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