Neonatal pemphigus foliaceus
Ranella Hirsch, MD,a Judy Anderson, MD,a Jeffrey M. Weinberg, MD,b Penina Burnstein, MD,a Audrey Echt, MD,a
Janet Fermin, MD,a Edward R. Heilman, MD,a and Teresita A. Laude, MDa
New York, New York
The term “pemphigus” refers to a group of diseases that are characterized by the presence of cutaneous or mucosal blisters and
erosions, and antiepidermal autoantibodies. There are several case reports of neonatal pemphigus vulgaris in the literature. Although
pemphigus foliaceus antibodies have been shown to cross the placenta, to our knowledge, this is only the second reported case of
neonatal pemphigus foliaceus. The proposed mechanism of disease transfer is the passive transfer of maternal IgG antibodies across
the placenta. (J Am Acad Dermatol 2003;49:S187-9.)
T he term “pemphigus” refers to a group of diseases that
are characterized by the presence of cutaneous or mu-
cosal blisters and erosions, and antiepidermal autoanti-
bodies. There are 6 known clinical variants of pemphigus; all but
one occurs rarely in sporadic distribution. The exception is fogo
selvagem (FS) or endemic pemphigus foliaceus (PF), which is
endemic to Brazil and South America. Pemphigus vulgaris (PV)
and PF are 2 of these autoimmune blistering diseases of the
epidermis that are characterized histologically by the presence of
epidermal cell-cell detachment, which results in intraepidermal
vesicle formation. Although there are several case reports of
neonatal PV in the literature,1-7 to our knowledge, this is only the
second reported case of neonatal PF.8 The proposed mechanism
of disease transfer is the passive transfer of maternal IgG anti-
bodies across the placenta.
CASE REPORT
A female infant was born to a 23-year-old woman (gravida 2,
abortus 1) at 40 weeks gestation. The mother was well known to
our clinic where, 3 years previously, she had been given a
diagnosis of PF by histopathology and immunofluorescence (IF)
(direct and indirect). Though her disease was extensive at the
time of diagnosis, she responded well to topical and oral ste-
roids. She was subsequently lost to follow up and received no
further treatment.
We became reacquainted with the mother after the birth of
her first child when we were called to evaluate the infant’s skin
condition. At the time of delivery, the mother had moderate
erosions on her face, ears, arms, legs, and chest. On the first day
of life, the infant had erosions develop on her face, ears, arms,
This supplement is made possible through an unrestricted
educational grant from Stiefel Laboratories to the American
Academy of Dermatology.
From the Departments of Dermatology, State University of New York
Health Science Center at Brooklyn, Brooklyn,a and St Luke’s-Roosevelt
Hospital Center, New York.b
Funding sources: None.
Conflict of interest: None identified.
Reprint requests: Jeffrey M. Weinberg, MD, Department of Dermatology,
St Luke’s-Roosevelt Hospital Center, 1090 Amsterdam Ave, Suite 11D,
New York, NY 10025. E-mail: jwein@bway.net
Copyright © 2003 by the American Academy of Dermatology, Inc.
0190-9622/2003/$30.00 ⫹ 0
doi:10.1067/mjd.2003.339
legs, and chest (Fig 1). Most of these were crusted lesions and
some had a fine collarette of scale. There was no mucous
membrane involvement. The infant was otherwise healthy and
the pregnancy had been an uneventful one.
Punch biopsy specimens were obtained from the infant and
evaluated by light microscopy and direct IF. The biopsy speci-
men revealed a cleft within the superficial epidermis with a
sparse neutrophilic infiltrate consistent with the diagnosis of PF
(Fig 2). Direct IF revealed an abnormal intercellular deposition
of IgG and C3 in the epidermis; no fibrin deposits were noted.
Indirect IF performed on sera from both mother and infant
revealed a titer of intercellular antibodies of 1:320.
The infant was treated conservatively with topical mupirocin
2% ointment and hydrocortisone valerate ointment, with excel-
lent clinical response noted in 2 days and no additional lesion
development. The mother and the baby were discharged home,
and topical and systemic steroids were restarted in the mother.
Both patients were seen for follow up in our clinic 2 weeks later,
at which time the infant’s lesions had totally resolved and the
mother’s lesions were also markedly improved. Repeated indi-
rect IF was performed on sera from both mother and baby; the
titer from the mother was unchanged at 1:320, whereas the
baby’s titers were now negative.
DISCUSSION
PV and PF are both bullous diseases with unique character-
istics. Although cutaneous vesicles with associated mucous
membrane involvement characterize PV, PF is characterized by
cutaneous involvement and is remarkable for the absence of oral
lesions. Histologic examination of the skin of the patient with PV
reveals suprabasilar acantholysis with preserved basal cell-der-
mal adherence in contrast to the epidermal vesicles located
beneath the stratum corneum of the patient with PF.
It is well established that female patients with active PV who
are capable of carrying a pregnancy to term can deliver infants
with a transient neonatal PV.1-7 The presumed mechanism is
transplacental passage of pathogenic antiepidermal autoantibod-
ies. This is in stark contrast to the infants with PF and FS, who
have been noted to present with normal skin, with the exception
of 1 previous report.8 At least 18 cases of pregnant women with
PF have been studied, but all of their infants were born free of
disease.9,10 In PV, the correlation of maternal autoantibody titers
with disease activity in the newborn and mother appear to
correlate well. This is in contrast to the correlation in those with
FS.11 This entity shares similar clinical and immunopathologic
S187
S188 Hirsch et al
Fig 1. Infant with erosions on her face, ears, arms, legs, and chest, with
her mother.
Fig 2. Histopathology revealed cleft within superficial epidermis with
sparse neutrophilic infiltrate consistent with diagnosis of pemphigus
foliaceus. (Hematoxylin-eosin stain; original magnification ⫻100.)
features with the nonendemic form of PF seen in the rest of the
world.9
Given the known pathogenicity of FS, the question of why
there is an absence of clinical disease in the newborn has
received some speculation. Some earlier theories hypothesized
the negligible titers of FS autoantibodies in the fetal circulation,
or the lack of reactive antigens on the fetal epidermis. Other
theories as to the mechanism that is protective for the infant
were that the placenta may limit the passage of FS autoantibod-
ies to the baby by its barrier function, or that the placenta may
J AM ACAD DERMATOL
AUGUST 2003
function as an immunoadsorbant of undesirable autoantibodies
as suggested by Swinburne.12 Swinburne explained that the
presence of any autoantibodies is the result of saturation of this
barrier at very high autoantibody levels, which exceeds the
adsorption capabilities of the placenta. The finding of weak
positive staining of epidermal intercellular substance by direct IF
has supported this.
Recent research had given further insight into the low fre-
quency of PF in neonates. Wu et al13 found that the distribution
of desmoglein in neonatal epidermis is unlike that in adult
epidermis. In adults, desmoglein 1 is present throughout the
epidermis, but desmoglein 3 is present only in the basal and
intermediate suprabasal layers. Wu et al13 demonstrated that
desmoglein 3 expression in the superficial epidermis in neonates
provides protection against the formation of blisters induced by
PF antibodies. In light of this report, infants who have neonatal
PF develop are truly unusual. Possible explanations for these
rare cases are that certain infants lack the normal neonatal
expression of desmoglein 3 in upper epidermis, or that the
mothers produce antidesmoglein 3 antibodies. Ishii et al14 re-
ported a patient with PF in whom PV subsequently developed.
This case makes it conceivable that mothers who deliver infants
with bullous pathology may have had an antigenic shift and may
be producing antidesmoglein 3 antibodies as well.
The other reported case of neonatal PF in the literature was
by Walker et al.8 This case had the highest measured autoanti-
body titer of a patient with the disease. In that case the infant had
an indirect IF titer of 1:80 and the mother had an IF titer of 1:640.
In our case, titers of 1:320 were measured in both mother and
child. It has been postulated that a threshold of neonatal anti-
body (1:40) must be reached before disease becomes manifest.8
Our case represents the highest fetal antibody titer reported, a
number that is much greater than the suggested threshold. Al-
though higher maternal antibody titers increase the likelihood of
positive fetal antibody titers, it is unclear if there is a direct
quantitative relationship between the two in PF. The rapid de-
cline of PF antibodies in early life over the subsequent 2 weeks
suggests that the antibody is of maternal origin. If true, it may
also be plausible that antibodies play a causal pathogenetic role
in the origin of cutaneous abnormalities. Although PV has been
induced in neonatal mice by the passive transfer of IgG derived
from patients with PV, the mechanism has not yet been eluci-
dated.
The management of pemphigus in pregnancy presents a
challenge. On one hand, in dealing with a mother who presents
with evidence of acute disease, one may argue that withholding
therapy is wise to prevent adverse effects on the fetus. However,
such a choice may yield a child severely affected by the trans-
placentally acquired maternal antibodies. We agree with the
guidelines for management as presented by Hup et al.6 Antibody
titers should be followed up closely during pregnancy in patients
with PF. They further recommend that oral corticosteroids
should be used to keep autoantibody titers as low as possible,
with the addition of the lowest necessary dose of an antimetab-
olite if necessary.
In conclusion, we report a second case of neonatal PF as
established by the clinical history, clinical findings, histopathol-
ogy, and IF studies. Because the number of reported cases of
neonatal PF is so few, it is premature to make conclusions
regarding fetal outcome and long-term prognosis. Further work
is needed to determine whether the risks of neonatal disease
outweigh the risks of systemic therapy in the treatment of ma-
ternal PF.
J AM ACAD DERMATOL
VOLUME 49, NUMBER 2
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