Clinical Relevance of Skin Barrier Changes Associated With the Use of Oral Isotretinoin: The Importance of Barrier Repair Therapy in Patient Management

June 2013 | Volume 12 | Issue 6 | Original Article | 626 | Copyright © June 2013

James Q. Del Rosso DO FAOCD

Dermatology Residency Program Director, Valley Hospital Medical Center, Las Vegas, NV

Oral isotretinoin is a non-aromatic oral retinoid that is highly effective for the treatment of severe inflammatory acne vulgaris that is refractory and/or prone to scarring, and has also been used successfully to treat several other disorders in selected cases. Since its introduction into the United States marketplace in 1982, it has been well recognized that cutaneous side effects characterized by xerotic and desquamative changes are very common, and appear to be related to epidermal dyscohesion, and to some extent the sebosuppressive effects of the drug. Additionally, increased susceptibility to staphylococcal colonization has also been observed. The epidermal barrier impairments that have been associated with oral isotretinoin are reviewed in this article along with clinical implications. Strategies to mitigate the altered effects of epidermal barrier functions are reviewed including the importance of topical barrier repair therapy.

J Drugs Dermatol. 2013;12(6):626-631.


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 “epidermal barrier” specifically refer to?

The “epidermal barrier” 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 “barrier responsibilities” of the SC work in harmony to maintain structural and functional integrity of skin (“healthy skin”).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 “restore the barrier” 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.

Corneocyte Dyscohesion

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 “sheets” of skin with wax stripping procedures to remove facial hair in patients on oral isotretinoin or topical retinoid therapy.