---

Treatment of Acne Vulgaris

---

Severity-Based Treatment Algorithm

---

Topical Therapies

Topical Retinoids

• Mechanism: Normalize follicular keratinization and corneocyte cohesion - expel existing comedones and prevent new ones. Also have significant anti-inflammatory properties.
• Agents: Tretinoin, adapalene, tazarotene, and trifarotene (4th-generation, RARγ-selective; 0.005% cream for face and back, approved ≥9 years)
• Combinations available: Tretinoin + clindamycin; tretinoin + BPO; adapalene + BPO
• Benefit: Concurrent retinoid use enhances BPO and antibiotic penetration into the sebaceous follicle
• Side effects: Local irritation (erythema, dryness, peeling, scaling) - peaks at 2-4 weeks, improves with continued use. An initial acne flare may occur in the first month but resolves spontaneously.
• Tip: Use slow-release delivery systems (microspheres, polyolprepolymer) to reduce irritancy at higher concentrations. Start every other day in sensitive patients.

Benzoyl Peroxide (BPO)

• Mechanism: Potent bactericidal (reduces C. acnes in follicle); mild comedolytic properties; no bacterial resistance reported - a key advantage over topical antibiotics.
• Formulations: Bar soaps, washes, gels, lotions, creams, foams, pads; concentrations 2.5%-10% (OTC and Rx)
• Combinations: BPO + clindamycin, BPO + erythromycin, BPO + adapalene, BPO + tretinoin
• Note: Bactericidal activity is NOT concentration-dependent, but irritation increases with strength. Can bleach clothing and bedding. Allergic contact dermatitis is possible.

Topical Antibiotics

• Agents: Clindamycin, erythromycin, minocycline (cream, gel, foam, solution, pledgets)
• Resistance problem: C. acnes resistance to clindamycin and erythromycin exceeds 50% in some countries. Topical antibiotic monotherapy is NOT recommended - always combine with BPO.

Azelaic Acid

• Naturally occurring dicarboxylic acid; Rx formulations: 15%-20%; OTC: 10%
• Inhibits C. acnes growth (anti-inflammatory) + reverses abnormal follicular keratinization (comedolytic)
• Non-inferior to adapalene 0.1% gel for maintenance therapy of inflammatory acne in women (with greater tolerability)
• Additional benefit: Lightens postinflammatory hyperpigmentation (useful in darker skin types)

Topical Dapsone

• 5% gel (≥12 years) and 7.5% gel (≥9 years) - FDA approved
• In RCTs (n=4340), dapsone 7.5% gel once daily: 30% of patients clear/almost-clear at week 12 vs 21% placebo
• Caution: Temporary yellow-orange staining of skin and hair with concomitant BPO use; methemoglobinemia with misuse/ingestion

Clascoterone 1% Cream

• Topical androgen receptor inhibitor - novel mechanism; effective in both males and females
• A newer alternative topical agent listed in moderate and severe acne regimens

Salicylic Acid

• Widely available OTC comedolytic agent (up to 2% concentrations)
• Available as gels, creams, lotions, foams, solutions, washes
• Side effects: erythema and scaling

Sodium Sulfacetamide

• Topical antibiotic via competitive inhibition of C. acnes PABA synthesis
• Formulated as lotion, suspension, foam, cleanser; alone or with 5% sulfur; tinted formulations available
• Caution: Orange fabric discoloration when used with BPO

Niacinamide (Nicotinamide)

• Common OTC ingredient; decreases sebum, increases ceramide production
• Niacinamide 2% gel is non-inferior to clindamycin 1% gel for moderate acne

---

Systemic Therapies

Oral Antibiotics

• First-line for moderate-to-severe inflammatory acne: Oral tetracyclines - primarily doxycycline, minocycline, or sarecycline
• Mechanism: Suppress C. acnes growth AND have intrinsic anti-inflammatory properties (downregulate TNF, IL-1, IL-6)
• Duration: Limited to 3-4 months; never as monotherapy - always combine with topical retinoid ± BPO
• Combining oral antibiotic with topical retinoid ± BPO gives greater improvement than antibiotic alone; continuing topicals after antibiotic course is beneficial

• Both are equally effective for inflammatory acne
• Subantimicrobial doxycycline (20 mg BID or 40 mg/day) has similar efficacy with fewer adverse effects than 100 mg/day
• Minocycline has higher risk of serious adverse events: minocycline-induced hypersensitivity syndrome, autoimmune hepatitis, lupus-like syndrome, cutaneous polyarteritis nodosa
• Some international guidelines prefer doxycycline over minocycline as first-line oral antibiotic

• Narrower antimicrobial spectrum than other tetracyclines
• Approved for acne in patients ≥9 years of age

• Macrolides (erythromycin, azithromycin) - for patients who are pregnant, cannot tolerate tetracyclines, or <8 years old
• Azithromycin has comparable efficacy to doxycycline, but high resistance risk limits use
• Trimethoprim-sulfamethoxazole: discouraged due to higher risk of severe adverse reactions

---

Hormonal Therapy (Female Patients)

• Effective regardless of serum androgen levels
• Combined oral contraceptive pills (estrogen + progestin): Block ovarian and adrenal androgen production
  • Meta-analysis: OCPs equivalent to oral antibiotics in reducing acne lesions after 6 months
  • Especially helpful for inflammatory acne
  • Choose progestins with low androgenic activity (e.g., norgestimate, desogestrel, gestodene) or anti-androgenic progestins (drospirenone, cyproterone acetate)
  • FDA-approved for acne: norgestimate/ethinyl estradiol, norethindrone acetate/ethinyl estradiol, drospirenone/ethinyl estradiol
• Spironolactone: Aldosterone antagonist with anti-androgenic properties; effective for acne in adult women at doses of 25-200 mg/day
  • Combined with OCP to prevent irregular menstrual bleeding and avoid pregnancy risk
• Flutamide: Nonsteroidal androgen receptor blocker (62.5-500 mg/day); limited by dose-related hepatotoxicity

---

Isotretinoin (Oral)

• Severe, nodulocystic acne (FDA-approved)
• Acne resistant to other therapies including oral antibiotics
• Acne that relapses quickly or causes scarring
• Gram-negative folliculitis, pyoderma faciale, acne fulminans

• Lidose-isotretinoin formulation can be taken without food
• An initial flare (first month) occurs in some patients - more likely with macrocomedones and higher starting dose
• Maintenance with topical retinoid ± BPO after isotretinoin may reduce recurrence

---

Surgical / Procedural Treatments

• Comedo extraction: Using Schamberg, Unna, or Saalfield expressers; #11 blade/18-gauge needle for closed comedones. Best for deep, inspissated comedones. Use with topical comedolytic for maximum benefit. Avoid on inflamed lesions (risk of scarring).
• Intralesional corticosteroids: Triamcinolone acetonide 2-5 mg/mL (~0.1 mL/lesion) for deep inflamed nodules/cysts. Risks: hypopigmentation, atrophy, telangiectasias, dermal deposits.
• Photodynamic therapy (PDT): Topical 5-aminolevulinic acid + blue/red/intense pulsed light or lasers (pulsed dye, 635 nm red diode); also methyl aminolevulinate + red light.
• Laser/light therapy: Blue light, intense pulsed light, pulsed dye laser, 1320 nm Nd:YAG, 1450 nm diode laser for inflammatory acne.
• Chemical peels: Alpha-hydroxy acids (glycolic acid), salicylic acid, trichloroacetic acid; reduce comedones by decreasing corneocyte cohesion. Well-tolerated in most skin types.
• Electrocautery / electrofulguration: For deep comedones.
• Cryotherapy: Option for comedonal acne in select patients.

---

Practical Tips for Topical Therapy

• Inform patients: 6-8 weeks for substantial improvement
• Apply topicals to the entire acne-prone region, not just individual lesions
• Simplify regimen to once daily when possible; use combination products
• For sensitive skin: start retinoid every other day for 2-3 weeks, then advance to daily
• Advise non-comedogenic moisturizers, sunscreens, and cosmetics
• Avoid harsh scrubs, toners, and irritating products
• Do not pick or manipulate lesions
• Address postinflammatory hyperpigmentation and scarring proactively

---