Katie Beleznay, MD FRCPC, FAAD

Clinical Instructor, Department of Dermatology and Skin Science University of British Columbia, Vancouver, BC, Canada

Introduction

According to the Canadian Dermatology Association1, acne affects approximately 20% of the Canadian population, somewhere between five and six million individuals. For most people, acne appears at puberty and may last until adulthood. In adolescence, acne is nearly ubiquitous, with approximately 90% of individuals experiencing it to some degree. However, adult acne is increasingly common with women making up about three-quarters of adult cases.1,2 In a large study, acne peaked in the teenage years, but 45% of women aged 21-30, 26% aged 31-40, and 12% aged 41-50 had acne.3 Acne can have a negative impact on the quality of life of patients, leading to a decrease in self-esteem, embarrassment, and frustration, as well as discrimination in the workplace and in other social situations.2 It is important to recognize and treat these patients early to prevent scarring, and to help improve quality of life as there is a high psychosocial impact of the disease. For the purposes of this article, the focus will be on the topical treatment of post-adolescent mild to moderate acne. A selection of over-the-counter and prescription based topical treatments are discussed below.

Background

  • Acne is a multifactorial inflammatory disease centered on the pilosebaceous gland of the skin.
  • Key pathogenic features in the development of acne are abnormal follicular keratinization, colonization with Propionibacterium acnes, sebum production, and complex inflammatory mechanisms. In addition, studies have suggested that hormones, diet, genetic and other factors may contribute to the multifactorial process of acne pathogenesis.4,5
  • To improve and prevent acne, treatment should target as many factors as possible.
  • Acne is usually classified by the number, type and distribution of acne lesions.
    • Mild acne tends to consist of comedones (whiteheads and blackheads), few papules and pustules.
    • Moderate acne has several papules, pustules, and may contain nodules.
    • Severe acne has numerous papules, pustules, multiple nodules, cysts and scarring. The distribution is commonly on the face, but may also involve the back, chest and upper arms.6

Therapy for acne can be broadly divided into four categories:

  1. Topical
  2. Systemic
  3. Light-based
  4. Physical therapies
  • The goals of treatment are to clear existing lesions, prevent new lesions, minimize scarring and dyspigmentation, and reduce the psychological impact.
  • For most patients with mild acne, and many with moderate, topical therapy will be sufficient to clear the skin lesions. If this proves insufficient, clinicians should not hesitate to change the regimen, either trying an alternative topical treatment or adding a systemic therapy.
  • The type of acne should be a primary consideration when evaluating treatment options.

Topical Treatments

Benzoyl Peroxide

  • This is antibacterial and mildly comedolytic (inhibits formation or treats comedones).
  • It does not cause bacterial resistance.
  • Benzoyl peroxide may cause mild skin irritation or dryness. It can also cause bleaching of hair, clothes, bed linens, etc.7
  • It is reasonable to initiate therapy with 2.5% products since limited evidence shows efficacy similar to 5% and 10% formulations but with less irritation.8
  • It is available as a monotherapy in several over-the-counter products (e.g., creams, lotions, gels, cleansers) and is also a component of prescription combinations with a topical antimicrobial.

Glycolic Acid

  • Glycolic acid (an alpha-hydroxy acid) is mildly comedolytic and is commonly used when other topicals are not tolerated.
  • It may also be used at higher concentrations in chemical peels to help clear comedones.4

Salicylic Acid

  • Salicylic acid is comedolytic.
  • Concentrations of 1-2% are tolerated but not as effective as topical retinoids. Higher concentrations are usually too irritating.
  • It is most commonly found in nonprescription products.4

Topical Retinoids

  • These are strong comedolytic agents and are the recommended first line treatment for mild comedonal acne in adult women.9, 10
  • Retinoids promote the reversal of comedogenesis, leading to a reduction of microcomedones, a precursor of both inflammatory and non-inflammatory lesions.
  • Several forms of retinoids are available on the market including tretinoin, adapalene, and tazarotene.
  • Tretinoin is the most cost effective but also the most photosensitizing. Adapalene is the least irritating and tazarotene the most potent.11
  • Tretinoin reverses thickening of the stratum corneum and the abnormal desquamation of keratinocytes and has been a mainstay of acne treatment for 30 years.12
  • Newer retinoid formulations, such as tretinoin microsphere gel, have been shown to retain photostability (i.e. protect against photodegradation).13
  • Tretinoin microsphere technology introduces small amounts of tretinoin to the skin over time, leading to higher efficacy and better tolerability versus tretinoin.14

Topical Antibiotics

  • Topical antibiotics are used to decrease skin colonization with P. acnes and can be anti-inflammatory.
  • Clindamycin is typically the preferred topical antibiotic therapy for acne.4
  • Monotherapy with topical antibiotics should not be used routinely, because of the risk of bacterial resistance.6
  • Combination with benzoyl peroxide reduces the risk of bacterial resistance.6

Azelaic Acid

  • This is comedolytic and antibacterial but does not lead to resistant organisms.
  • It can be irritating.
  • It also has a role in reducing hyperpigmentation.4

Topical Dapsone

  • This treatment comes as a topical gel formulation and is effective for inflammatory acne.
  • The benefit in women seems to exceed the benefit in male and adolescent patients.4

Topical fixed-dose combination therapies available include:

    • Clindamycin plus benzoyl peroxide
    • Clindamycin plus tretinoin
    • Benzoyl peroxide plus adapalene
  • The benefit of using topical combination therapies include targeting different pathogenic factors, faster resolution of lesions, and minimizing antibiotic resistance. They may also lead to improved adherence and efficacy.5,15
  • Both the fixed-dose combination of clindamycin 1.2% and tretinoin 0.025% gel (Biacna®) and benzoyl peroxide 2.5% and adapalene 0.1% gel (Tactuo®) were shown to be superior to the individual components and vehicle.15
  • Recent Canadian Practice Guidelines suggest treatment with benzoyl peroxide, topical retinoids or fixed dose combinations as first-line therapy for comedonal or mild to moderate papulopustular acne.15
  • Addition of systemic treatments such as oral contraceptive pills, oral antibiotics or isotretinoin can be considered particularly in the case of moderate to severe papulopustular acne.15
  • Adverse events related to topical acne therapies most commonly involve dryness, redness, burning, irritation and peeling.4 It is important to have strategies to manage these side effects (Box 1).

Box 1. Practical tips to increase adherence to topical retinoid containing acne medications


  1. Use at night. Cleanse your skin, pat dry. Can wait 10-15 minutes before applying the medication to lessen risk of irritation such as burning, stinging or itching.
  2. Apply a small amount of product evenly to each area of the face. Avoid eyes, mouth and nostrils.
  3. Don’t spot treat. Applying treatment to all areas is key to preventing new spots from developing.
  4. Use every other night to start. If well tolerated, increase to every night. Short-contact application of retinoids (minutes to a few hours) may be an option if significant irritation from the medication.
  5. Avoid using harsh cleansers, exfoliating scrubs, and astringents while using your topical treatment, especially if irritated.
  6. Consider applying a non-comedogenic moisturizer after the retinoid or mixing the retinoid with the moisturizer.
  7. If you develop significant irritation or stinging, stop treatment for 1-3 days, moisturize, and then restart your topical medication, applying it for 30-60 minutes for a few days before leaving it on for more prolonged time intervals.
  8. Make application part of your daily routine by placing the medication where you can easily see it, using it around the same time every day (ie. at the time of brushing your teeth), and setting up reminders on your phone.
  9. Protect your skin from the sun. Apply a broad-spectrum sunscreen with at least SPF30 daily.
  10. Don’t give up. It can take 6-8 weeks before any effect is seen.6

Tips for Acne Treatment

  1. To prevent development of new acne lesions, topical therapies should be applied to the affected areas (all over) rather than to the lesions alone.
  2. As many acne treatments are irritating, use a gentle skin-care regimen; avoid astringents and abrasive skin care products.
  3. Topical retinoids, benzoyl peroxide and topical combination therapies are effective and recommended as first-line therapy for many patients but are often underutilized due to patients having difficulty with irritation. It is important to review strategies to improve adherence (Box 1).
  4. Each time a topical medication is added or changed, allow several weeks of treatment before assessing effectiveness.
  5. Acne is a disease that commonly lasts years. Once control has been achieved, the treatment regimen may be simplified but maintenance therapy may be required.

Special Considerations

  • Adult acne may be seen in women of child bearing potential and may be seen after discontinuation of oral contraceptive pills, so it is important to understand treatments that are safe in pregnancy
  • Benzoyl peroxide and topical antibiotics such as clindamycin and erythromycin have been used extensively and both are generally considered safe in pregnancy.16
  • Glycolic acid and azelaic acid have low systemic absorption and are unlikely to pose a risk to the fetus.17
  • Although systemic absorption of topical dapsone appears low, safety in pregnancy has not been established.16
  • Safety of topical retinoids has not been sufficiently studied and their use remains contraindicated,17 however, one meta-analysis showing no major congenital malformations may be reassuring to those who have inadvertent exposure during early pregnancy.18
  • Consider adding a systemic therapy when topical therapy has not been effective after 2-3 months, or if topical treatments only have a small chance of success such as with moderate to severe acne.
  • Referral to a dermatologist can also be considered with refractory patients.

Summary

Acne remains a prevalent disease past the adolescence years. It is important to factor in the significant impact on quality of life for patients with this condition and to treat early to prevent complications such as dyspigmentation and scarring. Topical therapy is a cornerstone first-line treatment for mild to moderate acne. Education around proper application of the topical medicine and strategies to improve adherence should be reviewed with the patient. Maintenance treatment is important to prevent recurrence.

References

  1. Canadian Dermatology Association. Acne. Fact sheet, available at www.dermatology.ca. Last accessed May 17, 2017.
  2. Ramos-e-Silva M. Br J Dermatol. 2015 Jul;172(S1):20-6.
  3. Perkins AC, et al. J Womens Health. 2012 Feb;21(2):223-30.
  4. Zaenglien AL, et al. J Am Acad Dermatol. 2016 May;74(5):945-73.
  5. Lynde C, et al. J Cutan Med Surg. 2014 Jul-Aug;18(4):243-55.
  6. Kraft J, Frieman A. CMAJ. 2011 Apr 19;183(7):E430-5.
  7. Gollnick HPM. J Eur Acad Dermatol Venereol. 2015 Jun;29(S5):1-7.
  8. Brandstetter AJ, Maibach HI. J Dermatolog Treat. 2013 Aug;24(4):275-7.
  9. Dréno B, et al. J Eur Acad Dermatol Venereol. 2013 Sep;27(9):1063-70.
  10. Dréno B. J Eur Acad Dermatol Venereol. 2015 Jun;29(S5):14-9.
  11. Kakita L. J Am Acad Dermatol. 2000 Aug;43(2 Pt 3):S51-4.
  12. Rolewski SL. Dermatol Nurs. 2003 Oct;15(5)
  13. Nyirady J, et al. Cutis. 2002 Nov;70(5):295-8.
  14. Retin A Micro Product Monograph 2012.
  15. Asai Y, et al. CMAJ. 2016 Feb;188(2):118-26.
  16. Chien AL, et al. J Am Board Fam Med. 2016 Mar-Apr;29(2):254-62.
  17. Bozzo P, et al. Can Fam Physician. 2011 June;57(6):665-7.
  18. Kaplan YC, et al. Br J Dermatol. 2015 Nov;173(5):1132-41.