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An update on the management of acne vulgaris

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An update on the management of acne vulgaris

This article was published in the following Dove Press journal:

Clinical, Cosmetic and Investigational Dermatology
10 June 2009
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Jonette Keri 1,2 Abstract: Acne vulgaris is a common skin disorder that can affect individuals from childhood
Michael Shiman 1 to adulthood, most often occurring in the teenage years. Acne can have a significant physical,
emotional, and social impact on an individual. Many different treatment options are available
1
Department of Dermatology
and Cutaneous Surgery, University for the treatment of acne vulgaris. Commonly used topical treatments include benzoyl peroxide,
of Miami Miller School of Medicine, antibiotics, sulfur and sodium sulfacetamide, azelaic acid, and retinoids. Systemic treatment
Miami, FL, USA; 2Dermatology Service,
Miami VA Hospital, FL, USA
is frequently used and includes the use of systemic antibiotics, oral contraceptives, antiandro-
gens, and retinoids. Other treatment modalities exist such as the use of superficial chemical
peels as well as using laser and light devices for the treatment of acne. With the multitude of
treatment options and the rapidly expanding newer technologies available to clinicians, it is
important to review and be aware of the current literature and studies regarding the treatment
of acne vulgaris.
Keywords: acne vulgaris, treatment, benzoyl peroxide, antibiotics, retinoids, lasers

Introduction
Acne is a common skin disorder affecting most individuals in the teenage years but
also affecting anyone from childhood to middle age. The treatment for acne dates back
to Egyptian times when sulfur was used, to recent times with new forms of treatment
with lasers and lights. Why treat acne? Many in the lay community feel that acne is
a rite of passage into adulthood and needs no treatment. However, dermatologists
can vouch for the physical and emotional scars of acne when left untreated. The
psychosocial implications can be huge with serious implications regarding the effect
on self-image and the quality of life, so that the impact of acne may be equivalent to
that of asthma or epilepsy.1 This review will concentrate on prescription-based treat-
ments. A good review of over-the-counter acne treatments can be found in a recent
review of these products.2

Benzoyl peroxide
Benzoyl peroxide (BP) has long been the mainstay of treatment for acne. It is available
Correspondence: Jonette Keri in a variety of over-the-counter and prescription formulations. These formulations
Department of Dermatology and may include a number of ingredients that differentiate one product from another. For
Cutaneous Surgery, University of Miami
School of Medicine, 1444 NW 9th Ave., example, BP may be combined with glycolic acid, urea, or placed into microspheres
Miami, FL 33136, USA for a more gentle delivery. It may be used as a wash or leave-on product that may
Tel +1 (305) 575-3167
Fax +1 (305) 575-3125
be formulated as a gel or cream. BP washes are easy to use and show efficacy in the
Email jkeri@med.miami.edu 30% to 40% range. Such washes are good for truncal acne, as the medication can be

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Dovepress © 2009 Keri and Shiman, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
Keri and Shiman Dovepress

dispersed by water while having a shower. Its comedolytic Understanding the cost and efficacy of different treatment
and antibacterial properties are quite useful in the treatment options is important in deciding which one to choose. A rand-
of acne. Antibacterial resistance does not appear to occur omized controlled trial studying the cost and efficacy of using
with BP, and BP combinations are well documented in BP and topical erythromycin in different regimen combina-
decreasing the number of resistant organisms to commonly tions concluded that BP as an exclusive treatment option
used antiacne antibiotics by effectively destroying micro- was the most cost-effective option, yet caused more local
organisms before resistance can develop.3 When giving irritation. In combination with erythromycin, there was less
long-term oral antibiotics, BP is an important adjuvant drug irritation. There was little difference whether erythromycin
to employ, as it reduces the number of antibiotic resistant and benzoyl peroxide were administered separately or as a
organisms. Concerns in the use of BP include irritation combined formulation, in terms of efficacy and irritation;
and contact sensitivity. It also has a bleaching property, so however, the drugs applied seperately were three times more
that when it is not removed completely, it can often bleach cost-effective.7
clothing and bedding.4 In addition, it can bleach the skin of
darker individuals and this must be discussed while initiat- Topical sulfur and sodium
ing therapy in the ethnic population. Recently, combination sulfacetamide
products have been highly successful in the treatment of Sulfur, used for acne since the time of Cleopatra, is useful
acne. Patients have enjoyed the ease of applying only one as a drying and antibacterial agent. It is available in washes,
product that can deliver both BP and the topical antibiotics, leave-on lotions, creams, foam formulations, and also as
erythromycin and clindamycin. In the future, BP may be prescription and non-prescription masks. Sulfur can be useful
compounded with other agents as well. In many cases, acne when treating patients who may also have rosacea and/or
treatment requires a combination therapy, as monotherapy seborrheic dermatitis, as these conditions can also respond
is often less successful.5 to this medication. Sodium sulfacetamide is often combined
with sulfur and has anti-inflammatory properties. When used
Topical antibiotics alone, it can also treat acne and is marketed for the sensitive
In addition to the combination products described above, skin acne patient.8
topical antibiotics alone can be useful in the treatment of
acne. Clindamycin and erythromycin work by inhibiting Topical azelaic acid
Propionibacterium acnes at the 50S ribosomal subunit where Azelaic acid is useful in the treatment of acne and the
they bind irreversibly to inhibit protein synthesis. P. acnes post-inflammatory pigment changes that often accompany it.
can thrive in an environment that combines sebum and Its mechanism of action is by inhibition of protein synthesis,
desquamated cells, where it converts sebum to free fatty acids, although the exact mechanism is unknown. Though patients
which then stimulate the body’s immune response. Topical often report a burning or stinging sensation with topical
antibiotics act against this organism, in addition to having application, this usually dissipates in a few (1–4) weeks.
anti-inflammatory properties, making these medications use- This medication can be used daily and increased to twice-
ful in the treatment of acne.6 Alone, these medications come daily dosing to allow for some tolerance to build. Azelaic
in the form of solutions, pledgets, lotions, gels, ointments, acid has shown to be effective in combination with other
and foams. They can be used in such combination products topical agents such as benzoyl peroxide, clindamycin gel,
but can also be used in conjunction with BP washes, when erythromycin gel, and tretinoin cream.9
leave-on BP is too irritating. Choosing the formulation of
the antibiotic is dependent on the patients’ lifestyle and skin Topical retinoids
type. Gels are better suited for oily skin, whereas, lotions and The topical retinoids used in the treatment of acne include
ointments work better on drier skin. For truncal use, foams adapalene, tretinoin, and tazarotene. They are comedolytic and
and specific delivery systems using long armed applicators, anti-inflammatory. Different formulations aid in decreasing
such as ClindaReach® (DUSA Pharmaceuticals, Wilmington, irritation, which is the main side-effect that hinders
MA, USA) offer the advantage of application to difficult- continued use of this class of drugs. Such medications
to-reach areas of the body. Topical antibiotics, when mixed have been formulated into microsponge delivery systems
with BP and systemic agents, make a good combination in (Retin-A Micro®; OrthoNeutrogena, Skillman, NJ, USA),
treating acne. combined with topical antibiotics and formulated to have

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Dovepress Update on the management of acne vulgaris

a more extended release, made into a stable formulation of Since then, antibiotics used to treat acne have come to include
both solubilized and crystalline tretinoin (Ziana®; Medicis doxycycline, minocycline, trimethoprim/sulfamethoxazole,
Pharmaceutical Corporation Scottsdale AZ, USA), and made amoxicillin, azithromycin, and cephalexin. As with the
into cream rather than gel forms (Differin®; Galderma Labo- development of novel formulations for topical acne medica-
ratories, Fort Worth, TX, USA) with the goal of causing less tions, oral antibiotics have seen some modifications in their
irritation on the skin. Of the topical retinoids, adapalene has formulations as well. Antibiotic dosage for acne has generally
the least irritant effect among the three listed above, though followed treatment regimens as for other conditions treated
it still can cause irritation to the user, even when instructions with the same antibiotics. Such doses include, doxycycline
are followed. A recent review of adapalene cited it as a more 100 mg twice daily or erythromycin 500 mg twice daily.
stable molecule than tretinoin and one that can be used with Recently, two novel uses of antibiotics have come to the
BP, as well as during the day because of this stability.10 forefront. The first is by prescribing a sub-MIC (minimal
Conversely, another review of a large cohort of patients over inhibitory concentration) dose, where the antibiotic acts as
52 weeks found that an aqueous gel formulation of clindamy- an anti-inflammatory medication rather than an antibiotic.
cin (1.2%) and a stable combination of tretinoin, which were Doxycycline at 20 mg twice daily is considered to be a sub-
both crystalline and solubilized, was well tolerated and was MIC dose.14 Another novel dosage/formulation regimen
effective in treating both inflammatory and noninflammatory involves using a sustained release form of minocycline which
lesions.11 A novel way of getting around the irritant effect is prescribed in a weight based manner (1 mg/kg/day) with
with tazarotene is the short contact method, where, as little the idea that preventing high levels of the antibiotic in the
as 30 seconds of skin contact resulted in a decrease in acne blood, rapidly after ingestion will lead to less side-effects.
lesions.12 This technique can also be used to increase topical This preparation of sustained release minocycline (Solodyn®;
contact time in a gradual fashion. In general, retinoids are Medicis Pharmaceutical Corporation, Scottsdale, AZ, USA)
considered to be very important in long-term maintenance has been suggested to have less vestibular side-effects, but
therapy of acne. Drug companies are looking for ways to has yet to show a decrease in other minocycline induced side
improve compliance by decreasing the irritation factor of effects. Although most dermatologists prefer the tetracycline
topical retinoids. The important feature of the retinoids, treat- class of antibiotics when dealing with acne, there is evidence
ing not only the visible but also the invisible lesions must that other antibiotics can be helpful. An alternative dosage
be stressed to the patient. Patients should be given detailed plan with azithromycin 500 mg daily, for four days of the
instructions for use, which should include, the amount to be month had similar efficacy as doxycycline 100 mg daily.15
used, the duration that the medication would take to produce Multiple other studies using azithromycin as an alternate drug
visible changes, as well as potential side-effects. have also shown some positive results. Moreover, a recent
Finally, regarding retinoids, there is one recent reference study using cephalexin has reported positive results, (49%
question on whether the topical form of these medications of patients were clear of acne or much improved). Although
can lead to systemic side-effects. Though this issue comes the study design was a retrospective chart review, cephalexin
up repeatedly, there is very little evidence. Recently, there may be an inexpensive alternative when other medications
was a single case report of a 23-year-old woman using are not available.16
adapalene 0.1% gel, who developed severe headaches and There are multiple controversies when it comes to treating
neck stiffness.13 The patient was on no other medications, but acne patients with long-term antibiotics. These include risk
was found to have swollen optic discs, although she also had of antibacterial resistance and other conditions such as breast
a normal cerebrospinal fluid pressure on lumbar puncture. Six cancer, as well as serious autoimmune reactions. Regarding
weeks after discontinuation of the adapalene, the discs were antibacterial resistance, it is important to explain this concept
back to normal and the headaches were gone. The authors to the patients/caregivers and at the same time employ
note that the patient had no other risk factors except for being methods to decrease such resistance. This is as simple as
mildly overweight at 70.3 kg at a height of 164.5 cm. having patients use a combination product of BP and a topical
antibiotic, while they are on long-term oral antibiotics. It is
Systemic antibiotics important to note that there are some risks to systemic anti-
Oral antibiotics are an important treatment option for biotics with respect to bacterial resistance. In addition to the
moderate to severe acne. It was in the 1950s that oral obvious dermatologic complication of gram-negative acne or
tetracycline and erythromycin were used to treat acne. folliculitis after long-term oral antibiotics, there is also the risk

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Keri and Shiman Dovepress

of increased upper respiratory tract infections. Acne patients same antiandrogen activity of 25 mg of spironolactone.
on oral antibiotics are about two times more likely to develop Although hormonal manipulation will help many patients
an upper respiratory tract infection, though their household with acne, it is imperative that dermatologists also be on
contacts do not appear to be at an increased risk.17 the lookout for endocrinopathies such as polycystic ovarian
After a 9-year follow-up of 2.1 million women, the syndrome (PCOS). PCOS patients often have irregular
observed associations of tetracyclines and macrolides with menses, hirsutism, acne, infertility, and obesity. However,
breast cancer were weak and could be explained by other with this syndrome the patient may not fit the textbook
diseases or factors.18 description. A recent review of the evaluation of a patient
Autoimmune reactions to antibiotics used to treat acne with suspected hormonal imbalance and acne provides
have been associated most often with minocycline. A review great decision-making algorithms for those treating such
of serious adverse reactions to minocycline included autoim- patients.22 Early identification of such patients can have
mune hepatitis, serum sickness and vasculitis, and a lupus-like long-term health benefits, as these patients are more likely
syndrome where the complement remains normal, and these to develop insulin resistance and cardiovascular disease than
serious events appear to be genetically determined by HLA- women without PCOS. For patients with PCOS and acne, the
type, DR4+, DR2+.19 A more recent review of patients with ethinylestradiol/drosperinone combination pill can help with
minocycline induced autoimmunity (MIA) looked at a 10-year both conditions.23 In addition, this combination pill (YAZ®)
period of patients referred to a tertiary hospital rheumatology has been approved for premenstrual dysmorphic disorder
service for the treatment of MIA.20 This was found to be a very (PMDD), a psychiatric diagnosis, associated with severe
rare entity, accounting for 0.05% of all children referred to the symptoms prior to menstruation.
rheumatology clinic at the tertiary children’s hospital. Most Spironolactone is another option for patients with acne.
autoimmune reactions to minocycline are probably mild and go As an antiandrogen, spironolactone has produced good results
away undiagnosed. However, of the 27 patients in this study, in the PCOS patient, as well as in the patient without PCOS,
7 had persistent chronic autoimmune disease 48 months later, but who has menstrual acne flares and deep cystic acne.
requiring such medications as methotrexate, etanercept and Spironolactone should not be given to those who have renal
mycophenolate mofetil. There may be a genetic predisposition impairment. Since it can retain potassium, a good review of
as it is more common in women, and dermatologists should other medications the patient is on, is imperative, to exclude
be aware of this. Doxycyline is also known to trigger severe potassium retaining medications. Chronic nonsteroidal anti-
autoimmune reactions such as reported in a 20-year-old woman inflammatory medications can also increase potassium and
on doxycycline for facial acne who presented with fever, this should be considered when prescribing spironolactone.
lymphadenopathy, hepatitis, nephritis, and severe pneumonitis In addition, this is a category X drug in pregnancy and thus,
with respiratory failure.21 the patient should be counseled about this and if there is any
risk of pregnancy, it should be evaluated. Dosage ranges for
Oral contraceptives spironolactone are 50–200 mg daily with most prescribers
and antiandrogens starting at 50–100 mg a day.
Hormonal manipulation in the treatment of acne came to
the forefront in the early 1990s. Currently in the United Systemic retinoids
States there are three oral contraceptive pills approved by Isotretinoin is the main systemic retinoid used in the treatment
the Federal Drug Agency (FDA) for the treatment of acne of acne, specifically severe nodulocystic acne. The mecha-
in women. These include ethinyl estradiol and norgestimate nisms of action of this drug include inhibition of sebaceous
(Ortho Tri-Cyclen®; Ortho-McNeil-Janssen Pharmaceuticals, gland differentiation with a reduction in sebaceous gland size
Titusville, NJ, USA), norethindrone acetate and ethinyl and sebum production, normalization of follicular epithelial
estradiol (Estrostep®; Warner-Lambert, Morris Plains, NJ, desquamation, and inhibition of neutrophil chemotaxis.
USA) and ethinyl estradiol/drosperinone (YAZ®; Bayer, Recommended cumulative doses for the treatment of acne
Wayne, NJ, USA). In other countries around the world, are 120–150 mg/kg with many practitioners using the higher
cyproterone acetate (Diane-35®; Bayer Pty Ltd, Singapore) end of this range. Isotretinoin has a variety of adverse effects
is also used for the treatment of acne. The progestin associated with it. Almost every patient will have xerosis of
drosperinone, found in products of brands such as YAZ® the skin and chelitis. However, the side-effect of concern
and Yasmin® (Bayer, Wayne, NJ, USA), have about the with this medication is teratogenicity, which is quite major.

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Dovepress Update on the management of acne vulgaris

Up to 50% of fetuses exposed to this drug during the first Laser and light devices
trimester will have a major birth defect which includes major With technology progressing at a fast pace, it is not surprising
cardiovascular, craniofacial, ocular, auditory, central nervous that laser and light therapies would be of interest to those
system, and skeletal abnormalities.24 In the United States, treating acne. Recently, the range of treatments for acne
a federally mandated program, iPledge has been instituted has included photodynamic therapy (PDT), light-emitting
in an attempt to decrease the number of pregnancies while diode (LED) therapy and a combination of pneumatic energy
patients are on this medication. This program requires all and light for the treatment of acne. These therapies work
patients to be registered with an iPledge number and also best as adjuvant therapies when combined with traditional
requires physicians, pharmacists and pharmacy distributors to therapies.
also be registered if they are involved with the distribution of PDT, which is the treatment of skin with aminolevulinic
this drug. Long-term analysis has yet to show if this program acid followed by photo activation of the compound, has
decreases the number of pregnancies while on the drug. been shown to help treat acne.28 Most patients are able to
Another concern about isotretinoin is whether this tolerate the procedure well, but in rare cases PDT has been
medication increases the risk of suicide and depression. associated with a painful pustular reaction while being used
A recent review of nine studies evaluating this concern for the treatment of acne.
was published.25 This systemic review found the rates of Red and blue light therapy is also used to treat acne,
depression to be similar among users of isotretinoin and with the most recent advances being home-use products
nonusers. The studies examined did not show a statisti- that allow the patient to deliver the light therapy at home
cally significant increase in depression in isotretinoin by a handheld device. Recently, a report of a study using a
users before or after treatment, and some showed that the handheld LED red and blue light device found that the lesion
patients had less severe depressive symptoms after treat- counts decreased throughout the 4-week treatment period and
ment. The authors of this review note that all these studies continued for up to 8 weeks post-therapy with the average
have limitations, but the data do not support a meaningful reduction of 69% (p  0.001).29 Similarly, another study
causative association. However, this association must be looking at acne in patients with type IV skin showed that the
discussed with patients upon initiation of this drug and at red and blue light combination treatment twice weekly for
each follow-up visit. 4 weeks resulted in improvements in noninflammatory and
inflammatory lesions.30 As inflammatory lesions improved
Superficial chemical peels more, the authors felt this was a good treatment particularly
Chemical peeling of the skin has long been used in the for papulopustular acne.
treatment of acne. Most peeling for the treatment of acne is A novel combination product called Isolaz™ (Aesthera,
superficial. This discussion is focused on the treatment of Pleasanton, CA, USA) which uses a vacuum along with a
acne rather than that of acne scarring. In general, most prac- broad band light source, has been shown to be effective
titioners use salicylic acid, glycolic acid, or trichloroacetic in the treatment of acne.31 This small study (11 patients)
acid for the treatment of acne. Superficial chemical peeling treated patients with the device at 3-week intervals and had
can be done monthly, although some do the peels as often signifi­cant decreases in both inflammatory and noninflam-
as every 2 weeks and some wait until every 6 weeks. Good matory lesions. Most patients expressed satisfaction with
patient education is necessary as patients should know what this treatment.
to expect with the peel. A good review of regimens used
for patients in office settings is noted in a recent review.26 Future treatment options
In patients with ethnic skin, salicylic acid remains the peel- Probably the most interesting treatment on the horizon is
ing agent of choice as the others have been associated with vaccine therapy for acne. The vaccines are targeted against
post-inflammatory pigment alteration. A recent comparison the P. acnes bacteria. As mentioned at the beginning of this
of alpha-hydroxy (30% glycolic acid) versus beta-hydroxy article, acne is a multifactorial disease, and thereby targeting
(30% salicylic acid) peels in a double-blind, randomized one area may not result in eradication of the condition.
study found that both peels were equally effective in the However, P. acnes is involved in diseases other than
treatment of acne.27 However, there were more reported acne including infectious conditions such as endocarditis,
adverse events after the initial treatment with the glycolic endophthalmitis, osteomyelitis and post-surgery infections,
acid peel. and this has lead researchers to develop vaccines. A recent

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109
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 Keri and Shiman Dovepress

review highlights the latest work on the P. acnes vaccines 13. Givre SJ, Fleischman D. Intracranial hypertension in a patient using
topical adapalene. J Neuroophthalmol. 2008;28:156–158.
and how they have shown good results and immunity, when 14. Skidmore R, Kovach R, Walker C, et al. Effects of subantimicrobial-
used in mice challenged by P. acnes.32 dose doxycycline in the treatment of moderate acne. Arch Dermatol.
In conclusion, practitioners should be aware of the 2003;139:459–464.
15. Parsad D, Pandhi R, Nagpal R, et al. Azithromycin monthly pulse
traditional therapeutic choices for the treatment of acne, but vs daily doxycycline in the treatment of acne vulgaris. J Dermatol.
should work to refine their knowledge about the different 2001;28:1–4.
16. Fenner JA, Wiss K, Levin NA. Oral cephalexin for acne vulgaris:
formulations of products available to them to prescribe. As clinical experience with 93 patients. Pediatr Dermatol. 2008;25:
to newer technologies, it is imperative that physicians are 179–183.
aware of these modalities and even if they are not actively 17. Bowe WP, Hoffstad O, Margolis DJ. Upper respiratory tract infec-
tion in household contacts of acne patients. Dermatology. 2007;215:
using them, they should have a working knowledge of them 213–218.
to answer patient questions. 18. Friedman GD, Oestreicher N, Chan J, et al. Antibiotics and risk of
breast cancer: up to 9 years of follow-up of 2.1 million women. Cancer
Epidemiol Biomarkers Prev. 2006;15:2102–2106.
Disclosures 19. Dunphy J, Oliver M, Rands AL, et al. Antineutrophil cytoplasmic
Dr. Keri has served on an advisory panel and been a speaker antibodies and HLA class II alleles in minocycline-induced lupus-like
syndrome. Br J Dermatol. 2000;142:461–467.
for Medicis. 20. El-Hallak M, Giani T, Yeniay BS, et al. Chronic minocycline-induced
autoimmunity in children. J Pediatr. 2008;153:314–319.
21. Robles DT, Leonard JL, Compton N, et al. Severe drug hypersensitivity
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