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DOI 10.1007/s40257-013-0041-9
THERAPY IN PRACTICE
Abstract Acne vulgaris is a common condition in adolescence and also for many women of childbearing age.
The management of acne in pregnancy is complicated by
the lack of clinical studies and pharmacokinetic data in
this patient population and safety concerns regarding
retinoid use in pregnancy. Of primary concern to both
patients and clinicians is the safety profile of medications
used during pregnancy. This review seeks to clarify what
management options are available to treat acne during
pregnancy and what data are available to guide decision
making. Topical treatments are considered the safest
option during pregnancy. They have the best safety profile
and minimize the levels of systemic absorption, and
therefore the least risk of fetal exposure. If these are
applied properly with a strong emphasis on adherence,
excellent results can be achieved.
1 Introduction
1.1 Background
Acne vulgaris is an extremely common condition in the
adolescent population, with 1520 % of young people
having moderate to severe disease [1, 2]. This tends to
settle in adulthood but there is a group of women who
continue to have ongoing acne or develop acne for the first
F. M. Meredith
Department of Dermatology, Aberdeen Royal Infirmary,
Foresterhill, Aberdeen AB25 2ZN, UK
A. D. Ormerod (&)
Division of Applied Medicine, University of Aberdeen,
Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK
e-mail: a.d.ormerod@abdn.ac.uk
time when older [3]. One German study found that acne
persisted into the 20s and 30s in around 64 % and 43 % of
individuals, respectively [4]. A British study found 12 % of
women had facial acne that appeared to persist into middle
age [5].
In women with both new and pre-existing acne, the
management of the condition during pregnancy can be
particularly challenging as there are limited therapeutic
options available to them. Owing to the hazards associated
with clinical research in a pregnant population, no trials of
acne treatment have been published in this patient group.
This means that relevant safety data have been extrapolated
from the use of medications for other reasons. The available evidence is mainly restricted to observational studies
and often with small samples sizes. There are pregnancyexposure registries that collect data on the use of certain
medications in pregnancy. However, there are no relevant
registries for acne treatments [6].
Acne severity can vary significantly, from mild
comedonal disease to severe, scarring, inflammatory
lesions that can be accompanied by systemic symptoms.
Treatment decisions during pregnancy will inevitably be
influenced by the severity of the acne balanced against the
safety profile of proposed treatments. In addition, as
approximately half of the six million pregnancies in the
USA each year are unplanned, many women will be
exposed to drugs before they know they are pregnant [7]. It
is also important to note the stage of pregnancy at which
the exposure occurs as this will alter the risk substantially
depending on the medication.
Many guidelines have been created for the management
of acne [8, 9]. The aim of this review is to review the
published evidence to identify effective treatments for acne
and to then assess the safety of using these therapies in
pregnancy.
352
F. M. Meredith, A. D. Ormerod
Description
Controlled studies show no risk: Adequate, well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in
any trimester of pregnancy
No evidence of risk in humans: Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal
abnormalities despite adverse findings in animals,
or
In the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote, but remains a
possibility
Risk cannot be ruled out: Adequate, well-controlled human studies are lacking, and animal studies have shown a risk to the fetus or
are lacking as well
Positive evidence of risk: Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless,
potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a
life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective
Contraindicated in pregnancy: Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive
evidence of fetal abnormalities or a risk that clearly outweighs any possible benefit to the patient
There is a chance of fetal harm if the drug is administered during pregnancy, but the potential benefits may outweigh the potential risk
2 Topical Preparations
Topical agents are the mainstay of treatment for mild to
moderate acne [9]. Some topical medications do not have a
pregnancy category as systemic absorption is generally
considered to be minimal, unless use is extensive, intensive, or prolonged [19]. More recently, many combination
353
Category
Oral medications
Topical medications
Erythromycin, clindamycin
Spironolactone, trimethoprim,
corticosteroids
Tetracycline, doxycycline,
minocycline
Isotretinoin
Tazarotene
Table 3 Summary of case reports of birth defects associated with topical retinoid use
Case report
Duration of use
Quantity
used
Gestation at
delivery
Camera and
Pregliasco [23]
Not stated
41 weeks
Not stated
Not stated
Supraumbilical hernia,
diaphragmatic hemia, pericardial
defect, dextroposition of the
heart, right upper limb defect
Not stated
41 weeks
NavarreBelhassen et al.
[26]
Not stated
40 weeks
0.3 mg
daily
Termination
at 22 weeks
354
F. M. Meredith, A. D. Ormerod
3 Oral Preparations
3.1 Oral Antibiotics
Outside of pregnancy, oral antibiotics are commonly prescribed as a second-line therapy for acne. The most commonly prescribed are tetracyclines: doxycycline,
oxytetracycline, lymecycline (not available in the USA),
minocycline, and tetracycline.
There has been increasing concern about the risk of
antibiotic resistance [38] and the use of oral and topical
antibiotics concurrently (unless chemically similar agents).
Antibiotic resistance can develop within 12 weeks [39] and
is thought to impede therapeutic response.
Penicillins, erythromycin, and cephalosporins are
thought to have the best safety profile in pregnancy [40],
with erythromycin the oral antibiotic most commonly used
for acne in pregnancy.
3.1.1 Tetracyclines
Tetracyclines should not be used during pregnancy, as use
in the second and third trimester can cause discoloration of
teeth and bones. Fatty liver of pregnancy in the third trimester has also been attributed to tetracycline ingestion
[41]. There is no firm evidence that first-trimester use is
355
3.1.5 Azithromycin
3.5 Oral Corticosteroids
Azithromycin is an azalide antibiotic derived from erythromycin [45]. It has been used in the treatment of acne and has
been found to be as effective as doxycycline [49]. Animal
studies have shown that azithromycin crosses the placenta but
there are no adequate and well-controlled studies in pregnant
women. As such, the UK Medicines and Healthcare products
Regulatory Agency (MHRA) have recommended it only be
used if adequate alternatives are not available [50].
3.2 Anti-Androgens
Spironolactone is not licensed for use in acne, although it
has been found to decrease sebum secretion [51] and
356
F. M. Meredith, A. D. Ormerod
5 Conclusions
There are a limited number of options available for the safe
management of acne in pregnancy. Isotretinoin, which is
the mainstay of treatment for severe and nodulocystic acne,
is absolutely contraindicated in pregnancy.
The options for oral antibiotics are also limited with
erythromycin being the safest option available. Unfortunately, this is also the least effective oral antibiotic to be
used and evidence supporting its efficacy in acne is poor
[9].
Where possible, acne treatments in pregnancy should be
limited to topical treatments [41]. They have the best safety
profile and minimize the levels of systemic absorption, and
therefore have the least risk of fetal exposure. If these are
applied properly with a strong emphasis on adherence,
excellent results can be achieved. Previous reviews have
recommended topical erythromycin, clindamycin, and
benzoyl peroxide as the agents of choice [36, 41, 66, 67].
The purpose of this review is not to create a guideline
but to collate the available data on acne therapies in
pregnancy to help decision making for patients and
clinicians. To this end, we have tried to summarize our
findings in Table 4 and rank therapies based on their
safety profile. With more severe cases of acne, topical
treatments still have an important role in improving
symptoms and minimizing any ongoing scarring. These
may be safely supported by physical treatments including light-based therapies but not photodynamic therapy.
When systemic therapy is required, discussion between
the physician and patient is required to explain potential
risks, benefits, and paucity of evidence of the available
options including oral erythromycin, oral corticosteroids, and zinc as possible choices to augment topical
therapy.
Category
Medication
Contraindicated
6 Useful Resources
357
FDA http://www.fda.gov/ScienceResearch/SpecialTopi
cs/WomensHealthResearch/ucm134848.htm Information aimed at helping pregnant women make informed
choices about medicine use during their pregnancy.
The Organization of Teratology Information Specialists
(ORTIS) http://www.otispregnancy.org provides education and support to teratology services in North
America. It also provides many links to relevant government and professional bodies.
UK Teratology Information Service (UKTIS) http://
www.uktis.org collects data on all aspects of the toxicity of drugs and chemicals in pregnancy and has
helpful summary sheets available online for many
topical and oral medications.
The UK MHRA http://www.mhra.gov.uk is the government organization that collects, monitors, and reports
safety data on medications in the UK. They produce
drug analysis prints of suspected adverse drug reactions
and side effects that have been reported to them.
The electronic Medicines Compendium (eMC) http://
www.medicines.org.uk is a useful resource that contains patient information leaflets and summaries of
product characteristics
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