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isotretinoin-systemic-retinoid-mechanisms-and-side-effects

Isotretinoin (Systemic Retinoid): Mechanisms and Side Effects Isotretinoin Authors: Ayaa Alkhaleefa Reviewers: Mehul Gupta, Ben Campbell Stephen Williams, Lauren Lee, Yan Yu*, Laurie Parsons* * MD at time of publication ↑ Apoptotic signaling in sebocytes Inhibits androgen nuclear receptors responsible for sebum secretion ↓ Sebaceous lipogenesis ↑ Apoptotic signaling in neural crest cells during embryonic development Alterations in hindbrain, neural crest, otic anlage, and reduced pharyngeal arch in embryo Craniofacial, cardiac, thymic, and central nervous system malformations in fetus Isotretinoin isomerizes to all-trans retinoic acid (ATRA) ATRA enters cell nucleus and binds retinoic acid receptors and retinoic X receptors ATRA induces tumour necrosis factor-related apoptosis-inducing ligand ↑ Apoptotic signaling in epidermal keratinocytes ↑ Expression of FoxO1 ↑ Expression of p53 (tumour suppressor) Release of caspases 3, 6, 7, and 9 ↑ Cell cycle inhibitors p21 and p27 ↓ Pro-survival proteins (Survivin) Sebaceous gland involution Sebum suppression C. acnes unable to break down sebum into pro- inflammatory lipids ↓ Colonization with C. acnes Teratogenicity ↑ Cornification (death) of epidermal keratinocytes ↓ Corneodesmosomes (main adhesive structures of the stratum corneum) ↓ Cohesion of corneocytes (dead keratinocytes) ↓ Corneocyte buildup in pilosebaceous follicles C. acnes unable to populate and release cytokines in corneocytes Epidermis Dermis Pilosebaceous follicle ↓ Stratum corneum thickness ↑ Trans-epidermal water loss Dryness, peeling & inflammation of lips (cheilitis), skin (dermatitis) & mucosa (mucositis) ↓ Comedogenesis Sebum Hair follicle Dermal- Epidermal Junction Sebaceous gland (sebocytes) Death of sebocytes in pilosebaceous follicles Reduction of number and size of acne lesions Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 20, 2022 on www.thecalgaryguide.com