Acne vulgaris

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Acne vulgaris

Fragkiski Tsatsou and Christos C. Zouboulis

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit with a multifactorial pathogenesis and a highly variable morphology. Acne is one of the commonest dermatologic disorders encountered in everyday clinical practice with great impact on quality of life.

Management strategy

Treatment depends on the type and severity of acne lesions. Combination therapy is often appropriate to address the multifactorial pathophysiology. Treatment is addressed under the following headings: comedonal, mild papulopustular, moderate papulopustular acne without scarring, moderate papulopustular acne with scarring, nodulocystic and/or conglobate, acne fulminans. We also address post-acne scarring.

In mild forms of acne, topical therapy is most appropriate. Topical therapy is indicated in comedonal acne and mild to moderate papulopustular acne without scarring. Topical therapeutic agents also form a part of combination therapy with oral regimens or procedural therapies for treatment of more severe forms of acne. Topical agents include retinoids, antimicrobial and antibacterial agents, hormonal agents or herbal remedies. Four to 8 weeks should be allowed for most topical treatments to work before altering the regimen.

Treatment of choice for comedonal acne is monotherapy with topical retinoids as initiation therapy, due to its usually mild-to-moderate severity. Following successful treatment, topical retinoids are suitable for maintenance therapy. Topical retinoids act against comedones (macrocomedones) and microcomedones and have direct anti-inflammatory effects. Retinoids approved for topical acne treatment include tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), as well as the synthetic third-generation polyaromatic retinoids adapalene and tazarotene. Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild-to-moderate acne but they differ in speed of efficacy and tolerability. Adverse events are local and include erythema, dryness, itching, and stinging. Adapalene is preferred to tretinoin and isotretinoin, since it shows the best tolerability/safety profile.

Treatment of choice for mild and moderate papulopustular acne without scarring is a combination of benzoyl peroxide (BPO) and topical retinoids, or BPO and topical antibiotics. Fixed-dose combination of clindamycin phosphate + BPO or fixed-dose combination of adapalene and BPO are both recommended as first-line treatment of both mild and moderate papulopustular acne without scarring.

For moderate papulopustular acne with scarring in males, oral antibiotics are the treatment of choice. Oral antibiotics improve inflammatory acne by inhibiting Propionibacterium acnes and/or inducing a genuine anti-inflammatory activity. Although there is no correlation between the number of P. acnes and the severity of acne, the occurrence of antibiotic-resistant P. acnes correlates with poor clinical response. Several antibiotics exhibit anti-inflammatory properties, assisting in the improvement of acne through decreased leukocyte chemotaxis and alteration of cytokine production. Tetracyclines, erythromycin and nadifloxacin reduce reactive oxygen species formation by neutrophils and, therefore, acne inflammation. New antibiotics for the treatment of acne include lymecycline, a second-generation tetracycline, and roxithromycin, a macrolide that exhibits anti-inflammatory and anti-androgenic activities.

Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline, lymecycline) and macrolides (erythromycin, azithromycin), are the agents of choice for papulopustular acne. Second-generation tetracyclines (doxycycline, minocycline, lymecycline) have pharmacokinetic advantages over tetracycline. Doxycycline is used at 100 or 200 mg daily in two equal doses. Minocycline is not equally recommendable due to rare but potentially severe side effects and high cost. An initially higher dose of doxycycline or minocycline (4 weeks 100 mg daily, then 50 mg daily) is more effective than 50 mg daily over 12 weeks. Patients with strong seborrhea may require higher doses (doxycycline and minocycline up to 200 mg daily, lymecycline up to 600 mg daily). At such dosages increased side effects may be expected. Small daily doses with concomitant sub-inhibitory concentrations may promote resistance.

Systemic antibiotic therapy of moderate papulopustular acne should in general be continued for 3 months and should be combined with topical BPO (either continuously or at intervals) to prevent antibiotic resistance. Combination therapy with topical agents, especially retinoids, BPO or azelaic acid, also increases efficacy of treatment. It appears that antibiotic therapy longer than 3 to 6 months brings little additional effect but increases the risk of resistance. Treatment should be then switched to topical retinoids for maintenance therapy.

In nodulocystic or conglobate acne, oral isotretinoin is the treatment of choice. Systemic isotretinoin suppresses sebaceous gland activity, normalizes the pattern of keratinization within the pilosebaceous follicle, inhibits inflammation, and – in a secondary manner – reduces growth of P. acnes. It is the most effective anti-acne drug available, especially in the treatment of severe recalcitrant nodulocystic acne and in the prevention of acne scarring.

In most cases with severe acne, a 6- to 12-month course of isotretinoin 0.5 mg/kg/day is recommended. Higher doses are indicated particularly for severe involvement of the chest and back. Factors contributing to the need for longer treatment schedules include use of lower dose regimens, presence of severe acne, extrafacial involvement and prolonged history of the disease. The drug’s discontinuation may be followed by a disease relapse.

Isotretinoin treatment for acne can initially induce inflammatory flares of acne, occasionally leading to acne fulminans. This usually occurs 3 to 4 weeks after treatment initiation. Mild flares do not require modification of the oral dose and improve spontaneously. Severe episodes should be treated with addition of systemic prednisolone (30 mg/day), whereas dose reduction or discontinuation of isotretinoin may only be required in individual cases.

The adverse effect profile of oral isotretinoin includes characteristic dose-dependent mucocutaneous side effects (cheilitis, xerosis, dry mucosae, conjunctivitis, epistaxis), elevation of serum lipids, hyperostosis, extraskeletal calcification, arthralgia, and myalgia. Low-dose long-term regimens (0.1–0.2 mg/kg daily or intermittent use) and a micronized isotretinoin formulation with similar efficacy are associated with a lower risk of adverse events.

The teratogenic potential of isotretinoin with high rate of spontaneous abortions and life-threatening congenital malformations demands the use of secure contraception when it is prescribed for females of fertile age. Contraception is recommended 1 month before initiation of treatment, during the entire period of the drug administration, and over 3 months after discontinuation of the regimen. Oral isotretinoin is strictly contraindicated in pregnancy, during lactation, and in severe hepatic and renal dysfunction. Relative contraindications include hyperlipidemia, diabetes mellitus, and severe osteoporosis. Co-administration of vitamin A, tetracycline and high doses of aspirin is contraindicated. Liver enzymes and lipid levels in blood should be monitored.

For acne fulminans a combination of oral corticosteroid and isotretinoin is indicated. Infantile and pediatric acne may necessitate an alternative treatment. For patients with adrenal hyperandrogenism low-dose oral corticosteroid in combination with systemic retinoid is the treatment of choice.

Hormonal anti-androgen treatment is not a primary monotherapy and is largely reserved for female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. However, hormonal anti-androgens can be useful in females with acne tarda, persistent acne recalcitrant to other treatments, patients with an incidental need for contraception, and to provide contraceptive cover during systemic isotretinoin treatment.

Specific investigations

None are required routinely.

Consider microbiology to exclude Gram positive or Gram negative folliculitis

Consider endocrine work-up if hyperandrogenemia is suspected

First-line therapy

Comedonal acne
Topical retinoids	B
Dapsone gel with topical retinoid	B
Mild papulopustular acne
Benzoyl peroxide with topical retinoid	A
Benzoyl peroxide with topical antibiotic	A
Moderate papulopustular acne without scarring
Benzoyl peroxide with topical retinoid	A
Benzoyl peroxide with topical antibiotic	A
Moderate papulopustular acne with scarring
For males use oral antibiotics (tetracyclines, macrolides) with benzoyl peroxide or topical retinoid	A
For females use an oral anti-androgen contraceptive with benzoyl peroxide and topical antibiotic	A
Nodulocystic and/or conglobate acne
Oral isotretinoin*	A
Acne fulminans
Oral isotretinoin* with low-dose oral corticosteroids	C

^*In women add an oral anti-androgen contraceptive.

European evidence-based (S3) guidelines for the treatment of acne.

Nast A, Dréno B, Bettoli V, Degitz K, Erdmann R, Finlay AY, et al. J Eur Acad Dermatol Venereol 2012; 26 (Suppl 1): 1–29.

Guidelines developed through a European consensus procedure for the treatment of acne.

Topical retinoids in acne – an evidence-based overview.

Thielitz A, Naser MB, Fluhr JW, Zouboulis CC, Gollnick H. J Dtsch Dermatol Ges 2010; 8 (Suppl 1): S15–23.

A review on topical retinoids approved for topical acne treatment, their differences in efficacy and tolerability and their adverse effects, according to EBM-levels.

Clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0.1% in patients with acne vulgaris.

Tanghetti E, Dhawan S, Green L, Ling M, Downie J, Germain MA, et al. J Drugs Dermatol 2011; 10: 783–92.

A 12-week study. Combination therapy with dapsone gel 5% plus tazarotene cream 0.1% was more effective than tazarotene monotherapy for treatment of comedonal acne. It is suggested that anti-inflammatory agents, such as dapsone, can effectively treat early stages of acne (both comedonal and non-comedonal) when used in combination with a retinoid.

Effects of benzoyl peroxide 5% clindamycin combination gel versus adapalene 0.1% on quality of life in patients with mild to moderate acne vulgaris: a randomized single-blind study.

Guerra-Tapia A. J Drugs Dermatol 2012; 11: 714–22.

The fixed-dose combination of benzoyl peroxide 5%/clindamycin 1% gel provided earlier improvement of quality of life than adapalene 0.1% gel. This could result from better efficacy and tolerability.

A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide and adapalene in the treatment of mild to moderate facial acne vulgaris.

Langner A, Chu A, Goulden V, Ambroziak M. Br J Dermatol 2008; 158: 122–9.

Clindamycin phosphate + benzoyl peroxide 5% (CDP+BPO) ready-mixed gel once daily and once daily gel containing adapalene 0.1% are both effective treatments for acne, but CDP+BPO has a significantly earlier onset of action, is significantly more effective against inflamed and total lesions and is better tolerated.

A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide (Duac) and erythromycin + zinc acetate (Zineryt) in the treatment of mild to moderate facial acne vulgaris.

Langner A, Sheehan-Dare R, Layton A. J Eur Acad Dermatol Venereol 2007; 21: 311–19.

Comparison of two combination treatments for facial acne: a ready-mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn). Both regimens are effective but CDP + BPO has an earlier onset of action that should improve compliance.

Study of the efficacy, tolerability, and safety of 2 fixed-dose combination gels in the management of acne vulgaris.

Zouboulis CC, Fischer TC, Wohlrab J, Barnard J, Alió AB. Cutis 2009; 84: 223–9.

Comparison of clindamycin 1%/benzoyl peroxide 5% gel with hydrating excipients (C/BPO HE) and adapalene 0.1% benzoyl peroxide 2.5% gel. After 12 weeks of once daily application, the treatments showed similar improvements of inflammatory and non-inflammatory lesions, but C/BPO HE achieved better overall treatment success in less time with better tolerability and safety.

Clindamycin phosphate/tretinoin gel formulation in the treatment of acne vulgaris.

Abdel-Naser MB, Zouboulis CC. Expert Opin Pharmacother 2008; 9: 2931–7.

Clindamycin phosphate 1.2% with tretinoin 0.025% fixed-dose combination gel is approved by the FDA for treatment of acne vulgaris in patients ≥12 years old. This formulation enhances effectiveness and minimizes irritation. The once daily use, the rapid effect and good tolerability have a positive impact on disease duration, compliance, and cost.

Efficacy and safety of 3 mg drospirenone/20 mcg ethinylestradiol oral contraceptive administered in 24/4 regimen in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled trial.

Koltun W, Lucky AW, Thiboutot D, Niknian M, Sampson-Landers C, Korner P, et al. Contraception 2008; 77: 249–56.

This non-androgenic progestin-containing contraceptive with strong anti-androgenic activity (drospirenone 3 mg) but reduced concentration of ethinyl estradiol (20 µg) has been shown to be effective and may replace the classic cyproterone acetate/ethinyl estradiol and chlormadinone acetate/ethinyl estradiol oral contraceptives due to an improved side effect profile.

Efficacy of a combined oral contraceptive containing 0.030 mg ethinylestradiol/2 mg dienogest for the treatment of papulopustular acne in comparison with placebo and 0.035 mg ethinylestradiol/2 mg cyproterone acetate.

Palombo-Kinne E, Schellschmidt I, Schumacher U, Gräser T. Contraception 2009; 79: 282–9.

A combined oral contraceptive containing the anti-androgen dienogest with ethinylestradiol proved superior to placebo and not inferior to one containing the potent anti-androgen cyproterone acetate and ethinylestradiol.

Second-line therapy

Comedonal acne
Benzoyl peroxide (topical)	B
Azelaic acid	B
Superficial peels (lipohydroxy acid, salicylic acid)	B
Mild to moderate papulopustular acne
Azelaic acid	A
Benzoyl peroxide (topical)	C
Topical retinoid	A
Topical nadifloxacin	A
Azelaic acid with topical clindamycin	A
Azelaic acid with topical erythromycin	A
Dapsone gel	A
Dapsone gel with topical retinoid	A
Dapsone gel with benzoyl peroxide (topical)	A
Systemic antibiotic with adapalene	C
Topical erythromycin with topical retinoid	C
Picolinic acid	B
Oral zinc	C
Photodynamic therapy	C
Intense pulsed light (IPL)	B
Photodynamic therapy with IPL	B
Blue light	B
Blue/red light combinations	C
Red low-level laser therapy (LLLT)	B
1,450 nm diode laser	C
Topical cyproterone acetate	A
Zileuton	C
Topical copaiba essential oil gel	A
Topical 5% tea tree oil gel	A
Glycolic acid oil-in-water emulsion	A
Chemical peels (α-hydroxy acid, glycolic acid, β-hydroxy acid, salicylic acid)	B
Microdermabrasion	C
Nodulocystic and/or conglobate acne
Oral antibiotic plus topical retinoid	C
Oral antibiotic plus azelaic acid	C
Oral antibiotic plus topical retinoid plus benzoyl peroxide	C

Efficacy of topical azelaic acid gel in the treatment of mild-moderate acne vulgaris.

Iraji F, Sadeghinia A, Shahmoradi Z, Siadat AH, Jooya A. Indian J Dermatol Venereol Leprol 2007; 73: 94–6.

A double-blind, randomized clinical trial evaluating the efficacy of 20% azelaic acid gel compared to vehicle in 60 patients with mild to moderate acne vulgaris. Azelaic acid gel was effective.

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris.

Pazoki-Toroudi H, Nilforoushzadeh MA, Ajami M, Jaffary F, Aboutaleb N, Nassiri-Kashani M, Firooz A. Cutan Ocul Toxicol 2011; 30: 286–91.

The efficacy and safety of a 12-week course of treatment for mild-to-moderate acne vulgaris were evaluated in a multicenter, randomized, double-blind study. The combination formulation showed a greater reduction in lesion count in comparison to individual treatment with 5% azelaic acid or 2% clindamycin.

Dapsone gel 5% for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment.

Lucky AW, Maloney JM, Roberts J, Taylor S, Jones T, Ling M, et al. J Drugs Dermatol 2007; 6: 981–7.

A 12-month, open-label, long-term safety study. The gel was shown to be safe and effective for long-term treatment with a rapid onset of action.

Dapsone is a sulfone with anti-inflammatory and antimicrobial properties. Dapsone gel 5% delivers clinically effective doses of dapsone with minimal systemic absorption.

Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week, randomized, double-blind study.

Fleischer AB Jr, Shalita A, Eichenfield LF, Abramovits W, Lucky A, Garrett S, Dapsone Gel in Combination Treatment Study Group. J Drugs Dermatol 2010; 9: 33–40.

A 12-week, randomized, double-blind study on three formulations containing dapsone. Dapsone combined with adapalene showed a significantly better reduction of non-inflammatory and total acne lesion count than the moisturizer combination. There was no significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene or benzoyl peroxide gel compared to the moisturizer combination.

A pilot study of the safety and efficacy of picolinic acid gel in the treatment of acne vulgaris.

Heffernan MP, Nelson MM, Anadkat MJ. Br J Dermatol 2007; 156: 548–52.

In an open-label study on 20 patients, 10% picolinic acid gel applied twice daily on the face over 12 weeks was shown to be safe and effective.

Picolinic acid, an intermediate metabolite of tryptophan, is safe and effective in the treatment of mild to moderate acne vulgaris and is available as 10% picolinic acid gel for twice daily application.

New and emerging treatments in dermatology: acne.

Katsambas A, Dessinioti C. Dermatol Ther 2008; 21: 86–95.

An overview of the treatment of acne, including new therapies and future perspectives. Oral zinc sulfate and zinc gluconate have been used for the treatment of inflammatory acne vulgaris with conflicting results. Zinc acts via inhibition of polymorphonuclear cell chemotaxis and inhibition of growth of P. acnes. Its anti-inflammatory activity could also be related to a decrease in tumor necrosis factor-α production, the modulation of the expression of integrins, and the inhibition of TLR2 surface expression by keratinocytes. Zinc salts have been used at a dosage of 30–150 mg of elemental zinc daily for 3 months. Zinc gluconate does not induce bacterial resistance, has a favorable safety profile and can be administered to pregnant women.

Randomized trial comparing a chemical peel containing a lipophilic hydroxy acid derivative of salicylic acid with a salicylic acid peel in subjects with comedonal acne.

Levesque A, Hamzavi I, Seite S, Rougier A, Bissonnette R. J Cosmet Dermatol 2011; 10: 174–8.

A split face study. Twenty subjects received a total of six peels at 2-week intervals. There was no significant difference in response.

Lipohydroxy acid is a lipophilic derivative of salicylic acid with comedolytic properties.

Combination of azelaic acid 5% and erythromycin 2% in the treatment of acne vulgaris.

Pazoki-Toroudi H, Nassiri-Kashani M, Tabatabaie H, Ajami M, Habibey R, et al. J Dermatolog Treat 2010; 21: 212–16.

A 12-week, multicenter, randomized, double-blind study. The combination of azelaic acid 5% and erythromycin 2% produced greater effect than erythromycin 2% or azelaic acid 20% alone, and with fewer side effects.

Azelaic acid has a predominant antibacterial action and possesses a modest comedolytic effect. Burning upon application is common. Systemic side effects are not likely to occur, making it safe for acne treatment during pregnancy and lactation.

Lack of irritative potential of nadifloxacin 1% when combined with other topical anti-acne agents.

Wilhelm KP, Wilhelm D, Neumeister C, Zsolt I, Schwantes U. Clin Exp Dermatol 2012; 37: 112–17.

A randomized, observer-blinded, phase I clinical study with an intra-individual comparison showed that 1% nadifloxacin cream in combination with topical adapalene, benzoyl peroxide, azelaic acid, and isotretinoin formulations did not increase skin irritation in comparison to each product used alone.

Tolerability is critical for compliance. The simultaneous use of more than one topical preparation may increase irritation, but improves efficacy and response time.

Zileuton, a new efficient and safe systemic anti-acne drug.

Zouboulis CC. Dermato-Endocrinology 2009; 1: 188–92.

In a multicenter study, zileuton, an oral 5-lipoxygenase inhibitor, showed a significant decrease in inflammatory lesions compared to placebo. Zileuton appears to be safe and well tolerated.

Application of the essential oil from copaiba (Copaifera langsdori Desf.) for acne vulgaris: a double-blind, placebo-controlled clinical trial.

Da Silva AG, Puziol Pde F, Leitao RN, Gomes TR, Scherer R, Martins ML, et al. Altern Med Rev 2012; 17: 69–75.

Treatment with 1.0% copaiba oil significantly reduced the surface area affected with acne.

Copaiba oil-resin is widely used in traditional medicine due to its anti-inflammatory, healing, and antiseptic activities.

The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study.

Enshaieh S, Jooya A, Siadat AH, Iraji F. Indian J Dermatol Venereol Leprol 2007; 73: 22–5.

This was found to be effective.

A 10% glycolic acid containing oil-in-water emulsion improves mild acne: a randomized double-blind placebo-controlled trial.

Abels C, Kaszuba A, Michalak I, Werdier D, Knie U, Kaszuba A. J Cosmet Dermatol 2011; 10: 202–9.

Treatment was applied once daily in the evening in 120 patients with mild acne over 90 days and improved mild acne significantly after 45 days with good tolerability.

α-Hydroxy acids exhibit comedolytic and antimicrobial properties.

Lasers and photodynamic therapy for the treatment of acne.

Ferris KM, McLeod MP, Ahmed A, Nouri K. G Ital Dermatol Venereol 2012; 147: 277–84.

A review on the use of lasers and light treatments for acne, including photodynamic therapy (PDT) with and without photosensitizers, KTP laser, PDL laser, infrared and fractional lasers. The future application of these devices in acne therapy will likely include combination therapy and exploration of more precisely targeted chromophores.

Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: a comparative study.

Shaaban D, Abdel-Samad Z, El-Khalawany M. Dermatol Ther 2012; 25: 86–91.

A study on 30 patients with nodulocystic and inflammatory acne vulgaris on the face and back. The right side of the body was treated with PDT using intralesional 5-aminolevulinic acid (ALA) plus IPL, while the left side was treated with IPL alone. Photodynamic therapy gave superior results compared to IPL alone with tolerable side effects and lower recurrence rates.

Long-pulsed dye laser versus long-pulsed dye laser-assisted photodynamic therapy for acne vulgaris: a randomized controlled trial.

Haedersdal M, Togsverd-Bo K, Wiegell SR, Wulf HC. J Am Acad Dermatol 2008; 58: 387–94.

Evaluation of LPDL alone versus LPDL and photodynamic therapy with methylaminolevulinic acid (MAL-LPDL) for acne vulgaris in 15 patients receiving a series of three full-face LPDL treatments and half-face prelaser MAL treatments. MAL-LPDL was slightly superior to LPDL.

PDT with the porphyrin precursor 5-aminolevulinic acid or its methyl ester (MAL) is used in the treatment of inflammatory acne vulgaris for its immunomodulatory effects. ALA or MAL are applied topically. Side effects are transient, usually pain and erythema. There have been no significant differences seen in the response rate between ALA-PDT and MAL-PDT, but ALA-PDT resulted in more prolonged and severe adverse effects after treatment. Randomized, placebo-controlled studies are still lacking.

An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris.

Ammad S, Gonzales M, Edwards C, Finlay AY, Mills C. J Cosmet Dermatol 2008; 7: 180–8.

Significant improvement was demonstrated in this uncontrolled study with 21 subjects.

Clinical efficacy of home-use blue-light therapy for mild-to moderate acne.

Gold MH, Sensing W, Biron JA. J Cosmet Laser Ther 2011; 13: 308–14.

Blue-light light-emitting diode (LED) therapy is widely used for the treatment of inflammatory acne. This randomized self-control study on 30 patients evaluated the efficacy of a home-use blue-light LED application twice daily. The therapy was found to be effective.

Comparison of red and infrared low-level laser therapy in the treatment of acne vulgaris.

Aziz-Jalali MH, Tabaie SM, Djavid GE. Indian J Dermatol 2012; 57: 128–30.

In this single-blind randomized study, two different wavelengths of LLLT (630 and 890 nm) were evaluated. Twenty-eight patients with mild to moderate acne vulgaris were treated with red LLLT (630 nm) and infrared LLLT (890 nm) on the right and left sides of the face, respectively, twice a week for 12 sessions. There was significant clinical improvement with 630 nm but not with 890 nm.

Clinical evaluation of a 1450-nm diode laser as adjunctive treatment for refractory facial acne vulgaris.

Astner S, Tsao SS. Dermatol Surg 2008; 34: 1054–61.

The 1450 nm diode laser provides moderate improvement of refractory acne vulgaris and can be used as an adjunctive treatment for acne management.

Cyproterone acetate loading to lipid nanoparticles for topical acne treatment: particle characterisation and skin uptake.

Stecová J, Mehnert W, Blaschke T, Kleuser B, Sivaramakrishnan R, Zouboulis CC, et al. Pharm Res 2007; 24: 991–1000.

Topical cyproterone acetate may be an additional therapeutic option.

The efficacy of topical cyproterone acetate alcohol lotion versus placebo in the treatment of the mild to moderate acne vulgaris: a double blind study.

Iraji F, Momeni A, Naji SM, Siadat AH. Dermatol Online J 2006; 12: 26.

A trial with 86 female patients with mild to moderate acne vulgaris.

The use of cyproterone acetate alcohol lotion is suggested as one of the main treatments for mild to moderate acne in female patients and as an adjuvant treatment for moderate to severe acne vulgaris.

A review of phytotherapy of acne vulgaris: perspective of new pharmacological treatments.

Azimi H, Fallah-Tafti M, Khakshur AA, Abdollahi M. Fitoterapia 2012 [Epub ahead of print].

Plants currently used and some for future development as anti-acne products.

Current state of acne treatment: highlighting lasers, photodynamic therapy, and chemical peels.

Kim RH, Armstrong AW. Dermatol Online J 2011; 17: 2.

Adjunctive therapies, particularly blue light and photodynamic therapy may complement conventional therapy. Limitations include small number of randomized controlled trials and small sample sizes.

Superficial chemical peels and microdermabrasion for acne vulgaris.

Kempiak SJ, Uebelhoer N. Semin Cutan Med Surg 2008; 27: 212–20.

A description of the procedure steps and the complications in the office setting. The evaluation of patients prior to the procedure is discussed, as well as post-peel regimens. Comparative studies between the two most commonly used superficial peeling agents, glycolic and salicylic acid, are discussed.

Third-line therapy

Mild to moderate acne
Chemical peels (α-hydroxy acid, glycolic acid, β-hydroxy acid, salicylic acid)	B
Microdermabrasion	C
Acne sinuses and scars
Intralesional steroids	C
Medium-depth chemical peels (Jessner’s solution/trichloroacetic acid (TCA), TCA, phenol)	B
Dermabrasion	C
Radiofrequency	C
Fractional laser resurfacing (ablative, non-ablative)	B
Surgical scar revision	C
Injectable fillers	C