Cosmeceuticals: focus on topical retinoids in photoaging

Riccarda Serri, MD
a,

, Matilde Iorizzo, MD
b
a
Department of Dermatology, University of Milan, Milan, Italy
b
Department of Dermatology, University of Bologna, Bologna, Italy
Abstract Evidence from a randomized clinical trial showed that, in spite of the many surgical procedures
effective in ameliorating the clinical appearance of photoaged skin, the only medical therapy with
proven benefits in photoaged skin are topical retinoids, in particular tretinoin, isotretinoin, and
tazarotene. The application of retinoids might not only clinically and biochemically repair photoaged
skin, but their use might also prevent photoaging. Furthermore, new evidence suggests a beneficial role
of topical retinoids in the treatment of intrinsically aged skin.
2008 Elsevier Inc. All rights reserved.
Introduction
Vitamin A and its derivatives, both natural and synthetic,
have been popular additives in topicals for years and are
recognized as the gold standard for the prevention and
treatment of photoaging.
The following topical retinoids are recognized as being
useful:
Natural retinoids
Retinol (vitamin A alcohol)
Retinyl-palmitate (vitamin A ester)
Retinyl-acetate (vitamin A ester)
Retinaldehyde (vitamin A aldehyde)
Tretinoin (all-trans-retinoic acid)
Isotretinoin (13-cis-retinoic acid)
Alitretinoin (9-cis-retinoic acid)
Synthetic retinoids
Tazarotene
Adapalene
Tretinoin, isotretinoin, alitretinoin, tazarotene, and ada-
palene are registered as drugs; the others are cosmeceuticals
(medicinally active cosmetics).
Vitamin Aand its derivatives exert their action by binding to
specific nuclear receptors. The ligand-receptor complex
modulates the expression of the genes involved in cellular
differentiation and proliferation, normalizing cell keratinization.
Retinoids might also act independently from the binding
to nuclear receptors. Each of them exerts its own activity,
offering a further choice to the dermatologists who deal with
topical retinoids.
Although there are several studies proving the efficacy of
tretinoin as topical treatment of photoaging, few studies are
available for the other retinoids.
Tretinoin
Kligman and Willis
1
first introduced retinoids for use as
photoaging agents. After its application, the author noticed
improvement of skin depigmentation and rejuvenation.
2,3
When used on photodamaged skin, tretinoin's clinical
effects include improvement of wrinkles, roughness, mottled
pigmentation, and skin appearance as a whole.

Corresponding author. 46-7 Via della Moscova, Milan 20121, Italy.

Tel.: +39 02 6575245.
E-mail address: riccardaserri@gmail.com (R. Serri).
0738-081X/$ see front matter 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.clindermatol.2007.09.016
Clinics in Dermatology (2008) 26, 633635
The histologic changes observed are decreased corneo-
cyte adhesion (loss of desmosomes, decreased tonofila-
ments, increased autolysis of keratinocytes, intracellular
glycogen deposition), epidermal hyperplasia, increased
number of Langerhans cells, increased synthesis of collagen
and elastin, and angiogenesis. Tretinoin enhances epidermal
cell turnover, decreasing contact time between keratinocytes
and melanocytes and promoting a rapid loss of pigment
through epidermopoesis.
Tretinoin is available in different concentrations (0.01%,
0.25%, 0.5%, and 0.1%) and as different formulations
(cream, gel, solution). Creams are generally prescribed for
sensitive skins, whereas gels are prescribed for oily skins.
Continuous once-daily application is mandatory to
achieve maximum results, in any case not occurring before
a 3-month period.
4
The only clinical improvement that
appears after only 1 month is skin smoothness. To maintain
the results, long-term treatment is necessary. There are no
limits to the duration of tretinoin topical use.
Moderate cutaneous side effects, especially erythema and
desquamation, are observed in most patients even if after 2 to
4 weeks these side effects decrease without discontinuing the
treatment. It may be necessary to interrupt the treatment for 2
to 3 days, to apply a calming and moisturizing cream, and
then to restart treatment once every 2 days.
Whenever tretinoin is prescribed, the use of sunscreen is
very important to avoid sunburns (the treated skin is thinner)
and worsening of photodamage (UV radiations decrease the
expression of retinoid receptors in skin cells, thus limiting
the effects of retinoids).
Retinol
There are no studies comparing its effectiveness with that
of tretinoin, although retinol does not appear to be as
effective. In photoaging, it is used as a cream in different
concentrations, ranging from 0.075% to 1%. It can be
considered a light alternative to tretinoin in case of
sensitive skins.
5
Retinyl-palmitate and retinyl-acetate
Esters are not considered effective against photoaging if
used alone.
6,7
Most of the products available are, in fact, a
combination of esters and hydroxy acids.
Retinaldehyde
Retinaldehyde is formulated as cream or gel and in
concentrations varying from 0.015% to 0.1%. Its efficacy is
similar to that of tretinoin, but it is much less irritating.
8,9
Isotretinoin
Topical isotretinoin is available as a 0.05% cream or
gel. It appears to be less irritating, yet less effective, than
tretinoin.
10
Alitretinoin
The theoretic benefit of alitretinoin 0.1% gel in the
treatment of photoaging originates from the binding and
activation of all nuclear retinoid receptors, but larger,
blind, and controlled trials are necessary to better
investigate its role.
11
Tazarotene
Tazarotene is an analogue of tretinoin that belongs to the
family of acetylenic retinoids. It has a specific binding profile
for beta and gamma retinoid receptors. Tazarotene improves
skin roughness, fine wrinkling, and epidermal atrophy.
12
It is
available at 0.05% and 0.1% gel and cream.
Adapalene
Even if usually indicated for acne, adapalene has also
been tested for the treatment of photoaging.
13
Once-daily
application of adapalene 0.1% gel for 4 weeks, followed by a
twice-daily application for up to 9 months, significantly
reduced actinic keratoses and lentigines.
References
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635 Cosmeceuticals: focus on topical retinoids in photoaging