INTRODUCTION
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.
