Mast Cells in Gastrointestinal Disease

[Gloria]

Interesting article on mast cells published in December, 2010:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033552/

Mast cells can be found throughout normal connective tissue, often next to blood vessels or nerves or beneath epithelial surfaces, where these cells are exposed to the environment via the respiratory and gastrointestinal tracts. For example, mast cells located next to venules could influence the entry of foreign substances due to their fast response. Histamine and lipid mediators also affect vascular permeability, enabling a local influx of plasma proteins such as complement and immunoglobulins.

Is this saying that mast cells affect vascular permeability and therefore allow proteins to enter the bloodstream, similar to the Leaky Gut Syndrome?

Elsewhere in the article, they mention using an elimination diet. Oddly, nothing is mentioned about MC, though Irritable Bowel Syndrome is mentioned.

Gloria

[jme22]

So funny you found this Gloria. It was co-authored by my gastro (Dr. Doman). He and I discussed the article many times as it was being developed. Without his knowledge of mast cells and GI issues I'm certain I would still be carrying around a diagnosis of IBS rather than ME. He's pretty much my hero, which we can't often say about physicians!

Julie

[tex]

Is this saying that mast cells affect vascular permeability and therefore allow proteins to enter the bloodstream, similar to the Leaky Gut Syndrome?

Yes. Definitely. This is why mast cell issues in the intestines tend to cause systemic symptoms, (respiratory, cardiac, skin issues, etc.).

Oddly, nothing is mentioned about MC, though Irritable Bowel Syndrome is mentioned.

Remember, mastocytic enterocolitis is a form of MC, (that's one of the reasons why it's listed in the subtitle of this discussion board).

Several studies have noted an increased number of mast cells in the mucosa of patients with gastrointestinal diseases such as irritable bowel syndrome, mastocytic enterocolitis, and systemic mastocytosis.

Excellent article, by the way - thanks for the link.

Tex

[Gloria]

Julie,

You are so lucky to have Dr. Doman as your GI. I brought a paper to my GI over a year ago on Mastocytic Enterocolitis and he was clueless. I asked him to talk to one of the doctors who co-authored the paper because he knew him. When I didn't hear from him after a month, I called the office and it was clear that he never followed up on it. That's when I gave up on him. I get my Entocort prescription from him (I'm stockpiling it for when I'm on Medicare) and that's it.

Tex,

Isn't it possible that Leaky Gut Syndrome is caused by mastocytosis?

Applying this personally, I'm postulating that one explanation for my numerous intolerances is that I had undiagnosed mastocytosis for so long. I was Dx'd with MC within 6 months of the obvious symptoms and, after finding this board, went GF shortly thereafter. One month later, I was EF, DF, SF, and YF and have remained so for the past four years. I had mouth sores all along and didn't understand why.

I didn't consider that I might have mastocytosis until Mary Beth told me she suspected I had it last year. I didn't have the symptoms that Faithberry and Mary Beth described - only mouth sores. After I read the list of high-histamine foods, however, I realized I reacted to almost every one of them. Once I focused primarily on getting rid of my mouth sores, I began getting better.

It's understandable that I can't eat many low-histamine foods if mastocytosis allowed the proteins from them to enter my bloodstream. I have a feeling that the reason I'm able to eat corn and quinoa is because I didn't eat either for the three years that I was ingesting high-histamine foods. I wonder if this explains why I can't eat any root vegetables or squash?

I continue to be unable to eat fruits, even low-histamine ones, so I likely have fructose intolerance.

What does my culinary future look like if these foods are not irritants, but intolerances? Will my immune system eventually stop reacting to them?

Gloria

[tex]

Isn't it possible that Leaky Gut Syndrome is caused by mastocytosis?

I suppose, but that would imply that most of Dr. Fasano's work amounts to sort of a wild goose chase, (unless, of course, mast cell degranulation leads to increased production of zonulin). A more likely scenario is that multiple mechanisms exist, by which peptides can enter the blood stream. It appears that zonulin is one route, and mast cell protease is another.

Conclusion: Zonulin is structurally and functionally similar, but not identical, to MCP-II and may represent one of the possible intestinal luminal PAR-2 activators involved in the pathophysiological regulation of intercellular tight junctions.

MCP-II stands for mast cell protease-II, of course, and PAR-2 stands for protease-activated receptor-2.

http://journals.lww.com/jpgn/Fulltext/2 ... p.188.aspx

Note that the above article was co-authored by Dr. Fasano. So what he is saying, is that the knowledge that MCP-II activates the tight junctions by means of PAR-2, was previously established, and he is proposing that zonulin plays a similar role, in regulating the tight junctions, by means of PAR-2.

Unfortunately, this also implies that his anti-zonulin pill will probably not provide relief for patients whose leaky gut is caused by mast cell degranulation, (MCP-II). It may work for many/most celiacs, but it may not work for most people with MC. I say "most", because I believe that most of us have some degree of mast cell issues, (though the problem is much worse, of course, for those with unusually pronounced mast cell issues).

Incidentally, this quote from the article appears to explain the mechanism by which stress can trigger an MC reaction.

Mast cells are also affected by both acute and chronic stress. Anatomic connections between mast cells and enteric nerve fibers have been demonstrated in human gastrointestinal mucosa and are known to increase with inflammation.13 The mast cell–enteric nerve association provides a physiologic means for bidirectional communication between the central nervous system and intestinal tract through which stress may influence gastrointestinal function. As stress has been shown to induce mast-cell activation, mediators released secondary to an external stressor may affect motility, visceral sensitivity, and gut barrier function.7

Tex

[TooManyHats]

Instead of sending a witty letter such as the one Sarah had composed, I'd rather send my former GI doctor a copy of this article highlighting this part:

Cromolyn An inhibitor of mast-cell degradation, cro-molyn can be used at a dose of 100–200 mg orally 4 times per day. Small studies have shown improvement in gastrointestinal symptoms with cromolyn therapy.26,27 In a large multicenter trial evaluating 428 diarrhea-predominant irritable bowel syndrome patients, oral cromolyn was compared to elimination diet. Symptom improvement was seen in 67% of patients treated with oral cromolynsodium (1,500 mg/day) for 1 month compared to 60% of patients treated with elimination diet.

[Gloria]

Arlene,

IMHO, you have nothing to lose by sending it. I doubt that he would even read it, though. My GI never read the article on Mastocytic Enterocolitis that I gave him.

Gloria

[tex]

Arlene,

Imagine what the success rate might have been if the cromolyn sodium treatment had been combined with an elimination diet.

Tex

[TooManyHats]

Arlene,

Imagine what the success rate might have been if the cromolyn sodium treatment had been combined with an elimination diet.

Tex

That would take some thinking outside of the box, not this doc's strongest suit.

[tex]

Tex

[sarkin]

Arlene, thanks for drawing my attention back to this topic... again. (And your letter is a much better idea than mine.)

Although it's certainly true that *being* a thinking/reading/open-minded person is more important to your health than *having* a doctor who is... I still hope you find a doctor who can get past the cookie-cutter mold. I used to have a car mechanic who was genuinely happy when something outside the standard routine (symptom, obvious fix) came up. I had the perfect car for this sort of thing back then, unfortunately.

If only more of us could find doctors as bright and engaged and curious as my former car mechanic. Actually, our current mechanic is also far sharper than most of the physicians I've seen the past few years, for myself or my elderly parents. What is going ON in the medical profession???

I'm going to bring my GP a couple of articles, along with my Enterolab results. We'll see how she does with that. I would like her to do the tests Mary Beth recommended that might give me a clearer hint about mast cells (serum tryptase, and two other tests she mentioned that I think were urine tests). I hope she's open and interested.

sara

[mbeezie]

How did I miss this thread??

Great article Gloria. The only thing I was surprised by was that they didn't talk about the use of a low histamine diet, just an elimination diet.

Tex, I agree that many PP have mast cell involvement, which is transitory in most cases. I've suspected that for quite some time. The disruption of DAO with gut damage exacerbates the issue, but with gut healing and return of DAO function symptoms subside. We could and should try to educate doctors on mast cell issues. I have found that most doctors are very uncomfortable with the subject (I think they hate when a patient knows more than they do). But even mast cell researchers don't have all the answers. They know that there are people out there like me with all of the symptoms but not matching any diagnostic criteria. In mid-August I am seeing 2 new doctors (an allergist recommended by Dr. Castells and a cardiologist for symptoms of hyperadrenergic POTS, which is related to mast cell issues). I am armed with articles!

Gloria, I think you may have some version of mast cell activation, not mastocytosis. I think your gut and food sensitivity issues point in that direction, but I also think your episodes of non-specific cardiac issues a while back also could be related. I had similar cardiac issues that I now know were related to mast cell involvement. Have you thought about trying gastrcrom?

Mary Beth

[Ginny]

This thread is interesting! Since I feel that Gloria and I are very similar in our MC experiences and I am going through another relapse and cannot get it under control this might be something to try. I feel pretty confident that in some shape or form that I must have the Leaky Gut Syndrome, BUT caused by what???? I'm down to around 16 foods (eliminated pork), upped my Entocort to 2 a day, still taking Imodium and still no improvement. I'm at a loss!!

I have used the liquid version of Zyrtec (no lactose) and it zaps me and can't honestly say that it does my gut any good. Maybe I need to take it for a longer period of time, however, I will be in bed a lot

I am most afraid of the continual elimination of foods and no replacements; when will it stop! Recently I even tried combining foods; that's rather difficult when you only eat 16 types of foods ! I see my GI next week to get my prescription refilled but more importantly for him to know that I am at 100 #'s with very little food to eat, because the next time he might be seeing me in the hospital!

That sounded doom and gloom! Just one of those frustrating days we all go through. Love, G

[mbeezie]

Ginny,

Zyrtec is and H1 blocker type antihistamine and won't work on GI symptoms. H2 blockers are prescribed for that, but of course, their use is controversial. I would say try Histame, but you can't if you are intolerant to pork (it's source). Have you considered gatrocrom?

It sure does seem that people with mast cell issues have a very limited diet.

BTW, zyrtec also knocks me out. I just bought some OTC allegra but haven't tried it yet.

Mary Beth

[TooManyHats]

It's very odd that Histame's source is pork, because I can't eat pork but have been able to tolerate the Histame.

Actually, I'm down to 9 foods and one meal with an occasional snack of plain rice crackers, but have been eliminating them lately because well, who knows what the problem is?

Can I tell you how much I hate this?