PPI for Eosinophilic Duodenal Ulcer with Esophagitis
Tohoku J. Exp. Med., 2022, 257, 309-313

309

Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer
with Esophageal Involvement: A Pediatric Case
Yuji Fujita,1 Keiichi Tominaga,2 Kazuyuki Ishida,3 Hironori Masuyama4 andShigemi Yoshihara1
Department of Pediatrics, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan
Department of Gastroenterology, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan3
Department of Diagnostic Pathology, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan4Masuyama Gastrointestinal Clinic, Otawara, Tochigi, Japan
12Eosinophilic gastrointestinal disorders are diseases that cause inflammation and dysfunction due toinfiltration of eosinophils into various regions of the gastrointestinal tract. Symptoms and treatment varydepending on lesion severity. We describe the first pediatric case of an eosinophilic duodenal ulcer withesophageal involvement that was effectively treated using proton pump inhibitor monotherapy. A
12-year-old boy with no relevant family or medical history presented with a one-month history of epigastricpain. Laboratory test results were as follows: white blood cell count, 4,700/µ L; eosinophil count, 150/µ L(3.2%); and total IgE, 151.6 IU/L; and IgG antibodies for Helicobacter pylori were absent.
Esophagogastroduodenoscopy revealed longitudinal linear furrows in the esophagus, indicating
eosinophilic esophagitis with an A1 ulcer from the duodenal bulb to the descending duodenum. The patient
was diagnosed with an eosinophilic duodenal ulcer with esophageal involvement based on pathologicalfindings. Esomeprazole, a common proton pump inhibitor, was orally administered, after which thesymptoms promptly improved. After two months, the esophagogastroduodenoscopy and pathologicalexamination results showed improvement in both the esophagus and duodenum. There have been noprevious reports of an eosinophilic duodenal ulcer with esophageal involvement without post-duodenal
involvement at the time of diagnosis. The possibility of eosinophilic gastrointestinal disorders should beinvestigated in patients with duodenal ulcers by means of active biopsy, and patients should be investigatedfor other types of gastrointestinal lesions. Proton pump inhibitor monotherapy may be considered a firstline treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on lesion severity.
Keywords: duodenal ulcer; eosinophils; esophageal gastrointestinal disorder; proton pump inhibitor
Tohoku J. Exp. Med., 2022 August, 257 (4), 309-313.
doi: 10.1620/tjem.2022.J045

Introduction

Case Presentation

Eosinophilic gastrointestinal disorders (EGIDs) cause
various gastrointestinal symptoms, such as abdominal painand diarrhea. These symptoms are due to infiltration ofeosinophils into the gastrointestinal tract. Symptoms varydepending on the area of the gastrointestinal tract that has
been infiltrated. Treatment depends on lesion severity
within the gastrointestinal tract. We describe the first pediatric case of an eosinophilic duodenal ulcer with esophageal
involvement that was effectively treated using proton pumpinhibitor (PPI) monotherapy.

A 12-year-old boy with no relevant family or medical
history presented with a one-month history of epigastricpain. The results of his laboratory tests were as follows:white blood cell count, 4,700/µL; eosinophil count, 150/µL(3.2%); albumin level, 4.5 g/dL; C-reactive protein level, <0.01 mg/dL; and total IgE, 151.6 IU/L. IgE antibody levels
in relation to the following antigens were tested: egg white,
0.41 IU/L; milk, 0.37 IU/L; wheat, 0.25 IU/L; soy, < 0.10
IU/L; peanut, 0.16 IU/L; and salmon, < 0.10 IU/L.
Additionally, thymus and activation-regulated chemokine

Received April 20, 2022; revised and accepted May 18, 2022; J-STAGE Advance online publication June 3, 2022
Correspondence: Yuji Fujita, M.D., Department of Pediatrics, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga-gun,Tochigi 321-0293, Japan.
e-mail: fujitay@dokkyomed.ac.jp©2022 Tohoku University Medical Press. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivatives 4.0 International License (CC-BY-NC-ND 4.0). Anyone may download, reuse, copy, reprint, or
distribute the article without modifications or adaptations for non-profit purposes if they cite the original authors and source properly.
https://creativecommons.org/licenses/by-nc-nd/4.0/309

310

Y. Fujita et al.

levels were 522 pg/mL, and IgG antibodies for Helicobacter
pylori were absent. Abdominal ultrasonography showed noabnormal findings such as ascites. Esophagogastroduodenoscopy
revealed longitudinal linear furrows in the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from theduodenal bulb to the descending duodenum, and no abnormal findings in the stomach (Fig. 1A, B). A rapid urease
test result was negative. Colonoscopy and balloon-assistedenteroscopy revealed no abnormalities in the ileum andcolon. Pathological examination results showed eosinophilic infiltration of 60 per high-power field (/HPF) in theesophagus and > 100/HPF in the duodenum (Fig. 2A, B),
and no eosinophilic infiltration in the ileum and colon. The
patient was diagnosed with an eosinophilic duodenal ulcer
with esophageal involvement.
Esomeprazole was orally administered, after which his
symptoms promptly improved. After two months, theesophagogastroduodenoscopy (Fig. 1C, D) and pathologicalexamination (Fig. 2C, D) results showed improvement inboth the esophagus and duodenum. Esomeprazole treatment was discontinued and, over a year later, the symptoms
had not recurred. A follow-up endoscopy cannot be performed without parental consent. Written informed consent
was obtained from the patient’s parents.

Discussion
In this case presentation, we report the first pediatriccase of an eosinophilic duodenal ulcer with esophageal
involvement that was effectively treated by PPI monotherapy. EGIDs comprise eosinophilic esophagitis (EoE) andeosinophilic gastroenteritis (EGE) (Kinoshita et al. 2013).
One classification stratifies EGIDs into EoE and non-EoEEGIDs (Yamamoto et al. 2021). These classifications consider cases of no eosinophilic inflammation in the gastrointestinal tract below the esophagus to be EoE. One Japanesestudy reported that the rate of EGE with esophageal
involvement was 9% (Kinoshita et al. 2013). Yamamoto etal. (2021) also reported that eosinophilic enteritis andeosinophilic colitis had no esophageal lesions, but 49% of
patients with EGE had esophageal lesions. At the time ofdiagnosis, there had been no previous reports of an eosinophilic duodenal ulcer with esophageal involvement but
without post-duodenal involvement.
We summarized cases of EGIDs presenting with duodenal ulcers in Table 1 (Russell and Evangelou 1965;
Deslandres et al. 1997; Markowitz et al. 2000; Tee et al.
2009; Issa et al. 2011; Nakamura et al. 2014; Yamazaki etal. 2015; Riggle et al. 2015; Chen et al. 2017; Kubo et al.

Fig. 1. Esophagogastroduodenoscopy images.
Esophagogastroduodenoscopy showed longitudinal linear furrows in the esophagus (A) and a stage A1 ulcer from theduodenal bulb to the descending duodenum (B). These findings improved two months after treatment with esomeprazole (C, D).

PPI for Eosinophilic Duodenal Ulcer with Esophagitis

311

Fig. 2. Pathological findings of the biopsy tissue of esophagus and duodenum (hematoxylin and eosin staining).
Pathological examination results showed eosinophilic infiltration of 60 high-power field (/HPF) in the esophagus (A)and > 100/HPF in the duodenum (B). The eosinophilic infiltration improved to 3/HPF in the esophagus (C) and 10/HPF
in the duodenum (D) two months after initiation of treatment with esomeprazole (A-D, original magnification, × 400).

2020; Peck et al. 2020; Priyadarshni et al. 2020; Fujita et al.
2022). These studies involved many young people overall,and > 50% were children. Previously, we reported a pediatric patient who had been diagnosed with an eosinophilic
duodenal ulcer that was complicated with Helicobacter
pylori infection (Fujita et al. 2022). The possibility ofEGIDs should be investigated in patients with duodenal
ulcers by means of an active biopsy, and patients should beinvestigated for other types of gastrointestinal lesions(Kinoshita et al. 2013; Yamamoto et al. 2021).
A definitive treatment protocol for eosinophilic duodenal ulcers with esophageal involvement remains to be determined. Although PPIs are recommended as first-line treatment for EoE (Lucendo et al. 2017; Dellon et al. 2018),
their effectiveness in cases with esophageal involvement innon-EoE EGIDs has not been investigated. EGE may often
require various treatments, such as leukotriene receptor
inhibitors (LTRA), systemic corticosteroids, and diet therapy. Recently a case in which crushed budesonide waseffective was also reported (Kubo et al. 2020); however, theeffectiveness of PPIs for EGE, including eosinophilic duodenal ulcers, remains to be determined. A few case studies
have reported on the effectiveness of PPIs for eosinophilic
duodenal ulcers (Tee et al. 2009). In our previous casereport of a patient with eosinophilic duodenal ulcers, LTRA
was the most effective, but a PPI appears to have been partially effective (Fujita et al. 2022). PPIs reduce duodenal
eosinophilia in patients with functional dyspepsia (Wauterset al. 2021). Further studies are needed to determine theeffectiveness of PPIs for EGE, especially duodenal lesions.
Systemic glucocorticoids, which are associated with various side effects, especially in children, are more often indicated in non-EoE EGIDs than in EoE (Kinoshita et al.
2013; Yamamoto et al. 2021). In contrast, PPIs have fewerside effects and can be used safely. There have been noprevious reports of improvement using PPI monotherapy inrelation to both eosinophilic duodenal ulcers and esophageal involvement. In conclusion, PPI monotherapy may beconsidered as a first-line treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on theseverity.

Acknowledgments
We would like to thank Editage (https://www.editage.
com) for English language editing.

Author Contributions
Dr. Fujita collected and analyzed the data and drafted12our case

MM

M

M

FM

epigastric pain

periumbilical pain, melena

abdominal pain, vomiting

abdominal pain

dizziness

150

261

ND

6,800

ND

ND

860

epigastric pain, vomiting,inappetence

vomiting

1,000

normal455

ND1,666

1,254

574

Peripheral
eosinophil
count (/µL)

abdominal pain, etc

epigastric pain

epigastric pain, nausea

hematemesis, tarry stools

epigastric pain

nausea, epigastric pain

epigastric pain

Symptoms

M, male; F, female; ND, no data.

54

13M

31

28

1045

26

9

11

late adolescence

812

M

16

M

M

M

7

early teens

4M

15

14

3

F

16

11

2

M

5

11

1

Sex

6

Age (years)

Case
numberpositive

bronchial asthma and allergic
rhinitisnoneallergy to trimethoprim

contact dermatitis

ND

allergy to peanuts

ND

allergy to pollen

none

none

allergic rhinitis

negative

ND

ND

ND

ND

ND

negative

negative

negative

negative

negative

negativeenvironmental allergies andasthmabronchial asthma

negative

H.pylorinone

Allergic diseases

Fujita, et al. 2022

histamine 1 receptor antagonist
proton pump inhibitor
montelukast
proton pump inhibitor
prednisolone
esomeprazole
crushed budesonide

multiple ulcers in the duodenal bulb
an ulcer with a thickened, white, moss-likeappearance in the duodenal wall at the superior duodenal angulus
two A2-stage duodenal ulcers on the anterior walland greater curvature of the duodenal bulb

an A1 ulcer from the duodenal bulb to the descending duodenum

multiple ulcers in the duodenuma large perforation of a huge peptic ulcer in the first part of the duodenum

Chen et al. 2017

protom pump inhitibor
methylprednisolone
montelukast
esomeprazole

Russell and Evangelou 1965

death after surgical treatment

Tee et al. 2009

Priyadarshni et al. 2020

pantoprazole
prednisone
coiling and embolization byinterventional radiology service
high-grade duodenal stenosis,
severe pyloroduodenal deformity
and a duodenal ulcer with a visible vessel

proton pump inhibitor

Issa et al. 2011

pantoprazole
prednisolone
a duodenal ulcer with stenosis

duodenal ulceration

Nakamura et al. 2014

Peck et al. 2020

sucralfate
lansoprazole
diet therapy
swallowed fluticasone thrapy

Kubo et al. 2020
Riggle et al. 2015

diet therapy

proton pump inhibitor

an ulcer scar in the duodenal bulb

duodenal ulcer, located proximal to the ampulla of Vatera perforated ulcer in the first portion of the duodenum

Yamazaki et al. 2015

Markowitz et al. 2000

omeprazole
sucralfate
methylprednisolone

a large ulcer in the duodenal bulb

Deslandres et al. 1997

corticotherapy
cimetidine
diet therapy

deformed pylorus with erythema of the antrum and prepyloric area,
and an edematous and hyperemic duodenal bulb
with a scar noted in the duodenal bulb"

Reference

Treatment

Endoscopic findings

Table 1. Previous reported cases of eosinophilic duodenal ulcer.

312
Y. Fujita et al.

PPI for Eosinophilic Duodenal Ulcer with Esophagitis

and revised the initial manuscript. Dr. Tominaga, Prof.
Ishida, Dr. Masuyama, and Prof. Yoshihara interpreted allthe data and critically revised the manuscript for important
intellectual content. All the authors approved the final
manuscript and agreed to be accountable for all aspects ofthe work.

Conflict of Interest
The authors declare no conflict of interest.

References
Chen, B., Yang, Z., Lu, H., Wei, C., Wang, F. & Liu, C. (2017)
Eosinophilic gastroenteritis presenting as upper gastrointestinal hematoma and ulcers after endoscopic biopsy: a casereport and literature review. Medicine (Baltimore), 96, e8075.
Dellon, E.S., Liacouras, C.A., Molina-Infante, J., Furuta, G.T.,Spergel, J.M., Zevit, N., Spechler, S.J., Attwood, S.E., Straumann, A., Aceves, S.S., Alexander, J.A., Atkins, D., Arva,N.C., Blanchard, C., Bonis, P.A., et al. (2018) Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology, 155, 1022-1033 e1010.
Deslandres, C., Russo, P., Gould, P. & Hardy, P. (1997) Perforated
duodenal ulcer in a pediatric patient with eosinophilic gastroenteritis. Can. J. Gastroenterol., 11, 208-212.
Fujita, Y., Tominaga, K., Tanaka, T., Ishida, K. & Yoshihara, S.
(2022) Eosinophilic duodenal ulcer exacerbation after Helicobacter pylori eradication in a 14-year-old boy. Tohoku J. Exp.
Med., 257, 153-156.
Issa, H., Bseiso, B. & Al-Salem, A.H. (2011) Eosinophilic enteritis
presenting as a perforated duodenal ulcer. Endoscopy, 43
Suppl 2 UCTN, E358-359.
Kinoshita, Y., Furuta, K., Ishimaura, N., Ishihara, S., Sato, S.,
Maruyama, R., Ohara, S., Matsumoto, T., Sakamoto, C.,
Matsui, T., Ishikawa, S. & Chiba, T. (2013) Clinical characteristics of Japanese patients with eosinophilic esophagitis andeosinophilic gastroenteritis. J. Gastroenterol., 48, 333-339.
Kubo, K., Kimura, N., Mabe, K., Matsuda, S., Tsuda, M. & Kato,M. (2020) Eosinophilic gastroenteritis-associated duodenal
ulcer successfully treated with crushed budesonide. Intern.
Med., 59, 2249-2254.
Lucendo, A.J., Molina-Infante, J., Arias, A., von Arnim, U., Bredenoord, A.J., Bussmann, C., Amil Dias, J., Bove, M., GonzalezCervera, J., Larsson, H., Miehlke, S., Papadopoulou, A.,
Rodriguez-Sanchez, J., Ravelli, A., Ronkainen, J., et al. (2017)
Guidelines on eosinophilic esophagitis: evidence-based state-313

ments and recommendations for diagnosis and management inchildren and adults. United European Gastroenterol. J., 5,335-358.
Markowitz, J.E., Russo, P. & Liacouras, C.A. (2000) Solitary
duodenal ulcer: a new presentation of eosinophilic gastroenteritis. Gastrointest. Endosc., 52, 673-676.
Nakamura, A., Iwaya, Y., Iwaya, M., Okamura, T., Kobayashi, S.,
Daikuhara, S., Nozawa, Y., Fukuzawa, S., Nakamura, S.,
Okuhara, S., Yamada, S., Yokosawa, S., Suga, T., Arakura, N.
& Tanaka, E. (2014) Eosinophilic gastroenteritis complicatedwith Helicobacter pylori infection unresponsive to eradication
therapy. Intern. Med., 53, 2061-2065.
Peck, J., Kimsey, K.M., Harris, E., Monforte, H. & Wilsey, M. Jr.
(2020) Solitary duodenal ulcer causing biliary obstruction
requiring rendezvous procedure in a pediatric patient witheosinophilic gastroenteritis. Cureus, 12, e9377.
Priyadarshni, S., Surapaneni, B.K., Dave, K., Kaplan, S. & Patel,N. (2020) Upper gastrointestinal bleed in a young male- a rare
presentation of eosinophilic gastroenteritis. Cureus, 12,e7059.
Riggle, K.M., Wahbeh, G., Williams, E.M. & Riehle, K.J. (2015)
Perforated duodenal ulcer: an unusual manifestation of allergic
eosinophilic gastroenteritis. World J. Gastroenterol., 21,12709-12712.
Russell, J.Y. & Evangelou, G. (1965) Eosinophilic infiltration of
the stomach and duodenum complicated by perforation. Postgrad. Med. J., 41, 30-33.
Tee, H.P., Swartz, D., Tydd, T. & Leong, R.W. (2009) Gastrointestinal: eosinophilic enteritis manifesting as brown-pigmentedduodenal ulcers. J. Gastroenterol. Hepatol., 24, 1892.
Wauters, L., Ceulemans, M., Frings, D., Lambaerts, M., Accarie,A., Toth, J., Mols, R., Augustijns, P., De Hertogh, G., VanOudenhove, L., Tack, J. & Vanuytsel, T. (2021) Proton pumpinhibitors reduce duodenal eosinophilia, mast cells, andpermeability in patients with functional dyspepsia. Gastroenterology, 160, 1521-1531 e1529.
Yamamoto, M., Nagashima, S., Yamada, Y., Murakoshi, T.,
Shimoyama, Y., Takahashi, S., Seki, H., Kobayashi, T., Hara,Y., Tadaki, H., Ishimura, N., Ishihara, S., Kinoshita, Y., Morita,H., Ohya, Y., et al. (2021) Comparison of nonesophageal
eosinophilic gastrointestinal disorders with eosinophilicesophagitis: a nationwide survey. J. Allergy Clin. Immunol.
Pract., 9, 3339-3349 e3338.
Yamazaki, K., Sakashita, T., Iwata, H., Mizutani, T., Matsuura, K.,
Sugiyama, T., Sato, H., Ando, N., Iwata, K., Imose, M.,Shimizu, S., Imamura, A., Araki, H. & Sugihara, J. (2015) A
case of a teenage boy with eosinophilic gastroenteritis withesophageal involvement developing a hemorrhagic duodenal
ulcer. Clin. J. Gastroenterol., 8, 179-185.