Lisa W. Fu, BHSc and Ronald B. Vender, MD, FRCPC

Department of Medicine, McMaster University, Hamilton, ON, Canada


Acne vulgaris is a common chronic inflammatory cutaneous disease involving the pilosebaceous unit. Its pathophysiology is multifactorial and complex, including obstruction of the pilosebaceous unit due to increased sebum production, abnormal keratinization, proliferation of Propionibacterium acnes (P. acnes), and inflammation.

Topical agents are the most commonly used therapy for acne. First generation topicals mainly consist of single agent retinoids, benzoyl peroxide (BP), and antibacterials that target comedones, P. acnes, and inflammation. Novel topical therapies include combination products with advanced vehicle formulations that target multiple acne pathophysiologies and offer simplified treatment regimes. For example, the combination of clindamycin and tretinoin in a unique vehicle formulation of suspended crystalline tretinoin allows for progressive follicle penetration and decreased irritation, resulting in increased efficacy. Furthermore, adapalene or clindamycin with BP combinations target comedones, inflammation, and P. acnes synergistically. These newer combination products have the potential to increase both efficacy and patient adherence when compared with single agent treatment.

Disease Overview

Diagnostic Features and Grading (Table 1)

  • Acne vulgaris has distinguishing comedones (open and closed) and inflammatory lesions in the form of papules, pustules, or nodules and cysts.1,2
  • The presence of comedones confirms the diagnosis of acne vulgaris.3
MildIOpen and closed comedones and few inflammatory lesions
Mild to moderateIIComedones with occasional inflammatory papules and pustules that are confined to the face
Moderate to severeIIIMany comedones with small and large inflammatory papules and pustules; more extensive but confined to the face
SevereIVMany comedones and inflammatory lesions with nodules and cysts tending to coalesce and canalize; involving the face and the upper aspects of the trunk

Table 1: Severity grading of acne vulgaris2,3

Differential Diagnosis Include:

  • Rosacea
  • Perioral dermatitis
  • Bacterial folliculitis
  • Drug induced acneiform eruptions

Prevalence, Pathophysiology and Psychosocial Impacts

  • Acne is a common worldwide skin disease that affects about 85% of individuals between the ages of 12-24 years.4
  • The four main pathophysiologic features include:3
    1. androgen-mediated stimulation of sebaceous gland activity,
    2. abnormal keratinization leading to follicular plugging (comedone formation),
    3. proliferation of P. acnes within the follicle, and
    4. inflammation.
  • Genetic factors, stress, and possibly diet may influence the development of acne.3
  • Acne can cause a considerable amount of emotional distress and physical discomfort, thus, medical treatment must be accompanied by patient counseling and education, which can contribute to improved self-esteem and adherence to therapy.

Topical Treatment Overview and Options

Topical therapy (Tables 2 and 3) is used for mild to moderate acne and also for maintenance therapy in all levels of disease severity.

Acne SeverityTreatment
  • Topical retinoids for treatment and maintenance
Mild to moderate
  • Benzoyl peroxide + topical antibiotics +/– topical retinoids; 8 to 12 week course
Moderate to severe
  • Topical therapies used in mild to moderate acne + oral antibiotics for a minimum of 6 to 8 weeks
  • Oral isotretinoin; 16 to 20 week course

Table 2: Treatment indications based on acne severity3-5

Drug TypeTopical Acne AgentsOverview
  • Adapalene
  • Tazarotene
  • Tretinoin
  • Effective against acne vulgaris through comedolysis, which acts to reduce dyskeratosis at the pilosebaceous unit
  • Inhibits the formation of microcomedones and has mild anti-inflammatory effects6
  • Gel, cream, and solution formulations may induce irritation and dryness
  • Advanced formulations include an emollient cream and microsphere gel
  • Vehicle delivery advancements reduce irritation and enhance efficacy
  • Benzoyl peroxide
  • Clindamycin
  • Erythromycin
  • Sodium sulfacetamide
  • Bactericidal or bacteriostatic action directed against P. acnes
  • Formulated in creams, lotions, and gels
  • Can induce irritation and dryness
  • Benzoyl peroxide may bleach coloured fabrics
  • Antibiotics have anti-inflammatory properties
  • Sulfonamides inhibit P. acnes with limited potential for antibiotic resistance
Combination products
  • Benzoyl peroxide + antibiotic
  • Retinoid + antibiotic
  • Facilitates treatment of multiple pathogenic factors that are complementary and synergistic in mechanisms of action
  • Combined efficacy is greater than either agent alone6
  • Gel formulations
  • Simplifies treatment regimen and reduces dosing frequency
  • Combined use of benzoyl peroxide + topical antibiotic can reduce bacterial resistance; once opened, these products have a limited shelf life (3 to 4 months)

Table 3: Topical therapies currently used for acne vulgaris treatment5

Newer Novel Topical Agents

Clindamycin Phosphate 1.2% + Tretinoin 0.025% Gel (Biacna™)

  • This fixed-dose combination gel was approved by Health Canada in December 2010 for the topical treatment of acne vulgaris in patients ≥12 years of age.7
  • It combines the anti-inflammatory and antibacterial actions of clindamycin with the comedolytic and anticomedogenic actions of tretinoin7 to target several mechanisms in the pathogenesis of acne.
  • Multiple studies have demonstrated significantly greater reductions in comedones and inflammatory lesions by 12 weeks compared with either agent alone or vehicle.8-10
  • A more rapid reduction in acne lesions was observed by 8 weeks compared with either agent alone or vehicle.8
  • Application is recommended once-daily at bedtime (preferred) or morning (as the vehicle delivery formulation provides for the photostability of tretinoin).7
    • Patients should be instructed to use only a pea-sized amount.
  • Vehicle characteristics
    • It is available as an aqueous gel that is alcohol free with a unique formulation.11
    • It contains solubilized clindamycin phosphate and a stable combination of both solubilized and crystalline tretinoin.11
    • The crystalline suspension allows for tretinoin to be released in a rate-controlled manner, thereby resulting in slower and progressive follicular penetration and increased tolerability.11
    • Long-term efficacy and a favourable safety profile was shown in a 52 week study.12
  • Side-effects and contraindications
    • Crohn’s disease, ulcerative colitis, colitis with previous antibiotic therapy, use of concomitant erythromycincontaining products, pregnancy (category C)7
    • Side-effects from topical retinoids may include peeling, redness, dryness, itching, and photosensitivity
    • Because tretinoin increases the skin’s sensitivity to UV light, patients should be reminded to avoid excessive or unnecessary sun exposure and wear sunscreen and protective clothing daily.

Adapalene 0.1% + Benzoyl Peroxide 2.5% Gel (Tactuo™)

  • This combination treatment was Health Canada approved in May 2011.
  • Proposed mechanism of action: adapalene has comedolytic, anticomedogenic, and anti-inflammatory effects and BP is a highly lipophilic oxidizing agent with bacteriocidal and keratolytic effects.13
  • BP lowers the incidence of bacterial resistance compared with other topical antibiotics and can be used for the longterm management of acne.
  • The complementary modes of action address 3 out of the 4 pathophysiologic processes of acne:
    1. abnormal keratinization leading to follicular plugging (comedone formation),
    2. proliferation of the bacterium P. acnes within the follicle, and
    3. inflammation.
  • Large double-blinded randomized controlled trials showed that this combination gel was significantly more effective than the respective monotherapies, producing marked differences in total lesion counts.14,15
  • Studies demonstrated a comparable safety profile to adapalene.15
  • Adapalene is stable when combined with BP in the presence or absence of light.13
  • Once-daily dosing provides regime simplicity.

Bacterial Resistance in Acne

  • Antibiotics are recommended for use with BP (available in gel, lotion, and wash).
  • BP is an efficient bactericidal agent that will minimize the development of bacterial resistance at skin sites where topical antibiotic (i.e., clindamycin and erythromycin) therapy is applied.
  • BP is effective against both nonresistant and resistant P. acnes strains.16
  • A 4-week randomized study of patients with mild to moderate acne explored the safety and tolerability of fixed combination clindamycin phosphate and tretinoin gel (CT) once-daily in conjunction with morning use of a BP wash, targeting several pathologic factors and limiting the potential for clindamycin-induced P. acnes resistant strains.17
    • Side-effects were mild and included transient dryness, scaling, erythema, burning, stinging, and itching during the first week of therapy, then improving within 1-2 weeks.
    • CT gel + BP wash was shown to be a safe and welltolerated therapeutic regimen to effectively treat acne while mitigating the potential for bacterial resistance.

Patient Adherence

Acne is a chronic disease and poor medication adherence is a major contributor to treatment unresponsiveness.18 Factors that can impact treatment follow-through include:

  • Convenience and decreased complexity of treatment encourage patient adherence.
  • Treatment regimens that are effective and well-tolerated, as well as simple and easy to incorporate into the patient’s lifestyle, are more likely to increase adherence.
  • Patients most commonly attribute frustration with the therapeutic regimen and forgetfulness as reasons for failure to use prescribed medications.19


The successful topical treatment of acne depends on appropriate agent selection based on patient-specific acne severity, tolerance, adherence, and adequate follow-up. The advent of combinational therapeutic products provide increased efficacy by targeting multiple pathophysiologic processes. Additional advantages of using combination therapy include reduced complexity of treatment regimen and convenient once-daily dosing. The future of topical acne treatment holds the promise of more novel uses of conventional anti-acne agents formulated with advanced vehicle delivery systems that offer less side-effects, increased tolerance, dosing simplicity, and improved efficacy.


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