J AM ACAD DERMATOL Case reports 1057

VOLUME 60, NUMBER 6

32. Riveros CJ, Galivan MF, Franca LF, Sotto MN, Takahashi MD.
Acquired localized cutis laxa confined to the face: case
report and review of the literature. Int J Dermatol 2004;43:
931-5.
33. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF,
Offord JR, et al. Prevalence of monoclonal gammopathy of
undetermined significance. N Engl J Med 2006;354:
1362-9.
34. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR,
Plevak MF, et al. A long-term study of prognosis in monoclonal
gammopathy of undetermined significance. N Engl J Med
2002;346:564-9.
35. Usha AN, Kumar P, Rai M, Singh RG, Seth M, Saraf SK. Myeloma
in young age. Indian J Pathol Microbiol 2005;48:314-7.
36. Bladé J, Kyle RA, Greipp PR. Presenting features and prognosis
in 72 patients with multiple myeloma who were younger than
40 Years. Br J Haematol 2003;93:345-51.
37. Satta R, Casu G, Dore F, Longinotti M, Cottoni F. Follicular
spicules and multiple ulcers: cutaneous manifestations of
multiple myeloma. J Am Acad Dermatol 2003;49:736-40.

Neonatal pemphigus in an infant born to a mother

with serologic evidence of both pemphigus vulgaris
and gestational pemphigoid
Jacqueline Panko, MD, Scott R. Florell, MD, Jason Hadley, MD, John Zone, MD,
Kristin Leiferman, MD, and Sheryll Vanderhooft, MD
Salt Lake City, Utah

Neonatal pemphigus is a rarely reported transitory autoimmune blistering disease caused by transfer of
maternal IgG autoantibodies to desmoglein 3 to the neonate through the placenta when the mother is
affected with pemphigus. It is clinically characterized by transient flaccid blisters and erosions on the skin
and, rarely, the mucous membranes. Neonatal pemphigus vulgaris has never been reported to persist
beyond the neonatal period and progress to adult disease. Gestational pemphigoid is an uncommon,
pregnancy-associated, autoimmune blistering disease. This disease typically flares with delivery and then
spontaneously resolves within months without treatment. In 5% to 10% of cases, the antibodies responsible
for gestational pemphigoid are transferred to the neonate through the placenta, causing transitory blistering
in the neonate. While both gestational pemphigoid and pemphigus vulgaris can occur during pregnancy,
these clinically, histologically, and serologically distinct diseases are not known to occur simultaneously in
the same patient. We describe a case of a 36-year-old woman with clinical evidence of mucocutaneous
pemphigus, but not gestational pemphigoid, who had serum antibodies to the antigens responsible for
pemphigus as well as those responsible for gestational pemphigoid. This patient gave birth to a neonate
with neonatal pemphigus but no evidence of neonatal gestational pemphigoid. ( J Am Acad Dermatol
2009;60:1057-62.)

INTRODUCTION against desmoglein 3. Desmogleins are transmem-

Pemphigus vulgaris is a chronic autoimmune blis-
tering disease characterized by loss of adhesion be-
tween keratinocytes and blistering in the suprabasal
epidermis; it is associated with IgG autoantibodies
From the Department of Dermatology, University of Utah.
Funding sources: None.
Conflicts of interests: None declared.
Reprint requests: Jacqueline Panko, MD, University of Utah,
Department of Dermatology, 30 North 1900 East, 4B454
School of Medicine, Salt Lake City, UT 84132. E-mail: jackie.
panko@hsc.utah.edu.
0190-9622/$36.00
ª 2008 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2008.10.025
brane desmosomal cadherin proteins that mediate
epidermal cell cohesion.1 Neonatal pemphigus is a
rarely reported transitory autoimmune blistering dis-
ease caused by transfer of maternal IgG autoanti-
bodies to desmoglein 3 to the neonate through the
placenta when the mother is affected with pemphi-
gus.2 It is clinically characterized by transient flaccid
blisters and erosions on the skin and rarely the mucous
membranes.3 Neonatal pemphigus vulgaris has never
been reported to persist beyond the neonatal period
and progress to adult disease.4
Gestational pemphigoid (also known as herpes
gestationis) is an uncommon, pregnancy-associated,
autoimmune blistering disease with an estimated
1058 Case reports
Fig 1. Oral mucosa of a postpartum mother with pem-
phigus vulgaris.
incidence of one in 50,000 to 60,000 pregnancies.5 It
most commonly presents as pruritic papules and
plaques that evolve into blisters during the second
and third trimesters.6 Usually the eruption begins on
the abdomen and subsequently spreads over the
trunk, head, and extremities.7 Less commonly, ges-
tational pemphigoid involves the mucous mem-
branes.7 The autoimmune response is mediated by
complement binding IgG antibodies to the non-
collagenous domain, NC16a, of the180-kd hemi-
desmosomal antigen of basal keratinocytes (BPAg2
or Type XVII collagen).8 This disease typically flares
with delivery and then spontaneously resolves
within months without treatment. In 5% to 10% of
mothers with gestational pemphigoid,5 the anti-
bodies responsible for the disease are transferred to
the neonate through the placenta, causing urticated
erythema sometimes followed by blistering in the
neonate lasting 2 days to 10 weeks.9
Although both gestational pemphigoid and pem-
phigus vulgaris can occur during pregnancy, these
clinically, histologically, and serologically distinct
diseases have not been reported to occur simulta-
neously in the same patient. We describe a case of a
36-year-old woman with clinical evidence of muco-
cutaneous pemphigus, but not gestational pemphi-
goid, who had serum antibodies to the antigens
responsible for pemphigus as well as those respon-
sible for gestational pemphigoid. This patient gave
birth to a neonate with neonatal pemphigus but no
evidence of neonatal gestational pemphigoid.
CASE REPORT
A 36-year-old otherwise healthy woman with a
12-month history of progressive erosions in her oral
and nasal mucosae (Fig 1) became pregnant and
carried her baby to full term with no perinatal
complications. The oral and intranasal erosions
continued untreated throughout her pregnancy
without other cutaneous or mucosal disease.
J AM ACAD DERMATOL
JUNE 2009
Fig 2. Grouped vesicles and erosions on intramammary
area of postpartum mother’s chest.
Specifically, she had no cutaneous urticarial pla-
ques or papules, no blisters, and no ocular or
genital erosions. She had a normal spontaneous
vaginal delivery at 39 weeks. During the first 2
weeks after delivery, she developed an eruption of
grouped vesicles on her chest in her intramammary
area and in her bilateral inguinal folds (Figs 2 and
3). Her oral and nasal mucosal erosions worsened
while she continued to have no ocular or genital
involvement.
The infant of the mother described above had an
uncomplicated prenatal period and was healthy at
birth with no skin abnormalities or other clinical
problems. On the first day after birth, he developed
flaccid bullae, most prominently on his scalp with
smaller bullae on his trunk, chin, and anterior aspect
of his neck. There was no mucosal involvement.
These bullae quickly eroded and left crusted skin
patches (Figs 4 and 5). Bullae continued to erupt for
7 days after birth. The infant had no other clinical or
laboratory abnormalities. His blood and wound
cultures were negative for bacteria, and polymerase
chain reaction testing was negative for herpes sim-
plex virus. After his eighth postnatal day, no new
blisters had developed, and his remaining erosions
healed over the next 14 days without treatment or
complication. The total duration of disease in the
neonate was 21 days.
Skin biopsy specimens were obtained from both
mother and infant son. A vesicle on the chest of the
mother and the site of a healing erosion on the flank
J AM ACAD DERMATOL
VOLUME 60, NUMBER 6
Fig 3. A and B, Grouped vesicles in bilateral inguinal fold
of postpartum mother.
of the neonate were sampled. Hematoxylin-eosine
stained histopathologic examination of the specimen
from the mother demonstrated a suprabasal epider-
mal split with acantholysis and a few eosinophils in
the blister cavity (Fig 6). These findings were con-
sistent with a pemphigus. The specimen from the
neonate showed a mild interface and spongiotic
dermatitis with eosinophils. There was mild to
moderate edema within the papillary dermis but no
histologic evidence of a well-formed vesicle (Fig 7).
These findings were not specific, but were consistent
with a diagnosis of pemphigus.
Case reports 1059
Fig 4. Erosions on face of neonate with neonatal
pemphigus.
Fig 5. Crusted erosions on scalp of neonate with neonatal
pemphigus.
Perilesional skin biopsy specimens from sites of
erythema surrounding lesions on both the mother
and neonate (Figs 8 and 9)showed IgG and C3 cell
surface staining into the follicular epithelium consis-
tent with pemphigus on direct immunofluorescence.
There was no linear deposition of C3 or IgG at the
basement membrane of either the mother or neonate
as would be expected in gestational pemphigoid.
Enzyme-linked immunosorbent assay (ELISA) de-
termined the mother’s serum IgG desmoglein 1 and 3
antibody levels to be 68 and 213 units, respectively.
(These values are considered positive if [20 units.)
Progressive dilution of her serum beginning at 1:5 in
two-fold dilutions layered on human split skin and
monkey esophagus and stained with fluorescein-
conjugated antibodies showed no evidence of IgG
and IgA basement membrane antibodies. Progressive
dilution of the mother’s serum in calcium-containing
buffer beginning at 1:10 in two-fold dilutions, layered
in the substrates stained with fluorescein-conjugated
anti-IgG and anti-IgA showed the IgG cell surface
(pemphigus) antibodies to be positive at a titer of
1:10,240 on intact human skin substrate and a titer of
1:20,480 on monkey esophagus substrate. IgA cell
surface antibodies were negative. The mother’s
1060 Case reports
Fig 6. Biopsy specimen from mother’s back demonstrates
suprabasal epidermal split with acantholysis and a few
eosinophils in the blister cavity. (Hematoxylin-eosin stain;
original magnification: 3100.)
Fig 7. Biopsy specimen from neonate’s scalp shows a mild
interface and spongiotic dermatitis with eosinophils. There
was mild to moderate edema within the papillary dermis,
but no histologic evidence of a well-formed vesicle. (He-
matoxylin-eosin stain; original magnification: 3200.)
serum was negative for paraneoplastic pemphigus
antibodies on rodent bladder, liver, and heart
substrates. IgG and IgA basement membrane zone
antibodies were not detected by indirect immunoflu-
orescence on human split skin and monkey esoph-
agus substrates. IgG BP 180 and 230 levels were
negative at 3 units each by ELISA. At 3 month follow-
up, the mother’s IgG anti-desmoglein 1 level was
borderline/indeterminate at 16 units, but her IgG
antiedesmoglein 3 level remained elevated at 254
units by ELISA. At 9 month follow-up, new oral
lesions were still developing, despite treatment with
mycophenolate mofetil and prednisone. Her desmo-
glein 3 titer was still elevated at 192.
Testing of the mother’s serum for complement-
fixing IgG antibodies, herpes (pemphigoid) gestatio-
nis factor, showed a positive epidermal pattern with a
titer of 1:5 using human split skin substrate with a
fresh source of complement. At 3-month follow-up,
her herpes gestationis factor remained elevated at 1:5.
J AM ACAD DERMATOL
JUNE 2009
Fig 8. Perilesional skin biopsy specimen of erythema
surrounding blister on mother’s back shows IgG and C3
cell surface staining into follicular epithelium. (Direct
immunofluorescence; original magnification: 3200.)
Fig 9. Perilesional skin biopsy specimen of erythema
surrounding crusted papule on scalp of neonate shows
IgG and C3 cell surface staining into follicular epithelium.
(Direct immunofluorescence; original magnification:
3200.)
Testing of the neonate’s serum using the same
techniques described above showed IgG anti-
desmoglein 1 and 3 levels of 3 and 217, respectively.
The basement membrane IgG and IgA antibodies
were negative, whereas the IgG cell surface antibody
titer was 1:640 on intact human skin substrate and
1:5120 on monkey esophagus substrate by indirect
immunofluorescence. His BP 180 and 230 levels
were within normal range at 0 and 1 unit, respec-
tively, by ELISA. At 3-month follow-up, his IgG
antiedesmoglein 1 and 3 levels were both within
normal limits at 1 and 3 units. Testing of the neonate’s
serum for complement-fixing IgG antibodies, herpes
gestationis factor, showed a positive epidermal pat-
tern when undiluted. It was negative at a titer of 1:5
and negative when undiluted at 3-month follow-up.
DISCUSSION
Pemphigus vulgaris and gestational pemphigoid
are bullous diseases with unique clinical, histologic,
J AM ACAD DERMATOL
VOLUME 60, NUMBER 6
and serologic characteristics resulting from autoanti-
bodies targeted at different epidermal components.
Though similar in that IgG autoantibodies from preg-
nant women with either of these diseases can be
transplacentally passed to neonates resulting in tran-
sient clinical manifestations in the child, these diseases
have not been reported simultaneously in one patient.
In this report, we present a mother and her neonate
who had clinical, histologic, and serologic evidence of
pemphigus. Interestingly, the mother had comple-
ment-fixing IgG antibodies (herpes gestationis factor)
in her serum, although there was no histologic evi-
dence of basement membrane zone antibody deposi-
tion in perilesional tissue, and the clinical presentation
was not typical for gestational pemphigoid.
This case suggests that pemphigus can be transmit-
ted to neonates and that gestational pemphigoid can
occur serologically in the mother and the child without
clinical manifestation of the disease. More data would
be needed to definitively prove this, including addi-
tional biopsies of the mother that might have shown
pemphigoid and prenatal serologies which might
have proven preexisting disease. Only one biopsy
was performed on the mother; therefore, there is no
additional tissue to evaluate for the possibility of two
distinct histologies at different body sites.
Interestingly, the direct immunofluorescence for
gestational pemphigoid was negative. There are two
potential explanations for this. The first is that when
the keratinocyte cell surface antibody (pemphigus
antibody) titer is very high, the bright fluorescence
can blunt, distort, or obliterate the less bright or
weaker binding to the basement membrane zone.
The second is that the biopsy specimen for direct
immunofluorescence from the neonate came from a
healing lesion. Direct immunofluorescence is best
observed if the perilesional skin is adjacent to a
recently formed blister. If the pemphigus antigen had
first been blocked from binding to the substrate by
using a monoclonal antibody to desmoglein, and
then reacted with patient sera, basement membrane
zone staining may have been observed.
One possible explanation of how these two rare
diseases simultaneously occurred in our patient is
through immunogenetics. The mother is HLA
DRB1*0301 and DQB1*0501 positive, suggesting
that she has the potential to produce both the
pemphigus and the pemphigoid antibodies.
DQB1*0301 alleles confer a predisposition to all
subgroups of mucous membrane pemphigoid and
may have a role in T-cell recognition of basement
membrane antigens, resulting in the production of
antiebasement membrane zone IgG autoanti-
bodies.10 DQB1*501 has been significantly associ-
ated with susceptibility to pemphigus vulgaris.11
Case reports 1061
There are many reports of the simultaneous
presence of clinical and serologic pemphigus vul-
garis and bullous pemphigoid in the same pa-
tient,12 although in these patients the histologic and
direct immunofluorescence findings confirmed this
dual diagnosis. Our patient had only serologic
evidence of both diseases in producing two distinct
autoantibodies, whereas her clinical, histologic, and
direct immunofluorescence examinations were
consistent with the diagnosis of pemphigus vulga-
ris. It is possible that the patient did not, in fact,
have gestational pemphigoid as her levels of her-
pes gestationis factor, though present, were low,
much lower than her pemphigus antibody levels.
Neonatal pemphigus vulgaris has been reported to
be passively transmitted from a clinically asymptom-
atic mother,13,14 but there have been no reports of
neonatal gestational pemphigoid transferred from an
asymptomatic mother. It is possible the mother in this
case had subclinical asymptomatic gestational pem-
phigoid, as evidenced by complement fixing IgG
basement membrane zone antibodies in her serum.
BP 180 antibodies are not specific for gestational
pemphigoid; BP 180 is the antigenic target for base-
ment membrane zone antibodies in the majority of
patients with bullous pemphigoid. The prevalence of
BP 180 and BP 230 autoantibodies was determined to
be 7.1% in one population-based epidemiological
study.13 Some pemphigus vulgaris sera contain BP
180 antibodies that react with both the intracellular
and extracellular structures of desmosomes.14 Serum
from a patient with paraneoplastic pemphigus has
also been shown to demonstrate antibodies to
desmoglein 3, desmoglein 1, and anti-BP 180 anti-
bodies.15 Our patient had no clinical signs or symp-
toms of malignancy, and the serum was negative for
antibodies that are classically seen in paraneoplastic
pemphigus reacting with rodent substrates, so this
possible diagnosis as an explanation for the comple-
ment-fixing antibodies in her serum is unlikely.
It is possible that our patient’s serologic findings
demonstrate an atypical serological profile of pem-
phigus vulgaris or an overlap disease of pemphigus
and gestational pemphigoid with atypical or subclin-
ical cutaneous manifestations. This report demon-
strates the value of doing serological studies and
describes the novel occurrence of pemphigus in a
neonate born to a mother with serologic evidence of
pemphigus and herpes gestationis but only clinical
evidence of pemphigus.
REFERENCES
1. Hertl M, Eming R, Veldman C. T cell control in autoimmune
bullous skin disorders. J Clin Invest 2006;116:1159-66.
2. Parlowsky T, Welzel J, Amagai M, Zillikens D, Wygold T.
Neonatal pemphigus vulgaris: IgG4 autoantibodies to
1062 Case reports
desmoglein 3 induce skin blisters in newborns. J Am Acad
Dermatol 2003;48:623-5.
3. Campo-Voegeli A, Muniz F, Mascaro JM, Garcı́a F, Casals M,
Arimany JL, et al. Neonatal pemphigus vulgaris with extensive
mucocutaneous lesions from a mother with oral pemphigus
vulgaris. Br J Dermatol 2002;147:801-5.
4. Chowdhury MM, Natarajan S. Neonatal pemphigus vulgaris
associated with mild oral pemphigus vulgaris in the mother
during pregnancy. Br J Dermatol 1998;139:500-3.
5. Al-Mutairi N, Sharma AK, Zaki A, El-Adawy E, Al-Sheltawy M,
Nour-Eldin O. Maternal and neonatal pemphigoid gestationis.
Clin Exp Dermatol 2004;29:202-4.
6. Aoyama Y, Asai K, Hioki K, Funato M, Kondo N, Kitajima Y.
Herpes gestationis in a mother and newborn: immunoclinical
perspectives based on a weekly follow-up of the enzyme-
linked immunosorbent assay index of a bullous pemphigoid
antigen noncollagenous domain. Arch Dermatol 2007;143:
1168-72.
7. Lin MS, Arteaga LA, Diaz LA. Herpes gestationis. Clin Dermatol
2001;19:697-702.
8. Lin MS, Gharia M, Fu CL, Olague-Marchan M, Hacker M, Harman
KE, et al. Molecular mapping of the major epitopes of BP180
Cystic bone lesions in a boy with Darier disease:
A magnetic resonance imaging assessment
Michele L. Ramien, MD, MSc,a Julie S. Prendiville, MB, FRCPC,a Ken L. B. Brown, MD, MSc, FRCSC,b and
Robyn A. Cairns, MD, FRCPCc
Vancouver, British Columbia, Canada
We describe asymptomatic bone cysts in the right humerus of a 17-year-old boy with Darier disease. The
cysts were found when a radiographic skeletal survey was performed to monitor for adverse effects of oral
retinoid therapy. Magnetic resonance imaging was used to confirm that the lesions were cystic and to
delineate their extent. The literature was reviewed for previous reports of this association. ( J Am Acad
Dermatol 2009;60:1062-6.)
D arier disease is an autosomal-dominant dis-
order caused by a mutation in the ATP2A2
gene locus on chromosome 12q23-24.1.1 It
is characterized by abnormal keratinization of the
epidermis, nails, and mucous membranes. Skin-
From the Divisions of Pediatric Dermatology,a and Orthopedic
Surgery,b and Department of Radiology,c British Columbia
Children’s Hospital.
Funding sources: None.
Conflicts of interest: None declared.
Reprints not available from the authors.
Correspondence to: Julie S. Prendiville, MB, FRCPC, British Columbia
Children’s Hospital, Room K4-100 ACB, 4480 Oak St, Vancouver,
British Columbia V6H 3V4 Canada. E-mail: jprendiville@cw.bc.ca.
0190-9622/$36.00
ª 2008 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2008.10.049
J AM ACAD DERMATOL
JUNE 2009
recognized by herpes gestationis autoantibodies. Clin Immunol
1999;92:285-92.
9. Jenkins RE, Hern S, Black MM. Clinical features and manage-
ment of 87 patients with pemphigoid gestationis. Clin Exp
Dermatol 1999;24:255-9.
10. Setterfield J, Theron J, Vaughan RW, Welsh KI, Mallon E,
Wojnarowska F, et al. Mucous membrane pemphigoid: HLA-
DQB1*0301 is associated with all clinical sites of involvement
and may be linked to antibasement membrane IgG produc-
tion. Br J Dermatol 2001;145:406-14.
11. Delgado JC, Hameed A, Yunis JJ, Bhol K, Rojas AI, Rehman SB, et al.
Pemphigus vulgaris autoantibody response is linked to HLA-
DQB1*0503 in Pakistani patients. Hum Immunol 1997;57:110-9.
12. Sami N, Ahmed AR. Dual diagnosis of pemphigus and pem-
phigoid. Retrospective review of thirty cases in the literature.
Dermatology 2001;202:293-301.
13. Bonifazi E, Milioto M, Trashlieva V, Ferrante MR, Mazzotta F,
Coviello C. Neonatal pemphigus vulgaris passively transmitted
from a clinically asymptomatic mother. J Am Acad Dermatol
2006;55:S113-4.
14. Amer YB, Al Ajroush W. Pemphigus vulgaris in a neonate. Ann
Saudi Med 2007;27:453-5.
colored papules and distinctive nail changes may
first appear in children as young as 5 or 6 years of age,
with an increase in disease activity occurring during
adolescence. Phenotypic expression varies from
sparse keratotic papules to disfiguring extensive,
malodorous, warty plaques in a seborrheic distribu-
tion. The skin lesions are susceptible to superinfec-
tion with Staphylococcus aureus, herpes simplex
virus, and other organisms. Oral retinoid therapy
may be of benefit in moderate to severe cases.
Darier disease is rarely associated with extracuta-
neous findings. There is a potential comorbidity with
bipolar affective disorder and other neuropsychiatric
illness.2 There are at least 9 previous reports of cystic
bone disease.3-11 We describe an additional case of
bone cysts in an adolescent boy with severe skin
involvement.