Refractory Celiac disease - what to do

[ehb]

Hello, 

I was diagnosed with Celiac disease about 2 years ago. Since then, I have been on an increasingly strict gluten free diet, and have been in an entirely gluten free household since January 2025 (almost 6 months). However, since my second blood test, my ttg AB, IGA levels have been stuck at ~50 (<15 not detected), fluctuating occasionally between ~47-53.  I had a biopsy one year ago (June, 2024), which showed "Duodenum with mild villous blunting and intramucosal Brunner's glands, crypt hyperplasia and increased intraepithelial lymphocytes are seen, no features of collagenous sprue or lymphoma". Since January, I went on a low FODMAP diet to help manage symptoms, but have never cut out dairy or oats completely. I am at a loss for what to do. My doctor has recommended a clinical trial for Amlitelimab, which thankfully doesn't require a gluten challenge, so I am waiting to hear back from them to see if I am eligible. I have gotten no other guidance, advice or options other than that. My symptoms are up and down but feel like they have been getting worse recently so I am feeling more desperate for solutions. I feel like I am not getting the follow up and support that is recommended online in these situations, so I am trying to get a second opinion, but don't know how to navigate insurance and getting an appointment with another specialist. I have heard some people talking about dairy, oats and corn causing a reaction in some patients, but it's unclear if that is a secondary reaction to gut damage or if these things could cause actually trigger the celiac autoimmune response, and no doctors or dieticians have recommended cutting these out. I am also wondering if this could be caused by some other autoimmune disorder, and how I would get tested for that? I guess I am looking for any sort of advice for what to do in this situation, either about participating in clinical trials or finding doctors for a second opinion, or how to get support/information for other dietary changes that could be contributing to this? Thank you in advanced for any information or support! 

[ehb]

Some other things to note and that I am wondering about is that my Mom has Chron's disease and I am wondering if that could interact here somehow. I am also wondering if I should do some form of genetic testing and what the benefit of this would be? Could this tell me my risk for developing Sprue or Lymphoma? I am very worried about this developing into Lymphoma, and wondering if that's a common thing that happens in these cases? 

[trents]

Welcome to the forum, @ehb!

This might be helpful: https://www.verywellhealth.com/villous-atrophy-562583

and this: https://www.mayoclinicproceedings.org/article/S0025-6196(17)30892-3/fulltext

[ehb]

thank you @trents ! I am reading through these, and it gives some clarity on the other possible causes of villous atrophy, but given that I still have high ttg levels, I am thinking that the most likely cause is still the celiac disease, and any treatments for other causes would not address the increased ttg levels and villous atrophy caused by that?

[trents]

I believe you are falsely concluding that elevated tTG-IGA/tTG-IGG levels can only be caused by celiac disease. I will offer a link here to an article outlining the various blood antibody tests that can be used to diagnose celiac disease. Each one them has less than a 100% specificity for celiac disease: 

 

[trents]

When you say you have been in an "entirely gluten-free household" since January of 2025" does that include making sure you have checked that all medications, supplements and oral hygiene products are gluten free? I can also tell you that for some people, it can take several years for their antibody numbers to normalize.

[ehb]

@trents Thank you, but it is still not clear to me what else other than celiac disease could be causing the combination of increased tTg-IGA and villous atrophy? when I asked my doctor about other possibilities, he said it is only celiac disease and gluten that could be causing this. Do you have any advice about how to approach my doctor about this, or what to do if it is not caused by celiac disease? 

[ehb]

4 minutes ago, trents said:

When you say you have been in an "entirely gluten-free household" since January of 2025" does that include making sure you have checked that all medications, supplements and oral hygiene products are gluten free? I can also tell you that for some people, it can take several years for their antibody numbers to normalize.

I have changed my toothpaste, and all hair/face/body care products to be gluten free. When I pick up prescription medications I ask for the full ingredients list to check for possible gluten sources, and don't take advil anymore because they cannot verify it to be gluten free. I am not sure how to change my diet further, but please let me know if you have any other ideas for potential hidden sources. 

[trents]

19 minutes ago, ehb said:

@trents Thank you, but it is still not clear to me what else other than celiac disease could be causing the combination of increased tTg-IGA and villous atrophy? when I asked my doctor about other possibilities, he said it is only celiac disease and gluten that could be causing this. Do you have any advice about how to approach my doctor about this, or what to do if it is not caused by celiac disease? 

Doctors aren't always right. I have been participating on this forum for many years and you wouldn't believe the cockamamie things doctors say about celiac disease to our member base. It's often based on very outdated information and sometimes just plain ignorance. Many doctors neglect to tell their patients not to begin a gltuen free diet before the testing is finished. Others tell them just to cut back on gluten but a little is okay. Think about it. The tTG-IGA test has a 90-98% specificity rating. That means there is somewhere between a 2% and a 10% chance that elevated tTG-IGA levels can be caused by something other than a celiac reaction to gluten. The tTG-IGA antibodies are just an inflammatory response of the immune system, most likely to gluten but a certain percentage of the time to something else. And the villous atrophy is just the result of persistent inflammation, whatever the cause. Why don't you print out the article on blood antibody tests and show it to the doctor and ask him/her what it means that the test is less than 100% specific?

Edited June 12 by trents

[ehb]

12 minutes ago, trents said:

Doctors aren't always right. I have been participating on this forum for many years and you wouldn't believe the cockamamie things doctors say about celiac disease to our member base. It's often based on very outdated information and sometimes just plain ignorance. Many doctors neglect to tell their patients not to begin a gltuen free diet before the testing is finished. Others tell them just to cut back on gluten but a little is okay. Think about it. The tTG-IGA test has a 90-98% specificity rating. That means there is somewhere between a 2% and a 10% chance that elevated tTG-IGA levels can be caused by something other than a celiac reaction to gluten. The tTG-IGA antibodies are just an inflammatory response of the immune system, most likely to gluten but a certain percentage of the time to something else. And the villous atrophy is just the result of persistent inflammation, whatever the cause. Why don't you print out the article on blood antibody tests and show it to the doctor and ask him/her what it means that the test is less than 100% specific?

I hear you, but I am not sure where to go from here if there is a possibility that it is cause by something other than celiac and gluten. What other things should I be getting tested for and how? If I can't trust the doctors, who can I trust? How can I be sure that it is not from small amounts of gluten that are impossible to eliminate? Would you recommend the Amlitelimab trial? Should I continue eliminating things from my diet? there is so much conflicting information and research, I would prefer to defer to the doctors, but it seems that they don't have many more recommendations for me either... 

[Scott Adams]

Many people with celiac disease, especially those who are in the 0-2 year range of their recovery, have additional food intolerance issues which could be temporary. To figure this out you may need to keep a food diary and do an elimination diet over a few months.

Some common food intolerance issues are dairy/casein, eggs, corn, oats, and soy. The good news is that after your gut heals (for most people who are 100% gluten-free this will take several months to two years) you may be able to slowly add some these items back into your diet after the damaged villi heal.

This article may be helpful:

 

 

[ehb]

Thank you, @Scott Adams I am wondering if these additional food intolerances could explain the continued tTG-IgA elevation and villous atrophy? Am I required to eliminate these potential intolerances in order for my gut to heal, or could it heal on it's own with just the gluten free diet?

[trents]

19 minutes ago, ehb said:

I hear you, but I am not sure where to go from here if there is a possibility that it is cause by something other than celiac and gluten. What other things should I be getting tested for and how? If I can't trust the doctors, who can I trust? How can I be sure that it is not from small amounts of gluten that are impossible to eliminate? Would you recommend the Amlitelimab trial? Should I continue eliminating things from my diet? there is so much conflicting information and research, I would prefer to defer to the doctors, but it seems that they don't have many more recommendations for me either... 

Well, it certainly seems reasonable to get checked for Crohn's since you have a family member with it and SIBO. You might also consider talking to your physician about a trial on an immunosuppressant, like prednisone, to see if numbers go down and symptoms subside. Sometimes, just interrupting the inflammatory cycle can effect a reset and put you on the road to health.

Edited June 12 by trents

[Scott Adams]

As @trents mentioned, removing gluten if you have celiac disease would be key to villi recovery, and if you still are having issues trying to identify other triggers would be the next step, even though the additional intolerances will not likely contribute to villi recovery.

This study indicates that a majority of celiacs don't recover until 5 years after diagnosis and starting a gluten-free diet:

• Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet

However, it's also possible that what the study really shows is the difficulty in maintaining a 100% gluten-free diet. I suspect that if you looked closely at the diets of those who did not recover within 2 years might be that their diets were not 100% gluten-free. Perhaps they ate out more often, or didn't understand all of the hidden ingredients where gluten can hide. Either way, it shows how difficult recovery from celiac disease can be for most people.

According to this study:

Quote

After an average of 11 months on a gluten-free diet, 81% of patients with celiac disease and positive tissue transglutaminase IgA (tTG-IgA) at baseline will revert to negative tTG-IgA (SOR: C, disease-oriented evidence from retrospective cohort study). The intestinal mucosa of adult patients with celiac disease will return to normal after following a gluten-free diet for 16 to 24 months in only 8% to 18%. However, in children after 2 years, 74% will have a return to normal mucosa (SOR: C, diseaseoriented evidence from longitudinal studies).

This article explores other causes of flattened villi:

 

 

 

[Scott Adams]

1 hour ago, ehb said:

@trents Thank you, but it is still not clear to me what else other than celiac disease could be causing the combination of increased tTg-IGA and villous atrophy? when I asked my doctor about other possibilities, he said it is only celiac disease and gluten that could be causing this. Do you have any advice about how to approach my doctor about this, or what to do if it is not caused by celiac disease? 

Your doctor is most likely correct here, and if you had high tTg-IGA and villous atrophy you likely have celiac disease and need to be gluten-free. If regular small amounts of gluten get in your diet, it will prevent recovery. Eating out in restaurants is the primary source of such contamination.

[RMJ]

Sometimes it can take a long time for antibodies to get into the normal range.  My TTG IgA was normal after a year, but just barely and it bounced in and out of normal range for a few years.  It took five years to get the DGP IgA normal.

You may want to reevaluate your gluten free diet.  I started by not eating anything with gluten ingredients. All antibodies decreased but DGP IgA still elevated. Then if I ate processed foods I only ate those labeled gluten free.  Still not enough.  Now I only eat processed foods if certified gluten free or labeled gluten free and from a company with a good reputation in the celiac world.  

To answer another one of your questions, the incidence of intestinal lymphoma in general is very, very low.  Yes it is increased in those with celiac disease , but even with the increase incidence is still very, very low.

[ehb]

Thank you @Scott Adams and @trents this is very helpful, and I think I have some solid ideas to bring to my doctor (corticosteroids, testing for chron’s, increasingly strict gluten-free diet) 

@RMJ thank you this is definitely reassuring as well, I’m feeling frustrated and hopeless because I have gone through a similar progression of increasing strictness, and am now at a level similar to what you describe, but have not seen any changes in my blood results. I am now thinking to cut out processed foods altogether maybe with the help of a dietician? I’m also worried about cross contamination from the tables or microwave at my work (there is often free pizza and such sitting). It just feels so restrictive to not see or feel any results 

[ehb]

@RMJ what is the DPG test? I think my doctor never had me do that 

[RMJ]

50 minutes ago, ehb said:

@RMJ what is the DPG test? I think my doctor never had me do that 

Antibodies to Deamidated gliadin peptides.  It is another celiac antibody test. The main test is the one you had, TTG,  But a full panel will also include DGP IgA and IgG.  I was positive on all of them!

[trents]

2 hours ago, ehb said:

@RMJ what is the DPG test? I think my doctor never had me do that 

That is one of the tests covered in the article I linked you above.

[cristiana]

6 hours ago, RMJ said:

Sometimes it can take a long time for antibodies to get into the normal range.  My TTG IgA was normal after a year, but just barely and it bounced in and out of normal range for a few years.  It took five years to get the DGP IgA normal.

You may want to reevaluate your gluten free diet.  I started by not eating anything with gluten ingredients. All antibodies decreased but DGP IgA still elevated. Then if I ate processed foods I only ate those labeled gluten free.  Still not enough.  Now I only eat processed foods if certified gluten free or labeled gluten free and from a company with a good reputation in the celiac world.  

To answer another one of your questions, the incidence of intestinal lymphoma in general is very, very low.  Yes it is increased in those with celiac disease , but even with the increase incidence is still very, very low.

Agreed, and I can't remember exactly and haven't got time to check, but I think my blood didn't normalise for eight years! For years I read this forum thinking why can't I get my numbers down - everyone else manages to.   But my gastroenterologist didn't seem to worry about it, which makes me think he either thought I wasn't complying to the diet, or he'd seen similar cases.

[Scott Adams]

14 hours ago, ehb said:

@RMJ what is the DPG test? I think my doctor never had me do that 

This article might be helpful. It breaks down each type of test, and what a positive results means in terms of the probability that you might have celiac disease. 

 

 

[ehb]

Thank you, I think with the initial blood tests they did actually do the IgA tests first to make sure those are normal! I am wondering if there are any tests that actually test for the presence of the gluten protein? From my understanding, all of these test for gluten antibodies, which in the case of refractory celiac would switch to a gluten-independent mechanism of activation. Because my ttg levels havent changed at all with my increasingly strict diet, I am concerned about distinguishing between the possibilities that 1) I am super sensitive to very very small amounts of gluten and am getting cross contamination from somewhere I haven't identified or 2) have refractory celiac where even if I were to eliminate gluten 100%, my immune system is stuck in this activated state or is reacting to something else. The course of action should be different in these scenarios - in scenario 1, I should really lock in and stop eating processed foods all together (even if labeled gluten-free?) and identify any possible source of contamination no matter how small, but scenario 2 would require some other intervention like corticosteroids or a clinical trial. If I could somehow test the actual presence or amount of gluten in my body, I would think that could distinguish between these possibilities - if gluten is present it is more likely scenario 1, and if gluten is not present it's more likely scenario 2. I would probably need a test I could take regularly like once a day 

[Scott Adams]

Do you eat in restaurants, or food prepared in restaurants?

[Scott Adams]

Also, there is this product: