Systemic Acne Therapies

Systemic acne therapies are used for moderate to severe acne, acne that is scarring, resistant to topical therapy, or causing psychological distress. They include oral antibiotics (tetracyclines, macrolides), hormonal treatments (combined oral contraceptives, spironolactone) and oral isotretinoin. Treat early, since delayed treatment increases scarring and post-inflammatory pigmentation.

Mechanism. Oral antibiotics reduce C. acnes load and inflammation; combined contraceptives and spironolactone reduce androgen effects on the sebaceous gland; isotretinoin shrinks sebaceous glands, reduces sebum by up to 90 percent, normalises keratinisation and has anti-inflammatory effect, giving the only potential for lasting remission.

Pharmacokinetics. Doxycycline and lymecycline absorb well (reduced by cations); isotretinoin is lipophilic with absorption increased by fatty food; spironolactone is metabolised to active canrenone.

• Oral tetracyclines: doxycycline 100 mg daily (or 40 mg modified-release), lymecycline 408 mg daily, minocycline 50 to 100 mg twice daily (more side effects), sarecycline where available.
• Macrolides: erythromycin 500 mg twice daily or azithromycin pulsed regimens; for tetracycline intolerance and pregnancy; high resistance.
• Hormonal agents (women): combined oral contraceptives containing ethinylestradiol with cyproterone acetate, drospirenone, norgestimate or desogestrel; spironolactone 50 to 150 mg daily.
• Isotretinoin: the most effective single agent.

Regimens.

• Oral antibiotics: combine with benzoyl peroxide and/or a topical retinoid; limit to 3 months where possible, and stop at the first sustained improvement; maintain with topical retinoid. Do not use antibiotic monotherapy, and do not combine two oral antibiotics.
• Combined oral contraceptive: continue for at least 6 months; effect is slow.
• Spironolactone: start 25 to 50 mg daily, increase to 100 to 150 mg daily as needed; contraception is mandatory (risk of feminisation of a male foetus); check blood pressure and potassium.
• Isotretinoin: 0.5 mg/kg daily with food, increasing to 1 mg/kg as tolerated, until a cumulative dose of 120 to 150 mg/kg is reached (typically 16 to 24 weeks); low-dose regimens of 10 to 20 mg daily are alternatives. A second course may be needed.

Selection. Isotretinoin for severe nodular or scarring acne, failure of two courses of oral antibiotics plus topical therapy, relapse after antibiotics, or acne with significant distress. Hormonal therapy for women with premenstrual flare, jawline distribution or hirsutism or irregular periods.

Contraindications. Isotretinoin: pregnancy and breastfeeding, hepatic impairment, hyperlipidaemia, concurrent tetracyclines, vitamin A supplements. Tetracyclines: pregnancy and children under 8. Combined contraceptives: migraine with aura, thrombosis risk, smoking over 35 years, active liver disease. Spironolactone: hyperkalaemia, renal failure, pregnancy.

Serious effects. Isotretinoin: teratogenicity, hepatotoxicity, hypertriglyceridaemia, dryness of skin, lips, eyes and nose, muscle and joint pain, raised intracranial pressure, mood change and depression (relationship debated; monitor), bowel inflammation reports. Tetracyclines: photosensitivity, oesophagitis, raised intracranial pressure; minocycline: pigmentation, lupus-like syndrome, hepatitis, DRESS. Contraceptives: venous thrombosis. Spironolactone: hyperkalaemia, menstrual irregularity, breast tenderness, hypotension.

Interactions. Isotretinoin with tetracyclines or vitamin A. Spironolactone with ACE inhibitors, ARBs, potassium and NSAIDs. Rifampicin and enzyme inducers lower contraceptive efficacy.

Monitoring.

• Isotretinoin: liver tests and fasting lipids at baseline, 1 month and then if abnormal; pregnancy test before, monthly during and 5 weeks after; mood review each visit.
• Spironolactone: potassium and blood pressure at baseline and if risk factors exist.
• Review antibiotic response at 6 to 8 weeks; set a stopping date.

Special groups. Pregnancy: antibiotics are limited to erythromycin or azithromycin; no isotretinoin. Region: access to contraception, regular laboratory tests and dermatology care varies in East Africa; where the pregnancy prevention programme cannot be met, isotretinoin is not started. Scarring and keloid risk in darker skin favour early effective treatment.