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May 2021 Volume 5 Issue 3

COVID CONCEPT

New Bullous Eruptions in a COVID-19 Positive Patient in an
Intensive Care Unit

Angela Kim, DO, MPH1, Muneeb Khan, MD2, Ann Lin, DO, MS1, Hongbei Wang, MD, PhD3,
Louis Siegel, DO1, Suzanne Sirota-Rozenberg, DO1

1Division of Dermatology, St. John’s Episcopal Hospital, Far Rockaway, NY
2Department of Family Medicine, St. John’s Episcopal Hospital, Far Rockaway, NY
3Department of Dermatopathology, Hofstra Northwell School of Medicine, Hempstead, NY

Bullous pemphigoid (BP) is an autoimmune
blistering disorder that most commonly
affects older adults and is characterized by
tense bullae. Although most cases of BP
have no precipitating factors, virus-induced
BPs have been reported.1 We describe a
case of new onset BP in a patient with acute
COVID-19 infection during the pandemic
peak in New York.

A 76-year-old male from a nursing home
with a past medical history of hypertension,
diabetes mellitus, hyperlipidemia, and major
depressive disorder presented to the
emergency department with altered mental
status, hypotension, tachycardia, hypoxia,
and a fever of 100.9F. A positive COVID-19
polymerase chain reaction, labs with

elevated D-dimer, lactate dehydrogenase,
ferritin, C-reactive protein, and erythrocyte
sedimentation rate, and a chest X-ray
showing bilateral infiltrates, were all
consistent with progressing COVID-19
respiratory syndrome. Following respiratory
failure, the patient was intubated and
admitted to the Intensive Care Unit. Patient’s
home medications were discontinued at
admission.

Hydroxychloroquine and azithromycin were
initiated per hospital protocol, along with
intravenous methylprednisolone and
anakinra. There were no skin findings
initially. On day 3, multiple 2mm to 6cm
tense bullae developed on his left
arm(Figure 1). A shave biopsy of a 2mm
intact bullae for Hematoxylin & Eosin(H&E)
and a 3mm perilesional punch biopsy for
direct immunofluorescence(DIF) were
performed. The H&E stain(Figure 2) showed
a cell-poor subepidermal bulla, while
DIF(Figure 3) revealed linear

ABSTRACT

Bullous pemphigoid (BP) is an autoimmune blistering disorder that typically occurs in older
adults. The etiopathogenesis of BP is unclear, although viral triggers have been reported.1
We present a case of new onset pauci-cellular BP in a patient admitted to Intensive Care Unit
from an acute COVID-19 infection. New onset bullous eruptions in the setting of COVID-19
infection should elicit suspicions and consider the differential diagnosis of BP.

INTRODUCTION

CASE PRESENTATION

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May 2021 Volume 5 Issue 3

Figure 1. Bullous Pemphigoid. Clinical presentation
of tense and flaccid bullae with erosions on left upper
extremity

Figure 2. Bullous pemphigoid. Hematoxylin & Eosin
histologic examination of biopsy specimen showing a
pauci-cellular subepidermal bullae with minimal
infiltrate

Immunoglobulin G(IgG) at the
dermoepidermal junction. Bullae were

ruptured with a sterile needle, and wound
care was rendered with twice-daily
applications of topical betamethasone
dipropionate, augmented 0.05% ointment.
No new blisters recurred. Patient recovered
overall and was extubated and discharged.

Figure 3. Bullous Pemphigoid. Direct immuno-
fluorescence image of perilesional punch biopsy
specimen showing linear IgG

The etiopathogenesis of BP is complex and
not yet fully understood, although viral
infections with HIV, EBV, CMV, HHV, HHV-
6, HBV, and HCV have been reported to
trigger BP.1 A report of three pediatric cases
describes post-immunization and post-viral
induced BP.2 To date, there is little
information on the association between
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) virus and BP
and more studies are needed.

DISCUSSION

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Without a history of BP, our intubated
patient was non-verbal at the time of
examination and therefore was unable to
report any prodromal skin pruritus or
tenderness. New onset bullous eruptions
occurred while in critical care for COVID-19
and despite being on a systemic steroid.
Cutaneous symptoms of SARS-CoV-2 are
reported to present as petechial-,
erythematous-, urticarial-, and pernio-like
rashes,3 which our patient did not have.
Although the patient fit the usual age group
for new BP onset, the mechanism of
induction, especially in the setting of SARS-
CoV-2, remains unclear.

On day 1-2 of admission, the patient
received 2L of fluids/day and was oliguric,
but urine output normalized on day 3 when
skin eruptions occurred. Of note, the right
upper extremity and lower extremities were
not edematous and unaffected throughout
admission. Given these facts and the pauci-
cellar subepidermal bullae, a differential
diagnosis of edema blisters must be
considered. Edema blisters are generally
observed on lower extremities and are
associated with chronic venous
insufficiency, congestive heart failure,
hepatic or renal failures, which were
negative in our patient.4 Although pauci-
cellular, our H&E did not show any
epidermal spongiosis or dermal edema,
which is evident in edema blisters.

Typically, eosinophils are the defining
inflammatory infiltrates in BP. Although
pauci-cellular BP is uncommon, studies
have demonstrated IgG depleting BP180 in
the hemidesmosomes and weakening the
lamina lucida without complement activation
in BP.5,6 This may explain the minimal
inflammation within the bulla and positive
IgG on DIF in our case. Other reasons may
include systemic steroid received since

admission or biopsy specimen size not
ample enough to visualize eosinophils.

Most BP DIF shows IgG and/or C3 in the
basement membrane zone. The sensitivity
of DIF in BP ranges 88.3-84%7,8;
additionally, in a large group of BP patients,
DIF detected IgG was 91.4% and 73.6% for
C3. Isolated IgG deposition was 19.8%.8
Our patient showed a unique case of BP
with positive IgG but negative for C3, IgA,
and IgM on DIF. False positive DIF can
occur if biopsies are taken from lower
extremities or from the bullae itself, but our
DIF was taken from the upper extremity, the
only location involved, and from an
uninvolved perilesional skin within 1cm from
a blister. Correlating DIF with ELISA testing
for anti-BP180 and anti-BP230 antibodies
and/or indirect immunofluorescence(IIF)
may have been helpful. However, people
without BP can also have positive
autoantibodies on ELISA. ELISA and IIF
were not performed on our patient when
dermatopathology resulted, which was about
a week after the biopsy, as lesions resolved
and it did not change our management.

A cell-poor subepidermal blister and linear
IgG on DIF may be seen in epidermolysis
bullosa acquisita(EBA). However, EBA
typically occurs in a younger age group, on
sites of trauma, and heals with scarring,
dyspigmentation, and milia formation.
Bullous eruptions on our patient occurred on
day 3 without any previous or current IV
access on the affected extremity.
Furthermore, there was no trauma reported
or observed on the physical exam. Upon
topical treatment, all lesions on our patient
resolved and healed without scarring.
Although our patient had a history of
diabetes, positive DIF ruled out bullous
diabeticorum, edema blister, and coma
blister, which may have negative DIF or
positive IgM and C3.4

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Drug-induced BP, which is triggered by a
combination of genetic predisposition and
inciting medications, can be considered. The
exact mechanism is not well elucidated, but
it leads to alteration of the immune response
to the epidermal basement membrane.9 Our
patient’s long-term home medications were
discontinued at admission until discharge
and were non-contributory. A drug chart
while inpatient was created, and no inciting
medications commonly associated with BP
were given. Initially, a dose of vancomycin
and piperacillin/tazobactam each was given.
Vancomycin can induce linear IgA bullous
dermatosis but DIF would show linear IgA
deposition, which was negative in our
patient. No report has shown association
between BP and hydroxychloroquine or
azithromycin.

Bullous eruption only occurred on our
patient’s left upper extremity. Other
unilateral COVID related rashes have been
reported,10,11 and reasons behind its
localized presentations are still unclear. A
report of a unilateral BP on one leg with
chronic venous stasis, speculates that
inflammation from stasis may have triggered
the BP.12 Inflammation, as evidenced by
serum markers, may have contributed to our
bullous eruption.

Immunosuppressives and anti-inflammatory
medications are mainstay therapies for BP.
In our case, potent topical corticosteroid
resolved our localized BP when the systemic
corticosteroid for the respiratory disease did
not help. More studies are needed to
understand the complexities of SARS-CoV-2
and BP separately and together. When
encountering new bullous eruptions in
patients with active SARS-COV-2, clinicians
should take caution and consider BP in their
differential diagnosis as timely diagnosis and
management can improve patient outcome.

Acknowledgement: We would like to thank Dr.
Sadaf Sheikh (Department of Pathology, St. John’s
Episcopal Hospital, Far Rockaway, NY) for providing
the H&E pathology photos for our case

Conflict of Interest Disclosures: None

Funding: None

Corresponding Author:
Angela Kim, DO, MPH
Division of Dermatology
St. John’s Episcopal Hospital
327 Beach 19th Street
Far Rockaway, New York, 11691
Phone: 718-869-7108
Fax: 408-827-9056
Email: angelakim86@gmail.com

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mailto:angelakim86@gmail.com

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Immunofluorescence in the Diagnosis of
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