Ahmad Chehade1; Jaggi Rao, MD, FRCPC2

1PharmD Candidate at University of Alberta, Edmonton, AB, Canada
2Clinical Professor of Medicine, University of Alberta, Edmonton, AB, Canada

This manuscript was previously published in Skin Therapy Letter – Family Practice Edition Volume 12 Number 3, A Physician’s Guide to Treating Acne. Revised 2019.

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, dietary, and hormonal factors may also have a role.
  • Drug related causes of acne are not uncommon. Weighing the risks versus the benefit of continuing these medications must be considered. Some classes of medications notoriously known for acne eruption include, but are not limited to the following: anabolic steroids, corticosteroids, testosterone, lithium, and phenobarbital.6
  • Treatment should target as many factors as possible in order to prevent the formation of microcomedones and prevent scarring and post-inflammatory hyperpigmentation.5,7

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.8

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.9 The determination depends 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).
    • Three forms of topical retinoids: tretinoin, adapalene, and tazarotene. Mechanistically, each of these retinoids binds to a different set of retinoic acid receptors, therefore each retinoid is different in terms of potency, tolerability, and efficacy.10
    • 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.11,12
    • Adapalene is the least irritating.13
    • Tazarotene is the most potent but also the most irritating.13
  • Benzoyl Peroxide (BPO)
    • Mechanistically, benzoyl peroxide is a potent antimicrobial with no antibiotic resistance. It kills P.acnes via the release of free radicals.
    • BPO also has mild comedolytic effects.
    • It is important to note that Benzoyl may inactivate retinoids and topical antibiotics, therefore time spacing with administration or using combination products that are compatible is preferred.
  • 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 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.
  • 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.14,15

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.

Topical 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.
    • Category (X) interaction with tetracycline antibiotics, ensure to discontinue prior to its use.6
  • Combination Oral Contraceptives
    • The estrogen component of combined oral contraceptives suppresses ovarian androgen production and prevents androgen-mediated effects on the sebaceous follicle.
    • Estrogen products are contraindicated in those with clotting disorders and those with previous cardiovascular risk factors, history of these must be assessed.16

Tolerability and Adherence

  • Topical Benzoyl Peroxides
    • It’s best to avoid washes and soaps as the contact time is not sufficient to provide a sustained effect which is why gels, creams, and lotions are preferred.
    • Worsening may occur in the first few weeks of therapy, after which improvement will be seen. This initial worsening is commonly a reason why patients fail therapy with acne therapy in general.
    • Patients report dryness, stinging, bleaching, and erythema which usually subsides after a few days of treatment.
  • Topical Retinoids
    • Worsening may occur in the first few weeks, followed by notable improvement after that. Encouraging patients to maintain adherence is vital.
    • Adverse effects are similar to those of topical benzoyl peroxides, but photosensitivity is a distinctive characteristic of these agents (except for adapalene). Hence night time application is preferred.
  • Topical Combination Products
    • As per mentioned, products such as Biacna® gel (Clindamycin 1.2% + Tretinoin 0.025%) are important due to synergy in efficacy of the two active ingredients. Biacna’s alcohol free gel vehicle provides reduced irritation, which may help enhance patient adherence and potentially clinical outcomes.
    • Adverse effects are like their ingredients.
  • Oral Retinoids
    • Ensure patients have discontinued all tetracycline class antibiotics as these agents and oral retinoids interact, resulting in intracranial hypertension.6
    • Dual contraceptive methods should be used as these agents are teratogenic.
    • Reduced alcohol consumption or complete abstinence is recommended due to the risk of increased hepatotoxicity.
    • Monthly follow up of blood work is advised to assess ALT & AST
    • Worsening/flare is expected to be seen initially upon treatment (approximately the first eight weeks), coupled with a dryness to the skin and mucous membranes.
    • Photosensitivity is commonly reported with these agents, hence ensure the promotion of proper UV protectants.
    • Moisturization is vital with these agents.

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 (see 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 I (Comedonal) Acne Diagnosis:

  • Comedones (blackheads and whiteheads) only
  • No inflammation (pimples, pustules)
A Clinician’s Guide to Treating Acne - image
Figure 1. Grade 1 (Comedonal) Acne

Grade II (Inflammatory) Acne

  • Grade II acne (see 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 II (Inflammatory) Acne Diagnosis:

  • Inflammatory papules (pimples)
  • +/- coexistent comedones
A Clinician’s Guide to Treating Acne - image
Figure 2. Grade 2 (Inflammatory) Acne

Grade III (Inflammatory) Acne

  • Grade III acne (see 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 III (Inflammatory) Acne Diagnosis:

  • Inflammatory papules (pimples)
  • More intense or widespread
  • Presence of pustules
  • +/- coexistent comedone
Figure 3. Grade III (Inflammatory) Acne
Figure 3. Grade III (Inflammatory) Acne

Grade IV (Nodulocystic) Acne

  • Grade IV acne (see 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.17

Grade IV (Nodulocystic) Acne Diagnosis:

  • Presence of nodules and/or cysts
  • +/- Inflammatory papules (pimples), pustules and comedones
  • +/- textural scarring
Grade IV (Nodulocystic) Acne
Figure 4. Grade IV (Nodulocystic) Acne

Hormonal Acne

  • Hormonal acne (see 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.

Hormonal Acne Diagnosis:

  • Typically seen in females
  • Lower face (cheeks, chin, jawline), submental
  • Monomorphic inflammatory papules, cysts
  • Deep-seated and tender
Hormonal Acne
Figure 5. Hormonal Acne

Perioral Dermatitis

  • Perioral dermatitis (see 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.

Perioral Dermatitis Diagnosis:

  • Typically seen in females
  • Acneiform or eczematous papules
  • Superficial and deep
  • Around the mouth, nose and/or eyes
Perioral Dermatitis
Figure 6. Perioral Dermatitis

Practical Tips

  • It is very important to focus on individual patient considerations.
  • Topical therapies should be applied to entire affected areas not spot treated.
  • 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.
  • Picking and touching lesions will result in aggravation of acne and potentially inducing further scarring. Patients should be discouraged from such behaviour.
  • Consider patient tolerability and skin type.
    • Opt for a more tolerable retinoid, causing less irritation and dryness.
  • Counsel patient on proper application, moisturizing and cleansing.
    • Less is more.
    • Use non-oily moisturizers and gentle cleansers.
    • Use oil-free make-up, try to avoid multiple layers.

 


Updated on April 18, 2019. Numbering corrections have been made for citation superscripts and references. 

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