Background

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy

(see the image below). The disease was originally named herpes gestationis on t
he basis of the morphological herpetiform feature of the blisters, but this term
is a misnomer because pemphigoid gestationis is not related to or associated wi
th any active or prior herpes virus infection.
Tense bullae are present on the arms of this otherwise healthy 32-year-old primi
gravida woman.
SeeDiagnosing Dermatoses in Pregnant Patients: 8 Cases to Test Your Skills, a Cri
tical Images slideshow, for help identifying several types of cutaneous eruption
s associated with pregnancy.
Pathophysiology
Pemphigoid gestationis is a pregnancy-associated autoimmune disease. Most patien
ts develop antibodies against 2 hemidesmosomal proteins, BP180 (BPAG2, collagen
XVII) and less frequently BP230. Historically known as herpes gestationis factor
, these circulating antibodies belong to the heat-stable immunoglobulin G1 subcl
ass. The binding of immunoglobulin G to the basement membrane triggers an immune
response, leading to the formation of subepidermal vesicles and blisters. In 19
99, Chimanovitch et al[1]demonstrated that pemphigoid gestationis sera recognize
5 distinct epitopes within BP180 NC16A, 4 of which have been reported as major a
ntigenic sites targeted by bullous pemphigoid antibodies.
The trigger for the development of autoantibodies in persons with pemphigoid ges
tationis remains elusive. Cross-reactivity between placental tissue and skin has
been proposed to play a role. Pemphigoid gestationis has a strong association w
ith HLA-DR3 (61-80%) and HLA-DR4 (52%), or both (43-50%), and virtually all pati
ents with a history of pemphigoid gestationis have demonstrable anti-HLA antibod
ies. The placenta is known to be the main source of disparate (paternal) antibod
ies and can thus present an immunologic target during gestation.
Epidemiology
Frequency
United States
In the United States, pemphigoid gestationis has an estimated prevalence of 1 ca
se in 50,000-60,000 pregnancies.
International
Findings from European studies suggest that pemphigoid gestationis has an overal
l incidence of 0.5 cases per million people per year. In 1999, Jenkins et al[2]d
escribed the largest cohort of 87 patients in the United Kingdom with a total of
278 pregnancies, of which 142 were complicated by pemphigoid gestationis.
Mortality/Morbidity
No increase in fetal or maternal mortality has been demonstrated. A greater prev
alence of premature and small-for-gestational-age (SGA) babies is associated wit
h pemphigoid gestationis. Of infants, 5-10% born to affected mothers may present
with transient cutaneous involvement that resolves as maternal autoantibodies a
re cleared.
Patients with pemphigoid gestationis have a higher relative prevalence of other
autoimmune diseases, includingHashimoto thyroiditis,Graves disease, andpernicious
anemia, which are also associated with HLA-DR3 and DR-4 haplotypes
Race
Pemphigoid gestationis is less common among blacks than whites, which might refl
ect its association with specific HLA haplotypes.
Sex
This condition only affects females.
Age
Pemphigoid gestationis occurs in women of childbearing age.

Pemphigoid gestationis
What is pemphigoid gestationis?
Pemphigoid gestationis is a rare pregnancy-associated autoimmune skin disease th
at is characterised by an itchy rash that develops into blisters. It is most com
mon during the second and third trimesters of pregnancy. It was previously known
as herpes gestationis although it has no association with theherpes viruswhatsoev
er.
What causes pemphigoid gestationis?
Pemphigoid gestationis is an autoimmune blistering disease, which basically mean
s that an individual's immune system starts reacting against his or her own tiss
ue. Immunoglobulin type G (IgG) autoantibodies (known as the PG factor) cause th
e damage.
In pemphigoid gestationis the target is a protein known as BPAG2 (also called BP
180), found within the basement membrane, which is the zone between the epidermi
s and the dermis (the top and middle layers of skin). BPAG2 is within the hemide
smosome, the cell component that sticks the epidermal keratinocyte cells to the
dermis.
The antibody attack results in inflammation and separation of the epidermis from
the dermis allowing fluid to build up and create a blister.
What are the signs and symptoms of pemphigoid gestationis?
Most patients present with an intensely itchy hive-like rash during mid to late
pregnancy (13 to 40 weeks gestation).
* Initially there are itchy red bumps around the belly button
* Within days to weeks, the rash spreads to other parts of the body including th
e trunk, back, buttock, and arms. The face, scalp, palms, soles and mucous membr
anes are usually not affected.
* After 2-4 weeks, large, tense fluid-filled blisters form
* Some patients may have no blisters but instead have plaques (large raised patc
hes)
Pemphigoid
In
some cases,
gestationis
pemphigoid gestationis occurs throughout pregnancy. Symptoms may
lessen or spontaneously resolve towards the end of the pregnancy but this is sho
rt-lived, as 75-80% of women will experience a flare-up around delivery. In most
cases, symptoms resolve days later after giving birth, however in some, the dis
ease remains active for months or years. Commencement of menstrual periods, use
of oral contraceptives or further pregnancies may cause flare-ups.
Tests for pemphigoid gestationis
Diagnosis generally requires askin biopsy, which shows typical features of subepi
dermal blistering, similar in microscopic appearance tobullous pemphigoid(BP) or e
pidermolysis bullosa acquisita (EBA). Pemphigoid gestationis is confirmed by dir
ect immunofluorescence staining of the biopsy to reveal antibodies. It can be di
stinguished from BP and EBA using salt split samples of skin. In some cases, cir
culating antibodies can be detected by a blood test (indirect immunofluorescence
test).
Treatment of pemphigoid gestationis
The primary aim of treatment is to relieve itching, prevent blister formation an
d treat secondary infections.Topical corticosteroidsare used in mild disease whils
toral corticosteroidsare necessary in more extensive cases. Minimum effective dose
s should be used to reduce the risk of side effects to both mother and fetus. Or
alantihistaminesmay be used to relieve itching.
Intravenous immunoglobulinhas also been reported to be effective. Immunosuppressi
ve medications such asazathioprineorciclosporinmay also be used successfully but the

ir safety in pregnancy or during breast feeding must be carefully considered.

In most cases, pemphigoid gestationis resolves spontaneously within days after d
elivery so treatment can be tapered off and stopped. Complications are rare but
may include:
* Premature delivery
* Transient blistering on the infant that resolves with clearance of maternal an
tibodies (about 3-4 months)
* Secondary infection, which may leave scarring