This document discusses the definition and classification of chemical peels. It defines a chemical peel as a skin treatment that uses caustic solutions to improve skin structure through exfoliation and regeneration. Chemical peels can vary significantly based on factors like the molecule used, application technique, skin type, and practitioner experience. As such, rigid classification as "superficial", "medium", or "deep" is imperfect. However, peels can generally be classified based on the depth of skin affected, from very superficial affecting just the stratum corneum, to superficial affecting the epidermis, to medium affecting the papillary dermis, to deep affecting the reticular dermis. A table provides examples of molecules commonly used for peels and
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4. Textbook of
Chemical Peels
Superficial,Medium and Deep Peels
in Cosmetic Practice
Philippe Deprez MD
Medical Director
Policlinica Estetica & Anti-Aging
Empuriabrava
Spain
6. Acknowledgment vii
1 Chemical peels: definition and
classification 1
2 Pre-peel care 5
3 Post-peel care 13
4 Factors influencing chemical peels 27
5 Choosing the right peel 31
6 Alpha-hydroxy acids: chemistry, pH
and pKa, and mechanism of action 47
7 Alpha-hydroxy acids: histology and
factors influencing penetration 53
8 Alpha-hydroxy acids: indications
and results 55
9 Alpha-hydroxy acids: application as
cosmetics and as peels 59
10 Alpha-hydroxy acids: side-effects
of AHAs 67
11 Alpha-hydroxy acids: a new slow-release
AHA complex with no
neutralization required 69
12 Trichloroacetic acid: general
information, toxicity, formulations
and histology 79
13 Trichloroacetic acid: indications and
contraindications 95
14 Trichloroacetic acid: classic semiology 105
15 Easy TCA®: basic protocol and skin
aging 109
16 Treating melasma, chloasma and
post-inflammatory
hyperpigmentation 121
17 Treating acne 125
18 Treating multiple keratoses on
the scalp 131
19 Treating aging of the hands and
forearms 135
20 Treating the neck and décolletage 141
21 Stretch marks and scars:
dermabrasion and peeling 145
22 Actinic keratoses and lentigines 167
23 Trichloroacetic acid to the papillary
dermis: Unideep® 177
24 Resorcinol: Unna’s paste/Jessner’s
solution 183
25 Phenol: chemistry, formulations and
adjuvants 193
26 Phenol: properties and histology 203
27 Phenol: skin penetration and
detoxification 209
28 Toxicity of phenol: causes,
prevention and treatment 213
29 Phenol: choice of peel and
combination treatments 225
Contents
7. 30 Phenol: indications 233
31 Phenol: contraindications,
precautions and safety 249
32 Phenol: pre-peel preparation 253
33 Full-face phenol: nerve block
anesthesia and/or sedation 261
34 Full-face phenol: application 273
35 Phenol: post-peel care 283
36 Phenol: chemical blepharoplasty
and cheiloplasty 295
37 Complications of chemical peels 313
38 Combination of techniques 371
Index 377
vi Contents
8. The publication of this work has been assisted by an educa-tional
grant from Skin Tech (www.skintech.info;
www.peeling.com).
It should be noted that this textbook is comprehensive
about all available peel products, but that there are many
ancillary products (such as sunscreens) manufactured in
comparable formulations about which it cannot be
expected to be comprehensive; the author is most familiar
with and recommends those from Skin Tech, but does not
imply by this that other products may not be comparable.
Acknowledgment
9.
10. 1
Chemical peels: definition and classification
Definition of a chemical peel
A chemical peel is a skin treatment intended to visibly
improve the structure of treated tissue by the external
application of a caustic solution. It can simply accelerate
the natural processes of exfoliation, but can also com-pletely
destroy the epidermis and a more or less large pro-portion
of the dermis, essentially by protein coagulation or
lysis. The effect of any peel reaches the dermis, directly or
indirectly and to varying depths, where the processes of
regeneration are induced to a greater or lesser degree,
depending on the molecule or molecules used and the
application procedure.
Chemical peels are among the oldest forms of skin rejuve-nation
and form a group of treatments in their own right.
They are both flexible and effective, with a histological, chem-ical,
toxicological and clinical basis. They have an ancient his-tory,
have evolved rapidly and can be adapted to almost any
circumstances within the limits of their indications.
Most peels, to varying degrees, cause the same types of
histological changes, whose clinical results lead to a more
or less rejuvenating effect on all or part of the skin.
Classification is always restrictive, as it forces highly vari-able
events into a rigid framework. We will see in this book
that so many different factors come into play that it
becomes difficult to fit all chemical peels into a simplified
and rigid classification of ‘superficial’, ‘medium’ and ‘deep’.
Let us take the well-known glycolic acid peel as an exam-ple:
its depth of action depends on the patient’s skin type, the
presence of associated disorders (e.g. seborrheic dermatitis),
skin preparation in the long, medium and short term, the
galenical form (gel, liquid, mask or self-neutralizing pseudo-gel),
the concentration of the product, the m/m, m/v or m+v
calculation, whether or not it is combined with other acid
molecules (e.g. lactic or kojic), the pH of the solution (e.g.
0.5 or 3.5) and therefore the fraction of free glycolic acid,
what it is applied with (brush, cotton pad, etc.), the number
of coats, how forcefully it is applied, whether it is applied on
the face or body, the exact location on the face (e.g. nostrils
or eyelids1), the contact time, how or whether it is neutral-ized
or diluted at the end of the peel, the immediate post-peel
care, the quality of care between peels, the number and
frequency of repeat sessions,... And the list goes on!
It is clear that it does not take much to turn a very light
glycolic acid peel into a medium-depth peel that can even
reach the deeper layers of the dermis and risk discoloration
or even scarring. All it takes is for the peel not to be neu-tralized
properly. The same goes for all of these caustic
molecules, which is why, until recently, it was usually nec-essary
to have a thorough knowledge of chemical peels and
skin anatomy before undertaking this kind of treatment.
Every practitioner, through personal experience and prac-tice,
should aim to standardize their treatments in order to
eliminate the maximum number of variables. Fortunately,
new chemical peel formulas are now available that are eas-ier,
safer and quicker to use, allowing young physicians to
get on with the job of peeling without losing sleep and hav-ing
post-peel nightmares. Sound knowledge and experi-ence
are still essential for peels to the papillary dermis.
Criteria for classification
Molecular dependence
It is very simple to understand that phenol is more aggres-sive
than lactic acid.
Doctor dependence
Classification may be personal; it may be related to the
practice of one particular doctor who has standardized his
methods of treatment with a view to limiting uncontrol-lable
variables. But such a classification would not allow for
any scientific exchange.
What would produce a superficial peel with one practi-tioner
could in fact result in a medium peel with another
who uses the same product with a different application
technique. This is why peels are often considered to be
‘doctor-dependent’.
How can we give a valid classification for a treatment
that is doctor-dependent? We should also compare prod-ucts
of the same type only, and yet the quality of the prepa-rations
and excipients is highly variable and impossible to
control.
11. Chemical dependence
It is known that trichloroacetic acid (TCA) crystals, for
example, are very hydrophilic, which means that they must
be kept in perfect conditions so that the pharmacist can
prepare the solutions we prescribe properly. How can we
know how long the pharmacist’s bottle of TCA crystals has
been open? If the crystals have not been hydrated inadver-tently
(if the pharmacist closes the bottle as soon as he has
taken out the required amount), the final concentration
will be correct. If, on the other hand, the crystals are mostly
hydrated (if the pharmacist leaves the bottle of TCA open
in order to serve another customer), the concentration of
the solution provided by the pharmacy will be abnormally
low and not very effective. Peels are therefore also consid-ered
to be ‘chemical-dependent’.
Patient dependence
Each patient has a skin type that is genotypically and phe-notypically
unique. The skin has a history that the doctor
must know about. Stable products that are properly pre-pared
and applied with precise methodology, in the same
way, by the same doctor, on the same day, can produce dif-ferent
results on different patients. Every morning, or
maybe several times a day, patients go through their own
particular skincare routine that the doctor doing the peel
does not necessarily know about. Let us take for example
the application of large quantities of topical benzoyl perox-ide,
which some teenagers use secretly for acne. It reduces
the thickness of the stratum corneum and makes the skin
more permeable. This of course makes it easier for the acids
used for skin peeling to penetrate the skin, and can, in
2 Textbook of Chemical Peels
Table 1.1 Summary of chemical peels
Molecule Depth Application
Glycolic acid Very superficial 25–50% partially buffered, for 1–2 min
Superficial 50–70% partially buffered, for 2–10 min
Medium (not recommended) 70% unbuffered, for 5–10 min
Mixture of AHAs Dermal and epidermal stimulation Easy Phytic®: pH 0.5, but slow-release effect + self-neutralizing
Jessner (Resorcinol) Very superficial 1–3 layers
Superficial 4–8 layers
Medium (not recommended) 4–8 layers combined with 25% m/m TCA
Unna (Resorcinol) Superficial One application of 30% paste for 5 min
Intermediate Two applications of 40% paste for 30 min
Medium Three applications of 40% paste for 30 min, after skin preparation
TCA Very superficial • One application of 10% TCA
• 10–20% TCA solution, depending on number of coats and skin
preparation
Superficial • Easy TCA® or 10–15% m/m solutions, depending on number of
coats and preparation, or in combination (e.g. Abrasion, Dry
Ice, Jessner)
Medium • Unideep®
• Solutions of >35% m/m
Deep • Sandpaper abrasion + Easy TCA®
• Unideep®
• Only Touch® (AHA + TCA > 40% m/m – localized deep)
Phenol Localized deep Lip & Eyelid® (wrinkles on lips and eyelids)
Full-face deep Lip & Eyelid®, Baker, Litton, Exoderm, etc.
AHA, alpha-hydroxy acid; TCA, trichloroacetic acid.
12. some cases, cause unexpected burns. A similar situation
arises with patients who want to present their doctors with
perfectly clean skin and use abrasive creams – the intention
is noble but the consequences are sometimes unpleasant. A
peel is therefore also ‘patient-dependent’.
If we leave aside these variables, we can fit the different
types of peels into their appropriate slots. This is just for
the beauty of the exercise however, as the variables still
need to be taken into account. It is clearly possible to per-form
a superficial or medium peel using phenol. But, given
the inherent toxicity of phenol, what would be the point?
What is more, 70% unbuffered glycolic acid that is left for
10–15 minutes on a thin, sensitive skin that has been pre-pared
with retinoic acid can result in a cosmetic disaster. It
is possible to carry out good-quality, deep peels with TCA,
but the risks can be greater than if phenol is used correctly.
Summary table
Table 1.1 is intentionally incomplete. A peel is considered
as ‘very superficial’ when its action is limited to the stratum
corneum, ‘superficial’ if it does not go beyond the basal
Chemical peels: definition and classification 3
layer of the epidermis, ‘medium’ if it reaches the papillary
dermis and ‘deep’ if it reaches the reticular dermis.
In reality, it is better to determine the depth of a peel by
clinically observing what is happening to the skin during
the course of the treatment than by blindly applying set
recipes. When we say that the result of a glycolic acid peel is
‘time-dependent’, this does not mean having to watch the
clock but rather continuously analyzing how the skin is
reacting in order to determine the best moment to start
neutralization.
There is one basic principle to be respected: a peel
should not be unnecessarily deep or unnecessarily superfi-cial.
There is no point completely destroying the papillary
dermis when treating a purely epidermal problem, and it is
pointless and ineffective to use an intraepidermal peel,
even repeatedly, to treat a dermal problem.
Notes
1. The nostrils can tolerate glycolic acid better than the skin
around the eyelids, and many application procedures for
glycolic acid peels recommend avoiding application to the
eyelids.
13.
14. Is it necessary to prepare the
skin?
Depending on the type of peel, preparing the skin can be
essential, completely pointless or even dangerous. The
chapters devoted to the different types of peels give details
of the preparation recommended in each particular case.
This chapter deals with the generalities of pre-peel care.
Medium- and long-term
preparation
Alpha-hydroxy acid (AHA) peels produce the best results if
they are preceded by careful preparation and followed by
long-term daily cosmetic care. Easy Phytic® solution, on
the other hand, does not allow any pre-peel preparation
that is likely to accelerate penetration of the acids, as the
stratum corneum must be intact for the peel to be safe.
Classic trichloroacetic acid peels, in a simple aqueous solu-tion
in gel or mask form (TCA–SAS) always require around
1 month’s intensive pre-peel preparation. This preparation
stimulates keratinocyte regeneration and reduces the risk
of post-inflammatory pigmentary changes and/or scarring.
It blocks the first stages of the biochemical conversion of
tyrosine into indole groups and melanin and limits the
reaction of melanocytes to ultraviolet light. Easy TCA®
requires no preparation under its basic protocol (until
scattered pinpoint or cloudy white frosting appears). The
preparation required for its special deep-peel protocol or
when combined with abrasion is discussed later in this
book.
Resorcinol produces far better results and fewer compli-cations
if the skin is well prepared.
Phenol does not usually require any specific preparation,
but needs careful post-peel care.
As a general rule, it is worthwhile preparing the skin
carefully with tyrosinase inhibitors if there is any risk of
post-peel pigmentary changes or to optimize results when
treating melasma. Retinoic acid and sometimes glycolic
acid are used to make transepidermal penetration more
even or to deepen the action of the acid solution.
Immediate pre-peel preparation
Generally, patients must wash their skin with soap and
water before going to the appointment. The doctor will dis-infect
the skin with alcohol and degrease it with acetone or
ether. These degreasing products allow the peel solutions,
which are usually hydrophilic and have difficulty penetrat-ing
the skin’s protective oils, to penetrate more deeply and
evenly. They break down some of the proteins and phos-pholipids
in the cell membranes, which enhances the
action of the acids applied afterwards.
AHA peels require very careful preparation before being
applied. The skin should be cleaned with soapy water,
rinsed thoroughly, degreased with acetone and disinfected
with alcohol. Unlike the classic AHA peels, with Easy
Phytic®, the skin must be cleaned with a gentle, non-aggressive
cleansing foam that only contains surfactants, so
that the acids do not penetrate the skin too quickly and sat-urate
its natural buffer capacity, making it impossible for it
to neutralize the sudden inflow of acids in time. Thorough
cleansing and degreasing of the skin before Easy Phytic®
would oblige the doctor to neutralize it in the classic man-ner
– when there is no prior preparation, there is no need
to neutralize it.
With TCA–SAS, resorcinol, salicylic acid, azelaic acid or
phenol peels, the skin needs to be thoroughly cleansed of
make-up, degreased and disinfected. Easy TCA® solution,
on the other hand, contains saponins that make pre-peel
make-up removal and degreasing unnecessary; the skin’s
natural defenses are only very slightly diminished by this
peel, and therefore there is no need for any particular pre-peel
preparation against infections.
Products used to prepare the
skin
The products usually used to prepare the skin are sun-screens,
tretinoin, AHAs and tyrosinase inhibitors. Jess-ner’s
solution is sometimes used as a pre-peel preparation.
It is often necessary to take measures to prevent infection,
especially herpes.
2
Pre-peel care
15. Prevention of infection
Prevention of the herpes simplex virus is essential for
patients who have a history of the infection (a single inci-dence
of herpes is enough). Herpes prevention is necessary
with a peel to the papillary dermis. It is also worthwhile
when a more superficial peel is usually accompanied by a
severe inflammatory reaction, as is the case with resorcinol,
‘classic’ AHAs and TCA–SAS. It is not necessary when
using Easy TCA® under its basic protocol or Easy Phytic®.
General infection prevention measures should be taken,
depending on the depth of the peel. For more information,
see the discussion of infections in Chapter 37.
Pre-peel sun protection
It can be beneficial to protect the skin against the sun
before certain peels. Effective sun protection should start 2
weeks before a medium or deep peel and even before a
series of superficial peels to inhibit melanocyte activity and
avoid excessive stimulation of melanin production before
the peel.
Prevention of pigmentary changes
Before any ‘classic’ peel, steps must be taken to limit the
risk of pigmentary changes. Preparing the skin with tyrosi-nase
inhibitors (hydroquinone, kojic acid, azelaic acid,
arbutin, Morus Alba, licorice extracts, etc.) is especially
recommended to curb the enthusiasm that certain
melanocytes have for converting tyrosine into melanin.
Preventive measures should begin 3–4 weeks before a
medium or deep peel.
Combinations of hydroquinone (2–4%) plus kojic acid
(2–3%) or hydroquinone (2–4%) plus glycolic acid (8–10%)
are effective, as are certain formulas containing several
tyrosinase inhibitors, antioxidants and concentrated retinol
(Blending Bleaching® cream). Some patients may develop
hyperpigmentation, or even ochronosis, when treated with
hydroquinone. Patients with dark skin types are most at risk.
Long-term use of high-concentration hydroquinone can
also cause confetti-like depigmentation (Figure 2.1).
Hydroquinone is prohibited from sale as an ingredient
in cosmetic or cosmeceutical products in many countries
(although it is available on medical prescription) and has
been successfully replaced by new formulas combining
other tyrosinase inhibitors. Creams containing azelaic acid
(usually at a concentration of 20%) are considered slightly
bleaching when used for at least 4–6 months. Azelaic acid is
an irritant, and is used mainly when other formulations
cannot be used. For oily or thick skins, tyrosinase
inhibitors can be prescribed in a gel form that penetrates
the skin more easily and allows instant and easy application
of make-up. For more information, see the discussion of
pigmentary changes in Chapter 37.
Even penetration of acids and
stimulation of skin regeneration
To perform a medium or deep TCA–SAS peel, the active
molecule in the peel solution has to penetrate more deeply
and the skin must regenerate more quickly. We have two
large groups of molecules at our disposal: AHAs and
retinoids.
AHAs (e.g. 10–15% glycolic acid) break down cor-neodesmosomes
that maintain intercorneocyte cohesion;
they make it easier to shed this layer of dead cells (which
are, however, essential to the skin’s defenses, as they are
largely responsible for maintaining the permeability barrier
function in the skin as a whole). The epidermis is thinned
by the AHAs, making the stratum corneum more perme-able,
and the acids can penetrate more deeply and evenly.
The risk with this preparation is that the epidermis may
become too permeable and the effect of the peel can go too
deep. A peel that is meant to reach the papillary dermis
could penetrate as far as the reticular dermis as a result of
too ‘strong’ a preparation of AHAs. A peel that is meant to
remain intraepidermal could become intradermal and
result in post-peel complications and more downtime: an
intraepidermal peel removes several layers of ‘skin-color’
keratinocytes in light flakes for around 3 days, whereas an
intradermal peel removes the entire epidermis in the form
of strips of brownish skin. The darker the skin type, the
more visible is the flaking.
Retinoids form a growing range of products with ever-widening
indications. The retinoid most used in pre-peel
preparation is tretinoin. Among other things, it stimulates
keratinocyte growth in the basal layer and causes an overall
thickening of the epidermis but also a relative thinning of
the stratum corneum. The pre-peel use of tretinoin
6 Textbook of Chemical Peels
Figure 2.1
Confetti-like depigmentation.
16. enhances penetration of the acids at the same time as stim-ulating
the regeneration processes in the keratinocytes of
the basal layer.
The choice of one or another of these molecules depends
on the condition of the patient’s skin. Tretinoin is not used
if the patient has many telangiectasias; AHAs are avoided if
the skin is very thin. Conversely, the two products can be
mixed in the same prescription, in variable concentrations,
depending on the skin type and the desired effect. The con-centration
of tretinoin would be increased to stimulate
reepithelialization; the concentration of glycolic acid
would be increased to improve and even out transcorneal
penetration.
Tretinoin
Tretinoin (all-trans-retinoic acid, ATRA) is the carboxylic
acid form of vitamin A (retinol). It is one of the first-gener-ation
retinoids and has been used since the 1970s to treat
acne complaints and dyskeratosis. It is important to know
all about this molecule in order to obtain benefit from its
actions.
Histological changes
During long-term treatment with tretinoin, the results can
first be seen through a microscope, long before they are
clinically visible. These histological changes explain the
indisputable clinical efficacy of continuous treatment. The
epidermis increases in thickness by 10–40%, with a thick-ening
of the stratum granulosum to the detriment of the
superficial stratum corneum (which decreases by about
25%); the overall water content of the epidermis is thus
increased and the skin appears more hydrated. This epider-mal
hyperplasia is observed both on the face and on the rest
of the body, especially on the arms or forearms. Unfortu-nately,
it is not certain whether the improvement is perma-nent,
as some studies show a reversibility of the action of
tretinoin (a habituation phenomenon?) after 6 months’
treatment on the forearms and the disappearance of histo-logical
improvement altogether 1 year after the start of the
treatment, whereas clinically the improvement persists.
Normal epidermal differentiation is restored and ker-atinocyte
abnormalities gradually decrease. The atypical
keratinocytes are eliminated and the tretinoin prevents or
delays keratoses from reappearing. The melanocyte clusters
in the basal layer gradually disperse as a result of the
increased cell turnover. The marks on the skin thus tend to
be more diffuse, or even to disappear. The overall pigmen-tation
in the epidermis decreases in patients with black skin
(32%1 and 23%2) and in patients with yellow skin (41%3).
One year after the start of treatment, the melanin content
of the epidermis continues to decrease and causes the skin
to lighten in the long term. As with chemical peels, a newly
formed collagen layer appears, in horizontal bands, just
Pre-peel care 7
beneath the basal membrane, in the Grenz zone. New
active fibroblasts appear in the dermis, and new elastic and
collagen fibers are secreted. An increase in glycosaminogly-cans
thickens the dermis, and elastotic tissue is pushed
deeper down.
After 26 months of daily treatment with 0.05% tretinoin,
the events described above are extensive enough to push
the elastotic tissue deep down and hide it under the new
vascular, elastic, collagen and epidermal growth. It must be
noted, however, that not all authors accept the existence of
these histological changes in the dermis in the long term. In
particular, a study by Gilchrest4 on 500 biopsies carried out
during a 5-year observation of daily topical tretinoin treat-ments
(in concentrations between 0.001% and 0.1%) could
not find any evidence of histological changes in the dermal
parameters. This is surprising, and contradicts the estab-lished
fact that clinically visible angiogenesis exists.
Mechanism of action
Tretinoin is a synthetic (all trans) retinoic acid. Retinol and
retinaldehyde are also converted into retinoic acid in the
target cell where it participates in metabolic activity. The
retinoic acid penetrates the cell’s nucleus, where it binds
with a retinoic acid receptor (RAR). The complex formed
by the retinoic acid and the RAR (RA–RAR) interferes with
certain areas of DNA by modulating the expression of
some genes. It appears that retinoic acid alters the regula-tion
of the cell cycle.4
For many years, tretinoin was considered capable of
reducing sebum production in the sebaceous glands, but
serious doubt has been cast on this theory. It is generally
thought that the mode of action of tretinoin is essentially
linked to the increase in epidermal turnover and enhanced
exfoliation of the stratum corneum, which makes it easier
for the pilosebaceous units to drain. A reduction in
melanin production has also been observed. Used specifi-cally
as a pre-peel preparation, tretinoin evens out the
thickness of the stratum corneum and reduces overall skin
thickness. In these conditions, skin permeability increases
significantly. Tretinoin also stimulates keratinocyte divi-sion
and thus facilitates the regeneration phase, which can
sometimes be too slow with certain peels. Topical tretinoin
stimulates fibroblast production of collagen as well as other
components of the dermal extracellular matrix, and some-times
creates a new layer of ‘repair’ collagen that is laid on
top of the photodamaged collagen.
Indications
Clinical results appear slowly and gradually, after histolog-ical
improvement. The skin soon appears to be intensely
hydrated, once the erythema has disappeared or subsided.
Clinically, it takes a year for the rejuvenating action of
tretinoin to show. Patients, who hope to see rapid
17. improvement, are not best pleased with these slow clinical
results on aging skin. Progress can sometimes be seen more
quickly when treating dyschromia: some results may be
seen after 1 month of daily application of 0.1% tretinoin
cream.
Comedonal acne and acne rosacea respond well to
tretinoin. In fact, the anti-aging effect of tretinoin was first
observed in patients being treated with tretinoin for come-donal
acne: their skin texture and skin tone were gradually
seen to improve.
Oral isotretinoin (9-cis-retinoic acid) is often used in
treating severe or stubborn acne rosacea. A 1994 study5
compared the treatment of rosacea with 10 mg/day low-dose
oral isotretinoin, 0.025% low-dose topical tretinoin
and a combination of the two. The results showed that
before the 16th week of treatment, isotretinoin was more
effective, but that afterwards there was no difference
between tretinoin and isotretinoin. The combination of
systemic and topical treatment does not give any further
improvement in low doses.
It is generally accepted that tretinoin with a concentra-tion
of 0.05% is as active as 5% benzoyl peroxide. Topical
tretinoin makes the skin smoother: the same patients who
benefited from the visible rejuvenating effect of tretinoin
when being treated for acne noticed, among other things,
that their skin had become smoother and softer after treat-ment.
The improvement brought about by this topical
treatment is therefore visual as well as tactile.
The application of topical tretinoin improves senile
atrophy of the skin: a decrease in cell abnormalities and
dysplasias can be seen, as well as an antitumor effect that
persists after the end of treatment if it has been adminis-tered
correctly and for a sufficiently long period.6
Topical tretinoin reduces the size and number of lentig-ines
and other age-related discolorations. In some cases,
however, because of its photosensitizing potential,
tretinoin can aggravate certain types of dyschromia. This
can be problematic for Asian patients, for whom hyperpig-mentation
is more of a problem than wrinkles as they age.
The study by Griffiths et al3 proved (clinically, histologi-cally
and by colorimetry) that 0.1% tretinoin significantly
improved hyperpigmentation in these patients. There was
a 41% improvement with tretinoin, compared with a 37%
aggravation in patients receiving the vehicle alone.
Post-inflammatory hyperpigmentation is also improved
by tretinoin, as proved clinically, histologically and by col-orimetry,
in a study by Bulengo-Ransby et al2 on subjects
with black skin. A 40% improvement can be expected after
40 weeks of treatment with 0.1% tretinoin. In the treatment
of melasma, topical 0.1% tretinoin was studied in compari-son
with the vehicle alone in black patients.1 A 10-month
treatment lightened the melasma by 32% (an improvement
factor established both clinically and by colorimetry).
Histological studies have shown a significant decrease in
epidermal pigmentation in patients treated with tretinoin
compared with placebo. Of the patients treated with
tretinoin, 67% developed only one side-effect, a mild
‘retinoid dermatitis’ (which is to be expected when using a
concentration of 0.1%). This study also showed that the
finest wrinkles disappeared and other wrinkles improved.
Overall, skin tone improves because of the combination of
histological events in the dermis and epidermis described
above. The skin takes on a rosier complexion as a result of
angiogenesis occurring deep down.
How to prescribe tretinoin
One study7 showed that a tretinoin concentration of 0.01%
is effective for the face, hands and forearms, whereas
another8 showed that there is no difference between
placebo, 0.01% tretinoin and 0.001% tretinoin. A concen-tration
between 0.05% and 0.1% is, on the other hand,
always considered active. The average concentration used
is 0.05%, but different skin types or sensitivities may
require different concentrations, and it is recommended to
start any treatment with a trial dose of 0.02% or 0.03%.
The following is one frequently used formulation
(0.025%):
tretinoin 15 mg
urea (carbamide) 6 g
water 4 g
Neribase® cream ad 60 g
or Eucerin® O/W ad 60 g
If this dose is well tolerated, it is possible to go immedi-ately
or gradually to a concentration of 0.05%. This con-centration
is common in proprietary medicines, but if
prescription medicines are preferred, it is possible to pre-scribe
0.05% tretinoin in the following formulation:
tretinoin 30 mg
urea (carbamide) 6 g
water 4 g
Neribase® cream ad 60 g
or Eucerin® O/W ad 60 g
Formulations in alcohol gels dry out the skin, increase
the penetration of the tretinoin and make the treatment
more uncomfortable. Gels should only be used on thick
and oily skins.
When the patient can tolerate a concentration of 0.05%
without any notable side-effects, the concentration can
gradually be increased to 0.07%, 0.09% and 0.1%. Concen-trations
higher than this are rarely used. If, on the other
hand, the skin is very sensitive and becomes irritated in
spite of a low concentration of 0.025%, the concentration
must be decreased to 0.0125%9 or the patient should be
asked to do one of the following. The skin can be sprayed
with warm water immediately before applying a small
8 Textbook of Chemical Peels
18. quantity of cream. The cream will spread more easily and
less of the active ingredient will be applied on the skin.
Alternatively, the tretinoin cream can be mixed in the palm
of the hand with an equal quantity of hydrating vitamin E
cream10 in order to halve the final concentration.
If the skin is still sensitive to the treatment, as a last
resort, the treatment can be applied every other day or once
every 3 days for the first month. Experience shows that
daily application of low concentrations is a better way to
prepare the skin for higher doses than applying higher con-centrations
two or three times a week. The ‘normal’ con-centration
for daily application (0.05%) is reached
gradually over 2–3 months.
It makes little sense to combine tretinoin with a topical
corticosteroid to limit the inflammatory reaction. It may
well be that this combination is supposed to stop inflam-mation,
but inflammation is beneficial in that it stimulates
the process of skin repair. Furthermore, the combined
effect of corticosteroid and tretinoin could potentially
cause telangiectasia. The tretinoin would stop skin atrophy
as a result of the application of topical corticosteroid,
whereas it should increase the thickness of the epidermis
overall. A large part of the effect would therefore be lost.
Finally, corticosteroids should not be applied to the skin
for a prolonged period, whereas long-term application of
tretinoin is necessary.
If the skin is resistant from the start and does not
respond at all to the above formulation at 0.05%, a concen-tration
of 0.1% can be used. This high concentration has
been shown to produce results rapidly, but can often have
serious side-effects. Therefore, before such a sudden
increase in concentration, there are a few ‘therapeutic
tricks’ that can be tried: when the skin appears not to
respond to a single daily application of 0.05%, a 0.05%
cream can be applied twice a day – once in the morning fol-lowed
by a sunscreen and again in the evening. To increase
the effect, it is possible to prescribe an alcohol gel, starting
with a concentration of 0.05%, and increasing to 0.1% if
the patient can tolerate this. To increase the potency of the
tretinoin, the impermeability of the skin barrier can be
decreased, either by applying a 10% glycolic acid cream 20
minutes before applying the tretinoin or by using a mildly
abrasive sponge (Buf-Puf®) on the skin before using the
tretinoin. In some extreme cases, a light facial or body
scrub twice a week increases skin permeability and makes it
easier for the tretinoin to penetrate. Very superficial micro-dermabrasion
with corundum crystals or sandpaper can
also make the skin more permeable.
Age for starting treatment
The lighter the phototype, the better it is to start treatment
at a young age. For example, individuals with skin photo-type
II can start treatment in their 20s, whereas individuals
with skin phototype IV should only start in their 30s.
Pre-peel care 9
Various recommendations
Tretinoin cream should be kept out of direct sunlight and
away from heat sources, to which it is sensitive. In spite of
these precautions, it gradually loses its efficacy and it is rec-ommended
that the prescription be renewed every 3
months. Tretinoin is sensitive to oxidation, heat and ultra-violet
light: the refrigerator (4°C) seems to be the best place
to store this cream. The by-products of degradation turn
the cream a yellowish color, in which case it should no
longer be used.
Tretinoin is photosensitizing, and it is therefore prefer-able
to apply the cream in the evening and to use a hydrat-ing
antioxidant or a cream such as Blending Bleaching®
combined with a sunscreen (UVB + UVA + HSP) of factor
20 or above in the morning. The tretinoin cream is applied
after washing the skin with a mild soap (Avene® or Skin
Tech’s Pre-Peel Cleanser®), and is rubbed gently onto the
face and neck (very gently on the neck where the skin is
more sensitive). It is striking to note that the earlobe is
often missed out in skin rejuvenation or tretinoin cream
treatments – and can be a telltale sign of a person’s real age.
When tretinoin is applied to skin with seborrheic dermati-tis
(even when this is subclinical), it is common for erythema
to develop, often in the middle of the face. One week’s pre-ventive
treatment with topical nystatin can often prevent ery-thema,
and considerably improves treatment compliance.
Men whose skin tends to become irritated or infected after
shaving can use tretinoin as an aftershave cream. Shaving
soon becomes more comfortable: within 48 hours, the irrita-tion
or potential acneform dermatitis has subsided or disap-peared
altogether. The tretinoin cream should be applied
every day for at least 12–18 months and two or three times a
week thereafter to maintain the results. When the treatment
ends, the effect does not last indefinitely, and the skin slowly
returns to a state close to its original condition. However, if
the treatment is followed with one to three applications a
week afterwards, the positive effects remain visible.11 When
the treatment lasts 5–6 years, the elastotic material in the der-mis
is gradually replaced by new collagen and elastic struc-tures.
12 The results should last a long time if the skin is
protected from factors that accelerate the aging process.
Combining tretinoin and benzoyl peroxide could inacti-vate
the tretinoin. If absolutely necessary, benzoyl peroxide
can be applied in the morning and tretinoin in the evening.
Side-effects
Patients should be warned of the high probability of
adverse effects, which fortunately are only temporary.
Tretinoin is more irritant than glycolic acid. The irritation
is usually mild, but can take the form of ‘retinoid dermati-tis’
if high concentrations are used or if the skin is delicate.
This dermatitis is in fact a positive side-effect when
tretinoin is used to prepare for a TCA–SAS peel, at least to
19. the level of the papillary dermis, as it helps the TCA pene-trate
more deeply and evenly. A concentration of 0.05%
tretinoin should be used once or twice a day (depending on
the thickness and sensitivity of the skin) for 1 week; the fol-lowing
week, the concentration is increased to 0.07% and
the third week to 0.1%. This relatively aggressive prepara-tion
improves the penetration, evenness and re-epithelial-ization
of the TCA–SAS peel, but will not improve the
cosmetic results (or will do so only very slightly).
If the skin is not properly hydrated during treatment
with tretinoin, it will usually flake visibly and fairly rapidly
after a few days of treatment.
Erythema is to be expected with effective tretinoin treat-ment.
This is not an adverse effect, but rather is collateral
and natural. The skin of a patient properly treated with
tretinoin is pinker than normal, and this provides the doc-tor
with an essential means of observation: a patient show-ing
no erythema is undertreated or incorrectly treated.
Erythema that appears very rapidly, 2–3 days after treat-ment
begins, and that is localized in patches may be sebor-rheic
dermatitis; it soon clears up with nystatin cream.
Erythema that appears in the medium or long term, 1 or
more weeks later, can spread over the whole face and some-times
to the neck in patients with very sensitive skin. If this
should happen, treatment should be stopped for 1–2 weeks
and started again at a lower dose, as explained above, to
avoid excessive neoangiogenesis. More often than not,
retinoid erythema does not last long in patients with a dark
skin phototype, whereas patients with a lighter phototype
can suffer from persistent, if not permanent, retinoid ery-thema.
Sometimes, the redness is more of a passing flush
than fully established erythema.
The skin becomes more sensitive to the sun, perfumes
and detergents. In fact, right from the start of treatment,
the skin becomes more sensitive to any irritant: beware of
chemical hair removal products, waxes, dyes, etc.
People who use tretinoin often report that their skin is
more sensitive to the sun and burns more easily. This pho-tosensitization
is better explained by the thinning of the
stratum corneum rather than by a photochemical reaction
between the tretinoin and the sun’s rays. It is therefore
essential to recommend the use of a sunscreen (SPF 25–50
UVA + UVB + HSP induction) to patients being treated
with tretinoin. It should also be borne in mind that there is
a potential risk of skin cancers developing as a result of the
stratum corneum thinning and the enhanced penetration of
the sun’s rays. Nevertheless, it appears that patients on long-term
tretinoin treatment do not have a higher incidence of
skin cancers. Tretinoin has in fact proved to be effective in
the treatment of photoaging and actinic keratoses.
Teratogenicity of tretinoin
There is one important thing to note about the risk of ter-atogenicity:
to date, and in spite of the fact that no terato-genicity
has been officially attributed to tretinoin,13 we do
not have all the necessary facts at our disposal to allow its
unreserved use during pregnancy or in women who wish
to become pregnant. Despite the fact that application of
tretinoin under occlusion on more than 30% of the body
has not been found to lead to any abnormal increase in
plasma levels, and despite there being no higher incidence
of fetal deformities among the children of women who
have used tretinoin during the first months of pregnancy,
it is nonetheless possible for retinoic acid to penetrate the
cell nucleus and alter the expression of certain genes.4
Caution dictates that one should not go ahead with treat-ment
in a particular case until all the necessary facts are
available to allow a risk-free choice to be made. Hypervit-aminosis
A is theoretically possible and could be insidious
and chronic. 14 Practitioners should remain on their guard
and make sure that patients are not taking extra vitamin A
supplements.
Benefits of skin preparation
Major benefits
Avoiding various side-effects
Preparing the skin before a TCA–SAS peel helps prevent
herpes and bacterial and mycotic infections. It also helps
reduce the risk of inadequate results (thanks to combina-tion
with other treatments).
Improved penetration of the active
product
Preparation with AHAs or tretinoin reduces the thickness
of the stratum corneum, the skin’s natural barrier. As the
barrier is not as thick, it is easier for the products applied to
the skin to penetrate to the basal layer of the epidermis and
more deeply into the dermis. It should be noted that not all
peels require this kind of preparation.15
Even penetration of the peel
The skin does not have the same thickness all over, and this
can produce differences in the level of penetration. Correct
preparation with AHAs and/or tretinoin tends to even out
the thickness of the skin and allow the active products of
the peel to penetrate evenly.
Areas of hyperkeratosis (senile keratoses, and flat and
seborrheic warts) are a perfect example of this difference in
the level of penetration. Keratoses, which are characterized
by a localized thickening of the stratum corneum, are less
permeable to the acids. Pre-peel preparation with tretinoin
evens out the thickness of the stratum corneum and hence
the overall permeability of the epidermis.
10 Textbook of Chemical Peels
20. Reduced risk of pigmentary change
Patients with olive and dark skin, or of Hispanic or Asian
origin, are more prone to pigmentary changes than
patients of Caucasian origin. It should be remembered that
genotype does not always correspond to phenotype and
that there are light skins that react in the same way as dark
skins.16 Tretinoin, even more than AHAs, disperses
melanin granules and reduces the overall quantity of
melanin in the epidermis. This reduces the risk of post-inflammatory
or post-peel pigmentary changes.
Tyrosinase inhibitors should be used in post-peel treat-ment
as well as in pre-peel preparation (1 month before the
peel when there is a risk of pigmentary change, i.e. when
TCA–SAS or AHA peels are used).
Some commercial creams have interesting formulations
with AHAs (to enhance penetration of the other active
products), tretinoin precursors, lactic acid, extracts of
Morus Alba and kojic acid, combined with Transcutol®, an
adjuvant that concentrates the active products near the
basal layer and the melanocytes.
Accelerated healing of the skin
After a peel, the skin needs to heal as quickly as possible in
order to maintain homeostasis of the whole organism.
Tretinoin accelerates re-epithelialization if used before the
peeling. For this it must be used at a dose of 0.05%–0.1%,
sometimes to the point of irritative dermatitis. Ideally, the
treatment should start 3–4 weeks before a TCA–SAS peel. It
is accepted scientifically that the preventive application of
tretinoin promotes post-peel healing of the skin. In con-trast,
applying tretinoin during the post-peel period
appears to slow down skin regeneration. Not all peels
require this help with re-epitheliazation.
Minor benefits
Testing patient compliance
A patient who refuses to comply with instructions for
preparing the skin before a peel will not be naturally
inclined to heed advice for care during or after the peel ses-sions
either. It is always preferable not to ‘peel’ a patient
who is incapable of understanding or accepting these
instructions. Testing patient compliance is all the more
important since preparing the skin and keeping up cos-metic
care afterwards affect the quality of the results.
Getting an idea of follow-up care
For patients who accept it, preparation gives them a fore-taste
of between- and post-peel care.
Pre-peel care 11
Monitoring skin preparation
Monitoring the preparation process can give an idea of how
reactive and sensitive the skin is. Thus, a patient who cannot
tolerate hydroquinone during pre-peel preparation will tol-erate
it even less in the days following the treatment as the
skin becomes more sensitive to any irritant. Similarly, if the
patient develops an allergy to one of the products used in
the preparation, it can be isolated and avoided after the peel.
Combination treatments
Other treatments can be combined with the pre-peel
preparation: shave excision, electrocoagulation, ablations,
botulinum toxin, dermal filling, mesotherapy, etc. Some
peels can be used simultaneously with these techniques.
For example, a phenol peel can be immediately preceded
by shave excision of raised benign lesions. Easy TCA® can
be immediately preceded by botulinum toxin, dermal fill-ing,
electrocoagulation of telangiectasias (Figure 2.2),
mesolift, IPL, depilation, etc.
Figure 2.2
Treatment of telangiectasias by (Ellman®) radiofrequency
immediately before the application of Easy TCA®. Scattered
pinpoint frosting signals the penetration of the acid at each
point treated by radiofrequency. This combination
significantly reduces scabbing and includes a ‘pixillized’
deeper peeling.
Notes
1. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical
retinoic acid (tretinoin) for melasma in black patients. A
vehicle-controlled clinical trial. Arch Dermatol 1994; 130:
727–33.
2. Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et
al. Retinoic acid treatment for hyperpigmented lesions
caused by inflammation of the skin in black patients. N Engl
J Med 1993; 328: 1486–7.
3. Griffiths CE, Goldfarb MT, Finkel LJ, et al. Retinoic acid
treatment of hyperpigmented lesions associated with
photoaging in Chinese and Japanese persons. J Am Acad
Dermatol 1994; 30: 76–84
21. 4. Gilchrest BA. Retinoids and photodamage. Br J Dermatol
1992; 127(Suppl 41): 14–20.
5. Ertl GA, Levine N, Kligman AM. A comparison of the effi-cacy
of topical tretinoin and low-dose oral isotretinoin in
rosacea. Arch Dermatol 1994; 130: 319–24.
6. Published studies disagree on the efficacy of tretinoin.
7. Andreano JM, Bergfeld WF, Medandorp SV. Tretinoin
emollient cream 0.01% for the treatment of photoaged skin.
Cleve Clin J Med 1993; 60: 49–55.
8. Olsen EA, Katz HI, Levine N, et al. Tretinoin emollient
cream: a new therapy for photodamaged skin. J Am Acad
Dermatol 1992; 26: 215–29.
9. By altering the formulations given above: 7.5 mg tretinoin in
60 g of cream.
10. Vit E antioxidant® (Skin Tech) or a similar cream.
11. Thorne EG. Long-term clinical experience with a topical
retinoid. Br J Dermatol 1992; 127 (Suppl 41): 31–6.
12. Not all studies endorse this long-term treatment.
13. Guzzo CA, Lazarus GS, Werth VP. Dermatological pharma-cology.
In: Hardman JG, Limbird LE, Molinoff PB, Ruddon
RW, Gilman AG, eds. Goodman & Gilman’s The Pharmaco-logical
Basis of Therapeutics, 9th edn. New York: McGraw-
Hill, 1996: 1600.
14. Farnes SW, Setness PA. Retinoid therapy for aging skin and
acne. Postgrad Med 1992; 92: 191–6, 199–200.
15. For example: Easy TCA® and Easy Phytic® need no pre-peel
preparation.
16. Which is why it is important to question the patient.
12 Textbook of Chemical Peels
22. Immediate post-peel care is described in detail in the chap-ters
dealing with each type of peel. As a general rule,
tretinoin and creams with an alpha-hydroxy acid (AHA)
concentration of over 10% should be avoided before the
exfoliation phase is completely finished.
Sun protection
Any peel, even a very superficial one, reduces the thickness
of the stratum corneum that protects the skin against the
effects of radiation: the diffractive and reflective protection
usually afforded in these outermost layers is no longer
available, and the overall quantity of rays that penetrate the
skin increases. This extra radiation can cause actinic dam-age
in cells that are usually physically protected by the
thickness of the skin. Melanocytes are more strongly stim-ulated,
and there is an increased likelihood of pigmentary
change. All peels thus allow the sun’s rays to penetrate
more easily to at least the basal layer of the epidermis,
where keratinocytes ensure re-epithelialization and
melanocytes can induce hyperpigmentations.
Greater irradiation increases the risk of these cells being
genetically modified. All peels put the skin at risk of light
stress, which makes the use of sun protection creams essen-tial.
A powerful, broad-spectrum sunscreen provides
greater protection. The deeper the peel, the more important
it is to use sun protection. After any medium or deep peel, it
is necessary to use an effective sunscreen of factor 25–50
(Figure 3.1) (UVA + UVB + HSP inducers) for 6–12 weeks
(depending on the depth of the peel). The sunscreen should
be applied immediately after washing in the morning,
preferably with a cleansing lotion. Post-peel sun protection
should be re-applied every 3 hours on average under any
make-up, even if the make-up itself is considered to be pho-toprotective.
After a peel, sun protection is necessary even if
the patient does not go outside and even in foggy or cloudy
weather: windows block out most UVB but not UVA, and
not all clouds filter UV. Halogen lamps and spotlights and
cathode-ray screens also appear to produce a sufficient
quantity of radiation to induce post-inflammatory hyper-pigmentation
(PIH) in sensitive individuals.
Effective sun protection factor
The sun protection factor should be even more ‘aggressive’
when treating post-inflammatory hyperpigmentation, and
should protect against UVA as well as UVB. Protection
from the sun means not only avoiding lying on the beach
but also avoiding daylight. The skin is subjected to many
light shocks; it is constantly under attack from the sun and
daylight. One pitfall to be avoided is applying sunscreens
that contain tanning accelerators that could have a harmful
effect.1 Between peels and during the first few weeks after a
peel, a generous amount of Melablock HSP® 50+ sun
cream, for example, should be applied every 3 hours.2
Thereafter, daily sun protection can be lighter: for example
Melablock HSP® 25+ every 3 hours. Patients should be
advised to keep their backs to the sun and to wear light pro-tective
clothing. UV is not the only cause of hyperpigmen-tary
reactions: infrared can also cause them.
Heat-shock proteins (HSPs)
The process of wound healing after thermal injury (e.g.
from laser treatment) involves re-epithelialization that
starts within the first few hours after injury and continues
throughout the different proliferative phases of skin repair.
Viable keratinocytes (Figure 3.2) that are at the edge of the
wound and have not suffered lethal or sublethal heat shock
3
Post-peel care
96 98
90
50
0
SPF0 SPF2 SPF10 SPF25 SPF50
110
100
90
80
70
60
50
40
30
20
10
0
% UVB blocked
Figure 3.1
An SPF of 50 protects the skin against 98% of UV. A higher
protection factor is not necessary.
23. migrate horizontally and centripetally in order to form an
initial single cell layer of keratinocytes, the ‘new basal
layer’, before starting vertical growth that will regenerate a
normal epidermal structure.
Re-epithelialization uses up a lot of proteins, both dur-ing
the synthesis of the temporary matrix that acts as a pro-tein
highway for the new keratinocytes and during the
intense mitotic activity that creates new skin cells. Proteins
are absolutely essential to cell life; each enzyme in the body
is a protein whose unique three-dimensional structure is
responsible for its highly specific action. They have vital
functions that are specific and strictly linked to their three-dimensional
structure. The spatial structure of proteins is
altered by even the slightest increase in temperature;3 any
thermal stress can ‘unfold’ the cell proteins, making them
ineffective and leading to apoptosis (programmed all
death). In laser or flashlamp treatments, the temperature of
the target must be raised in order to destroy it, but the nor-mal
cells around the target also undergo sufficient heat
stress to induce apoptosis or severely disrupt cell function.
The rise in temperature thus creates a central zone of
lesions that are lethal to cells, surrounded by a peripheral
zone of sublethal damage in which the heat-damaged cells
must be repaired or replaced. As a result, skin regeneration
may be slower than it should be as the cells on the edge of
the treated area grow and migrate. Preventive protection of
the proteins in the cells surrounding the target, increasing
their resistance to heat, can help enhance the skin healing
process and reduce the incidence of complications associ-ated
with slow re-epithelialization.
Where there is sublethal damage, or very light damage,
the cells must eliminate or repair the damaged and ineffec-tive
proteins, increase protection of the proteins that did
resist the heat and synthesize new replacement proteins.
This is where heat-shock proteins (HSPs or stress proteins)
are necessary. HSPs were discovered at the beginning of the
1960s in the fruit fly in response to an increase in cell tem-perature
of just a few degrees. These proteins were subse-quently
found in all types of living cells; they are secreted in
response to any kind of stress, not only in response to
increased temperatures. HSP70 and other similar stress
proteins appear rapidly in the cytoplasm and mitochondr-ial
matrix of cells that are subjected to stress. Essentially,
their role is to ensure protein viability. HSP70 binds to
polypeptide chains as soon as the latter have been synthe-sized
in ribosomes (which translate RNA information into
the amino acid sequence of the polypeptide) and facilitate
the folding of these chains into the three-dimensional
structure essential for protein activity. The HSP70 then
separates from the folded protein. HSP70 is a member of a
group of diverse proteins (also including HSP60 and the
chaperonins) that play an essential role in creating the
appropriate three-dimensional structures of other proteins
– but do not themselves form part of that final structure.
This group of proteins are also known as ‘molecular chap-erones’
and have a fivefold role: do well as providing the
correct spatial structure for a new protein coming out of
the ribosome, they also protect the structure of existing
proteins, repair damaged proteins by refolding them cor-rectly,
and act as protein transporters, carrying proteins
from one place to another within the cell and eliminating
proteins that are irreparable. Some HSPs are constitutional
and others are inducible. The latter are synthesized in
greater numbers after stress and give the cell increased
resistance to future stress, thus allowing the cell more time
to repair itself without having to resort immediately to
apoptosis.
With age, HSP function deteriorates in human skin, and
aging cells are increasingly more prone to protein destruc-tion.
Sun protection and HSPs
It is therefore beneficial to boost the synthesis of HSPs in
the cytoplasm and mitochondrial matrix of cells subjected
to heat and light stress, thus improving not only their resis-tance
but also their defenses and better equipping them to
repair proteins in case of stress. An interesting disaccha-ride,
trehalose (Figure 3.3), was isolated from cells of
organisms that can survive in extreme conditions such as
dehydration; having this disaccharide in sufficient concen-trations
allows these organisms to increase their resistance
to the lack of water. It has been shown4 that trehalose can
stimulate HSP70 production. An interesting experiment
showed that this disaccharide increases cell viability after
exposure to UVB. The study involved subjecting a culture
of keratinocytes to a slight increase in temperature of 3°C
for 1 hour in order to induce slight heat stress. The ker-
14 Textbook of Chemical Peels
Figure 3.2
Diagram of the peripheral thermal damage after ablative
laser treatment. The number of lethal lesions is proportional
to the degree of shading. The skin is repaired from peripheral
keratinocytes: some have suffered sublethal damage. Heat-shock
protein (HSP) inducers help improve keratinocyte
resistance to heat shock.
24. OH
atinocytes were then cultured for 6 hours either in a
medium containing trehalose or in a medium without the
disaccharide. After 6 hours, the culture medium was
replaced by physiological saline solution and the ker-atinocytes
were exposed to UVB radiation. Cell viability
was studied after 48 hours. There was a huge difference in
keratinocyte survival in the cells from the different culture
media: only around 4% of viable keratinocytes remain
when cultured without trehalose eter, whereas the survival
rate was nearer 40% in the group of keratinocytes cultured
in the medium rich in trehalose (Figure 3.4).
Specific care for different peels
AHAs
If an AHA peel is done correctly, no particular medical care
is necessary, no matter what concentration or pH is used.
In general, after an AHA peel, all that is necessary is good
hydration and effective sun protection for 2 weeks. AHA
peels weaken the barrier function of the stratum corneum
Post-peel care 15
and thus increase its permeability; they make it easier for
the active molecules to penetrate the epidermis when
creams are applied both immediately after and between
peeling sessions. The type of cream depends on the prob-lem
being treated. The results for acne treatment can, for
example, be improved by applying a layer of anti-acne
cream immediately after a ‘classic’ AHA peel has been neu-tralized
and leaving it to act under an occlusive dressing5
for around 30 minutes. The patient can apply the same
cream twice daily thereafter. The same applies for melasma
and aging or sagging skin, etc.6 After an AHA peel, the
patient’s daily care routine plays an essential role in deter-mining
the quality of the results. Mesotherapy can be com-bined
with AHA peels in a number of ways: the ‘mesolift’
mixture7 can be injected before the peel or immediately
after the peel has been neutralized and before creams are
applied under occlusion. There is no danger of the glycolic
acid penetrating beneath the skin through the perforations
made by the mesotherapy needle. Most often, however, the
treatments are alternated every other week: in the first
week, the peel and the cream under occlusion are applied,
and in the following week, the mesolift is injected, followed
by the cream under occlusion. If an AHA peel is done cor-rectly,
there is usually no downtime. Nevertheless, there
can be complications, which are described in Chapter 10.
Resorcinol
Resorcinol in paste form9 is used in a very specific manner:
the paste is usually applied three times, once a day for 3
days in a row. Post-peel care is very important during the
following week: the skin should not be hydrated at all, as it
has to dry out completely for the peel to be effective and,
above all, the patient must not pull off or pick at the flaking
skin. Only the doctor can safely cut off any strips of flaking
skin with sterile scissors. Cosmeceutical creams for age
spots, acne, aging or sagging skin, etc. should only be
applied after the skin has flaked. Effective sun protection
(UVA + UVB + HSP inducers) is absolutely essential for
approximately 6 weeks after the peel.
Downtime may be around 4–5 days. After the first appli-cation
of the paste, the patient can usually have a normal
social life, but subsequent applications dry out the skin and
leave it looking papery.
TCA–SAS
Trichloroacetic acid in simple aqueous solution
(TCA–SAS) involves pre-peel preparation, application of
the TCA–SAS solution to the required depth (usually the
papillary dermis), flaking, natural skin regeneration and
post-peel care.
The post-peel period for TCA–SAS requires special atten-tion
and, even if the peel is applied correctly, pigmentary
changes are the most common and benign complication. It
HO
H
OH HO
H
H
H
O
H
OH O
H
HO H
O
H
H
HO
OH
H
Figure 3.3
Chemical structure of trehalose.
0% 0.5% 1%
Trehalose eter concentration
40
35
30
25
20
15
10
5
0
Keratinocytes
percentage survival
Figure 3.4
The viability of keratinocytes exposed to UV after a 3ºC
increase in temperature is very low: just a few percent. When
cultivated in an environment rich in trehalose eter, the
viability is close to 40% under the same conditions.
25. is clear from the many illustrations in books on TCA–SAS
peels that there is an astonishing variety of post-TCA pig-mentary
changes, with varying degrees of severity. If pre-peel
prevention does not prove effective, or in cases of localized
overpeeling, post-inflammatory hyperpigmentation (PIH)
usually appears within a week after the peel in the form of
dark patches or persistent erythema that will become pig-mented
under the effect of the sun’s rays. For more informa-tion,
see the section on hyperpigmentation in Chapter 37.
These genuine pigmentary changes should not be confused
with the darkening of epidermal melasma appearing the
next day after the peeling, and caused by dehydration of the
hydrophilic spaces between melanosomes, which makes the
skin seem to have a greater concentration of melanin and
hence appear darker. This darkening, which is temporary, is
a positive sign and will fade at the end of the first week.
Flaking should not be helped along under any circum-stances.
Peeling off any bits of skin can result in uneven skin
tone, infection, hyperpigmentation, scars or localized
achromia. It is also essential to take preventive measures
against infection after a papillary TCA–SAS peel, as the lat-ter
destroys most of the skin’s defenses. An antibiotic cream
is applied during the first week after the peel. The skin
should be cleaned before each application of cream, and any
occurrence of contact allergies, which can sometimes be
confused with secondary infections, should be monitored.
The results of a TCA–SAS peel also depend on the qual-ity
and consistent use of cosmeceuticals after the peel. It is
clear that a melasma treatment will produce better results if
the TCA–SAS peel is followed by the application of a
retinol–anti-tyrosinase–anti-oxidant cream or a hydro-quinone-
based preparation. For acne or aging or sagging
skin, the same comments apply as for AHAs above. These
creams can be applied as soon as flaking is finished, usually
on the 7th day.
Effective sun protection is absolutely essential and should
be used in the first few days after the peel, before the skin has
stopped flaking. Even a total sunblock is not enough to avoid
pigmentary changes altogether, and the patient should be
told to completely avoid exposure to the sun. Sun creams
containing tanning accelerators should, of course, not be
used after the peel.9 Chemical tanning with sprays contain-ing
dihydroxyacetone should also be avoided, as these prod-ucts,
which are non-toxic when picked up by the
corneocytes and eliminated within 1 week, are not intended
for keratinocytes, which are the cells exposed to the external
environment during the first days after a peel.
Downtime is around 1 week following a TCA–SAS peel,
after which make-up can be used from the 8th day to cover
up any persistent erythema.
Easy TCA®
Easy TCA® is an exception among TCA peels, and should
be distinguished from TCA–SAS, as it does not require pre-peel
care in the medium term nor any immediate pre-peel
preparation, and pigmentary changes are very rare if the
‘basic protocol’ is followed.10 Some brown discoloration is
possible after the first or second application, but this
should fade after the following peel. Flaking skin can be
peeled off or a light cosmetic scrub can be used. With
deeper protocols, which are not usually necessary with this
peel, there is a greater likelihood of complications.
Combining Easy TCA® with appropriate post-peel cos-meceuticals
helps improve and maintain results. The cos-meceuticals
should be applied the day after the first peel
and continued between sessions and for at least 6 weeks
after the last application. As with any peel, effective sun
protection is necessary to make up for the temporary loss
of the stratum corneum. Easy TCA® causes the skin to
flake, but not so much as to disrupt the patient’s social life,
although certain activities may be compromised: television
presenting, customer contact in the food industry, etc. Easy
Phytic® is recommended in these cases as there is almost no
visible flaking of the skin (see Chapter 11).
Phenol
Phenol entails the most complex post-peel care: occlusive
masks, healing masks and cosmetic care during the months
following the peel. Chapters 25–36 are devoted to this tech-nique.
The expected downtime is between 7 and 15 days,
depending on the formula used. The patient will have to
wear camouflage make-up to hide any redness, which can
last for several weeks or months.
Post-peel cosmetics
Chemical peels do not always treat the underlying cause of
a skin problem. For example, there can be many causes of
acne, and chemical peels do not alter the synthesis of
testosterone or the potency of the 5α-reductase that con-verts
testosterone into its active derivative, dihydrotestos-terone.
Acne may also be partly due to excessive cell
cohesion that blocks the sebaceous glands or to an immun-odeficiency
of genetic origin. Chemical peels do not alter
an individual’s genetic make-up. Follow-up care should
come after the peel, which is only the first phase of the
treatment. Topical anti-acne treatments or cosmetics
should be used between and after the peels to improve and
prolong results. The same goes for blemishes, melasma and
aging.
Peels can provide quick cosmetic results, but it is the care
between and afterwards that improves and maintains
them. This is why the same peel may be indicated for the
treatment of acne, which typically affects young patients, as
for aging, which affects older patients. In short, we can say
that chemical peels regenerate, restructure and stimulate
the skin, and that care between and after peels widens their
16 Textbook of Chemical Peels
26. indications to problems such as acne, dyschromia and
aging.11
There are cosmetic products that have been specially cre-ated
for application very soon after a peel. They can be used
the morning after the first AHA peel, Easy Phytic® or Easy
TCA®. With TCA–SAS, Only Touch® or phenol peels, cos-metics
usually are not applied until the 8th day after the
peel. With Unideep®, an anti-oxidant cream (Renutriv
ACE Lipoic Complex®) can be applied two days after the
peel.
Treatment for acne
Tretinoin should be avoided between and after sequential
peels, as it would irritate the skin and increase penetration
of the acids during the next peel. Other topical products
can be used. Glycolic acid can be applied in low concentra-tions
(8%); it makes the skin softer to the touch. Like
retinol, it prevents pores from clogging, helps the piloseba-ceous
units to drain and stimulates skin turnover. Toco-pheryl
acetate can be used as an antioxidant to combat the
free radicals generated by inflammation. Triclosan12 is anti-septic,
anti-inflammatory and antimycotic. Glycyrrhetinic
acid is used for its hydrating, antipruritic and anti-allergic
properties. It stops patients scratching. Tea tree oil
(Melaleuca alternifomlia) is extracted from an Australian
shrub and has a similar action to benzoyl peroxide but
without its pro-oxidant effects. It is antiseptic (antibacter-ial:
anti-gram-positive and -negative), anti-inflammatory
(it can suppress the production of pro-inflammatory medi-ators),
antimycotic (anti-candida and anti-dermatophyte)
and even antiviral, acting before and after viral adsorption.
Other topical treatments can also be applied: azelaic acid,
antibiotic creams, disinfectants, etc.
Treatment for hyperpigmentation
Chemical peels are one of the preferred indications for
hyperpigmentation. A number of cosmetics can be used
between and after peels. Hydroquinone was used for a long
time, and still is in many countries. Its cosmetic use, how-ever,
is forbidden in Europe. There are many depigmenting
derivatives that can be used in its place. Kojic acid can be
used pure or as an extract of Aspergillus, and has an anti-tyrosinase
and antioxidant action. It even potentializes
leukocyte phagocytosis. Glabridin (a licorice extract)
inhibits the pigmentation and erythema caused by UV; it is
anti-tyrosinase and anti-inflammatory. Liquiritin contains
glycyrrhizin and glycyrrhetinic acid (which are anti-inflammatory
as they inhibit the degradation of endoge-nous
cortisol) and antioxidant flavonoids. Extracts of
Morus alba contain arbutin and mulberroside F, which are
both tyrosinase inhibitors. Mulberroside F is also an anti-oxidant.
Transcutol® helps build up a reserve of active
products near the dermoepidermal junction and improves
Post-peel care 17
Figure 3.5
Blending bleaching cream, contains antityrosinases and
antioxidants.
the action of tyrosinase inhibitors (Figure 3.5). AHAs can
be used to enhance penetration of active products through
the skin. Lactic acid has also been described as having a
tyrosinase-inhibiting action. Finally, various vitamins (A,
C and E) can be used in the treatment of hyperpigmenta-tion:
they are antioxidant and anti-inflammatory, protect
against UV damage and stimulate epidermal turnover.
The well-known Kligman’s formulas combine the action
of tretinoin, a corticosteroid and hydroquinone, but are
more irritating than medical cosmetics. The cosmetics used
for hyperpigmentation should be applied very soon after the
peels (if possible the very next day). If possible they should
be applied two or three times a day, before effective sun pro-tection.
For more information on topical depigmenting
agents, see the section on hyperpigmentation in Chapter 37.
Treatment for aging
The author’s cosmetic post-peel treatment for aging skin is
simple.
Patients under 40–45 years old
The main thrust of the treatment is daily oxidation. In the
morning, an antioxidant cream with vitamin E should be
applied, and in the evening another anti-oxidant cream:
Renutriv ACE Lipoic Complex®.
Vit E Antioxidant® is a cream with a relatively complex
but complete formulation. It does not contain AHAs, so
27. can be applied daily without the risk of interference with
the protective function of the corneocytes. It has been spe-cially
formulated for use very soon after a chemical peel. Its
qualitative formulation is as follows:
Biosaccharides: these are polymers of the sugar, fucose.
– They have filmogenic properties that induce immedi-ate
hydration.
– They are slowly metabolized on the surface of the
skin, giving a long-term hydrating effect.
– They have an anti-inflammatory effect.
Ceramides: these are natural components of the skin.
– They have an anti-aging action.
– They have hydrating and protecting actions.
– They encourage skin repair after different types of
injury.
Vitamin E: this protects against anti-free radicals. The
tocopheryl acetate used in this cream is one of the most
stable derivatives of vitamin E, and forms a reservoir in
the skin after penetration
Glycyrrhetinic acid: this is hydrating and anti-allergic; it
reduces itching.
Natural moisturizing factor (NMF): this comprises
amino acids + hexoses + urea + aspartic acid + hexyl-nicotinate
PFPE (perfluoro polymethyl isopropyl ether): this is a
filmogenic polymer that protects the skin without any
occlusive effect.
Renutriv ACE Lipoic Complex® is ideal for dry skin, and
can also be applied in the morning. With normal or oily
skin, it is better applied in the evening. It does not contain
any AHAs, for the reasons explained above. Its qualitative
formulation includes the following ingredients:
vitamin A: pure encapsulated retinol
vitamin C: pure encapsulated ascorbic acid
vitamin E: tocopheryl acetate
lipoic acid
Lipoic acid exists in different racemic forms. Only the R
form is active (Figure 3.6). Lipoic acid is absorbed rapidly
both orally and topically. Enzymes in cell cytoplasm con-vert
it into dihydrolipoate (DHLA). DHLA penetrates the
cell and mitochondrial membranes easily. It is a mitochon-drial
cofactor that boosts mitochondrial activity at the
same time as protecting against excess production of free
radicals. Lipoic acid has the major advantage of being both
fat-soluble and water-soluble, which means that it is active
at all levels in the cell. It recycles vitamin C, when it is con-verted
into the ascorbyl radical after acquiring a free elec-tron,
thus restoring its antioxidant activity. It also recycles
vitamin E indirectly. Lipoic acid protects the natural enzy-matic
antioxidant defenses, such as catalase, coenzyme Q-
10, glutathione and cysteine. It is an iron, copper, mercury
and aluminum chelator (Figure 3.7). It combats excessive
secondary cell apoptosis resulting from various stresses.
Patients over 40–45 years old
The fight against aging should take into account not only
the damage caused by the various sources of cell oxidation
but also the fall in hormone levels. For menopausal or post-menopausal
women, a standard formula is testosterone
propionate 100 mg, estrone 5 mg, estradiol benzoate 5 mg,
and water in oil excipient ad 100 g.
Extracts of Mexican wild yam (Dioscorea) can also be
used, or other estrogen precursors or dehydroepiandros-terone
(DHEA).
Sagging skin – DMAE
One of the common signs of aging is loss of skin elasticity.
The skin appears devitalized and slack. One substance that
18 Textbook of Chemical Peels
HO
O
S
H S
Figure 3.6
Chemical structure of (R)-lipoic acid.
SH S
O
O
O
S S
Fe2+
O–
Fe2+
Figure 3.7
Iron chelation by lipoic acid.
28. A B
Figure 3.8
A tightening effect can be seen after the first application of N,N-dimethylaminoethanol (DMAE) in the form of Skin Tech’s Actilift®:
(a) before; (b) after. Photograph by John Jairo Hoyos, Colombia.
is of special interest in the treatment of sagging skin is
N,N-dimethylaminoethanol (DMAE) (Figure 3.8).
DMAE has been used for several years as a topical appli-cation
to produce a ‘face-lift’ effect. Even if there is no
doubt that it produces a tightening effect on the face, there
is no definitive evidence regarding its mode of action. We
will see below what type of skin structures respond to
DMAE and why it would be difficult to explain this action
by an improvement in tension of the striated muscle mass
of the face.
Chemistry of DMAE
DMAE (also called deanol, dimethylethanolamine and
norcholine) is a small hydrophilic molecule. Its low molec-ular
weight (89.1) allows it to penetrate the skin easily.
DMAE is a precursor of acetylcholine (ACh), via choline
(Figure 3.9). It is a viscous liquid, as transparent as water,
that is often said to smell like ammonia but is in fact more
reminiscent of fish long past its sell-by-date. Anchovies,
sardines and salmon are important natural sources of
DMAE. It is naturally present in the body, and there are
traces of it in the brain. DMAE is a very basic molecule
(pH 11) that cannot be used in its pure state without the
risk of causing chemical skin burns. It must be partially
neutralized for use at pH 7. Many derivatives have been
used in its place (e.g. DMAE bitartrate or acetamidoben-zoate),
but these are more suitable for oral rather than top-ical
use.
DMAE formulations tend to give only the total dosage of
the DMAE derivative used, of which pure DMAE is only
Post-peel care 19
(CH3)2NCH2CH2OH
DMAE
(CH3)3N+CH2CH2OH
Choline
O
(CH3)3N+CH2CH2OCCH3
Acetylcholine
Figure 3.9
Chemical structures of N,N-dimethylaminoethanol (DMAE),
choline and acetylcholine.
part of the weight. For example, 100 mg of DMAE cyclo-hexylcarboxylate
contains only 33 mg of pure DMAE,
while 350 mg of DMAE bitartrate contains 130 mg of pure
DMAE. The author prefers to use a formulation with
DMAE lactate (Skin Tech’s Actilift®) in order to benefit
from the properties of an AHA (lactic acid) combined with
the DMAE.
Side-effects and precautions
The high pH of DMAE means that the pure compound
should not be brought into contact with strong acids,
mucous membranes or the eyes. Pure DMAE is also
incompatible with copper and zinc. DMAE is volatile and
should be contained in sealed tubes rather than bottles, to
prevent its evaporation. Some cases of allergic dermatitis
have been reported after prolonged contact with very high
29. concentrations of DMAE, and it should be applied with
extreme caution around the eyelids of atopic subjects.
DMAE is not considered to be carcinogenic, cocarcino-genic
or immunosuppressive. Chronic exposure to con-centrated
fumes of DMAE in the workplace can cause
visual problems.
Toxicity
DMAE has mostly been used orally. It is most widely avail-able
in 100 mg tablets for the treatment of cognitive disor-ders
associated with senile dementia, at a dose of
600 mg/day. The LD50 for oral administration in rats is
2 g/kg. The LD50 in rabbits after application to the skin is
1.370 mg/kg. For subcutaneous injection in mice, the LD50
is 961 mg/kg. In a human clinical study,13 oral administra-tion
of 1600 mg/day showed no side-effects. The doses
used in topical applications are nowhere near the theoreti-cal
toxicity limit. It takes a twice-daily application of
around 30–50 mg of DMAE on the skin to improve skin
tension and achieve the ‘lifting’ effect. It is important to
remember that a topical application, even if it is very effec-tive,
cannot as yet compete with a surgical procedure.
DMAE and N,N-dimethylisopropanolamine (DMIPA)
solutions are used in high concentrations (45–50%) in
industry, especially in the printing industry. They are used
in sprays, and a study was conducted on their role in the
appearance of intermittent corneal opacity in workers in
certain types of printing works.14 The corneal opacities
caused blurry vision on the way home from work. These
problems were only evident from Mondays to Thursdays,
but never at the end of the week. Eye tests revealed the
appearance of intermittent and reversible corneal opacity,
limited to the part of the cornea in contact with the
droplets of vaporized solution and lasting just a few hours.
A complete study was undertaken that put the blame on
DMIPA but cleared DMAE of involvement. Lowering the
concentrations of DMIPA without changing the concen-trations
of DMAE solved the problem once and for all and
produced no visual sequelae.
DMAE has also been claimed to be teratogenic. Studies
on this subject remain controversial: some have shown that
DMAE can be teratogenic in mouse embryos at high
doses;15,16 other studies have shown no evidence of toxicity
in rodents.17 In my knowledge nothing has been published
on teratogenic effects in humans, and no research has
shown teratogenicity in humans, despite the wide use of
DMAE in industry.
Historical and ‘usual’ use of
DMAE
Procaine, which is used widely in mesotherapy, is one of
the active principles of the well-known (and at times much
O
criticized) Gerovital H3 developed by Dr Ana Aslan of
Rumania. Procaine or 2-diethylaminoethyl 4-aminoben-zoate
hydrochloride (Figure 3.10) was synthesized in 1905
by the German chemist Alfred Einhorn, who called it
‘novocaine’ (from the Latin novus = new, with the added
suffix of cocaine, a gold-standard product up until then).
Another German, Dr Heinrich Braun, introduced the use
of novocaine in medicine.
In the body, the ester link of procaine is hydrolyzed,
yielding p-aminobenzoic acid (PABA) and N,N-diethyl-aminoethanol
(DEAE), an analog of DMAE. It is PABA
(Figure 3.11) that is responsible for the large majority of
allergic reactions to ‘procaine’; it is excreted rapidly by the
kidneys. PABA is most often used as a sunscreen, but is
sometimes called ‘vitamin B-x’, although it is not essential
for humans and the body cannot synthesize folate from
PABA. According to some authors, the ‘Aslan’ method
relies solely on the combined action of PABA and
DEAE/DMAE. It is assumed that the action of PABA is due
to its anti-free-radical properties.
Another local anesthetic used in mesotherapy, lidocaine,
goes through a different metabolic pathway from procaine,
being converted into monoethylglycine, xylididide
(MEGX) and acetaldehyde. Its action in this context must
therefore have a different basis from that of procaine.
As well as having an anti-oxidant19 and anti-inflamma-tory
effect, DMAE taken orally has been claimed to have
many properties: an anti-aging effect, improvement of
memory and intelligence, increased synthesis of acetyl-choline,
amelioration of depressive states, improvement in
motor coordination, improvement in compulsive, impul-sive,
hyperactive or antisocial behavior, reduction of
chronic fatigue and improvement in the quality of sleep,
aid in giving up alcohol and tobacco, reduction of
headaches, improved ability to concentrate, improvement
in schizophrenia, improved muscle tone, and overall
higher energy levels.
DMAE can be incorporated into the membrane struc-ture
of cells, where its anti-oxidant properties improve
20 Textbook of Chemical Peels
NH2 CO.CH2CH2N(C2H5)2
Figure 3.10
Chemical structure of procaine.
NH2 C
O
OH
Figure 3.11
Chemical structure of p-aminobenzoic acid (PABA)
30. membrane resistance to the oxidative stress resulting from
the release of free radicals from the phospholipid bilayer
and the production of eicosanoids associated with skin
inflammation. The degradation of cell membranes and
subsequent inactivation of the transmembrane proteins
and receptors are considered to be the main factors respon-sible
for cell aging.
Carbachol (Figure 3.12), and the closely related bethane-chol,
is a powerful cholinergic agent (used to induce mio-sis).
Its structure is similar to that of choline and its
precursor, DMAE. Other muscarinic agents (e.g. pilo-carpine),
have a completely different chemical structure to
choline.
O
Topical skin application of DMAE
Topical application of DMAE has a visible tightening, firm-ing
effect, often called the ‘lifting effect’. This tightening
effect can already be felt 20–30 minutes after the product
has been applied to the skin, and, when only one side of the
face is treated with DMAE, the difference in tension
between the two sides is clear. Skin tension continues to
improve during the first 6 months of twice-daily applica-tion,
with individual variations, and remains stable for 4–8
weeks after topical treatment is finished. This would seem
to indicate that the product accumulates in the skin and
forms a reservoir.
Potential mode(s) of action of
DMAE
DMAE is a precursor of choline; it also inhibits the metab-olism
of choline in the tissues. As there is more choline
available, the biochemical reactions may tip the balance
towards an increase in ACh synthesis. DMAE may stimu-late
macrophage activity and improve the skin’s defenses.
The mode of action of DMAE is not yet fully understood,
and its action as a local application even less so. We must
therefore put forward several hypotheses in an attempt to
understand this tightening effect.
Action on the striated facial muscles
Botulinum toxin (BTX), which is used to ‘smooth the skin’,
like DMAE, acts on ACh, although its action is the reverse
Post-peel care 21
of that of DMAE. BTX relaxes the muscles, whereas DMAE
increases muscle tone. Are these two compounds therefore
incompatible? It appears not, as they have different targets,
and the muscle cells that are deactivated by BTX are not the
same as those activated by DMAE. BTX is a large molecule
with a high molecular weight, which means that it cannot
pass through the skin when applied topically. To achieve a
cosmetic result, BTX must be injected directly into the
muscle to be paralyzed. BTX has no effect on the epidermis
or dermis, as it blocks cholinergic transmission in the neu-romuscular
junction of the striated muscles and in this way
limits the facial expressions that cause expression lines.
BTX is picked up immediately, and there is no chance of it
diffusing up through the hypodermal fat layer. DMAE, on
the other hand, is a very small hydrophilic molecule with a
molecular weight of 89.1 that can easily penetrate the epider-mis
and the dermis but cannot penetrate the hypodermal
fatty layer. DMAE cannot act on the striated muscle groups
that produce voluntary facial movements, and so cannot
counter the effects of BTX. This physiological hypothesis is
confirmed clinically when the two treatments are used
together. The physicochemical properties of DMAE give this
molecule a great affinity for the dermis and epidermis. As the
action kinetics of DMAE lead to the hypothesis of a cuta-neous
‘reservoir’, this could only be located in the deep epi-dermal
layers, as, if it was in the dermis, this small molecule
would soon be eliminated by venous or lymphatic resorp-tion
because of its concentration gradient.
The way in which they are administered, their targets,
their characteristics and their different modes of action do
not make BTX and DMAE incompatible: administering
one will not alter the effectiveness of the other. There is no
established link between age-related sagging skin and mus-cles
and a deficiency in ACh in the muscles. Any action of
DMAE on striated facial muscles is thus not only unlikely
but also pointless. We must therefore look for other more
likely modes of action than muscle stimulation, especially
as there have been reports of improvements in tone and
younger-looking skin around the eyes and lips after only a
few days of treatment. Given that it is accepted that paraly-sis
(or hypotonia) of the muscles by BTX ‘smoothes’ the
skin, it would be illogical to claim that stimulating the same
muscle groups (with DMAE) can give similar results. We
must therefore look elsewhere: in the skin structures that
have cholinergic receptors.
Epidermal action
Human keratinocytes express cholinergic receptors in the
cells of the stratum basale, the stratum spinosum and the
stratum granulosum. They use ACh, among other things,
to stick together. They also synthesize, store, degrade and
release ACh.
ACh synthesis has been shown to occur in the perinu-clear
regions of human keratinocytes due to the presence of
(CH3)3N+CH2CH2CNH2
Figure 3.12
Chemical structure of carbachol. Note the similarity between
part of the molecule and DMAE and choline.
31. a choline acetyltransferase (this enzyme converts acetyl
coenzyme A into ACh). On the other side of the cell, inside
or near the cell membranes, an acetylcholinesterase has
been identified. This enzyme degrades ACh in order to pre-vent
a toxic build-up. Keratinocytes can move, which is
essential during the second phase of healing, thanks to
cytoplasmic myosin and actin: the actin moves in relation
to the myosin when the two interact,19 in the same way that
an oar stroke moves a kayak or an athlete runs on a tread-mill
(the athlete representing the myosin and the treadmill
the actin). It has recently been shown, by immunohisto-chemistry,
that there are free nerve endings in all of the lay-ers
of the epidermis, and it is now suspected that
keratinocytes have a neurotropic function. The ACh acts
locally, in the epidermis, like a hormone that can also be a
‘messenger’ stimulating the dermis. We can then suppose
that an epidermal reservoir of DMAE can interact with the
dermis via ACh, of which it is a precursor.
DMAE is also assumed to inhibit formation and enhance
elimination of lipofuchsin, a waste product of the aging cell
metabolism of fatty acids. Experiments have shown that
lipofuchsin is eliminated from the liver by DMAE. This
build-up, which occurs in all organs, has not been associ-ated
with any disorder apart from lentigines. Some authors
have reported a gradual reduction in lentigines on the
hands with oral DMAE treatment. To date, there have been
no studies published on the topical use of DMAE in the
treatment of lentigines.
Dermal action
DMAE is used for its antioxidant properties, membrane
stabilization and inhibition or repair of protein cross-links
that clearly play a role in the aging process. It could thus
help maintain good-quality collagen and elastin and slow
down dermal aging.
Vasomotor effect
The dermal blood vessels are innervated by adrenergic
fibers, which cause vasoconstriction, and cholinergic
fibers, which cause vasodilation. DMAE, as a precursor of
ACh, could cause vasodilation that is clinically unde-tectable
but sufficient to produce temporary edema, a
build-up of water in the hydrophilic structures of the der-mis,
and, as a result, a tightening of the skin. This hypothe-sis
only partly explains the particular kinetics of topical
DMAE. The fact that treating one side of the face only
shows improvement on one side only suggests that the
DMAE has a purely local action and is not converted into
ACh throughout the organism. Local blood flow, which
decreases with age, is vital for the nutrition and defense of
the dermis and epidermis. Constant slight vasodilation
would thus improve skin perfusion – especially in smokers
– and by diffusion would bring in more of the elements
that contribute to the overall rejuvenating effect observed
when DMAE is applied topically.
Effect on myofilaments and smooth
muscle cells
Myofilaments make up the endoskeleton of a cell (Figure
3.13). They can be found in the smooth muscle cells
(SMCs) and in the cytoplasm of ‘non-muscle’ cells, where
they are capable of moving and contracting. SMCs can reg-ulate
contraction far more subtly than striated muscle cells.
SMCs can shorten to a greater extent than striated muscle
cells. Shortening of striated muscle cells is limited to move-ment
within the sarcomere, whereas with SMCs, the
myosin filaments can move over a far greater distance,
along the network of actin filaments in the cytosol. The
force generated by SMCs is less than that generated by stri-ated
muscle cells, but can be sustained for much longer.
The arrector pili muscle is under adrenergic control and
does not respond to a local increase in ACh concentration.
The fibroblasts and myofibroblasts are very interesting cells
as far as the possibilities of the action of DMAE is con-cerned.
Fibroblasts have cytoplasmic myofilaments that
help them move in the dermis when necessary.20 There are
different types of fibroblast subpopulations. Some authors
maintain that these different subpopulations expand when
they are needed through different phenotype expressions,
whereas others believe that these subpopulations coexist
permanently in the dermis. These two hypotheses are not
incompatible. Myofibroblasts (MFBs) are phenotypically
modified fibroblasts that have the secretory capacity of
fibroblasts, which helps them synthesize strong fibronectin
fibers. They express the phenotypic characteristics of ‘non-muscle’
cells, but with the contractile capacities (of SMCs)
that make them responsible for most of the phenomena of
fibrotic contraction in the body. The fibronectin fibers syn-
22 Textbook of Chemical Peels
+
Direction of displacement
Nucleus
Microtubule
Dense bodies
Cellular
center
+
+
+
+
+
+
+
+
+
‘Stress’ contractile fibers
Network tightened with
actin microfibrils
Radial network with
actin microfibrils
Loose network with
actin microfibrils
in all cytosol
Figure 3.13
Different types of organization of actin microfibrils (MF) and
microtubules (MT) in a moving cell – organized polarization
of the MF and the MT.
