Isotretinoina
Summary
Isotretinoin is an oral retinoid (vitamin A derivative) used to treat severe, refractory nodulocystic acne. It reduces sebaceous gland size and sebum production but is highly teratogenic, requiring strict pregnancy prevention protocols (iPLEDGE program in the US).
Detail
Isotretinoin (13-cis-retinoic acid) works by decreasing sebaceous gland size and activity, normalizing follicular keratinization, and having anti-inflammatory and mild antimicrobial effects against Cutibacterium acnes. It is the most effective treatment for severe nodulocystic or scarring acne unresponsive to conventional therapy (antibiotics, topical retinoids, benzoyl peroxide).
Key adverse effects (high-yield for boards): - Teratogenicity: causes severe birth defects (CNS, cardiac, craniofacial, thymic abnormalities) - Pregnancy Category X. Requires two forms of contraception, monthly pregnancy tests, and enrollment in iPLEDGE. - Mucocutaneous: cheilitis (very common), dry skin/mucous membranes, photosensitivity. - Hepatotoxicity: elevated LFTs. - Hypertriglyceridemia and hypercholesterolemia - monitor lipids. - Pseudotumor cerebri (benign intracranial hypertension) - avoid concurrent tetracyclines. - Bone effects: premature epiphyseal closure, hyperostosis (long-term use). - Mood changes: depression, suicidal ideation (controversial but monitored). - Night blindness (rare).
Monitoring: baseline and periodic LFTs, lipid panel, pregnancy tests (monthly) in females of reproductive age.
Mechanism relates to retinoid receptor (RAR/RXR) binding, altering gene transcription related to keratinocyte differentiation and sebocyte apoptosis.
Clinical pearls: Contraindicated with tetracyclines (risk of pseudotumor cerebri) and vitamin A supplements (additive toxicity). Long washout period needed before pregnancy after discontinuation.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- UpToDate: Isotretinoin therapy for acne
- Fitzpatrick's Dermatology in General Medicine
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