Jaggi Rao, MD, FRCPC 
Clinical Professor of Medicine, University of Alberta, AB, Canada

Introduction

Acne is among the most common dermatological conditions seen in primary care. It is estimated to affect 2 million Canadians, and 85 to 90% of adolescents.1 Individuals of all ages can have acne, but most cases develop in adolescence.2 Acne is considered a chronic disease with up to 50% of cases persisting into adulthood.3 Its impact on psychological, social, and emotional wellbeing can be devastating, and can be worse than that reported by patients with chronic asthma, epilepsy, back pain, or arthritis.4 Early and aggressive treatment is important to prevent scarring and help improve quality of life. Maintenance therapy is recommended for optimal outcomes. In this article, we provide a guide to address a growing need by primary care physicians to have a logical and practical approach to treating various forms of acne.

Background

  • Acne is a chronic inflammatory disorder of pilosebaceous units of the skin.
  • Acne nearly always affects the face (99%), but can also affect the back (60%) and chest (15%).5
  • The pathogenesis of acne is multifactorial. The most notable pathophysiologic factors that influence its development are: hyperkeratinization, increased sebum production, Propionibacterium acnes colonization of the follicle, and inflammation. Studies have also suggested that genetic, hormonal, and dietary factors may also have a role.
  • Treatment should target as many factors as possible in order to prevent the formation of microcomedones and prevent scarring and post-inflammatory hyperpigmentation.5,6

The Lesions of Acne

  • Microcomedones are microscopic plugged follicular openings that are not visible to the naked eye. They are the precursors for all acne lesions.
  • Noninflammatory lesions include:
    • Closed comedones (whiteheads) are small, skin-colored papules that lack an obvious follicular opening.
    • Open comedones (blackheads) have a dilated follicular opening filled with a keratin plug, which has a black color due to oxidized lipids and melanin.
  • Inflammatory lesions include:
    • Erythematous papules and pustules.
    • Nodules and cysts, which may contain pus or serosanguinous fluid.
  • Inflammation has been demonstrated to some degree, in all acne lesions.
    • Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways.7

Clinical Severity

Acne is commonly described as mild, moderate or severe. A descriptive scale, known as the Physician’s Global Assessment (PGA), is also used to categorize acne.8 The determination depend on types, severity, and number of lesions.

Treatments

Topical Treatments

Topical treatments are widely considered to be a mainstay of care because they effectively target the pathogenic factors and address the other key considerations of acne. Generally, once daily is the suggested frequency of application for any topical agent, to increase compliance and reduce irritation side effects. Most experts advocate only a thin layer of topical agent be applied to the affected areas. Topical treatments for acne include:

  • Topical Retinoids
    • These are both anti-inflammatory and comedolytic (i.e. inhibit formation of or treat comedones).
    • Tretinoin is the most cost effective but is slightly irritating and the most photosensitizing; also available in a controlled release microsphere formulation for better tolerability and photostability.9,10
    • Adapalene is the least irritating.11
    • Tazarotene is the most potent but also the most irritating.11
  • Benzoyl Peroxide (BPO)
    • This is a potent antimicrobial with no antibiotic resistance. It kills P. acnes via the release of free radicals.
    • BPO also has mild comedolytic effects.
  • Topical Antibiotics
    • Topical antibiotics act directly on P. acnes and reduce inflammation.
    • Clindamycin and erythromycin are most commonly used.
    • Antibiotics tend to be very well tolerated compared with other topical agents.
    • Should not be used as monotherapy due to the potential for antibiotic resistance.
  • Combination Therapy
    • BPO with an antibiotic
    • BPO with a topical retinoid
    • Topical retinoid with an antibiotic
    • BPO and retinoids have a synergistic effect with topical antibiotics, increasing efficacy, and possibly mitigating the risk of developing resistant bacterial strains.
  • Topical Dapsone
    • Dapsone is a sulfone with anti-inflammatory and antibacterial properties.
    • It has been shown to be more effective in female patients than males.12, 13

Over-the-counter lotions and cleansers, such as those containing BPO, salicylic acid or alpha hydroxy acids are also available, but can be less efficacious than prescribed products depending on acne severity.

Oral Treatments

  • Oral Antibiotics
    • Like topical antibiotics, these have both antimicrobial and anti-inflammatory properties.
    • The most common include doxycycline, minocycline and tetracycline.
    • Antibiotic resistance is a concern. Most experts suggest using oral antibiotics for no more than 6 continuous months of duration.
  • Oral Retinoid (Isotretinoin)
    • Oral isotretinoin is used for severe and treatment-resistant acne.
    • It is the only agent that targets all four of the pathogenic mechanisms of acne.
    • It is teratogenic.
  • Combination Oral Contraceptives
    • The estrogen component of combined oral contraceptives suppresses ovarian androgen production and prevents androgen-mediated effects on the sebaceous follicle.

A Physician’s Guide for Treating Acne

There is an increasing need by primary care physicians to have a logical and practical approach to treating acne. The following recommendations will effectively assist physicians in diagnosing and treating acne.

Grade I (Comedonal) Acne:

  • Grade I acne (Figure 1) consists of only comedones (blackheads and whiteheads). No inflammation (i.e. no pimples or pustules) is present.
  • The best topical treatment options are retinoids or fixed-dose combination as per Canadian guidelines.
    • Retinoids:
      • Tretinoin – 0.025%, 0.05%, 0.1% cream or gel
      • Tretinoin gel microsphere – 0.04% gel or 0.1% gel
      • Adapalene – 0.1% or 0.3% gel, 0.1% cream
      • Tazarotene – 0.1% cream or gel
    • Fixed-dose combinations:
      • Clindamycin 1%/ BPO 5%
      • Clindamycin 1.2% / Tretinoin 0.025%
      • Adapalene 0.1% / BPO 2.5% gel pump
      • Adapalene 0.3% / BPO 2.5% gel pump
      • Erythromycin 3% / BPO 5%

Grade II (Inflammatory) Acne

  • Grade II acne (Figure 2) presents with inflammatory papules (pimples) with or without comedones.
  • The best topical treatment options include:
    • Clindamycin 1.2% / Tretinoin 0.025%
    • Clindamycin 1% / BPO 5% gel pump
    • Adapalene 0.1% / BPO 2.5% gel pump
    • Adapalene 0.3% / BPO 2.5% gel pump

Grade III (Inflammatory) Acne

  • Grade III acne (Figure 3) presents with more intense or widespread inflammatory papules (pimples) as well as pustules. Comedones may or may not be involved.
  • The best topical treatment options include the following:
    • Clindamycin 1.2% / Tretinoin 0.025%
    • Clindamycin 1% / BPO 5% gel pump
    • Adapalene 0.1% / BPO 2.5% gel pump
    • Adapalene 0.3% / BPO 2.5% gel pump
    • An oral antibiotic such as doxycyline, minocycline, tetracycline, trimethoprim-sulfamethoxazole, or erythromycin can be used in combination with BPO.

Grade IV (Nodulocystic) Acne

  • Grade IV acne (Figure 4) presents with nodules and/or cysts; inflammatory papules (pimples), pustules. Comedones and textural scarring may or may not be involved.
  • The best treatment options include the following:
    • Oral isotretinoin
    • Systemic antibiotics in combination with topical benzoyl peroxide, with or without a topical retinoid for patients unwilling or unable to use oral isotretinoin and those with intolerance.14

Hormonal Acne

  • Hormonal acne (Figure 5) is typically seen in females on the lower face (cheeks, chin, jawline), submental region and presents with monomorphic inflammatory papules and cysts that are deep-seated and tender.
  • The best topical treatment options include:
    • Dapsone 5% gel or Clindamycin 1%/BPO 5% gel pump
    • WITH an oral anti-hormonal medication such as an oral contraceptive or spironolactone.

Perioral Dermatitis

  • Perioral dermatitis (Figure 6) is typically seen in females. It presents around the mouth, nose and/or eyes with acneiform or eczematous papules that are superficial and deep.
  • The best topical treatment options include:
    • Pimecrolimus 1% cream
    • Tacrolimus 0.1% ointment
    • WITH oral antibiotic such as doxycyline, minocycline, tetracycline, trimethoprim-sulfamethoxazole, or erythromycin and or in combination with BPO.

Types of acne and diagnosis

Practical Tips

  • It is very important to focus on individual patient considerations.
  • Topical therapies should be applied to entire affected areas of the face.
  • Combination treatment leads to better patient adherence. Simpler and combined regimens provide increased convenience and better outcomes.
  • Manage patient expectations (i.e. efficacy, side effects, and treatment duration). Minimum follow up time should be eight weeks between appointments. This will give sufficient time to see the effects of interventions.
  • Consider patient tolerability and skin type.
    • Opt for a more tolerable retinoid, causing less irritation and dryness.
  • Counsel patient on proper application and moisturizing.
    • Less is more.
    • Use non-oily moisturizers and gentle cleansers.

References

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  2. James WD. N Engl J Med. 2005 Apr 7;352(14):1463-72.
  3. Thiboutot D et al. J Am Acad Dermatol. 2009 May;60(5 Suppl):S1-50.
  4. Mallon E et al. Br J Dermatol. 1999 Apr;140(4):672-6.
  5. Nast A et al. J Eur Acad Dermatol Venereol. 2016 Aug;30(8):1261-8.
  6. Gollnick H et al. J Am Acad Dermatol. 2003 Jul;49(1 Suppl):S1-37.
  7. Dreno B, et al. J Eur Acad Dermatol Venereol. 2015 Jun;29(4 Suppl):3-11.
  8. Pascoe VL et al. JAMA Dermatol. 2015 Apr;151(4):375-81.
  9. Berger R et al. Clin Ther. Jun;29(6):1086-97.
  10. Nyirady J et al. Cutis. 2002 Nov;70(5):295-8.
  11. Kalita L. J Am Acad Dermatol. 2000 Aug;43(2 Pt 3):S51-4.
  12. Zaenglein AL et al. J Am Acad Dermatol. 2016 May;74(5):945-73.
  13. Tanghetti E, et al. J Drugs Dermatol. 2012 Dec;11(12):1417-21.
  14. Asai Y. CMAJ. 2016 Feb 2;188(2):118-26.