Skin disease in pregnancy

BMJ 2014;348:g3489 doi: 10.1136/bmj.g3489 (Published 3 June 2014)
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Clinical Review
CLINICAL REVIEW
Skin disease in pregnancy
1
Samantha Vaughan Jones consultant dermatologist , Christina Ambros-Rudolph consultant
2
3
dermatologist , Catherine Nelson-Piercy professor of obstetric medicine
Department of Dermatology, Ashford and St Peter’s Foundation Trust, Chertsey, Surrey KT16 0PZ, UK; 2Department of Dermatology, Medical
University of Graz, Austria; 3Women’s Services, Guy’s and St Thomas’ Foundation Trust, London
1
Skin problems are common during pregnancy, but accurate
diagnosis can be difficult. Skin changes in pregnancy can be
broadly divided into physiological (box 1),1 specific dermatoses
of pregnancy, and other common skin diseases in pregnancy.
In our experience of pregnancy skin clinics, approximately 50%
of women present with an exacerbation of a common
inflammatory skin disease (for example, eczema, psoriasis, acne,
rosacea) or a skin infection. Around 30-50% of women present
with one of the specific dermatoses of pregnancy (pemphigoid
gestationis, polymorphic eruption of pregnancy, or atopic
eruption of pregnancy).2 Pregnancy causes specific management
issues, and there is often confusion over which treatments can
be used safely for treating skin disease in pregnancy. Itching
can occur in up to 1 in 5 normal pregnancies (physiological
pruritus) but is also the presenting symptom of many of the
pregnancy dermatoses (box 2).
This review aims to familiarise readers with the clinical
presentations of common skin diseases in pregnancy, outline
the steps for confirming an accurate diagnosis, and evaluate the
safest and appropriate treatments.
Why is skin disease common in
pregnancy?
To prevent rejection of the fetus during pregnancy, profound
changes occur in the woman’s immune system, with a shift from
a predominantly T helper 1 lymphocyte profile to a T helper 2
profile.3 This transition changes the cytokines that are produced
by the placenta, so that levels of interleukin 12 and γ interferon
are reduced and levels of interleukins 4 and 10 are increased.
These changes influence a woman’s susceptibility to skin
disease, increasing the risk of autoimmune disease and reducing
cell mediated immunity (thereby increasing the risk of skin
infections). Diseases such as psoriasis that are driven by the T
helper 1 immune response tend to improve, whereas those driven
by the T helper 2 immune response, such as atopic eczema and
systemic lupus erythematosus, may be exacerbated.4
What are the specific dermatoses of
pregnancy?
The specific dermatoses of pregnancy represent a heterogeneous
group of severely pruritic inflammatory dermatoses associated
exclusively with pregnancy or the immediate postpartum period.
These dermatoses have been reclassified recently.2 Atopic
eruption of pregnancy, a new term, describes a disease complex
that includes women with a former diagnosis of atopic eczema
in pregnancy, prurigo of pregnancy, and pruritic folliculitis of
pregnancy. A large retrospective two centre study of over 500
pregnant women with pruritus showed considerable overlap
both clinically and histopathologically among these entities
(together accounting for 50% of the cohort).2
The pruritus associated with polymorphic and atopic eruption
of pregnancy is distressing to the mother, but pemphigoid
gestationis may also be associated with prematurity and small
for date babies, and intrahepatic cholestasis of pregnancy
increases the risk for fetal distress, prematurity, and stillbirth.
Itching in intrahepatic cholestasis is often nocturnal and affects
the palms and soles (unlike physiological pruritus). In patients
with pruritus and absence of skin lesions other than excoriations
it is important to exclude a diagnosis of intrahepatic cholestasis
of pregnancy by carrying out a clinical assessment for signs of
liver disease and performing liver function tests.5 As intrahepatic
cholestasis of pregnancy has been discussed extensively,5 this
review concentrates on the other three conditions.
Pemphigoid gestationis
Pemphigoid gestationis is a rare, self limiting autoimmune
bullous disorder of mainly late pregnancy but can occur in any
of the three trimesters. Its incidence varies from 1 in 2000 to 1
in 50 000-60 000 pregnancies, depending on the prevalence of
the HLA haplotypes DR3 and DR4.6
Circulating complement fixing IgG antibodies bind to a 180
kDa protein, BP-180 or bullous pemphigoid antigen 2, in the
hemidesmosomes of the basement membrane zone of the skin,
leading to tissue damage and blister formation. These antibodies
Correspondence to: S Vaughan Jones [email protected]
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BMJ 2014;348:g3489 doi: 10.1136/bmj.g3489 (Published 3 June 2014)
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CLINICAL REVIEW
Summary points
Pregnancy causes changes in the immune system that result in an increase in autoimmune disease and reduction in cell mediated
immunity
The two commonest skin conditions in pregnancy are atopic eruption of pregnancy and polymorphic eruption of pregnancy
Pemphigoid gestationis is a rare autoimmune bullous disease that can cause reduced fetal growth and prematurity
Many common skin diseases may flare in pregnancy and treatment may need to be modified for the safety and wellbeing of the mother
and fetus
Pemphigoid gestationis, pemphigus vulgaris, and systemic lupus erythematosus can all lead to neonatal involvement from passive
transfer of maternal antibodies across the placenta
Emollients are the mainstay of treatment in reducing pruritus and giving women relief of symptoms
Box 1 Physiological skin changes in pregnancy
• Hyperpigmentation—linea nigra, areolae, melasma, naevi, vulvar melanosis
• Striae distensae—increased in third trimester
• Pruritus gravidarum—common in the first and second trimester (affects 1 in 5 women)
• Hair changes—telogen effluvium (post partum)
• Nail changes—ridging, splitting, distal onycholysis, longitudinal melanonychia
• Vascular changes—telangectasia, varicosities, pyogenic granulomas, haemangiomas, peripheral oedema
• Eccrine glands—activity increased (increased sweating)
• Apocrine glands—activity reduced (reduced sweating and apocrine secretion)
• Sebaceous glands—activity increased (in third trimester)
• Immune system—shift from T helper 1 to T helper 2 lymphocyte profile
Box 2 Causes of itching in pregnancy
Skin rash present
• Atopic eruption of pregnancy
• Polymorphic eruption of pregnancy
• Pemphigoid gestationis
• Scabies
• Urticaria
• Drug eruptions
• Allergy
Skin rash absent
• Intrahepatic cholestasis of pregnancy
• Exacerbation of underlying liver disease—for example, primary biliary cirrhosis
Sources and selection criteria
We searched Medline, Embase, the Cochrane Database of Systematic Reviews, and Clinical Evidence online using the terms “skin and
pregnancy” and “pregnancy dermatoses”. When possible, we used evidence from randomised controlled trials and systematic reviews. In
the absence of higher level evidence (as trials are lacking in pregnant women) we included case series. We also referenced review articles
by experts and included expert opinion based on clinical experience.
can be detected by direct immunofluorescence of perilesional
skin as well as by indirect immunofluorescence of the serum in
30-100% of cases.7 Pemphigoid gestationis presents with intense
pruritus followed by urticarial papules and plaques, which
typically develop on the abdomen and mostly within the
umbilical region. Lesions may involve the entire body surface
and usually progress to tense blisters.6 Improvement in late
pregnancy is often followed by postpartum flare (75% of cases)
after which lesions usually resolve within weeks to months.
Recurrence may occur with menstruation and hormonal
contraception and should be expected in subsequent pregnancies.
There is an increase in prematurity and small for date babies,
which correlates with the severity of disease, as represented by
early onset and blister formation.8 As a result of passive transfer
of antibodies from the mother to the fetus, about 10% of
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newborns may develop mild skin lesions, which resolve
spontaneously within days to weeks.6
Polymorphic eruption of pregnancy
Polymorphic eruption of pregnancy usually affects primigravidas
in the last few weeks of pregnancy or immediately post partum.9
It occurs in about 1 in 160 to 1 in 200 pregnancies. Polymorphic
eruption of pregnancy has been linked to excessive maternal
weight gain and multiple pregnancy (fig 1⇓).9 10 The
pathogenesis of the condition remains unclear, although theories
include abdominal distension and hormonal and immunological
factors.10 11 Polymorphic eruption of pregnancy starts within the
striae distensae on the abdomen, with severely pruritic urticarial
papules that coalesce into plaques, spreading to the buttocks
and proximal thighs and in severe cases becoming generalised.
In contrast with pemphigoid gestationis, the umbilical region
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BMJ 2014;348:g3489 doi: 10.1136/bmj.g3489 (Published 3 June 2014)
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CLINICAL REVIEW
is typically spared (fig 2⇓). Subsequently, skin lesions become
more polymorphic, with small vesicles, widespread non-urticated
erythema, and targetoid and eczematous lesions.9 Maternal and
fetal outcomes are not affected and neither is the neonate.
Lesions are self limiting, usually resolving within 4-6 weeks,
independent of delivery,9 and recurrence is unusual, except in
multiple pregnancy.
Atopic eruption of pregnancy
Atopic eruption of pregnancy is the most common dermatosis
of pregnancy, accounting for 50% of patients seen in a typical
pregnancy skin clinic. It includes eczematous or papular lesions
in patients with a history of atopy and usually develops early
in gestation, in 75% of cases before the third trimester.2 Atopic
eruption of pregnancy is thought to be triggered by the dominant
T helper 2 immune response in pregnancy.12 About 20% of
women experience an exacerbation of pre-existing eczema in
pregnancy, whereas 80% experience atopic skin changes for
the first time or after a long remission (for example, since
childhood). Of these, about two thirds present with widespread
eczematous changes (so called E-type atopic eruption of
pregnancy) often affecting typical atopic sites such as the face,
neck, décolleté, and flexural surfaces of the arms and legs,
whereas one third have papular lesions (P-type atopic eruption
of pregnancy).2 The papular lesions include small erythematous
papules disseminated on the trunk and limbs, as well as typical
prurigo nodules, mostly located on the shins and arms. Severe
dryness of the skin is a key finding. Maternal prognosis is good
even in severe cases, as skin lesions usually respond quickly to
treatment; recurrence in subsequent pregnancies is common
because of the atopic background. The fetus is unaffected but
is at increased risk of atopic skin disease in infancy.
Algorithmic approach to the specific
dermatoses of pregnancy
A retrospective analysis of a large patient sample showed
important differences that are helpful for differential diagnosis.2
The algorithm in figure 3⇓ may facilitate discrimination between
the various pruritic dermatoses in pregnancy and highlights their
appropriate investigation and management.
How are the specific dermatoses of
pregnancy treated?
Treatment of the specific dermatoses of pregnancy depends on
the stage and severity of the disease and aims to control pruritus
and skin lesions. In all cases treatment with corticosteroids, both
topically and systemically, and systemic antihistamines can be
effective. In the case of mild pemphigoid gestationis, topical
corticosteroids with or without oral antihistamines may be
sufficient. All other cases of pemphigoid gestationis generally
require systemic corticosteroids (prednisolone, usually started
at a dose of 0.5-1 mg/kg/day).6 When the disease improves, the
dose can usually be reduced, but should be increased in time to
prevent the common disease flare that occurs at delivery. Cases
that are severe or unresponsive to systemic corticosteroid
treatment may benefit from other agents (pulsed
methylprednisolone or intravenous immunoglobulins, see box
3).6 After delivery, if necessary, the full range of
immunosuppressive treatment may be administered. In
polymorphic eruption of pregnancy, symptomatic treatment
with topical corticosteroids with or without antihistamines is
usually sufficient to control pruritus and skin lesions. In severe
generalised cases, a short course of systemic corticosteroids
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(prednisolone, 40-60 mg/day, for a few days in tapering doses)
may be necessary and is usually effective.10 Also in atopic
eruption of pregnancy, basic treatment together with topical
corticosteroids for several days will usually lead to rapid
improvement of skin lesions. Severe cases may require a short
course of systemic corticosteroids and antihistamines; bacterial
and viral superinfection needs to be treated accordingly (box 3)
and ultraviolet B phototherapy is a safe additional tool that can
be used under specialist supervision, particularly for severe
cases in early pregnancy.13
What are the other common skin diseases
in pregnancy?
Inflammatory skin diseases
Psoriasis vulgaris
Pregnancy has a variable effect on psoriasis. Patients typically
improve because of changes in immunity, although in 10-20%
of women psoriasis can worsen and they require a more
advanced/complex treatment.14 A life threatening severe form
of generalised pustular psoriasis exists that requires systemic
treatment. A large Taiwanese study showed an increased risk
of women with severe psoriasis delivering low birthweight
infants, whereas mild psoriasis was not associated with an excess
risk of adverse birth outcome.15
Impetigo herpetiformis is thought to be a severe variant of
pustular psoriasis, and debate still continues as to whether this
should be regarded as a separate disease. It typically presents
with a flexural pustular eruption associated with fever, tetany,
and hypocalcaemia. Recurrence in subsequent pregnancies is
characteristic, with earlier onset and increased severity.
Topical corticosteroids can be used to treat psoriasis in
pregnancy (and calcipotriol for localised disease). No studies
have shown prenatal toxicity.16 17 The preferred treatment for
mild psoriasis is with emollients and topical corticosteroids.
Severe cases of psoriasis can be treated effectively in secondary
care with prednisolone and phototherapy using narrowband
ultraviolet B light.18 Ultraviolet B light should be used in
preference to psoralen combined with ultraviolet A light, and
systemic drugs such as methotrexate, hydroxyurea, and acetretin
should be avoided during pregnancy as they are all teratogenic.
Ciclosporin and biological drugs (tumour necrosis factor alpha
inhibitors) can be used under specialist supervision for more
severe disease.
Acne vulgaris
Acne vulgaris often improves in early pregnancy but worsens
in the third trimester as maternal androgen levels increase. Mild
acne vulgaris can be treated with topical treatments such as
benzoyl peroxide or azelaic acid. Systemic and topical retinoids
are teratogenic and should be avoided.19 Oral erythromycin
would normally be the first choice of antibiotic for acne vulgaris
or acne rosacea in pregnancy after the first trimester. Two recent
Swedish studies showed an increased risk (1.8%) of
cardiovascular defects (atrial and ventricular septal defects) in
the neonates of pregnant women who had taken erythromycin
in early pregnancy. In these studies it is not clear whether these
cardiac defects were due to confounding factors (such as the
underlying disease or condition) or a true effect of the drug.20 21
As a result, azithromycin or clarithromycin are preferred
treatments in the first trimester. Erythromycin estolate has also
been shown to cause hepatotoxicity, so this salt should be
avoided during pregnancy.16 In secondary care, narrowband
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BMJ 2014;348:g3489 doi: 10.1136/bmj.g3489 (Published 3 June 2014)
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CLINICAL REVIEW
Box 3 Treatment of the specific dermatoses of pregnancy6 10 13
Pemphigoid gestationis
Prebullous stage
• Potent topical corticosteroids
• Emollients
Bullous stage
• Systemic corticosteroids* (prednisolone 0.5-1.0 mg/kg daily)
Refractory cases
• Immunopheresis*
• Pulsed methylprednisolone*
• Intravenous immunoglobulins*
Polymorphic eruption of pregnancy
• Moderately potent topical corticosteroids
• Emollients
• Systemic antihistamine
Severe cases
• Systemic corticosteroids* (prednisolone)
Atopic eruption of pregnancy
• Emollients with or without antipruritic additives (menthol, polidocanol, urea)
• Mild to moderate potent topical corticosteroids
• Systemic antihistamines
Severe cases
• Systemic corticosteroids*
• Phototherapy using ultraviolet B light*
Secondary infections
• Bacterial
Systemic antibiotics (penicillin, cephalosporins), topical antibiotics (mupirocin, fusidic acid)
• Herpes simplex virus
Systemic aciclovir
*Management in secondary care under specialist supervision
ultraviolet B phototherapy can be used as second line treatment
for acne vulgaris.22
Severe acne conglobata may require treatment with systemic
corticosteroids in addition to oral antibiotics. Acne neonatorum
may occur as a result of passive transfer of maternal androgens
across the placenta during the third trimester.
Acne rosacea
Acne rosacea often worsens during pregnancy and may require
systemic treatment. Topical azelaic acid and metronidazole can
be used in pregnancy for mild disease. High doses of
metronidazole should be avoided during pregnancy. Oral
tetracyclines should be avoided owing to their effect on the
development of fetal bones and teeth.
Pityriasis rosea
Pityriasis rosea is another inflammatory skin condition that can
present during pregnancy and may be misdiagnosed as guttate
psoriasis or tinea corporis. It classically presents with oval scaly
plaques on the trunk, often preceded by a “herald patch.” It has
been associated with human herpesvirus 6 infection. A previous
study of 38 women presenting with pityriasis rosea in pregnancy
associated with active human herpesvirus 6 infection showed
that nine delivered preterm and five miscarried.23 Treatment is
normally conservative as the rash fades rapidly within a few
weeks in most cases.
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Urticaria
Urticaria (or hives) presents commonly during pregnancy and
can mimic other pregnancy dermatoses, particularly the
prebullous phase of pemphigoid gestationis or polymorphic
eruption of pregnancy. Oral antihistamines are the treatment of
choice. Chlorpheniramine is known to be safe and should be
the treatment of choice in the first trimester.24 25
Erythema nodosum
Erythema nodosum is a reactive inflammation of the dermis
and subcutaneous fat, secondary to a wide variety of underlying
conditions. Pregnancy can also trigger this eruption, which
presents with tender erythematous nodules or plaques over the
anterior part of the lower legs. Fever, malaise, and arthralgia
often occur and the eruption typically lasts up to 6-8 weeks.
Supportive treatment is normally all that is required—rest,
elevation of the affected leg, analgesia, and bandaging can all
help to alleviate symptoms. More resistant or severe cases may
justify a short course of oral corticosteroids.26
Skin infections and infestations
Herpes simplex virus
Primary herpetic infection (herpes simplex viruses 1 or 2) occurs
in 2% of pregnancies and is often more severe than in
non-pregnant women. Primary or recurrent genital infection
with herpes simplex virus is an indication for caesarean section
and drug treatment. Systemic aciclovir is safe in pregnancy and
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has been used extensively without adverse effects. Three studies
in animals did not show any teratogenic effects.16 Prophylactic
treatment with aciclovir can be used from 36 weeks’ gestation
in women with recurrent herpes genitalis. Intravenous treatment
is indicated for life threatening disseminated infection to reduce
maternal and fetal mortality. Aciclovir has been used most
frequently in humans compared with similar antiviral agents
(valaciclovir and famciclovir) during pregnancy and is therefore
still the preferred treatment.16
Varicella zoster virus
Herpes zoster in pregnancy (reactivation of latent varicella zoster
virus infection) is not associated with viraemia and does not
pose a risk for the fetus (fig 4⇓). Primary infections (chicken
pox) occur in 5 of 10 000 pregnancies and may put both the
mother and the fetus at risk (of pneumonia and encephalitis).
Infection during weeks 1-20 can lead to fetal varicella syndrome
in 1-2% of pregnancies, with major neurological and growth
defects. Passive immunisation with varicella zoster
immunoglobulin to seronegative mothers within 72 hours after
exposure to the virus may prevent or ameliorate maternal
infection. Women with confirmed varicella should be treated
early for pneumonia or other complications with aciclovir either
orally or intravenously. High dose intravenous aciclovir is used
to treat varicella in neonates.27
Scabies
Infestation with scabies (Sarcoptes scabiei) is common during
pregnancy. The preferred treatment is topical permethrin 5%,
the treatment of choice for pregnant women with scabies in both
the United Kingdom and the United States. Permethrin 5% is
highly active in treating scabies infection, with systemic
absorption occurring with less than 2% of the dose and no
known adverse effects.28 Second line treatment is with benzoyl
benzoate 25%.28 Treatment must be repeated after a week to kill
eggs and persistent mites and all potentially infectious close
contacts should also be treated. Antihistamines and mild to
moderately potent topical steroids may be needed to control the
irritant dermatitis that often follows treatment.
Autoimmune skin diseases
Systemic lupus erythematosus
About 60% of women with pre-existing systemic lupus
erythematosus have a flare during pregnancy or the puerperium
compared with 40% of non-pregnant women over the same
period.29 Corticosteroids are the treatment of choice, but they
do not prevent flares. Systemic lupus erythematosus is associated
with increased risks of miscarriage, fetal loss, pre-eclampsia,
preterm delivery, and fetal growth restriction. A recent large
retrospective review of 396 pregnancies in women with systemic
lupus erythematosus found a higher risk of adverse pregnancy
outcomes associated with antiphospholipid antibodies, lupus
nephritis, Raynaud’s phenomenon, hypertension, and active
disease at the time of conception.30
About 30% of women with systemic lupus erythematosus have
anti-Ro antibodies. They are more common in those with
subacute lupus erythematous (fig 5⇓) and Sjogren’s syndrome.29
These antibodies cross the placenta and can cause cutaneous
neonatal lupus erythematosus (5% risk), which typically presents
in the first two weeks of life with a scaly, annular eruption on
the face and scalp. The rash disappears spontaneously within
six months and scarring is unusual. Congenital heart block (2-3%
risk) is usually detected in utero at around 18-20 weeks.
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Perinatal mortality is 20% and most of those who survive need
a pacemaker.31
Pemphigus vulgaris
Pemphigus is a family of rare and potentially fatal autoimmune
blistering diseases of the skin and mucosae often associated
with high morbidity and mortality, characterised by the presence
of antibodies targeted against desmoglein 3 or 1 (which are
epidermal proteins). Pemphigus vulgaris is the commonest
subtype and this classically presents with flaccid blisters or
erosions on the trunk and limbs (as blisters frequently burst
when the skin is rubbed or scratched). The oral and genital
mucosae are often involved with erosions and blisters.
Pemphigus vulgaris can develop or worsen during pregnancy
and can also be transmitted to the fetus. Fetal skin shares the
same desmoglein 3 profile as that of the oral mucosa in adults
so that neonatal pemphigus is more likely to occur if the mother
has oral disease. Fetal prognosis is variable and there is no direct
correlation between the severity of the mother’s disease and the
extent of neonatal involvement. Women in remission have given
birth to neonates with extensive disease, and conversely women
with active pemphigus have delivered disease-free babies.32-35
Direct and indirect immunofluorescence are required for an
accurate diagnosis. Enzyme linked immunosorbent assay using
recombinant desmoglein 3 can also confirm the diagnosis.36
Systemic treatment is usually required (prednisolone,
plasmapheresis, plasma exchange, dapsone, or azathioprine).35 36
Close collaboration between obstetricians and dermatologists
is essential to reduce maternal and infant mortality.
Skin tumours
Benign melanocytic naevi
Pre-existing naevi may darken in pregnancy as a result of the
increased circulating levels of melanocyte stimulating hormone.
This change can lead to anxiety and concern about possible
malignant melanoma. The advent of dermoscopy and digital
mole mapping has improved our ability to define and monitor
changes in moles more clearly. Dermoscopy increases diagnostic
accuracy by assessment of pigmentation, colour, size, symmetry,
and borders. The assessment of ABCD (asymmetry, border,
colour, and diameter) can help to diagnose early malignant
melanoma. Total dermoscopic score on the Stolz ABCD scoring
system37 may increase at the end of pregnancy, as moles can
expand or darken.38 39 Early referral and skin biopsy should be
recommended in any pregnant woman with a suspicious or
changing pigmented lesion (fig 6⇓).
Malignant melanoma
Malignant melanoma represents the fourth commonest cancer
in pregnancy, accounting for about 8% of all malignant tumours
arising in gestation. Several studies have shown similar survival
rates between pregnant and non-pregnant women, although
debate continues.40-42 Close follow-up of pigmented lesions
during pregnancy with clinical and dermoscopic documentation
is vital. In more advanced cases of melanoma, transplacental
metastatic spread can occur, therefore the placenta should be
examined closely after delivery to exclude metastases.43 44
What drugs can be used systemically in
pregnancy?
Many commonly used dermatology drugs are safe in pregnancy,
but the potential benefit of any drug should be carefully balanced
against possible risks to the mother and fetus. When doubt exists
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over the safety of any drugs during pregnancy and lactation,
reliable sources should be consulted.16 17
A multinational survey indicated that 86% of women take an
average of 2.9 drugs during pregnancy.45 Drugs have the greatest
potential to cause harm in the first trimester, during the period
of organogenesis. Women may be unaware that they are
pregnant at this stage, so careful counselling and prescribing is
necessary in those of childbearing age. Equally, much harm can
result if drugs necessary for disease control are omitted or
discontinued precipitously, and as such an individual risk-benefit
analysis is essential. Topical and oral retinoids (isotretinoin and
acitretin),19 methotrexate, and mycophenolate mofetil are
teratogenic and should be avoided in women planning
pregnancy. They should not be given to young women of
childbearing age without specific advice to avoid pregnancy.46 47
Oral steroids should be used under specialist supervision. The
table⇓ lists the potential adverse effects of commonly used
systemic drugs to treat dermatological conditions. A recent
review of this topic was published in the American literature,
highlighting the safety of dermatological drugs in pregnancy
and lactation.24
What are the recommendations for use of
topical corticosteroids?
Recent evidence based guidelines have been published on the
use of topical corticosteroids in pregnancy.48 This systematic
review showed no association between maternal use of topical
steroids and orofacial cleft, preterm delivery, or fetal death.
However there was a significant association between fetal
growth restriction and maternal use of potent or ultrapotent
topical corticosteroids. Analysis of these data in a more recent
study49 showed that the risk of a low birthweight infant was
significantly increased in women where the dispensed amount
of potent or very potent topical corticosteroid exceeded 300 g
during the whole pregnancy (P=0.02). By contrast, the risk of
growth restriction was not increased with the use of less than
200 g of topical corticosteroid. Thus, guidance when prescribing
topical corticosteroids either in pregnancy or in women of
potential childbearing age should be to use the mildest effective
formulation required for clinical improvement. If a potent topical
corticosteroid is required to treat a more severe inflammatory
dermatosis in pregnancy, then the dose prescribed should be
kept to a minimum (<200 g during the entire pregnancy) and
fetal growth should be monitored closely (box 4).
We thank Martin Black for his contribution to the understanding of the
pregnancy dermatoses and for his support and encouragement to the
authors.
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Competing interests: We have read and understood the BMJ Group
policy on declaration of interests and declare the following interests:
none.
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Provenance and peer review: Commissioned; externally peer reviewed.
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Patient consent: Obtained.
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Yang YW, Chen CS, Chen YH, Lin HC. Psoriasis and pregnancy outcomes: a nationwide
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Briggs G, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation—a reference guide
to foetal and neonatal risk. 9th ed. Lippincott, Williams and Wilkins, 2011.
Schaefer C, Peters P, Miller R. Drugs during pregnancy and lactation. 2nd ed. Elsevier,
2007.
Bozdag K, Ozturk S, Ermete M. A case of recurrent impetigo herpetiformis treated with
systemic corticosteroids and narrowband UVB. Cutan Ocul Toxicol 2012;31:67-9.
Lipson AH, Collins F, Webster WS. Multiple congenital defects associated with maternal
use of topical tretinoin. Lancet 1993;341:1352-3.
Kallen BA, Otterblad Olausson P. Maternal drug use in early pregnancy and infant
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Kallen BA, Otterblad Olausson P, Danielsson BR. Is erythromycin therapy teratogenic in
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Zeichner JA. Narrow band UV-B phototherapy for the treatment of acne vulgaris during
pregnancy. Arch Dermatol 2011;147:537-9.
Drago F, Broccolo F, Zaccaria E, Malnati M, Cocuzza C, Lusso P, et al. Pregnancy
outcome in patients with pityriasis rosea. J Am Acad Dermatol 2008;58:S78-83.
Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and
lactation. J Am Acad Dermatol 2014;70:401-14 (part I) and 417-26 (part II).
British Medical Association, Royal Pharmaceutical Society of Great Britain. Antihistamines
in pregnancy. British national formulary. BMA, RPS, 2014:3.4.1. (No 67).
Acosta KA, Haver MC, Kelly B. Etiology and therapeutic management of erythema
nodosum during pregnancy: an update. Am J Clin Dermatol 2013;14:215-22.
Harger JH, Ernest JM, Thurnau GR, Moawad A, Thom E, Landon MB, et al. Frequency
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Box 4 Topical corticosteroid potency classes
• Mild: 1% hydrocortisone
• Moderate: betamethasone valerate 0.025% (Betnovate-RD) and clobetasone butyrate 0.05% (Eumovate), Trimovate, Daktacort
• Potent: betamethasone valerate 0.1% (Betnovate, hydrocortisone butyrate 0.1% (Locoid), mometasone furoate 0.1% (Elocon, Fucibet,
Lotriderm)
• Ultrapotent: clobetasol propionate 0.05% (Dermovate)
The information in this box is from box 3 in BMJ 2012;345:e4770
Questions for future research
What are the causes and pathogenesis of polymorphic eruption of pregnancy?
What causes the high prevalence of atopic eruption of pregnancy and is this partly due to the increasing prevalence of atopic eczema?
Do melanomas behave differently during pregnancy and, if so, why?
Are biologicals safe for the treatment of psoriasis in pregnancy?
Tips for non-specialists
Consider referral for skin biopsy where diagnosis is unclear (and request histopathology and direct immunofluorescence)
Mild to moderate topical corticosteroids can be used in the management of several common dermatoses in pregnancy
Avoid using potent topical corticosteroids as they may affect fetal growth
Aqueous cream with 1-2% menthol can be effective in reducing pruritus
Systemic antihistamines can be a useful adjunct to treatment
Emollients and bath emollients are useful to reduce itch in the pruritic dermatoses of pregnancy
Many women are anxious about the safety of treatments and potential adverse effects on the fetus, so supplying patient information
leaflets and giving appropriate counselling can be helpful to reassure, educate, and improve compliance
Additional educational resources
Resources for patients
British Association of Dermatologists (www.bad.org.uk)—patient information leaflets on pemphigoid gestationis and polymorphic eruption
of pregnancy
EADV Task Force for Skin Disease in Pregnancy (www.eadv.org)—Patient Corner—leaflets on several pregnancy related skin problems
DermNetNZ (www.DermNetNZ)—discusses acne, psoriasis, polymorphic eruption of pregnancy, and skin problems in pregnancy
DermNetNZ. Skin problems in pregnancy (www.dermnetnz.org/site-age-specific/pregnancy.html)—information on specific dermatoses
of pregnancy
National Childbirth Trust (www.nct.org.uk)—provides information on pregnancy, birth, parenting, breast feeding, postnatal services,
courses, and local events. It also has a helpline for practical and emotional support in all areas of pregnancy, birt,h and early parenthood,
including help with feeding
Royal College of Obstetricians and Gynaecologists (www.rcog.org.uk)—guidelines on management of intrahepatic cholestasis of
pregnancy
46
47
48
Zip C. A practical guide to dermatological drug use in pregnancy. Skin Therapy Lett
2006;11:1-4.
Anderka MT, Lin AE, Abuelo DN, Mitchell AA, Rasmussen SA. Reviewing the evidence
for mycophenolate mofetil as a new teratogen: case report and review of the literature.
Am J Med Genet Part A 2009;149A:1241-8.
Chi CC, Kirtschig G, Aberer W, Gabbud J-P, Lipozencic J, Karpati S, et al. Evidence-based
(S3) guideline on topical corticosteroids in pregnancy. Br J Dermatol 2011;165:943-52.
For personal use only: See rights and reprints http://www.bmj.com/permissions
49
Chi CC, Wang S-H, Mayon-White R, Wojnarowska F. Pregnancy outcomes after maternal
exposure to topical corticosteroids. A UK population-based cohort study. JAMA Dermatol
2013;149:1274-80.
Cite this as: BMJ 2014;348:g3489
© BMJ Publishing Group Ltd 2014
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CLINICAL REVIEW
Table
Table 1| Safety of commonly used drugs for dermatological conditions in pregnancy
Safety of drugs
Adverse effects
Unsafe:
Isotretinoin, acitretin
Teratogenic: face, central nervous system defects
Methotrexate
Teratogenic: fetal death (folate antagonist)
Cyclophosphamide
Teratogenic
Mycophenolate mofetil
Teratogenic: congenital malformations, especially ear
Rituximab
Teratogenic: potential fetal B cell depletion
Trimethoprim
Teratogenic in animal studies (folate antagonist)
Safe:
Penicillins and cephalosporins
None known
Azithromycin
None known
Aciclovir
None known
Chlorpheniramine
Sedation of infant in late third trimester
Cetirizine, loratadine
None known
Can be used (under specialist guidance)*:
Prednisolone
Risk of maternal diabetes and hypertension
Azathioprine
Risk of bone marrow suppression
Ciclosporin
Hypertension
Anti-tumour necrosis factor drugs (adalimumab, etanercept, infliximab) Avoid live vaccinations (for example, BCG) in infant for
six months
*When benefits outweigh risk.
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Figures
Fig 1 Polymorphic eruption of pregnancy on abdomen and upper chest of woman with triplet pregnancy at 34 weeks’
gestation and at four weeks after delivery following treatment with prednisolone
Fig 2 Diffuse erythema and sparing of umbilical region in woman with polymorphic eruption of pregnancy
Fig 3 Algorithm to help distinguish various pruritic dermatoses in pregnancy
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CLINICAL REVIEW
Fig 4 Herpes zoster infection on lower trunk presenting in pregnancy (36 weeks’ gestation) showing intact vesicles and an
excoriated patch of skin secondary to scratching as affected area of skin resolves
Fig 5 Subacute cutaneous lupus erythematosus of the lower leg during pregnancy
Fig 6 Atypical pigmented lesion on upper arm in pregnancy, suspicious of melanoma. On excision this was confirmed as
a blue naevus arising in a compound naevus
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