Review CMAJ

Management of acne

John Kraft MD, Anatoli Freiman MD

A
cne vulgaris has a substantial impact on a patients Key points
quality of life, affecting both self-esteem and psychoso-
cial development.1 Patients and physicians are faced Effective therapies for acne target one or more pathways
in the pathogenesis of acne, and combination therapy
with many over-the-counter and prescription acne treatments, gives better results than monotherapy.
and choosing the most effective therapy can be confusing. Topical therapies are the standard of care for mild to
In this article, we outline a practical approach to managing moderate acne.
acne. We focus on the assessment of acne, use of topical Systemic therapies are usually reserved for moderate or
treatments and the role of systemic therapy in treating acne. severe acne, with a response to oral antibiotics taking up
Acne is an inflammatory disorder of pilosebaceous units to six weeks.
and is prevalent in adolescence. The characteristic lesions are Hormonal therapies provide effective second-line
open (black) and closed (white) comedones, inflammatory treatment in women with acne, regardless of the presence
or absence of androgen excess.
papules, pustules, nodules and cysts, which may lead to scar-
ring and pigmentary changes (Figures 1 to 4). The pathogene-
sis of acne is multifactorial and includes abnormal follicular
keratinization, increased production of sebum secondary to ing and follicle-stimulating hormone levels.5 Pelvic ultra-
hyperandrogenism, proliferation of Propionibacterium acnes sonography may show the presence of polycystic ovaries.5 In
and inflammation.2,3 prepubertal children with acne, signs of hyperandrogenism
Lesions occur primarily on the face, neck, upper back and include early-onset accelerated growth, pubic or axillary hair,
chest.4 When assessing the severity of the acne, one needs to body odour, genital maturation and advanced bone age.
consider the distribution (back, chest, upper arms), type and Treatment for acne vulgaris should aim to reduce severity
number of lesions (comedones, papules, pustules, nodules) and and recurrences of skin lesions as well as to improve appear-
the presence or absence of scarring (Table 1).2,3 ance. The approach depends on the severity of the acne, the
Different variants of acne exist, including acne conglobata, treatment preferences and age of the patient, and adherence and
acne fulminans, acne mechanica, excoriated acne, chloracne, response to previous therapy (Table 2).3,6 Various acne treat-
drug-induced acne (e.g., from anabolic steroids, corticos- ments target different steps in the pathogenesis of acne, from
teroids, isoniazid, lithium, phenytoin), neonatal and infantile counteracting androgens and decreasing sebum production to
acne, and occupational acne. These variations have a similar preventing follicular occlusion, reducing P. acnes proliferation
clinical and histologic appearance to acne vulgaris, but they and decreasing inflammation.
are distinguishable by clinical setting, severity and associated Many research studies on acne therapies are small trials
symptoms. The common differential diagnosis of acne comparing the active drug with placebo or larger studies com-
includes folliculitis, keratosis pilaris, perioral dermatitis, seb- paring different formulations of the same drug.
orrheic dermatitis and rosacea.
How well do topical treatments work?
Is there an underlying cause?
Topical therapy is the standard of care for mild to moderate
The diagnosis of acne vulgaris is primarily clinical.4 History acne.3 Retinoids and antimicrobials such as benzoyl peroxide
and physical examination can help determine if there is an and antibiotics are the mainstay of topical acne therapy. Such
underlying cause of the acne, such as an exacerbating medica- treatments are active at application sites, and they can prevent
tion or endocrinologic abnormality causing hyperandro- new lesions.4 The main side effect is local irritation. Gels,
genism (e.g., polycystic ovarian syndrome). Other dermato- pledgets (medication-soaked pads), washes and solutions tend
logic manifestations of androgen excess include seborrhea, to be drying and are helpful for oily skin. Lotions, creams and
hirsutism and androgenetic alopecia. Endocrinologic testing is ointments are beneficial for dry, easily irritated skin. Most top-
DOI:10.1503/cmaj.090374

not ordered routinely for women with regular menstrual ical preparations require at least six to eight weeks before an
cycles.2,3 Older women, especially those with new-onset acne improvement is seen; they may be used for years as needed.6
and other signs of androgen excess (e.g., hirsutism, andro-
genic alopecia, menstrual irregularities, infertility), should be
tested for androgen excess with measurements of total and From the Division of Dermatology, University of Toronto, Toronto, Ont.

free serum testosterone, dihydroepiandrosterone, and luteiniz- CMAJ 2011. DOI:10.1503/cmaj.090374

E430 CMAJ APRIL 19, 2011 183(7)

2011 Canadian Medical Association or its licensors
 Review

Retinoids Antimicrobials
The main target of acne treatment is the microcomedone. Topi- Topical antimicrobials, including benzoyl peroxide and antibi-
cal retinoid therapy acts on follicular keratinocytes to prevent otics, are effective in treating inflammatory disease.3,4 Benzoyl
excessive cornification and follicular blockage.4 It may also peroxide is a bactericidal agent that prevents the resistance of
reduce the release of proinflammatory cytokines. Such therapy P. acnes to antibiotic therapy9 and has moderate comedolytic
decreases the number of comedones and inflammatory lesions and anti-inflammatory properties. It is available in various top-
by 40% to 70%.2 The most common side effect is irritation with ical preparations, ranging in strength from 2.5% to 10.0%.
erythema and scaling. Patients should be instructed to apply Any strength can be used initially, although it may be more
very small amounts initially. Optimal response occurs after 12 prudent to start with a lower concentration; stronger prepara-
weeks.7 Continuous maintenance therapy can prevent flares.3 tions are more irritating and not necessarily more effective.10
The most commonly available topical retinoids are Benzoyl peroxide kills P. acnes by releasing oxygen within
tretinoin, adapalene and tazarotene. A meta-analysis of five the follicle. It can be fast-acting, with a response as early as
multicentre randomized investigator-blind trials involving five days.4 The main drawback is that it is a potent bleaching
900 patients showed adapalene 0.1% gel to be as effective as,
but less irritating than, tretinoin 0.025% gel.8 Different con-
centrations of retinoids affect tolerability. One commonly
used approach is to start with the lowest concentration and
increase as tolerated.

Figure 3: Grade III (moderately severe) acne showing numer-

Figure 1: Grade I (mild) acne showing comedones with few ous large painful nodules and pustules as well as some
inflammatory papules and pustules. inflamed nodules.

Figure 4: Grade IV (severe) acne showing many large inflamed

Figure 2: Grade II (moderate) acne showing papules and pustules. nodules and pustules as well as scarring.

CMAJ APRIL 19, 2011 183(7) E431

Review

agent.2 Patients should be warned that fabrics that come in zinc, resorcinol, sulfur and aluminum chloride is also either
contact with benzoyl peroxide, including towels, bed sheets limited or negative.
and clothing, may be bleached. There is no clear evidence that acne vulgaris is related to
Topical erythromycin and clindamycin are generally well- poor hygiene or that frequent face washing lessens acne.
tolerated and have been shown to reduce inflammatory lesions Patients should be instructed to wash their face gently with
by 46% to 70% in several randomized controlled trials.2 warm water and mild soap twice daily; rough scrubbing can
Monotherapy with topical antibiotics should not be used rou- cause new lesions because of follicular rupture. The only
tinely beause P. acnes may become resistant within one month antibacterial soaps that may be effective are those containing
after daily treatment has begun.6 Some argue that this resis- benzoyl peroxide.19
tance is not relevant because the antibiotics (e.g., clindamycin, Patients should ensure that their facial products, includ-
tetracyclines, erythromycin) also have intrinsic anti-inflamma- ing sunscreens, are noncomedogenic. They should also
tory and antimicrobial effects.11 However, antibiotic-resistant avoid oil-based makeup. Some topical acne products contain
Staphylococcus epidermidis and Staphylococcus aureus may a sunscreen.
also develop with monotherapy; resistance can be avoided
when a topical antibiotic is combined with benzoyl peroxide.12 When should systemic therapy be started?
Combination therapy Patients with mild acne can be treated with topical therapies;
Combination therapy, for example with retinoids and antibi- however, those with moderate to severe acne will require sys-
otics, is more effective than either agent used alone.13 However, temic therapy. Oral antibiotic treatment, hormonal therapies
the agents should be applied at separate times, unless they are and isotreretinoin are the mainstay systemic therapies for
known to be compatible.3 Benzoyl peroxide may oxidize a acne.
retinoid such as tretinoin if it is applied simultaneously.14 A 12-
week randomized controlled trial involving 249 patients with Antibiotics
mild to moderate acne showed treatment with adapalene gel When topical agents are insufficient or not tolerated, or in
0.1% and clindamycin 1.0% to be superior to that with clin- cases of moderate to severe acne, especially when the chest,
damycin 1.0% used alone.15 If inflammatory lesions are present, back and shoulders are involved, systemic antibiotics are
topical antibiotics containing benzoyl peroxide should be com- often considered the next line of treatment (Table 3).20,21 How-
bined with a topical retinoid (e.g., topical antibiotic with ben- ever, regular use of a combination of topical antibiotics and
zoyl peroxide in the morning and retinoid at night). A review of benzoyl peroxide may be similarly effective, as shown in a
three clinical studies with 1259 patients showed that a combi- randomized controlled trial of five antimicrobial regimens.22
nation of clindamycin 1% and benzoyl peroxide 5% was more Response to oral antibiotics is usually seen after at least six
effective than either drug used alone in reducing lesions and weeks of therapy.4 If control is maintained for several months,
suppressing P. acnes.16 the antibiotic may be discontinued gradually and only the top-
ical therapy continued. Systemic antibiotics should not be
Over-the-counter therapy used to treat mild acne because of the risk of increasing resis-
Before seeing a physician, patients frequently use over-the- tance.23,24 The additional use of nonantibiotic topical agents in
counter therapies for their acne. Such treatments may be more combination with oral antibiotics should be considered.4 Topi-
accessible, cosmetically elegant, less expensive and less irri- cal retinoids with oral antibiotics may give a faster response
tating than prescription therapies.17 However, there is insuffi- and be more effective than either drug used alone.3
cient evidence to evaluate and compare the efficacy of over- Treatment with tetracyclines and erythromycin reduces P.
the-counter formulations.2 acnes within the follicles, thereby inhibiting production of
The most popular over-the-counter products, such as Proactiv, bacterial-induced inflammatory cytokines.25 These agents also
contain benzoyl peroxide but at lower concentrations than most have inherent anti-inflammatory effects, such as suppressing
prescription-strength products. Proactiv, a system of cleansing
products in which benzoyl peroxide 2.5% is the active ingredi-
ent, is claimed to enhance compliance by providing a cosmeti- Table 1: Grading severity of acne2,3
cally elegant product that also minimizes irritation. The makers
Grade Severity Clinical findings
of Proactiv also market Gentle Formula, which replaces benzoyl
peroxide with salicylic acid for people with allergy or intoler- I Mild Open and closed comedones
ance. There have been few studies assessing the efficacy of the with few inflammatory papules
Proactiv system. In one open-label study of 23 patients with mild and pustules
to moderate acne, inflammatory lesions were reduced by 39% in II Moderate Papules and pustules, mainly on
patients using a combination of butenifine (an allylamine) and face
benzoyl peroxide compared with 34% in those using Proactiv.18 III Moderately Numerous papules and pustules,
severe and occasional inflamed nodules,
Salicylic acid 2% wash is moderately effective but less
also on chest and back
potent than a topical retinoid in acne therapy. Although it has
IV Severe Many large, painful nodules and
been used for many years, well-designed trials of its safety pustules
and efficacy are lacking. The evidence for the use of topical

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 Review

leukocyte chemotaxis and bacterial lipase activity. Minocy- Clinical trials have shown that estrogen-containing oral
cline and doxycycline also inhibit cytokines and matrix met- contraceptives can be helpful;3133 the various formulations are
alloproteinases that are thought to promote inflammation and thought to decrease levels of free testosterone by increasing
tissue breakdown.26 Although P. acnes has a resistance rate to sex-hormone-binding globulin and are considered equally
tetracyclines of 20% to 60%, it is uncertain if this is signifi- effective. The choice of combined oral contraceptive should
cant in the treatment of acne.27,28 be based on a patients tolerance and potential side effects. It is
Oral antibiotics have been shown to be effective in reducing not known whether other estrogen-containing contraceptives
the number of inflammatory lesions (52% to 67% reduction), (e.g., vaginal rings, transdermal patches) are effective. Contra-
but this is based on limited evidence.3 Higher doses can be tried ceptives containing only progesterone may worsen acne.4
if a patient seeks better control. Doxycycline and minocycline A randomized controlled trial with 128 women showed a
are considered more effective than tetracycline.29 Erythromycin reduction in acne lesions of 63% with 35 g ethinylestradiol
is reserved for patients in whom tetracyclines are contraindi- and 3 mg drospirenone and a 59% reduction with 35 g
cated (e.g., pregnant women and children under nine years of ethinylestradiol and 2 mg cyproterone acetate.34 Antiandrogen
age), although the development of resistance to erythromycin is therapy is usually needed for at least three to six months to see
more common than with the other antibiotics.23 significant improvement.
The oral antiandrogen spironolactone can be added if oral
Hormonal therapies contraceptives are not effective.3 Spironolactone is a 5-reduc-
Hormonal agents provide effective second-line treatment in tase inhibitor when administered at higher doses.35 Spironolac-
women with acne regardless of underlying hormonal abnor- tone, used alone or as an adjunct at doses of 50200 mg/d, has
malities.30 It is not necessary to demonstrate androgen excess been shown to be effective in improving acne, but this is based
to achieve a benefit from antiandrogen therapy. Clinical on limited evidence.2 However, patients should be warned about
observation suggests that deep-seated nodules on the lower possible side effects, including hyperkalemia, menstrual irregu-
face and neck are especially responsive to hormonal therapy.6 larities and feminization of a male fetus. Antiandrogen therapy
alone may be successful, but in less than
3,6
half of women;36 the acne may recur when
Table 2: Approach to therapy for acne vulgaris
it is discontinued. Combination therapy
Treatment options
with topical agents or oral antibiotics pro-
Severity; vides substantially more benefit.37
clinical findings First line Second line
Isotretinoin
Mild
Isotretinoin affects all causative mecha-
Comedonal Topical retinoid Alternative topical retinoid
nisms of acne it changes abnormal fol-
Salicylic acid washes
licular keratinization, decreases sebum pro-
Papular/pustular Topical retinoid Alternative topical retinoid duction by 70%, decreases P. acnes
Topical antimicrobial plus alternative topical
antimicrobial
colonization and is anti-inflammatory.38
benzoyl peroxide Indications for isotretinoin include scarring
Salicylic acid washes
clindamycin disease, severe nodulocystic acne and less
erythromycin than 50% improvement with oral antibi-
Combination products otics or hormonal therapies after four
Moderate months.38 Isotretinoin therapy must be
Papular/pustular Oral antibiotics Alternative oral antibiotic
monitored carefully because adverse
effects include potent teratogenicity,
tetracyclines Alternative topical retinoid
hypertriglyceridemia and pancreatitis,
erythromycin Benzoyl peroxide
hepatoxicity, blood dyscrasias, hyperosto-
trimethoprim
sulfamethoxazole
sis, premature epiphyseal closure and night
blindness. An association with severe skin
Topical retinoid
benzoyl peroxide reactions, such as erythema multiforme,
StevensJohnson syndrome and toxic epi-
Nodular Oral antibiotic Oral isotretinoin
dermal necrolysis, has been reported.39
Topical retinoid Alternative oral antibiotic
benzoyl peroxide Although a causal relationship has not
Alternative topical retinoid
been shown, patients must be warned
Benzoyl peroxide about depression, suicidal thoughts and
Severe Oral isotretinoin High-dose oral antibiotic psychosis, and monitored closely.40
Topical retinoid (also Before a patient starts oral isotretinoin
maintenance therapy) therapy, baseline blood work is recom-
Benzoyl peroxide mended.38 This testing includes serum
Note: In women with acne, oral contraceptives or androgen receptor blockers (e.g., spironolactone)
blood lipid measurements, complete
may be used in addition to the above treatment options. blood count and differential, liver

CMAJ APRIL 19, 2011 183(7) E433

Review

enzyme tests and blood glucose levels (and a pregnancy test ing acne.3 One clinical trial showed that topical tea tree oil
for women of child-bearing age).41 These tests should be was effective but had a slower onset of action than traditional
repeated at monthly intervals during treatment. In women of topical agents.43 The Cochrane Collaboration is undertaking a
childbearing age, two forms of birth control should be used systematic review of the effects of treatments in the manage-
during and for one month after therapy, unless the patient has ment of acne that are currently considered complementary or
had a hysterectomy or is sexually abstinent.41 alternative.
Cutaneous side effects of isotretinoin include dry eyes,
nose and lips, and dermatitis. Patients should use artificial What physical treatments are available?
tears, and generous amounts of moisturizer on the nose, lips
and skin. Physical treatments for acne include comedone extraction,
According to a 10-year follow-up study of 88 patients, chemical peels and microdermabrasion, intralesion cortico-
those who had received a cumulative dose of isotreretinoin steroid injection for acne cysts, and high-intensity, narrow-
120150 mg/kg had a substantially lower rate of recurrence band blue light photodynamic therapy, as well as injectable
(30%) than those who received less than 120 mg/kg (82%).42 fillers and laser resurfacing for acne scarring. However, there
An additional course can be prescribed for patients in whom is limited evidence in peer-reviewed literature to support such
the acne recurs after isotretinoin is discontinued. treatments.3,44 The results of small pilot studies have supported
the use of chemical peels,45 and some evidence suggests that
What about alternative therapies? corticosteroid injections are helpful for treating large inflam-
matory lesions.46
Herbal therapies such as tea tree oil, and topical and oral
ayurvedic compounds seem to be well tolerated; however,
there are limited data about their efficacy and safety in treat-
How should children and pregnant women
be treated?
Table 3: Oral antibiotic therapy for acne vulgaris20,21 The treatment of acne in children is similar to that in adults.
Because topical therapies may be more irritating in children, ini-
Antibiotic, dose Notes
tiation with low concentrations is preferred. Systemic treatments
Tetracycline Inexpensive should be reserved for more extensive cases. Erythromycin is
250500 mg twice Contraindicated in pregnant women preferred over tetracyclines for children under nine years of age,
daily or in children under nine years of age because tetracyclines can affect growing cartilage and teeth.
Chelated by antacids and milk; to be Although treatment with isotretinoin has numerous poten-
taken on empty stomach tial minor side effects in patients of all ages, an uncommon
Minocycline Can be taken with food complication in young patients is premature epiphyseal clo-
50200 mg daily Contraindicated in pregnant women sure.38 This generally occurs when isotretinoin is administered
or in children under nine years of age in high doses, thus limiting long-term therapy.
Adverse reactions: dizziness, pigment Selecting appropriate treatment in pregnant women can be
changes, hepatitis, lupus-like challenging because many acne therapies are teratogenic; all
reactions
topical and especially oral retinoids should be avoided.38 Oral
Doxycycline Can be taken with food therapies such as tetracyclines and antiandrogens are also
100200 mg daily Acceptable for use in patients with contraindicated in pregnancy. Topical and oral treatment with
renal failure
erythromycin may be considered.
Contraindicated in pregnant women
or in children under nine years of age
Whats new in treating acne?
Adverse reactions: gastrointestinal
upset; phototoxicity (greatest of all
tetracyclines) Trials are being conducted with currently available therapies,
Erythromycin Safe in pregnant women and
in different strengths and combinations. Combining an ally-
500 mg twice daily children lamine antifungal agent with benzoyl peroxide may prove to
Adverse reaction: may cause enhance the effectiveness of benzoyl peroxide in treating acne
gastrointestinal upset while preventing antibiotic resistance.18 Topical dapsone 5%
42% of patients may show resistance gel is a newer option for treating acne. A large multicentre
to Propionibacterium acnes18 randomized controlled trial in adolescents with acne found
Trimethoprim/ Useful in patients resistant to other that when the gel was applied twice daily on the affected
sulfamethoxazole antibiotics areas, 40% of the treatment group and 28% of the placebo
80/400 mg or Adverse reactions: 3%4% of group (p < 0.001) achieved the desired outcome at 12 weeks.47
160/800 mg four patients experience rash;21 risk of
times a day
The same trial and an additional study found that topical dap-
serious skin reactions, such as sone 5% gel is a safe treatment option in patients with a defi-
StevensJohnson syndrome
ciency in glucose-6-phosphate dehydrogenase.48
More studies are needed to resolve the long-standing con-

E434 CMAJ APRIL 19, 2011 183(7)

 Review

troversy about the role of diet and acne. As well, further direct 23. Eady EA, Cove JH, Holland KT, et al. Erythromycin resistant propionibacteria in
antibiotic treated acne patients: association with treatment failure. Br J Dermatol
treatment comparison and long-term trials are needed to deter- 1989;121:51-7.
mine the optimal sequence of treatment selection as well as to 24. Miller YW, Eady EA, Lacey RW, et al. Sequential antibiotic therapy for acne pro-
motes the carriage of resistant staphylococci on the skin of contacts. J Antimicrob
establish the effects on quality of life and long-term efficacy. Chemother 1996;38:829-37.
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This review was solicited and has been peer reviewed. ble factor of propionibacterium acnes: implications for chronic inflammatory acne.
Infect Immun 1995;63:3158-65.
Competing interests: None declared. 26. Golub LM, Lee HM, Ryan ME, et al. Tetracyclines inhibit connective tissue break-
down by multiple non-antimicrobial mechanisms. Adv Dent Res 1998;12:12-26.
27. Ross JI, Snelling AM, Carnegie E, et al. Antibiotic resistant acne: lessons from
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