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 intractable diarrhea and abdominal pain of no other cause who had elevated mast cell counts on 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 than an average of 12 per HPF. My experience indicates that this condition may be another hidden epidemic to be added to that of celiac disease and non-celiac gluten sensitivity (NCGS). My colleague, Dr. Rodney Ford, suggested the term “gluten syndrome” for the broader problem of non-celiac gluten sensitivity, and I agree that this may be a more appropriate term. Now, he suggests that mast cell inflammatory bowel disease (MIBD) be considered a better term for the newly recognized mast cell enterocolitis.
Until recently, the presence of increased mast cells was either overlooked due to a lack of ability to see mast cells in biopsies in the background of normal cells or only noted in association with inflammatory bowel diseases and celiac disease. Some pediatric studies have observed increased 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 covert cell and its role in postoperative ileus and its association with stress. Mast cells have been associated with diarrhea-predominant IBS in some studies, but it was not until Jakate’s article that a distinct entity was defined.
The problem of linking mast cells to IBS and other digestive symptoms has been compounded 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 been asking pathologists to perform mast cell stains on intestinal biopsies in my GI patients with diarrhea and abdominal pain. I recently began expanding this to include as many patients as possible, as well as requesting that these stains be done on biopsies previously done on patients I suspected might have this condition.
I have now accumulated fifty patients who meet the criteria for mast cell enterocolitis or mast cell enteritis. These patients are in various stages of evaluation and treatment. I am collecting and analyzing clinical information with the intention of submitting the data for publication. What I observed in the initial review is that there appears 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 intolerances.
The latest finding of multiple food intolerance determined by abnormalities in mediator release tests (MRT, Signet Diagnostic Corporation, and Alcat) makes sense. The principle of these tests is the detection of changes in cell volumes that occur due to the release of a chemical mediator from the cells present in the blood. The tests are not specific to the mediator(s) released, but it is assumed that the larger the reaction, the greater the number of mediators released and the more likely it is that a particular food, chemical, or food additive could cause an adverse reaction. .
Laboratories that provide mediator release tests report great success in treating a variety of symptoms commonly attributed to food intolerance or chemical/additive sensitivity. I think mast cells are very involved in this process. This would make sense since success with conditions now associated with mast cells is reported to 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 mast cell-releasing mediators of degranulation.
Mediator release tests, particularly quackwatch.com, are criticized by some US physicians for not being tested or validated for the evaluation of “food allergies.” However, they are not food allergy tests. Food allergy is an immediate IgE-mediated type I immune response known as allergy. MRT tests for non-immune delayed-type reactions resulting from the release of mediators from immune cells. The point is that 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 articles published in the January 2008 issue of the journal Gut reveal exciting new associations of mast cell degranulation with postoperative ileus and a link to a stress hormone. The first study may be the first to show that mast cells in the human intestine release mediators when the intestine is manipulated during surgery, resulting in temporary intestinal paralysis known as postoperative ileus. The minimally invasive surgical technique of laparoscopy results in less mechanical stimuli to the bowel and has a lower incidence of postoperative ileus.
The association of stress with IBS and inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) has been known for a long time, but a mechanism has not been definitively determined. In the same issue of Gut, the researchers demonstrated that the stress hormone, corticotropin-releasing hormone (CRH), regulates intestinal permeability (leaky gut) via mast cells. The researchers even identified specific receptors on mast cells. This new information sheds new light on the possible link of leaky gut and mast cells to IBS, IBD, and celiac disease.
So how do I think this new information can help us? Since stress can increase mast cells in the intestine and these cells can release mediators that cause intestinal lesions and symptoms, stress reduction is important. These cells can cause abdominal pain, diarrhea, and constipation, as well as other symptoms outside the intestine, so they are important. However, 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 stains performed on intestinal tissue obtained during upper GI endoscopy or colonoscopy. Those stains are not routinely done, but usually require the doctor performing the biopsy to order them. If a biopsy is not done, obviously these cells cannot be found. There may be a genetic predisposition for what I think may be a better term for 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 and play a role in MIBD.
As stated above, stress reduction and probiotic therapy can be helpful in reducing mast cells and leaky gut, but what happens once mast cells increase in the gut? Once there are elevated mast cells, treatment may include medication and dietary interventions. Antihistamines, both type I (eg, Claritin, Allegra, Zirtec) and type II (eg, Zantac, Tagamet, Pepcid) 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 reduces symptoms. It is an accepted therapy for the more severe condition of generalized mastocytosis.
In my experience, it is also helpful to screen for food allergies and intolerances (by mediator release testing), followed by dietary elimination of problematic foods until leaky gut resolves and the number of mast cells in the gut is reduced. Food allergy testing consists of skin tests and IgE RAST antibody tests. These tests do not exclude non-allergic food intolerance and sensitivity. Antibody tests for IgG in blood or IgA in stool or saliva have been used for food sensitivities. In my experience, MRT tests are much more useful, looking for any abnormal release of mediators in a variety of foods, chemicals, or additives, regardless of nature.
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 GI community should adopt the broader term mast cell inflammatory bowel disease as there is information indicating that mast cells play an important role in allergic problems of the esophagus and stomach.
Selected references:
El, FO et al. “Mast cell activation and inflammation induced by intestinal manipulation in human postoperative ileus”. gut 2008; 57:33-40
Valon, C et al. “Corticotropin-releasing hormone (CRH) regulates macromolecular permeability across mast cells in normal human colon biopsies in vitro”. gut 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 http://www.thefooddoc.com