Oral isotretinoin is highly effective for the treatment of severe and recalcitrant acne vulgaris (AV), especially in patients with nodulocystic disease.1-4 Almost all patients treated with oral isotretinoin develop dose-dependent mucocutaneous side effects.1-8 The predominant reported cutaneous side effect is xerosis, often with superficial desquamative changes. The xerotic and desquamative changes captured in clinical studies have often focused on facial and acral changes, however, diffuse xerosis is common in patients treated with oral isotretinoin.
What does the term â€œepidermal barrierâ€ specifically refer to?
The â€œepidermal barrierâ€ refers to the collective result contributed to by multiple physiologic responsibilities of the epidermis, many of which occur within the stratum corneum (SC). These responsibilities include homeostatic control of water content and flux (permeability barrier), recognition and neutralization of microbial organisms (antimicrobial barrier), countering of reactive oxygen species (antioxidant barrier), protection from effects of ultraviolet light exposure (photoprotection barrier), and response to exogenous allergens and haptens (immunologic barrier).9
Ultimately, the multiple â€œbarrier responsibilitiesâ€ of the SC work in harmony to maintain structural and functional integrity of skin (â€œhealthy skinâ€).9 Aberrations of any of the components of the epidermal barrier can lead to clinical manifestaions. The central barrier responsibility of the epidermis is the SC permeability barrier (epidermal permeability barrier). When the SC is unable to maintain proper water content and gradient, impaired SC integrity and suboptimal function of SC enzymes occur, and signals to â€œrestore the barrierâ€ are set into motion. When SC permeability barrier impairment persists without correction, signal amplification produces cascades that lead to clinically evident cutaneous abnormalities (ie, xerosis, fissuring, desquamative changes, eczematous dermatitis, hyperkeratosis). 9
How does oral isotretinoin alter the structure and function of skin? How does oral isotretinoin affect epidermal barrier integrity and function?
It is readily apparent that oral isotretinoin alters the structure, function, immunology, and bacteriology of the skin, although little is known about the effects of oral isotretinoin on specific SC components. The following structural and functional changes have been reported to occur in association with isotretinoin.
Oral isotretinoin causes increased epidermal turnover and skin fragility, with propensity for intraepidermal separation.10-12 Loss of desmosomes and decrease in tonofilaments occurs.10-12 Oral isotretinoin causes easier separation of corneocytes of the outermost SC, accounting for the superficial desquamative changes that are frequently observed in treated patients.10-12 This includes easy removal of superficial â€œsheetsâ€ of skin with wax stripping procedures to remove facial hair in patients on oral isotretinoin or topical retinoid therapy.