What are the recommended treatments for acne?

Recommended Treatments for Acne

Start with a topical retinoid (adapalene 0.1-0.3% or tretinoin 0.025-0.1%) applied once nightly combined with benzoyl peroxide 2.5-5% once daily as first-line therapy for most acne, escalating to oral antibiotics (doxycycline or minocycline) plus the topical combination for moderate-to-severe inflammatory disease. 1, 2

Treatment Algorithm by Acne Severity

Mild Acne (Primarily Comedonal)

• Begin with topical retinoid monotherapy applied once nightly—options include adapalene 0.1% gel (available over-the-counter), tretinoin 0.025-0.1%, or tazarotene 0.05-0.1%. 1, 2
• Topical retinoids directly target the pathophysiology by normalizing follicular keratinization, resolving microcomedones, and providing anti-inflammatory effects. 1, 3
• Add benzoyl peroxide 2.5-5% once daily if comedones are moderate or to prevent future inflammatory lesions—lower concentrations (2.5%) cause less irritation than higher concentrations with similar efficacy. 1, 4
• Benzoyl peroxide releases free oxygen radicals with antimicrobial activity and no bacterial resistance develops. 5, 1

Alternative agents for mild acne:

• Azelaic acid 15-20% applied twice daily is mildly comedolytic, antibacterial, and particularly useful for patients with post-inflammatory hyperpigmentation or Fitzpatrick skin types IV or greater due to its lightening effect. 5, 1
• Salicylic acid 0.5-2% is available over-the-counter as a comedolytic agent for patients who cannot tolerate retinoids, though clinical trial evidence is limited. 5, 1

Moderate Acne (Mixed Comedonal and Inflammatory)

• Use fixed-dose combination products containing topical retinoid + benzoyl peroxide as first-line treatment. 2
• Add topical antibiotics (clindamycin 1% or erythromycin 3%) combined with benzoyl peroxide for inflammatory lesions—never use topical antibiotics as monotherapy due to rapid resistance development. 2, 6
• Fixed-combination products (erythromycin 3%/BP 5%, clindamycin 1%/BP 5%, or clindamycin 1%/BP 3.75%) enhance treatment compliance. 5, 2
• Topical dapsone 5% gel applied twice daily is particularly effective for inflammatory acne in adult females and does not require glucose-6-phosphate dehydrogenase testing before initiation. 5, 2

Moderate-to-Severe Inflammatory Acne

• Initiate triple therapy: oral antibiotics + topical retinoid + benzoyl peroxide. 2
• Doxycycline and minocycline are first-line oral antibiotics—both are more effective than tetracycline and equally effective to each other. 5, 6
• Typical dosing is doxycycline 100 mg once daily or minocycline 100 mg once daily. 2
• Limit systemic antibiotic use to 3-4 months maximum and re-evaluate to minimize bacterial resistance development. 5, 2
• Always use benzoyl peroxide concurrently with oral antibiotics to prevent resistance. 5, 2
• Subantimicrobial dosing of doxycycline (20 mg twice daily to 40 mg daily) has shown efficacy in moderate inflammatory acne. 5, 2

Avoid these antibiotics except in specific circumstances:

• Erythromycin and azithromycin should be limited to patients who cannot use tetracyclines (pregnant women or children <8 years) due to increased resistance risk. 5
• Trimethoprim-sulfamethoxazole and trimethoprim should be restricted to patients unable to tolerate tetracyclines or treatment-resistant cases. 5

Severe Nodular or Treatment-Resistant Acne

• Isotretinoin is indicated for severe nodular/conglobate acne, moderate acne with scarring or significant psychosocial burden, and treatment-resistant moderate acne after 3-4 months of appropriate therapy. 2
• Standard dosing is 0.5-1.0 mg/kg/day targeting cumulative dose of 120-150 mg/kg. 2
• Mandatory pregnancy prevention through iPledge program for persons of pregnancy potential. 2
• Monitor liver function tests and lipids, but routine monitoring for depression or inflammatory bowel disease is not required based on population studies. 2
• Isotretinoin is the only single agent affecting all four pathogenic factors of acne. 2, 7

Hormonal Therapy Options for Female Patients

• Combined oral contraceptives (COCs) are effective for inflammatory acne in females with hormonal components. 2
• Spironolactone 25-200 mg daily is useful for females with hormonal acne patterns, premenstrual flares, or those who cannot tolerate or prefer to avoid oral antibiotics—no potassium monitoring needed in healthy patients without risk factors. 2

Maintenance Therapy After Clearance

• Continue topical retinoid monotherapy indefinitely to prevent recurrence—retinoids prevent new microcomedone formation and maintain clearance. 1, 2
• Benzoyl peroxide can be continued as maintenance therapy to prevent recurrence. 2
• Topical retinoids carry no risk of inducing bacterial resistance, making them suitable for long-term use. 3

Managing Side Effects

Topical retinoid side effects:

• Common effects include dry skin, peeling, scaling, erythema, burning sensation, and photosensitivity. 1
• Mitigate by reducing frequency of use and applying concurrent emollients. 1
• Apply daily sunscreen to reduce photosensitivity and sunburn risk. 1, 4
• Adapalene 0.1% is better tolerated than tretinoin 0.025%, tretinoin 0.05%, and tazarotene 0.1%. 5, 8

Benzoyl peroxide precautions:

• Avoid contact with eyes, lips, mouth, and mucous membranes. 4
• Can bleach hair and dyed fabrics—wear old or white clothing when applying. 6, 4
• Skin irritation may be reduced by using the product less frequently or in lower concentration. 4

Topical dapsone interaction:

• May be oxidized by coapplication of benzoyl peroxide, causing orange-brown coloration of skin that can be washed off—apply at different times of day. 5

Critical Pitfalls to Avoid

• Never use topical or oral antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide. 1, 2
• Do not extend oral antibiotics beyond 3-4 months without re-evaluation, as this dramatically increases resistance risk. 5, 2
• Do not underestimate severity when scarring is present—this warrants more aggressive treatment regardless of lesion count. 2
• Avoid applying retinoids to broken skin or areas with active wounds. 2
• Some tretinoin formulations should be applied in the evening due to photolability and should not be used simultaneously with benzoyl peroxide. 2
• If using multiple topical acne medications, skin irritation and dryness is more likely—if irritation occurs, use only one topical acne medication at a time. 4

Special Populations

• Topical adapalene, tretinoin, and benzoyl peroxide can be safely used in preadolescent children with acne. 2
• Azelaic acid is pregnancy category B. 5
• Topical dapsone 5% gel is pregnancy category C with efficacy and safety data down to patients 12 years of age. 5
• For adapalene: use once daily in patients 12 years and older—applying more than directed will not provide faster results but may worsen skin irritation. 9

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