Mastocytic Enterocolitis or Mastocytic Inflammatory Bowel Disease (MIBD), A New Epidemic?

Mastocytic enterocolitis is a new clinical entity characterized by increase mast cells of
20 or more per high-powered field in the duodenum or colon. Jakate et al. described 47
patients with intractable diarrhea and abdominal pain without other cause who had elevated
mast cell numbers in intestinal biopsies and responded to therapy directed at mast cells.
The patients generally met criteria for diarrhea predominant irritable bowel syndrome
(IBS). Normal subjects had much lower levels of mast cells of an average of 12 per HPF.
My experience indicates that this condition may be another hidden epidemic that should be
added to the 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 this may be a more appropriate term. Now, I
am suggesting that mastocytic inflammatory bowel disease (MIBD) be considered as a better
term for the newly recognized mastocytic enterocolitis. I review my reasons below.

Until recently the presence of increased mast cells was either missed due to lack of
ability to see mast cells on biopsies in the background of normal cells or was only noted
in association with inflammatory bowel diseases and celiac disease. A few pediatric
studies have noted increase 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 bowel symptoms such as abdominal pain and diarrhea. Now two new
studies are shedding more light on this covert cell and its role in postoperative ileus
and association with stress. Mast cells have been linked to diarrhea predominant IBS in a
few studies but it wasn’t until the Jakate article that a distinct entity defined.

The problem with linking mast cells with IBS and other digestive symptoms has been
hampered by the difficulty seeing these cells in intestinal biopsies. However, now
commercially available special stains utilizing immunohistochemistry for the enzyme
tryptase allows the mucosal mast cells to be seen and counted in intestinal tissue
obtained from routine random intestinal biopsies. Over the past year I have been asking
the pathologists to perform mast cell stains on intestinal biopsies in my GI patients with
diarrhea and abdominal pain. Recently, I began expanding this to include as many patients
as possible as well as requesting these stains be done on biopsies performed previously in
patients who I suspected might have this condition.

I have now accumulated fifty patients meeting criteria for mastocytic enterocolitis or
mastocytic enteritis. These patients are in various stages of evaluation and treatment. I
am collecting and analyzing the clinical information with the intent to submit the data
for publication. What I have observed on initial review is that 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 with the incidence in the general population.
There also appears to be an association with celiac disease, non-celiac gluten sensitivity
and multiple food intolerance.

The latter finding of multiple food intolerance determined by mediator release testing
abnormalities (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 chemical
mediator release from cells present in the blood. The tests are not specific for the
mediator or mediators released but is assumed that the greater the reaction the greater
the number of mediators released and more likely a particular food, chemical or food
additive can cause an adverse reaction.

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

Mediator release tests are criticized by some U.S. doctors, in particular quackwatch.com
as being unproven or not validated for “food allergy” evaluation. However, they are not
food allergy tests. Food allergy is an IgE mediated type I immediate immune response known
as allergy. MRT tests for non-immune delayed type reactions resulting from mediator
release from immune cells. The point is that mediator release testing 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 human bowel release
mediators when the bowel is handled during surgery resulting in temporary bowel paralysis
known as postoperative ileus. The minimally invasive surgery technique of laparoscopy
results in less mechanical stimuli to the bowel and has a lower incidence of postoperative
ileus.

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

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

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

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

Searching for food allergies and food intolerance (by mediator release testing) followed
by dietary elimination of problem foods until leaky gut resolves and mast cell numbers in
the bowel reduce is also helpful in my experience. Food allergy testing consists of skin
testing 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 sensitivity. In my experience MRT tests are much more helpful as
they look for any abnormal mediator release to a variety foods, chemicals, or additives,
regardless of the nature.

Stay tuned for new developments about the role of mast cells and look for more interest in
mastocytic enterocolitis in the future. I propose that the GI community should adopt the
broader term mastocytic inflammatory bowel disease since there is information indicating
mast cells have an important role in allergic esophagus and stomach problems.

Selected References:

The, FO et al. “Intestinal handling-induced mast cell activation and inflammation in human
postoperative ileus.” Gut 2008; 57:33-40

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

Jakate, S. “Mastocytic Enterocolitis: Increased mucosal mast cells in chronic intractable
diarrhea.” Arch Pathol Lab Med 2006; 130:362-367.

Copyright 2008 Dr. Scot M. Lewey www.thefooddoc.com

The Food Doc, Dr. Scot Lewey, is an expert medical doctor specializing in digestive
diseases and food related illness, especially food allergies, celiac disease and colitis.
Dr. Lewey’s expert reputation as the Food Doc is established by a foundation of formal
training in internal medicine, pediatrics, and gastroenterology (diseases of the digestive
tract), his personal and family experience with gluten and milk sensitivity, and over two
decades as a practicing physician, clinical researcher, author and speaker. Access this
expert knowledge online today at www.thefooddoc.com