What is the recommended stepwise treatment regimen for acne, including first‑line topical therapy, indications for oral antibiotics, hormonal therapy in females, and isotretinoin for severe disease?

Treatment for Acne Vulgaris

Start all acne patients on a fixed-dose combination of topical retinoid (adapalene 0.1-0.3%) plus benzoyl peroxide 2.5-5% applied once nightly, then escalate based on severity by adding oral doxycycline 100 mg daily for moderate-to-severe inflammatory disease, or proceed directly to isotretinoin for severe nodular acne, treatment-resistant cases after 3-4 months, or any acne causing scarring or psychosocial burden. 1, 2

Severity-Based Treatment Algorithm

Mild Acne (Comedonal or Minimal Inflammatory Lesions)

• First-line: Topical retinoid (adapalene 0.1-0.3%, tretinoin 0.025-0.1%, tazarotene 0.05-0.1%, or trifarotene) combined with benzoyl peroxide 2.5-5% applied once daily in the evening 1, 3
• Apply after washing and allowing skin to dry for 20-30 minutes, using a pea-sized amount for each facial area (forehead, chin, each cheek) 3
• Adapalene is preferred because it lacks photolability restrictions, can be applied with benzoyl peroxide without oxidation concerns, and is available over-the-counter 3
• Adjunctive options:
  • Azelaic acid 15-20% for post-inflammatory hyperpigmentation, particularly in darker skin tones 2, 3
  • Topical dapsone 5% gel for inflammatory acne, especially in adult females (no G6PD testing required) 2, 3
  • Salicylic acid 0.5-2% as an over-the-counter alternative, though evidence is limited compared to retinoids 3

Moderate Acne (Mixed Comedonal and Inflammatory)

• First-line: Fixed-dose combination topical retinoid + benzoyl peroxide 1, 3
• Add: Topical antibiotic (clindamycin 1% or erythromycin 3%) combined with benzoyl peroxide—never as monotherapy due to rapid resistance development 1, 2
• Fixed-combination products (clindamycin 1%/benzoyl peroxide 5% or 3.75%, erythromycin 3%/benzoyl peroxide 5%) enhance compliance 3, 4
• If inadequate response after 6-8 weeks: Add oral doxycycline 100 mg once daily 2, 3

Moderate-to-Severe Inflammatory Acne

• Triple therapy (strongly recommended): Oral antibiotic + topical retinoid + benzoyl peroxide 1, 2, 3
• Oral antibiotic selection:
  • Doxycycline 100 mg once daily (strong recommendation, moderate evidence) 1, 2, 4
  • Minocycline 100 mg once daily (conditional recommendation, moderate evidence) as second-line if doxycycline not tolerated 1, 3, 4
  • Sarecycline (conditional recommendation, high evidence; limited by cost) 1
• Critical antibiotic stewardship principles:
  • Limit systemic antibiotics to 3-4 months maximum to prevent resistance 1, 2, 3, 4
  • Always combine with benzoyl peroxide—monotherapy is explicitly contraindicated 1, 2, 3
  • Continue topical therapy throughout antibiotic course and for maintenance after discontinuation 2, 3
• Intralesional therapy: Inject triamcinolone acetonide 2.5-10 mg/mL into large, painful nodules for rapid pain relief within 48-72 hours; use low concentrations and minimal volumes to minimize atrophy risk 1, 3, 4

Severe Nodular/Cystic Acne

• Isotretinoin is the definitive treatment for severe acne, addressing all four pathogenic factors 1, 3
• Indications for isotretinoin:
  • Severe nodular or conglobate acne 1, 3
  • Moderate acne resistant to 3-4 months of appropriate therapy (oral antibiotic + topical retinoid + benzoyl peroxide) 1, 3, 4
  • Any acne with active scarring, regardless of severity 1, 3
  • Significant psychosocial burden or distress 1, 3
• Dosing: 0.5-1.0 mg/kg/day targeting cumulative dose of 120-150 mg/kg 1, 3, 5
• Higher doses (1 mg/kg/day) reduce relapse rates, especially in young males with truncal acne 5
• Traditional daily dosing is preferred over intermittent dosing 1
• Monitoring:
  • Baseline liver function tests and lipid panel, repeat at 2 months 1, 3
  • CBC monitoring is not needed in healthy patients 1, 3
  • Population-based studies have not identified increased risk of neuropsychiatric conditions or inflammatory bowel disease 1, 3
• Mandatory pregnancy prevention through iPledge program for persons of childbearing potential 1, 3

Hormonal Therapy for Female Patients

Indications for Hormonal Therapy

• Premenstrual flares 2, 3
• Jaw-line distribution 2, 3
• Moderate-to-severe inflammatory acne unresponsive to topical therapy 3
• Patients who cannot tolerate or prefer to avoid oral antibiotics 3

Spironolactone

• Dosing: Start 50 mg daily, titrate to 100-200 mg daily based on response 1, 3
• For acne, 50-100 mg daily is usually sufficient; higher doses reserved for hirsutism or hair loss 3
• No routine potassium monitoring needed in healthy patients without risk factors for hyperkalemia (e.g., renal disease, potassium-sparing diuretics, ACE inhibitors/ARBs) 1, 3
• Clinical improvement typically seen after 3 months, maximal benefit at 6 months 3
• Menstrual irregularities occur in up to 68% of patients; concurrent COC use mitigates this risk 3
• Always combine with reliable contraception due to teratogenic potential 3

Combined Oral Contraceptives (COCs)

• Reduce inflammatory lesions by approximately 62% at 6 months 1, 3
• FDA-approved formulations: norgestimate, norethindrone, or drospirenone with ethinyl estradiol 3
• Can be used as monotherapy or combined with topical agents 3
• Drospirenone-containing COCs have intrinsic anti-androgenic activity 3
• Avoid during first 2 years after menarche or in patients <14 years unless clear indication exists 3

Maintenance Therapy After Clearance

• Continue topical retinoid monotherapy indefinitely to prevent recurrence 2, 3
• Benzoyl peroxide can be continued as maintenance to limit bacterial colonization 3
• Maintain long-term hormonal therapy (spironolactone or COC) in females, as discontinuation commonly leads to relapse 3

Critical Pitfalls to Avoid

• Never use topical or oral antibiotics without concurrent benzoyl peroxide—resistance develops rapidly 1, 2, 3, 4
• Never extend oral antibiotics beyond 3-4 months without re-evaluation; this dramatically increases resistance risk 1, 2, 3, 4
• Do not underestimate severity when scarring is present—such cases warrant isotretinoin regardless of lesion count 1, 3
• Avoid combining topical dapsone with benzoyl peroxide—causes orange-brown skin discoloration 2
• Do not apply traditional tretinoin with benzoyl peroxide simultaneously—oxidation inactivates tretinoin 3
• Oral antibiotics alone are insufficient for severe cystic/nodular acne and delay definitive isotretinoin therapy 4

Essential Patient Counseling

• Sunscreen: Apply broad-spectrum SPF 30+ every morning; retinoids and benzoyl peroxide increase photosensitivity 2, 3
• Avoid tanning beds and sun lamps completely during treatment 2, 3
• Use gentle, non-soap cleansers; avoid harsh scrubbing, astringents, or alcohol-based products 3
• Apply fragrance-free moisturizer after topical medications dry to counteract treatment-related dryness 3
• Never pick, squeeze, or vigorously scrub lesions—heightens inflammation and scarring risk 3
• Dietary considerations: High-glycemic foods and skim milk may worsen acne in susceptible individuals 3
• Start retinoids with reduced frequency and concurrent emollients to mitigate initial irritation 3