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\begin{document}

\title{Erythema multiforme-like bullous pemphigoid following COVID-19 mRNA
vaccine}



\author[1]{Azza Ghannem}%
\author[1]{Faten Rabhi}%
\author[1]{Faten Gargouri}%
\author[2]{Kahena Jaber}%
\author[3]{Raouf Dhaoui}%
\affil[1]{Military Hospital of Instruction of Tunis}%
\affil[2]{Military Hospital of Tunis}%
\affil[3]{Military Hospital of Instruction of Tunis, }%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
Cases of bullous pemphigoid following Covid-19 vaccines have been
recently reported. We describe herein an atypical case of acral bullous
pemphigoid after Pfizer BionTech vaccine. Clinicians should be aware of
this reaction and encourage full vaccination as the disease displays a
rapid improvement treatment.%
\end{abstract}%



\sloppy


\textbf{Title:} Erythema multiforme-like bullous pemphigoid following
COVID-19 mRNA vaccine: A case report

\textbf{Type:} CASE REPORT

\textbf{Key words} : Bullous pemphigoid, COVID-19, vaccines

\textbf{Short title:} Bullous pemphigoid following COVID-19 mRNA vaccine

\textbf{Authors:} Azza Ghannem \textsuperscript{1}, MD, Faten
Rabhi\textsuperscript{1}, MD, Faten Gargouri \textsuperscript{2}, MD,
Kahena Jaber \textsuperscript{1}, MD, Raouf Dhaoui \textsuperscript{1},
MD.

\textbf{Affiliations:} \textsuperscript{1} Department of Dermatology,
Military Hospital of Tunis, Tunisia.

\textsuperscript{2} Department of Pathology, Military Hospital of Tunis,
Tunisia.

\textbf{Corresponding author: Azza Ghannem} , MD

Address: Department of Dermatology, Military Hospital of Tunis, Tunisia.

Phone: + 21695650035

Email:\emph{Azzaghannem5@gmail.com}

\textbf{Funding:} None. The authors have received no funding from any
agency in the public, private, or not-for-profit sectors.

\textbf{Conflict of Interest:} The authors declare that there are no
conflicts of interest in this work.

\textbf{Authorship:} All authors had access to the data and a role in
writing this manuscript.

\textbf{Prior publication:} No

\textbf{Data availability statement:} Authors agree to make data and
materials supporting the results or analyses presented in their paper
available upon reasonable request from the corresponding author.

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

\textbf{Introduction:}

COVID-19 messenger RNA (mRNA) vaccines have been recently associated
with cutaneous adverse events. \textsuperscript{\emph{1}} Only few cases
of bullous pemphigoid (BP) were reported among these reactions. We
report herein a new case of atypical presentation of BP following Pfizer
BioNTech COVID-19 vaccine.

\textbf{Case report:}

A 55-year-old man attended our dermatology department complaining of
painful blisters on his hands and feet, that insidiously appeared over a
one-month period. He had no medical history of dermatologic or
auto-immune diseases. Pruritus of hands and feet first appeared four
days after the first dose of the Pfizer BioNTech COVID-19 vaccine, then
blisters appeared after the second dose, received one month later.
Physical examination revealed clustered vesicles and tense bullae,
mainly distributed on upper and lower extremities with crusted erosions
on the elbows and the forearms. Lesions with a target-like appearance
were seen on the back of the hands (Fig 1: a,b,c). There was no mucosal
involvement. The Nikolsky sign was negative. The laboratory test results
were within normal limits, including complete blood count and blood
chemistry profile. Skin biopsy was performed showing subepidermal
blister with lymphocytic and eosinophilic infiltrate, spongiosis and
dermal edema. Direct immunofluorescence study revealed linear band of
IgG and C3 along the dermo--epidermal junction confirming the diagnosis
of BP (Fig 2: a,b,c). Pharmacovigilance imputability score was I1B2.
Given the severity of the cutaneous reaction, oral prednisone was
started at 0.5 mg/kg/day with rapid clinical improvement.

\textbf{Discussion:}

Cases of BP related to vaccine administration have been reported mainly
in children, including influenza, varicella zoster, tetanus, hepatitis
B, human papilloma virus and recently COVID-19
vaccines.\textsuperscript{\emph{2},\emph{3}}To our knowledge, BP induced
by Covid 19 vaccines are most commonly related to mRNA
vaccines.\textsuperscript{\emph{3}} In our patient, itching followed the
first injection of Pfizer BioNTech and blisters secondary appeared in
the same areas. It could also happen after the second dose in some other
cases.\textsuperscript{\emph{3,4}} Trunk and extremities were the most
affected sites.\textsuperscript{\emph{3}}Vaccine--associated BP disease
may differ from conventional BP in some individuals. Atypical~target
lesions and acral distribution seen in our patient had not been
described yet. That raised the differential diagnosis of erythema
multiforme. One case of a patient who developed maculo-papular and acral
vesicular rashes evolving into BP~was associated to prolonged Covid19
infection. \textsuperscript{\emph{5}} Our patient showed full cutaneous
recovery with no clinical relapse after two months of follow up. In all
cases, resolution within a few weeks was obtained.
\textsuperscript{\emph{3,4}} This~could imply that BP induced by covid
19 vaccine may have atypical presentations and displays a good response
to treatment with a better prognosis than conventional BP. Thus, it
should not contribute to unnecessary avoidance of future vaccination
doses.

\emph{REFERENCES:}

\begin{enumerate}
\tightlist
\item
  McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A,
  Desai SR, French LE, Lim HW, Thiers BH, Hruza GJ, Blumenthal KG, Fox
  LP, Freeman EE. Cutaneous reactions reported after Moderna and Pfizer
  COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad
  Dermatol. 2021 Jul;85(1):46-55.
\item
  de la Fuente S, Hern\selectlanguage{ngerman}ández-Martín Á, de Lucas R, González-Enseñat MA,
  Vicente A, Colmenero I, González-Beato M, Suñol M, Torrelo A.
  Postvaccination bullous pemphigoid in infancy: report of three new
  cases and literature review. Pediatr Dermatol. 2013
  Nov-Dec;30(6):741-4.
\item
  Tomayko MM, Damsky W, Fathy R, McMahon DE, Turner N, Valentin MN,
  Rallis T, Aivaz O, Fox LP, Freeman EE. Subepidermal blistering
  eruptions, including bullous pemphigoid, following COVID-19
  vaccination. J Allergy Clin Immunol. 2021 Sep;148(3):750-751.
\item
  Afacan E, Edek YC, \selectlanguage{polish}İ\selectlanguage{english}lter N, G\selectlanguage{ngerman}ülekon A. Can Covid-19 vaccines cause or
  exacerbate bullous pemphigoid? A report of seven cases from one
  center. Int J Dermatol. 2022 Jan 26.
\item
  Goon PKC, Bello O, Adamczyk LA, Chan JYH, Sudhoff H, Banfield CC.
  Covid\selectlanguage{english}-19 dermatoses: Acral vesicular pattern evolving into bullous
  pemphigoid. Skin Health Dis. 2020;e6.
\end{enumerate}

\emph{LEGENDS}

\textbf{Figure 1 a:} Bullous lesions with target-aspect lesions on the
hand

\textbf{Figure 1 b:} Crusted and vesicular lesions on the forearms

\textbf{Figure 1 c:} Tense sero-hematic bullous lesion of 4 cm on
erythematous base

\textbf{Figure 2 a:} Subepidermal blister (H\&E, x 2)

\textbf{Figure 2 b :} Eosinophilic infiltration (H\&E, x 20)

\textbf{Figure 2 c:} Linear deposition of IgG and C3 along the
dermo--epidermal junction on the direct immunofluorescence study\selectlanguage{english}
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