Clinical dermatology • Original article

Clinical features and management of 87 patients with pemphigoid

gestationis
R. E. Jenkins, S. Hern and M. M. Black
St John’s Institute of Dermatology, Department of Dermatopathology, Guy’s, King’s and St Thomas’ School of Medicine, St Thomas’ Hospital, London, UK

Summary Pemphigoid gestationis is a rare vesiculo-bullous disorder of pregnancy. In this review

we summarize the clinical data on 142 pregnancies in 87 patients complicated by
pemphigoid gestationis. Our aim is to provide a comprehensive clinical overview of this
disease.

transmembrane 180 kDa PG antigen.4 PG is associated

Introduction
Pemphigoid gestationis (PG) is a rare autoimmune bul-
lous disease of pregnancy and the puerperium, being
occasionally associated with trophoblastic tumours,
hydatidiform mole or choriocarcinoma.1–3 Clinically
and immunopathologically PG is related to the
pemphigoid group of disorders and therefore the term
pemphigoid gestationis is preferable to herpes gestationis
which may otherwise encourage confusion with viral-
mediated disease. Despite a clinical resemblance to
herpetic lesions, viral studies in PG have been
consistently negative.
The pathogenesis of PG is unknown. The disease is
characterized by linear deposition of C3, and
occasionally IgG, along the basement membrane zone
of peri-lesional skin on direct immunofluorescence
(Fig. 1). Under light microscopy there is often papillary
oedema with eosinophilic spongiosis and subsequent
subepidermal bullae formation (Fig. 2). Frequently,
indirect immunofluorescence demonstrates a circulating
IgG1 autoantibody (PG factor), directed against a
component of the hemidesmosome of the basement
membrane zone which avidly binds complement. Epitope
mapping has demonstrated that PG and bullous
pemphigoid autoantibodies bind a common antigenic
site within the noncollagenous domain (NC16A) of the
Correspondence: Dr M. M. Black, St John’s Institute of Dermatology,
Department of Dermatopathology, Guy’s, King’s and St Thomas’ School of
Medicine, St Thomas’ Hospital, London SE1 7EH, UK.
Accepted for publication 8 April 1999
with HLA DR3 and DR45 and the so-called C4 null allele
which may be important in terms of impaired immune
complex degradation.6
We summarize here the data from 142 pregnancies
complicated by PG with the principle aim being to
provide a comprehensive clinical overview of the disease
that will provide a basis for further study of disease
pathogenesis.
Patient cohort
The patients were recruited from three sources: the
Institute of Dermatology, a survey of Consultant
Dermatologists within the UK and from reference
laboratories. The study included 87 patients with a
total of 278 pregnancies of which 142 were complicated
by PG.
The age of the patients at the time of study varied from
18 to 38 (mean 28) years. Information about the onset
of PG was available in 117 pregnancies. The time of
onset of the disease ranged from 5 weeks gestation to
35 days postpartum. Of the 117 pregnancies, 21
(17.9%) presented in the first trimester, 40 (34.2%)
presented in the second trimester and a further 40
(34.2%) presented in the third trimester; in 16 of the
117 (13.7%) the eruption began postpartum. Therefore,
although the time of onset of PG is variable, it is much
more likely to begin in the second or third trimester than
in the first, confirming the findings of previous studies.7,8
Pruritus was universal with lesions beginning as
areas of pruritic erythema which subsequently developed

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Features and management of pemphigoid gestationis • R. E. Jenkins, S. Hern and M. M. Black
into urticated papules and plaques (Fig. 3a,b). This was
followed by the development of blisters, over a few days to
a month, which were localized to areas of urticated
erythema (Fig. 3c). In 90% of patients, the eruption
began in the peri-umbilical area and spread to involve
the abdomen, thighs, palms and soles. The duration of
the active disease ranged from 2 weeks postpartum to
12 years postpartum; the majority of patients were
disease-free after about 6 months (mean disease
duration, 28.4 weeks; median duration 16 weeks).
Parity and paternity change
At the time of the study, 17 out of 87 patients with PG
were primiparous and the remaining 70 were
multiparous with parity ranging from one to eight
pregnancies. Of the 87 patients, 41 developed PG
during their first pregnancy. Of the multiparous patients,
46 out of 70 (65.7%) were spared PG in their first
pregnancy, but subsequently had one or more episodes
of PG.
Of the 87 patients 15 had a change in partner and
three of these 15 had three different partners. This group
of patients accounted for a total of 30 pregnancies, of
Figure 1 Direct immunofluorescence of peri-lesional skin showing
linear deposition of complement (C3) counterstained with propidium
iodide (× 40).
256
which 18 out of 30 (60%) were complicated by PG
compared with 124 out of 248 (50%) pregnancies
with no change in partner. Among the 15 patients
with a change in partner, there were eight (53.3%) in
whom the onset of PG coincided with the change. This
incidence is similar to those with no change in partner
and an onset of PG in subsequent but not in the first
pregnancy (31/55; 56.3%).
Uninvolved or skip pregnancies
Seven of the 87 (8%) patients had an uninvolved or ’skip’
pregnancy following a previously affected pregnancy.
These skip pregnancies cannot be attributed solely to
the sharing of a common HLA-DR antigen complement
between the mother and child. In the present study, the
HLA haplotype analysis of one skip pregnancy
demonstrated that the mother and the male foetus had
identical DR antigens (DR3,4). However, this was not the
case for another patient in which a skip pregnancy
occurred when the mother and foetus were not fully
compatible at the DR locus (Fig. 4). Interestingly, this
patient had HLA DR7/11 and not the typical DR3/4
pattern found in most PG patients. Both children had
different DR antigens (DR2/7) from their mother despite
Figure 2 Early lesion with eosinophilic spongiosis in upper dermis
(heamatoxylin & eosin × 25).
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 Features and management of pemphigoid gestationis • R. E. Jenkins, S. Hern and M. M. Black

the first pregnancy being complicated by PG. Her second
pregnancy was a skip pregnancy (DR2/11).
Spontaneous abortions, stillbirths and
neonatal disease
In the 278 pregnancies, there were 44 (16%)
spontaneous abortions and four (1.5%) ectopic
pregnancies compared with a combined figure of 15%
in the normal population.9 Of the 44 abortions 34
(77.3%) and all of the ectopic pregnancies occurred
during the first trimester.
Previous investigators have suggested that cutaneous
lesions occur in 5% of infants born to mothers with
PG.10 Only two infants (2.8%) had evidence of skin
disease in our series. One developed urticated erythema
in the first few days of life followed by the rapid appear-
ance of bullae. The bullae resolved spontaneously within
1 week although the rash persisted on the hands and feet
for a further 10 weeks. The mother had developed PG in
a previous (her first) pregnancy with no effect on the
child from that pregnancy. The second child had normal
skin at birth but then developed a widespread,
erythematous, papular eruption, with no pustules or
bullae, at the age of 1 month. This eruption only lasted
for 2 days. The mother developed PG only in this, her
second pregnancy.
Associated autoimmune disease
Twelve out of 87 (13.8%) patients with PG had asso-
ciated autoimmune disease with nine developing Graves’
Disease at some stage. One patient had alopecia areata
on its own, one had Hashimoto’s thyroid disease and one
had autoimmune thrombocytopenia. The female preva-
lence of Graves’ disease in the normal population is
0.4%, accordingly, the incidence in PG (10.3%; 9/87)
is significantly increased. This confirms the findings of
our earlier work.11 Of this group of nine patients, two
also had alopecia areata and one had vitiligo.

Figure 3 (a) Pruritic urticarial lesions developing a periumbilical pattern on the abdomen. (b) Widespread annular erythema. (c) Tense blisters
developing on dorsum of the feet.

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Treatment
Treatment was not standardized in this study as patients
were managed by different physicians although 69 out of
87 (79.3%) had fully documented treatments available.
Most patients were prescribed chlorpheniramine which
appeared to suppress pruritus. Fifty-six out of 69 (81.2%)
required systemic corticosteroids with initial doses of
prednisolone in the range of 5–110 mg daily with
suppression of blistering in most. Two patients in this
study were exceptional in that their eruptions were not
brought under control with high dose systemic cortico-
steroids, with disease persistence for > 10 years and
conversion to bullous pemphigoid in both cases.12
Thirteen out of 69 (18.8%) patients were treated with
topical corticosteroids without systemic therapy.
Azathioprine (2/56 patients), dapsone (6/56),
pyridoxine (5/56) and sulphapyridine (2/56) were also
occasionally used as adjunctive therapy with oral steroids.
A further two patients had androgenic steroids and one
had goserelin13 for continuing disease several years post-
partum with only initial success.12 Plasmapheresis
was used in two cases with only temporary relief of
itching, which recurred 6 weeks after treatment was
stopped.
Figure 4 HLA family study of one patient.
258
Oral contraceptive use
The combined oral contraceptive pill had been prescribed
at some time in 56 out of 87 (64.4%) patients; only six
out of 56 (10.7%) complained of a flare in their PG. Two
small studies have previously suggested the risks of
exacerbation of around 50%.7,14 Accordingly most
patients were taking the pill before the development of
PG and did not recommence the pill after an affected
pregnancy. Thus, the low incidence of exacerbation of PG
by the pill in our series probably represents improved
clinical practice.15
Conclusions
This review is the largest clinical overview of PG to be
published. Several points are highlighted. First this study
shows that there is no association between change in
partner and development of PG as previously
suggested.14 Holmes et al.. reported that in five out of
25 patients the development of PG coincided with a
change in partner suggesting that the development of
PG may depend on exposure to an antigen derived from
the father.14 Second, the frequency of skip pregnancies in
our study was 8% which is similar to that reported
previously.14 The explanation as to why skip pregnancies
occur remains uncertain but it is not due to the mother
and foetus being fully compatible at the DR locus, nor is
it due to a change in partner.14
The series suggests that standard approaches to ther-
apy are generally successful: in mild cases of PG, topical
fluorinated corticosteroids with or without an
antihistamine such as chlorpheniramine are adequate.
However, topical corticosteroids are rarely useful once
the vesiculo-bullous phase has developed and systemic
corticosteroids continue to be the therapeutic mainstay.
Prednisolone, 20–30 mg daily can be effective, but in
severe disease higher doses of 40–80 mg prednisolone
will usually be required. Occasionally short-term, higher
doses may be required with appropriate precautions. In the
last trimester of pregnancy, the dose of oral prednisolone
can often be tapered, but may have to be increased after
delivery to offset potential postpartum flares.
PG remains an enigmatic and baffling disorder.
Despite many problems, it offers a potential model that
will further understanding of many fundamental aspects
of the necessarily complex immunological interaction
between mother and foetus.
Acknowledgements
The authors thank R. Charles-Holmes, S. Kelly and J.
Shornick for their earlier work in PG which was carried
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 Features and management of pemphigoid gestationis • R. E. Jenkins, S. Hern and M. M. Black
out at St John’s Institute of Dermatology and which
contributed to this paper. We also thank K. Welsh,
Department of Immunology, Transplant Centre, Oxford
and D. Briggs, Department of Immunology, Middlesex
Hospital, London for assistance with MHC class II sub-
types, complement polymorphisms and estimation of
anti-HLA antibodies.
References
1 Dupont C. Herpes gestationis with hydatidiform mole.
Trans St John’s Hosp Dermatol Soc 1974; 60: 103.
2 Tindall JG, Rea TH, Shulman I, Quismorio P. Herpes
gestationis in association with a hydatidiform mole. Arch
Dermatol 1981; 117: 510–2.
3 Tillman WG. Herpes gestationis with hydatidiform
mole and chorion epithelioma. Br Med J 1950; 1:
1471.
4 Guidice GJ, Emery DJ, Zelickson BD et al. Bullous
pemphigoid and herpes gestationis autoantibodies
recognize a common non-collagenous site on the
BP180 ectodomain. J Immunol 1993; 151: 5742 –
50.
5 Shornick JK, Stastny P, Gilliam JN. High frequency of
histocompatability antigens HLA DR3 and DR4 in herpes
gestationis. J Clin Invest 1981; 68: 553–5.
q 1999 Blackwell Science Ltd • Clinical and Experimental Dermatology, 24, 255–259
6 Shornick JK, Artlett CM, Jenkins RE et al. Complement
polymorphism in herpes gestationis: association with C4
null allele. J Am Acad Dermatol 1993; 29: 545–9.
7 Shornick JK, Bangert JL, Freeman RG, Gilliam JN. Herpes
gestationis: Clinical and histological features of twenty-
eight cases. J Am Acad Dermatol 1983; 8: 241–24.
8 Yancey KB. Herpes gestationis. Dermatol Clin 1990; 8:
727–35.
9 Sigal LH, Ron Y In: Immunology and Inflammation: Basic
Mechanisms and Clinical Consequences. New York:
McGraw-Hill, 1994: 547–61.
10 Lawley TJ, Stingl G, Katz SI. Fetal and maternal risks in
herpes gestationis. Arch Dermatol 1978; 114: 552–5.
11 Shornick JK, Black MM. Secondary autoimmune diseases
in herpes gestationis (pemphigoid gestationis). J Am Acad
Dermatol 1992; 26: 563–6.
12 Jenkins RE, Vaughan Jones SA, Black MM. Conversion of
pemphigoid gestationis to bullous pemphigoid – two
refractory cases highlighting this situation. Br J Dermatol
1996; 135: 595–8.
13 Garvey MP, Handfield-Jones SE, Black MM. Pemphigoid
gestationis: response to chemical oophrectomy with
goserelin. Clin Exp Dermatol 1992; 17: 443–5.
14 Holmes RC, Black MM, Jurecka W et al. Clues to the
aetiology and pathogenesis of herpes gestationis. Br J
Dermatol 1983; 109: 131–139.
259