Mast cell enterocolitis or mast cell inflammatory bowel disease (MIBD), a new epidemic?

Mast cell enterocolitis is a new clinical entity characterized by an increase of 20 or more mast cells per high power field in the duodenum or colon. Jakate et al. described 47 patients with refractory diarrhea and abdominal pain without other cause who had elevated mast cell counts in intestinal biopsies and responded to mast cell-directed therapy. Patients generally met criteria for diarrhea-predominant irritable bowel syndrome (IBS). Normal subjects had much lower levels of mast cells averaging 12 per HPF. My experience indicates that this condition may be another hidden epidemic that should be added to that of celiac disease and non-celiac gluten sensitivity (NCGS). My colleague, Dr. Rodney Ford, has suggested the term “gluten syndrome” for the broader problem of non-celiac gluten sensitivity and I agree that may be a more appropriate term. Now, I suggest that mast cell inflammatory bowel disease (MIBD) be considered a better term for the newly recognized mast cell enterocolitis. I review my reasons below.

Until recently, the presence of increased mast cells was either missed due to the lack of ability to see mast cells on biopsies against the background of normal cells, or was only noted in association with inflammatory diseases. bowel and celiac disease. A few pediatric studies have noted an increase in mast cells in the esophagus in association with eosinophilic esophagitis or “allergic esophagus”. Systemic mastocytosis has been known for years and has been associated with intestinal symptoms such as abdominal pain and diarrhea. Now, two new studies shed more light on this secret cell and its role in postoperative ileus and its association with stress. Mast cells have been linked to diarrhea-predominant IBS in a few studies, but it was not until Jakate’s article that a separate entity was defined.

The problem of linking mast cells with IBS and other digestive symptoms has been hampered by the difficulty in seeing these cells in intestinal biopsies. However, special stains now commercially available using immunohistochemistry for the enzyme tryptase make it possible to see and count mucosal mast cells in intestinal tissue obtained from routine random intestinal biopsies. For the past year, I have had pathologists perform mast cell stains on intestinal biopsies in my gastrointestinal patients with diarrhea and abdominal pain. Recently, I have begun to expand this to include as many patients as possible and request that these stains be performed on biopsies previously taken from patients I suspected of having this disease.

I have now accumulated fifty patients meeting the criteria for mast cell enterocolitis or mast cell enteritis. These patients are in various stages of evaluation and treatment. I collect and analyze clinical information with the aim of submitting the data for publication. What I observed during the initial examination is that there seems to be a higher than expected prevalence of the celiac disease risk genes DQ2 and DQ8. In particular, DQ8 appears to be overrepresented compared to the incidence in the general population. There also appears to be an association with celiac disease, non-celiac gluten sensitivity, and multiple food intolerance.

This latest finding of multiple food intolerances determined by mediator release test abnormalities (MRT, Signet Diagnostic Corporation and Alcat) makes sense. The principle of these tests is the detection of changes in cell volumes due to the release of chemical mediators by the cells present in the blood. The tests are not specific to the mediator or mediators released, but it is assumed that the larger the reaction, the greater the number of mediators released and the more likely a particular food, chemical or food additive may be. cause an adverse reaction.

Laboratories that provide mediator release testing report great success in treating a variety of symptoms commonly attributed to food intolerance or chemical/additive sensitivity. I believe mast cells are heavily involved in this process. This would make sense since success with conditions currently associated with mast cells would respond favorably to dietary elimination of foods or substances with abnormal MRT reactions. Classic examples include IBS, headaches and interstitial cystitis which have been linked to mast cells as well as stress which is now linked to increased mast cells and mediators releasing mast cell degranulation.

Mediator release tests are criticized by some US physicians, particularly, as unproven or unvalidated for the assessment of “food allergies”. However, these are not food allergy tests. Food allergy is an IgE-mediated immediate type I immune response known as an allergy. MRT tests for delayed-type non-immune reactions resulting from the release of mediators by immune cells. The thing is, the mediator release test is not a form of food allergy testing. MRT is a form of non-immune food intolerance or sensitivity reaction.

New papers published in the January 2008 issue of the journal Gut reveal exciting new associations of mast cell degranulation with postoperative ileus and a stress hormone link. The first study may be the first to show that human intestinal release mediators mast cells when the intestine is manipulated during surgery lead to temporary intestinal paralysis known as postoperative ileus. The minimally invasive surgical technique of laparoscopy results in less mechanical stimuli in the bowel and has a lower incidence of postoperative ileus.

The association of stress with IBS and inflammatory bowel disease (ulcerative colitis, Crohn’s disease) has been known for a long time, but a mechanism has not been determined with certainty. In the same issue of Gut, researchers showed that the stress hormone corticotropin-releasing hormone (CRH) regulates intestinal permeability (leaky gut) through mast cells. Researchers have even identified specific receptors on mast cells. This new information sheds new light on the possible link between leaky gut and mast cells with IBS, IBD and celiac disease.

So how can I believe that this new information can help us? Since stress can increase mast cells in the intestine and these cells can release mediators that cause intestinal damage and symptoms, stress reduction is important. These cells can cause abdominal pain, diarrhea and constipation as well as other symptoms outside of the gut, so they are important. Yet the importance of these cells is generally not recognized because most physicians, including gastroenterologists and pathologists, are unaware of their presence and importance.

These cells cannot be seen in the intestine without special staining performed on the intestinal tissue obtained during upper endoscopy or colonoscopy. These stains are not performed routinely but generally require the doctor performing the biopsy to request it. If no biopsy is performed, these cells are obviously not found. There may be a genetic predisposition for what I think would be better called mast cell inflammatory bowel disease (MIBD) rather than mast cell enterocolitis. There may also be the same genetically determined white blood cell protein patterns that are associated with celiac disease playing an important role in MIBD.

As stated above, stress reduction and probiotic therapy can be helpful in reducing mast cells and leaky gut, but what about once mast cells are increased in the gut. Once elevated mast cells are present, treatment may include medications and dietary interventions. Type I (eg Claritin, Allegra, Zirtec) and Type II (eg Zantac, Tagamet, Pepcid) antihistamines to block the effects of histamine have been used successfully to reduce abdominal pain and diarrhea in people with mast cell enterocolitis. A very specific mast cell stabilizer, Cromalyn sodium (Gastrocrom), also reduced symptoms. It is an accepted therapy for the more serious condition of generalized mastocytosis.

Testing for food allergies and food intolerances (through mediator release testing) followed by dietary elimination of problematic foods until the leaky gut resolves and the number of mast cells in the shrinking gut is also helpful in my experience. Food allergy tests consist of skin tests and IgE RAST antibody tests. These tests do not exclude non-allergic food intolerances and sensitivities. Antibody tests for IgG in blood or IgA in feces or saliva have been used for food sensitivity. In my experience, MRT tests are much more useful as they look for any abnormal release of mediators in a variety of foods, chemicals or additives of any kind.

Stay tuned for new developments on the role of mast cells and look for more interest in mast cell enterocolitis in the future. I propose that the gastrointestinal community adopt the broader term mast cell inflammatory bowel disease, as there is information indicating that mast cells play an important role in allergic esophageal and stomach problems.

Selected references:

Le, FO et al. “Bowel manipulation-induced mast cell activation and inflammation in human postoperative ileus.” Intestine 2008; 57:33-40

Walloon, C et al. “Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colon biopsies in vitro.” Intestine 2008; 57:50-58.

Jakate, S. “Mast cell enterocolitis: increased mucosal mast cells in chronic intractable diarrhea.” Arch Pathol Lab Med 2006; 130:362-367.

Copyright 2008 Dr. Scot M. Lewey

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