Acne%20vulgaris Treatment

• Management is based on types of acne lesions and severity of acne, patient history (history of previous acne treatments, childbearing potential), with all contributing factors identified and treated accordingly 
  • Topical therapy is the primary form of treatment for mild acne
  • Topical and systemic therapies are the principal forms of treatment for moderate to severe acne

Goals of Therapy

• Induce clearance of acne lesions
• Prevent physical and psychological complications
• Maintain remission and prevent relapse

Phases of Pharmacological Therapy

• Initial or induction phase: Induce acne remission using topical or systemic agents
• Maintenance phase: Use of mainly topical agents has been shown to control acne, prevent relapses and minimize sequelae

Topical Agents

• Used for induction of remission and maintenance phases of treatment
• Applied directly on the skin which increase exposure of the pilosebaceous units to the treatment while limiting systemic absorption
• Principal treatment for patients with mild acne and useful for patients with moderate acne

Retinoids

• Eg Adapalene, Tazarotene, Tretinoin, Trifarotene
• 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 and moderate to severe acne
• Treatment of choice for maintenance therapy for the duration of 12 months
• Childbearing status of female patient should be assessed prior to initiation of treatment

• Adapalene
  • May be useful as monotherapy in mild to moderate forms of acne by reducing both inflammatory and non-inflammatory lesions
  • 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
  • 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
  • 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
• Trifarotene
  • Gamma-selective retinoid cream suitable for acne on the face and trunk
  • Comedolytic, anti-inflammatory and anti-pigmenting properties

Azelaic acid

• Mild comedolytic and anti-inflammatory 
• Used in combination with oral Lymecycline/Doxycycline in treating moderate to severe acne
• 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)
• 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 moderate acne; considered a mainstay in acne therapy
• Bactericidal activity reduces C acnes by producing reactive O₂ species in the sebaceous follicle
  • Inflammatory and non-inflammatory lesions are rapidly improved
• Mild comedolytic, antibacterial, and anti-inflammatory effects

Antibiotics

• Eg Clindamycin, Dapsone, Erythromycin, Minocycline
• Useful for mild to moderate acne with inflammatory lesions in combination with other topical agents
• Reduce C acnes in sebaceous follicles and have anti-inflammatory properties
• Because of the risk of antimicrobial resistance, the following should be considered:
  
  • Should not be used as monotherapy for moderate to severe acne or as maintenance therapy for acne
  • Recommend that topical antibiotics be used in combination with Benzoyl peroxide or retinoid
  • 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 (bacteriostatic) and anti-inflammatory properties, is used as an option for patients with mild to moderate acne preferably in combination with a topical retinoid
• Sodium sulfacetamide, available alone or combined with Sulfur, acts as a keratolytic and may be used for patients with mild to moderate acne
• Minocycline was recently been approved for moderate to severe acne vulgaris

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
• Has mild comedolytic and anti-inflammatory effects
• Various products containing Salicylic acid are available. Please see the latest MIMS for specific formulations and prescribing information.

Clascoterone

• Androgen receptor inhibitor which is approved for treatment of acne vulgaris in patients aged ≥12 years
• Alternative topical therapy for patients who fail to respond sufficiently to initial therapies

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, Azelaic acid + Lymecycline/Doxycycline)
  • 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

• Preferred treatment option for acne resistant to topical therapy, acne with high scarring potential or in patients with nodular acne

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
• Suppress the growth of C 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
  • May be used in patients with contraindications to Tetracyclines

• Erythromycin
  • Has direct anti-inflammatory effect by reducing neutrophil chemotactic factors and reactive oxygen species
  • Considered as alternative agent when other therapies have failed
  • Associated with less anti-inflammatory activity and more gastrointestinal side effects than Tetracycline
  • There tends to be more resistance of C acnes to Erythromycin than to Tetracycline
  • Decreased risk of photosensitivity compared to Tetracycline

• Tetracycline
  • Considered as a 1st-line agent for moderate to severe inflammatory acne as an alternative to Doxycycline
  • Penetrates into the follicular canal
  • Development of C 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 and moderate to severe acne
  • C acnes resistance has also been reported

• Lymecycline
  • Considered as 1st-line therapy in combination with other agents for moderate to severe acne
  • Less frequent occurrence of gastrointestinal and dermatological side effects

• Minocycline
  • May be used as 2nd-line antibiotic treatment for inflammatory acne 
  • Fewer reports of C acnes resistance compared to Tetracycline and Doxycycline
  • Tendency to produce rare serious side effects is greater than Tetracycline and Doxycycline
• Sarecycline
  • May be used in patients ≥9 years old for treatment of non-nodular inflammatory moderate to severe acne

• 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
• Reduces sebum excretion, comedogenesis, ductal and surface C 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; factors for higher risk for relapse after treatment include severe seborrhea, young age, family history of acne, and prepubertal and truncal acne
• A known teratogen and therefore, childbearing-aged females must be tested for pregnancy prior to therapy
• Severe adverse effects may limit use
  • Low-dose Isotretinoin may be used to reduce the frequency and severity of adverse effects

Corticosteroids

• May be considered in patients with severe acne who suffer from acne flare after initiation of oral Isotretinoin therapy and in patients with acne fulminans

Intralesional Agents

Intralesional Corticosteroid Agents

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

Adjunctive Therapy

Chemical Peels (Other than Salicylic acid)

• Eg Glycolic acid, Lactic acid, Trichloroacetic acid
• Inhibit tyrosinase activity
• Involve facial resurfacing wherein removal of epidermis stimulates re-epithelialization and skin rejuvenation
  • May reduce hyperpigmentation and skin superficial scarring
• 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 C acnes
• Though herbal and complementary therapies seem to be well tolerated, data on the safety and efficacy of these therapies are limited

Oral Contraceptives

• Eg Ethinyl estradiol/Norgestimate, Ethinyl estradiol/Norethindrone acetate, Ethinyl estradiol/Norethindrone acetate/Ferrous fumarate, Ethinyl estradiol/Drospirenone, Ethinyl estradiol/Drospirenone/Levomefolate, Ethinylestradiol/Gestodene
• Combined oral contraceptive (COC) (estrogen and progestin) 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
  • Absolute contraindications to COCs:
    • <6 weeks postpartum
    • >35 years of age and smoking history of >15 cigarettes/day
    • Hypertension (>160/>100 mmHg)
    • Coronary artery disease/cerebrovascular disease
    • Deep venous thrombosis, pulmonary embolism, known thrombogenic mutations
    • Major surgery with prolonged immobilization
    • Valvular heart disease with complications (eg atrial fibrillation, pulmonary hypertension)
    • Migraine with aura or no aura if >35 years old
    • Current breast cancer
    • Diabetes with complications
    • Acute viral hepatitis, decompensated liver cirrhosis, liver tumor
  • Relative contraindications to COCs:
    • 6 weeks to 6 months postpartum
    • >35 years of age and smoking history of <15 cigarettes/day
    • Hypertension (140-160/90-100 mmHg)
    • Multiple risk factors for cardiovascular disease and hyperlipidemia
    • History of breast cancer >5 years ago with no recurrence
    • Mild compensated liver cirrhosis, previous COC-induced cholestasis, gallbladder disease, concurrent medication with potential for transaminitis
• 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
• 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 Ethinyl estradiol 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
• 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

Skin Care Recommendations

• Importance of cleansing, treatment, moisturization and photoprotection in holistic skin care
• 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
  • Sunscreen can also be applied indoors to help protect from visible light (blue light from computers, cell phones, indoor lighting) which patients are exposed to for longer periods of time while staying indoors during the pandemic
• 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
• Can modulate the skin microbiome in acne, making it a potential alternative in the treatment of acne without the risk of antibacterial resistance
• 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

Intense Pulsed Light (IPL)

• Causes decrease in sebum output by directly damaging the sebaceous glands

Laser Therapy

• Eg Erbium glass laser, neodymium-doped yttrium aluminum garnet laser (Nd:YAG), pulsed dye laser, non-ablative fractional laser
• Mechanism is by photocoagulation/photothermal injury causing bactericidal effect and reduction in the size of sebaceous gland

Light-based Therapy

• Blue light therapy has a shorter wavelength and bactericidal effect on C acnes
• Red light can penetrate deeper tissues which can lead to anti-inflammatory reaction and promote skin repair

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
• 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

Radiofrequency (RF) Treatment

• Eg unipolar RF, bipolar RF, fractional RF
• Delivers high energy causing thermal injury to deep dermis leading to destruction of sebaceous glands