What is the recommended stepwise management for mild‑to‑moderate acne, including first‑line topical therapy, criteria for adding oral antibiotics or hormonal treatment, and indications for oral isotretinoin?

Management of Acne Vulgaris

Begin all acne patients on topical adapalene 0.1–0.3% combined with benzoyl peroxide 2.5–5% as the foundation, then escalate based on severity by adding topical antibiotics for moderate disease or oral doxycycline 100 mg daily for moderate-to-severe inflammatory acne, always with concurrent benzoyl peroxide to prevent resistance. 1, 2

Severity Assessment

• Assess acne severity consistently using the Physician Global Assessment (PGA) or other standardized scales to guide treatment selection 1, 2
• Evaluate for scarring, post-inflammatory hyperpigmentation, and psychosocial impact—these factors warrant more aggressive treatment regardless of lesion count 1, 2
• Look specifically for premenstrual flares and jaw-line distribution as markers of hormonal acne in female patients 2

First-Line Topical Therapy (All Severity Levels)

Multimodal topical therapy combining multiple mechanisms of action is recommended as a good practice statement. 1

• Topical retinoids (strong recommendation, moderate evidence): Adapalene 0.1–0.3% is preferred due to superior tolerability, lack of photolability, and ability to be applied with benzoyl peroxide without oxidation 1, 2

  • Alternative retinoids include tretinoin 0.025–0.1% (apply in evening, avoid concurrent benzoyl peroxide due to oxidation) or tazarotene 0.05–0.1% 1, 2
  • Retinoids are the cornerstone because they resolve microcomedones, the precursor to all acne lesions 2

• Benzoyl peroxide 2.5–5% (strong recommendation, moderate evidence): Provides antimicrobial activity without bacterial resistance 1, 2

  • Lower concentrations (2.5%) cause less irritation than higher concentrations 2

• Apply adapalene/benzoyl peroxide combination once nightly after washing and allowing skin to dry for 20–30 minutes, using a pea-sized amount for each facial area 2

Treatment Algorithm by Severity

Mild Acne

• First-line: Topical retinoid (adapalene preferred) + benzoyl peroxide 1, 2
• Alternative options:
  • Azelaic acid 15–20% for patients with post-inflammatory hyperpigmentation 2
  • Clascoterone 1% (conditional recommendation, high evidence) as a topical antiandrogen 1

Moderate Acne

• First-line: Fixed-dose combination of topical retinoid + benzoyl peroxide 1, 2
• Add if needed: Topical antibiotic (clindamycin 1% or erythromycin 3%) combined with benzoyl peroxide for inflammatory lesions 1, 2
  • Never use topical antibiotics as monotherapy—this rapidly induces bacterial resistance 1, 2
  • Fixed-combination products (clindamycin 1%/BP 5% or erythromycin 3%/BP 5%) enhance compliance 2
• Alternative: Topical dapsone 5% gel is particularly effective for inflammatory acne in adult females 2

Moderate-to-Severe Inflammatory Acne

• First-line: Oral antibiotics + topical retinoid + benzoyl peroxide (triple therapy) 1, 2
• Oral antibiotic selection:
  • Doxycycline 100 mg once daily (strong recommendation, moderate evidence) 1, 2
  • Minocycline 100 mg once daily (conditional recommendation, moderate evidence) as second-line 1, 2
  • Sarecycline is a newer tetracycline option 2
• Critical antibiotic principles:
  • Limit systemic antibiotics to 3–4 months maximum to minimize resistance 2
  • Always combine with benzoyl peroxide—never use oral antibiotics as monotherapy 2
  • Counsel patients on doxycycline to avoid tanning beds and sun lamps due to phototoxicity risk 2

Hormonal Therapy for Female Patients

Indications

• Premenstrual flares, jaw-line distribution, moderate-to-severe acne unresponsive to topical therapy 2
• Clinical signs of hyperandrogenism (hirsutism, oligomenorrhea, androgenic alopecia) warrant endocrine testing 1

First-Line Hormonal Options

• Spironolactone 50–100 mg daily (titrate from 25 mg as needed) 1, 2

  • Improvement typically seen after 3 months, maximal benefit at 6 months 2
  • Potassium monitoring is unnecessary in healthy patients without renal disease or concurrent potassium-affecting medications 1, 2
  • Menstrual irregularities occur in up to 68% of patients; concurrent COC use mitigates this 2

• Combined oral contraceptives (COCs) containing norgestimate, norethindrone, or drospirenone 1, 2

  • Reduce inflammatory lesions by 62% at 6 months 2
  • Can be used as monotherapy or combined with topical agents 2
  • Avoid during first 2 years after menarche or in patients <14 years unless clearly indicated 2

Indications for Oral Isotretinoin

Isotretinoin is the only drug affecting all four pathogenic factors of acne and should be considered for: 1, 2

• Severe nodular or conglobate acne 1, 2
• Moderate acne with scarring or significant psychosocial burden 1, 2
• Treatment-resistant moderate acne after 3–4 months of appropriate therapy (including oral antibiotics + topical retinoid + benzoyl peroxide) 1, 2

Isotretinoin Dosing and Monitoring

• Standard dosing: 0.5–1.0 mg/kg/day targeting cumulative dose of 120–150 mg/kg 1, 2, 3

  • Daily dosing is preferred over intermittent dosing 1
  • Higher doses (1 mg/kg/day) reduce relapse rates, especially in young males with truncal acne 3
  • Either lidose-isotretinoin or standard isotretinoin formulations are acceptable 1

• Monitoring: Obtain baseline liver function tests and lipid panel; repeat at 2 months 1, 2

  • CBC monitoring is not required in healthy patients 2
  • Population-based studies have not identified increased risk of neuropsychiatric conditions or inflammatory bowel disease 1, 2

• Mandatory pregnancy prevention for persons of childbearing potential through iPledge program 1, 2

Adjunctive Treatments

• Intralesional triamcinolone acetonide 2.5–5 mg/mL for larger acne papules or nodules at risk of scarring 1, 2
  • Provides rapid improvement in inflammation and pain within 48–72 hours 1, 2

Maintenance Therapy After Clearance

• Continue topical retinoid monotherapy indefinitely after achieving clearance to prevent recurrence 2
• Benzoyl peroxide can be continued as maintenance to prevent bacterial colonization 2
• Maintain long-term hormonal therapy (spironolactone or COC) in female patients, as discontinuation commonly leads to relapse 2

Critical Pitfalls to Avoid

• Never use topical or oral antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 1, 2, 4
• Never extend oral antibiotics beyond 3–4 months without re-evaluation, as this dramatically increases resistance risk 2
• Do not underestimate severity when scarring is present—escalate promptly to isotretinoin regardless of lesion count 2
• Do not apply tretinoin with benzoyl peroxide simultaneously due to oxidation inactivating tretinoin (adapalene does not have this limitation) 2
• Do not forget daily sunscreen (SPF 30+) with retinoids due to photosensitivity risk 2

Special Populations

• Preadolescent children (>9 years): Topical adapalene, tretinoin, and benzoyl peroxide can be safely used 2
• Pregnant patients: Azelaic acid is safer (pregnancy category B) compared to retinoids (category C) or tazarotene (category X); oral isotretinoin is absolutely contraindicated 2