Celiac Disease, Lymphocytic colitis and Bowel rupture

[MoniqueCham]

I was diagnosed with celiac disease 40 years ago and lymphocytic colitis 20 years ago along with refractory celiac disease affecting mid jejunum to mid ileum (diagnosed using a capsule endoscopy). My antibodies to tissue transglutaminase were normal on a strict gluten free diet. Both the lymphocytic colitis and the refractory celiac disease responded well to entocort. I have a number of autoimmune conditions including systemic granuloma annulaire (a skin condition) which was treated with methotrexate. I was on a low dose of methotrexate (15 mg once a week with folic acid every day when not taking methotrexate). In 5 months my sigmoid colon ruptured. Pathology reports show that I had significant necrosis of my sigmoid bowel due to no known cause and a large hole in the bowel. My surgeons felt that the methotrexate may have caused the damage and rupture to my bowel (1 in a million chance). My question is has anyone experienced similar issues with methotrexate given that the integrity of our intestines may be compromised in celiac disease?

[trents]

Welcome to the celiac.com community @MoniqueCham!

Celiac disease damages the villous lining of the small bowel but, as far as I know, doesn't affect the underlying smooth muscle tissue of the bowel.

[Scott Adams]

I’m so sorry you’ve been through all of that — that’s an incredibly complex history. While methotrexate is widely used at low weekly doses for autoimmune conditions, it can, in rare cases, cause serious gastrointestinal side effects, including ulceration, mucosal injury, or even perforation. That said, a spontaneous sigmoid rupture from methotrexate at 15 mg weekly is extremely uncommon. In people with celiac disease — especially refractory celiac — there can already be underlying intestinal inflammation or altered mucosal integrity, which might theoretically increase vulnerability, but there isn’t strong published evidence clearly linking stable celiac disease to a markedly higher risk of methotrexate-related bowel perforation. Other factors such as concurrent inflammation, vascular compromise, infection, steroid use, or microscopic colitis may also contribute. It would be reasonable to review the case with a gastroenterologist familiar with refractory celiac and possibly a rheumatologist, and to report the event as a potential adverse drug reaction. I’d also be very interested to hear if others in the community have had similar experiences.

[MoniqueCham]

Thanks for your reply Scott! A long time ago I realized I didn’t fit neatly into uncomplicated celiac disease. Over the years I’ve been diagnosed and treated for SIBO, pancreatic insufficiency and diagnosed with Stage 2 liver fibrosis. I think all the complications occurred because of the refractory celiac disease. When I hit menopause my gut issues seemed to calm down and because I was stable I made the mistake of not following up with my gastroenterologist. Then other autoimmune problems flared and I tried the methotrexate. It worked like a charm for my skin condition… then my sigmoid colon ruptured. Strange but my autoimmune skin condition remains in remission after 6 months off the medication. We have a very long waiting list to get back into see my GI doctor… I was an emergency referral but am still waiting 6 months after the perforation. I need more surgery to fix a fistula that has formed and to reconnect my colon… I have a colostomy at present. I became a dietitian who specializes in bowel diseases but have never met anyone who’s had so many complications with celiac disease. I have a brother and son who also have been diagnosed. My mother had 4 autoimmune diseases including a vasculitis that eventually resulted in her death and it was my father who had the HLA DQ2 gene. Think I inherited some tendencies from each of them. Thanks again for your response… it feels a little lonely dealing with GI issues when I work so hard to remain gluten free. 
 

[knitty kitty]

Welcome to the forum, @MoniqueCham,

What a challenging journey you've had!  Like you, I studied nutrition, but I earned a degree in Microbiology because I wanted to understand what essential vitamins and minerals were doing inside our bodies.  

I've come across some information that may be of interest to you.  I'll post links below.  On my journey, I suffered from malnutrition due to the malabsorption of Celiac disease.  I regained my health by supplementing with essential vitamins, especially Thiamine B1.  Thiamine is needed by every cell, so a low level of thiamine can cause many problems over time.  I was put on some medications that aggravated my thiamine deficiency. 

Many medications can cause interactions with vitamins resulting in deficiencies.

Methotrexate causes folate deficiency, but can also cause thiamine deficiency because folate and thiamine share some of the same cellular transporters.  

Notes on Folate Carriers, Anti-Folate Medications, and Thiamine Deficiency

https://hormonesmatter.com/notes-on-folate-carriers-anti-folate-medications-and-thiamine-deficiency/

Thiamine deficiency can affect the health of the digestive tract.  Thiamine helps regulate the intestinal microbiome, and keeps SIBO in check.  

Thiamine, gastrointestinal beriberi and acetylcholine signaling

https://pmc.ncbi.nlm.nih.gov/articles/PMC12014454/

Thiamine deficiency aggravates experimental colitis in mice by promoting glycolytic reprogramming in macrophages

https://pubmed.ncbi.nlm.nih.gov/39890689/

Other organs can be affected by thiamine insufficiency.  The thyroid, gallbladder, liver and pancreas can be affected by low thiamine.

High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition

https://pmc.ncbi.nlm.nih.gov/articles/PMC7988776/

Thankfully, I found that Thiamine in the form Benfotiamine can improve gastrointestinal dysfunction, as well improve liver function, and thyroid and pancreas health.  

Benfotiamine can improve harm done by Methotrexate...

Protective effect of benfotiamine on methotrexate induced gastric damage in rats

https://pubmed.ncbi.nlm.nih.gov/33325753/

I was deficient in other vitamins.  I had skin issues that improved with niacin.  Perhaps niacin can help your skin problem if it comes back.  

Response of generalized granuloma annulare to high-dose niacinamide

https://pubmed.ncbi.nlm.nih.gov/6225398/

I'm very curious as to what you did to correct your nutritional deficiencies caused by refractory Celiac disease.  

Refractory Celiac Disease: What the Gastroenterologist Should Know

https://pmc.ncbi.nlm.nih.gov/articles/PMC11477276/

Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis

https://pubmed.ncbi.nlm.nih.gov/28545781/

Hope this is helpful!

[Scott Adams]

19 hours ago, MoniqueCham said:

Thanks for your reply Scott! A long time ago I realized I didn’t fit neatly into uncomplicated celiac disease. Over the years I’ve been diagnosed and treated for SIBO, pancreatic insufficiency and diagnosed with Stage 2 liver fibrosis. I think all the complications occurred because of the refractory celiac disease. When I hit menopause my gut issues seemed to calm down and because I was stable I made the mistake of not following up with my gastroenterologist. Then other autoimmune problems flared and I tried the methotrexate. It worked like a charm for my skin condition… then my sigmoid colon ruptured. Strange but my autoimmune skin condition remains in remission after 6 months off the medication. We have a very long waiting list to get back into see my GI doctor… I was an emergency referral but am still waiting 6 months after the perforation. I need more surgery to fix a fistula that has formed and to reconnect my colon… I have a colostomy at present. I became a dietitian who specializes in bowel diseases but have never met anyone who’s had so many complications with celiac disease. I have a brother and son who also have been diagnosed. My mother had 4 autoimmune diseases including a vasculitis that eventually resulted in her death and it was my father who had the HLA DQ2 gene. Think I inherited some tendencies from each of them. Thanks again for your response… it feels a little lonely dealing with GI issues when I work so hard to remain gluten free. 
 

This is a general article that may be helpful: