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\begin{document}

\title{Proton pump inhibitor for eosinophilic duodenal ulcer with esophageal
involvement in a 12-year-old boy}



\author[1]{YUJI FUJITA}%
\author[1]{Keiichi Tominaga}%
\author[1]{Kazuyuki Ishida}%
\author[2]{Hironori Masuyama}%
\author[1]{Shigemi Yoshihara}%
\affil[1]{Dokkyo Medical University}%
\affil[2]{Masuyama Gastrointestinal Clinic}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\textbf{Clinical Letters to the Editor}

\textbf{Proton pump inhibitor for eosinophilic duodenal ulcer with
esophageal involvement in a 12-year-old boy}

Yuji Fujita\textsuperscript{1}, MD, Keiichi Tominaga\textsuperscript{2},
MD, PhD, Kazuyuki Ishida\textsuperscript{3}, MD, PhD, Hironori
Masuyama\textsuperscript{4}, MD, PhD, Shigemi
Yoshihara\textsuperscript{1}, MD, PhD

\textbf{Affiliations:}

\begin{enumerate}
\tightlist
\item
  Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan
\item
  Department of Gastroenterology, Dokkyo Medical University, Tochigi,
  Japan
\item
  Department of Diagnostic Pathology, Dokkyo Medical University,
  Tochigi, Japan
\item
  Masuyama Gastrointestinal Clinic, Tochigi, Japan
\end{enumerate}

\textbf{Corresponding author:}

Yuji Fujita, MD

Department of Pediatrics, Dokkyo Medical University, 880 Kitakobayashi,
Mibu, Shimotsuga, Tochigi 321-0293, Japan

Phone: 81-282-86-1111, Fax: 81-282-86-7521

Email\emph{: fujitay@dokkyomed.ac.jp}

\textbf{Funding Sources:} This research did not receive any specific
grant from funding agencies in the public, commercial, or not-for-profit
sectors.

\textbf{Financial Disclosure:} The authors declare they have no relevant
financial relationships.

\textbf{Conflict of Interest Statement:} The authors declare they have
no conflicts of interest.

\textbf{Author contributions:} Y.F. collected and analyzed the data and
drafted and revised the initial manuscript. K.T., K.I., H.M., and S.Y.
interpreted all the 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 of the work.

To the Editor,

A 13-year-old boy with no relevant family or medical history presented
with a one-month history of epigastric pain. Laboratory tests indicated
a white blood cell count of 4700/\selectlanguage{greek}µ\selectlanguage{english}L; eosinophil count, 150/\selectlanguage{greek}µ\selectlanguage{english}L (3.2\%);
albumin, 4.5 g/dL; C-reactive protein, \textless{} 0.01 mg/dL; and total
IgE, 151.6 IU/L. The specific IgE antibody levels to the following
antigens were tested: egg white, 0.41 IU/L; milk, 0.37 IU/L; wheat, 0.25
IU/L; soy, \textless{} 0.10 IU/L; peanut, 0.16 IU/L; and salmon,
\textless{} 0.10 IU/L. Additionally, thymus and activation-regulated
chemokine levels were at 522 pg/mL, and the IgG antibody
for\emph{Helicobacter pylori} was absent. Abdominal ultrasonography
depicted no abnormal findings such as ascites.
Esophagogastroduodenoscopy (EGD) revealed longitudinal linear furrows in
the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from
the duodenal bulb to the descending duodenum, and no abnormal findings
in the stomach (Fig. 1A and B). The rapid urease test result was
negative. Colonoscopy and balloon-assisted enteroscopy revealed no
abnormalities in the ileum and colon. Pathological examination
illustrated eosinophilic infiltration of 60 per high-power field (/HPF)
in the esophagus and more than 100/HPF in the duodenum (Fig. 2A and B),
and no eosinophilic infiltration in the ileum and colon. The patient was
diagnosed with an eosinophilic duodenal ulcer with esophageal
involvement. Esomeprazole, a proton pump inhibitor (PPI), was orally
administered, after which his symptoms promptly improved. After 2
months, the EGD (Fig. 1C and D) and pathological examination (Fig. 2C
and D) results revealed improvement in both the esophagus and duodenum.

Herein, we describe the first pediatric case of eosinophilic duodenal
ulcer with esophageal involvement that was effectively treated by PPI
monotherapy. Eosinophilic gastrointestinal disorders (EGIDs) comprise
eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis
(EGE).\textsuperscript{1,2} Another classification stratifies EGIDs into
EoE and non-EoE EGIDs, and further classifies non-EoE EGIDs into the
following: eosinophilic gastritis (EG), which is localized in the
stomach and esophagus; EGE, which occurs in the stomach and small
intestine (with or without esophagus involvement); eosinophilic
enteritis (EE), which is localized in the small intestine; and
eosinophilic colitis (EC), which is localized in the
colon.\textsuperscript{3} However, none of the classifications consider
cases of eosinophilic inflammation in the gastrointestinal tract below
the esophagus as EoE. The rate of EGE with esophageal involvement is
reported to be 9\% according to a Japanese study\textsuperscript{2}.
Yamamoto et al.\textsuperscript{3} also reported that EE and EC had no
esophageal lesions, but 49\% of EGE cases had esophageal lesions. To
date, there have been no reports of an eosinophilic duodenal ulcer with
esophageal involvement but without post-duodenal involvement at the time
of diagnosis. The possibility of EGIDs should be investigated in case of
duodenal ulcers by an active biopsy, and other gastrointestinal lesions
should be probed for.\textsuperscript{2-4}

A definitive treatment protocol for eosinophilic duodenal ulcer with
esophageal involvement remains unestablished. Although PPIs are
recommended for EoE as the first line treatment,\textsuperscript{5,6}the
effectiveness of PPI for esophageal involvement in non-EoE EGIDs has not
been investigated. However, some case studies have reported the
effectiveness of PPI for eosinophilic duodenal
ulcers.\textsuperscript{7} Systemic glucocorticoids, which are
associated with various side effects, especially in children, are more
often indicated in non-EoE EGIDs than in EoE\textsuperscript{2,3},.
Elimination dietary treatment may be useful in non-EoE EGIDs; however,
it is not an easy treatment as it can lead to failure to thrive in
children. In contrast, PPI have fewer side effects and can be used
safely. In conclusion, PPI monotherapy may be considered as a first line
treatment for eosinophilic duodenal ulcers with esophageal involvement,
depending on the severity.

\textbf{List of abbreviations:}

EG: eosinophilic gastritis

EGD: Esophagogastroduodenoscopy

EoE: eosinophilic esophagitis

EGE: eosinophilic gastroenteritis

EGID: Eosinophilic gastrointestinal disorder

HPF: high-power field

PPI: proton pump inhibitor

\textbf{Acknowledgments:} We would like to thank Editage
(\emph{www.editage.com}) for English language editing.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Kinoshita Y, Oouchi S, Fujisawa T. Eosinophilic gastrointestinal
  diseases -- Pathogenesis, diagnosis, and treatment. \emph{Allergol
  Int} 2019; \textbf{68} : 420-429.
\item
  Kinoshita Y, Furuta K, Ishimaura N, Ishihara S, Sato S, Maruyama R, et
  al. Clinical characteristics of Japanese patients with eosinophilic
  esophagitis and eosinophilic gastroenteritis. \emph{J
  Gastroenterol}2013; \textbf{48} : 333-9.
\item
  Yamamoto M, Nagashima S, Yamada Y, Takatsugu M, Shimoyama Y, Takahashi
  S, et al. Comparison of nonesophageal eosinophilic gastrointestinal
  disorders with eosinophilic esophagitis: A nationwide survey. \emph{J
  Allergy Clin Immunol Pract} 2021; \textbf{S2213-2198} : 00714-5.
\item
  Yamazaki K, Sakashita T, Iwata H, Mizutani T, Matsuura K, Sugiyama T
  et al. A case of a teenage boy with eosinophilic gastroenteritis with
  esophageal involvement developing a hemorrhagic duodenal
  ulcer.\emph{Clin J Gastroenterol} 2015; \textbf{8} : 179-85.
\item
  Lucendo AJ, Molina-Infante J, Arias A, von Arnim U, Bredenoord AJ,
  Bussmann C,~et al. Guidelines on eosinophilic esophagitis:
  evidence-based statements and recommendations for diagnosis and
  management in children and adults. \emph{United European Gastroenterol
  J} 2017; \textbf{5} : 335-58.
\item
  Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM,
  Zevit N, et al. Updated International Consensus Diagnostic Criteria
  for Eosinophilic Esophagitis: Proceedings of the AGREE
  Conference.\emph{Gastroenterology} 2018; \textbf{155} : 1022-33.
\item
  Tee HP, Swarts D, Tydd T, Leong RWL. Gastrointestinal: Eosinophilic
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\end{enumerate}

\textbf{Figure legends}

Figure 1. Esophagogastroduodenoscopy images showing longitudinal linear
furrows in the esophagus (A) and a stage A1 ulcer from the duodenal bulb
to the descending duodenum (B). These findings improved 2 months after
treatment with esomeprazole (C, D).

Figure 2. Pathological examination results showing eosinophil
infiltration of 60 per high-power field (/HPF) in the esophagus (A) and
more than 100/HPF in the duodenum (B). The eosinophil infiltration
improved to 3/HPF in the esophagus (C) and 10/HPF in the duodenum (D) 2
months after initiation of treatment with esomeprazole. (A-D, original
magnification, x400)\selectlanguage{english}
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