What is the recommended stepwise management for acne, including skin care, topical and oral therapies, hormonal options, and isotretinoin?

Stepwise Management of Acne Vulgaris

Foundation: Universal First-Line Therapy

Start all acne patients on topical adapalene 0.1-0.3% combined with benzoyl peroxide 2.5-5% applied once daily in the evening, regardless of severity, then escalate based on disease severity. 1, 2

• Adapalene 0.1% is available over-the-counter, making it highly accessible 1, 2
• 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) 1
• This combination addresses comedones, microcomedones, and provides antimicrobial activity more effectively than either agent alone 1
• Daily sunscreen is mandatory due to photosensitivity risk 1

Severity-Based Treatment Algorithm

Mild Acne (Comedonal or Minimal Inflammatory Lesions)

Continue topical retinoid + benzoyl peroxide as monotherapy. 1, 2

• Alternative: Add azelaic acid 15-20% for patients with post-inflammatory hyperpigmentation, particularly those with darker skin tones 1
• Salicylic acid 0.5-2% can be used as an adjunct for comedonal acne, but avoid concurrent use with adapalene due to increased irritation risk 1

Moderate Acne (Inflammatory Papules/Pustules)

Add a fixed-dose combination topical antibiotic with benzoyl peroxide (clindamycin 1%/BP 5% or erythromycin 3%/BP 5%) to the retinoid + benzoyl peroxide foundation. 1, 2

• Apply the antibiotic/BP combination in the morning and retinoid/BP in the evening 1
• Never use topical antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 1, 2
• Topical dapsone 5% gel is particularly effective for inflammatory acne in adult females and requires no G6PD testing 1

Moderate-to-Severe Inflammatory Acne

Initiate triple therapy: oral doxycycline 100 mg once daily + topical retinoid + benzoyl peroxide. 1, 2

• Doxycycline is strongly recommended as first-line systemic therapy with moderate-certainty evidence 1, 2
• Minocycline 100 mg once daily is a conditionally recommended alternative if doxycycline is not tolerated 1, 2
• Sarecycline is a newer tetracycline option with dosing based on weight 1
• Limit systemic antibiotics to 3-4 months maximum to prevent resistance, then transition to topical retinoid monotherapy for maintenance 1, 2
• Counsel patients receiving doxycycline to avoid tanning beds and sun lamps due to severe phototoxic reaction risk 1

Severe Nodular/Cystic Acne

Initiate isotretinoin 0.5-1.0 mg/kg/day immediately, targeting a cumulative dose of 120-150 mg/kg. 1

• Isotretinoin is the only drug addressing all four pathogenic factors of acne 1
• Daily dosing is preferred over intermittent or pulsed regimens 1
• For large, painful nodules, add intralesional triamcinolone acetonide 10 mg/mL for rapid pain relief within 48-72 hours 1
• Mandatory pregnancy prevention through iPledge program for persons of childbearing potential 1
• Monitor liver function tests and lipids at baseline and at 2 months; CBC monitoring is not needed in healthy patients 1
• Population-based studies have not identified increased risk of neuropsychiatric conditions or inflammatory bowel disease 1

Hormonal Therapy Options for Female Patients

For females with hormonal acne patterns (jaw-line distribution, premenstrual flares), add spironolactone 50-100 mg daily or combined oral contraceptives. 1, 2

• Spironolactone 25-200 mg daily is effective for hormonal acne, with most patients responding at 50-100 mg daily 1
• No potassium monitoring is needed in healthy patients without renal disease or concurrent ACE inhibitors/ARBs 1
• Clinical improvement typically occurs after 3 months, with maximal benefit at 6 months 1
• Combined oral contraceptives reduce inflammatory lesions by 62% at 6 months 1, 2
• FDA-approved COC formulations include norgestimate, norethindrone, or drospirenone for females aged ≥14-15 years 1
• Avoid COCs during the first 2 years after menarche or in patients younger than 14 years unless clearly indicated 1
• Spironolactone can be combined with oral antibiotics, but benzoyl peroxide must be continued to prevent resistance 1

Maintenance Therapy After Clearance

Continue topical retinoid monotherapy indefinitely to prevent recurrence. 1, 2

• Benzoyl peroxide can also be continued as maintenance 1, 2
• Never stop treatment once acne clears—maintenance is essential to prevent relapse 2

Special Considerations for Back Acne

Follow the same severity-based approach as facial acne. 3

• For mild back acne, use adapalene 0.1% gel (available over-the-counter) + benzoyl peroxide 3
• For moderate-to-severe back acne, add topical or oral antibiotics as outlined above 3
• Warn patients that benzoyl peroxide bleaches clothing and bedding; recommend wearing old or white clothing 3

Isotretinoin Indications Beyond Severe Acne

Consider isotretinoin for any of the following, regardless of lesion count: 1

• Treatment-resistant moderate acne after 3-4 months of appropriate triple therapy
• Any acne with scarring present
• Significant psychosocial burden or quality-of-life impairment

Critical Pitfalls to Avoid

• Never use topical or oral antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 1, 2
• Never extend oral antibiotics beyond 3-4 months without re-evaluation 1, 2
• Do not underestimate severity when scarring is present—this warrants more aggressive treatment 1
• Do not apply tretinoin with benzoyl peroxide simultaneously (oxidation inactivates tretinoin); adapalene does not have this limitation 1
• Do not use oral antibiotics as primary therapy for acne conglobata—they are inadequate and delay definitive isotretinoin treatment 1

Adjunctive and Alternative Options

• Subantimicrobial-dose doxycycline (20 mg twice daily to 40 mg daily) has efficacy in moderate inflammatory acne 1
• Oral corticosteroids provide temporary benefit in severe inflammatory acne while initiating standard therapy 1
• Salicylic acid 20-30% chemical peels provide intensive treatment for resistant comedonal acne 1
• Topical clascoterone is a newer antiandrogen that inhibits androgen-mediated lipid and inflammatory cytokine synthesis 1
• Low-glycemic diet and reducing dairy/whey protein intake may provide benefit 1

Skin Care Recommendations

• Use gentle, non-comedogenic cleansers twice daily 1
• Apply moisturizers to mitigate retinoid-induced irritation; start with reduced frequency of retinoid application if needed 1
• Daily broad-spectrum sunscreen is mandatory with retinoid therapy 1, 3