Partial Positive Biopsy/Negative Serology - is celiac still possible?

[gameboy68]

Hi Folx,

I have had GI issues for a while, but more recently (~2 yr), I’ve had increased issues in response to gluten- it’s gotten to the point where I’m not comfortable driving after gluten because of how exhausted and brain fogged I get. 

Some symptoms I have when i eat gluten are: 

-severe, painful bloating (stomach is very bloated but hard and pain feels like it is sharp and ripping from the center)

-diarrhea/constipation/vomiting

-rashes

-facial flushing

-extreme fatigue & brain fog

- nausea

-joint/bone pain

-it can also trigger my migraines

2 months ago I had an endoscopy and colonoscopy for other reasons. I was almost completely (at most gluten 1x/week) in the months leading up to it. I was also still on my PPI until the day before (which I know can cloud results) per the prep instructions. The GI I’m seeing isn’t the best [forgot to check for what he did the procedure for (after 6+ months of waiting for a slot)].

 GI took a biopsy of my duodenum which showed “Small bowel mucosa with increased intraepithelial lymphocytes”. The notes about it say “intact villous architecture with increased intraepithelial lymphocytes has a broad differential which includes partially treated/clinically latent celiac disease, infectious etiologies, NSAID or other medication-type injuries, collagen vascular disease, inflammatory bowel disease, and a variety of allergic-type/immune disorders as well as non-specific lymphocytic enteritis.” I also had mild chronic gastritis in my stomach. 

Doc ordered 3 blood tests. He told me it didn’t matter if I ate gluten before the tests, but I tried to do a gluten challenge 5 weeks before (having one meal w gluten at night). Results were: 
1. Gliadin Ab, IgG and IgA: 4 
2. Transglutaminase IgA, IgG Abs: <2
3. IgA: 174

Not sure if relevant, but here are some other blood tests I recently had:
1. Vitamin D 25 Hydroxy: 22.6
2. Vitamin B12: 195
3. AST/ALT: 10/6
4. Sodium: 130
5. Potassium: 3.5
6. CO2: 20
7. MCV: 79

TLDR: Biopsy indicated potential partially treated celiac (while on gluten-free free diet), serology was negative.

I am planning to continue a gluten-free free diet regardless for comfort, but I’m wondering if it is still possible for it to be celiac/if anyone else has had a similar experience/if I should be looking into something else. Thanks. 

[trents]

Welcome to the forum, @gameboy68!

The lab numbers you gave are not helpful to us because you did not include the reference ranges for negative vs. positive. Especially for the celiac antibody tests this is critical info since there are no industry standards. Each lab develops their own tests and uses custom reference ranges.

[gameboy68]

Thank you! 

Below are the reference ranges for my lab:

• Gliadin Ab, IgG and IgA: Reference Range = below <20 Units | My value: 4
• Transglutaminase IgA, IgG Abs: Reference Range = below <4 U/ml | My value: <2
• IgA: Reference Range = 70-400 | My value: 174

 

• Vitamin D 25 Hydroxy: Reference Range = 31-80 | My value: 22.6
• Vitamin B12: Reference Range = 232-1245 | My value: 195
• AST: Reference Range = 13-35 U/L | My value: 10
• ALT: Reference Range = 7-38 U/L | My Value: 6
• Sodium: Reference Range = 136-144 mmol/L | My value: 130
• Potassium: Reference Range = 3.7-5.1 mmol/L | My value: 3.5
• CO2: Reference Range = 22-30 mmol/L | My value: 20
• MCV: Reference Range = 80-100 | My value: 79

[plumbago]

@gameboy68

 

First, it looks like you do indeed have celiac disease, and a follow up with a gastroenterologist would seem to be in order.

Many on these boards will draw your attention to the B12 and D3 levels. While those are important (you may have macrocytic anemia, often caused by low B12), what strikes me is your low sodium level. Your potassium is low, too, but for me, while yes, concerning, not as concerning as that low sodium. You need to follow up with your primary care provider about those two electrolytes. Often, if people are on certain blood pressure medications, those two numbers (those of sodium and potassium) bear monitoring. [Going back to read your OP, it may be loss of content from the GI tract, but I'm just speculating.] A good doc will repeat the labs (in the second batch) to verify that indeed they are accurate, and it's not lab or collection error. If they repeat, then your doctor will drill down to the cause. Please do follow up.

Plumbago

Edited April 16, 2024 by plumbago

[trents]

Your symptoms definitely align with celiac disease and your endoscopy/biopsy certainly points to possible celiac disease. However, your celiac antibody testing does not. This could very likely be due to inadequate gluten consumption during the weeks/months leading up to the blood draw. Guidelines for the gluten challenge are evolving but the current trend is pointing to former challenge guidelines being too conservative, i.e. not enough gluten exposure leading up to testing. More recent challenge guidelines are calling for daily consumption of 10g of gluten (an amount found in about 4-6 pieces of regular bread) for at least 2 weeks and preferably longer leading up to the day of the blood draw or the endoscopy/biopsy. 

It is also possible you have NCGS (Non Celiac Gluten Sensitivity) which shares many of the same symptoms with celiac disease but for which there is no test. celiac disease must first be ruled out. NCGS is 10x more common than celiac disease and both require a serious lifelong commitment to gluten-free eating. Some experts feel NCGS can be a precursor to the development of celiac disease. I mention this because of your biopsy report. I'm not a betting man but if I were, I'd put my money on a diagnosis of celiac disease in your case, given all the overall evidence.

[plumbago]

Thanks for clarifying that, Trents. In my response, I misread the celiac panel results, totally! So I retract that first sentence which was based on the misread of the antibody tests. But @gameboy68, as Trents says, the endoscopy/biopsy results do likely point to  (or align with) celiac disease.

[gameboy68]

Thank you for your insight @plumbago @trents !

I am taking supplements for B12 and D3 now, but after retest, I am still low. I am hoping to be approved for B12 shots soon. My Neurologist mentioned that the B12 deficiency could be due to malabsorption and thought that the supplements would not work because of it; she said that is a common issue with Celiac. I have tested low on sodium a few times before (132 and 133), but my doctor hasn't addressed it nor my potassium being low. 

As for the gluten challenge, I definitely was not eating as much gluten as @trents listed each day. I was hesitant to do the challenge at all because my GI said that I did not need to/it did not matter, so I did it more minimally. 

I am not sure where to go from here in terms of testing/diagnosis. If anyone has been in a similar situation/has advice, I would appreciate it. Thanks!

 

[plumbago]

The supplements should work with time on a gluten free diet.

I would be concerned about that sodium level. From the other results you posted, the trend seems to be downward. Please do follow up about that. It's not normal to walk around constantly with a sodium of 130.

As for diagnosis, you could go back on a full gluten containing diet and blood test again.

You could supplement the biopsy with a genetic test (expensive). A positive genetic test, combined with the biopsy, while not a slam dunk, does point to celiac disease.

BTW, do you take a lot of NSAIDs?

Edited April 17, 2024 by plumbago

[gameboy68]

@plumbago Thanks again! I do not take any NSAIDs. I appreciate your advice, and I will follow up re. sodium with my provider. 

 

 

[trents]

How many mg or IU of B12 are you taking daily? One way to address malabsorption inefficiency is to just take more of the supplement. For example, if your absorption efficiency is 25% of normal, you could theoretically, uptake the same amount as someone with 100% absorption efficiency by taking four times as much. Are you also anemic by some chance? B12 uptake is necessary to iron uptake. You needn't worry about overdosing on the B vitamins. The common forms are all water soluble and we just pee out any excess. They are not toxic in high doses.

Edited April 17, 2024 by trents

[gameboy68]

I am taking 1000 mcg of B12 each morning @trents. I also eat a lot of B12 in my diet which is why I was surprised it was so low. My OBGYN (who ordered the test) said that most of her patients are at 900+ for B12, which also shocked me! I have not been tested for iron deficiency/anemia, but I will look into that.

[trents]

1000 mcg of B12 supplementation is peanuts. You should be taking 5000 mcg. and you should be taking a high potency B-complex to boot. The B-vitamins are seldom found in isolated deficiencies but are usually deficient as a group. If you live near a Costco, their Nature Made product line is a good choice and if gluten free will be labeled as such. Most of them are. You should also be taking 5000IU of D3 daily, zinc and about 400 mg. of magnesium glycinate daily. Vitamin and mineral deficiencies are part and parcel of having long term, undiagnosed celiac disease because of the absorption impairment caused by the damage to the villous lining of the small bowel, where all of our nutrition is absorbed  from what we eat. And by the way, the common blood tests for vitamin deficiencies do not necessarily mean much as they only reflect how much is circulating in the body, not how much is being assimilated by the cells and tissues. Symptoms are probably a better indicator.