an ezine article -

Mastocytic Enterocolitis or Mastocytic Inflammatory Bowel
Disease (MIBD), A New Epidemic?
By Dr. Scot Lewey

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.