New with question about mast cells and LC

[faithberry]

Hello Everyone,

I was dx’d with mild LC a few years ago. The loose stools resolved on a gluten/casein free diet. However, my food intolerances have progressively worsened as well as having a big range of systemic symptoms. These might be related to the release of histamine and other mediators from mast cells.

The E-medicine article on LC and CC states that some people with LC have increased levels of mast cells in addition to lymphocytes. There was a study done a few years ago at Rush Hospital in Chicago on D and increased levels of mast cells, when there’s no other known cause, which they termed ‘mastocytic enterocolitis.’ It seems there haven’t been follow-up studies to confirm their findings so this is a diagnosis in limbo. There are several articles about mastocytic enterocolitis on the Food Doc blog. I was a little suspicious of the latter at first, but he is a board certified gastroenterologist and seems to be a colleague of Dr. Fine.

I was wondering if:
Anyone here has been diagnosed with increase mast cells in the intestines (small or large) in addition to LC/CC?

If anyone has had success in getting their prior biopsy results re-stained with the special stain now used to identify mast cells?

Has anyone used Gastrocrom, the first-line treatment of choice for gut-related mast cells problems in addition to H1 and H2 blockers and what your experience has been?

Your input and experience would be greatly appreciated. I feel like my immune system got turned on and won’t turn off, even though it seems the LC is in remission.

The links to articles referenced above---
http://www.rush.edu/Rush_Document/Masto ... itis,0.pdf
thefooddoc.blogspot.com

[tex]

Hi Faith,

Welcome to our internet family of students of MC. You seem to have a pretty good grasp of the issues involved with LC. I "think" I recall at least one or two members mentioning increased mast cells as part of their diagnoses, but I don't recall any details, nor who they might be. It's not something that has been commonly mentioned on this board. I'm not aware of anyone here who has had their biopsy sample slides re-stained, and subsequently assessed for increased mast cells, but that doesn't mean that it hasn't happened - it simply means that I'm not aware of it, if it has indeed happened.

To be honest, most of the GI docs that we as a group have encountered, (at least in the past), were lucky to be able to diagnose MC, let alone mastocytic enterocolitis. Many of them failed to even take biopsies, so they weren't even qualified to make a reasonable guess at a realistic diagnosis. Fortunately, more and more of them seem to be making a bit of progress in learning about MC, now, but I suspect that most of them still don't even realize that there are more than two types of MC.

Yes, to the best of our knowledge, we believe that Dr. Lewey is quite credible. We've discussed many of his articles in the past, including his blogs about mast cells. You might find some of the comments in some of the posts in this thread, interesting:

http://www.perskyfarms.com/phpBB2/viewt ... mast+cells

I'm not aware that any member here has ever tried Gastrocrom. (To be honest, I had never heard of it before). A quick search didn't turn up any information on the specific mechanism by which Gastrocrom works. Am I correct in assuming that it is designed specifically to target H4 histamine receptors?

Again, welcome aboard.

Tex (Wayne)

[faithberry]

Hi Tex,

Thanks for the synopsis! I found the thread you linked to interesting. As you mention there, mast cells may be the reason that some people here have not been able to achieve remission. However, if they are taking immune suppressor drugs, that should do the trick for mast cells too, I believe. They are used in the more serious cases of mastocytosis.

I've learned what I know about this through reading about mastocytosis, mast cell activation disorder, and chronic urticaria, all mast cell connected problems. Gastrocrom (sodium cromoglycate) is a mast cell stabilizer, not an H4 antihistamine. It takes 4-6 weeks to work and can have side effects. It has been a lifesaver for many people with mastocytosis who have D, abdominal pain, reflux, and big problems with food. It can help with some systemic symptoms too. The H1 anti-histamines are recommended for D in the case of a mast cell problem as they effect smooth muscle contraction in the gut; I think I read that in the Rush Hospital study. H2s for the stomach. I don't think this type of mast cell problem is necessarily an IgE mediated process. But I'm not certain. It doesn't seem to be a diagnostic marker in the reading I've done.

I'm just learning about this so I'm not absolutely certain about anything. For awhile I thought I might have mastocytosis, but it is very rare and hard to diagnose. Mast cells in the gut seem more probable in my case. Just trying to figure out what might be the next step for me in addressing my problems. I've been taking H1 and H2's and both have helped. I've been able to gain weight, but have not been able to add any foods back. It seems many people need the Gastrocrom for that. My new GI is not helpful, so I'm hoping I can get my GP to give me a trial of the Gastrocrom. I don't have D; just the abdominal pain, reflux, or vomiting when I eat some foods and other foods cause systemic symptoms like headaches, itching, rashes. I stopped the ranitidine (H2) though since it's been implicated in the onset and recurrence of MC, and I don’t tolerate the corn starch in the other H2 drugs.

Thanks for your reply and warm welcome. It's good to hear that people in the forum are onto this, and maybe our discussion will be helpful to someone here, someday.

[tex]

Faith,

This is all very interesting, and I agree that we need to learn more about mast cells, and how this all fits together. Do you feel that you have gastroparesis, (abnormal motility of the stomach, resulting in delayed gastric emptying), during these episodes? Some of us have that problem, at least part of the time, during reactions, resulting in nausea, a feeling of fullness, and occasionally, vomiting.

When it comes to defining what we know, what we think we know, and what we don't know, about these related diseases, it's obvious that all of us are students, and the more we learn, the more we realize we have left to learn.

Thanks for the insight,
Tex

[faithberry]

Tex,

Sorry to hear about people's problems with gastroparesis. I find that interesting though as no one knows what happens in MC long run.

I don't think I have gastroparesis because I don't have a problem eating some high fiber foods like brown rice, which are very problematic in that disorder. But the symptoms are similar to what you list. When I took the H2's that feeling of fullness after eating went away and I could eat a lot more. I seem to have some type of motility or slow transit problem though because my intestines seem to have ground to a halt. Mast cells are involved in both hyper and hypo motility according to the Rush Hospital Study. They collect around nerves (and blood vessels) and at least the Food Doc says they can paralyse the gut. That might mean any part of the gut, I presume, as in gastroparesis or intestinal dysmotility. I did think it might be GP for awhile, so that's why I did my homework on it.

People with mast cells disorders also get these same gut symtpoms...abdominal pain, cramping, vomiting, nausea and/or reflux along with many other symptoms. They usually have D, but sometimes C, and sometimes GP or slow transit. Mast cell disorders are rare, but there has been recent research about mast cells and the gut and IBS and MC and UC and Crohns...like the studies in the thread you linked to. I had one histamine test that showed mildly elevated histamine levels, which is odd since I am on just about a 0 histamine diet and the test was after an overnight fast. High histamine foods give me the worst symptoms. I know that I also react to some drugs that liberate mast cells like morphine. And the H1 and H2 antihistamines help me. So there's something going on connected to histamines, at the very least.

I don't think increased mast cells in the gut are the answer to everyone's problems, but it's the next logical step in terms of my own gut issues. If you want to learn more, the Rush Hospital study has a good overview about mast cells.

The thread you linked to wondered about an 'opioid' issue with mast cells. Opiates like morphine are mast cells liberators. I wonder how that might relate with wheat and casein which contain opioid-like substances. Aspirin is another liberator.There are some foods that directly liberate mast cells as well like tomatoes, raspberries, pineapple, strawberries, uncooked egg whites, chocolate, shellfish, alcohol...among some others others. People with mastocytosis have too many mast cells and almost any food can liberate mast cells in their case, but there are the worse offenders like those listed above which seems a problem for almost everyone with the disease. Mast cells are also connected with some AI diseases like RA and MS.

My strategy at this point is to try gastrocrom if I can get a trial from my GP. If I can tolerate it and if it helps me tolerate more foods, then I'll have my answer about mast cells or at least a really good guess. My first concern is being able to tolerate more foods, rather than motility which I have under control.

Looks like we have to be the pioneers as this is still a new research area without many collectively agreed upon conclusions!

[tex]

Opiates like morphine are mast cells liberators. I wonder how that might relate with wheat and casein which contain opioid-like substances. Aspirin is another liberator.There are some foods that directly liberate mast cells as well like tomatoes, raspberries, pineapple, strawberries, uncooked egg whites, chocolate, shellfish, alcohol...among some others others. People with mastocytosis have too many mast cells and almost any food can liberate mast cells in their case, but there are the worse offenders like those listed above which seems a problem for almost everyone with the disease.

I find it very, very interesting that many of us have problems with some or all of the foods, (and NSAIDs, of course), that you mentioned. We don't seem to be actually intolerant of them, and yet they bother us, if we eat them - at some times, more than others.

This effect may also be connected with the phenomenon whereby stopping a longtime smoking habit, triggers MC.

On the other hand, opioid-based andidiarrheals, such as Imodium and Lomotil, seem to be quite helpful for many MC patients, for short-term use, at least.

When I can find the time, I need to do a lot more reading on this topic.

Throughout history, pioneers have almost always been the movers and shakers, who establish the most important guidelines for the lives of those who follow later, and I've always been of the opinion that we should never be afraid to try new options, or new technology. While it's true that many roads lead to disappointing destinations, occasionally we "luck out", and find one that leads to an "oasis", and when that happens, it's a very gratifying experience, that more than makes up for all the disappointments. As they say, if you're not the lead dog, (in a team pulling a dogsled, at least), the scenery never changes.

Thanks for sharing your knowledge.

Tex

[faithberry]

It looks like you've already started your homework on mast cells, given the excellent explanation you gave to Dee. I'm happy if I can contribute a little, given all the beneficial information you've all provided. It's helping me now and in the past when I've browsed now and then. I think my situation is very weird and may not apply to anyone else. But who knows!

I find it interesting that bismuth sub-salicylate (Pepto Bismal) is used for treatment for MC, when it is a salicylate like aspirin. I wonder if people who don't respond to it might also be sensitive to foods with higher levels of salicylates as well. Although the levels in aspirin are much higher, some people seem to be sensitive even to the smaller amounts in food.

I know I have a problem with high histamine foods even though I don't have classic allergies. I suspect it's because they add to one's total histamine burden if you already have too much histamine due to mast cell activity. For some people, the mast cells just slowly leak their contents which leads to chronic problems, rather than the sudden problems like anaphylaxis. But of course, too much histamine might be due to other causes.

Most of the foods I listed above (the histamine liberators) are high in salicylates and/or histamines as well. The International Chronic Urticaria Society says that some people with chronic hives may be helped by a low salicylate diet; others by a histamine free diet. I wonder if these diets would have any relevance for people with MC since food intolerance is such a big issue for us. But it may be just the big five. Here are some links.

http://www.urticaria.thunderworksinc.co ... tediet.htm

http://www.urticaria.thunderworksinc.co ... tamine.htm

Here's a link to a low salicylate, low amine (includes histamine), and low food additive diet.
http://www.plantpoisonsandrottenstuff.i ... ction.aspx

This may not have any relevance for MC, but it's interesting that some of the foods I mentioned above continue to cause some types of problems for some people.

[tex]

Faith,

Your insight is very inspiring. I, too, have wondered about the salicylate content of Pepto. Presumably, it's a major part of the reason why some of us react adversely to the Pepto treatment.

In fact, most of the original treatments for IBDs were/are based on salicylic acid, including all of the Mesalamine family, (Asacol, Colazal, Pentasa, Lialda, etc.), which are based on a derivative of salicylic acid and which is also presumed to be the active component of sulfasalazine, (Azulfidine). IOW, most of the treatments prescribed for IBDs, contain ingredients known to be contraindicated for IBDs. The other options, the corticosteroids, the various other immune system suppressants, and especially the anti-TNF drugs, for example, are certainly not without their own serious risks of Draconian side effects. Therefore, it's no wonder that the treatment of IBDs is so difficult and frustrating. If meds are to be used in the treatment plan, then one has to choose the lessor of all the evil treatments available, so to speak.

I suspect you're quite correct about accumulated total histamine "loads" causing "subtle" problems. This is, I believe, very similar to the problem of gluten-sensitive people ingesting enough gluten to trigger a reaction, by eating several "safe" foods, that happen to have trace amounts of gluten, which, when added together, adds up to enough gluten to exceed the threshold for a reaction, based on that individual's sensitivity level.

I notice that you have Gilbert's syndrome listed in your signature line. Are you able to use acetaminophen? I notice that the condition is protective of coronary heart disease, and atherosclerosis. That's interesting. It seems that many clouds have a silver lining.

Thanks for the insight, and the links.

Tex

[faithberry]

Tex,

That's very interesting about the IBD medicines. You know so much!

You are right, with the salicylates and amines (including histamines) it has to do with a cumulative effect if your problem is inefficient detoxification. Apparently, people vary widely in the ability to detoxify natural food chemicals.

My last attempt at taking Tylenol left me feeling sick for a couple of days!

[tex]

My last attempt at taking Tylenol left me feeling sick for a couple of days!

I assume then, that you are aware that you probably are unable to metabolize paracetamol, (acetaminophen), due to the GS, which can lead to an increased risk of paracetamol toxicity for some people with GS.

http://www.ncbi.nlm.nih.gov/pubmed/10412886

Tex

[faithberry]

I didn't know it at the time! Thanks for the link. Here's a link to an interesting journal article on Histamine and Histamine Intolerance, you may find of interest. Particular the discussion of diamine oxidase and the gut.

www.ajcn.org/cgi/content/full/85/5/1185

[tex]

Faith,

That's an extremely interesting article. It suggests answers to lot of questions we have had about many aspects of MC reactions.

The following quotes are from the article you cited. The gene discussed in this sentence may well be one more of a group of genes that are apparently triggered when MC and gluten sensitivity are triggered. (The red emphasis is mine, of course.)

Thus, histamine intolerance seems to be acquired mostly through the impairment of DAO activity caused by gastrointestinal diseases or through the inhibition of DAO, but the high interindividual variations in the expression of DAO in the gut and the association of SNPs in the DAO gene with gastrointestinal diseases provide evidence for a genetic predisposition in a subgroup of patients with histamine intolerance(27).

Besides headache, gastrointestinal ailments including diffuse stomach ache, colic, flatulence, and diarrhea are leading symptoms of histamine intolerance. Elevated histamine concentrations and diminished DAO activities have been shown for various inflammatory and neoplastic diseases such as Crohn disease (17), ulcerative colitis (67), allergic enteropathy (39), food allergy (33, 68, 69), and colorectal neoplasmas (24). In the colonic mucosa of patients with food allergy, a concomitant reduced HNMT (70) and an impaired total histamine degradation capacity (THDC) (69) have been found (33), so that the enzymes cannot compensate each other. Therefore, an impaired histamine metabolism has been suggested to play a role in the pathogenesis of these diseases.

Clearly, then, impaired histamine metabolism has to be a part of the development of MC. Some of the questions that remain to be answered, are, "just how large a role does impaired histamine metabolism play in MC, and other IBDs?" "Does it only affect the symptoms, or could it be a part of the triggering mechanism that initiates it, in the beginning?"

In mammals, DAO expression is restricted to specific tissues; the highest activities are shown for small bowel and colon ascendens (4, 5, 33) and for placenta and kidney (28, 31). Lower DAO activity has been discussed as a potential indicator of intestinal mucosa damage in inflammatory and neoplastic diseases (17, 24, 34) and in persons undergoing chemotherapy (35).

This is pretty profound information. If DAO, (previously known as histaminase), is produced in the brush border region of the small intestine, (as most digestive enzymes are), then clearly, the accumulated damage to the small intestinal mucosa, (including villous atrophy), caused by gluten, and other food intolerances, would absolutely have to suppress DAO production. I can't find any references in the literature, but this effect may also exacerbate the leaky gut syndrome, thus further amplifying the problem.

In pregnancy, DAO is produced at very high concentrations by the placenta (119, 120), and its concentration may become 500 times that when the woman is not pregnant (120). This increased DAO production in pregnant women may be the reason why, in women with food intolerance, remissions frequently occur during pregnancy (14).

I've been attributing this effect, (remission during pregnancy), to increased progesterone production, but the extreme DAO production in the placenta may well be the primary reason for the remission of MC symptoms that most women with MC experience during pregnancy.

There is a huge amount of valuable information in that article. Many thanks.

Tex

[faithberry]

Tex,

I didn’t quite get the significance of the genetic link and IBD, until you pointed it out in your post. Thank you so much. You’re right, this is profound!

You said:

The gene discussed in this sentence may well be one more of a group of genes that are apparently triggered when MC and gluten sensitivity are triggered.

Is there a handy list some place of what these genes are and the conditions with which they are associated?

In my case, I’ve never had any indication of damage to the villi either through biopsy or the fecal fat score at Enterolab. Not sure if this fully excludes the possibility. I still don’t know how to fit all the pieces of my puzzle together: MC in remission, Gilbert’s Syndrome (impaired glucuronidation effects salicylates, isoflavones, and a few other food chemicals), possible DAO issue, possible mast cell issue. No wonder why I can only eat a handful of foods. Anyone else here dealing with reactivated EBV/CMV?

The DAO enzyme is now sold in pharmacies in Germany under the name ‘DAOsin.’ I had a chance to try DAOsin, but could not tolerate it. It contains many ‘other ingredients’ and I often have trouble with one or more of these. Plus, you still have to stay on a low-histamine diet.

I’m glad the article is useful. It has been pointed out to me that this is still at the level of research and there is no conclusive evidence that a condition such as ‘histamine intolerance’ actually exists. Nevertheless, I find it quite compelling!

[tex]

Is there a handy list some place of what these genes are and the conditions with which they are associated?

I'm not aware of any official compilation. In, fact, it seems to be rather difficult to track down any meaningful research on this topic. Most of what I said amounts to mostly "conclusions" and "speculation", based on articles such as this:

How are microscopic colitis and gluten sensitivity (or celiac sprue) related?
I have shown in a previous study that the most common cause of diarrhea in patients with celiac sprue treated with a gluten-free diet for many years is microscopic colitis. Other individuals are found at the time of diagnosis to have both of these syndromes. this realtes to the fact that the same immune system regulatory genes, called HLA, are involved in producing both syndromes, as well as many other autoimmune syndromes. The celiac sprue diagnosed in patients found to have microscopic colitis is usually of a mild variety, and appears to me to be the result of the colitis itself. This occurs because the genes causing microscopic colitis are also programmed to react with gluten if they are triggered to do so. This is why people can go their whole lives withjout apparent gluten sensitivity and then suddenly become gluten intolerant. Thus, testing for the presence of gluten sensitivity in patients with microscopic colitis, sometimes combined with assessment for the presence of the gluten-sensitive gene, is necessary in many if not all such patients. Unfortunately, as mentioned above, the currently most widely used test for this is a blood test that rarely if ever detects gluten sensitivity in patients with microscopic colitis (because it was designed for patients with full blown celiac sprue). However, my new stool test, which is being offered by EnteroLab, can detect this.

http://www.finerhealth.com/Educational_ ... c_Colitis/

http://www.ncbi.nlm.nih.gov/pubmed/10950045

And, of course, Dr. Lewey's comments here, (you have to scroll about halfway down the page to get to something other than the DQ2 and DQ8 stuff):

http://www.celiac.com/articles/21628/1/ ... Page1.html

This one has some additional information:

http://ezinearticles.com/?Celiac-Diseas ... &id=208578

There is a complete list, (I think), of the various haplotypes, (for Caucasian Americans), at the following Wikipedia link. Some day, we may be able to look at a person's gene type, and draw specific conclusions about which foods that individual might be intolerant to, if/when the genes are triggered. At the present stage, though, (as you mentioned about "histamine intolerance"), about the best we can do, (as far as drawing conclusions about actual physical consequences), is to make educated guesses, and draw general inferences. For example, we have noticed that members of this board who have "double DQ" genes, always have more food intolerances, and typically have a much more difficult time achieving remission.

http://en.wikipedia.org/wiki/HLA-DQ

I can recall a member or two suspecting EBV, but I'm not sure that any of our members actually had a diagnosis, though. CMV, doesn't ring a bell, unless I have just totally forgotten that someone posted about it, at some point in the past.

There is a much more extensive article somewhere out there on the web, written by Dr. Fine, about the details of his findings concerning various genes as related to MC, but at the moment, I apparently can't think of the proper key words that would enable me to find it, and I don't have it bookmarked on this computer, unfortunately.

Tex

[Dee]

Autoimmune Urticaria (Hives)
Mast cells are the cells in the skin and mucous membranes that contain histamine. Release of histamine causes the allergic symptoms of hives and angioedema (swelling of large areas of the body). Itching is a common symptom when histamine is released. Anti-histamines are often prescribed to help control this symptom.

The immune system normally protects us by making antibodies against foreign invaders such as bacteria and viruses. These antibodies are called IgG and are often referred to as gammaglobulins. Usually, IgG is not formed to any normal body tissue but occasionally, by error, this does happen. If antibody binds to normal tissues it can cause damage to the body or create other disease symptoms. Rheumatoid arthritis is a good example of an autoimmune disease. Antibodies that react with body tissues are felt to contribute to joint swelling and pain. Many other common diseases are caused by autoimmunity such as juvenile diabetes and low thyroid disease.

It has been recently discovered that some persons who suffer with hives or angioedema also have an autoimmune disease. In these cases, autoantibodies have been formed that bind to the Fc-receptor on mast cells. The normal function of the Fc-receptor is to anchor allergic antibodies, called IgE, to the mast cell surface (see the mast cell diagram below). IgE is formed in allergic persons and binds specifically to allergens in the environment. When airborne allergens land on nasal tissues or eye conjunctiva, or are eaten (foods) and enter the body through the intestinal tract they bind to the specific IgE. As a result of this interaction, a signal is sent by the IgE antibody to the mast cell causing it to release its histamine. Histamine release causes the nasal and eye symptoms seen in those who suffer with "hay fever" and can produce hives, angioedema, or even life-threatening symptoms such as respiratory compromise or low blood pressure.



In persons with autoimmune hives, the IgG autoantibody that binds to the Fc-receptor tricks the mast cell into believing that the IgE on its surface has encountered an allergen. When this happens, hives or tissue swelling can result. (The diagram above shows a Mast cell with purple histamine granules. The "patient IgG" is the autoantibody that binds to the Fc-receptor.)

Once it has been discovered that the anti-IgE Fc-receptor antibody is present in a patient’s blood, it is no longer necessary to look for any other cause for hives. Why this autoantibody triggers hives only intermittently is unknown. Many people with this autoantibody feel that their hives are more likely to occur when they are stressed. Some women feel that hormonal changes that occur just prior to their menstrual periods also trigger their hives. Some medications, especially aspirin, ibuprofen (Advil), or naproxsen (Aleve) are also more likely to trigger hives. However, Tylenol (acetominophen) does not usually trigger hives or swelling.

Once the diagnosis of autoimmune hives has been made, the goal is then to select the best combination of medications to reduce the frequency of outbreaks.

Long-term, this autoantibody may go into remission and it may be reasonable to try periods off suppression medications every few month to see if they are still needed.

There has been a high incidence of autoantibody to thyroid glands reported among those with anti-Fc-receptor antibodies and it is suggested that yearly thyroid testing be done by the primary care physician.