\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Esophageal Tuberculosis as a Rare Cause of Dysphagia: Case Report}



\author[1]{Billy Zhao}%
\author[1]{Hyun Jae Kim}%
\author[2]{Jessica Farrell}%
\author[1]{Wei Xiong}%
\author[1]{Jennifer Telford}%
\author[1]{Sarvee Moosavi}%
\affil[1]{The University of British Columbia Faculty of Medicine}%
\affil[2]{Mount Saint Joseph Hospital}%


\vspace{-1em}



  
  \date{May 29, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Introduction:}

Gastrointestinal tuberculosis (TB) is a rare extrapulmonary
manifestation of TB.\textsuperscript{1} Involvement of terminal ileum,
cecum, and peritoneum are more commonly documented while esophageal
involvement accounts for less than 0.2\% of all TB
patients.\textsuperscript{2-4} Despite the lower incidence of TB in
Western countries, given the vague clinical manifestations of
gastrointestinal TB, clinicians are required to keep TB on their
differentials in work-up of various gastrointestinal symptoms, even if
the patient has been previously vaccinated. We present a unique case of
esophageal and duodenal TB in a patient who was vaccinated with BCG,
with a prior negative Mantoux tuberculin skin test (TST).

\textbf{Case report:}

A 37-year-old Filipino female presented to the emergency department with
a four-month history of progressive dysphagia to solids and then
liquids. She was otherwise healthy and did not take any prescribed
medication. She denied odynophagia, food bolus obstruction, chest pain,
regurgitation, heartburn, and respiratory symptoms. She had
unintentional weight loss of 3kg over 4 months with no other
constitutional symptoms.

The patient had received BCG vaccination in the Philippines as a child.
Her chest x-ray on Canadian immigration screening in 2009 was negative
for latent or active TB. Her only known TB exposure occurred 14 months
ago when her mother visited Canada and was diagnosed with active
pulmonary TB after returning to the Philippines. Interestingly, she had
a negative TST as a part of her care aide employment screening five
months before her emergency department presentation.

Cardiac, respiratory, and abdominal examinations revealed no
abnormalities with no palpable lymphadenopathy. Complete blood count
with differential showed mild normocytic anemia with hemoglobin of 108
g/L (115-155). WBC was normal at 5.3*10\textsuperscript{9}/L (4.0-11.0).
She had a normal neutrophil count of 3.6 *10\textsuperscript{9}/L
(2.0-8.0), mildly decreased lymphocyte at 1.1 *10\textsuperscript{9}/L
(1.2-3.5), and normal monocyte, eosinophil, and basophil counts.
Electrolytes and hepatic panels were normal. Her chest x-ray in the
emergency department showed no signs of lung scarring.

Esophagogastroduodenoscopy (EGD) revealed a 2 cm ulcerated mass,
abutting the gastroesophageal junction (GEJ) inferiorly on retroflexion
(Figure 1) and a subepithelial lesion in the duodenal bulb with normal
overlying mucosa. The exam was otherwise normal. Mucosal biopsies were
taken from both lesions and histopathology revealed ulcerated mucosa
with acute and chronic inflammatory infiltrates composed of histiocytes,
granulocytes, and lymphocytes (Figure 2). No granulomas were identified.
Ziehl-Neelsen stain was negative for acid-fast bacilli. Although a
lymphoproliferative disorder was not identified, it could not be
excluded in the limited tissue sample.

Additionally, computed tomography (CT) scan of her chest, abdomen, and
pelvis was performed for staging due to suspicion of lymphoma or other
malignancy. This demonstrated infiltrative soft tissue masses at the GEJ
and duodenal bulb, each measuring up to 4.5 cm in size (Figure 3). There
was linear scarring and several discrete nodules at the left lung apex,
the largest 12 mm (Figure 4). No pathologically enlarged lymph nodes
were noted.

Endoscopic ultrasound (EUS) demonstrated an ill-defined, hypoechoic
lesion, involving the GEJ, extending into the region of the celiac axis.
A second lesion, involving the proximal duodenum, was round with
well-defined margins and measured 20 mm x 14 mm (Figure 5). No enlarged
lymph node was seen. EUS-guided fine-needle biopsy of both lesions was
performed, which revealed fragments of necrotizing granulomatous
inflammation (Figure 6). No mycobacteria were seen on Ziehl-Neelsen
stain (Figure 6). Concurrent flow cytometry was completed with a
10-color lymphoma screening panel. The CD45 gated lymphocyte population
accounted for 4\% of all events. T-cells were 66\% of the lymphocyte
gate and showed normal antigen expression. The CD4/CD8 ratio is 1.7.
Overall, the flow cytometry analysis was not consistent with
lymphoproliferative disorders. Given this finding along with the fact
that previous infectious investigations are not highly sensitive,
infectious etiologies cannot be ruled out and the patient was referred
to the infectious disease team and underwent an IGRA/QuantiFERON assay,
which came back positive. Diagnosis of TB was further confirmed by a
positive TB PCR testing on paraffin block on esophageal biopsies from
index EGD. The patient was subsequently referred to a TB-specialized
clinic and was started on Rifampin, isoniazid, vitamin B6, and
pyrazinamide for 6 months. Given the lack of respiratory symptoms or
active findings on chest imaging, isolation was not required, and her
immediate family members were all screened for TB.

\textbf{Discussion:}

Dysphagia is the most common presenting symptom of esophageal TB;
however, this is a common presenting symptom of a rare
disease.\textsuperscript{5-7} Other symptoms of esophageal TB include
chest pain, fever, odynophagia, and weight loss.

Endoscopic findings of esophageal TB can vary, but typically present as
either ulcerated, bulging mucosal or submucosal mass and rarely as a
stricture or fistula.\textsuperscript{5,8-10} Given its appearance,
upper gastrointestinal TB is often mistaken for malignancy in reported
cases, as it was in our case.\textsuperscript{11,12}

Adding to the diagnostic dilemma was the fact that our patient was both
previously vaccinated with BCG and had a prior negative TST five months
before presentation. BCG has an effectiveness of 46-50\% regardless of
the time of vaccination.\textsuperscript{13,14} TST has a sensitivity of
60-98\% but is prone to false-negative results from technical errors or
decreased skin reactivity.\textsuperscript{15} Acid-fast bacilli
staining on biopsied tissue has high specificity but low sensitivity for
TB.\textsuperscript{16} Instead, tissue PCR should be used, given the
higher sensitivity estimated to be between 74\% to 100\% with most
false-negatives as a result of insufficient tissue
sampling.\textsuperscript{16-18}

The most common etiology of esophageal TB is local spread from adjacent
respiratory tract or mediastinal lymph nodes.\textsuperscript{5,19}While
our patient had no respiratory symptoms, normal chest x-ray, and
negative TST, lung scarring seen on her CT chest may indicate latent
pulmonary TB. Lymphadenopathy was absent on both EUS and cross-sectional
imaging, making spread from lymph nodes less likely.

Other than enlarged lymph nodes, other EUS features of esophageal TB
include thickened esophageal wall and hypoechoic lesions that may
contain hyperechoic calcifications, which we did not see in our
patient.\textsuperscript{19} However, none of these features is
sensitive nor specific to esophageal TB.

Primary esophageal TB is also unlikely as it is rare and occurs when
mycobacterium tuberculosis adheres to the esophageal wall after direct
ingestion and needs to bypass protective mechanisms such as the mucus
barrier and stratified squamous epithelium of the
esophagus.\textsuperscript{9,19}

Despite previous vaccination, a negative skin test, and the absence of
other features of TB other than generalized weight loss, our patient was
found to have esophageal and duodenal TB. Although rare in a Western
setting, an index of suspicion is needed to keep gastrointestinal TB as
part of the differential for workup of dysphagia for patients from
endemic areas, even with prior BCG vaccination and negative screening
TST.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Evans RP, Mourad MM, Dvorkin L, Bramhall SR. Hepatic and
  intra-abdominal tuberculosis: 2016 update. Current Infectious Disease
  Reports. 2016;18(12). doi:10.1007/s11908-016-0546-5
\item
  Sheer TA, Coyle WJ. Gastrointestinal tuberculosis. Curr Gastroenterol
  Rep. 2003;5(4):273-278. doi:10.1007/s11894-003-0063-1
\item
  Carr DT, Spain DM. Tuberculosis in a Carcinoma of the Oesophagus.
  American Review of Tuberculosis. 1942;46(3):346-349.
\item
  Xiong J, Guo W, Guo Y, Gong L, Liu S. Clinical and endoscopic features
  of esophageal tuberculosis: a 20-year retrospective study. Scand J
  Gastroenterol. 2020;55(10):1200-1204.
  doi:10.1080/00365521.2020.1813799
\item
  Puri R, Khaliq A, Kumar M, Sud R, Vasdev N. Esophageal tuberculosis:
  role of endoscopic ultrasound in diagnosis. Dis Esophagus.
  2012;25(2):102-106. doi:10.1111/j.1442-2050.2011.01223.x
\item
  Vahid B, Huda N, Esmaili A. An unusual case of dysphagia and chest
  pain in a non-HIV patient: esophageal tuberculosis. Am J Med.
  2007;120(4):e1-e2. doi:10.1016/j.amjmed.2005.12.026
\item
  Park JH, Kim SU, Sohn JW, et al. Endoscopic findings and clinical
  features of esophageal tuberculosis. Scand J Gastroenterol.
  2010;45(11):1269-1272. doi:10.3109/00365521.2010.501524
\item
  Birda CL, Kumar A, Gupta P, Singh H, Sharma V. Oesophageal
  Tuberculosis: A Systematic Review Focusing on Clinical Management
  {[}published online ahead of print, 2021 Sep 4{]}. Dysphagia.
  2021;10.1007/s00455-021-10360-x. doi:10.1007/s00455-021-10360-x
\item
  Jain SK, Jain S, Jain M, Yaduvanshi A. Esophageal tuberculosis: is it
  so rare? Report of 12 cases and review of the literature. Am J
  Gastroenterol. 2002;97(2):287-291.
  doi:10.1111/j.1572-0241.2002.05456.x
\item
  Nie D, Li J, Liu W, et al. Esophagomediastinal fistula due to
  secondary esophageal tuberculosis: report of two cases. J Int Med Res.
  2021;49(7):3000605211023696. doi:10.1177/03000605211023696
\item
  Fujiwara Y, Osugi H, Takada N, et al. Esophageal tuberculosis
  presenting with an appearance similar to that of carcinoma of the
  esophagus. J Gastroenterol. 2003;38(5):477-481.
  doi:10.1007/s00535-002-1088-1
\item
  Zhu R, Zhou Y, Wang H, et al. Gastric tuberculosis mimicking
  submucosal tumor: a case series. BMC Gastroenterol. 2020;20(1):23.
  Published 2020 Jan 30. doi:10.1186/s12876-020-1175-x
\item
  Michelsen SW, Soborg B, Koch A, Carstensen L, Hoff ST, Agger EM, et
  al. The effectiveness of BCG vaccination in
  preventing\emph{mycobacterium tuberculosis} infection and disease in
  Greenland. Thorax. 2014;69(9):851--6.
\item
  Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV,
  et al. Efficacy of BCG vaccine in the prevention of tuberculosis.
  meta-analysis of the published literature. JAMA: The Journal of the
  American Medical Association. 1994;271(9):698--702.
\item
  WHO Tuberculosis Research Office. FURTHER studies of geographic
  variation in naturally acquired tuberculin sensitivity.~\emph{Bull
  World Health Organ} . 1955;12(1-2):63-83.
\item
  Ma J, Yin H, Xie H. Critical role of molecular test in early diagnosis
  of gastric tuberculosis: a rare case report and review of literature.
  BMC Infect Dis. 2019;19(1):589. Published 2019 Jul 5.
  doi:10.1186/s12879-019-4225-7
\item
  Baylan O, Kilciler G, Albay A, Tuzun A, Kisa O, Dagalp K. Polymerase
  chain reaction based diagnosis of primary gastric tuberculosis in an
  80-year-old woman: a case report and review of the literature. New
  Microbiol. 2009;32(2):217-221.
\item
  Kaul KL. Molecular detection of Mycobacterium tuberculosis: impact on
  patient care. Clin Chem. 2001;47(8):1553--8.
\item
  Zhu R, Bai Y, Zhou Y, et al. EUS in the diagnosis of pathologically
  undiagnosed esophageal tuberculosis. BMC Gastroenterol.
  2020;20(1):291. Published 2020 Aug 28. doi:10.1186/s12876-020-01432-7
\end{enumerate}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/FIgure-4/FIgure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/FIgure-6/FIgure-6}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

