Hindawi Publishing Corporation
Gastroenterology Research and Practice
Volume 2012, Article ID 950582, 6 pages
AllergicMastocytic Gastroenteritis andColitis:
AnUnexplainedEtiology inChronicAbdominalPain and
1Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, 1600 SW Archer Road, HD512A,
P.O. Box 100214, Gainesville, FL 32610, USA
2Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
3Department of Medicine, Mercy Medical Center, Chicago, IL 60616, USA
4Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA
Correspondence should be addressed to S. C. Glover, firstname.lastname@example.org
Received 23 September 2011; Revised 17 November 2011; Accepted 18 November 2011
Academic Editor: Giovanni Barbara
Copyright © 2012 A. Akhavein M et al.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abdominal pain, bloating, early satiety, and changes in bowel habits are common presenting symptoms in individuals with
functional GI disorders. Emerging data suggests that these symptoms may be associated with mast cell excess and/or mast cell
instability in the GI tract. The aim of this retrospective study was to evaluate the contribution of mast cells to the aforementioned
66.7% and 37.5% had a history of environmental and/or food allergy. Solid gastric emptying was increased as were the mean
number of mast cells reported on biopsies from the stomach, small bowel, and colon (>37/hpf) by CD117 staining. Mean whole
blood histamine levels were uniformly elevated. This study suggests that in individuals with these characteristics, consideration
should be given to staining their gastrointestinal biopsies for mast cells as this may provide them with relatively non-toxic but
highly targeted treatment options. Allergic gastroenteritis and colitis may represent a third type of GI mast cell disorder along with
mast cell activation syndrome and mastocytic enterocolitis.
Chronic abdominal pain together with symptoms of altered
gastrointestinal motility defines a rather common presenting
tableauin thegastroenterologypractice,shared byidiopathic
gastroparesis (IGP) and functional GI disorders such as
irritable bowel syndrome (IBS) and functional dyspepsia
(FD), among others.
IBS is defined as a chronic continuous or remittent gas-
trointestinal illness characterized by frequent unexplained
symptoms that include abdominal pain, bloating, and bowel
disturbance, which may be either diarrhea or constipation
or an erratic bowel habit that has features of both. IBS is
a common illness with an overall prevalence of about 10–
15% within the general population [1–3]. Similar to FD
and IGP, IBS also presents with chronic abdominal pain and
symptoms of GI dysmotility (GID). Dysmotility is one of the
proposed mechanisms in the pathophysiology of IBS [4, 5].
On the other hand, one of the most studied immune
cells associated with IBS is the mast cell. Increased numbers
of GI mast cells have been documented in a subset of
IBS patients throughout the small and large intestine :
in the duodenum , jejunum , ileum [9, 10], cecum
[11, 12], ascending and descending colon, and rectum .
Mast cells and their mediators play a potential role in the
of the gut through interactions with the enteric nervous
system [13–15]. Moreover, IBS has been increasingly linked
to food allergy [16–19] in which mast cells play a critical role
Another functional GI disorder with chronic abdominal
pain and GID symptoms is functional dyspepsia (FD),
2 Gastroenterology Research and Practice
characterized by abdominal pain and symptoms of GID,
such as early satiety and postprandial fullness, without any
evidence of structural diseases.
The goal of this retrospective caseseries was to describe a
subgroup of patients whose main symptomatology consisted
of chronic abdominal pain and symptoms suggestive of GID,
who had associated increased numbers of GI mast cells,
history of food/environmental allergy, nocturnal awakening,
and/or mast cell instability. Gastrointestinal mast cells excess
is defined as the presence of greater than 20 mast cells per
high-power field of microscopy in the GI tract mucosa.
Mast cell instability is marked by an increase in mast
cells mediators’ release, for example, increased circulating
A retrospective chart review of the patients seen at the
University of Illinois GI clinics between years 2006 and 2009
was performed. Inclusion criteria were defined as follows:
(1) patients with GID symptoms or symptoms of func-
tional disorders such as IBS or FD,
(2) patients with available GI tract mucosal biopsies
and CD117 staining of the specimens for mast cell
The data extracted from the patients’ charts included the
(i) demographic data including age, sex, and race,
(ii) history and physical examination with emphasis on
ing, history of food/environmental allergy, history of
immunotherapy, and presence of succussion splash,
whole-blood histamine, and stool studies,
(iv) history of medications, including improvement in GI
complaints after being put on medication,
(v) pathology reports and histological slides,
(vi) radiology reports including nuclear medicine studies
and CT scans,
(vii) results of food allergy testing by RAST (radioaller-
gosorbent test) or SPT (skin prick testing),
(viii) CD-25 marker assessment and serum tryptase levels
measurement were not recorded since these had
already been studied in previous papers.
Staining options available for mast cells include tolui-
dine blue staining, tryptase staining, the Giemsa staining,
and CD117 marker detection . Unlike CD25 which
is expressed on neoplastic mast cells , the CD117
marker (The c-Kit antigen) is detectable both in normal
and neoplastic mast cells either by flow cytometry or by
immunohistochemistry. The stem cell factor (SCF) receptor
Kit (CD117) antigen is expressed on all types of mast cells
Table 1: Summary of signs and symptoms of the subjects (n = 24).
Sign or SymptomPresent
Abdominal pain24 (100%)
Early satiety/bloating 23 (95.8%)
Succussion splash13 (54.2%)
Nocturnal awakening 19 (79.2%)
Table 2: Summary of the allergic history of the subjects (n = 24).
Immunotherapy 8 (33.3%)
Food allergy9 (37.5%)
Environmental allergy 16 (66.7%)
independent of maturation and activation status. Therefore,
CD117/Kit was used in these patients as a robust mast cell
marker antigen (Figure 1) . The biopsies taken were
mucosal, so the CD117 (+) cells detected were mucosal mast
cells and not interstitial cells of Cajal or submucosal mast
cells. CD-25 marker assessment and serum tryptase levels
measurement were not done since these had already been
studied in previous papers [20, 24].
Delayed gastric emptying was defined as emptying time
greater than 200 minutes on solid-phase gastric emptying
The cutoff point for increased number of GI mucosal-
mast cells was defined as more than 20 mast cells per high
power field (hpf) on microscopy using immunostaining for
CD117. Other inflammatory and allergy parameters col-
lected included serum IgE and whole-blood histamine levels.
Normal whole-blood histamine level range was defined by
our lab as less that 300nmol/L, which is in concordance with
the ranges proposed in the literature . Normal serum IgE
level range was defined by our lab as 10–179IU/mL.
The collected data was analyzed using descriptive statisti-
cal methods, with means, standard deviations, and standard
errors being reported.
This population consisted of 21 females and 3 males, with
an age range of 16 to 64 and a mean age of 34.5. All the
having diarrhea and 37.5% having constipation (Table 1).
Of subjects with available data, 5.5% had a history of food
allergy only, 50% had a history of environmental allergies
only, and 43.7% had both. Specific details of patients’
histories and symptoms are summarized in Tables 1 and 2.
For the 14 out of 24 patients who had a gastric emptying
scintigraphy done to explain their upper GI symptoms,
the mean emptying time was 204 minutes on the solid-
phase gastric emptying scan (Figure 2 and Table 3). The
scintiscanning was performed over 90 minutes using the
Gastroenterology Research and Practice3
cells are brown. Abnormal CD117 is considered to be more than 20 cells per high-power field (hpf). Bar length is equal to 64µm.
Table 3: Summary of solid-phase gastric emptying time (minutes).
emptying time (min)
Total number of values
Lower 95% CI∗of mean
Upper 95% CI∗of mean
∗CI: confidence interval.
Gastric emptying time (solids)
Figure 2: Frequency distribution of solid-phase gastric emptying
times. Scan was performed over 90 minutes. Data was available for
14 of 24 patients. Mean emptying time was 204 minutes. Emptying
times greater than 200 minutes are suggestive of gastroparesis.
standard protocol at the University of Illinois Nuclear
Medicine Division at that time (Figure 2 and Table 3).
The mean number of the mast cells in the stomach was
39 cells per high-power field (hpf), in the small bowel was 57
Mast cells per HPF
Mast cell numbers by CD117
Figure 3: The distribution of mast cells based on the location in the
GI tract. Mean number in the stomach was 39 cells per high-power
field (hpf). Mean number in the small bowel was 57 cells per hpf.
Mean number in the colon was 37 cells per hpf.
cells per hpf, and in the colon was 37 cells per hpf (Figure 3
and Table 4). Unlike dense aggregates of mast cells seen in
systemic mastocytosis biopsies , our specimens showed
diffused mast cell infiltration of the mucosa (Figure 1).
The inflammatory and allergy markers studied included
serum IgE level and whole-blood histamine levels. The
mean serum IgE level was 213IU/mL, and the median
was 37IU/mL. The mean whole-blood histamine level was
798nmol/L (Figure 4 and Table 5). Elevated serum IgE levels
were seen in 13.6% of patients with available data, and 95%
of patients with available data had an elevated whole-blood
histamine level. Serum IgE levels data was available for 22
for 20 patients. Summary of collected values is shown in
Tables 3, 4, and 5 and Figures 2, 3, and 4.
The study’s retrospective design imposed limitations in-
herent in the nature of such studies. Therefore, the date
4Gastroenterology Research and Practice
Table 4: Summary of the GI tract biopsy/CD117 staining results: number of mast cells per high power field (hpf).
# Mast cells/hpf
Total number of values available
Lower 95% CI∗of mean
Upper 95% CI∗of mean
∗CI: confidence interval.
Table 5: Summary of serum IgE levels and whole blood histamine
Total number of values
Lower 95% CI∗of mean
Upper 95% CI∗of mean
∗CI: confidence interval.
presented herein is of a descriptive nature. In spite of this,
this current study serves as a basis for future cohort studies
and clinical trials that evaluate the role of mast cells in GI
This study uses data from a 90-minute gastric emptying
scintigraphy scans. At the time these individuals were seen,
the 90-minute gastric emptying study was standard protocol
in the University of Illinois Nuclear Medicine division. The
authors acknowledge that the 4-hour gastric emptying scan
is the new standard of care [27–29].
This paper describes a distinct group of GI patients with
chronic abdominal pain and symptoms of GI dysmotility,
features that mimic the features of entities such as IBS, FD,
excess and/or instability. These patients frequently exhibit
features of mast cell excess, including positive history of
food and/or environmental allergies, signs and symptoms
such as flushing, pruritus, tachycardia, asthma, headache, or
dermatographism, and suggestive lab data such as elevated
Figure 4: Frequency distribution of serum IgE level and whole
blood Histamine levels in the group. Mean IgE level was 213IU/mL
and and Median was 37IU/mL. Mean Histamine level was
798nmol/L. Data was available for 22 and 20 patients, respectively.
serum IgE levels or whole-blood histamine levels greater
than 300nmol/L [24, 25, 30]. The corresponding plasma
histamine level would be 3nmol/L .
In the current literature, there are two loosely defined
entities associated with increased numbers on mast cells
on gastrointestinal biopsies. The first of these is mastocytic
enterocolitis. Mastocytic enterocolitis is defined as more
than 20 mast cells per high-power field by tryptase stain in
individuals with chronic diarrhea of unknown etiology .
symptoms associated with mast cell instability including der-
matographism, flushing, mental fog, or poor concentration,
a dramatic improvement in their symptoms in response to
antihistamines and H2 blockers. Intriguingly, in this group,
the numbers of mast cells on gastrointestinal biopsies by
CD117 or tryptase were between 17 and 23 cells per high-
power field . These distinguishing features between our
summarized in Table 6.
Gastroenterology Research and Practice5
Table 6: Comparison between different GI mast cell diseases [20, 24].
Cardinal symptoms Number of mast cells/HPFSerum markers
Mast cell Activation
Abdominal pain, diarrhea
Abdominal pain, dermatographism,
Abdominal pain, dysmotility
symptoms (e.g., early satiety,
bloating), nocturnal awakening
17–23 Serum tryptase
As mentioned in the introduction to this paper, IBS
has been associated with elevated mast cell numbers [6–
9, 11, 12] and food allergy [16–19]. The cohort we describe
enterocolitis and mast cell activation syndrome. They are
(1) documented GI dysmotility, (2) nocturnal awakening,
(3) elevated histamine levels, (4) history of food or envi-
ronmental allergy, (5) significantly higher numbers of mast
cells per high-power field, that is, approximately 40 per
high-power field on average. As such, we propose that our
cohort of patients represents a possible third entity wherein
elevated numbers of mast cells are noted on gastrointestinal
biopsies in patients who have previously been classified as
having IBS, functional dyspepsia, or idiopathic gastroparesis.
We suggest that this disorder could potentially be referred
to as allergic mastocytic gastroenteritis and colitis as these
patients have documented allergies, elevated histamine lev-
associated with uncontrolled asthma  and in our cohort
awakening in our cohort was due to a spike in leukotrienes.
As other authors have suggested, treatment of gas-
trointestinal mast cell disease should be focused on block-
ade of H1 and H2 and mast cell stabilization. These
therapeutic approaches include H1 receptor antagonists
such as diphenhydramine (Benadryl), cetirizine (Zyrtec),
loratadine (Claritin) , H2 receptor antagonists such
as ranitidine (Zantac) and famotidine (Pepcid), and mast
cell membrane stabilizers such as oral cromolyn sodium
(Gastrocrom) [32–36]. Because of the nocturnal awakening
observed in our patients, we would also suggest adding
an antileukotriene such as montelukast (Singulair) or a 5-
liopoxygenase inhibitor such as zileuton extended-release
tablets (Zyflo CR). In patients with more severe symptoms
that significantly disrupt their activities of daily living and/or
sleep, we suggest the addition of budesonide (Entocort) or a
short course of prednisone.
In conclusion, herein we report a cohort of patients with
gastrointestinal mast cell disease separate and distinct from
systemic mastocytosis and the aforementioned GI mast cell
disorders. Further characterization of this possible disorder
is needed in order to clearly distinguish these patients from
those with IBS or systemic mastocytosis.
Conflict of Interests
The authors declare that they have no conflict of interests.
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