Acne Vulgaris: Treatment

Overview & Pathogenesis

1. Increased sebum production — androgen-driven (peaks at puberty)
2. Abnormal follicular keratinization — retention of keratin and sebum forms comedones
3. Cutibacterium acnes colonization — releases free fatty acids from sebum, triggering inflammation
4. Inflammatory cascade — rupture of comedone wall → foreign-body reaction → papules, pustules, nodules

Severity Classification & Treatment Algorithm

Topical Therapies

Retinoids (first-line for all grades)

• Agents: tretinoin, adapalene, tazarotene, trifarotene
• Mechanism: normalize follicular keratinization, prevent comedone formation, enhance penetration of other agents
• Start at lower strength to minimize irritation; titrate up as tolerated
• Apply at night; sun protection is essential

Benzoyl Peroxide (BPO)

• Mechanism: bactericidal against C. acnes; does not induce antibiotic resistance
• Available as washes or leave-on preparations (2.5–10%)
• Should always be combined with topical antibiotics to prevent resistance

Topical Antibiotics

• Clindamycin (most common) and erythromycin
• Must not be used as monotherapy — always combine with BPO to prevent C. acnes resistance
• Limited to acute control phases; avoid long-term monotherapy

Alternative Topicals

Systemic Therapies

Oral Antibiotics

• Doxycycline and minocycline (100 mg twice daily, or low-dose extended-release) — most used
• Anti-inflammatory effects independent of antibacterial activity
• Expect response at 3 months
• Limit duration to reduce resistance; always co-prescribe BPO
• Sarecycline — narrow-spectrum tetracycline (FDA-approved 2018); less GI side effects, reduced resistance potential

Hormonal Therapy (females only)

• Combined oral contraceptives (OCPs): several FDA-approved for acne (norgestimate/ethinyl estradiol; norethindrone acetate/ethinyl estradiol; drospirenone/ethinyl estradiol)
• Spironolactone (50–200 mg/day): anti-androgen; safe, effective, and durable in women; particularly useful for adult female acne
• Not appropriate for males (gynecomastia risk)

Isotretinoin (13-cis-retinoic acid)

• Indications: severe nodulocystic acne; moderate acne unresponsive to conventional therapy; acne causing significant psychosocial distress or scarring
• Mechanism: reduces sebaceous gland size and activity (~90% reduction in sebum); normalizes desquamation; anti-inflammatory
• Dosing: weight-based; cumulative dose approach (~120–150 mg/kg total)
• Monitoring: lipids, liver function, CBC; monthly pregnancy tests in women of childbearing potential
• iPLEDGE program (USA): mandatory enrollment to prevent teratogenicity; two negative pregnancy tests before initiation; monthly negative test before each refill
• Common side effects: dry skin, cheilitis, dry eyes, elevated triglycerides
• Severe/rare: teratogenicity (Category X), potential IBD risk (controversial), mood changes (monitor)
• Results are excellent in appropriately selected patients; often produces long-term remission

Acne Fulminans (Very Severe)

1. Oral prednisolone 0.5–1 mg/kg/day to suppress acute inflammation
2. Add low-dose isotretinoin once inflammation subsides; slow titration upward

Special Considerations

Practical Pearls

• Overly vigorous scrubbing aggravates acne — gentle cleansing is recommended
• Comedogenic cosmetics and hair products can worsen acne; non-comedogenic formulations preferred
• Maintenance therapy after achieving control (typically retinoid ± BPO) is essential — acne commonly recurs
• Response to oral antibiotics expected at 3 months; if inadequate, reassess adherence or escalate to isotretinoin
• Lack of response should prompt evaluation for endocrine disorders (PCOS, hyperandrogenism, Cushing's) or medication-induced acne

Recent Evidence (2024–2025)

• A 2025 systematic review (PMID 39269130) highlights the cutaneous microbiome's role in acne pathogenesis, suggesting future probiotic/microbiome-modulating treatments may complement standard therapy.
• A 2025 meta-analysis (PMID 39509291) found that combining isotretinoin with laser/light-based treatments does not provide superior outcomes over isotretinoin alone for active acne.
• A 2024 network meta-analysis (PMID 39110247) on acne scarring found microneedling combined with PRP or other adjuncts offers greater improvement in scar appearance than microneedling alone.