Negative Gene test, villious atrophy, negative biopsy

[Kav]

Hello friends,

I am a 44 year old female. i have been suffering with digestive issues since 2019. prior to that no issues. i started having bloating, thin stools, gas, sleep issues. H. pylori breath test has been negative on multiple tests. first endoscopy showed hiatal hernia with some redness in stomach lining (reactive gastropathy of unknown cause). I was given antibiotics and PPI. felt better. then again same issues. was given amitriptyline and FODMAP diet. I stopped eating so many things. no improvement. slowly joint pain, bloating, sleep issues, anxiety all got worse. colonoscopy showed 2 ulcers in terminal ileum but negative for Crohns. then suddenly after an episode of joint pain, ANA test became positive (was negative before that). All autoimmune work up was negative for lupus, sjrogren, arthritis, etc. Then after another round of SIBO antibiotics, complete elimination diet (per food intolerance test), I started introducing some foods again (including gluten). Also, I  stopped antidepressant slowly. I had terrible anxiety, sleep jerks/ hypnic jerks, joint pain, reflux and was in miserable state. In Feb 2020, another round of endoscopy showed some intra epilitheal lymphocytes. Colonoscopy showed non specific inflammation. Video capsule endoscopy showed many small ulcers all over small intestine. TTG test for celiac was negative. but i had barely started eating gluten for a month (after being Gluten free for almost a year).  So I am not sure if that test was reliable. SO the GI diagnosed me with Crohns and gave me budesonide (gut specific steroids). Also TB preventive medication (in anticipation of starting long term immunosuppressive medications). Repeat endoscopy showed villious blunting in duodenum, Jejunum and colonoscopy showed villious blunting in terminal ileum too. They sent blood work for gene testing but it shows negative for both genes (HLA DQ2 & HLA DQ8). The GI started me on Humira for Crohns disease in October 2021 after  a round og preventiveTB meds, gene test and MRI.

I was on a very restrictive diet due to multiple food intolerances (no diarreha or bloody stool. But a lot of Bloating, gas, sleep issues, anxiety). GI did repeat endoscopy and colonoscopy in May 2022. It still showed villious blunting in duodenum and also in terminal ileum. But my GI thinks its not celiac. I asked what could cause villious blunting. She said even malnutirion and malabsorption can cause villious blunting. I have had 5 endoscopies and all of them show reactive gastropathy in stomach lining via biopsy. 3 endoscopies and 2 colonoscopies have shown villious blunting but biopsy negative for celiac, gene testing negative for celiac. i am so confused.

Can anyone please guide me if it could still be celiac disease? Villious blunting makes no sense to me. But gene testing is negative.

[trents]

You say, "3 endoscopies and 2 colonoscopies have shown villious blunting but biopsy negative for celiac".

But if there is villous blunting how can that be considered negative for celiac disease? Villous blunting is what defines celiac disease. That is what they look for when when celiac disease is suspected and villous blunting is the hallmark symptom of celiac disease. Now having said that, Crohn's can also cause villous blunting as can the dairy protein casein for some celiacs. There are some medications that can cause villous blunting as well. You might want to google, "What can cause villous blunting besides celiac disease?"

"She said even malnutirion and malabsorption can cause villious blunting." Wrong! malnutrition and malabsorption are caused by villi blunting, not the cause of villi blunting.

Now, you may have Crohn's disease as well and that is statistically more common in the celiac population than it is in the general population but I certainly would not abandon the notion of celiac disease. And concerning the genes, there is a lot we don't know about the genetics of celiac disease/gluten sensitivity and on this forum we have had reports of people with celiac disease who didn't have those two genes. Researchers are beginning to suspect that DQ2 and DQ8 may not be the only ones involved in celiac disease. 

[knitty kitty]

Egads!  I don't understand why your doctors don't think it's Celiac from the biopsies!  

There are other genes for Celiac Disease than just those two.  

This article offers information on genetic variations for Celiac Disease based on geographic location....

"Celiac disease: Prevalence, diagnosis, pathogenesis and treatment"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496881/

And this one...

Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807782/

 

Your doctors should run complete panels of Celiac tests after gluten challenge (yuk!)

https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/digestive-diseases/celiac-disease-health-care-professionals

 

PPI's and SSRI's and dairy can cause continuing inflammation in Celiac people on a gluten free diet.

Get checked for vitamin and mineral deficiencies! 

Antibiotics and SIBO can deplete your Thiamine Vitamin B1!  Gastrointestinal Beriberi causes symptoms similar to yours and those in Celiac Disease.  You can have Gastrointestinal Beriberi without having Celiac Disease.  Thiamine deficiency can damage the small intestine.  High dose Thiamine supplementation for months can treat it.  

"Gastrointestinal Beriberi Mimicking a Surgical Emergency in a Well-Nourished Patient: A Case Report"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978589/

 

If nothing else, have your biopsy samples read by another lab that's familiar with Celiac Disease.

Best wishes to you.  Keep us posted on your progress!

[Scott Adams]

How did you feel when you were gluten-free? Did your symptoms improve? If so, perhaps just go gluten-free? You don't need a doctor to allow you to go gluten-free, but it is a good idea to let them know if you make this decision. At the very least it appears you may have celiac disease or non-celiac gluten sensitivity.

[miguel54b]

I am very sensitive to gluten, I was at the end of my rope when finally figured out. This is the result of my genes test. 

Interpretation of HLA-DQ Testing:  Although you do not possess the main HLA-DQB1 genes predisposing to celiac disease (HLA-DQ2 or HLA-DQ8), HLA gene analysis reveals that you have two copies of a gene that predisposes to gluten sensitivity, in your case HLA-DQB1*0202 and HLA-DQB1*0501. While most individuals with celiac disease possess the HLA-DQ2*0201 subtype, the possibility of developing celiac disease with other DQ2 subtypes still exists. Having two copies of a gluten sensitive gene means that each of your parents and all of your children (if you have them) will possess at least one copy of the gene. Two copies also means there is an even stronger predisposition to gluten sensitivity than having one gene, and the resultant immunologic gluten sensitivity may be more severe. This test was developed and its performance characteristics determined by the American Red Cross - Northeast Division. It has not been cleared or approved by the U.S. Food and Drug Administration. EnteroLab did my testing, research them.

[Scott Adams]

@miguel54b I know EnteroLab well, and know the owner Dr. Kenneth Fine...he has written some articles for us:

https://www.celiac.com/profile/81334-kenneth-fine-md/

Given your symptoms and genetic results I think you've found your answer!

[Kav]

On 9/15/2022 at 9:06 PM, miguel54b said:

I am very sensitive to gluten, I was at the end of my rope when finally figured out. This is the result of my genes test. 

Interpretation of HLA-DQ Testing:  Although you do not possess the main HLA-DQB1 genes predisposing to celiac disease (HLA-DQ2 or HLA-DQ8), HLA gene analysis reveals that you have two copies of a gene that predisposes to gluten sensitivity, in your case HLA-DQB1*0202 and HLA-DQB1*0501. While most individuals with celiac disease possess the HLA-DQ2*0201 subtype, the possibility of developing celiac disease with other DQ2 subtypes still exists. Having two copies of a gluten sensitive gene means that each of your parents and all of your children (if you have them) will possess at least one copy of the gene. Two copies also means there is an even stronger predisposition to gluten sensitivity than having one gene, and the resultant immunologic gluten sensitivity may be more severe. This test was developed and its performance characteristics determined by the American Red Cross - Northeast Division. It has not been cleared or approved by the U.S. Food and Drug Administration. EnteroLab did my testing, research them.

thank you so much for this this explanation. Can we contact the lab directly for testing or do we have to go through the Gastroenterologist?

 

[Kav]

On 9/15/2022 at 6:06 PM, miguel54b said:

I am very sensitive to gluten, I was at the end of my rope when finally figured out. This is the result of my genes test. 

Interpretation of HLA-DQ Testing:  Although you do not possess the main HLA-DQB1 genes predisposing to celiac disease (HLA-DQ2 or HLA-DQ8), HLA gene analysis reveals that you have two copies of a gene that predisposes to gluten sensitivity, in your case HLA-DQB1*0202 and HLA-DQB1*0501. While most individuals with celiac disease possess the HLA-DQ2*0201 subtype, the possibility of developing celiac disease with other DQ2 subtypes still exists. Having two copies of a gluten sensitive gene means that each of your parents and all of your children (if you have them) will possess at least one copy of the gene. Two copies also means there is an even stronger predisposition to gluten sensitivity than having one gene, and the resultant immunologic gluten sensitivity may be more severe. This test was developed and its performance characteristics determined by the American Red Cross - Northeast Division. It has not been cleared or approved by the U.S. Food and Drug Administration. EnteroLab did my testing, research them.

thank you so much for this this explanation. Can we contact the lab directly for testing or do we have to go through the Gastroenterologist? i checked the Enterolab website and saw only stool test. But I have been gluten free for a long time so stool test may not show anything.

[trents]

58 minutes ago, Kav said:

thank you so much for this this explanation. Can we contact the lab directly for testing or do we have to go through the Gastroenterologist?

 

What testing do you refer to? Since you have been gluten free you would have to go back to eating regular amounts of gluten (equivalent of two slices of wheat bread daily) for 6-8 weeks if you want to get retested for serum antibodies. If you do this I would certainly request a "full celiac panel" and not just the tTG-IGA. If you are referring to a repeat of the endoscopy/biopsy you would need to be eating regular amounts of gluten for two weeks.

[Kav]

53 minutes ago, trents said:

What testing do you refer to? Since you have been gluten free you would have to go back to eating regular amounts of gluten (equivalent of two slices of wheat bread daily) for 6-8 weeks if you want to get retested for serum antibodies. If you do this I would certainly request a "full celiac panel" and not just the tTG-IGA. If you are referring to a repeat of the endoscopy/biopsy you would need to be eating regular amounts of gluten for two weeks.

I got tested all the times via biopsy. I was gluten free for 6 months, then  eating 2 slices of bread for a month but stopped eating due to reflux symptoms. then ate 2 slices of bread for 5 days (as per GI instructions). Second time went to a different GI and she said to eat 2 slices of bread for 5 days before endoscopy.

The most recent time, I was strictly gluten free for over a year. But started eating wheat for more than a 6 weeks before endoscopy/colonoscopy. all three times the GI comments said "localized duodenal flattening" and even in terminal ileum "localized visible flattening". But biopsy showed everything normal, no celiac. 

[trents]

So, you're wanting the serum antibody testing this time around, correct?

[Kav]

25 minutes ago, trents said:

So, you're wanting the serum antibody testing this time around, correct?

my GI said negative biopsy and negative gene test means no celiac. she doesnt think i need TTg test.  my old GI did anti ttg test which was negative (but i had not been eating gluten at that time, so that test was not a good marker). I have MRI of small intestines in first week of October, so I started eating wheat again in September. But i dont know if eating wheat will affect MRI. I dont know what other test I can ask my GI to run. any advice will be helpful in term of testing.

[trents]

This might be helpful: https://celiac.org/about-celiac-disease/screening-and-diagnosis/screening/

I would ask for:

1. Total IGA

2. tTG-IGA

3. Endomysial IGA

4. Deamidated gliadin peptide (DGP IgA and IgG)

[miguel54b]

I did the testing just to please my family that did not wanted to believe all I was saying. For me, to go gluten free and start getting better from all my medical problems (counted 24) is enough proof that I have a problem with gluten. I even have vision 20/20 now, I used to wear glasses and have difficulty driving at night (I got owl vision now).

[miguel54b]

On 9/16/2022 at 10:30 PM, Kav said:

thank you so much for this this explanation. Can we contact the lab directly for testing or do we have to go through the Gastroenterologist?

 

I paid of my own pocket, I got taken for crazy by doctors. 

[Scott Adams]

7 minutes ago, miguel54b said:

I did the testing just to please my family that did not wanted to believe all I was saying. For me, to go gluten free and start getting better from all my medical problems (counted 24) is enough proof that I have a problem with gluten. I even have vision 20/20 now, I used to wear glasses and have difficulty driving at night (I got owl vision now).

The vision improvement was also an unexpected side effect when I went gluten-free over 25 years ago. I also wore classes at the time, and was able to give them up for almost 20 years.