L-12 Acne Vulgaris: Classification and Treatment

• Acne vulgaris is the most common chronic skin disease in the U.S., affecting about 50 million people each year, mainly adolescents and young adults.
• Sequelae include scarring, dyspigmentation, and low self-esteem, acne can lead to significant morbidity.
• Typical acne lesions involve the pilosebaceous follicles and the interrelated processes of sebum production, Cutibacterium acnes colonization, and inflammation.

Classification

• Acne is classified as mild, moderate, or severe based on the number and type of skin lesions.
• Treatments target a specific area within acne pathogenesis, and are selected based on disease severity, patient preference, and tolerability.
• Topical retinoids are indicated for acne of any severity and for maintenance therapy.
• Antibiotics should only be used in combination with benzoyl peroxide and retinoids for a maximum of 12 weeks.
• Isotretinoin is used for severe, recalcitrant acne and requires registration with the iPledge program.
• Limited evidence supports physical modalities and complementary therapies, so further study is required.

Pathogenesis

• Acne vulgaris originates within the pilosebaceous follicles.
• Four interrelated processes involved are sebum overproduction, abnormal shedding of follicular epithelium, follicular colonization by Cutibacterium acnes, and inflammation.
• Sebum overproduction results from excessive androgen hormones or heightened sebaceous gland sensitivity.
• Inflammatory pathway activation is evident at all stages.
• There may be a genetic component to acne.
• Foods and drinks with high glycemic index and skim milk seem to affect acne severity.
• Other factors include psychological stress, tobacco smoke, and damaged skin.

Types of Lesions

• Acne lesions typically occur on the face, chest, or upper back and may be noninflammatory closed comedones (whiteheads).
• Open comedones (blackheads) are another type of lesion.
• Inflammatory papules, nodules, pustules, and cysts often occur.
• Inflammatory lesions result from follicle rupture triggering an inflammatory response.
• Acne severity is classified as mild, moderate, or severe.
• There is currently no universally accepted grading system for acne.

SORT Key Recommendations

• Use topical retinoids as monotherapy for mild comedonal acne
• Use them in combination with other topical or oral agents for moderate to severe inflammatory acne.
• Use topical retinoids for maintenance therapy once treatment goals are achieved and oral agents are discontinued.
• Use systemic antibiotics for the treatment of moderate to severe inflammatory acne.
• Use oral isotretinoin for severe nodular acne or refractory acne in adults and adolescents.
• Consider combined oral contraceptives for menarchal females who do not respond to past therapies.

Treatment Options

• Treatment is based on severity and location on the skin.
• Effective topical therapies are available over the counter and by prescription in multiple formulations and strengths, for individualized treatment.

Benzoyl Peroxide

• It is comedolytic, anti-inflammatory, and bactericidal against C. acnes.
• Available over the counter and by prescription in multiple strengths and formulations.
• It can be used alone or in combination with topical antibiotics or retinoids.
• Reduction in acne lesion count may occur within days.
• It does not induce bacterial resistance.
• It is safe to use during pregnancy.
• Adverse effects include burning, dryness, stinging, erythema, peeling, hypersensitivity, and bleaching of hair or clothing.

Topical Antibiotics

• Clindamycin and erythromycin are used for mild to moderate acne in combination with benzoyl peroxide.
• They possess anti-inflammatory and bacteriostatic or bactericidal properties.
• Clindamycin is favored over erythromycin because of declining effectiveness of erythromycin.
• To reduce the risk of resistance, do not use topical antibiotics as monotherapy.
• The duration of therapy should be limited to 12 weeks.
• Erythromycin and clindamycin are available in combination with benzoyl peroxide, and clindamycin is available in combination with retinoids.
• The use of combination agents reduces the risk of resistance.
• Adverse effects include burning, erythema, and pruritus and a rare serious adverse effect is Clostridium difficile colitis.

Retinoids

• Retinoids are vitamin A derivatives recommended as a primary treatment.
• They are effective against microcomedo and comedo formation regardless of severity and have anti-inflammatory effects
• They are indicated as monotherapy for mild comedonal acne, in combination with other topical or oral agents for the treatment of moderate to severe acne, and as maintenance therapy once treatment goals are achieved.
• Approved treatments include adapalene, tazarotene, and tretinoin.
• Tazarotene is more effective than tretinoin or adapalene, although adapalene is less irritating than tazarotene.
• Gradual increase in strength minimizes skin irritation.
• Combination agents like clindamycin phosphate/tretinoin and adapalene/benzoyl peroxide may enhance compliance.
• Simultaneous application of benzoyl peroxide and tretinoin should be avoided.

Adverse Effects for Retinoids

• Include erythema, dryness, pruritus, stinging, and photosensitivity.
• Retinoids are not indicated during pregnancy.
• Adapalene/benzoyl peroxide is approved for patients nine years and older.
• Tretinoin micronized gel is approved for patients 10 years and older.
• All other retinoids are approved for patients 12 years and older.

Azelaic Acid

• 20% azelaic acid is FDA approved as an alternative treatment for acne, alone or in combination with other agents.
• It has comedolytic, antibacterial, and anti-inflammatory properties and is safe for use in pregnancy.
• It may cause burning, stinging, and hypopigmentation in individuals with dark skin.

Dapsone

• 5% or 7.5% dapsone gel has anti-inflammatory and antibacterial properties
• It is effective as an adjunct therapy in the treatment of acne.
• Dapsone is more effective in adult women compared with men or adolescent females and may cause mild to moderate local irritation.

Other Agents

• There is insufficient evidence to support the use of over-the-counter therapies containing salicylic acid, niacinamide, sulfacetamide, sulfur, zinc, or resorcinol.

Systemic Antibiotics

• Tetracyclines, macrolides, trimethoprim/sulfamethoxazole, trimethoprim, penicillins, and cephalosporins have been used effectively in the treatment of inflammatory acne.
• Systemic antibiotics are indicated in the management of moderate to severe inflammatory acne.
• They should be used in combination with nonantibiotic topical agents to prevent resistance and enhance effectiveness.
• A recent systematic review found that no antibiotic class, individual antibiotic, or dosage is superior.
• The American Academy of Dermatology (AAD) recommends doxycycline and minocycline as first-line therapies.
• Macrolide use should be restricted to when tetracyclines are contraindicated.
• Penicillins and cephalosporins are not recommended, but may be indicated in special circumstances.
• Sarecycline is an oral, narrow-spectrum tetracycline-derived antibiotic FDA approved for the treatment of nonnodular moderate to severe acne vulgaris in children nine years and older.
• Sarecycline significantly reduced inflammatory acne lesion counts.

Isotretinoin

• It is a vitamin A derivative that inhibits sebaceous gland function, decreasing sebum production and comedolysis, leading to less inflammation.
• It is FDA approved for the management of severe, recalcitrant nodular acne.
• The AAD endorses its use in treatment-resistant or relapse-prone acne.
• It may be used for acne that is causing significant psychosocial distress or scarring.
• Common dose-dependent adverse effects of isotretinoin include xerosis, cheilitis, dry eyes, headache, and elevated lipid and hepatic enzyme levels.
• Patients receiving isotretinoin should be counseled about associated risks.
• Female patients must have contraceptive counseling and monthly urine pregnancy tests.

Hormonal Agents

• Combination oral contraceptives are antiandrogenic.
• They are effectice in menarchal females.
• They are FDA approved for treatment of acne in females older than 15 years who also desire contraception.
• Best when used with other acne treatments.

Antiandrogens

• Limited studies demonstrate effectiveness of spironolactone and flutamide.
• The AAD recommends spironolactone in women with resistant and hormonally mediated acne and should be used with contraception.

Corticosteroids

• Prednisone has demonstrated effectiveness in treatment but has limited use.
• It is indicated for the treatment of acne fulminans and intralesional triamcinolone injections reduce inflammation and pain in nodular acne.

Physical Modalities

• Laser and light-based modalities have been studied for the treatment of noninflammatory acne.
• High-quality evidence is lacking.
• There is limited evidence to support chemical peels and comedo extraction.

Complementary Therapies

• Dietary interventions, acupuncture, cupping, herbal medicines, tea tree oil, and purified bee venom reviewed.
• Some evidence is that purified bee venom, tea tree oil, a low-glycemic-load diet, or skim milk avoidance is associated with a reduction in skin lesions.

Reassessment and Referral

• Goals of therapy include reduction in lesions, improvement of psychosocial symptoms, and avoidance of scarring.
• Therapeutic interventions for acne should have a minimum duration of eight weeks to assess effectiveness.
• If the patient shows inadequate improvement after sequential interventions, referral to a dermatologist is recommended.