Possible Refractory Celiac Disease

[Anonym]

Hi!

I joined this forum to ask a question regarding refractory celiac disease.

Here is my background. I am a 26 year old male. I was diagnosed with asymptous celiac disease with tTG IgA test and biopsy over 15 years ago. These tests were run because multiple of my family members were also confirmed as celiacs. Around the same time I was also diagnosed with type 1 diabetes.

Despite a strict gluten free diet, my tTG IgA levels didnt normalize. However, a biopsy after two years of the original diagnosis confirmed that the healing had begun. The normal range for the utilized tTG IgA test is from 0.0 - 7.0 U/ml. My IgA hovered around 8-9 for the following 10 years, before finally in 2018 dipping below the limit at 6.9 U/ml. Not much was thought of this, as it was presumed to remain a little high due to the coincidental diabetes condition. Thus, the biopsy was never renewed.

Following this, the tTG IgA test was run again in early 2021. To my surpise, the result was 28 U/ml. I only eat foods cooked by myself, so there is literally no chance of contamination or any mistakes. My diet is as strict as it can be. I have checked everything, including cosmetics, for gluten free ingredients. What is more, I was even more careful after this serology result. 8 weeks later, my serology was renewed. Even more surprisingly, the tTG IgA result was elevated to 42 U/ml despite a confirmed 100% adherance to gluten free diet. The EMA IgA test was also run this time, with a result of 50 (normal range <5).

Here is my question. Is there anything other than refractory celiac disease which could explain these results? Refractory celiac disease is super rare, and I havent found any indication that it could occur in relatively young patients. However, these serology results give little no chance of anything else. I am going to have a new biopsy in four weeks. In the mean time I thought I would ask for guidance from this forum.

Thanks!

 

 

 

[plumbago]

19 minutes ago, Anonym said:

Here is my question. Is there anything other than refractory celiac disease which could explain these results?

Yes. Diabetes.

[Anonym]

Thank you for your answer!

I have a couple of counterpoints to that. I do not have medical education so I might have gotten some things wrong, but isnt the EMA IgA highly specific to gastro intestinal damage? At least in my country, these serology results (both tTG and EMA up ~10-fold) are enough to have a diagnosis to untreated celiac disease.

Further, at least the tTG has been in a stable range up just to 8-9 for the last ten years. Now that it has suddenly spiked my own reaction was to immediately think of refractory celiac disease.

[trents]

4 hours ago, Anonym said:

Hi!

I joined this forum to ask a question regarding refractory celiac disease.

Here is my background. I am a 26 year old male. I was diagnosed with asymptous celiac disease with tTG IgA test and biopsy over 15 years ago. These tests were run because multiple of my family members were also confirmed as celiacs. Around the same time I was also diagnosed with type 1 diabetes.

Despite a strict gluten free diet, my tTG IgA levels didnt normalize. However, a biopsy after two years of the original diagnosis confirmed that the healing had begun. The normal range for the utilized tTG IgA test is from 0.0 - 7.0 U/ml. My IgA hovered around 8-9 for the following 10 years, before finally in 2018 dipping below the limit at 6.9 U/ml. Not much was thought of this, as it was presumed to remain a little high due to the coincidental diabetes condition. Thus, the biopsy was never renewed.

Following this, the tTG IgA test was run again in early 2021. To my surpise, the result was 28 U/ml. I only eat foods cooked by myself, so there is literally no chance of contamination or any mistakes. My diet is as strict as it can be. I have checked everything, including cosmetics, for gluten free ingredients. What is more, I was even more careful after this serology result. 8 weeks later, my serology was renewed. Even more surprisingly, the tTG IgA result was elevated to 42 U/ml despite a confirmed 100% adherance to gluten free diet. The EMA IgA test was also run this time, with a result of 50 (normal range <5).

Here is my question. Is there anything other than refractory celiac disease which could explain these results? Refractory celiac disease is super rare, and I havent found any indication that it could occur in relatively young patients. However, these serology results give little no chance of anything else. I am going to have a new biopsy in four weeks. In the mean time I thought I would ask for guidance from this forum.

Thanks!

 

 

 

Are you still eating dairy and oats? Cow's milk protein has been proven to produce villi damage for some people. And for about 10% of celiacs. oat protien (gluten free oats) harms the gut like wheat, barley, rye. In addition, there are some meds that can cause villi damage, apart from containing gluten.

Edited April 23, 2021 by trents

[Scott Adams]

I agree with @trents regarding oats and dairy, you may want to exclude them from your diet for a few months, then re-test. This article might be helpul:

 Also, it may make sense to get another biopsy to check your villi condition, as there are a small percentage of celiacs who do develop refractory celiac disease. We have many articles summarizing the research on this here:

https://www.celiac.com/celiac-disease/celiac-disease-amp-related-diseases-and-disorders/refractory-celiac-disease-collagenous-sprue/ 

[RMJ]

Is there anything in your diet that changed prior to the antibody increase?  Different brand of something, etc.?

I’m glad you’ll be getting another biopsy.  There are specific things that can be seen in a biopsy that indicate refractory celiac.  I hope they aren’t seen in yours!

[Anonym]

A big thanks for your advice! I have been eating oats and milk. Will cut them of from now on.

Few questions popped into my mind:

1) Is there any evidence that other ingredients such as soy or maize could trigger the same transglutaminase response?

2) Could the biopsy indicate by itself that omitting ingredients such as milk and oats could be useless? Some studies I found promisingly described that omitting ingredients such as milk "cured" most of the considered RCD patients (mostly children). Are there forms of RCD that cannot be cured with any changes to diet?

Thanks! This discussion has been really helpful!

[Anonym]

1 hour ago, RMJ said:

Is there anything in your diet that changed prior to the antibody increase?  Different brand of something, etc.?

I’m glad you’ll be getting another biopsy.  There are specific things that can be seen in a biopsy that indicate refractory celiac.  I hope they aren’t seen in yours!

I have thought of this but I havent been able to find any significant changes. All of my foods are labeled as "gluten free" and I live in the Nordics where there are _really_ strict laws around food labelling and inspections, so a mislabeled item or a mistake in the manufacturing process seems really unlikely, although possible.

[Posterboy]

2 hours ago, Anonym said:

Few questions popped into my mind:

1) Is there any evidence that other ingredients such as soy or maize could trigger the same transglutaminase response?

Anonym,

Corn has been shown to have a similar reaction in some Celiac's.

Here is some fairly recent research about it

Entitled "Maize prolamins (aka Corn) resistant to peptic-tryptic digestion maintain immune-recognition by IgA from some celiac disease patients

https://pubmed.ncbi.nlm.nih.gov/22298027/

Where they note quoting

"Results concur to indicate that relative abundance of these zeins, along with factors affecting their resistance to proteolysis, may be of paramount clinical relevance, and the use of maize in the formulation and preparation of gluten-free foods must be reevaluated in some cases of celiac disease."

The condition causing Pellagra (traditionally diagnosed in heavy Corn consumers) will often mimic Celiac disease.

Here is a nice overview article about it....

You can also search for Pellagra on Celiac.com and many threads will come up about it.....

I had originally thought I had developed Pellagra but I had only developed Pellagra Sine Pellagra instead.

This Posterboy blog post will explain the difference between Pellagra and Sine Pellagra and Beri Beri which often occurs in Celiac disease as well going undiagnosed in each case.

I hope this is helpful but it is not medical advice.

Good luck on your continued  journey!

Posterboy,

[plumbago]

@Anonym

I should have been more precise. What I should have said is that ttg-iga is often elevated in cases of diabetes, not (necessarily) refractory celiac disease. Apologies.

[plumbago]

12 hours ago, Anonym said:

Thank you for your answer!

I have a couple of counterpoints to that. I do not have medical education so I might have gotten some things wrong, but isnt the EMA IgA highly specific to gastro intestinal damage? At least in my country, these serology results (both tTG and EMA up ~10-fold) are enough to have a diagnosis to untreated celiac disease.

Further, at least the tTG has been in a stable range up just to 8-9 for the last ten years. Now that it has suddenly spiked my own reaction was to immediately think of refractory celiac disease.

Yes, EMA-IgA is highly specific to GI damage.

EMA stands for antiendomysial antibodies, which are antibodies produced by the body that attack the body's own tissue. When the EMA-IgA is positive, the patient almost certainly has celiac disease.

Second, it's quite likely I'm not understanding something. In your response to me (above), you said your "tTG has been in the stable range." But in your original post, you said

14 hours ago, Anonym said:

Despite a strict gluten free diet, my tTG IgA levels didnt normalize. However, a biopsy after two years of the original diagnosis confirmed that the healing had begun. The normal range for the utilized tTG IgA test is from 0.0 - 7.0 U/ml. My IgA hovered around 8-9 for the following 10 years, before finally in 2018 dipping below the limit at 6.9 U/ml. Not much was thought of this, as it was presumed to remain a little high due to the coincidental diabetes condition. Thus, the biopsy was never renewed.

Following this, the tTG IgA test was run again in early 2021. To my surpise, the result was 28 U/ml.

So, I'm not sure what to make of that difference. At any rate, you did understand that the ttg IGA can be high due to diabetes.

I hope you get to the bottom of it. Good luck!

Plumbago

Edited April 23, 2021 by plumbago

[Anonym]

17 hours ago, plumbago said:

Second, it's quite likely I'm not understanding something. In your response to me (above), you said your "tTG has been in the stable range." But in your original post, you said

The tTG was "stable" in the range from 6.9 to 9 U/ml for the years 2010-2018. Then there was a 3 year break from measuring it. Now, in early 2021, the tTG was 28 U/ml, and 2 months later 42 U/ml. The sudden spike from the "stable" range has lead me to believe that in cant be contributed to type 1 diabetes.

[plumbago]

1 minute ago, Anonym said:

The tTG was "stable" in the range from 6.9 to 9 U/ml for the years 2010-2018. Then there was a 3 year break from measuring it. Now, in early 2021, the tTG was 28 U/ml, and 2 months later 42 U/ml. The sudden spike from the "stable" range has lead me to believe that in cant be contributed to type 1 diabetes.

Maybe not. How well has your diabetes been controlled?

[Anonym]

Thanks for all the replies.

I will now start omitting oats and milk and maize/corn completely from my diet. I hope this would bring both the tTG and EMA tests down to normal range. If not, I think the next step will be steroids and other medication used for RCD. These are my own thoughts and actions. Will wait for the official diagnosis but I hope these actions would help, as there are atleast some scientific results backing them.

Would love to hear more if there are other ingredients that could cause these abnormal serology results. Further, any experiences if similar actions have helped others are always of interest.

 

[Anonym]

1 minute ago, plumbago said:

Maybe not. How well has your diabetes been controlled?

I would say well. My HbA1c has been in the range of 5.5 to 6.1 for the past 10 years.

[Anonym]

3 minutes ago, Anonym said:

I will now start omitting oats and milk and maize/corn completely from my diet.

 

Forgot to mention that I found some people mentioning in other conversations that soy or eggs could also be culprits for this. However, I cant of course omit everything from my diet. Would love to hear opinions regarding which ingredients (milk, soy, oats, maize, eggs, etc) are the most likely to cause inflammation and thus higher antibody levels?

[RMJ]

Unless your oats are labeled gluten free, they would be the most likely due to contamination.

I hope elimination of a few foods takes care of your antibody levels. Before starting steroids, I would think a biopsy, and if that is positive, perhaps a visit with a registered dietician skilled in celiac disease would be suggested.  First to be sure there is damage that needs to be healed, and second to have someone else do a thorough review of your diet for hidden gluten.

In your country, what is the limit for gluten allowed in foods labeled gluten free?  In the US it is 20ppm, but that isn’t low enough for me.  I have to only eat foods that are certified gluten free, which is less than 10ppm, or my antibody levels go up.

Is your household gluten free?  Could there be sources of contamination besides your food?

[Anonym]

4 minutes ago, RMJ said:

Unless your oats are labeled gluten free, they would be the most likely due to contamination.

I live in the EU so in my country is the level same 20ppm. The oats and all of the other products I use are either naturally gluten free or branded as such (meaning <20ppm). How do you differentiate <20ppm products from <10ppm?

My household is gluten free. I have checked everything including toothpaste and shampoo and so on. If this was any other year I would have considered the possibility of a mistake in restaurant etc. However, "luckily" I havent been in restaurants or eaten food prepared by others in 7 months.

There is an ingredient "Hydrogenated starch hydrolysate" in my toothpaste. However, I dont exactly eat it and I am not sure if could contain enough gluten to cause a reaction. Should I change my toothpaste?

[GFinDC]

1 hour ago, Anonym said:

I live in the EU so in my country is the level same 20ppm. The oats and all of the other products I use are either naturally gluten free or branded as such (meaning <20ppm). How do you differentiate <20ppm products from <10ppm?

My household is gluten free. I have checked everything including toothpaste and shampoo and so on. If this was any other year I would have considered the possibility of a mistake in restaurant etc. However, "luckily" I havent been in restaurants or eaten food prepared by others in 7 months.

There is an ingredient "Hydrogenated starch hydrolysate" in my toothpaste. However, I dont exactly eat it and I am not sure if could contain enough gluten to cause a reaction. Should I change my toothpaste?

Even gluten-free oats are a problem for some celiacs.  Oat gluten can cause the same immune response for about 10% of celiacs as rye, barley, and wheat does..

[RMJ]

In the US there is an organization that “certifies” foods as being gluten free.  To differentiate these (<10ppm) from regular gluten free (<20ppm) there is a special symbol on the packaging.

Hydrogenated starch hydrolysate is highly processed but MIGHT be manufactured from wheat starch and thus MIGHT have small amounts of gluten.  It also might be manufactured from corn starch and be gluten free. The FDA estimates that hydrogenated starch hydrolysate from wheat starch could have up to 40mg/kg of gluten (number is from their guidance on labeling of gluten in drug products). Guessing that there is maybe a gram in a “serving” of toothpaste that would be 0.04mg, a tiny amount.

[Anonym]

Thanks!

Is it common that celiac gets "worse". Meaning, according to the serology results and biopsies from early 2010s, my body first responded well to a "normal" gluten free diet. Is it possible, that the condition has since gotten worse so that something like milk protein and avenin from oats trigger the same reaction? Is it possible that it even continues to get worse? I guess everything is possible but to put it another way is this kind of development common in celiac patients?

[plumbago]

I am not an expert at all on celiac disease, and know just enough to manage my own condition. According to my book Recognizing Celiac Disase: signs, symptoms, associated disorders and complications, refractory "sprue" (celiac disease) is not responsive to a gluten-free diet. But yours was, at least for a number of years, right?

Just so I understand your current situation, you are not having any symptoms? (Question: did you have signs or symptoms prior to being diagnosed with celiac disease, if you or a parent can remember?) And the only current sign that you think may pointing to refractory celiac disease is the elevated ttg ig and elevated ema iga?

Me in your position, I am not sure I'd start steroids without either an expert opinion from a good doctor or GI specialist or another colonoscopy (from your OP, I see you will have another biopsy in 4 weeks). Just to cover all my bases, I'd also take a double and triple look at the tests and maybe the lab just to make sure there were no errors either in the lab or in documentation.

 

ADD: My diagnostic test reference book is limited on the celiac disease antibodies, but it does say, severe lactose intolerance can cause elevated gliadin antibodies. You didn't mention those (if I recall correctly), and if you had severe lactose intolerance, I can only imagine you'd have known! One other thing, though I never eat it, I only recently discovered or more likely re-discovered that couscous is not gluten free. That is not something that, me personally, I would have known enough to investigate before eating when I was 26! You sound mature and knowledgeable, but I only mention this in the event that there may be things you are still consuming (long shot: beer?) that are not gluten-free.

Edited April 25, 2021 by plumbago

[Anonym]

34 minutes ago, plumbago said:

I am not an expert at all on celiac disease, and know just enough to manage my own condition. According to my book Recognizing Celiac Disase: signs, symptoms, associated disorders and complications, refractory "sprue" (celiac disease) is not responsive to a gluten-free diet. But yours was, at least for a number of years, right?

Just so I understand your current situation, you are not having any symptoms? (Question: did you have signs or symptoms prior to being diagnosed with celiac disease, if you or a parent can remember?) And the only current sign that you think may pointing to refractory celiac disease is the elevated ttg ig and elevated ema iga?

Me in your position, I am not sure I'd start steroids without either an expert opinion from a good doctor or GI specialist or another colonoscopy (from your OP, I see you will have another biopsy in 4 weeks). Just to cover all my bases, I'd also take a double and triple look at the tests and maybe the lab just to make sure there were no errors either in the lab or in documentation.

 

ADD: My diagnostic test reference book is limited on the celiac disease antibodies, but it does say, severe lactose intolerance can cause elevated gliadin antibodies. You didn't mention those (if I recall correctly), and if you had severe lactose intolerance, I can only imagine you'd have known! One other thing, though I never eat it, I only recently discovered or more likely re-discovered that couscous is not gluten free. That is not something that, me personally, I would have known enough to investigate before eating when I was 26! You sound mature and knowledgeable, but I only mention this in the event that there may be things you are still consuming (long shot: beer?) that are not gluten-free.

To the first question, according to the biopsy in the early 2010s and the yearly serology results after that I was responsive at least for 8 years. I dont have the information about the exact Marsh level from the biopsy, but the doctors back then assured me I was healing.

To the second, I did not have and do not currently have any symptoms. I had low hemoglobin levels when I was young but not anything more than that. Despite not having any symptoms the celiac disease was confirmed with a biopsy (I was tested only since the celiac disease is prominent in my family / extended family). Currently, the ttg iga (test run two times in two different labs) and ema iga (test run once) are the signs currently pointing to a refractory celiac disease, since the chance of wrongly digesting gluten can pretty much be ruled out. I am going to have a biopsy in a next month to confirm the damage in the glut.

Thank you for all of the tips! I assure you, I am one of the diligent gluten free persons around there 😀 I have had some diet mistakes when I first was diagnosed, but after that eating gluten free has become a sort of a passion / obsession for me, and I have read and googled pretty much every ingredient I consume. I will try to document the upcoming journey here, so that my experiences or diet experiments could be of help to others finding themselves in a similar situation.

[plumbago]

39 minutes ago, Anonym said:

To the first question, according to the biopsy in the early 2010s and the yearly serology results after that I was responsive at least for 8 years. I dont have the information about the exact Marsh level from the biopsy, but the doctors back then assured me I was healing.

To the second, I did not have and do not currently have any symptoms. I had low hemoglobin levels when I was young but not anything more than that. Despite not having any symptoms the celiac disease was confirmed with a biopsy (I was tested only since the celiac disease is prominent in my family / extended family). Currently, the ttg iga (test run two times in two different labs) and ema iga (test run once) are the signs currently pointing to a refractory celiac disease, since the chance of wrongly digesting gluten can pretty much be ruled out. I am going to have a biopsy in a next month to confirm the damage in the glut.

Thank you for all of the tips! I assure you, I am one of the diligent gluten free persons around there 😀 I have had some diet mistakes when I first was diagnosed, but after that eating gluten free has become a sort of a passion / obsession for me, and I have read and googled pretty much every ingredient I consume. I will try to document the upcoming journey here, so that my experiences or diet experiments could be of help to others finding themselves in a similar situation.

Great, please do let us know. And yes, you certainly sound more diligent than I was, at your age. Last (ish) question - are your total IGA levels normal? Apologies if this has already been addressed.

[Anonym]

16 minutes ago, plumbago said:

Great, please do let us know. And yes, you certainly sound more diligent than I was, at your age. Last (ish) question - are your total IGA levels normal? Apologies if this has already been addressed.

The serology results show that they are in the middle of the "normal" range. I have an appointment next week where a doctor explains these results and what they could mean in more detail.