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\begin{document}

\title{Pemphigus Vulgaris Presenting with Epigastric Pain}



\author[1]{Marawan Elmassry}%
\author[1]{Jerapas Thongpiya}%
\author[1]{Pitchaporn  Yingchoncharoen}%
\author[1]{Jali Garza}%
\author[1]{Matthew  Soape}%
\author[1]{Kanak Das}%
\affil[1]{Texas Tech University Health Sciences Center}%


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  \date{June 18, 2024}


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\textbf{Pemphigus Vulgaris Presenting with Epigastric Pain}

\textbf{Authors:} Marawan Elmassry MD\textsuperscript{1}, Jerapas
Thongpiya MD\textsuperscript{1}, Pitchaporn Yingchoncharoen
MD\textsuperscript{1}, Jali Garza MS\textsuperscript{1}, Matthew Soape
MD\textsuperscript{2}, Kanak Das MD\textsuperscript{1}

\textsuperscript{1}Department of Internal Medicine, Texas Tech
University Health Sciences Center, Lubbock, TX, USA

\textsuperscript{2}Department of Gastroenterology, Covenant Medical
Center, Lubbock, TX, USA

\textbf{Corresponding author: Marawan Elmassry MD}

Department of Internal Medicine, Texas Tech University Health Sciences
Center, Lubbock, TX, USA

3601 4th St, Lubbock, TX 79430

Email: Marawan.Elmassry@ttuhsc.edu

\textbf{Conflict of interest:} The authors have no financial conflicts
to disclose.

\textbf{Patient's consent:} Written informed consent was obtained from
the patient to publish this report in accordance with the journal's
patient consent policy.

\textbf{Abstract:} Pemphigus vulgaris is an autoimmune mucocutaneous
disease with an involvement in gastrointestinal tract especially in oral
cavity and esophagus. Ulcers can be the initial presentation even before
visible mucosal or cutaneous lesions. The presenting symptoms will be in
accordance with the affected organ such as throat pain, hoarseness,
dysphagia, odynophagia or even bleeding. Here, we report a case of
undiagnosed pemphigus vulgaris presenting with epigastric pain whose
endoscopy showed oropharyngeal involvement and isolate esophageal ulcer,
which failed proton pump inhibitor treatment.

\textbf{Keywords:} Pemphigus Vulgaris, Autoimmune Mucocutaneous Disease,
Epigastric Pain, Esophageal Ulcer.

\textbf{Introduction}

Pemphigus is a group of potentially life-threatening autoimmune
mucocutaneous diseases characterized by epithelial blistering affecting
cutaneous and/or mucosal surfaces secondary to IgG antibody synthesis
against a desmosome glycoprotein, desmoglein (Dsg), present in
keratinocytes. Its estimated incidence is at two new cases/
millions/year. Most are seen in the fifth and sixth decades of life with
rare cases seen in children and the elderly.\textsuperscript{1} Although
there are variants within pemphigus, pemphigus vulgaris accounts for
80\% of cases. There are two clinical forms of pemphigus vulgaris:
mucosal (MPV) and mucocutaneous (MCPV) which patients' mucosa is
affected and over five skin lesions are present.\textsuperscript{2} The
recent study showed that patients with pemphigus vulgaris have oral
lesion about 90\% with solely oral mucosal lesion around
50\%.\textsuperscript{3} The presentation symptoms include tenderness in
the throat, pain on swallowing, hoarseness or
dysphonia.\textsuperscript{2} The authors present a case of pemphigus
vulgaris with oropharyngeal and esophageal involvement presenting
uniquely with an epigastric pain.

\textbf{Case Report}

A 59-year-old female with past medical history of hypertension presented
to the hospital with severe epigastric pain radiating to the neck 4
days. Recently the patient had been prescribed with pantoprazole daily
with titration to twice daily for 2 months for her epigastric pain with
no relief. Initial labs including CBC, CMP, throat swab and culture were
unremarkable. Computed tomography (CT) soft tissue neck showed possible
tonsilitis. Gastroenterology was consulted and patient underwent
esophagogastroduodenoscopy (EGD) that revealed a single esophageal ulcer
in the upper esophagus with subsequent benign biopsies. Patient was
managed with pain control and continued pantoprazole once per day. At
her outpatient follow up visit, she complained of continued pain and
weight loss due to inability to eat. One month after the initial
hospital stay, the patient returned to the ED with worsening symptoms.
EGD was repeated at this point with similar finding of one superficial
esophageal ulcer with oozing blood in the proximal esophagus just below
the upper esophageal sphincter (Fig. 1). Biopsies once again revealed
benign esophageal ulcer. There was also noted to be inflammation and
nodularity in the posterior pharynx below the vocal cords (Fig. 2). At
this point ENT was consulted, and it was decided to perform biopsies of
the tongue and soft palate. Biopsy results were consistent with a
diagnosis of oral pemphigus vulgaris. The patient was started on steroid
therapy and saw resolution of her epigastric pain. She continues low
dose prednisone every day for maintenance therapy 6 months after
diagnosis.\selectlanguage{english}
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Fig 1: Bleeding esophageal ulcer just below the upper esophageal
sphincter\selectlanguage{english}
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Fig 2: Nodularity and inflammation above the upper esophageal sphincter

\textbf{Discussion}

The evolution of PV typically begins with painful mucosal ulceration,
especially in the mouth. These ulcers may be persistent or intermittent,
but the new lesion will continue to appear. Many patients will develop
skin lesions over the following weeks or months with an average of 5
months. Pemphigus vulgaris can affect any site of oral mucosa which
gingival papillary tips are common. White patches of hyperkeratosis can
be seen after PV heals.\textsuperscript{4} In fact, esophageal
involvement has a relatively high incidence ranging from 46-87\%, but
EGD was done infrequently enough to detect.\textsuperscript{5}Esophageal
involvement in pemphigus vulgaris usually presents with throat pain,
dysphagia, odynophagia or even bleeding. However, patient with
oropharyngeal and upper esophageal involvement presented with an
epigastric pain is very uncommon.

Espana et. Al.\textsuperscript{2} found that PV patients usually have
active lesions in both pharyngeal and laryngeal mucosa leading to
throat, pharyngeal or laryngeal symptoms.

Nakamura et al.\textsuperscript{6}found that esophageal involvements of
PV include blisters, erosions, erythema, scattered red spots and
longitudinal erythematous lines with positive Nikolsky sign, mostly in
the upper esophagus. The distribution of lesions can be whole esophagus
with more severity in proximal than distal or more rarely isolated
lesion.

In our patient, she presented with epigastric and neck pain, which might
not be a straightforward manifestation of PV, but can be explained by
her oropharyngeal involvement. Her isolate esophageal ulcer found on EGD
with benign biopsy initially didn't lead us to the diagnosis but with
retroflexion of EGD, the inflammation of pharynx helped further identify
the clues to diagnosis. In addition, the friable ulcer with bleeding as
seen here could also be considered as a positive Nikolsky sign. Early
diagnosis of the disease becomes very important as the disorder can be
life-threatening. Once a diagnosis is made, treatment should be
initiated.

Management of PV is considered in two main phases: remission induction
(to achieve disease control with no new lesion formation and existing
ones to be healed) and remission maintenance (disease-free for at least
2 weeks). First-treatment includes corticosteroid, usually in form of
oral prednisolone (0.5-1 mg/kg/day) and start tapering at the end of
remission maintenance. It is also thought to lower dosing and duration
of steroid therapy in patients which allows for lesser risk of adverse
side effects of therapy Second-line treatment indicated if treatment
failure occurs and it includes azathioprine, mycophenolate mofetil,
cyclophosphamide or methotrexate. Rituximab is recently approved as a
third line treatment.\textsuperscript{4}

\textbf{Conclusion}

It is important to keep in mind that a patient with pemphigus vulgaris
and oral involvement can present with an unusual presentation such as an
epigastric pain like this patient.

\textbf{References:}

1. Porro AM, Seque CA, Ferreira MCC, Enokihara MMS. Pemphigus
vulgaris.\emph{Anais brasileiros de dermatologia} . 2019;94:264-278.

2. Espa\selectlanguage{ngerman}ña A, Fernández S, Del Olmo J, et al. Ear, nose and throat
manifestations in pemphigus vulgaris. \emph{British Journal of
Dermatology} . 2007;156(4):733-737. doi:10.1111/j.1365-2133.2007.07783.x

3. Batistella E, Sabino da Silva R, Rivero ERC, Silva CAB. Prevalence of
oral mucosal lesions in patients with pemphigus vulgaris: A systematic
review and meta-analysis. \emph{J Oral Pathol Med} . Sep
2021;50(8):750-757. doi:10.1111/jop.13167

4. Melchionda V, Harman KE. Pemphigus vulgaris and pemphigus foliaceus:
an overview of the clinical presentation, investigations and
management.\emph{Clin Exp Dermatol} . Oct 2019;44(7):740-746.
doi:10.1111/ced.14041

5. Okamura A, Nakamura R, Yamagami J, et al. Evaluation of
pharyngo-oesophageal involvement in pemphigus vulgaris and its
correlation with disease activity. \emph{Br J Dermatol} . Jan
2017;176(1):224-226. doi:10.1111/bjd.14725

6. Nakamura R, Omori T, Suda K, et al. Endoscopic findings of
laryngopharyngeal and esophageal involvement in autoimmune bullous
disease. \emph{Dig Endosc} . Nov 2017;29(7):765-772.
doi:10.1111/den.12893\selectlanguage{english}
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