetic diagnosis make sure it's a call 3a1 mutation and not a mimiker we perform cascade screening so this is testing relatives if indicated because as we said 50 of the time it will be inherited we almost always start with baseline head to pelvis imaging usually an mra just to look if we have any chronic dissections any aneurysms that we were unaware of so we think this is really important if they're under three i might wait till three because an mri needs anesthesia but we don't always do that and if they're very young we'll offer a ct versus mra because the ct does not need to be sedated we talk extensively at our first visit usually two hours do we talk extensively make sure families are educated about risks and warning signs and they have an emergency plan we do so i have some activity limitations mainly for older children i'm going to talk a little bit about beta blocker therapy that i'm going to talk is a little controversial in our group we do give beta blocker therapy usually beta wall or curvature these are third generation beta blockers we do serial imaging depending on severity so we're going to talk a little bit about high risk versus low risk but for patients who have a lot of features who are high risk and older we might do those mris every year every other year if we have patients who have a lower risk of variant and don't really have easy bruising don't really have a strong family history we'll probably see them every year with an echo but we won't do the head pelvis imaging except every four to five years we do try to minimize procedures only procedures that are necessary we talk about and when we do that we make sure the team is all prepared and knowledgeable about what's going on and one of the most important things we do is try to connect families with other families you know this is a and hopefully you'll get the sense from heidi and katie but it's a incredibly supportive community it's a really wonderful community that i feel blessed to be a part of and i think that's a really important part of getting through this diagnosis so then talking about um risk modification can we predict what's going to happen so i'm going to briefly talk about the the different um severities of vascular eds but it's not perfect so the specific mutation the exact mutation in call 3 when how it alters type 3 collagen can matter so if the mutation just has a lower if it has a lower amount of levels with less than 15 percent of levels you're more likely to have gut or uterine involvement at a younger age at first event and then we also have what are called null variants and this is where in the entire second copy of collagen is missing and so you have all your collagen's normal it's just a lower amount if you have what's called the splice acceptor site splice donor site or glycine substitutions these actually alter the protein so it's abnormal the protein folds abnormally versus null you just have less protein but it's still normal so this is the kaplan-meier survival curve and you can see that patients that have um a splice donor site or a slice acceptor site or even a glycine substitution have much worse survival than those with a null variant and we don't even see people with no variance usually having any um life-threatening events to their 30s or 40s versus it can definitely happen in childhood in patients that have a splice splice site mutation or glycine substitution so the good news is for pediatric providers is survival in children with vascular abs is very high this is a beautiful survival curve published by dr peter byers who's sort of the world expert in genetics on this condition and what this is this is the u.s population and our the normal survival curve this is the vets population with males being lower than females but you can see that you know most of these events are happening in adulthood so most kids when we're caring for kids are going to survive but we really what we need to do is really help them recognize us get them through surgeries safely listen to parents support families and get them through and this is definitely definitely a doable thing these survival curves are often also taken from the last 20 years and we hope that we're modifying these curves so um and there's an old mantra that says that you can't do surgery on these patients because their aortas are too fragile their vessels are too fragile but that's not really true even though it's difficult it can be successful these are some of the patients in my practice so there's a 13 year old who's had multiple aortic surgeries for aneurysms a 15 year old who had his right subclavian artery rupture it ruptured in the picu thank goodness and he almost died we saved him and he had a successful repair a 13 year old had a stint placed in one of his arteries into the intestines after dissection to prevent mesenteric ischemia and he survived and another 14 year old survived after a near lethal rupture of the subclavian artery and um some of these have been written up and one of those is not my case one is from belgium so lastly i'm going to mention this trial and there's two other trials ongoing that i'm not going to go into but this is a clinical trial published in 2010 um published in the lancet down in europe and there's a beta blocker called saliperolol and it's a third generation beta blocker so it's thought to have some of the main beta blocking effects plus vasodilatory effects and they did a randomized controlled trial in patients with beds to see if they had less life-threatening events now um they enrolled 53 patients so it was not a lot of patients between france and belgium and assigned them randomly to saliprolol or placebo the ages were 15 to 65 the medicine was increased and titrated and they were followed for five years now um so they ended up having 25 in one group and 28 in the other group and they looked at how many patients had dissection eruption artery so in the drug group 20 person had an event and placebo 50 had an event so this was study was ended early it was published in the lancet and it said oh this is a great success so liberal prevents events i don't know if i put the kaplan meyer no i didn't hear um the problem was going back into the study there were some limitations of this study first of all not everyone had genetic testing so the numbers were actually about half of this that actually had proven call 3a1 the um how they were surveilled might have been different and so there's been some questions about this on the efficacy of ciliprolol so there's a lot of debate on whether celipalol works prevent dissections or not and so different practices have different um perspectives on this and our perspective in both in our pediatric hospital texas children's and the two adult hospitals in our community is that beta blocker therapy is pretty benign most people tolerate pretty well so in case it has an effect we do prescribe beta blockers but it's not a hill we're going to die on especially if patients having side effects you know we don't really know we're open and we're really excited about the trials coming up but um this is kind of the only potential therapy out there right now some people do use losartan just as a blood pressure lowering agent but there's no data that that helps either so the conclusion of this study was that slip role might be the treatment of choice for physicians and again that is really different across the world whether they're using it france and belgium are using it and we use a different beta blocker in the southern united states but in london they use losartan in dr diese's patients i believe he uses losartan and in the west coast near seattle with dr buyer's group i think they typically don't use any medication so i just wanted to walk through in our last couple of minutes before katie speaks about a family story and just the importance of knowing so there's a family that i care for and i met this three-year-old little boy and he came to me with his dad and his stepmother and he said and i heard this awful story that his mom when she was pregnant with him you know young healthy woman i think she was 22 years old pregnant athlete went in with some chest pain and had massive bleeding and died died in the emergency room at a hospital not too far from us and it was totally unclear what happened she had cardiac arrest she had cpr they did save the baby which is my young patient and no one ever knew what happened to her it was totally unclear it was a mystery to the family it was very heart-wrenching and difficult to handle also because no one knew what happened and he came to me he and the stepmom had realized had seen lots of bruising and lots of bleeding on him and cps had been called and they'd seen hematology and hematology said this doesn't seem like a bleeding disorder maybe you need to see someone who knows about genetic disorders and they saw us and he had all the classic features in fact his his um face is one of the ones i showed you earlier and we diagnosed him with vascular eds now thankfully his story ends up being very different so in retrospect we're pretty sure that his mother had beds we don't have a way to test her but you know she dies in childbirth unknowing now what happened with him we met him when he was three years old about six months later his mom called his stepmom called and said he's got severe pain his abdomen is really blowing up i don't i don't know what's happening we said come into the emergency room right away he had had to go to the potty and had run to the bathroom and had tripped on a plastic stool running to the bathroom and then developed this massive pain and abdominal swelling when he got to our emergency room he had a bladder rupture his butter had just ruptured it probably full falling on a full bladder which can be life threatening and we had to figure out what to do but because we knew we had vascular ideas we got the anesthesia team to be thoughtful about the anesthetics we got the urologist and thought talked to him about being thoughtful about the type of repair he put in a drain that lasted longer he put in sutures that were slightly different and he had a lot of repair and did fantastically he's nine now and he's doing really well and that could have gone way worse had we not realized he had beds and he's a happy healthy young man and so it just shows you how knowing can really change the course for these patients so in summary um i just wanted to remind you so vascular eds is rare but it's very serious it's you know the most severe aortopathy that is out there highly lethal it's caused by a problem with collagen formation specifically type 3. the common features in children are thin translucent skin easy bruising aged hands and feet and the echo is usually normal so don't be reassured by a normal echocardiogram most often pick up in children due to family history easy bruising club foot hip dislocations and skin findings and a ct or an mri is best to evaluate for aneurysms dissections and ruptures and x-rays never the right answer knowing the diagnosis of ed's can significantly improve outcomes surgery can be done if necessary it just needs to be planned and beta blockers may help prevent adverse events in vascular eds but we need a lot more work in the therapy realm so uh thank you so much i look forward to hearing from katie this is just a picture with two of the families i care for that are incredibly supportive both to me and to the community so thank you guys i'll stop sharing my screen thank you so much shane can you hear me okay yes great okay so my name is katie wright i am the director of the beds movement and i also have vascular ehlers-danlos syndrome and i'm going to tell you a little bit about my story before i hop into some resources that are available for your patients and for you as physicians so growing up i had many of the features that heidi mentioned about her daughter isabella i had very thin you know translucent skin you can see my veins all over my body i've had these like old looking hands most of my life slept with my eyes open when i was little easy bruising very easy skin tearing all of these things were present throughout my life including gi issues but we never found an answer when i was a child and so in 2016 i was 26 years old and had no idea that i had this condition i lived my life with this big mystery that you know never had an answer and was told i was healthy and kind of it was in my head in march of 2016 i woke up with the most severe neck pain i had ever experienced in my life and i truly thought that i'd slept on my neck wrong and that this is what people felt when they slept on their neck wrong i really could not turn my neck in either direction but my whole life i had issues and so i was like you know what i'm gonna power through it i'm gonna go to work and i made it an hour at work i got to work and made it an hour but i really could not turn my head it was just this incredibly severe pain and if you had asked me at the time to pinpoint exactly where on my neck this pain hurt i might tell you it was the left side but truly i described it as if my head was going to fall off that was the only way i could describe this pain i drove home barely made it every bump in the road every time i pressed the brakes it just felt like i was not going to make it home but again i felt like the most logical thing for me to do is go home and sleep it off right i had icy hot i had ice packs i had heat packs and i was rotating them obviously sleeping office pain did not work i went to my pcp i think within 24 hours and he told me that i probably pulled a muscle and he prescribed me a muscle relaxer and an anti-inflammatory within a few weeks i was out of those medications and i was on the you know tylenol and ibuprofen over the counter as much as i could take or this persisted for a couple months i had scans on my neck i went to a chiropractor there were no answers for this pain about two months into it i woke up with this like more severe pain this room spinning sensation i felt nauseous i had my aunt drive me to the emergency room where i waited just a little while to be told that i probably pulled a muscle and to go home and take some motrin and i never did a scan so now we're in like june july of 2016. i finally wake up one day feeling better it's like the best day of my life no pain for the first time in like three months and i was getting ready for work reach down and kick something off of the floor and instantly it was back it was just this excruciating um pain that it just felt like my head was going to fall off and i could not figure out truly what i was doing wrong to cause this but this pattern recurred for about a year and a half so i'm going to take you through some of these experiences that led to my diagnosis of beds um but it did become this pattern of you know pain for two months or so followed by a day of no pain followed by instantaneous return of this pain with no explanation over the course of the next several months i did move across country i was living in florida at the time and then i moved all the way across the country to washington state pretty much as far from florida as you could get and had a new care team i was setting up and this happened again i went to physical therapy like i said chiropractic care i was in a massage therapy thing like once a week at least all acupuncture like everything you could think of and now we're in january of 2017. i had a new pcp i told him what was going on and we ordered us like you know he put in an order to see a vascular surgeon as well as like a nerve conduction study to make sure that i didn't have thoracic outlet syndrome and the vascular surgeon the thought was that they would order a scan a vibrational plexus and make sure that there was not an artery being compressed in that area truly at this point it had been almost a year since the initial onset of the pain and i felt kind of like we were grasping at straws at this point i went to lunch with my brother over the weekend and said hey this week i'm going to see a vascular surgeon and they're going to do you know this scan here and he joked you know very lightheartedly that they wouldn't have to do a scan because you can see all the veins in my body anyway and it was really funny to us because it had been true my entire life but i went home that afternoon and i felt truly convinced that somebody had missed something at that point and throughout my life i had this feeling that somebody was missing something and i would you know push for a test and it would be normal i've been tested for scleroderma three times in my life because of the way my hands look you know there are always these periods of is there something wrong and then no there isn't but this time i felt like there was absolutely no way that there wasn't something wrong so i grabbed my box of medical records and i spread them out on my living room floor this is maybe i think it was about the end of january 2017 or the beginning of february 2017 and i started writing down things kind of a combination of things that had always been wrong with me along with things that just happened and didn't make sense and for instance when i was 18 years old i slept on a little little tiny bit of water that was drying from a mop and i tore my acl almost all the way through um in 2013 i had been experiencing a year and a half worth of something that looked like ringworm and that ended up being something called elastosis perforanz serpaginosa or the elastin tissue is actually pushing out through my skin and making it look like ringworm and the dermatologist at that time in 2013 told me hey you know you might have eller's download syndrome sometimes this is associated with that and you should go see this geneticist at mayo clinic well in 2013 i was in my senior year of college i had a 15 credit class load and i was also working 40 hours a week and at the time i said no way i'm not going to drive to mayo clinic i don't even have paid time off you know and this is like finals week this isn't happening and i put it out of my mind i saw a geneticist in 2014 though who told me that i did not meet the criteria for any form of ehlers-danlos especially not the vascular type and did not do any testing so in 2017 here i am on my living room floor and i find this little this little thing about elastosis perforance serpogenosa and i see the little tiny note on there about eller's download syndrome and i said you know what this is my most obvious clue this is where i'm going to start and i looked up ehlers-danlos syndrome i found a reputable source the nih website and i found vascular ehlers-danlos syndrome and it was one of the most devastating moments of my life seeing myself and every feature of myself on this website it had the translucent skin it had the old looking hands it had this small hypermobility like of my small joints it had my bruising at one point i got 15 stitches from a cat jumping off my lap and it also told me that my median life expectancy at that time was 48 years old so here i am living across the country from where i had seen that geneticist in florida and trying to get a genetic test again for three months i tried to get a genetic test from my local doctors i had a vascular surgeon that that i saw for thoracic outlet syndrome i basically bombarded him that week and said hey by the way i think i have vascular ehlers-danlos syndrome and he was like why would you think that and after telling him he said you know what i think he might be right but he couldn't order a genetic test i spent really three months devastated trying to find an answer and eventually i called in a last-ditch effort the geneticist i had seen in florida in 2014 and basically begged them to look up my file told them i thought they missed this a day later they called me and said you know what we're going to send you a genetic test i got a genetic test in the mail and i was on a waiting list at this point and failed to mention to see the geneticist locally in washington for a year and a half out so this is why this was such a desperate feeling but on may 3rd 2017 or month after my 28th birthday i did get genetic confirmation of vascular ehlers-danlos syndrome over the phone by the by the geneticist in florida who had originally told me i didn't meet any of the criteria and didn't need genetic testing this got me pretty fired up and this is why i'm advocating but in a couple weeks i saw the geneticists in washington told him about this neck pain that i was experiencing and i was doing all sorts of stretching like i had learned things from the physical therapist and my massage therapist and the chiropractor and i was really very dedicated to trying to solve this problem for myself and he said you know it might be an artery dissection just hang on until you see the expert vascular surgeon and maybe don't do so much stretching for a little while so i stopped and within a month i started to really feel better i saw the the vascular surgeon unfortunately not until september of that year so in september 2017 i had a cta of my head and neck that showed that i had had an internal camaraderie internal carotid artery dissection in my left internal carotid artery and i had a nice little pseudoaneurysm there that was from that dissection it was a you know an aneurysm that had formed from the tear and the artery and this is what had been causing my pain for the last year and a half so that is how i got involved i'm gonna go ahead and share a presentation with you now um but obviously this really did get me very fired up to advocate for other people with this i truly felt like i shouldn't have gone through that but i felt even more so that nobody should go through that and if they're going through it they shouldn't go through it alone so in 2017 i started this youtube channel where i started advocating for beds it was a very vague idea at that point like really i was very emotional raw and fired up and so a lot of my older videos are just me blabbing away but you know now there's about 1050 people across the world who subscribe to this channel and i use it to advocate for this condition and share information about my life and other people's life with this condition the most close thing to me though i would say is the podcast in april of 2018 i started this podcast called staying connected to talk to other people who are impacted by vets and these stories i really encourage you to go and listen to them they're very raw very truthful and it's a really good look into what people are actually living with with this condition today there are 54 episodes of the podcast out and unfortunately a few of the people that i have talked to in the last four years have passed away since their episodes were recorded and i will say the podcast the youtube channel any of my blogs are not associated with the marvin foundation or the beds movement these are just things that i do in my quote unquote free time heidi green who you heard from at the beginning of this presentation shared her and her daughter isabella's story on the podcast earlier this month in april of 2022 you can find that on the website translucent1.blog and you can also find it on all major podcast players by searching for staying connected really grateful to heidi for sharing her story on the podcast and raising awareness and for organizing this grand rounds presentation she's truly growing into an amazing advocate and so grateful to know her so now i'm going to share some resources with you that are available through the beds movement in late 2019 i actually joined the mark in foundation to start a vets division which is now known as the beds movement at the time it was just this idea that we were going to do something for events and we did so these are some things that you might see patients come in with or have available to them through the beds movement one of the things that we did very early on is do this emergency preparedness kit this is something very close to me that i felt was very important for people to have for themselves since my diagnosis of beds i've had five transient ischemic attacks for many strokes and also in october of this past year my spleen ruptured spontaneously after my diagnosis of beds i truly thought that my battle was over that people would know about beds and i could just go to the emergency room and say look i have beds and they would know what that means but i very quickly found out that that was not the case and so this emergency preparedness kit was really developed to help people affected by vets or parents of kids with beds be as prepared as they could be for emergencies it has a checklist to help them compile all their medical records it contains a letter to the emergency department which i'll show you on the next slide it has a wallet card there's a recorded information line a fact sheet for first responders this is this is really packed with tools to help them be as prepared as they can be in an emergency this is what our letter to the emergency department looks like we developed this alongside the medical experts on our professional advisory board including dr shane morris who you heard from today so you may see somebody with beds bring this letter with info about this condition to the emergency department and this is a real thing it didn't make them this themselves you know this is a real thing developed alongside our professional advisory board to help people in an emergency and it does contain the information about some of the medical experts so that you can reach out to them if you have questions about this condition this is a picture of the wallet card it folds into about a credit card size and again it has pretty much the same information it just really drives home that point that these emergencies are known to happen with beds and if somebody with beds presents to the emergency room it's very very important to rule these things out before sending them home and for our patients we've done a lot of webinars since we started the vets movements including on vascular surgery genetics gastrointestinal surgery management of beds and children creating a care team abc's like there's so many and they're all available at the bedsmovement.org they're too neat to put here but i think that not only are these important for the patients to have but if you as physicians would like to go look at them i think that's also helpful as well there's a lot of information in these webinars we also have a lot more resources for individuals including support groups as shane mentioned it's really important for families to connect with each other and we do have a very very connected community with this condition and i think it's pretty unique i think to this condition how connected people are with each other so we have virtual support groups that meet monthly there's a help and resource center that is staffed by a registered nurse that can help get patients answers to their questions from the experts there's events to meet others and the experts there's research opportunities conference it's all available at the vetsmovement.org and i really encourage you to recognize this condition and also give people this information so they can get the most support they possibly can we recently developed this information line for emergency physicians so now we're just transitioning into some of the resources available to you this is a pre-recorded line with basic information about beds for medical professionals to know in an emergency it's also available in the form of a fact sheet at the vetsmovement.org emergency and we encourage people with beds to give this information to the emergency department it's just another tool for them to get the information across to the hospital what they're dealing with this line is not monitored and does not help and decide if it's in an emergency it's really truly a recorded line with just information about beds very basic information and we do have a continuing medical education course this was developed by the beds movement our professional advisory board and the sullivan group which is a group that really specializes in cme offerings and high risk situations and like risk management and it really focuses on signs of beds and the medical emergencies associated with them so it has some cases and examples of what might come in and it will give you one and a half hours of cme credits i believe we recently had this edited to also provide credits for nurses i think it's ceus so those are available as well so really thank you for having us today i really appreciate your dedication and you know i hope that this really helps you learn and recognize vets and your patients

Channel: The Marfan Foundation

Views: 11,507

Keywords: VEDS, Vascular Ehlers-Danlos Syndrome, Grand Rounds

Id: 0TvW7gbsl88

Length: 61min 52sec (3712 seconds)

Published: Wed May 25 2022