[SPEAKER_00]: Welcome back to Run the List.
[SPEAKER_00]: Today, we will be discussing another high yield topic for primary care and GI clinic, and that is celiac disease.
[SPEAKER_00]: We are, again, so lucky to have Dr. Sith, Saker joining us as our expert.
[SPEAKER_00]: Dr. Saker is a general guest orologist at the Brigham Women's Hospital and soon to be gastroenterology hospitalist, who has a particular interest in medical education.
[SPEAKER_00]: Sith, thank you so much for joining us today.
[SPEAKER_01]: and to help teach about this very important topic today with you.
[SPEAKER_00]: Same here, Sith.
[SPEAKER_00]: Let's go ahead and run the list.
[SPEAKER_00]: Let's set the stage in GI clinic.
[SPEAKER_00]: You are seeing a 34-year-old healthy female with a history of iron deficiency inemia who is presenting with bloating, a change in her stool quality, and fatigue.
[SPEAKER_00]: She recalls being told to start an iron supplement in the past, but that it did not improve her fatigue or her blood count.
[SPEAKER_00]: Her family history is notable for Type 1 diabetes and her mother, and on exam, you know it's skin paler and a mildly-distant abdomen with hyperactive bowel sounds and slight tenderness in the upper abdomen.
[SPEAKER_00]: Sith.
[SPEAKER_00]: Given that case presentation, what differential diagnosis comes to mind and how would you approach the initial workup?
[SPEAKER_01]: Yeah, I think the differential is pretty broad with this presentation.
[SPEAKER_01]: I think the first thing that really comes to my mind would be celiac disease, a couple of things really sort of stand out to me.
[SPEAKER_01]: I think dire deficiency in Nemia that's refractory to supplementation is one thing.
[SPEAKER_01]: The family history of the type one diabetes, which increases the risk of celiac disease.
[SPEAKER_01]: And I think that'll be the number one thing that comes to my mind.
[SPEAKER_01]: Other things to consider would be things like small intestinal bacterial or overgrowth, inflammatory bowel disease, Crohn's, all sort of quite as could present like this, and then IBSD in general.
[SPEAKER_01]: But I think celiac is sort of at the top, especially with iron, especially when you think about three to five
[SPEAKER_01]: refractory-dominal supplementation, especially where COIC effects in the drawdenum in the digital genome, where IR is absorbed.
[SPEAKER_01]: And then, you know, some basic work of I would get would be things like CBC, TSH, COEXerologies, and then vehicle calprotectin, especially to evaluate that change in or still quality.
[SPEAKER_00]: All right, so that's a great starting point.
[SPEAKER_00]: I love the emphasis on the iron deficiency andemia that is not improving with PO iron supplementation, which suggests that there could be some issue with malibosorption, and that's kind of hinting to you that this could be celiac disease.
[SPEAKER_00]: All right, so SIF, you mentioned celiac surallegies.
[SPEAKER_00]: Can you discuss specifically what surallegies you send?
[SPEAKER_00]: I know we talk about them in general, but what do you specifically send?
[SPEAKER_00]: And why are those the labs that you send?
[SPEAKER_01]: Yeah, I think when we sensile accelerologies, the big one that we're looking at is TTG IGA that's sort of the most the best combination of sensitivity and specificity for celiac disease, the important thing to know about that is that you need to also check the IGA level as well and then.
[SPEAKER_01]: Also need to ask if the patient is still taking glue in a lot of these patients by the time they get to you.
[SPEAKER_01]: They try to do a different dietary modifications, including stopping gluten.
[SPEAKER_01]: So it's really important to ask about if they're still consuming gluten, because that can really affect the testing.
[SPEAKER_00]: Perfect.
[SPEAKER_00]: I've also had the situation where a patient has gotten a positive celiac serology, and then they were advised to stop eating gluten right away.
[SPEAKER_00]: And then by the time they get to GI clinic, as you mentioned,
[SPEAKER_00]: we're left in this situation where they had a positive CLX or algae, but now they're on a gluten-free diet.
[SPEAKER_00]: And so we'll talk about that in a bit what we need to do in that case.
[SPEAKER_00]: But getting back to what you just discussed.
[SPEAKER_00]: So what happens if you send the tissue, transgutaminase IgA level, along with the IgA level, and the IgA level comes back undetectable?
[SPEAKER_00]: What do you do with that result?
[SPEAKER_01]: Yeah, I think that's sort of, you know, why you send IJ because you want to make sure there's no IGA deficiency because if it comes back undetectable and there's deficiency then the TTG IGA is not reliable at all and in that case, then you would use IGG trans tissue glutaminate instead.
[SPEAKER_01]: Or you can use any other sort of IDG based test sort of like a deaminated gluid in protein testing.
[SPEAKER_01]: But when it comes back and there's IDA deficiency then you want to use more of a route of an IDG testing for it.
[SPEAKER_01]: That's sort of where I would go when it's an IDA deficiency.
[SPEAKER_00]: it great.
[SPEAKER_00]: So nice teaching point there to always send the IGA level, the total IGA level with any TTG IGA CLI test.
[SPEAKER_00]: And then getting back to the scenario in which a patient comes to you on a gluten-free diet, but at some point had an elevated TTG IGA or other CLIxorology.
[SPEAKER_00]: So, how do you think about working up those patients who have already started gluten-free diet, but had a positive celiac serology as part of their work up?
[SPEAKER_01]: Yeah, I think in the next test, I really think about a sort of genetic testing.
[SPEAKER_01]: And luckily, we have some pretty good genes that we mapped to Celiac, and that would be HLA DQ2 and DQ8.
[SPEAKER_01]: And these are sort of really helpful because if negative, you know, they're very, very sensitive.
[SPEAKER_01]: So negative, you can exclude Celiac in these cases.
[SPEAKER_01]: If positive is on us, hopefully, you sort of still have to go down the pathway, but it being negative can exclude the Celiac.
[SPEAKER_01]: So if it is positive,
[SPEAKER_01]: And you're in that case where they've already started a gluten-free diet, then we would ask, you know, just re-challenged gluten, which can be difficult for patients for at least two weeks and then repeats forology.
[SPEAKER_01]: And gluten-challenged is sort of 20, about one to three pieces of bread a day for sort of those two weeks or four weeks before repeating surologies or other testing, including a doc, which we'll talk about coming up.
[SPEAKER_00]: So, all right, that was super helpful to review those situations as they do come up.
[SPEAKER_00]: I have to say with some frequency.
[SPEAKER_00]: All right, so let's say our patient is consuming gluten and the initial labs are notable for a mild and anemia.
[SPEAKER_00]: Well, see, it's microstatic with a hemoglobin of 11.
[SPEAKER_00]: And the TTG IGA returns significantly elevated at 500 units per milliliter.
[SPEAKER_00]: And you did check the IGA level and that was normal.
[SPEAKER_00]: So, what is the next step in diagnosis for this patient?
[SPEAKER_01]: Yeah, the next step is to proceed to an upper endoscopy, and it's important that the patient remains on gluten, so you can get the best sort of testing from biopsies, and you want to take doodinal biopsies, multiple.
[SPEAKER_01]: We usually try to get at least thick, and we want to get it both from the bowl, which is the first part of the doodinal, as well as more from the distal doodinal.
[SPEAKER_01]: And actually, see like preferably affects the more distal doodinal, so we try to get more of our pieces from there, and sort of look for things on pathology that are consistent with celiac.
[SPEAKER_00]: Perfect set.
[SPEAKER_00]: Yeah, that's such a good point about the biopsying approach and so one thing I do I know you do it as well as I indicate in my procedure report that I have obtained biopsies both from the duodenal bulb and the more distal duodenum and like you said to get more from the distal duodenum because that's often where the celiac disease is presenting itself.
[SPEAKER_00]: So all right.
[SPEAKER_00]: So now some cases we will see these discordant results where the celiac serology is positive but then the biopsies come back normal
[SPEAKER_00]: So in those situations, what's your approach?
[SPEAKER_00]: What are you thinking are the possibilities?
[SPEAKER_01]: Yeah, I think in those cases, you can either have a false positive of the TTG.
[SPEAKER_01]: It's less likely, especially if the titers are high.
[SPEAKER_01]: Or you more likely will get false negative biopsies because celiac is just so patient.
[SPEAKER_01]: That's why we get so many biopsies from the dood.
[SPEAKER_01]: No, I think this is an excellent sort of use case for the genetic testing of the HLA DQ2 and DQ8 similarly as before.
[SPEAKER_01]: If it's negative, you can exclude celiac in these cases.
[SPEAKER_01]: If it is positive, as it most likely will be, then you can perform more intensive gluten challenge, have them, you know, eat sort of three pieces of toast for about one to three months, and then continue to eat that, and then repeat the EGD after sort of about three months.
[SPEAKER_01]: Sometimes you even need them on a gluten challenge for up to six or twelve months before repeating the EGD.
[SPEAKER_00]: So that HLA DQ2 DQA testing again comes in very handy in this discordant result scenario.
[SPEAKER_00]: All right.
[SPEAKER_00]: So Sith, that was a great review.
[SPEAKER_00]: Let's get back to our case.
[SPEAKER_00]: So our patient undergoes an upper endoscopy while continuing to consume gluten.
[SPEAKER_00]: The endoscist notes a scallop appearance of the Duanol mucosa, which is suggestive of celiac disease.
[SPEAKER_00]: And then the biopsy's of the duodenal bulb and the second part of the duodenum are obtained.
[SPEAKER_00]: You receive the pathology report that indicates that the biopsy's noted significant villous blunting and increased intraepothelial lymphocytes, which in combination with her significantly elevated TTG, IGA confirms her diagnosis of celiac disease.
[SPEAKER_00]: Sith, when you see this patient follow up with now confirmed celiac disease, how do you begin counseling the patient about management?
[SPEAKER_01]: Yeah, that's excellent question now.
[SPEAKER_01]: They have the confirms heliect disease.
[SPEAKER_01]: So the most important thing is to start talking about a gluten-free diet and the main sources that I mentioned or things like wheat, rye, and barley.
[SPEAKER_01]: And this can be a very big major lifestyle change, especially compared with the Western diet.
[SPEAKER_01]: It's really important to read all nutrition labels and pay attention to any additive, especially because gluten can be snuck into anything.
[SPEAKER_01]: A big alcoholic drink that people need to start avoiding is no beer unless it clearly is marked as gluten free, but again you have to really pay attention to the labeling and then you have to be careful with oats because they are also often cross contaminate with gluten.
[SPEAKER_01]: I actually often up front really advise and refer people to nutrition for additional support because they can really walk people through their diets and bake sources of gluten and how to avoid and I found that that's very helpful especially up front when it's the diagnosis of COX diseases made.
[SPEAKER_00]: That's great Sith.
[SPEAKER_00]: So I know this comes up often especially with patients who are asymptomatic and found to have COX disease.
[SPEAKER_00]: What do you do if your patient asks if it was okay to have gluten
[SPEAKER_01]: Yeah, this comes up almost every time, especially if they're asymptomatic.
[SPEAKER_01]: You know, there's a whole host of micronutrient deficiencies that can develop, and we'll get into that a little bit later, but the biggest thing that I counsel them on, especially is the development and the small risk of lymphoperative disease and small intestinal lymphoma that can develop.
[SPEAKER_01]: If there's continued exposure to gluten, even if they're asymptomatic, and you know, this is pretty rare, but you know, it can be profound when it does develop.
[SPEAKER_01]: So it's important for patients to understand this, and that's why we really harp on the gluten-free diet, because that's really our biggest management for celiac disease currently.
[SPEAKER_00]: Got it.
[SPEAKER_00]: So you always advise a strict gluten-free diet.
[SPEAKER_00]: And once the patient has made this life's sound change, when and how do you assess their response to the gluten-free diet?
[SPEAKER_01]: Yeah, the first starts with repeat serologic testing, especially the tissue trans glutanaase, especially if they didn't have any issues with IGA deficiency or anything.
[SPEAKER_01]: Before hand, then I get that at the 6 and 12 month mark.
[SPEAKER_01]: It's really only helpful if it was elevated at the time of diagnosis and now the second step that I do is I do repeat and ask me on them with repeat biopsies of the dawn to ensure that there's going to be coastal healing this is typically around the one year mark I don't typically do it sooner than the one year mark they need to be on strictly and free diet for at least a year and then also ideally the serologic testing would be normalized prior to proceeding with repeat andoscopy.
[SPEAKER_00]: perfect.
[SPEAKER_00]: So in addition to specifically monitoring the response of the celiac disease at therapy, what other items do you need to manage?
[SPEAKER_01]: Yeah, like I mentioned above, I think the biggest things are nutritional deficiencies and these are labs that I send off at the time of diagnosis and he fats all he will vitamin so ADE vitamin K and using PT is potential worker for that but PTI and are vitamin B12 fall acid and then iron studies as well these are all can develop especially.
[SPEAKER_01]: And any patient would say like, these aren't important to monitor a lot while we go along.
[SPEAKER_01]: And then I also get a deck set at the time of diagnosis because people can develop bone loss with this.
[SPEAKER_01]: And the other thing is important is vaccination and pneumococcal vaccine is recommended because there's an association with hypospelanism.
[SPEAKER_01]: So those are the biggest things that you know, looking for monitoring and the response of celiac disease therapy.
[SPEAKER_00]: That's great.
[SPEAKER_00]: So yeah, there is, you know, there is a lot to review beyond just following a gluten-free diet.
[SPEAKER_00]: And this is why I find it's helpful for patients with celiac to actually establish themselves with the GI provider who can counsel them not only on the gluten-free diet, but also check for all of these other potential abnormalities you mentioned, really nicely just there.
[SPEAKER_00]: So is there anything else that you recommend to your patients who have been newly diagnosed with
[SPEAKER_01]: One of the things that can sometimes go miss, but it's important to keep in mind is the screen any first degree family member, even anyone that's asymptomatic for select disease, just because there's such a huge genetic relation with it.
[SPEAKER_01]: So it's important to screen all first degree family members forward and then that way you can pick up any risk of micronutrient disease, bone loss, and then the small risk of malignancy as we had mentioned before.
[SPEAKER_00]: Excellence Sith has a fantastic review, one last question before we conclude, what about the individuals who start a gluten-free diet but do not respond?
[SPEAKER_00]: That is, they have persistent seerologic and histologic abnormalities consistent with celiac disease.
[SPEAKER_01]: Yeah, we do run into this quite a bed, you know, typically the vast majority or either non-linear or they are trying to be adherent and they have unknown gluten and gestion.
[SPEAKER_01]: So I talk about cost contamination especially in the kitchen and then really reading those labels.
[SPEAKER_01]: And this is where nutrition referral can be very helpful.
[SPEAKER_01]: As they can go through your diet, making sure there's no cost contamination, making sure there's no
[SPEAKER_01]: unknown gluten ingestion because this can really, you know, affect it and as we talk to whether there's so many risks associated with and keep those serologic values high.
[SPEAKER_01]: So that's where I start with.
[SPEAKER_01]: There's other less common situations that can happen and this includes sort of having concurrent disorders such as SIBO or lactose intolerance.
[SPEAKER_01]: And a big one that you want to watch out for is microscopic colitis, sort of masquerading as well.
[SPEAKER_01]: And you know, people should get a colonoscopy with biopsies, just sort of rule this out.
[SPEAKER_01]: If people are having sort of persistent diarrhea or other things with celiac disease, a very rare case, you know, if you rule out that they're being very adherent, that there's no cross-contamination, there's no other concurrent disorder that's happening, is refractory spru.
[SPEAKER_01]: And there's two types of a type 1 and type 2 and it requires sort of histologic diagnosis from that.
[SPEAKER_01]: And sometimes patients do require stairroids for this and even stepping up to immunomodulator therapy.
[SPEAKER_01]: It's very rare, but it is something that I always keep in the back of my mind.
[SPEAKER_00]: That was great, Seth.
[SPEAKER_00]: So, thank you so much for taking us through the key parts of Managing Sea Lyact disease beyond just the recommendation to start a gluten-free diet.
[SPEAKER_00]: So before we leave, can you leave us with some RTL pearls from today's episode?
[SPEAKER_00]: Absolutely.
[SPEAKER_01]: You know, the biggest thing is sort of when you think about celiac disease, I think number one, anytime you have a patient with iron deficiency in anemia, celiac disease should be something you screen for with surologies.
[SPEAKER_01]: Other things can be sort of non-specific GI symptoms as well.
[SPEAKER_01]: We often see people with bloating, can present with celiac disease, and then even sort of food sensitivities, and even sort of diarrhea can also present as celiac disease.
[SPEAKER_01]: So,
[SPEAKER_01]: just having a high suspicion and screening for with serologies is important.
[SPEAKER_01]: And then in terms of workup, you want to send the TTG IGA and anytime you're sending that, you want to send the total IGA as well, the screen priority efficiency.
[SPEAKER_01]: And as prior, if there is IGA deficiency, then you want to use an IGG modality, either TTG IGG, or you want to use the DM and it glidden protein IGG.
[SPEAKER_01]: And then these just corn results where you have serology that's positive, biopsy-negative, or even sometimes you get biopsy-depositives and the COX-erologies are negative.
[SPEAKER_01]: Then you can use the HLA-DQ-2-DQ-A genetic testing to see if negative it excludes your active disease, if positive then you need to do more testing.
[SPEAKER_01]: The biggest thing in sort of the thing that we see a very often action in GI clinics that is really important for the patients to continue on gluten until they're diagnosed with upper endoscopy, because that really increases the diagnostic yield of biopsies.
[SPEAKER_01]: It's important to check the response to gluten-free diet after you made the diagnosis of the disease and you do this with both serologies, as well as repeat duodenal biopsies.
[SPEAKER_01]: Important to keep in mind other potential complications, including micronutrient deficiencies,
[SPEAKER_01]: bone loss and hyposponism make sure people are getting the vaccines they're needed the labs that they're needed to sort of monitor this and then most importantly do not forget to recommend screening of all first-degree relatives so that people get diagnosed and caught earlier so that they're managed well.
[SPEAKER_00]: Amazing.
[SPEAKER_00]: Thank you so much, Sith.
[SPEAKER_00]: We had a great time discussing how to manage celiac disease and I definitely look forward to having you back for another episode very soon.