Clinical r e v i e w

I IIIII II I

The specific dermatoses of pregnancy

Robert Charles Holmes, M.R.C.P., and Martin M. Black, M.D.
London, England

The terminology of the specific dermatoses of pregnancy has become

increasingly confusing, with several names in use for identical
clinical disorders. On the basis of our own study of sixty-four
patients and a review of the literature, we propose a simplified
classification: (1) herpes gestationis (pemphigoid gestationis); (2)
polymorphic eruption of pregnancy; (3) prurigo of pregnancy; and (4)
pruritic folliculitis of pregnancy. (J AM ACAD DERlVlATOL8:405-412,
1983.)

Pregnancy is frequently accompanied by distur-
bances of the skin; these include physiologic
changes, pruritus gravidarum, and the specific
dermatoses o f pregnancy. It is only the last group
which we will consider in this review. We have
excluded patients with impetigo herpetiformis
from this discussion as we feel that they have a
type of pustular psoriasis which, although asso-
ciated with pregnancy, is not specific to it. We
have also excluded dermatoses which are based on
isolated case reports ~ or have had inadequate in-
vestigation. 2 The terminology of the specific der-
matoses of pregnancy has become increasingly
confusing as new disorders are added to the list
with little attention paid to their systematic classi-
fication. Therefore, we have attempted to ratio-
nalize the nomenclature by a critical review
of the literature and also on the basis of our own
study of sixty-four patients with pregnancy der-
matoses.
HERPES GESTATIONIS
Herpes gestationis (HG) is a bullous disease
which is usually related to pregnancy and the
puerperium, although it may occur in association
with a hydatidiform mole 2 or a choriocarcinoma. 4
From the Department of Dermatology, St. Thomas' Hospital.
Reprint requests to: Robert C. Holmes, M.R.C.P., Department of
Dermatology, St. Thomas' Hospital, LambethPalace Rd., London
SE1 7EH, England/928-9292, ext. 2532.
Its incidence is often stated to be one in 4,000
pregnancies, ~ but this is probably a considerable
overestimate as Kolodny 6 found that it occurred in
only one in 60,000 pregnancies. We have studied
twenty-four patients with HG in a national survey
of this disorder. 7 Most patients were multigravida
when they had their first episode of HG, and once
it had occurred it invariably recurred in subsequent
pregnancies. The stage of pregnancy at which HG
began varied considerably from patient to patient,
ranging from 9 weeks' gestation to 6 days'
postpartum. With subsequent pregnancies the on-
set tended to be earlier. When the eruption began
in the mid trimester there was usually a period of
relative remission in the last 6 weeks of preg-
nancy, followed by an abrupt flare immediately
after delivery. We found the average duration
postpartum to be 4 weeks for the bullous eruption
and 60 weeks for the urticarial lesions.
At the onset of the eruption the lesions consisted
of urticarial papules and polycyclic wheals. Sub-
sequently, target lesions and vesicles and, finally,
large tense bullae developed (Fig. 1). The interval
between the onset of the eruption and the devel-
opment of bullous lesions was usually 4 weeks. In
87% of cases the lesions began at the umbilicus
(Fig. 2), and other commonly affected sites were
the thighs, palms, and soles. Although HG fre-
quently became widespread, the face and oral mu-
cosa were only rarely involved.
The histopathology of the urticarial papules
405
 Journal of the
406 Holmes and Black American Academy of
Dermatology

Fig. 1. Pemphigoid gestationis: large, tense bullae on the thighs. (Courtesy Dr. Peter
Hudson, Peterborough District Hospital, Peterborough, England.)
Fig. 2. Pemphigoid gestationis: umbilical erythema and vesicles.
Fig. 3. Polymorphic eruption of pregnancy: urticarial papules and vesicles developing
within and around striae.
Fig. 4. Polymorphic eruption of pregnancy: urticarial papules and prominent striae on the
lower abdomen.
showed epidermal and upper dermal edema with a In the early stages of HG and in mild cases, it
perivascular lymphohistiocytic infiltrate. As the was sometimes possible to achieve adequate
edema increased, it produced spongiotic and sub- symptomatic control with topical corticosteroids.
epidermal vesicles and eventually subepidermal Systemic corticosteroids were required when the
bullae. Eosinophils were frequently prominent in eruption reached its bullous stage, and it usually
the perivascular infiltrate and the spongiotic vesi- responded satisfactorily to 40 mg of prednisolone
cles, while the bullae always contained numerous daily. As the disease settled, the dose of predniso-
eosinophils, s lone could be steadily reduced. One should antici-
Immunofluorescence (IMF) studies demon- pate that a brisk increase in the prednisolone
strated that all patients with HG had deposition of therapy will probably be required immediately
C3 at the basement membrane zone (BMZ) of le- postpartum to cover the clinical exacerbation that
sional skin. 7 Indirect IMF was positive for C3 at occurs at this time. Plasmapheresis has been used
the BMZ in 91% of patients. Deposition of im- successfully in HG in the postpartum period u and
munoglobulin G (IgG) at the BMZ was seen in also during pregnancy itself. TM
27% of cases by direct IMF and in 21% by in- Lawley et al's 11 review of the world literature
direct IMF. on HG suggested that it was associated with an
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March, 1983
increased fetal morbidity and mortality. However,
data collected from reported patients tend to be
biased toward cases with a more severe outcome.
In our study o f twenty-four patients with thirty-
nine pregnancies affected by HG, there were no
stillbirths or neonatal deaths. 7 The average birth
weight was 2.86 kg, and the average gestation, 39
weeks. The fetal prognosis in HG has probably
been beneficially affected by the advent of corti-
costeroid therapy. Before such therapy was avail-
able, patients with HG often became systemically
unwell and went into labor prematurely or were
induced early. We feel that with the present man-
agement of H G there is only a minimal increase in
the fetal risk. Occasionally infants may have a
bullous eruption which has been attributed to pas-
sive placental transfer of the BMZ antibody, v_,.l~
Their bullous lesions resolve spontaneously within
a few weeks o f delivery.
Relationship between herpes gestationis and
bullous pemphigoid
The clinical, histopathologic, and immunopath-
ologic features of HG are very similar to those of
bullous pemphigoid (BP). Both disorders are
characterized b y pruritic urticarial lesions which
develop into large, tense bullae. They are both
highly responsive to systemic corticosteroids and
rarely respond to dapsone. Their histopathology is
similar, demonstrating subepidermal bullae con-
taining numerous eosinophils. IMF studies show
that C3 is deposited at the BMZ of lesional skin in
both disorders. 'a'14 There is some difference be-
tween HG and BP in the frequency with which
IgG may be demonstrated at the BMZ by direct
and indirect IMF. 7"14"15 However, this apparent
difference is probably of no pathologic signifi-
cance because in HG IgG may be detected by im-
munoelectron microscopy when the IMF is nega-
tive.11~ Also, Honigsmann et al ~7demonstrated that
the fine structural patterns of immunoglobulin de-
position within the lamina lucida in HG and BP
are similar. Further evidence in support of the
overlap between HG and BP comes from their
disease associations. BP has been described in as-
sociation with several autoantibody-related dis-
orders.1 s-22
Recently attention has also been drawn to an
association between HG and Graves' disease. '-'z~In
Dermatoses of pregnancy 407
addition to BP there are several other conditions
which are classified within the group of pem-
phigoid disorders. These include cicatricial pem-
phigoid, polymorphic pemphigoid) 4 and localized
pemphigoid. In view of the considerable overlap
between HG and BP, we feel that HG should also
be included within the pemphigoid group. There-
fore we propose that HG should be renamed pem-
phigoid gestationis. This would have the advan-
tage not only of placing considerations of HG in
the appropriate immunopathologic setting, but
also of obviating the enormous confusion gen-
erated by its present name. Although we feel that
HG should be included within the spectrum of
pemphigoid disorders, we recognize that it un-
doubtedly differs from BP in several respects. The
most striking clinical differences are the frequency
of umbilical lesions in HG 7 and the susceptibility
of the eruption to hormonal modulation. 23 It has
also been suggested that there are subtle electron
microscopic differences between H G and BP.
Yaoita et al '-'6 found that in the early lesions of HG
there was destruction of basal cells, but that this
was absent in BP. They also noted differences in
immunoelectron microscopy, with uniform depo-
sition of reaction product along the lamina lucida
in HG and focal accumulation of the deposit at
hemidesmosomes in BP. However, Honigsmann
et aW found that similar accumulation of reaction
product around hemidesmosomes could also occur
in HG. Recent studies have revealed that HG and
BP differ immunogenetically. In H G there is a
significantly increased frequency of the HLA anti-
gens B8 and DR3, 7'27whereas in BP the frequen-
cies of HLA antigens are normal, z8,2',) It has also
been suggested that in HG there is an increased
frequency of anti-HLA antibodies? °
We conclude that although H G has many
similarities to BP, which justify its inclusion
within the pemphigoid group of disorders, it is
nevertheless a distinct disorder.
THE URTICARIAL ERUPTIONS OF
PREGNANCY
In approximately 1 in 200 pregnancies a pru-
ritic urticarial eruption develops in and around the
abdominal striae. Several names have been given
to this disorder, including toxemic rash of preg-
nancy, ~ late-onset prurigo of pregnancy, ~2':~:~pru-

408 Holmes and Black
ritic urticarial papules and plaques of pregnancy, 34
and we have also referred to it as toxic erythema of
pregnancy, r A critical review o f the literature sug-
gested that these were all synonyms for a single
disorder, 35 and this was supported by our prospec-
tive study of thirty patients. 7 As this eruption con-
sists not only of papules and plaques, but also of
target lesions, polycyclic erythematous wheals,
and vesicles, we have proposed the name poly-
morphic eruption of pregnancy (PEP). a~
Estimations of the incidence of PEP vary be-
tween one in 120 pregnancies al and one in 240. 7 It
is undoubtedly much more common than HG. We
have found that PEP is predominantly a disorder
of first pregnancies, with 76% of women being
primigravida, r There are very little data on the
frequency with which PEP recurs in subsequent
pregnancies, but it appears to do so only occa-
sionally. In the few patients that we have seen
with second episodes of PEP, the eruption was
much less severe than the first, which is a contrast
to the finding in HG.
In our study of PEW the eruption usually began
in the last 5 weeks of pregnancy and rarely per-
sisted for more than a few weeks. The morphology
of the lesions consisted of urticarial papules which
frequently coalesced to produce plaques and
polycyclic wheals. Vesicles occurred in 44% of
cases (Fig. 3) and target lesions in 19%. The ves-
icles never enlarged beyond 2 m m in diameter, so
that frankly bullous lesions were not seen. Promi-
nent striae were found in over 80% of patients,
and it was within the striae on the lower abdomen
that the eruption usually began (Fig. 4). The erup-
tion often remained confined to the abdomen with
relative sparing of the umbilicus. However, occa-
sionally it became widespread, sparing only the
face, palms, soles, and mucous membranes.
The histopathology of PEP varied with the clin-
ical stage of the eruption. 8 In the early urticarial
papules there was epidermal and upper dermal
edema with a perivascular infiltrate composed of
lymphocytes, histiocytes, and eosinophils. The
fully developed lesions had the additional finding
of vesicular spongiosis, and in one case the papil-
lary dermal edema was so intense that there was
subepidermat vesicle formation. Eosinophils were
prominent in 24% of biopsies. In the resolving
Journal of the
American Academy of
Dermatology
stage mere was acanthosis and loci of paraker-
atosis. IMF studies in PEP were consistently
negative. 7
Only symptomatic treatment was required for
PEP as the eruption was so transient; adequate
relief was usually provided by topical corticoste-
roids. The fetal prognosis was normal. In our
study of thirty patients with thirty-two affected
pregnancies, there were no stillbirths or neonatal
deaths and the average birth weight and gestation
were entirely normal. 7
There has been one isolated case report of PEP
in which it was suggested that the infant was af-
fected by a similar r a s h ) 6 However, this may
simply have been a fortuitous association with the
very common neonatal eruption known as ery-
thema neonatorum. In our study none of the in-
fants were affected by PEP.
Relationship between PEP and HG
As there is considerable clinical and histo-
pathologic overlap between PEP and HG, it has
been suggested that PEP may, in fact, be a mild
prebullous stage of HG. a2 However, our studies
have revealed clinical and immunologic evidence
which supports their classification as separate
disorders. 7 First, there was a difference in the way
that their clinical activity varied with the stage of
gestation. HG usually began in the mid trimester
and entered a phase of relative remission after 34
weeks' gestation. In contrast, PEP invariably
began in the last few weeks of pregnancy. While
HG tended to flare immediately postpartum, PEP
usually settled. There was a marked difference in
the involvement of the umbilicus; HG frequently
began at the umbilicus (Fig. 2) while it was usu-
ally spared in PEP (Fig. 4). One other clinical
difference which we noted was that in PEP there
were invariably urticated abdominal striae (Fig.
4), whereas in HG striae were not prominent. The
evidence which gave strongest support to the sepa-
rate identity of HG and PEP was immunologic. In
HG there was always C3 deposition at the BMZ of
lesional skin, whereas in PEP IMF studies were
consistently negative. Holubar et al ~6 demon-
strated that peroxidase-antiperoxidase immuno-
electron microscopy was more sensitive than IMF
in the detection of immunoreactant deposition,
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March, 1983
and therefore we have used this technic in a study
of six patients with PEP. aT Once again we found
no evidence o f C3 deposition at the BMZ in PEP.
Finally, immunogenetie studies supported the
separate identity of HG and PEP. HG was associ-
ated with an increased frequency of the HLA anti-
gens B8 and DR3, whereas their frequency in PEP
was normal. 7
Erythema multiforme of pregnancy
This is probably yet another synonym for PEP
. as target lesions are not uncommon in this disor-
der. 7 Also in the cases described by Crawford and
Leeper a8 there was no histopathologic confir-
mation of erythema multiforme. Therefore we feel
that at present there is no justification for the in-
clusion of erythema multiforme within the specific
dermatoses of pregnancy.
Papular dermatitis of pregnancy
Spangler et a139 suggested that there was a dis-
tinct subgroup of patients among those with papu-
lar eruptions of pregnancy that could be identified
both clinically and biochemically. They termed
this disorder "papular dermatitis of pregnancy"
and they stressed its importance as they found that
it was associated with a considerably increased
fetal risk which was preventable with appropriate
treatment. The clinical feature which they felt dis-
tinguished their twelve patients from those with
the much more common eruption termed "prurigo
gestationis o f Besnier"4° was that the lesions were
widespread rather than in groups on the extensor
surfaces of the limbs. They stated that the charac-
teristic biochemical findings in papular dermatitis
of pregnancy were raised urinary human chorionic
gonadotropin, reduced plasma cortisol, and re-
duced urinary estriol. 4~ They calculated that the
associated fetal mortality was 30%, but that this
could be dramatically improved by systemic ther-
apy with either prednisone up to a dosage of 200
mg daily or diethylstilbestrol, 600-2,500 mg
daily. In view of these important assertions, we
have reevaluated several aspects of their studies.
We feel that the widespread distribution of the
lesions in Spangler et al's cases a9 did not neces-
sarily indicate a separate disorder, but may simply
have represented the more severe cases of prurigo
Dermatoses of pregnancy 409
Table I. The specific dermatoses of
pregnancy
Proposedelassifica- I
fion Established terminology
Pemphigoid gesta- Herpes gestationis
tionis
Polymorphic Toxemic rash of pregnancy
eruption of Late-onset prurigo of preg-
pregnancy nancy
Pmritic urticarial papules and
plaques of pregnancy
Toxic erythema of pregnancy
Erythema multiforme of
pregnancy
Prurigo of preg- Pmrigo gestationis of Besnier
nancy Early-onset prurigo of preg-
nancy
Pruritic folliculitis Pruritic folliculitis of preg-
of pregnancy nancy
Classification un- Papular dermatitis of preg-
certain nancy
gestationis of Besnier or PEP. It would seem that
Spangler et al's main reason for the separate
classification of their patients was the abnormal
biochemical findings of raised urinary chorionic
gonadotropin, low urinary cortisol, and low uri-
nary estriola°'41; however, similar biochemical
studies were not performed in other pregnancy
dermatoses. Therefore, we consider that there was
little justification for the separate classification of
Spangler et al's cases and that they were possibly
florid examples of prurigo gestationis of Besnier
or PEP. However, this question will not be re-
solved until further information on the biochem-
ical findings in pregnancy dermatoses is available.
We feel that the fetal mortality of 30% which
Spangler et al3° reported in their cases also re-
quires reassessment. They interpreted fetal deaths
which occurred in pregnancies preceding the de-
velopment of the papular eruption as related to the
skin disorder, which we feel was hardly justified
and grossly exaggerated the fetal risk. Also, when
recording fetal deaths they included not only
stillbirths but also spontaneous abortions, with no
indication as to the type of fetal death in each case.
In the fetal deaths caused by spontaneous abor-
tion, it would have been important to indicate their
gestation as first-trimester spontaneous abortions

410 Holmes and Black
are not uncommon in a normal population. There-
fore, we consider that the fetal mortality in Spang-
ler et al's cases z9 was overestimated and the way
that the mortality data were presented has pre-
cluded any valid reassessment.
PRURIGO OF P R E G N A N C Y
Nurse ~2 found that one in 300 pregnancies was
complicated by a pruritic papular eruption which
began earlier in pregnancy than the urticarial
eruption which we have already discussed. He re-
ferred to this condition as "early onset prurigo
of p r e g n a n c y , " although another synonym fre-
quently used is prurigo gestationis of Besnier.
Nurse's a2 study of thirty-one patients remains the
only detailed clinical description of this disorder.
Its onset was usually between 25 and 30 weeks'
gestation, and it tended to persist for up to 3
months' postpartum. There was no apparent ten-
dency for it to recur in subsequent pregnancies.
The lesions consisted of grouped excoriated pap-
ules distributed on the extensor surfaces of the
limbs, the abdomen, and the shoulders, although
occasionally they became widespread. There was
no associated increased risk to either the mother or
the fetus, and Nurse z2 recommended simply symp-
tomatic treatment.
We have studied eight patients with eruptions
that were clinically identical to those described by
Nurse. 32 The histopathology of their lesions dem-
onstrated parakeratosis and acanthosis frequently
accompanied by full-thickness excoriation with
serous crusting. In the dermis there was a loose
perivascular lymphocytic infiltrate and occasional
localized areas of fibroplasia. Both direct and indi-
rect IMF studies were negative. There was no as-
sociated fetal morbidity or mortality. In accord
with Nurse's patients, the morphology of their
eruption consisted of papules with varying degrees
of excoriation. Although none of our patients had
typical eczematous lesions, they each had features
suggestive of an underlying atopic diathesis. Three
patients were undoubtedly atopic as they had a
personal history of asthma, allergic rhinitis, or
atopic eczema, a family history of these disorders,
and raised IgE. A further patient gave a clear his-
tory of childhood atopic eczema. In the remaining
four patients the evidence for atopy was less con-
Journal of the
American Academyof
Dermatology
clusive; in three it consisted of a positive family
history and in one the only feature was a raised
IgE at 730 KU IgE/liter (normal range, 14-120).
At present there is little information as to the
etiology or pathogenesis of prurigo of pregnancy.
However, the propensity of atopic individuals to
develop prurigo as a result of scratching is well
recognized. 4~ As 18% of pregnancies are compli-
cated by pruritus 43 and 10% of the population are
atopic, 44 then, assuming that these are indepen-
dent phenomena, they will coincide in approxi-
mately 2% of pregnancies. Therefore, we are
investigating the possibility that prurigo of preg-
nancy might simply be the result of pruritus
gravidarum occurring in women with an atopic
diathesis.
PRURITIC FOLLICULITIS OF PREGNANCY
The development in pregnancy of a widespread
pruritic folliculitis was described by Zoberman
and Farmer 45 in six patients. They did not at-
tempt to estimate its incidence. The eruption
began between the fourth and ninth months of
pregnancy and had usually resolved by 2 weeks
postpartum. There was a history of recurrence of
the eruption in succeeding pregnancies in two pa-
tients. The lesions consisted of follicular ery-
thematous papules which were widespread in all
but one case. In this instance, they were confined
to the abdomen and the arms. The fetal and mater-
nal prognosis was normal. No satisfactory symp-
tomatic treatment was found. The histopathology
demonstrated acute folliculitis in five of six biop-
sies. There was also focal spongiosis with exocy-
tosis of polymorphonuclear and mononuclear
ceils. In the dermis there was edema and a peri-
vascular infiltrate of variable intensity. Direct IMF
studies were negative.
We have studied two patients with similar pru-
ritic eruptions. The lesions consisted of multiple
small follicular pustules distributed mainly on the
shoulders, back, buttocks, abdomen, and thighs.
The histopathology was identical to that described
by Zoberman and Farmer, 4~ and IMF studies were
similarly negative. There were no fetal complica-
tions. Our patients derived considerable symp-
tomatic relief from the topical application of a
cream containing 10% benzoyl peroxide and 1%
Volume 8
Number 3
March, 1983
hydrocortisone. The clinical appearance of this
eruption was very similar to the monomorphic
type of acne which may be seen in patients taking
systemic corticosteroids. We have also seen this
pattern of acne after the administration of proges-
togenic steroids. Therefore, although it is impor-
tant to recognize pruritic folliculitis as a compli-
cation of pregnancy, we feel that it may be a form
of hormonally induced acne rather than a specific
dermatosis of pregnancy.
CONCLUSION
W e have reviewed the cutaneous eruptions
w h i c h we term "the specific dermatoses of preg-
n a n c y , " and we have classified them into four
disorders: herpes gestationis (pemphigoid ges-
tationis), polymorphic eruption o f pregnancy,
prurigo of pregnancy, and pruritic folliculitis of
p r e g n a n c y . We have indicated that our inclusion
o f prurigo of pregnancy and pruritic folliculitis of
pregnancy within this group o f disorders is provi-
sional. Further studies may show that they are
more appropriately classified as disorders exacer-
bated by pregnancy rather than specific derma-
roses of pregnancy. The classification o f Spang-
ler's patients remains unclear.
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412 Holmes and Black American Academy of
Dermatology

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