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
  • 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
    • Effective as monotherapy in treatment of non-inflammatory and mild-moderate inflammatory acne
    • Effects: Normalizes 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

  • 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
  • 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

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.

Benzoyl Peroxide

  • Monotherapy is used in the treatment of comedonal or mild acne, & 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-moderate acne with inflammatory lesions in combination with other topical agents
  • Should not be used as monotherapy for moderate to severe 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
  • Sodium sulfacetamide: Available alone or combined with Sulfur, which acts as a keratolytic

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 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
  • Products containing a fixed combination of agents from different classes are available
    • Fixed combination products may be more convenient and may increase patient compliance

Oral Agents

Antibiotics

  • Must never be used as monotherapy for moderate to severe acne
  • Typically used for moderate-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 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 w/ less associated side effects compared to Erythromycin 
  • Erythromycin
    • Effects: Associated with less anti-inflammatory activity and more GI 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 acne 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 acne resistance has also been reported
  • Minocycline
    • 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
    • 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

  • Most effective agent for severe acne and nodulocystic acne
  • 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: Inhibits tyrosinase activity
  • Further studies are needed to prove the efficacy of chemical peels for acne

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-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-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 & 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 & sebum production
  • Effects: Decreases testosterone production, inhibits testosterone & dihydrotestosterone binding to dermal androgen receptors, inhibits 5-alfa-reductase, & 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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