DOJ
Pemphigus vulgaris with nail involvement presenting
with vegetating and verrucous lesions
Contents
R Mascarenhas MD, B Fernandes MD, JP Reis MD, O
Tellechea MD PhD, and A Figueiredo MD PhD
Dermatology Online Journal 9 (5): 14
Dermatology Department, University Hospital, Coimbra.
Abstract
We report the case of a 68-year-old female with longstanding
insulin-treated diabetes mellitus, observed for the first time in our
department in August 1999 with multiple painful erosive lesions of
the oral cavity and many bullous or erosive lesions on the
abdominal wall, back, and thigh. She also had vegetating and
verrucous lesions, similar to common warts, involving the hands
and feet, mainly on the palms, palmar surface of the fingers, and
nail folds. Her lesions were present for 1 year. Skin and mucous
biopsies showed the characteristic histopathologic findings of
pemphigus vulgaris, with an epidermal intercellular IgG deposition
on direct immunofluorescence. Histology of a warty lesion of the
finger also showed suprabasal acantholysis. After partial
improvement with low doses of oral steroids and azathioprine, her
disease progressed to involve the oral cavity, trunk, hands, feet, and
scalp. Control of her disease required successive treatments of
mycophenolate mofetil and cyclophosphamide, as well as
corticosteroids. A partial response was obtained with all these
treatments. After being controlled by cyclophosphamide that was
slowly tapered, she is now well controlled with azathioprine and
oral steroids, showing only discrete lesions of the oral mucosa after
1 year of followup. We report this case of pemphigus vulgaris with
unusual clinical aspects, namely vegetating and verrucous lesions
as well as nail involvement, rarely described in this disease.
Introduction
Pemphigus vulgaris (PV) is an autoimmune blistering disease,
with blisters occurring in the deeper part of the epidermis, above
the basal layer.
Clinically it is characterized by flaccid bullae that lead to
erosions. These may occur anywhere on the skin, and the
involvement of oral mucosa is very common. More rarely,
esophagus, rectum, uterus, and vagina may also be affected.
Histopathology reveals suprabasal acantholysis. Direct
immunofluorescence (DIF) using the patient's perilesional skin as
substrate shows IgG deposition in the intercellular spaces between
the keratinocytes. Desmoglein 3, a 130 Kda component of
desmosome, is the target antigen in this disease.
Before the corticosteroid era this disease was fatal in 60
percent of patients. Nowadays, with new treatments available
(corticosteroids, immunosuppressive drugs, anti-inflammatory
drugs and immunomodulatory procedures) mortality is reduced to
less than 10 percent, but we now must consider severe adverse side
effects of these agents [1, 2].
We report a case of pemphigus vulgaris (PV) with nail
involvement and atypical verrucous lesions, rarely described in this
entity.
Case report
Figure 1
Figure 2
Erosive lesions of the oral mucosa (fig. 1).
Bullous and erosive lesion of the thigh (fig. 2).
Figure 3
Figure 4
Vegetating and verrucous lesions of the left hand, simulating
common warts (fig. 3).
Warty lesions of the right hand (fig. 4).
A 68-year-old female was first observed in our department in
August 1999 with multiple painful erosive lesions, mainly
involving the oral cavity (palate, buccal mucosa, tongue, and lips),
and bullous-erosive lesions and crusts involving the skin of thighs,
abdominal wall, and back (figs. 1, 2). She also had vegetative
verrucous lesions on the periphery of fingernails and digits (palmar
surface), some of them clinically similar to common warts (figs. 3,
4), and bullous and vegetating lesions on the skin of both feet (fig.
5), with nail plate destruction of the first toe of left foot and of the
third toe of the right foot. Both bullous-erosive and verrucous
lesions were present for 1 year. There was no involvement of the
axillary or inguinal folds.
Figure 5
Figure 6
Bullous and vegetating lesions on both feet, with nail-plate
destruction on the first toe of the left foot and third of the
right foot (fig. 5).
Histology of a warty lesion of the finger, showing important
acantholysis above the basal cell layer, as well as, acanthosis
and papillomatosis (fig. 6).
She had a longstanding history of insulin-dependent diabetes
mellitus. Her mother was also diabetic.
Cutaneous biopsies performed on lower limb and back
showed the characteristic histopathologic findings of PV, with
prominent suprabasalar acantholysis. DIF, using the patient's
perilesional skin as a substrate, showed intercellular deposition of
IgG in the epidermis and intercellular deposition of C3 in the
epidermis and along the dermal-epidermal junction. Histology of a
crusted, verrucous lesion of the finger also showed prominent
acantholysis above the basal cell layer, as well as acanthosis and
papillomatosis (fig. 6).
She started treatment with oral corticosteroids
(methylprednisolone 48 mg per day), azathioprine (50 mg bid) and
topical cyclosporine in oral mucosa (100 mg bid). Mucous and
cutaneous lesions, including the warty lesions of the fingers and
toes, improved considerably, but the use of higher doses of
methylprednisolone led to the aggravation of her diabetes, which
could not be controlled with the increased doses of subcutaneous
insulin, necessitating hospitalization to perform insulin perfusion.
For that reason, oral steroids were progressively tapered and finally
withdrawn in April 2000.
The patient remained well until October 2000, when mucous
and skin lesions recurred, affecting also the face and scalp. A
partial response was obtained with the introduction of oral steroids
(methylprednisolone 32 mg per day), alone or in association with
azathioprine (50 mg bid) or mycophenolate mofetil (2 g daily).
However this partial response was followed closely by relapse even
under therapy. Azathioprine had to be withdrawn when she
developed liver toxicity.
In November she started treatment with cyclophosphamide
(50 mg daily and later 100 mg daily) and methylprednisolone (16
mg daily), showing improvement of the disease, maintaining
discrete asymptomatic oral lesions and some verrucous lesions of
the hands. After 10 months, her disease progressed again and
cyclophosphamide was replaced with azathioprine (50 mg daily)
and methylprednisolone (24 mg on alternate days). Lesions
improved considerably and after 1 year of followup, she maintains
this therapy with no liver toxicity from azathioprine, with control
of her diabetes on subcutaneous insulin, and with only discrete
lesions of oral mucosa.
Discussion
This case has an unusual presentation with peculiar clinical
aspects, vegetating and verrucous lesions as well as nail
involvement. These particular clinical findings showed parallel
clinical course and response to therapy as did the more typical skin
lesions of PV. Vegetating verrucous lesions had the typical
histologic hallmark of PV, suprabasalar acantholysis.
Nail involvement in pemphigus is rare and presents mainly as
hemorrhagic paronychia. However, other nail findings have been
reported, including paronychia, onychomadesis, onycholysis,
subungual hyperkeratosis, Beau lines, trachyonychia, and
vegetative lesions over paronychia. Although the presence of
pemphigus lesions on the skin of the distal phalanges surrounding
the nail is well known, none of the reported nail manifestations of
pemphigus have the same warty aspect of our patient [3-13]. Nail
changes appearing as the primary manifestation of pemphigus
vulgaris, either in the nail bed, nail matrix, or nail fold (as seen in
our patient), is a rare and infrequently reported phenomenon. Nail
involvement usually occurs when the disease is severe, and, in the
majority of cases, nail recovery is complete or almost complete
after systemic therapy, as in our patient [3].
Verrucous and vegetating lesions in pemphigus are usually
described in pemphigus vegetans, but they are localized to skin
folds and characteristic histological findings include epidermal
hyperplasia and eosinophilic abscesses, which were absent in our
case [1].
In pemphigus, the deposition of C3 along the dermal
epidermal junction is usually associated with paraneoplastic
pemphigus. However, in our patient there were no clinical findings
such as erythema-multiforme-like, bullous-pemphigoid-like, or
lichen-planus-like cutaneous lesions. Our patient had no apparent
lymphoproliferative disorder or other neoplasia, and histology did
not show keratinocyte necrosis, vacuolar interface dermatitis, or
lichenoid infiltrate. Although our patient had treatment difficulties,
common in paraneoplastic pemphigus, in our patient the treatment
problems could be ascribed to her very severe diabetes mellitus [1,
14].
Despite not achieving total remission, we tried to obtain the
right balance between disease activity and iatrogeny. We report this
case because of the unusual presentation of pemphigus vulgaris
with nail involvement and vegetating and verrucous lesions.
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