What is the recommended first‑line therapy for a patient with moderate cystic acne?

Moderate Cystic Acne Treatment

For moderate cystic acne, start with oral doxycycline 100 mg daily combined with a fixed-dose topical retinoid/benzoyl peroxide combination (adapalene 0.1-0.3% + benzoyl peroxide 2.5-5%), and add intralesional triamcinolone for individual large, painful nodules. 1, 2

Treatment Algorithm for Moderate Cystic Acne

First-Line Triple Therapy Approach

Oral antibiotic therapy is mandatory for moderate cystic acne because topical agents alone are insufficient for inflammatory nodules and cysts. 1, 2

• Doxycycline 100 mg once daily is the strongly recommended first-line oral antibiotic with moderate certainty evidence 1, 2
• Minocycline 100 mg once daily is a conditional second-line alternative if doxycycline is not tolerated 1, 2
• Never use oral antibiotics as monotherapy—this rapidly induces bacterial resistance 1, 2

Essential Topical Combination Therapy

All patients must receive concurrent topical therapy to optimize efficacy and prevent antibiotic resistance. 1, 2

• Fixed-dose combination of adapalene 0.1-0.3% + benzoyl peroxide 2.5-5% applied once daily in the evening 1, 2
• This combination addresses comedones, microcomedones, and provides antimicrobial activity 2
• Alternative: Add fixed-dose clindamycin 1%/benzoyl peroxide 5% for additional inflammatory control 1, 2

Adjunctive Intralesional Therapy for Nodules

For individual large, painful cystic nodules, inject intralesional triamcinolone acetonide to provide rapid pain relief and inflammation reduction within 48-72 hours. 1, 2

• Use lower concentrations (2.5-10 mg/mL) and minimal volumes to minimize atrophy risk 1
• This is particularly important for nodules at risk of scarring 1

Critical Duration and Monitoring Guidelines

Antibiotic Duration Limits

Limit systemic antibiotics to 3-4 months maximum to minimize bacterial resistance development. 1, 2, 3

• Re-evaluate at 3-4 months and transition to maintenance therapy 2, 3
• Extending beyond this timeframe dramatically increases resistance risk 2

Maintenance After Antibiotic Discontinuation

After completing 3-4 months of oral antibiotics, transition to topical retinoid monotherapy indefinitely to prevent recurrence. 2

• Continue adapalene 0.1-0.3% nightly as maintenance 2
• Benzoyl peroxide can be continued as needed 2

When to Escalate to Isotretinoin

Consider isotretinoin if moderate cystic acne fails to respond after 3-4 months of appropriate triple therapy (oral antibiotic + topical retinoid + benzoyl peroxide). 1, 2

Additional isotretinoin indications include:

• Any acne with active scarring, regardless of severity 1, 2
• Significant psychosocial burden or distress 1, 2
• Treatment-resistant moderate acne after appropriate therapy duration 1, 2

Isotretinoin dosing: 0.5-1.0 mg/kg/day targeting cumulative dose of 120-150 mg/kg 2

Hormonal Therapy Considerations for Female Patients

For female patients with hormonal patterns (premenstrual flares, jawline distribution), add spironolactone 25-200 mg daily or combined oral contraceptives. 1, 2

• Spironolactone requires no potassium monitoring in healthy patients without risk factors for hyperkalemia 1, 2
• Combined oral contraceptives reduce inflammatory lesions by 62% at 6 months 2, 4
• These can be used concomitantly with oral antibiotics and topical therapy 2

Critical Pitfalls to Avoid

Never use topical or oral antibiotics without concurrent benzoyl peroxide—resistance develops rapidly without it. 1, 2, 3

Never extend oral antibiotics beyond 3-4 months without re-evaluation—this dramatically increases resistance risk and antibiotic-associated complications. 1, 2, 3

Do not underestimate severity when scarring is present—any scarring warrants consideration for isotretinoin regardless of lesion count. 1, 2

Avoid using oral antibiotics as primary therapy for severe cystic/nodular acne—this delays definitive isotretinoin treatment and is inadequate for severe disease. 2

Practical Application Tips

• Apply topical retinoid/benzoyl peroxide combination once daily in the evening after washing and allowing skin to dry 20-30 minutes 2
• Counsel about photosensitivity with doxycycline and recommend daily sunscreen 2, 3
• Start with reduced frequency of retinoid application if irritation occurs, then increase as tolerated 2
• Expect clinical improvement within 1-2 weeks of starting oral antibiotics 3