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