Hindawi Publishing Corporation

Gastroenterology Research and Practice

Volume 2012, Article ID 950582, 6 pages
doi:10.1155/2012/950582

Research Article
Allergic Mastocytic Gastroenteritis and Colitis:
An Unexplained Etiology in Chronic Abdominal Pain and
Gastrointestinal Dysmotility

A. Akhavein M,1 N. R. Patel,2 P. K. Muniyappa,3, 4 and S. C. Glover1, 2

1 Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, 1600 SW Archer Road, HD512A,
P.O. Box 100214, Gainesville, FL 32610, USA
2 Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
3 Department of Medicine, Mercy Medical Center, Chicago, IL 60616, USA
4 Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA

Correspondence should be addressed to S. C. Glover, [email protected]

Received 23 September 2011; Revised 17 November 2011; Accepted 18 November 2011

Academic Editor: Giovanni Barbara

Copyright © 2012 A. Akhavein M et al. This is an open access article distributed under the Creative Commons Attribution License,
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
symptoms in individuals with a history of atopic disease. A retrospective chart review of individuals seen in a university GI practice
was conducted and twenty-four subjects were identified. The majority had abdominal pain, early satiety, and nocturnal awakening.
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.

1. Introduction symptoms of GI dysmotility (GID). Dysmotility is one of the

proposed mechanisms in the pathophysiology of IBS [4, 5].
Chronic abdominal pain together with symptoms of altered On the other hand, one of the most studied immune
gastrointestinal motility defines a rather common presenting cells associated with IBS is the mast cell. Increased numbers
tableau in the gastroenterology practice, shared by idiopathic of GI mast cells have been documented in a subset of
gastroparesis (IGP) and functional GI disorders such as IBS patients throughout the small and large intestine [6]:
irritable bowel syndrome (IBS) and functional dyspepsia in the duodenum [7], jejunum [8], ileum [9, 10], cecum
(FD), among others. [11, 12], ascending and descending colon, and rectum [10].
IBS is defined as a chronic continuous or remittent gas- Mast cells and their mediators play a potential role in the
trointestinal illness characterized by frequent unexplained pathophysiology of IBS by causing sensorimotor dysfunction
symptoms that include abdominal pain, bloating, and bowel of the gut through interactions with the enteric nervous
disturbance, which may be either diarrhea or constipation system [13–15]. Moreover, IBS has been increasingly linked
or an erratic bowel habit that has features of both. IBS is to food allergy [16–19] in which mast cells play a critical role
a common illness with an overall prevalence of about 10– [20].
15% within the general population [1–3]. Similar to FD Another functional GI disorder with chronic abdominal
and IGP, IBS also presents with chronic abdominal pain and pain and GID symptoms is functional dyspepsia (FD),
2 Gastroenterology Research and Practice

characterized by abdominal pain and symptoms of GID, Table 1: Summary of signs and symptoms of the subjects (n = 24).
such as early satiety and postprandial fullness, without any
Sign or Symptom Present Not Present Not Available
evidence of structural diseases.
The goal of this retrospective caseseries was to describe a Abdominal pain 24 (100%) 0 (0%) 0 (0%)
subgroup of patients whose main symptomatology consisted Early satiety/bloating 23 (95.8%) 1 (4.2%) 0 (0%)
of chronic abdominal pain and symptoms suggestive of GID, Constipation 9 (37.5%) 15 (62.5%) 0 (0%)
who had associated increased numbers of GI mast cells, Diarrhea 11 (45.8%) 13 (54.2%) 0 (0%)
history of food/environmental allergy, nocturnal awakening, Succussion splash 13 (54.2%) 5 (20.8%) 6 (25%)
and/or mast cell instability. Gastrointestinal mast cells excess Nocturnal awakening 19 (79.2%) 0 (0%) 5 (20.8%)
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 Table 2: Summary of the allergic history of the subjects (n = 24).
cells mediators’ release, for example, increased circulating
histamine levels. History Positive Negative Not available
Immunotherapy 8 (33.3%) 16 (66.7%) 0 (0%)
Food allergy 9 (37.5%) 11 (45.8%) 4 (16.7%)
2. Methods
Environmental allergy 16 (66.7%) 2 (8.3%) 6 (25%)
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: independent of maturation and activation status. Therefore,
(1) patients with GID symptoms or symptoms of func- CD117/Kit was used in these patients as a robust mast cell
tional disorders such as IBS or FD, marker antigen (Figure 1) [23]. The biopsies taken were
mucosal, so the CD117 (+) cells detected were mucosal mast
(2) patients with available GI tract mucosal biopsies cells and not interstitial cells of Cajal or submucosal mast
and CD117 staining of the specimens for mast cell cells. CD-25 marker assessment and serum tryptase levels
evaluation. measurement were not done since these had already been
studied in previous papers [20, 24].
The data extracted from the patients’ charts included the
Delayed gastric emptying was defined as emptying time
following:
greater than 200 minutes on solid-phase gastric emptying
(i) demographic data including age, sex, and race, scan.
The cutoff point for increased number of GI mucosal-
(ii) history and physical examination with emphasis on
mast cells was defined as more than 20 mast cells per high
GI symptoms: abdominal pain, early satiety, diarrhea,
power field (hpf) on microscopy using immunostaining for
constipation, abdominal bloating, nocturnal awaken-
CD117. Other inflammatory and allergy parameters col-
ing, history of food/environmental allergy, history of
lected included serum IgE and whole-blood histamine levels.
immunotherapy, and presence of succussion splash,
Normal whole-blood histamine level range was defined by
(iii) laboratory data including CBC, ESR, CRP, serum IgE, our lab as less that 300 nmol/L, which is in concordance with
whole-blood histamine, and stool studies, the ranges proposed in the literature [25]. Normal serum IgE
(iv) history of medications, including improvement in GI level range was defined by our lab as 10–179 IU/mL.
complaints after being put on medication, The collected data was analyzed using descriptive statisti-
cal methods, with means, standard deviations, and standard
(v) pathology reports and histological slides, errors being reported.
(vi) radiology reports including nuclear medicine studies
and CT scans,
3. Results
(vii) results of food allergy testing by RAST (radioaller-
gosorbent test) or SPT (skin prick testing), This population consisted of 21 females and 3 males, with
(viii) CD-25 marker assessment and serum tryptase levels an age range of 16 to 64 and a mean age of 34.5. All the
measurement were not recorded since these had patients had a history of abdominal pain, with 45.8% of them
already been studied in previous papers. having diarrhea and 37.5% having constipation (Table 1).
Of subjects with available data, 5.5% had a history of food
Staining options available for mast cells include tolui- allergy only, 50% had a history of environmental allergies
dine blue staining, tryptase staining, the Giemsa staining, only, and 43.7% had both. Specific details of patients’
and CD117 marker detection [21]. Unlike CD25 which histories and symptoms are summarized in Tables 1 and 2.
is expressed on neoplastic mast cells [22], the CD117 For the 14 out of 24 patients who had a gastric emptying
marker (The c-Kit antigen) is detectable both in normal scintigraphy done to explain their upper GI symptoms,
and neoplastic mast cells either by flow cytometry or by the mean emptying time was 204 minutes on the solid-
immunohistochemistry. The stem cell factor (SCF) receptor phase gastric emptying scan (Figure 2 and Table 3). The
Kit (CD117) antigen is expressed on all types of mast cells scintiscanning was performed over 90 minutes using the
Gastroenterology Research and Practice 3

64 µm 64 µm
(a) (b)

Figure 1: Anti-CD117 staining was used to identify the mast cells. Images of positive CD117 in the small bowel (a) and the colon (b). Positive
cells are brown. Abnormal CD117 is considered to be more than 20 cells per high-power field (hpf). Bar length is equal to 64 µm.

Table 3: Summary of solid-phase gastric emptying time (minutes). Mast cell numbers by CD117
100
Solid-phase gastric
emptying time (min) 80
Total number of values Mast cells per HPF
14
available
60
Minimum 10.0
25% percentile 86.5
Median 132.0 40
75% percentile 338.75
Maximum 500.0 20
Mean 204.357
Std. deviation 162.67
Std. error 43.4753 0
Stomach Small bowel Colon
Lower 95% CI∗ of mean 110.434
Upper 95% CI∗ of mean 298.28 Location
∗
CI: confidence interval. 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
600 field (hpf). Mean number in the small bowel was 57 cells per hpf.
Mean number in the colon was 37 cells per hpf.

400 cells per hpf, and in the colon was 37 cells per hpf (Figure 3
Time (min)

and Table 4). Unlike dense aggregates of mast cells seen in

systemic mastocytosis biopsies [26], our specimens showed
diffused mast cell infiltration of the mucosa (Figure 1).
200
The inflammatory and allergy markers studied included
serum IgE level and whole-blood histamine levels. The
mean serum IgE level was 213 IU/mL, and the median
was 37 IU/mL. The mean whole-blood histamine level was
0
798 nmol/L (Figure 4 and Table 5). Elevated serum IgE levels
Gastric emptying time (solids)
were seen in 13.6% of patients with available data, and 95%
Figure 2: Frequency distribution of solid-phase gastric emptying of patients with available data had an elevated whole-blood
times. Scan was performed over 90 minutes. Data was available for histamine level. Serum IgE levels data was available for 22
14 of 24 patients. Mean emptying time was 204 minutes. Emptying patients, and whole-blood histamine levels data was available
times greater than 200 minutes are suggestive of gastroparesis. for 20 patients. Summary of collected values is shown in
Tables 3, 4, and 5 and Figures 2, 3, and 4.

standard protocol at the University of Illinois Nuclear 4. Limitations

Medicine Division at that time (Figure 2 and Table 3).
The mean number of the mast cells in the stomach was The study’s retrospective design imposed limitations in-
39 cells per high-power field (hpf), in the small bowel was 57 herent in the nature of such studies. Therefore, the date
4 Gastroenterology 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 Stomach Small Bowel Colon

Total number of values available 16 22 13
Minimum 16.0 30.0 1.0
25% percentile 30.75 39.0 28.0
Median 35.5 48.5 40.0
75% percentile 43.0 70.0 47.5
Maximum 82.0 90.0 68.8333
Mean 39.25 52.9545 37.9103
Std. deviation 15.7628 17.5105 17.177
Std. error 3.94071 3.73325 4.76404
Lower 95% CI∗ of mean 30.8506 45.1908 27.5304
Upper 95% CI∗ of mean 47.6494 60.7183 48.2902
∗
CI: confidence interval.

Table 5: Summary of serum IgE levels and whole blood histamine 2000
levels.
Total IgE Histamine
1500
IU/mL nmol/L
Total number of values
22 20
Units

available 1000
Minimum 3.0 <300
25% percentile 14.75 547.75
Median 37.0 776.0 500
75% percentile 90.0 1025.75
Maximum 1556.0 1597.0
Mean 213.409 798.1 0
Std. deviation 465.573 319.255 Total IgE Histamine
Std. error 99.2605 71.3876 Laboratory test
Lower 95% CI∗ of mean 6.98497 648.682
Upper 95% CI∗ of mean 419.833 947.518 Figure 4: Frequency distribution of serum IgE level and whole
∗
CI: confidence interval.
blood Histamine levels in the group. Mean IgE level was 213 IU/mL
and and Median was 37 IU/mL. Mean Histamine level was
798 nmol/L. Data was available for 22 and 20 patients, respectively.
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 serum IgE levels or whole-blood histamine levels greater
disease. than 300 nmol/L [24, 25, 30]. The corresponding plasma
This study uses data from a 90-minute gastric emptying histamine level would be 3 nmol/L [25].
scintigraphy scans. At the time these individuals were seen, In the current literature, there are two loosely defined
the 90-minute gastric emptying study was standard protocol entities associated with increased numbers on mast cells
in the University of Illinois Nuclear Medicine division. The on gastrointestinal biopsies. The first of these is mastocytic
authors acknowledge that the 4-hour gastric emptying scan enterocolitis. Mastocytic enterocolitis is defined as more
is the new standard of care [27–29]. than 20 mast cells per high-power field by tryptase stain in
individuals with chronic diarrhea of unknown etiology [20].
5. Discussion Mast cell activation syndrome occurs in individuals who have
symptoms associated with mast cell instability including der-
This paper describes a distinct group of GI patients with matographism, flushing, mental fog, or poor concentration,
chronic abdominal pain and symptoms of GI dysmotility, abdominal pain, diarrhea, anaphylaxis, and asthma who have
features that mimic the features of entities such as IBS, FD, a dramatic improvement in their symptoms in response to
or IGP, but who actually suffer from gastrointestinal mast cell antihistamines and H2 blockers. Intriguingly, in this group,
excess and/or instability. These patients frequently exhibit the numbers of mast cells on gastrointestinal biopsies by
features of mast cell excess, including positive history of CD117 or tryptase were between 17 and 23 cells per high-
food and/or environmental allergies, signs and symptoms power field [24]. These distinguishing features between our
such as flushing, pruritus, tachycardia, asthma, headache, or cohort and the two other published GI mast cell disorders are
dermatographism, and suggestive lab data such as elevated summarized in Table 6.
Gastroenterology Research and Practice 5

Table 6: Comparison between different GI mast cell diseases [20, 24].

Cardinal symptoms Number of mast cells/HPF Serum markers

Mastocytic
Abdominal pain, diarrhea >20 N/A
enterocolitis
Mast cell Activation Abdominal pain, dermatographism,
17–23 Serum tryptase
syndrome flushing
Allergic mastocytic Abdominal pain, dysmotility
Gastroenteritis and symptoms (e.g., early satiety, >40 Histamine, IgE
colitis bloating), nocturnal awakening

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