acne%20vulgaris
ACNE VULGARIS
Acne vulgaris is a chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads) and inflammatory lesions including papules, pustules or nodules.
Mild acne has <20 comedones or <15 inflammatory lesions or <30 total lesion count.
Moderate acne has 20-100 comedones or 15-20 inflammatory lesions or 30-125 total lesion count.
Severe papules/pustules or nodulocystic acne is the acne resistant to topical treatment or if scarring/nodular lesions are present.

Pharmacotherapy

Topical Agents

Retinoids

  • Eg Adapalene, Tazarotene, Tretinoin
  • Comedolytic and occasionally anti-inflammatory
    • Reduce formation of acne precursor lesions (microcomedones), limit development of new lesions, promote desquamation of follicular epithelium and reduce inflammatory and non-inflammatory lesions
  • Effective 1st-line agents in the treatment of comedonal (non-inflammatory) and inflammatory acne
  • Used as monotherapy for uninflamed, mild, comedonal acne and in combination with antibiotics for inflamed lesions
  • Treatment of choice for maintenance therapy for the duration of 12 months
  • Adapalene
    • May be useful as monotherapy in mild to moderate forms of acne by reducing both inflammatory and non-inflammatory lesions
    • Effects: Potent modulator of keratinization, cellular differentiation and inflammatory process
    • Most tolerated topical retinoid, more effective and less irritating than Tretinoin for the treatment of inflammatory and non-inflammatory lesions
  • Tazarotene
    • Has been shown to reduce the number of non-inflammatory lesions counts in mild to moderate acne
    • Effects: Modifies the accumulation and cohesion of corneocytes, and the inflammation process
    • Associated with a higher incidence of erythema, burning, pruritus and peeling than Tretinoin or Adapalene
  • Tretinoin
    • Effective as monotherapy in treatment of non-inflammatory and mild to moderate inflammatory acne
    • Effects: Nomalizes the keratinization process within the hair follicle and prevents formation of comedones
    • Patients should be warned that they may suffer pustular flare during 1st few weeks of therapy
      • Should not stop therapy because this flare indicates accelerated resolution of existing acne
  • Tretinoin Gel Microsphere
    • Formulation which is designed to improve tolerability of topical Tretinoin
    • Microspheres allow for gradual release of medication which may limit delivery to the lower layers of the skin
    • May reduce irritation and therefore increase patient compliance
  • Tretinoin Polyoprepolymer-2 (PP-2)
    • Drug delivery system which retains the drug on and in the upper layers of skin which may limit irritation
      • May be better tolerated because of the decrease in irritation

Azelaic Acid

  • Mild comedolytic and anti-inflammatory 
  • Has been shown to be as effective as Benzoyl peroxide, Tretinoin and topical Erythromycin in patients with mild to moderate inflammatory acne
  • 2nd choice for maintenance therapy, an alternative to retinoids
  • Treatment option for pregnant women with acne or patients with acne and postinflammatory hyperpigmentation (PIH)
  • Effects: Has bacteriostatic properties and may reduce follicular microbial colonization by >97%
    • Normalizes keratinization along with reducing inflammation
  • Local adverse effects are generally less than Benzoyl peroxide or Tretinoin

Benzoyl Peroxide

  • Monotherapy is used in the treatment of comedonal or mild acne, and usually given in combination with topical antibiotics or retinoids for mild to severe acne; considered a mainstay in acne therapy
  • Effects: Bactericidal activity reduces P acnes by producing reactive O2 species in the sebaceous follicle
    • Inflammatory and non-inflammatory lesions are rapidly improved

Antibiotics

  • Useful for mild to moderate acne with inflammatory lesions in combination with other topical agents
  • Should not be used as monotherapy for moderate to severe acne or as maintenance therapy for acne
  • Effects: Reduce P acnes in sebaceous follicles and have anti-inflammatory properties
  • Recommend that topical antibiotics be used in combination with Benzoyl peroxide or retinoid to decrease antibiotic resistance
  • When possible, treatment duration is only up to 12 weeks
  • Erythromycin and Clindamycin: Equally effective in treating moderate acne
  • Dapsone 5% gel, which possesses both antimicrobial and anti-inflammatory properties, is used as an option for patients with mild acne preferably in combination with a topical retinoid
  • Sodium sulfacetamide, available alone or combined with Sulfur, acts as a keratolytic

Salicylic Acid

  • May be used in mild acne or as an adjunctive agent when patients are intolerant of standard therapy
  • Commonly found in facial cleansers
  • 3rd choice for maintenance therapy
  • Effects: Has mild comedolytic and anti-inflammatory effects
  • Various products containing Salicylic acid are available. Please see prescribing information for specific formulations in the latest MIMS.

Considerations When Choosing Topical Agent

Patient Skin Type

  • Oily skin: Gel or solution are usually preferred
    • In hot, humid countries, acne lotion containing Salicylic acid and Resorcinol is useful to make skin dry
  • Dry skin: Creams or ointment are usually preferred

Combinations

  • If >1 topical agent is being used, it is best to instruct patient to apply 1 agent in the morning and the other agent at night
  • Combination topical therapy for the treatment of acne is found to be more effective and is preferrable than topical antibiotic alone
  • Combination should consist of agents from different classes (eg Benzoyl peroxide + topical antibiotic, Benzoyl peroxide + Tretinoin)
    • Retinoid-Benzoyl peroxide combinations are limited because of the instability of retinoids (except Adapalene) with Benzoyl peroxide
      • Recommended 1st-line therapy in patients with inflammatory acne, comedonal acne, or both
  • Products containing a fixed combination of agents from different classes are available
    • Fixed combination products may be more convenient and may increase patient compliance
    • Adapalene + Benzoyl peroxide is the first topical fixed combination therapy for severe inflammatory acne
      • Has greater efficacy seen as early as the first week of treatment compared with monotherapy
      • May be used alone or in combination with other therapies before Oral Isotretinoin is prescribed
      • Adapalene + Benzoyl peroxide + Doxycycline is an alternative to Isotretinoin in patients with severe acne who are intolerant pr unwilling to take Isotretinoin

Oral Agents

Antibiotics

  • Must never be used as monotherapy for moderate to severe acne
  • Typically used for moderate to severe inflammatory acne that does not respond to topical combinations or for acne with high scarring potential
  • Choice of antibiotic is based on side effect profiles and local patterns of resistance
  • Maximum course of treatment should be 3-4 months but treatment response assessment should be at 6-8 weeks
  • Effects: Suppress the growth of P acnes which helps to reduce the production of inflammatory factors
  • Azythromycin
    • Antibiotic resistance with Azithromycin use has been reported
    • Should be used with caution in patients at risk for severe adverse effects such as toxic epidermal necrolysis,but with less associated side effects compared to Erythromycin
  • Erythromycin
    • Effects: Associated with less anti-inflammatory activity and more gastrointestinal side effects than Tetracycline
    • There tends to be more resistance of P acnes to Erythromycin than to Tetracycline
    • Decreased risk of photosensitivity compared to Tetracycline
  • Tetracycline
    • Penetrates into the follicular canal
    • Development of P acnes resistance is a potential problem and should be suspected if acne worsens after several months of treatment
  • Doxycycline
    • Considered as an excellent 1st-line agent for inflammatory acne
    • P acnes resistance has also been reported
  • Minocycline
    • May be used as 2nd-line antibiotic treatment for inflammatory acne 
    • Fewer reports of P acnes resistance compared to Tetracycline and Doxycycline
    • Tendency to produce rare serious side effects is greater than Tetracycline and Doxycycline
  • Co-trimoxazole
    • Considered as 3rd-line therapy when other therapies have failed 
    • Effective in patients refractory to other oral antibiotics or for Gram-negative acne
    • Low but possible risk for major side effects should be considered

Isotretinoin

  • Recommended 1st-line therapy for very severe (cystic and conglobate) acne 
  • Most effective agent for severe acne and nodulocystic acne and provides a prolonged remission period
  • Effects: Reduces sebum excretion, comedogenesis, ductal and surface P acnes by 80%
    • Shown to have anti-inflammatory properties
  • Treatment is usually for 20 weeks with continuation of improvement for up to 5 months after ending treatment
    • Relapse may occur in 15% of patients
  • Isotretinoin is a known teratogen and therefore, childbearing-aged females must be tested for pregnancy prior to therapy
  • Severe adverse effects may limit use

Intralesional Agents

Intralesional Corticosteroid Agents

  • Eg Triamcinolone acetate
  • May be used for large nodulocystic lesions

Adjunctive Therapy:

Chemical Peels (Other than Salicylic acid)

  • Eg Glycolic acid, Lactic acid, Trichloroacetic acid
  • Actions: Inhibit tyrosinase activity
  • Found to be safe, effective and can significantly improve moderate acne in Asians

Keratolytic Agents

  • Eg Sulfur, Resorcinol
  • May be used as an adjunctive treatment together with other anti-acne agents
  • Further studies are needed to prove the efficacy of chemical peels for acne

Other Therapies for Acne

  • Comedo removal: For treatment-refractory comedones
  • Tea tree oil (Melaleuca alternifolia): Reduces number of lesions in mild to moderate acne
  • Psidium guajava extract: With antimicrobial effects against P acnes
  • Though herbal and complementary therapies seem to be well tolerated, data on the safety and efficacy of these therapies are limited

Adjunctive Hormonal Therapy

Oral Contraceptives

  • Eg Ethinyl estradiol/Norgestimate, Ethinyl estradiol/Norethindrone acetate, Ethinyl estradiol/Norethindrone acetate/Ferrous fumarate, Ethinyl estradiol/Drospirenone, Ethinyl estradiol/Drospirenone/Levomefolate 
  • Combined oral contraceptive (estrogen andprogestin) is an alternative for women with moderate to severe acne who do not respond to conventional acne therapies or with lesions limited to lower half of face
  • Progestin-only oral contraceptives are not effective and may aggravate acne
  • Responses may not be observed until after 3-6 months of treatment, and some patients may experience a flare of symptoms during early cycle
  • Effects: Androgen-modulating properties are attributed to the estrogen component, decreases androgen production and reduces excess testosterone by increasing sex-hormone binding globulin production, thereby deactivating free androgen receptors; suppresses sebum formation

Cyproterone acetate

  • Anti-androgen given with either Ethinylestradiol or a contraceptive

Spironolactone

  • Alternative antiandrogen therapy with potential to significantly improve acne severity and sebum production
  • Alternative for women with moderate to severe acne and unresponsive to conventional therapy or unwilling to take Isotretinoin
  • Effects: Decreases testosterone production, inhibits testosterone and dihydrotestosterone binding to dermal androgen receptors, inhibits 5-alfa-reductase, and increases steroid hormone-binding globulin

Flutamide

  • A nonsteroidal selective androgen receptor blocker being studied for use in the management of acne
  • Flutamide-induced fatal hepatitis limits the use of this agent for acne, unless benefit outweighs the risk

Non-Pharmacological Therapy

Skin Care Recommendations

  • Wash affected area 2x daily with pH-balanced mild soap or cleanser, pat dry then apply acne treatment
    • Frequent washing especially with harsh soaps may aggravate the condition
  • Topical acne therapy needs to be applied as a thin coat to all acne-prone areas, not just to individual lesions
  • Proper selection of topical formulation may decrease side effects and increase compliance
    • Creams and lotion for very dry skin
    • Gel and solutions for very oily skin
    • Cream-based cleansers should be avoided
  • If skin becomes dry from topical treatments, patient may use oil-free, non-comedogenic and fragrance-free moisturizers
  • Use sunscreen if photosensitizing antibiotics or retinoids are prescribed
  • Picking at lesions should be avoided
    • Traumatizing lesions can lead to increased inflammation, prolonged resolution and increased chance of scarring
  • Do not cover acne with tight-fitting clothing or bandages

Dermatocosmetics

  • “Cosmeceuticals” that are used as adjuncts to standard acne therapy and aid in decreasing side effects (eg irritation, dryness, photosensitivity) and need for topical antibiotics 
    • Include skin cleansers, comedolytics, moisturizers, sebum-controlling agents, anti-inflammatory/antimicrobial agents, sunscreens, skin-lightening agents and camouflage products 
  • Moderate use of non greasy lubricants and water-based cosmetics is usually well tolerated, but a gradual decrease in the use of cosmetics is encouraged as acne improves

Photodynamic Therapy

  • Photodynamic therapy (PDT) involves the use of light to activate photosensitive products
    • Eg 5-aminolevulinic acid (ALA), methyl aminolevulinate (MAL), indocyanine green (ICG)
  • May be used as an adjunct to medical therapy until its effectiveness has been better validated
  • Effects: Causes structural damage to bacterial cell membranes, decreases bacterial populations and results in reduction of inflammatory acne lesions by 59-67%
  • ALA-PDT is the most extensively studied modality
    • Provides the best results when used to treat inflammatory and cystic acne
  • The treatment can be administered in 8-15 minutes and is generally well tolerated
  • An average of 3 treatments can yield significant long-term improvement
  • Sun avoidance and protection is necessary for up to 48 hours following therapy
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