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\begin{document}

\title{Extensive keloid scarring in a patient with pemphigus vulgaris}



\author[1]{Dorsaf Elinkichari}%
\author[1]{Anissa Zaouak}%
\author[2]{Amal Chamli}%
\author[2]{Houda Hammami Ghorbel}%
\author[1]{Samy Fenniche}%
\affil[1]{Habib Thameur Hospital}%
\affil[2]{University of Tunis El Manar Faculty of Medicine of Tunis}%


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  \date{May 21, 2024}


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\begin{abstract}
Since pemphigus blisters are intraepidermal, scarring should induce at
most a post-inflammatory hyperpigmentation. We describe a very atypical
and unusual course of pemphigus vulgaris with extensive keloid formation
despite high systemic steroids. This could be promoted by the severe
flare of the disease, the delay of scarring and the superinfection.%
\end{abstract}%



\sloppy


\textbf{Extensive keloid scarring in a patient with pemphigus vulgaris}

\textbf{Dorsaf Elinkichari\textsuperscript{1,2}, Anissa
Zaouak\textsuperscript{1,2}, Amal Chamli\textsuperscript{1,2}, Houda
Hammami\textsuperscript{1,2} Samy Fenniche\textsuperscript{1,2}}

\textsuperscript{1}Department of Dermatology, Habib Thameur Hospital,
Tunis, Tunisia

\textsuperscript{2}Faculty of Medicine of Tunis, University of Tunis El
Manar, Tunis, Tunisia

\textbf{Correspondence}

Dorsaf Elinkichari, Department of Dermatology, Habib Thameur Hospital,
Tunis, Tunisia.

Email:\emph{dorsaf.elinkichari@gmail.com}

\textbf{Key Clinical message}

Keloid scarring in PV may be promoted by the severity of the flare, the
delay of scarring and the superinfection. Treatment in such cases may be
challenging.

\textbf{Abstract}

Since pemphigus blisters are intraepidermal, scarring should induce at
most a post-inflammatory hyperpigmentation. We describe a very atypical
and unusual course of pemphigus vulgaris with extensive keloid formation
despite high systemic steroids. This could be promoted by the severe
flare of the disease, the delay of scarring and the superinfection.

\textbf{Key words}

Clinical Dermatology, Pemphigus vulgaris, Keloid

The patient has given written informed consent to the publication of his
case details.

\textbf{Introduction}

Keloid scarring in pemphigus vulgaris (PV) is uncommon. Since pemphigus
blisters are intraepidermal, scarring should induce at most a
post-inflammatory hyperpigmentation. Only four cases of keloid scars
following pemphigus have been reported {[}1--4{]}. Herein, we describe
an unusual extensive keloid scarring following a severe flare of PV.

\textbf{Observation}

A 47-year-old Caucasian woman with a 4-month history of PV presented
with extensive keloid scarring at areas of prior PV erosions. Four
months ago, she had been hospitalized for a severe PV flare with
erosions affecting her trunk, upper and lower limbs (figure 1a). Oral,
nasal and conjunctival mucosa were also involved. In addition, nail
damage was noted with onycholysis, onychomadesis and necrotic paronychia
(figure 1b). The Pemphigus Disease Area Index (PDAI) was 55. The
diagnosis of PV was confirmed by histological and immunological
investigation showing intraepidermal blistering, supra-basal epidermal
acantholysis and inter-keratinocyte IgG deposits in direct
immunofluorescence. ELISA was positive for anti-desmoglein 3 (120 U/ml)
and anti-desmoglein 1 (180 U/ml). The erosions did not heal after 16
days of treatment with 1.5mg/kg/day of prednisone-equivalent and became
extensive and hemorrhagic. The patient was apyretic. The complete blood
count revealed hyperleukocytosis and hyperneutrophilia. CRP level was
386 mg/l. Two days later, a greenish malodorous discharge covered almost
all the erosions (Figure 2a). Cultures grew \emph{Pseudomonas
aeroginosa} . Thus, the diagnosis of ecthyma gangrenosum complicating a
PV was retained. A dramatic improvement of the patient's skin erosions
was observed two weeks after introducing an antibiogram-adjusted
antibiotic therapy based on Tazobactam and Amikacin. After two weeks,
the erosions had re-epithelialized with post-inflammatory
hyperpigmentation, and the patient was discharged. We started oral
steroids tapering without relapse. At the four-month follow-up,
extensive keloids were noted on previous superinfected PV sites (figure
2b), for which intralesional corticosteroids were scheduled.

\textbf{Discussion}

Three main factors of keloids are known: infection, deep injury and
mechanical trauma {[}5{]}. So far, only four cases of keloid scars
following pemphigus have been reported {[}1--4{]}. Gupta et al. reported
a case of uninfected PV erosions that healed with keloids despite high
dose of systemic steroids {[}2{]}. Shivaswamy et al. described keloids
in a patient whose pemphigus was treated\emph{, inter alia} , with
cyclosporin. The onset of keloids in this patient was attributed to
cyclosporin {[}3{]}. In the latest two cases, such as in our patient,
extensive keloids appeared in patients whose pemphigus had been
superinfected. Authors suggested that secondary infection induced
keloids via dermal damage. However, the paucity of cases of keloids
following PV flares contrasts with the frequency of superinfections
which are common in pemphigus, suggesting the presence of other unknown
factors {[}1,4{]}.

Our case is notable due to the severity of the PV flare which was
refractory to conventional treatment and then complicated by ecthyma
gangrenosum. Re-epithelialization took more than one month and ended
with extensive keloids after three months. It is reasonable that
superinfection led to deep intradermal inflammation and keloid
formation. In fact, keloids occurred in previously superinfected PV
areas. In this context, there are reports of keloid onset following
herpetic infections, with the keloids involving previously infected
areas {[}6{]}. An alternative hypothesis is that erosions in our patient
took exceptionally long to heal, which maintained a long inflammation
and scarring process with a chronic fibroblast activation. This does not
exclude the potential role of apoptotic cells as well as increased
levels of tumor necrosis factor-alpha, found in PV, that may contribute
to the dysregulation of fibroblasts, and lead to keloids in susceptible
patients {[}7{]}. Intralesional steroids are generally proposed in
patients with keloids. Yet, our patient is under high systemic doses of
steroids, making this alternative debatable as we can opt for
compression clothing and active monitoring.

\textbf{Conclusion}

This case is being reported to highlight a very atypical and unusual
course of PV with extensive keloid formation despite high systemic
steroids. This could be promoted by the severe form of PV, the delay of
scarring and the superinfection. Moreover, treatment in such cases may
be challenging since patients are usually under systemic steroids making
intralesional steroids contestable.

\textbf{CONFLICT OF INTEREST}

None. This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.

\textbf{AUTHOR CONTRIBUTIONS}

Dorsaf Elinkichari is the guarantor of the content of the manuscript,
including the data and analysis. Anissa Zaouak contributed to
acquisition of data, conception, and interpretation of information and
gave final approval of the version to be submitted. Amal Chamli revised
data critically for important intellectual content. Houda Hammami and
Samy Fenniche contributed to interpretation of data and revision of the
manuscript.

\textbf{ETHICAL STATEMENT}

Written informed consent was obtained from the patient.

\textbf{References}

{[}1{]} Sako EY, Workwick S. Extensive keloid formation after pemphigus
vulgaris. Dermatol Online J 2015;21:13030/qt7sc4z88j.

{[}2{]} Gupta SD, Khanna N, Rathi S. Extensive keloidal healing of
pemphigus vulgaris. Indian J Dermatol Venereol Leprol 1997;63:199--200.

{[}3{]} Shivaswamy K, Thappa D. Extensive keloids following cyclosporin
therapy in a pemphigus vulgaris patient. J Eur Acad Dermatol Venereol
2007;21:111--112.

{[}4{]} Nguyen J, Amber KT, Chapman LW. Pemphigus vulgaris complicated
by extensive keloid scarring. Clin Exp Dermatol 2018;43:76--77.

{[}5{]} Gira AK, Brown LF, Washington CV, Cohen C, Arbiser JL. Keloids
demonstrate high-level epidermal expression of vascular endothelial
growth factor. J Am Acad Dermatol. 2004;50(6):850-3.

{[}6{]} Koley S, Saoji V, Salodkar A. Unusual formation of keloids after
each episode of recurrent herpes zoster in an HIV positive patient.
Indian J Sex Transm Dis AIDS 2009;30:109--111.

{[}7{]} Chiapa-Labastida M, Zentella-Dehesa A, Le\selectlanguage{ngerman}ón-Dorantes G.
Pemphigus vulgaris: accumulation of apoptotic cells in dermis and
epidermis possibly relates to pathophysiology through TNF-alpha
production by phagocytes. Eur J Dermatol 2011;21:874--888.\selectlanguage{english}
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