What are the stepwise treatment options for acne?

Stepwise Treatment of Acne Vulgaris

Start all patients with a topical retinoid (adapalene 0.1-0.3% or tretinoin 0.025-0.1%) plus benzoyl peroxide 2.5-5% applied once nightly and once daily respectively, then escalate based on severity and response. 1

Step 1: Assess Severity Using Standardized Scale

• Use the Physician Global Assessment (PGA) to consistently classify acne severity as mild, moderate, or severe 2, 1
• Evaluate for scarring, post-inflammatory dyspigmentation, and psychosocial impact, as these factors warrant more aggressive treatment regardless of lesion count 2, 1

Step 2: Mild Acne (Comedonal or Minimal Inflammatory Lesions)

First-line therapy:

• Topical retinoid (adapalene 0.1% gel or tretinoin 0.025% cream/gel) applied once nightly to completely dry skin PLUS benzoyl peroxide 2.5-5% gel applied once daily 1, 3
• Adapalene is more photostable and can be used with benzoyl peroxide, while tretinoin should be applied in the evening due to photolability 1, 4

Alternative options for specific situations:

• Azelaic acid 15-20% gel twice daily for patients with post-inflammatory hyperpigmentation or Fitzpatrick skin types IV or greater 1, 3
• Salicylic acid 0.5-2% for patients who cannot tolerate retinoids, though evidence is limited 3

Critical pitfall: Never use topical antibiotics as monotherapy for comedonal acne—they are ineffective against comedones and promote bacterial resistance 3

Step 3: Moderate Acne (Mixed Comedonal and Inflammatory)

First-line therapy:

• Continue topical retinoid + benzoyl peroxide as foundation 1
• Add fixed-dose combination topical antibiotic with benzoyl peroxide (clindamycin 1%/BP 5% or erythromycin 3%/BP 5%) applied twice daily 2, 1

Alternative for adult females:

• Topical dapsone 5% gel is particularly effective for inflammatory acne in adult females (no G6PD testing required) 1

Key principle: Always combine topical antibiotics with benzoyl peroxide—never use antibiotics alone due to rapid resistance development 2, 1

Step 4: Moderate-to-Severe Inflammatory Acne

First-line triple therapy:

• Oral doxycycline 100 mg once daily OR minocycline 100 mg once daily (doxycycline has stronger evidence) 2, 1, 5
• PLUS topical retinoid once nightly 1, 5
• PLUS benzoyl peroxide once daily (mandatory to prevent antibiotic resistance) 2, 1, 5

Duration limits:

• Limit systemic antibiotics to 3-4 months maximum to minimize resistance development 1, 5
• Subantimicrobial doxycycline (20 mg twice daily to 40 mg daily) may be used for longer duration if needed 1

Adjunctive option for rapid improvement:

• Intralesional triamcinolone acetonide for larger nodules at risk of scarring provides rapid pain relief and inflammation reduction 2
• Short-term oral corticosteroids can provide temporary benefit while starting standard therapy for severe inflammatory acne 1

Step 5: Hormonal Therapy for Female Patients

Indications:

• Hormonal acne patterns (jawline/lower face distribution) 1
• Premenstrual flares 1
• Patients who cannot tolerate or prefer to avoid oral antibiotics 1

Options:

• Combined oral contraceptives at standard contraceptive dosing (62% reduction in inflammatory lesions at 6 months) 5, 6
• Spironolactone 25-200 mg daily (no potassium monitoring needed in healthy patients without risk factors) 2, 5

Step 6: Isotretinoin for Severe or Treatment-Resistant Acne

Indications:

• Severe nodular or conglobate acne 2, 7
• Moderate acne with scarring or significant psychosocial burden 2
• Treatment-resistant moderate acne after 3-4 months of appropriate therapy 1

Dosing:

• Standard: 0.5-1.0 mg/kg/day targeting cumulative dose of 120-150 mg/kg 5
• Low-dose alternative: 0.25-0.4 mg/kg/day for moderate treatment-resistant acne with fewer side effects 5
• Daily dosing preferred over intermittent dosing 2

Monitoring:

• Monitor only liver function tests and lipids—no routine monitoring for depression or inflammatory bowel disease needed based on population studies 2
• Mandatory pregnancy prevention for persons of pregnancy potential through iPledge program 2, 8

Key advantage: Isotretinoin is the only drug affecting all four pathogenic factors of acne (sebum production, ductal cornification, bacterial colonization, inflammation) 7, 9

Step 7: Maintenance Therapy After Clearance

Standard maintenance:

• Continue topical retinoid monotherapy once nightly indefinitely to prevent recurrence 1, 3, 5
• Add benzoyl peroxide 2.5-5% once daily if baseline disease was more severe 5

Critical principle: Topical retinoids prevent new microcomedone formation and are essential for maintaining clearance 3

Managing Side Effects and Optimizing Tolerability

Retinoid irritation (dryness, peeling, erythema):

• Start with lower concentrations and increase as tolerated 4
• Apply to completely dry skin 20-30 minutes after washing 4
• Reduce frequency to every other night initially for sensitive skin 4
• Apply daily moisturizer and sunscreen every morning 4

Benzoyl peroxide bleaching:

• Warn patients about bleaching of fabrics and hair 1
• Lower concentrations (2.5%) cause less irritation with similar efficacy to higher concentrations 1

Critical Pitfalls to Avoid

• Never use topical or oral antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 1, 3, 5
• Never extend oral antibiotics beyond 3-4 months without re-evaluation and transition to maintenance therapy 1, 5
• Never underestimate severity when scarring is present—these patients warrant more aggressive treatment including consideration of isotretinoin 2, 1
• Never apply tretinoin to wet skin—wait 20-30 minutes after washing for skin to be completely dry to minimize irritation 4
• Never combine tretinoin with benzoyl peroxide in the same application due to photolability (use adapalene instead or apply at different times) 1