Gastroenteritis

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Eosinophilic gastroenteritis: A state-of-the-art review
Author’s names
Zhang MingMing, MD，Li YanQing, MD, PhD
Authors’ institutional affiliations
Zhang Ming-Ming, Li Yan-Qing, Department of Gastroenterology, Laboratory of
Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong, China.
Corresponding author:
YanQing Li, MD/PhD
Department of Gastroenterology, Laboratory of Translational Gastroenterology, Shandong
University, Qilu Hospital, 107 Wenhuaxi Road, Jinan 250012, China
Tel & Fax: +86-531-82166090
E-mail: liyanqing@sdu.edu.cn
Disclosure statement
The authors disclose no conflicts with any commercial groups concerning the manuscript.

Acknowledgements
This study was funded by National Natural Science Foundation of China (grant number
81330012, 81300284) and the Shandong Province Science and Technology Committee (grant
number 2013GSF11833).
Abstract
Eosinophilic gastrointestinal disorders are a series of diseases which include eosinophilic
esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and
eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and
heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in
the absence of secondary causes, presenting with a variety of gastrointestinal manifestations.
Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear.
Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal
tract wall, eosinophilic gastroenteritis is classified into three different patterns including
predominantly mucosal pattern, predominantly muscular pattern and predominantly serosal
pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a
high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other
evidences such as laboratory results, radiological findings and endoscopy can also provide
important diagnostic evidences for eosinophilic gastroenteritis. And these indirect
information together with histological results will lead to a definitive diagnosis of
eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered

as initial treatment strategy before drug treatment. Corticosteroids are the main medication
for eosinophilic gastroenteritis, and have a dramatic therapeutic efficacy. Yet others
medications need further verify their effects in clinical practice, and surgery should be
avoided as far as possible.
Key words: eosinophilic gastroenteritis, eosinophilia, eosinophil
Introduction
Eosinophilic gastrointestinal disorders are a series of diseases which selectively affect the
segments of gastrointestinal (GI) tract with eosinophilic inflammation in the absence of
secondary causes for eosinophilia [1]. These disorders can be divided into five principal
groups: eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis (EG),
eosinophilic enteritis, and eosinophilic colitis [1]. Among these disorders, EG is an
uncommon and heterogeneous disease characterized by eosinophilic infiltration of the
gastrointestinal (GI) tract, presenting with a variety of GI manifestations which depend on the
site of affected GI tract and the layer of the GI wall involved [2, 3]. In 1937, Kaijser
described this disorder for the first time [2]. Then in 1970, Klein et al [3] defined three types
of this disorder based on the clinical manifestations and the depth of involvement including
predominantly mucosal disease, predominantly muscular disease, and predominantly serosal
disease. Although stomach and duodenum are the most commonly affected organs, it might
involve any segment of the GI tract from the esophagus to the rectum [4, 5]. There are
hundreds of cases reported in the medical literatures, most of them are just single case reports
or rather small case series [6-8]. Thus we have only a limited understanding of this disease

until now. The underlying molecular mechanisms of this disease are still unknown, and
definitive epidemiological features have also not been established. Moreover, the etiology has
yet to be fully elucidated, and its diagnosis requires a high degree of clinical suspicion.
Fortunately, good therapeutic efficacy has been achieved by oral corticosteroids for a short
period based on empirical experience and it is used as the main therapeutic options for EG
patients [6].
Although there is a complete lack of a large, randomized, controlled trial to clearly
establish definitive information referring to EG, information provided by single case reports
or small case series over several decades and from different countries could also allow us to
assume some common observations as characteristics for this disease. Therefore, our review
aims to completely summarize the latest, most relevant published information referring to EG
and provide a more comprehensive understanding.
Epidemiology of EG
Eosinophilic gastroenteritis is an uncommon and heterogeneous disease, so there is no large
survey to investigate its incidence. Although hundreds of cases or small case series have been
reported worldwide, the exact incidence of eosinophilic gastroenteritis is still difficult to
estimate. The current case reports suggest that EG can affect any age group from infancy to
the aged, however, most commonly between thirties to forties years of age, with a slightly
male predominance [2, 3, 6-8]. Though no accurate epidemiological estimation for EG exists
up to now, some previous studies have also provided population-based prevalence estimates.
Guajardo et al [9] reported that the prevalence in the USA is approximately 2.5/100,000 for
EG with a male: female ratio of 1.2:1. However, extrapolating responses from US samples,

Spergel et al [10] recently estimated an overall prevalence of 28/100,000 for EG. Kinoshita et
al. [11] concluded that the prevalence of EG in Japan is approximately 5.5 times higher than
that of USA and the male/female ratio for EG was also 1.2:1. However, the exact prevalence
of EG is unclear. Reed et al [12] conducted a retrospective cohort study in 2014 and
calculated that EG was seen in approximately 30/100,000 procedures. The prevalence is
basically coincided with a published prevalence estimate of 28/100,000 by Spergel et al [10].
However, they found that EG may be more prevalent in male children and female adults,
which is quite different from those have been reported [2, 3, 6-9, 11]. Considering the
relatively small amount of patients with EG, the results may be underpowered to conclude
differences between subgroups. With the increased awareness of EG by clinicians and
pathologists, this disease will be diagnosed more accuracy, and further contributing to the rise
in its epidemiology. In addition, it must be taken into account that the larger series in future
will provide a more comprehensive analyzes of EG’s epidemiology.
Pathophysiology of EG
Though eosinophils are normally present in the lamina propria except esophagus, the number
of eosinophils along the GI tract is various and the highest concentrations are found in the
cecum and appendix [13, 14]. It is involved in the mucosal immune system of GI tract, and
has a role in host defense for healthy individuals [15]. The number of eosinophils increases in
the pathogenesis of numerous inflammatory processes, including parasitic infections and
allergic diseases. Then, the activated eosinophils produce and release highly bioactive
inflammatory mediators like eosinophil cationic protein (ECP), eosinophil-derived
neurotoxin (EDN), eosinophil peroxidase (EPO) and major basic protein (MBP). These

cationic proteins possessing ribonuclease and antiviral activity are cytotoxic to the GI
epithelium. This could trigger degranulation of mast cells and release of cytokines (e.g., IL-1,
IL-3, IL4, IL5, IL13, transforming growth factors), chemokines (e.g., eotaxin, Regulation
upon Activation Normal T-cell Expressed and Secreted (RANTES)), lipid mediators (e.g.,
leukotrienes, platelet activating factor), and neuromediators (e.g., substance P, vasoactive
intestinal polypeptide) [14, 16, 17].
Moreover, the Th2-type immune response seems to be involved in EG [18-22]. Recent
studies also strongly support that Th-2 cytokines (e.g., IL-4, IL-5 and IL-13) and chemokines
such as eotaxin (e.g., CCL26) play a critical role in the pathogenesis of eosinophilic
gastroenteritis. It was found that levels of TH2 cytokines (e.g., IL4, IL5, and IL13) and the
eosinophil-related chemokine eotaxin-3 (CCL26) are upregulated [22]. But different from
eosinophilic esophagus, EG has a prominent and conserved transcriptome that has minimal
overlap with that of EE, the respective transcriptome of which provides a rationale for shared
and unique therapeutic intervention strategies.
Histopathology of EG
Except for the squamous mucosa of the esophagus, the lamina propria of the remaining GI
tract contains constitutive eosinophils. And intramucosal eosinophils counts vary widely
among normal individuals, depending on region, climate, age, exposure to food allergens and
infectious agents, etc. Furthermore, the number of eosinophil in the same individual is
believed to vary within different segments of GI tract.
Up to now, there are relatively limited information available regarding normal counts or
distribution of eosinophils in GI tract. In 19 children from Ohio, DeBrosse et al [23] found

peak eosinophil counts of 8 eosinophils/HPF in antral and 11 in oxyntic mucosal biopsies.
Talley et al [24] found a mean eosinophil count of 12 eosinophils in 5 HPF in biopsies from
the cardia, body, and antrum of asymptomatic adult volunteers from Northern Sweden.
Recently, Lwin et al [25] noted that the mean eosinophil count for the 135 normal controls
was 4 eosinophils/HPF (±4 SD), equivalent to 15 ± 17 SD eosinophils/mm2
(range, 0 to 110).
And there were no significant differences between the counts in biopsies from the antrum and
corpus. These results are in agreement with those of DeBrosse [23] and Tally [24]. Moreover,
these studies also confirms that, in the population of the United States, the normal gastric
eosinophilic counts are usually ＜ 38 eosinophils/mm2
，equivalent to 9 eosinophils/HPF. In
2015, Matsushita T et al [26] first elucidated the number and distribution of eosinophils in the
mucosa throughout GI tract in a Japanese adult population. The results showed a significant
increase in the number of eosinophils from the esophagus to the right colon (mean ± SD/mm2
:
0.07 ± 0.43 for the esophagus, 12.18 ± 11.39 for the stomach, and 36.59 ± 15.50 for the right
colon), compared with a decrease in the left colon (8.53 ± 7.83). They also found race and
environmental factors seem to have only a little effect on eosinophil densities and
distributions. However, based on current available data，there is no established consensus on
a diagnostic threshold with regard to eosinophil count for EG. However, based on current
available data, there is no established consensus on a diagnostic threshold with regard to
eosinophil count for EG. Due to eosinophilic patchy infiltrates, eosinophilia was potentially
missed in these patients. And the diagnostic threshold number of gastric eosinophils required
in EG varies among investigators, ranging from 20 eosinophils in one HPF to 30 eosinophils
per HPF in at least five HPFs [27, 28]. In clinic practice, a benchmark of more than 20

eosinophils/HPF has been suggested when EG is a high degree of suspicion [29]. In a review,
Collins et al [30] tactfully suggested less emphasis on eosinophil quantity and focusing more
on additional pathologic changes and also proposed using the term “mucosal eosinophilia” to
describe increased numbers of mucosal eosinophils without other histologic alterations, and
reserving the term “EG/colitis” for cases with additional pathologic changes. A recent study
[25] recommend that the term ‘histological eosinophilic gastritis’ be used for the diagnosis in
patients who: (1) have gastric biopsies that show an average density ＞127 eosinophils/mm2
(or ＞30 eosinophils/HPF on microscopes equipped with wide-lens oculars) in at least five
separate HPFs; (2) have no known associated causes of eosinophilia (e.g., Helicobacter
pylori infection, Crohn’s disease, parasitic infections, and hematological or lymphoid
disorders).
Clinical manifestations of EG
EG is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of
the GI tract, presenting with a variety of GI manifestations which depend on the site of
affected GI tract and the layer of the GI wall involved [2, 3]. And many patients had a history
of atopic conditions including asthma, allergic rhinitis or atopic dermatitis, and allergy to
medicine food or pollen [12, 31]. Although symptoms of EG were non-specific and various,
abdominal pain and nausea/vomiting were the most frequent presenting symptoms in children
and adults [12, 27, 31, 32]. Especially, children and adolescents maybe present with growth
retardation, failure to thrive, delayed puberty or amenorrhea.
Based on clinical manifestations and depth of eosinophilic infiltration into the GI tract wall,
Klein et al. [3] proposed a classification of EG into three different patterns, including

predominantly mucosal pattern, predominantly muscular pattern and predominantly serosal
pattern. Predominantly mucosal pattern is the most common presentation, characterized by
mucosal and submucosal involvement [33]. These patients present mainly with abdominal
pain, nausea, vomiting, diarrhea, bleeding, anemia, protein-losing enteropathy, malabsorption,
and weight lose. Predominantly muscular pattern is the second common presentation,
characterized by muscle layers involvement [33]. Patients present more with bowel
thickening and symptoms of pyloric or intestinal obstruction. And the stomach and
duodenum are the most commonly affected segments. Predominantly serosal pattern is the
rarest presentation of EG, in which eosinophil-rich inflammatory infiltrate permeates all
layers of the digestive wall and reaches the serosal cover [33]. And eosinophilic ascites are
regarded as the special feature of this pattern, which has favorable response to corticosteroid
treatment [34]. Interestingly, according to Klein et al classification, a French study [27] found
that predominantly serosal pattern of EG seemed to have a relatively good prognosis
presenting a majority of single flare and no continuous chronic course. On the contrary,
predominantly mucosal pattern presented mostly a chronic continuous course, and
predominantly muscular pattern was more likely to relapse.
Though there is classification of EG, the layers involved are still not easy to find in a real
clinical practice. This was caused by that only mucosal and submucosal biopsies were taken
in almost all cases and clinical and pathologic features often overlap. Recently studies [32]
debated that it was necessary to focus more on the correlation of the layers of GI wall
predominately affected and symptoms.
In addition to the common presentations noted above, there are single case reports or case

series of patients with EG presenting with a variety of unusual complications. Pancreatitis
secondary to EG was the common complication caused by mechanical obstruction of the
pancreatic duct secondary to eosinophilic infiltration of the duodenum [27, 34]. It was
reported that eosinophilic infiltration could lead to edema, fibrosis and distortion in the
ampulla and periampullary duodenum, resulting in pancreatitis [35]. Some cases will
typically present as an acute bowel obstruction which is a combination of both mechanical
obstruction due to stricture and functional obstruction due to inflammation, edema, and
decreased GI motility [36]. In most cases, these obstructions are reversible with corticosteroid
treatment, avoiding the unnecessary surgery treatment. Several studies also had reported
patients presenting with duodenal ulcer or perforation [37, 38]. Only treatment with proton
pump inhibitor therapy is ineffective for duodenal ulcer of EG, suggesting an etiology for the
ulcer other than acid peptic disease. In stark contrast, duodenal ulcer does respond well to
corticosteroid treatment. Perforation usually requires surgical repair immediately and
represents a transmural involvement of eosinophilic infiltration. Other compilations, such as
cystitis, hepatic dysfunction, had also been reported as single case report [39-41].
Diagnosis of EG
Though there is no standard guideline for the diagnosis of EG, a high degree of clinical
suspicion is especially necessary [20]. Definitive diagnosis requires typical GI symptoms
coupled with increased eosinophils in biopsy specimens from the GI tract wall. Moreover,
exclusion of other potential causes for the intestinal eosinophilia including parasitic
infections, side effects of drugs, inflammatory bowel disease (IBD), connective tissue
diseases, and lymphoproliferative malignancies [42] (Table 1). Thus, the clinical history,

laboratory results, endoscopy and radiological findings are essential before the final diagnosis
of EG (Figure 1).
Laboratory results
Peripheral eosinophilia in the context of GI symptoms is a useful clue to EG，but this test is
not a reliable diagnostic criterion. Many studies found that peripheral eosinophilia was absent
in some EG patients [11, 31, 43]. Therefore, absence of peripheral eosinophilia should not be
a deterrent from performing an endoscopy with biopsies when EG is clinically suspected.
Furthermore, it was [31] found that peripheral eosinophil count was not a reliable
observational index to estimate disease activity. Therefore it was not reliable for following up
patients after therapy, because patients continued to have similarly elevated eosinophil counts
regardless of their histological response to therapy. Allergy evaluation includes total IgE
level and the use of commonly available tests including skin prick tests (SPT) and
radioallergosorbent tests (RAST) detecting IgE antibody specific to inhaled and ingested
allergens [14]. Although positive skin prick tests and/or elevated serum total IgE levels had
been detected indeed in some of patients [1], they also could be found in parasitic infection,
food allergy etc.，resulting in being not a special indicator for EG. Moreover, it was reported
that higher levels of fecal eosinophilic cationic protein (ECP), serum ECP and
eosinophil-derived neurotoxin (EDN) were found in EG compared with other inflammatory
bowel diseases, such as ulcerative colitis and Crohn’s disease [44]. Zhang et al [32] reported
that 92.8% of patients in their study had an elevated a 2-macroglobulin level, which maybe a
useful clue to EG.

Radiological findings and endoscopy
The radiological findings in only about two thirds patients with EG are variable and
unspecific [6]. In most of patients with EG, radiological findings are normal. Moreover,
nonspecific diffuse or local mucosal fold thickening may be the common manifestation in
predominantly mucosal pattern of EG, and other manifestations include polyps, ulcerations,
luminal narrowing. Stenosis or obstruction, rigidity and dysmotility may be found in patients
with predominantly muscular pattern. Radiological findings show that the present of ascites is
regarded as the feature of predominantly serosal pattern. Given multiple layers of the GI wall
can be involved, radiological findings often coexist. If patents with EG present with
pancreatitis, radiological findings may reveal the sign of pancreatitis, diffuse wall thickening
in the duodenum, and/or ascites [34]. If patents present with cystitis, diffuse wall thickening
of the bladder wall may exist [40]. Several reports had shown endoscopic exams were normal
in about half of patients. The most common gastric and duodenal finding was mucosal
erythema [12, 32]. In addition to mucosal erythema, other signs include mucosal hyperemia,
thickening of folds, friability, areas of roughening, whitish specks, erosions, superficial ulcers,
or nodularity. Some studies reported that eosinophilic infiltration was found in biopsies from
areas of relatively normal endoscopic appearance or radiological findings, but such
infiltration was absent in some areas with abnormities as described above in [2, 32]. This
apparent inconsistency may result from the characteristically patchy involvement of
eosinophilic infiltration as noted in previous studies [7, 31, 32]. Therefore, multiple biopsies
in both abnormal and relative normal appearing mucosa, particularly in the second part of
duodenum, are strongly suggested.

Furthermore, if eosinophilic infiltrations are restrictive mainly to the submucosa or serosa,
mucosal biopsies may be negative. In the circumstances, a full-thickness surgical biopsy may
be necessary if confirmed by a high degree of suspicion derived from clinical manifestations
and radiologic findings [8, 45, 46]. Because of the inherent limitations of endoscopically
obtained biopsies，it is likely that intestinal eosinophilia was potentially missed. Capsule
endoscopy is a good selection to find intestinal abnormalities including multiple erythema,
villous atrophy [2], incomplete obstruction with ulcerated mucosa alternating with preserved
areas [47] or a mimicking of mucosal diaphragms with complete capsule retention [48].
Treatment of EG
Up to now, there is no consensus optimal treatment strategy of EG. On account of
heterogeneous presentations and extremely low incidence of EG, there is a complete lack of
the large, randomized, controlled trials to clearly establish standard treatment guideline.
Current treatment of EG is based mainly on evidence in case reports and case series for a
variety of agents, including dietary treatment, corticosteroid therapy and other drugs. If
patients with EG appear to perforation or obstructive manifestation, it should be necessary to
consider undergoing surgery to repair damages or relieve obstruction. One study [49]
proposed a therapeutic strategy. First, they recommended avoiding specific allergen (airborne
and food allergen). If this is not feasible or failed to achieve improvement, then they
recommended glucocorticoid therapy, including starting with topical delivery and then
considering systemic delivery (Table 2).
Dietary treatment
A high proportion of cases of EG are associated with food allergy [7, 9]. As a result, use of

elimination or elemental diets is recommended. And the use of dietary treatment not only has
been effective in reducing the dose for corticosteroids, but also has improved the poor growth
associated with the disease [50]. However, in clinical practice, the elimination of these foods
based on the results of skin prick tests or radioallergosorbent test has shown variable results
[1, 7, 27]. The response to elimination diet not correlate with the patients’ food sensitization
profile [31]. Thus, it is difficult to identify the causative foods, resulting in limiting the
efficacy and application of elimination diet. Now, an empiric diet, preferentially devoid of the
6 most common food-allergens, milk, soy, eggs, wheat, peanuts/tree nuts, and shellfish/fish
(6-FED), has also been used for EG. And the reintroduction process was helpful to identify
the causative foods. Some studies had also reported EG in children and adults showed
remission of symptoms after this elimination diet [31, 51]. Except for elimination diet,
elemental diet has often been chosen for the treatment of EG, aimed at avoiding all protein
antigen exposure. Good efficacy in EG can also be achieved by exclusively amino acid-based
elemental diet [50]. However, elemental diet can lead to reduce quality of life [52] due to the
restricted nature of the diet, poor palatability and relatively high expense. As a result, the
application may be limited.
In addition, dietary treatment for EG is used in combination with other interventions in
most cases. Its efficacy need to be further confirmed in large and prospective trials.
Drug treatment
Corticosteroids
If dietary treatment is not feasible or failed to achieve improvement, corticosteroids would be

the optimum therapeutic drugs [1, 17]. A number of uncontrolled studies and case series have
demonstrated that corticosteroids as main drugs have an important role for treating EG in
children and adults [6, 53]. Among the patients with EG, those with predominantly serosal
pattern seem to have the greatest response to corticosteroids [8].
Prednisone, budesonide, fluticasone were the main therapeutic drugs in corticosteroid
treatment. Doses of prednisone of 0.5 to 1 mg/kg typically achieve a markedly symptomatic
remission in 2 to 14 days. The results indicated that short-term systemic corticosteroids
treatment is a fantastic therapeutic strategy to achieve clinical remission. Once clinical
symptoms are controlled, dose of prednisone is tapered over the next 2 or more weeks until
prednisone is stopped. But some steroid-dependent patients relapse during steroids tapering
or after withdrawal of corticosteroid treatment [27]. These patients should resume taking
initial doses, maintain remission by the minimum required dose. Meanwhile, budesonide can
be used as an alterative drug of Prednisone for maintenance therapy and successful treatment
with budesonide has been reported. The major advantage of budesonide is its high
metabolism rate, leading to a lower risk of long-term treatment’s side effects [54]. Most
patients achieve a symptomatic remission improvement of symptoms at 9 mg/d doses of
budesonide, and the dose of 3 to 6 mg/d long term is preferable [42]. Compared with
prednisone, budesonide has a similar efficacy and even a better safety profile. Fluticasone is a
fluorinated corticosteroid with an extremely low oral bioavailability of less than or equal to
1% [55]. This low oral bioavailability makes it potentially an optimum drug for topical
delivery in EG. Unfortunately, fluticasone is the only available commercial formulation in
pulmonary and nasal inhalers, neither of which contain sufficient dose to treat EG.

Despite their dramatic efficacy, the long-term use of corticosteroids is not desirable due to
serious side effects, such as adrenocortical suppression, fluid and electrolyte disturbances,
hyperglycemia, cushingoid state. Hence, we still need to drill down into other therapeutic
strategies.
Other drugs
With regard to the efficacy of other therapeutic drugs in treating EG, most of the available
evidence comes from single cases or small case series and this limits us to verify its real
application value. Nevertheless, these evidence points out the new thoughts on future
treatment. Nowadays, other drugs used with some success include mast cell inhibitors,
leukotriene receptor antagonists, antihistamines, anti-interleukin-5.
Mast cell inhibitors
Disodium cromoglycate is a mast cell stabilizer that prevents release of toxic mediators like
histamine, platelet activating factors and leukotrienes from mast cells. There have been
sporadic case reports of a beneficial response to the drug [35, 56, 57]. Some studies reported
that disodium cromoglycate might result in a positive response at a dose of 200 mg four times
a day [35, 56]. Ketotifen, an antihistaminic agent and mast cell membrane stabilizer, also
produced a clinical improvement with a dose of 2–4 mg per day in some cases [58, 59].
Leukotriene receptor antagonists
Montelukast, a selective and competitive leukotriene receptor antagonist, may be considered
as a relatively safe and effective steroid-sparing therapy for EG [60, 61]. Some studies
suggested that montelukast treatment for several months at a dose range of 10–40 mg orally
per day achieved a beneficial improvement in both peripheral eosinophilia and symptoms

[61-63]. Therefore, montelukast seems promising to be an effective long-term treatment in
patients with EG, in particular when they are steroid-dependent.
Anti-interleukin-5
In regard with anti-interleukin-5, the information is contradictory in some cases. Despite a
humanized anti-IL-5 monoclonal antibody (mepolizumab) had been found to be effective in a
small, open-label, uncontrolled study in which had four patients with hypereosinophilia
syndrome (HES) [64], the rebound eosinophilia was seen after anti-IL-5 treatment in patients
with HES and EG in a small clinic trail [65]. Thus, further randomized, controlled trials must
be conducted to verify the potential therapeutic value of anti–IL-5 antibody in patients with
EG.
Antihistamines
Antihistamines cannot probably become the first-line therapy in the current circumstance,
because evidence for application of antihistamines (H-1 receptor antagonists) in EG is based
merely on the murine model of aeroallergen induced EE, and several reports of EG in
association with seasonal allergies [66-68]. In consequence, a comprehensive understanding
of the mechanisms underlying idiopathic EG is need in the future.
Fecal microbiota transplantation (FMT)
Intestinal microbiota constitute a microbial organ that is indispensable to overall host
physiological function, including pivotal roles in metabolism and immune system function
[69], resulting in attracting more and more attention. Recently, a case report first found fast
therapeutic efficacy of FMT in EG cases presenting as long-term diarrhea [70]. But it remains
unclear whether FMT could cure EG or maintain long-term clinical remission. If sufficient

evidence in support of FMT efficacy is confirmed in the future, it will be served as more
effective, safer and promising therapeutic strategies against EG.
Surgery
Predominantly muscular pattern of EG can present obstructive symptoms, due to bowel wall
thickening and narrowing of the lumen caused by eosinophilic infiltration. In most cases,
these obstructions can be reversible with corticosteroid treatment [37, 38]. Nevertheless,
some cases of EG had been diagnosed only after resection of the obstructing segment after
laparotomy or laparoscopic full thickness biopsy [36]. Thus, it is necessary for clinicians to
have a high degree of suspicion for EG. If EG can be diagnosed in time and obstructions can
be reversible with treatment, an unnecessary surgery treatment is avoided as far as possible.
But patients with EG presenting with GI perforation need to be considered to undergo surgery
for repairing damage. Notably, these complications may persist or often occur, warranting
close follow-up and dietary therapy and appropriate medical treatment [71-73].
Natural history of EG
With regard to natural history of EG, many questions remain largely unknown. Indeed, only
single case reports or small cases series reported follow-up survey after treatment with
limited and shot in detail [6-8]. Recently, a published French study analyzed the data on
clinical presentation and long-term outcomes of 43 adult patients with EG who were followed
up for a median period of 13 years [27]. They identified three different patterns of disease
course: (1) a single flare of EG, defined by GI symptoms present for less than 6 months
associated with the absence of any relapse after initial flare; (2) a recurring course of EG,
defined by at least 2 flares of the disease separated by a period without GI symptoms and

without peripheral blood eosinophilia; (3) a continuous course of the disease, defined by
chronic persistent GI symptoms for more than 6 months without period of remission. They
also found that absence of spontaneous remission and high blood eosinophil counts at
diagnosis were significantly associated with a high risk of clinic relapse [27] (Figure 2).
Unfortunately, very few studies continue to focus on elucidating natural history of EG.
Further research from large studies is needed to validate the three different patterns of disease
course.
Conclusion
Eosinophilic gastroenteritis is an uncommon and heterogeneous disease, and many problems
still left to be answered. Up to now, there is no standard guideline for the diagnosis of EG,
and a high degree of clinical suspicion is especially necessary. Although corticosteroids as
main mediscation have a dramatic efficacy for treating EG, the serious side effects of
long-term application cannot be ignored. In the future, large and high-quality studies are
needed to further investigate the epidemiology and pathophysiology of EG, make the
consensus diagnostic criteria, evaluate optimal treatment strategy, and verify its natural
history.
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Table 1: Differential diagnosis of eosinophilic gastroenteritis
Systemic disorders: vasculitis, connective tissue disease, hyper-eosinophilic syndrome,
graft-versus-host disease, systemic mastocytosis, tuberculosis, etc.
Gastrointestinal diseases: Crohn’s disease, ulcerative colitis, celiac disease, acute abdomen,
intestinal perforation, pyloric narrowing and obstruction, malabsorption syndrome, etc.
Food/drug allergy: food (milk, soy, egg, wheat, peanuts tree nuts, and shellfish_fish, etc);
drug (penicillin, cephalosporin, aspirin, sulfonamides, etc.)
Tumor: carcinomas, lymphomas, etc.
Parasitic infection: ascaris, trichuris, schistosomiasis, ancylostoma caninum, enterobius
vermicularis, giardia lamblia, anisakis, trichinella spiralis, etc.

Table 2: The treatment of eosinophilic gastroenteritis
Treatment Classification Application
Dietary treatment elimination diet initial therapy
elemental diet initial therapy
Drug treatment
corticosteroids main therapy
mast cell inhibitors often combined with corticosteroids
leukotriene receptor antagonists often combined with corticosteroids
anti-interleukin-5 need further verify efficacy
antihistamines need further verify efficacy
fecal microbiota transplantation need further verify efficacy
Surgery treatment — avoid unnecessary surgery treatment

Figure Legends
Figure 1: Flowcharts for diagnosis and treatment of eosinophilic gastroenteritis (EG).

Figure 2: Three types of eosinophilic gastroenteritis. (A) a single flare of EG, defined by GI
symptoms present for less than 6 months associated with the absence of any relapse after
initial flare; (B) a recurring course of EG, defined by at least 2 flares of the disease separated
by a period without GI symptoms and without peripheral blood eosinophilia; (C) a
continuous course of the disease, defined by chronic persistent GI symptoms for more than 6
months without period of remission of EG (modified, based on de Chambrun et al. [27]).

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