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