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\title{New-onset pemphigus after COVID-19}



\author[1]{Yihang Xie}%
\author[1]{Mei Yang}%
\author[1]{Peimei Zhou}%
\author[1]{Jiaming Fan}%
\author[1]{Sijie Zhou}%
\affil[1]{Chengdu Second People's Hospital Department of Dermatology}%


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  \date{May 24, 2024}


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New-onset pemphigus after COVID-19

Yihang Xie\textsuperscript{1} Mei Yang\textsuperscript{1} Peimei
Zhou\textsuperscript{1}* Jiaming Fan\textsuperscript{1} Sijie
Zhou\textsuperscript{1}

1.Department of Dermatovenereology, Chengdu Second People's Hospital,
Chengdu, China

* Corresponding Author: 46551704@qq.com

\textbf{running head:} pemphigus after COVID-19

\textbf{The category of the article:} Letter

\textbf{Keywords:} COVID-19, pemphigus

\textbf{Manuscript word count:} 690 words

\textbf{The number of figures:} 2

\textbf{The number of tables:} 0

\textbf{The number of references:} 8

\textbf{Correspondence to:} Peimei Zhou, M.D, Ph.D., Department of
Dermatovenereology, Chengdu Second People's Hospital, Qingyun Street,
Chengdu, 610041, China.

Tel: +86 18908176315; E-mail:\emph{46551704@qq.com}

\textbf{Full conflict of interest statement:} Y. Xie, and my co-authors
have no conflict of interest to declare.

\textbf{Ethics statement:} The patient has consented to publish this
information.

\textbf{Data availability statement:} Data sharing does not apply to
this article as no new data were created or analyzed in this study.

\textbf{Funding sources:} none

Dear Editor,

Cutaneous manifestations of coronavirus disease (COVID-19), the disease
caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2;
family \emph{Coronaviridae,} genus \emph{Betacoronavirus,}
subgenus\emph{Sarbecovirus} ), have been increasingly reported.
SARS-CoV-2 infection is multisystemic and leads to potentially
detrimental effects on various organs. Maculopapular, urticarial,
vesicular, livedoid, and Chilblain-like lesions (CBLL) have been
commonly reported to be associated with COVID-19\textsuperscript{1}.
Here, we encountered an intriguing case of pemphigus that developed
after COVID-19 infection.

A 73-year-old male presented with a 42-day history of pruritic flaccid
blisters that arose on the trunk and both upper limbs on normal and
erythematous skin. Cutaneous lesions started 3 days after the positive
reverse transcription polymerase chain reaction (RT-PCR) test diagnostic
for SARS-CoV-2. He denied any history of systemic diseases, medication,
and medicine or food allergies, and had not used any medication before
symptom onset. The patient had first been diagnosed with allergic
dermatitis caused by COVID-19 at another hospital and was prescribed
oral prednisone (8 mg once daily for 4 days). The patient reported no
new blisters, but the erythema did not fade; therefore, he visited our
hospital. Physical examination revealed cutaneous lesions on the trunk
and both upper limbs without mucosal involvement and scattered
superficial blisters that developed into crusted erosions on an
erythematous base(Figure1 A-D). Laboratory examination revealed normal
white cell count (8.63 \selectlanguage{ngerman}Ã--10\textsuperscript{9}/L; normal 3.5-9.5
Ã--10\textsuperscript{9}/L) with eosinophilia (6\%; normal 0.5\%-5.0\%).
Desmoglein (Dsg) 1 antibody levels were \textgreater{} 150 U/mL
(positive: \textgreater{} 20), while Dsg3, BP(bullous pemphigoid)180,
and BP230 antibody levels were within normal ranges. Other laboratory
tests including RT-PCR targeting SARS-CoV-2, immunoglobulin, erythrocyte
sedimentation rate, the spectrum of antinuclear antibodies, and T-spot
were negative or normal. Chest and abdominal computed tomography
revealed chronic inflammatory changes but no obvious tumors.
Histological analysis of an incisional cutaneous biopsy taken from the
patient's abdomen showed subcorneal blister formation, acantholytic
cells within the blister, and marked spongiotic edema in the spongiosa
layer that had mixed inflammatory infiltrate with eosinophils,
leukomonocytes, and neutrophils(Figure2A). Direct immunofluorescence
(DIF) showed deposition of intracellular IgG and C3 in subepidermal 2/3
interspinous cells, though was negative for IgA and IgM, confirming
pemphigus(Figure2B,C). Considering the good response to hormone
treatment, the patient continued oral prednisone at 8 mg once daily
along with the use of topical corticosteroids. Symptoms were completely
absent after 3 weeks(Figure1 E-F).

An increasing number of studies on cutaneous manifestations of COVID-19
have been reported; however, knowledge is still lacking on the common
skin manifestations of this disease. Nonspecific cutaneous
manifestations due to SARS-CoV-2 infection have also been reported, such
as immune thrombocytopenic purpura (ITP), dengue-like exanthem,
pityriasis rosea-like eruptions, acral ischemia, mucositis, dusky
lesions, and bullae\textsuperscript{2.3.4}. We searched all relevant
articles and found only two cases of pemphigus vulgaris induced by
COVID-19. In the case presented here, we realized that COVID-19 may be
responsible for the rash eruption, possibly due to an inflammatory
reaction\textsuperscript{5}. The onset time of the rash was similar to
that in the cases of pemphigus previously reported by De
Medeiros\textsuperscript{5} and Mohaghegh F\textsuperscript{6} (within
1.5 months). In our case, although direct immunofluorescence showed
subepidermal 2/3 deposition, we still diagnosed pemphigus foliaceus in
combination with the pathological presentation, indirect
immunofluorescence, and good treatment outcome. We speculate that the
reason why direct immunofluorescence showed subepidermal 2/3 deposition
may be the marked sponge edema of the epidermis, which may lead to a
discontinuity of acantholysis, resulting in leakage of Dsg1 into the
deeper epidermis.

Pemphigus is defined as a group of rare mucocutaneous autoimmune
diseases. Its etiology is unknown, though there are studies on
autoimmune etiology which is believed to be related to stimulation by
certain drugs, ultraviolet radiation, and malignant tumors; these induce
autoimmune reactions by making the adhesive substances between the spiny
cell layers become autoantigens\textsuperscript{7}. It is rarely
considered, however, that viral infections might cause pemphigus. The
ability of SARS-CoV-2 to induce a hyper-stimulated immune state was
discovered at the beginning of the pandemic\textsuperscript{8}. As an
instrumental trigger of autoimmunity, SARS-CoV-2 infection could be a
trigger for autoimmune reactions, possibly through more than one
mechanism. Because of this, all factors should be considered in any
patient presenting with new-onset or exacerbating cutaneous reactions.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Huynh T, Sanchez-Flores X, Yau J, Huang JT. Cutaneous Manifestations
  of SARS-CoV-2 Infection. Am J Clin Dermatol 2022;23:277-286.
\item
  Bhattacharjee S, Banerjee M. Immune Thrombocytopenia Secondary to
  COVID-19: a Systematic Review. SN Compr Clin Med 2020;2:2048-2058.
\item
  J Joob B, Wiwanitkit V. COVID-19 can present with a rash and be
  mistaken for dengue. J Am Acad Dermatol 2020;82:e177.
\item
  Ehsani AH, Nasimi M, Bigdelo Z. Pityriasis rosea as a cutaneous
  manifestation of COVID-19 infection. J Eur Acad Dermatol Venereol
  2020;34:e436-e437.
\item
  De Medeiros VLS, Monteiro-Neto AU, França DDT, Castelo Branco R, de
  Miranda Coelho ÉO, Takano DM. Pemphigus Vulgaris After COVID-19: a
  Case of Induced Autoimmunity. SN Compr Clin Med 2021;3:1768-1772.
\item
  Mohaghegh F, Hatami P, Refaghat A, et al. New-onset pemphigus
  foliaceus following SARS-CoV-2 infection and unmasking multiple
  sclerosis: A case report. Clin Case Rep 2022;10:e05910.
\item
  Korman N. Pemphigus. J Am Acad Dermatol 1988;18:1219-1238.
\item
  Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y. The
  SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev
  2021;20:102792.
\end{enumerate}\selectlanguage{english}
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\toprule
Figure 1: (A-D) Scattered superficial blisters on the trunk and upper
limbs that devolved into crusted erosions on a erythematous base.(E-F)
erythema and blisters almost disappeared.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
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\toprule
Figure 2: (A) Hematoxylin--eosin, \selectlanguage{ngerman}×100, Subcorneal blister formation,
acantholytic cell within the blister, and marked spongiotic edema in the
spongiosa layer with mixed inflammatory infiltrate with eosinophils,
leukomonocyte and neutrophil. (B.C)Direct immunofluorescence (DIF)
showed the deposition of IgG and C3 in subepidermal 2/3 interspinous
cell with negative IgA and IgM.\tabularnewline
\bottomrule
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