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A Case of Eosinophilic Gastroenteritis Associated with Eosinophilic Ascites Diagnosed by Full-Thickness Biopsy of the Small Intestine

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Patient: Male, 28 Final Diagnosis: Eosinophilic gastroentritis Symptoms: Abdominal and/or epigastric pain • ascites Medication: — Clinical Procedure: Full-thickness biopsy Specialty: Diagnostics, Laboratory Objective Unusual clinical course Background Eosinophilic gastroenteritis is a rare disease, characterized by infiltrates of eosinophils in the intestinal mucosa, muscularis propria, and serosa. Eosinophilic gastroenteritis is due to Type 1 hypersensitivity and can be associated with other atopic diseases. The clinical course of eosinophilic gastroenteritis varies depending on the location, extent, and depth of eosinophilic infiltration of the gastrointestinal tract, which can make the diagnosis challenging. A case of eosinophilic gastroenteritis associated with eosinophilic ascites is presented that emphasizes the importance of full-thickness intestinal biopsy, which includes the muscularis propria, to allow the definitive diagnosis to be made. Case Report A 28-year-old man presented with vague abdominal pain, nonspecific gastrointestinal symptoms, unintentional weight loss, and progressive ascites during the previous several months. A diagnosis of eosinophilic gastroenteritis was made after the exclusion of other possible causes, which was confirmed by histopathology of a full-thickness intestinal biopsy. The patient was treated with steroids. At one-month follow-up, the patient reported reduced abdominal pain. Conclusions A case of eosinophilic gastroenteritis associated with eosinophilic ascites is presented that emphasizes the importance of full-thickness intestinal biopsy, which includes the muscularis propria, to allow the definitive diagnosis to be made.
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Received: 2018.09.21
Accepted: 2018.11.03
Published: 2019.02.13
1826 1 4 11
A Case of Eosinophilic Gastroenteritis Associated
with Eosinophilic Ascites Diagnosed by Full-
Thickness Biopsy of the Small Intestine
ABDEF 1 Haneen Thabit Salah
ABDEF 2 Hussa Fahad Al-Hussaini
ABEF 3 Abdullah Mohammed Alqaraawi
BEF 4 Khulud Muhammed Alanazi
Corresponding Author: Hussa Fahad Al-Hussaini, e-mail: Halhussaini@kfshrc.edu.sa
Conflict of interest: None declared
Patient: Male, 28
Final Diagnosis: Eosinophilic gastroentritis
Symptoms: Abdominal and/or epigastric pain • ascites
Medication:
Clinical Procedure: Full-thickness biopsy
Specialty: Diagnostics, Laboratory
Objective: Unusual clinical course
Background: Eosinophilic gastroenteritis is a rare disease, characterized by infiltrates of eosinophils in the intestinal mucosa,
muscularis propria, and serosa. Eosinophilic gastroenteritis is due to Type 1 hypersensitivity and can be asso-
ciated with other atopic diseases. The clinical course of eosinophilic gastroenteritis varies depending on the
location, extent, and depth of eosinophilic infiltration of the gastrointestinal tract, which can make the diag-
nosis challenging. A case of eosinophilic gastroenteritis associated with eosinophilic ascites is presented that
emphasizes the importance of full-thickness intestinal biopsy, which includes the muscularis propria, to allow
the definitive diagnosis to be made.
Case Report: A 28-year-old man presented with vague abdominal pain, nonspecific gastrointestinal symptoms, unintentional
weight loss, and progressive ascites during the previous several months. A diagnosis of eosinophilic gastroen-
teritis was made after the exclusion of other possible causes, which was confirmed by histopathology of a full-
thickness intestinal biopsy. The patient was treated with steroids. At one-month follow-up, the patient reported
reduced abdominal pain.
Conclusions: A case of eosinophilic gastroenteritis associated with eosinophilic ascites is presented that emphasizes the im-
portance of full-thickness intestinal biopsy, which includes the muscularis propria, to allow the definitive diag-
nosis to be made.
MeSH Keywords: Ascitic Fluid • Gastroenteritis • Pathological Conditions, Anatomical
Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/913319
Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G
1 College of Medicine, AlFaisal University, Riyadh, Saudi Arabia
2 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital
and Research Center, Riyadh, Saudi Arabia
3 Department of Medicine, King Faisal Specialist Hospital and Research Center,
Riyadh, Saudi Arabia
4 College of Medicine, King Saud University, Riyadh, Saudi Arabia
e-ISSN 1941-5923
© Am J Case Rep, 2019; 20: 189-193
DOI: 10.12659/AJCR.913319
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Background
The gastrointestinal tract consists of four layers, the mucosa,
the submucosa, the muscularis propria, and the adventitia
or serosa. Eosinophilic gastroenteritis is a rare disease that
may have a varied presentation and is characterized by eo-
sinophilic infiltration of the gastrointestinal tract that may in-
volve some or all of the layers of these layers [1,2]. Eosinophilic
gastroenteritis is characterized histologically by the presence
of a dense and diffuse infiltrate of eosinophils of the lamina
propria of more than 20 eosinophils per high power field [3].
A recent prospective study of patients presenting with lower
abdominal symptoms showed that the prevalence of eosino-
philic gastroenteritis was 2.6% [3].
Eosinophilic gastroenteritis is a form of Type 1 hypersensitivity
disease that can be associated with other atopic diseases [2].
Personal and family history of food allergy and atopy can be
found in up to 50% of cases, with an increased incidence of
eosinophilic gastroenteritis in patients with a history of other
atopic diseases, including asthma, and allergic rhinitis [2,4].
The clinical presentation of eosinophilic gastroenteritis varies
depending on the extent of involvement of the gastrointesti-
nal tract, and the depth of infiltration of the gastrointestinal
wall [4]. Klein et al. classified eosinophilic gastroenteritis ac-
cording to the depth of eosinophilic infiltration into the mu-
cosa, muscularis propria, and serosa [2].
The diagnosis of eosinophilic gastroenteritis requires a high in-
dex of suspicion, as it can present with a wide range of symp-
toms and signs, and can present with no specific findings on
clinical history and physical examination [2]. Eosinophilic gas-
troenteritis can have a variable clinical course. Following steroid
treatment, a subset of patients will have no recurrence, while
others undergo repeated and long courses of steroidal ther-
apy due to frequent recurrences [4]. There remains no agree-
ment regarding the ideal treatment for eosinophilic gastro-
enteritis, but systemic steroid therapy remains the standard
therapeutic approach [3]. Other treatments for eosinophilic
gastroenteritis include mast cell inhibitors, antihistamines, or
leukotriene receptor antagonists [4]. Serosal eosinophilic in-
filtrates are present in 10% of the cases of eosinophilic gas-
troenteritis, and a hallmark if this subtype is peripheral eosin-
ophilia and ascites [5].
A case of eosinophilic gastroenteritis associated with eosino-
philic ascites is presented that emphasizes the importance of
full-thickness intestinal biopsy, which includes the muscularis
propria, to allow the definitive diagnosis to be made.
Case Report
A 28-year-old man presented with severe epigastric and ab-
dominal pain, nausea, vomiting, diarrhea, loss of appetite,
and unintentional weight loss of 32 kg during the previous six
months. He had a history of seasonal bronchial asthma. None
months previously, he presented with intermittent episodes
of epigastric and abdominal pain, nausea, vomiting, and diar-
rhea, and was diagnosed and treated as a case of Helicobacter
pylori with an initial improvement of his symptoms.
On this hospital admission, the initial differential diagnosis in-
cluded inflammatory bowel disease (IBD), gastroenteritis due
to nonsteroidal anti-inflammatory drugs (NSAIDs), primary gas-
trointestinal malignancy, lymphoma, and infectious disease,
including tuberculosis (TB). Laboratory investigations included
a QuantiFERON test for TB, measurement of fecal calprotectin,
Brucella agglutination titer, serology for human immunodefi-
ciency virus (HIV), and measurement of the erythrocyte sedi-
mentation rate (ESR), and C-reactive protein (CRP). All the lab-
oratory tests were normal. The patient underwent computed
tomography (CT) enterography, colonoscopy, and esophago-
gastroduodenoscopy (EGD).
CT enterography showed diffuse edema of the intestinal wall
with increased imaging enhancement of the intestinal mucosa
with nodularity involving a 20-cm segment in the left upper
quadrant of the small bowel, mild ascites, and omental en-
hancement. EGD showed severe gastritis, hiatal hernia, and
polypoid duodenitis.
The patient was treated with a proton pump inhibitor (PPI) for
one month with no significant improvement. Colonoscopy was
performed that showed external hemorrhoids and a sessile
adenomatous polyp. The patient was diagnosed with Crohn’s
disease, and was discharged from hospital on the anti-inflam-
matory agent, mesalamine. Two weeks later, the patient re-
ported minimal improvement.
On examination at the most recent hospital admission, his ab-
domen was distended, with diffuse tenderness that was worse
in the epigastric area. Rectal examination showed no external
or internal hemorrhoids, anal fissures, skin tags, or fistulas.
Paracentesis was performed, and a sample of ascitic fluid was
sent for cytological examination. The ascitic fluid was negative
for malignant cells, but showed numerous eosinophils mixed
with reactive histiocytes (Figure 1). The cytology of the ascites
fluid raised the possibility of a diagnosis of eosinophilic gastro-
enteritis, and full thickness intestinal biopsy was advised for
histopathology. The complete blood count (CBC) and differen-
tial cell count showed marked peripheral eosinophilia (22.6%).
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A case of eosinophilic gastroenteritis
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EGD was planned to obtain the intestinal biopsies. The histol-
ogy of the initial proximal biopsies showed mild chronic fo-
cal gastritis and focal chronic esophagitis. There was minimal
and focal eosinophilic cell infiltration in the proximal esopha-
geal biopsies that was not adequate for the diagnosis of eo-
sinophilic gastroenteritis. Because the EGD biopsy results were
inconclusive, the patient underwent a diagnostic laparoscopy
and full-thickness small bowel Tru-cut needle biopsy that in-
cluded all layers of the small bowel wall.
Histopathology of the intestinal biopsy showed dense eosino-
phil cell infiltrates predominantly involving the muscularis pro
-
pria and serosa and included small foci of eosinophil micro-
abscesses, as shown in Figures 2 and 3. Histopathology also
showed that the muscularis propria layer of the small intes-
tine was less involved and showed few scattered eosinophils
(Figure 4). On histology, the eosinophil count of the muscularis
propria and serosa was >15 eosinophils per high power field.
Given that the patient’s CBC and differential showed marked
peripheral eosinophilia, he underwent a bone marrow biopsy
and peripheral blood smear to exclude hematological malig-
nancy and hypereosinophilic syndrome (HES). However, no
clonal abnormalities and or features of malignancy or blasts
were found. After exclusion of all other possible causes, the
diagnosis of eosinophilic gastroenteritis was made. The di-
agnosis was based on the presence of persistent periph-
eral eosinophilia (22.6%), eosinophilia on cytology of the
ascitic fluid, and eosinophilic infiltration of the muscula-
ris propria and serosal layers of the small intestine on full-
thickness biopsy.
The patient was treated with prednisone (40 mg) for three
weeks, followed by tapering down of the dose. The patient
reported reduced abdominal pain after one month of steroid
Figure 1. Photomicrograph of the cytology of the ascitic fluid.
The ascitic fluid contains abundant eosinophils. Diff-
Quick stain. Magnification ×60.
Figure 2. Photomicrograph of the histology of the biopsy of the
small intestine. Eosinophils are shown to infiltrate the
intestinal muscularis propria. Hematoxylin and eosin
(H&E). Magnification ×40.
Figure 3. Photomicrograph of the histology of the biopsy of the
small intestine. The serosa is heavily infiltrated by
eosinophils with the formation of eosinophil micro-
abscesses. Hematoxylin and eosin (H&E). Magnification
×40.
Figure 4. Photomicrograph of the histology of the biopsy of the
small intestine. The mucosal surface of the small bowel
shows fewer eosinophil infiltrates. Hematoxylin and
eosin (H&E). Magnification ×20.
191
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A case of eosinophilic gastroenteritis
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therapy. He was scheduled for immunological follow-up at
the allergy clinic to identify a possible associated food allergy.
Discussion
Eosinophilic gastroenteritis is commonly associated with gas-
trointestinal symptoms and is diagnosed histologically by eo-
sinophil infiltration of the intestinal wall without evidence of
extra-intestinal disease [6]. Eosinophilic gastroenteritis is more
common in the pediatric population, young adults, and adults
between the third and fifth decade of life [7].
The recently reported incidence of eosinophilic gastroenteritis
is estimated to be 28 per 100,000 per year, and studies have
shown an increased prevalence during the past 16 years [3]. The
pathogenesis of eosinophilic gastroenteritis involves a Type 1
hypersensitivity reaction, and many patients will have a his-
tory of atopy [8]. The associated allergic disorders, including
asthma, allergic rhinitis, and atopic eczema are present in be-
tween 54–63% of reported cases of eosinophilic gastroen-
teritis [7]. Also, immunoglobulin E (IgE) levels are reported to
be elevated in patients with eosinophilic gastroenteritis [5].
Elimination of antigen triggers of atopy and treatment with
corticosteroids are the mainstay of patient management and
lead to improvement in up to 90% of patients [2]. Second-line
treatment includes mast cell stabilizers, antihistamines, and
leukotriene antagonists [5].
The classification of eosinophilic gastrointestinal disease is
based on the histological findings, and is based on the Klein
classification, according to the predominance of eosinophils in
the layers of the intestinal wall, the mucosa, muscularis pro-
pria, and serosa, and results in a wide range of clinical pre-
sentations, as summarized in Table 1 [9,10]. Compared with
other subtypes, mucosal eosinophilic gastroenteritis is the
most common, presenting mainly with nonspecific symptoms
that include abdominal pain, nausea, diarrhea, and vomiting,
and may mimic other gastrointestinal disorders [5]. More
rarely, patients may present with severe with blood in the
stool, iron deficiency anemia, or protein-losing enteropathy [5].
The recent increase in the reported incidence of mucosal eosin-
ophilic gastroenteritis may be because it is an easier diagnosis
to make by from routine endoscopic biopsy [2]. Eosinophilic
gastroenteritis that involves the muscularis propria is the sec-
ond most commonly reported subtype [5]. Infiltration of eo-
sinophils that mainly involves the muscularis propria causes
thickening of the intestinal wall and can present with symp-
toms of intestinal obstruction [5].
The serosal subtype of eosinophilic gastroenteritis is often as-
sociated with peripheral eosinophilia and with eosinophilia of
the ascitic fluid in between 45–90% of cases [2,11]. However,
eosinophilic ascites is a rare presentation of eosinophilic gas-
troenteritis and is most commonly seen with the serosal sub-
type [4]. It has been reported that the serosal subtype has a bet-
ter response to steroid therapy, without a chronic course [2,4].
The diagnosis of eosinophilic gastroenteritis requires the pres-
ence of three main features that include gastrointestinal symp-
toms, eosinophilia of one or more areas of the gastrointes-
tinal tract on histology, and the exclusion of other causes of
tissue eosinophilia, including intestinal tuberculosis, parasit-
osis, and malignancy [5,7]. Although the clinical history and
physical examination are important, the definitive diagnosis
of eosinophilic gastroenteritis is made histologically, which re-
quires gastrointestinal biopsy [8]. To confirm the histological
diagnosis, at least 15–20 eosinophils per high power micro-
scopic field are required [5]. Endoscopic findings suggestive
of eosinophilic gastroenteritis include an erythematous and
friable mucosa, pseudopolyps, polyps, and ulcers, but none of
these findings is sensitive or specific, and endoscopic biop-
sies are required to establish the diagnosis [4]. The pathology
of eosinophilic gastroenteritis usually follows a patchy distri-
bution, which requires multiple biopsies from normal and ab-
normal sites during endoscopy [7].
A recently published prospective study showed that 92.9% of
patients with eosinophilic gastroenteritis had a normal endo-
scopic appearance during colonoscopy and if biopsies were
taken only from abnormal appearing areas, 92.2% of cases
of eosinophilic gastroenteritis would have been missed [3].
Type Clinical presentation Pathology
Mucosa Abdominal pain, nausea, vomiting, diarrhea,
hemorrhage, protein-losing enteropathy, anemia,
weight loss
Mucosal eosinophils with degranulation, crypt
abscesses, and variable villous blunting
Muscularis mucosa Abdominal pain, obstruction, colicky abdominal
pain
Thickened wall, muscularis mucosa and serosal
and eosinophilic infiltrates, edema
Serosa Peritoneal irritation, Abdominal pain, bloating,
ascites, peritonitis, perforation, intussusception
Eosinophils and edema limited to serosa, and
ascitic fluid with abundant eosinophils
Table 1. Klein histological classification of eosinophilic gastroenteritis [10].
192
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A case of eosinophilic gastroenteritis
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The preferred method of obtaining biopsies is during laparos-
copy, particularly for muscular and serosal types, which pro-
vides an inclusive full-thickness specimen for accurate histo-
pathology diagnosis [7]. According to the clinical guidelines
published in 2014 by the Japanese Ministry of Health, Labor
and Welfare, negative endoscopic mucosal biopsies cannot
exclude the muscularis propria or serosal subtypes of eosino-
philic gastroenteritis, and so full-thickness biopsies obtained
at laparoscopy are essential to establish the diagnosis [5].
Conclusions
This case report has shown that when there is a clinical sus-
picion of eosinophilic gastroenteritis, prompt histopathologi-
cal evaluation of a full thickness biopsy should be performed
to prevent treatment delay. In this case, the predominance of
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Department and Institution where work was done
Department of Pathology and Laboratory Medicine, King Faisal
Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Conflict of increase
None.
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193
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A case of eosinophilic gastroenteritis
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Eosinophilic digestive diseases (EDD) are relatively rare disorders associated with increased gastrointestinal eosinophilic infiltrates without any underlying primary etiology. The pathophysiology of EDD is unclear, but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Given the overall relative increase of various atopic conditions, it is important for clinicians to understand the presentation and diagnosis and treatment options available. We present here a review of EDD, including the proposed pathophysiology, diagnosis and current treatment options for these disorders.
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Eosinophilic ascites is a rare disorder. It may be associated with lymphoma, eosinophilic gastroenteritis, peritoneal dialysis, and parasites. Eosinophilic ascites is probably the most unusual and rare presentation of eosinophilic gastroenteritis, and it is generally associated with the serosal form of eosinophilic gastroenteritis. Eosinophilic gastroenteritis is an uncommon disorder characterized by tissue and peripheral blood eosinophilia in the absence of a known cause in the latter. Eosinophilic gastroenteritis presents with non-specific symptoms, including abdominal pain, nausea, and diarrhea (1-3). We report a case medically managed with budesonide for abdominal pain and eosinophilic ascites. A 24 year-old male with a past medical history significant for abdominal distension presented with a three week history of intermittent abdominal pain. Physical examination revealed periumbilical and epigastric tenderness. Laboratory tests revealed a white blood cell count of 10,500 cells/mm3 with 15% eosinophils (normally < 1%). Serum IgE level was 30 U/mL (normal 6-12 U/mL). A stool test for ova and parasites was negative. Erythrocyte sedimentation rate, antinuclear antibody, and anti-neutrophil cytoplasmic antibody antibodies were normal. Ultrasound examination performed at the time of admission revealed moderate ascites. Computerized tomography of the patients abdomen demonstrated thickening of the transverse colon, as well as ascites. The ascitic fluid was aspirated under ultrasound guidance and sent for cytological evaluation. Fluid analysis was remarkable with 45% eosinophils. Serum-ascites albumin gradient was < 1.1 g/dL. Microbiology cultures of the ascitic fluid were negative for bacteria, mycobacteria, and fungal organisms. Esophagogastroduodenoscopy and colonoscopy with mucosal biopsies were performed. Thickened colonic mucosa and erythema were also noted, but no esophagitis, gastritis or duodenitis were noted. Following a diagnosis of eosinophilic colitis with associated eosinophilic ascites, oral treatment with 9 mg of budesonide daily was subsequently started. The patient responded very well to this therapy and was therefore discharged. Three months later, a follow-up ultrasound of the abdomen demonstrated virtually complete resolution of his intra-abdominal fluid. He stopped the treatment, and is doing well at the time this letter was composed. Eosinophilic gastroenteritis presents with eosinophilic esophagitis, gastritis, enteritis, and colitis. Eosinophilic gastroenteritis can be classified based on the location of the eosinophilic infiltrate in the gastrointestinal wall, as well as associated symptoms. Eosinophils in eosinophilic gastroenteritis frequently infiltrate the gastrointestinal mucosa and, only rarely, the muscular or subserosal layers (4). Mucosal disease generally presents with bleeding, protein-losing enteropathy, or malabsorption. Involvement of the muscle layer may cause bowel wall thickening resulting in subsequent intestinal obstruction. The subserosal form usually presents with peritonitis and eosinophilic ascites, as in our patient. The histopathologic diagnosis of eosinophilic gastroenteritis requires the presence of greater than or equal to 25 eosinophils on microscopic examination, which was the case in the patient presented (5). Eosinophilic colitis in our patient was characterized by numerous eosinophils extending from the muscular wall of the colon to the subserosa, and even involved the serosal surface of the colon. In our case, severe eosinophilic colitis with serosal involvement was the likely cause of this patient's eosinophilic ascites. In conclusion, clinicians should have suspicion of eosinophilic gastroenteritis when forming a differential diagnosis regarding gastrointestinal symptoms. Definite diagnosis is made by histopathological assessment. Treatment with steroids is the mainstay in the management of eosinophilic gastroenteritis. Clinical improvement is usually seen after treatment with a low dose of steroid.